“Once the principle is admitted that it is the duty of the government to protect the individual against his own foolishness, no serious objections can be advanced against further encroachments.”
“The champions of socialism call themselves progressives, but they recommend a system which is characterized by rigid observance of routine and by a resistance to every kind of improvement. They call themselves liberals, but they are intent upon abolishing liberty. They call themselves democrats, but they yearn for dictatorship. They call themselves revolutionaries, but they want to make the government omnipotent. They promise the blessings of the Garden of Eden, but they plan to transform the world into a gigantic post office. Every man but one a subordinate clerk in a bureau.”
~ Ludwig von Mises
Senate GOP leaders on Thursday finally released their secret health-care reform bill, which would repeal Obamacare taxes, restructure subsidies to insurance customers, and both phase out Medicaid’s expansion program and cap Medicaid spending.
Republicans plan to bring the controversial bill that was drafted in secret to a quick vote next week, but face potentially fatal opposition to it from several members of their own caucus.
The 142-page bill, if passed into law, would sharply reduce financial aid that currently helps millions of people obtain health coverage, while at the same time offering a tax break to primarily wealthy Americans to the tune of hundreds of billions of dollars. And it would loosen rules in a way that could lead to states allowing insurers to offer less-generous health plans.
The bill would repeal, retroactive to the beginning of 2016, the Obamacare rule requiring most Americans to have some form of health coverage or pay a tax penalty fine. That repeal is expected to sharply increase the number of people who don’t have insurance, which could in turn lead insurers to raise premiums.
And it would repeal, retroactively to the beginning of 2016, the “employer mandate,” which requires large employers to offer health insurance to workers or be fined.
The bill also would continue for at least two years to offer reimbursements to health insurance companies for subsidies that reduce out-of-pocket costs for low income customers of Obamacare plans. But those subsidies would end in 2020, which would increase deductibles and other out-of-pocket health expenses for millions of customers.
The federal government’s share of funding for Medicaid, which is jointly run with individual states, would fall over the course of seven years to end up at around 57 percent of the cost of that program, which offers health coverage to the poor.
Under Obamacare, the federal government had guaranteed that its funding for adults newly eligible for Medicaid because of the Affordable Care Act would fall to no lower than 90 percent of their costs. That expansion program would begin being phased out in 2021, and fully repealed by three years later.
In another cost-cutting move, the bill would lower the maximum income level a household could have to still qualify for federal subsidies that help reduce the premiums people pay for enrollment for individual health plans. Obamacare currently bars subsidies to families that earn more than 400 percent of the federal poverty level. The new bill would reduce that cap to 350 percent of the poverty level.
Younger people, as a group, would end up paying less of a share of their income toward their individual health plans under the bill in comparison to what they pay now under Obamacare, while older people as a group would end up paying a larger share of their income.
Health plans that offer abortion services would not be eligible for the subsidies, according to the draft released Thursday.
The federal government also would end up spending less money subsidizing people’s insurance purchases by changing how the value of those subsidies are calculated. The bill would use a less-expensive type of individual health plan to calculate those subsidies, as opposed to the pricier plan used under Obamacare.
The bill also seeks to repeal, to the start of 2017, the 3.8 percent tax on net investment income.
The Trump administration is expected to back the bill, which most GOP senators were learning the details of during a meeting Thursday morning. The bill is named the “Better Care Reconciliation Act of 2017.”
“It’s going to be very good,” President Donald Trump said about an hour after the bill’s release. “A little negotiation, but it’s going to be very good.” Trump did not elaborate.
The House’s version of the bill, dubbed the American Health Care Act, is broadly unpopular among the public, and had been reportedly called “mean, mean, mean,” by Trump during a meeting with senators. Weeks earlier, Trump and House members who voted for the ACHA celebrated its passage in the Rose Garden of the White House.
A new NBC News/Wall Street Journal Poll released Thursday found that just 16 percent of Americans thought the House bill was a good idea, with 48 percent saying it is a bad idea.
“In broad strokes, the Senate bill is just like the House: Big tax cuts, big cut in federal heath spending, big increase in the uninsured,” tweeted Larry Levitt, an Obamacare expert at the Kaiser Family Foundation.
“Under the Senate bill, low-income people would pay higher premiums for bigger deductibles,” Levitt said.
He had noted on Twitter on Wednesday that “A 60 year-old at 351% of poverty currently gets a premium subsidy of $5,151 per year on average.” The Senate bill would eliminate all of that federal financial aid if it becomes law.
Senate GOP leaders want to have a vote on the bill by late next week, before Congress’ Fourth of July recess. They do not plan to hold any hearings on the legislation, infuriating Democrats, who were frozen out of the drafting process.
To pass, Republicans must get at least 50 GOP senators to vote for the bill, since no Democrat or independent is expected to vote for it. Vice President Mike Pence would break any tie, and would be expected to vote for the bill. There are 52 Republican senators.
On Thursday, about an hour after the bill was posted online, NBC’s Chuck Todd tweeted that a group of a conservative Republican senators were meeting, and that there are at least three GOP senators, and possibly more, who plan to announce later today that they will oppose the bill.
If that number proves to be accurate, it could be a death blow to the bill.
Sen. Rand Paul, R-Ky., told NBC that he and several other members of the GOP caucus would be making a statement on the bill later Thursday.
“It looks like we’re keeping Obamacare, not repealing it,” said Paul, who declined to say whether that meant he would vote against the bill.
Senate Majority Leader Mitch McConnell, R-Ky., said Thursday, “There will be ample time to analyze” and discuss the bill before the legislation is put to a vote.
While McConnell praised the bill on the floor of the Senate, many of his Republican caucus members avoided speaking with reporters staking them out in Congress, who wanted to ask about the legislation.
Democrats promptly blasted the bill, and castigated Republicans for planning to call a vote on it just a week after its details were released.
“The Republicans want to give a tax break to the wealthiest Americans,” said Senate Minority Leader Chuck Schumer, D-NY, on the floor of the Senate after release of the bill. “Simply put this bill will result in higher costs, less care, and millions of Americans will lose their health insurance.”
“It’s every bit as bad as the House bill. In many ways it’s even worse,” Schumer said. “The Senate bill is a wolf in sheep’s clothing, but this wolf has even sharper teeth than the House bill.”
House Speaker Paul Ryan, R-Wisc., during a press conference said, “From what I understand, their bill tracks along lines of House bill … [I] think that’s very good.”
Leslie Dach, director of the Obamacare-supporting group Protect Our Care Campaign, tore into the Senate’s bill, which, like Ryan, he compared to the House’s earlier bill.
“Senate Republicans promised to start over and write a plan that improves people’s health care,” Dach said. “Instead they doubled down on the failed House repeal approach that puts everyone’s health care last, and tax breaks for the wealthy first.”
“The heartless Senate health care repeal bill makes health care worse for everyone — it raises costs, cuts coverage, weakens protections and cuts even more from Medicaid than the mean House bill,” said Dach, who had served as senior counselor at the Department of Health and Human Services in the Obama administration.
“They wrote their plan in secret and are rushing forward with a vote next week because they know how much harm their bill does to millions of people.”
But Seema Verma, administrator for the federal Centers for Medicare and Medicaid Services, praised the Senate’s bill as she criticized Obamacare, a program that CMS oversees.
“I appreciate the work of the Senate as they continue to make progress fixing the crisis in health care that has resulted from Obamacare,” Verma said. “Skyrocketing premiums, rising costs and fewer choices have caused too many Americans to drop their insurance coverage.”
“Today, Obamacare is in a death spiral and millions ofAmericans are being negatively impacted as a result. They are trapped by mandates that force them to purchase insurance they don’t want and can’t afford,” she said. “The Senate proposal is built on putting patients first and in charge of their health-care decisions, bringing down the cost of coverage and expanding choices. Congress must act now to achieve the President’s goal to make sure all Americans have access to quality, affordable coverage.”
The Congressional Budget Office said it expects to release an analysis of the bill early next week Monday. The analysis will estimate how many people are likely to become uninsured in the next decade if the bill becomes law, as well as how premiums for individual health plans would be affected.
CBO aims to release estimate for Senate health care plan early next week https://www.cbo.gov/publication/52843 …
CBO aims to release estimate for Senate health care plan early next week
CBO and the staff of the Joint Committee on Taxation are in the process of preparing an estimate for the Senate health care plan and aim to release it early next week.
cbo.gov
The CBO “score” would also include projections on the bill’s impact on federal spending.
The release of the draft comes more than six weeks after GOP leaders in the House barely managed to win passage for their own health-care legislation.
The House bill, the American Health Care Act, is widely unpopular, multiple polls have shown.
The nonpartisan CBO, in analyzing that bill, found that 23 million more Americans would become uninsured by 2026 if it became law than if Obamacare remained in place.
While many of those people would voluntarily cease buying insurance plans because of the elimination requirement that they have some form of health coverage or pay a fine, millions more would find their plans unaffordable because of either rising prices, the loss of government subsidies or both factors.
By Hannah Recht, Zachary Tracer and Mira Rojanasakul
Currently, the federal government generally reimburses states for a fixed percentage of Medicaid expenditures, regardless of total spending or number of enrollees. The GOP bill would limit Medicaid reimbursement by a per-enrollee cost, based on 2016 average costs.
Allows states to choose from two formulas for how they get federal Medicaid funding, and boosts the funding for elderly and disabled Medicaid enrollees, relative to the initial bill.
Like the House bill, the Senate bill would allow states to choose between two formulas for federal Medicaid funding. But starting in 2025, the Senate bill would set a lower funding growth rate than the House bill would, meaning states would receive less money. Certain Medicaid enrollees would not be subject to these limits, including people with disabilities and children.
Budget impact: In the House bill, Federal Medicaid spending would decrease by $834 billion, from 2017 to 2026, relative to current law.
The ACA allowed states to expand Medicaid to individuals making as much as 138 percent of the federal poverty level, with federal funding. The GOP bill winds down Obamacare’s Medicaid expansion starting in 2020.
Won’t provide extra funding to states that newly expand Medicaid.
Medicaid expansion funding would be phased out between 2021 and 2024.
Human impact: In the House bill, Medicaid enrollment would decrease by 14 million people by 2026, about 17 percent.
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The ACA introduced subsidies based on income and the cost of health insurance, with some help available to people making up to 400 percent of the poverty level, or about $47,000 for an individual. The House bill would base subsidies mainly on age, phasing out funding beginning at an income of $75,000 for an individual.
The Senate bill would maintain the ACA’s subsidies through 2019, but change how subsidies are allocated starting in 2020. The ACA calculates subsidies based on a mid-level coverage plan, while the Senate bill would use a cheaper type of plan. Subsidies would no longer be available to those above 350 percent of the poverty level, or about $42,000 for an individual.
Human impact: Many low-income subsidy recipients would lose thousands in premium subsidies, particularly older enrollees in higher-cost areas. In the House bill, some people who currently earn too much to qualify for subsidies would receive new assistance. The Senate bill does not offer similar assistance. Instead, it would place additional limits on who qualifies for subsidy assistance, making some middle-class recipients who currently receive subsidies ineligible.
The ACA requires health insurance plans to cover 10 broad categories of essential health benefits, as well as to provide preventive services at no cost. The bill initially left the requirement intact, but an amendment that would repeal that requirement was added. Instead, states will define their own list of benefits that are required for plans receiving premium subsidies beginning Jan. 1, 2018.
An amendment was added that would leave essential health benefits intact—reinstating the federal standard. Instead, states could opt out of the requirement and apply for a waiver to define their own list of benefits that are required for plans receiving premium subsidies beginning Jan. 1, 2020.
Senate bill adopts changes in House bill.
Human impact: The Congressional Budget Office expects that half of the U.S. population live in states that would waive some required benefits. Plans in these states would likely have lower premiums, but they would cover less. For instance, maternity care premiums could cost an additional $1,000 per month or more. Customers seeking comprehensive coverage could face premiums and out-of-pocket charges that are significantly higher than under current law.
Budget impact: Insurers in some states could offer plans with such limited coverage that CBO does not consider them health insurance. Those plans would still be eligible for millions of dollars in federal subsidies.
The ACA requires health insurers to sell plans to individuals who are sick with so-called pre-existing conditions and not charge them more than healthy customers. An amendment would allow states to apply for a waiver that would let insurers charge higher premiums to people with pre-existing conditions that had a gap in coverage of at least 63 days in the prior year. To do so, states would have to establish some method (a special “high-risk” insurance pool, or subsidies) to help sick people.
Insurance companies would not be allowed to charge customers with pre-existing conditions more than healthy customers.
Human impact: In states that allow insurers to charge people with pre-existing conditions more than healthy people, those less healthy individuals would face increasingly prohibitive premiums under the House bill. Eventually, the CBO predicts, less-healthy people may not be able to afford any coverage.
Obamacare lets health insurers charge their oldest customers no more than three times as much as their youngest ones. The GOP bill introduced widens the ratio to 5 to 1.
Adds a provision that would let the Senate decide whether to increase subsidies that go to older Americans.
Adds a provision that would allow states to apply for a waiver to give insurers permission to charge older customers even more than the 5 to 1 ratio.
Senate bill adopts changes in House bill.
Human impact: Premiums would significantly rise for older people and decrease for younger people. Low-income older adults would face much higher premiums than under current law, even with federal subsidies.
Includes a new $100 billion fund designed to help states stabilize their individual health insurance markets or help low-income people get health care.
Adds $15 billion to the fund to be used for maternity, newborn, mental health and substance abuse coverage.
Adds $15 billion for the Federal Invisible Risk Sharing Program, designed to help insurers cover the costs of sick and expensive patients.
Adds $8 billion in funding from 2018 through 2023 to help individuals afford higher premiums in states that let insurers charge sick people more.
The Senate bill would include $112 billion in state grant funds, primarily to stabilize state insurance markets and cover expensive patients. It would also allocate $2 billion in 2018 for substance abuse treatment.
Human impact: The grants would lead to slightly lower premiums in the individual market and encourage insurer participation. The new funding would not be enough to significantly lower costs for people with pre-existing conditions.
Budget impact: Both bills would require more than $100 billion in additional federal spending.
Gives states the option of requiring some Medicaid recipients to work or pursue job training.
Senate bill adopts changes in House bill.
Human impact: According to the Kaiser Family Foundation, 10 million non-elderly adult Medicaid recipients who don’t receive Social Security are not working. Some of these adults would be excluded from work requirements due to disability, pregnancy or caretaker status, but many would be expected to complete job training or find employment in order to keep their insurance.
The House bill ends Obamacare’s requirement that individuals have health coverage and that most employers offer it. Instead, when people who’ve gone uninsured decide to buy health insurance, they’ll have to pay a 30 percent surcharge on their premiums for one year.
The Senate bill ends Obamacare’s requirement that individuals have health coverage and that most employers offer it.
Human impact: Though about 1 million people are expected to buy insurance in 2018 in order to avoid future surcharges, twice as many would choose not to purchase insurance long-term because of the House bill surcharge or insurance documentation requirements.
Budget impact: Revenue loss of $210 billion from 2017 to 2026 from repealing insurance penalties. The new premium surcharge would go to insurers directly, not the government.
Ends all federal funding for Planned Parenthood for one year. The bill also prohibits federal funds from going to insurance plans that cover abortions, other than those necessary to save the life of the woman, or in cases of rape or incest.
Adds additional safeguards to prevent government funds from being used for some abortions.
Senate bill adopts changes in House bill.
Human impact: Several thousand Medicaid-covered births would occur because of the loss of Planned Parenthood contraceptive and abortion care, particularly among women in areas without other providers that serve low-income patients.
Budget impact: Direct spending would decrease by $234 million between 2017 and 2026, but new births due to the Planned Parenthood provision would increase Medicaid spending by $77 million over the same period.
Repeals a 0.9 percent Medicare payroll surtax and a 3.8 percent investment-income tax on wealthy individuals that were introduced in the ACA, effective 2018.
Ends the taxes in 2017, rather than 2018.
Postpones repeal of the additional Medicare tax to 2023.
Senate bill adopts changes in House bill.
Human impact: Wealthy individuals would get a tax break. In counties that backed Trump, taxpayers would save $6.6 billion, while taxpayers in Clinton counties would save $21.6 billion.
Budget impact: From 2017 to 2026, the repeal would lose $172 billion in Net Investment Tax revenue and about $64 billion in Medicare tax revenue from 2023 to 2026. Repealing the Medicare tax in 2017 would have resulted in an additional $63 billion loss.
Repeals ACA taxes imposed on health insurers, pharmaceutical companies, medical-device companies and tanning salons, effective 2018.
Ends the taxes in 2017, rather than 2018.
Repeals most taxes immediately. A tax on providers would be phased out in 2025.
Budget impact: Loss of $199 billion in tax revenue from 2017 to 2026.
Obamacare imposes a tax on very generous health insurance benefits, which was delayed to 2020. The bill introduced further pushes the tax back to 2025.
Delays the tax to 2026.
Senate bill adopts changes in House bill.
Budget impact: Loss of $66 billion in tax revenue through 2026.
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The ACA requires health insurers to allow children to remain on their parents’ plans, up to age 26.
https://www.bloomberg.com/graphics/2017-healthcare-bill-changes/
https://www.conservativereview.com/scorecard?chamber=senate&state=&party=R
| Member | Party | State | Liberty Score® | Years in DC | Next Election | |
|---|---|---|---|---|---|---|
SenatorSusan Collins |
R | ME | F 12% | 20 | 2020 | |
SenatorLamar Alexander |
R | TN | F 17% | 14 | 2020 | |
SenatorLisa Murkowski |
R | AK | F 22% | 14 | 2022 | |
SenatorThad Cochran |
R | MS | F 24% | 38 | 2020 | |
SenatorJohn Hoeven |
R | ND | F 26% | 6 | 2022 | |
SenatorRoger Wicker |
R | MS | F 30% | 9 | 2018 | |
SenatorOrrin Hatch |
R | UT | F 31% | 40 | 2018 | |
SenatorJohnny Isakson |
R | GA | F 31% | 12 | 2022 | |
SenatorMike Rounds |
R | SD | F 32% | 2 | 2020 | |
SenatorShelley Capito |
R | WV | F 32% | 16 | 2020 | |
SenatorLindsey Graham |
R | SC | F 33% | 14 | 2020 | |
SenatorJohn McCain |
R | AZ | F 33% | 30 | 2022 | |
SenatorThom Tillis |
R | NC | F 37% | 2 | 2020 | |
SenatorJohn Cornyn |
R | TX | F 40% | 14 | 2020 | |
SenatorRichard Burr |
R | NC | F 40% | 12 | 2022 | |
SenatorRoy Blunt |
R | MO | F 41% | 6 | 2022 | |
SenatorMitch McConnell |
R | KY | F 42% | 32 | 2020 | |
SenatorCory Gardner |
R | CO | F 42% | 6 | 2020 | |
SenatorJohn Thune |
R | SD | F 44% | 12 | 2022 | |
SenatorBill Cassidy |
R | LA | F 47% | 8 | 2020 | |
SenatorBob Corker |
R | TN | F 47% | 10 | 2018 | |
SenatorRob Portman |
R | OH | F 49% | 6 | 2022 | |
SenatorJohn Barrasso |
R | WY | F 52% | 9 | 2018 | |
SenatorJeff Flake |
R | AZ | F 53% | 4 | 2018 | |
SenatorDan Sullivan |
R | AK | F 53% | 2 | 2020 |
| Member | Party | State | Liberty Score® | Years in DC | Next Election | |
|---|---|---|---|---|---|---|
SenatorPat Roberts |
R | KS | F 53% | 20 | 2020 | |
SenatorRon Johnson |
R | WI | F 56% | 6 | 2022 | |
SenatorJohn Boozman |
R | AR | F 58% | 6 | 2022 | |
SenatorDeb Fischer |
R | NE | F 58% | 4 | 2018 | |
SenatorPat Toomey |
R | PA | F 59% | 6 | 2022 | |
SenatorMichael Enzi |
R | WY | D 60% | 20 | 2020 | |
SenatorDean Heller |
R | NV | D 61% | 5 | 2018 | |
SenatorJoni Ernst |
R | IA | D 63% | 2 | 2020 | |
SenatorJames Lankford |
R | OK | D 68% | 6 | 2022 | |
SenatorJerry Moran |
R | KS | D 69% | 6 | 2022 | |
SenatorCharles Grassley |
R | IA | C 70% | 36 | 2022 | |
SenatorJim Inhofe |
R | OK | C 70% | 22 | 2020 | |
SenatorRichard Shelby |
R | AL | C 70% | 30 | 2022 | |
SenatorDavid Perdue |
R | GA | C 72% | 2 | 2020 | |
SenatorMarco Rubio |
R | FL | C 74% | 6 | 2022 | |
SenatorSteve Daines |
R | MT | C 74% | 4 | 2020 | |
SenatorMichael Crapo |
R | ID | C 74% | 18 | 2022 | |
SenatorJim Risch |
R | ID | C 78% | 8 | 2020 | |
SenatorTom Cotton |
R | AR | C 79% | 4 | 2020 | |
SenatorTim Scott |
R | SC | A 90% | 4 | 2022 | |
SenatorRand Paul |
R | KY | A 92% | 6 | 2022 | |
SenatorBenjamin Sasse |
R | NE | A 94% | 2 | 2020 | |
SenatorTed Cruz |
R | TX | A 97% | 4 | 2018 | |
SenatorJohn Kennedy |
R | LA | A 100% | 0 | 2022 | |
SenatorMike Lee |
R | UT | A 100% | 6 | 2022 |
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CINCINNATI — Otto Warmbier has died, University of Cincinnati Medical Center announced Monday.
Warmbier died at 2:20 p.m. Monday, days after he was released from captivity in North Korea.
In a statement, family members said Warmbier had been unable to speak, see or react to verbal commands since his return to Cincinnati June 13.
“He looked very uncomfortable – almost anguished,” family members said. “Although we would never hear his voice again, within a day the countenance of his face changed – he was at peace. He was home and we believe he could sense that.”
Family members thanked the hospital’s staff for the care they provided Warmbier but said ” the awful torturous mistreatment our son received at the hands of the North Koreans ensured that no other outcome was possible beyond the sad one we experienced today.”
“It would be easy at a moment like this to focus on all that we lost – future time that won’t be spent with a warm, engaging, brilliant young man whose curiosity and enthusiasm for life knew no bounds,” the family said. “But we choose to focus on the time we were given to be with this remarkable person. You can tell from the outpouring of emotion from the communities that he touched – Wyoming, Ohio and the University of Virginia to name just two – that the love for Otto went well beyond his immediate family.”
Check back for more on this breaking story.
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| Clinical data | |
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| AHFS/Drugs.com | Monograph |
| Routes of administration |
Intravenous (most common), oral or rectal |
| ATC code | |
| Legal status | |
| Legal status |
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| Pharmacokinetic data | |
| Biological half-life | 5.5[1]-26 hours[2] |
| Identifiers | |
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| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| ECHA InfoCard | 100.000.896 |
| Chemical and physical data | |
| Formula | C11H17N2NaO2S |
| Molar mass | 264.32 g/mol |
| 3D model (Jmol) | |
| Chirality | Racemic mixture |
  (what is this?) (verify) |
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Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories, not to be confused with pentobarbital), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic that is an analogue of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization‘s “Essential Drugs List“, which is a list of minimum medical needs for a basic healthcare system, but was supplanted by propofol.[3] It was previously the first of three drugs administered during most lethal injections in the United States, but the U.S. manufacturer Hospira stopped manufacturing the drug and the EU banned the export of the drug for this purpose.[4]
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Sodium thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of general anesthesia. Its use has been largely replaced with that of propofol, but retains popularity as an induction agent for rapid sequence intubation and in obstetrics.[citation needed] Following intravenous injection, the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body, and in about 5–10 minutes the concentration is low enough in the brain that consciousness returns.[citation needed]
A normal dose of sodium thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarian section) rapidly makes her unconscious, but the baby in her uterus remains conscious. However, larger or repeated doses can depress the baby.[5]
Sodium thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an inhaled anesthetic (gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. Sodium thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5- to 26-hour half-life, consciousness would take a long time to return.[6]
In veterinary medicine, sodium thiopental is used to induce anesthesia in animals. Since it is redistributed to fat, certain lean breeds of dogs such as sight hounds will have prolonged recoveries from sodium thiopental due to their lack of body fat and their lean body mass. Conversely, obese animals will have rapid recoveries, but it will be some time[vague] before it is entirely removed (metabolized) from their bodies. Sodium thiopental is always administered intravenously, as it can be fairly irritating; severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.[citation needed]
Sodium thiopental decreases the cardiac stroke volume, which results in a decrease in cardiac output. The decrease in cardiac output occurs in conjunction with a decrease in systemic vascular resistance, which results in hypotension. However, in comparison with propofol, the reflex tachycardia seen during states of hypotension is relatively spared (a bradycardia is common after administration of propofol) and therefore the observed fall in blood pressure is generally less severe.
In addition to anesthesia induction, sodium thiopental was historically used to induce medical comas.[7] It has now been superseded by drugs such as propofol because their effects wear off more quickly than thiopental. Patients with brain swelling, causing elevation of intracranial pressure, either secondary to trauma or following surgery, may benefit from this drug. Sodium thiopental, and the barbiturate class of drugs, decrease neuronal activity and therefore decrease the production of osmotically active metabolites, which in turn decreases swelling. Patients with significant swelling have improved outcomes following the induction of coma. Reportedly, thiopental has been shown to be superior to pentobarbital in reducing intracranial pressure.[8] This phenomenon is also called a reverse steal effect.[citation needed]
In refractory status epilepticus, thiopental may be used to terminate a seizure.
Sodium thiopental is used intravenously for the purposes of euthanasia. In both Belgium and the Netherlands, where active euthanasia is allowed by law, the standard protocol recommends sodium thiopental as the ideal agent to induce coma, followed by pancuronium bromide.[9]
Intravenous administration is the most reliable and rapid way to accomplish euthanasia. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium (Nesdonal) in a small volume (10 ml physiological saline). Then, a triple dose of a non-depolarizing neuromuscular blocking drug is given, such as 20 mg pancuronium bromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should be given intravenously to ensure optimal availability but pancuronium bromide may be administered intramuscularly at an increased dosage level of 40 mg.[9]
Along with pancuronium bromide and potassium chloride, thiopental is used in 34 states of the U.S. to execute prisoners by lethal injection. A very large dose is given to ensure rapid loss of consciousness. Although death usually occurs within ten minutes of the beginning of the injection process, some have been known to take longer.[10] The use of sodium thiopental in execution protocols was challenged in court after a study in the medical journal The Lancet reported autopsies of executed inmates showed the level of thiopental in their bloodstream was insufficient to cause unconsciousness.
On December 8, 2009, the State of Ohio became the first to use a single dose of sodium thiopental for its capital execution, following the failed use of the standard three-drug cocktail during a recent execution, due to inability to locate suitable veins. Kenneth Biros was executed using the single-drug method.[11]
The state of Washington is now the second state in the U.S. to use the single-dose sodium thiopental injections for death penalty executions. On September 10, 2010, Cal Coburn Brown was executed. This was the first execution in the state to use a single dose, single drug injection. His death was pronounced approximately one and a half minutes after the intravenous administration of five grams of the drug.[12]
After its use for execution of Jeffrey Landrigan in the U.S., the UK introduced a ban on the export of sodium thiopental in December 2010,[13] after it was established that no European supplies to the U.S. were being used for any other purpose.[14] The restrictions were based on “the European Union Torture Regulation (including licensing of drugs used in execution by lethal injection)”.[15] From 21 December 2011 the European Union extended trade restrictions to prevent the export of certain medicinal products for capital punishment, stating that “the Union disapproves of capital punishment in all circumstances and works towards its universal abolition”.[16]
Thiopental (Pentothal) is still used in some places as a truth serum to weaken the resolve of a subject and make them more compliant to pressure.[17] The barbiturates as a class decrease higher cortical brain functioning. Some psychiatrists hypothesize that because lying is more complex than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the truth. The drug tends to make subjects loquacious and cooperative with interrogators; however, the reliability of confessions made under thiopental is questionable.[18] “Sodium pentathol” as a truth serum has become a trope in films, comics and literature, and even appears in popular music.[19]
Psychiatrists have used thiopental to desensitize patients with phobias,[20] and to “facilitate the recall of painful repressed memories.”[21] One psychiatrist who worked with thiopental is the Dutch Professor Jan Bastiaans, who used this procedure to help relieve trauma in surviving victims of the Holocaust.[22]
Sodium thiopental is a member of the barbiturate class of drugs, which are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is one of several representatives. This superfamily of ion channels includes the neuronal nAChR channel, the 5HT3R channel, the GlyR channel and others. Surprisingly, while GABAA receptor currents are increased by barbiturates (and other general anesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anesthetic concentrations of both sodium thiopental and pentobarbital.[23] Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.[24]The GABAA receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance the inhibitory action of the GABAA receptor.[25]
Following a shortage that led a court to delay an execution in California, a company spokesman for Hospira, the sole American manufacturer of the drug, objected to the use of thiopental in lethal injection. “Hospira manufactures this product because it improves or saves lives, and the company markets it solely for use as indicated on the product labeling. The drug is not indicated for capital punishment and Hospira does not support its use in this procedure.”[26] On January 21, 2011, the company announced that it would stop production of sodium thiopental from its plant in Italy because Italian authorities couldn’t guarantee that exported quantities of the drug would not be used in executions. Italy was the only viable place where the company could produce sodium thiopental, leaving the United States without a supplier.[27]
Thiopental rapidly and easily crosses the blood brain barrier as it is a lipophilic molecule. As with all lipid-soluble anaesthetic drugs, the short duration of action of sodium thiopental is due almost entirely to its redistribution away from central circulation towards muscle and fat tissue, due to its very high fat:water partition coefficient (aprx 10), leading to sequestration in fat tissue. Once redistributed, the free fraction in the blood is metabolized in the liver. Sodium thiopental is mainly metabolized to pentobarbital,[28] 5-ethyl-5-(1′-methyl-3′-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1′-methyl-3′-carboxypropyl)-2-thiobarbituric acid.[29]
The usual dose range for induction of anesthesia using thiopental is from 3 to 6 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as benzodiazepines or clonidine will reduce requirements, as do specific disease states and other patient factors. Among patient factors are: age, sex, and lean body mass. Specific disease conditions that can alter the dose requirements of thiopentone and for that matter any other intravenous anaesthetic are: hypovolemia, burns, azotemia, hepatic failure, hypoproteinemia, etc.[citation needed]
As with nearly all anesthetic drugs, thiopental causes cardiovascular and respiratory depression resulting in hypotension, apnea and airway obstruction. For these reasons, only suitably trained medical personnel should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache, agitated emergence, prolonged somnolence, and nausea. Intravenous administration of sodium thiopental is followed instantly by an odor and/or taste sensation, sometimes described as being similar to rotting onions, or to garlic. The hangover from the side effects may last up to 36 hours.
Although individual molecules of thiopental contain one sulfur atom, it is not a sulfonamide, and does not show allergic reactions of sulfa/sulpha drugs.
Thiopental should be used with caution in cases of liver disease, Addison’s disease, myxedema, severe heart disease, severe hypotension, a severe breathing disorder, or a family history of porphyria.[30][31]
Co-administration of pentoxifylline and thiopental causes death by acute pulmonary edema in rats. This pulmonary edema was not mediated by cardiac failure or by pulmonary hypertension but was due to increased pulmonary vascular permeability.[32]
Sodium thiopental was discovered in the early 1930s by Ernest H. Volwiler and Donalee L. Tabern, working for Abbott Laboratories. It was first used in human beings on March 8, 1934, by Dr. Ralph M. Waters[33] in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia.[34] Three months later,[35] Dr. John S. Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott.[36]Abbott continued to make the drug until 2004, when it spun off its hospital-products division as Hospira.
Thiopental is famously associated with a number of anesthetic deaths in victims of the attack on Pearl Harbor. These deaths, relatively soon after the drug’s introduction, were said to be due to excessive doses given to shocked trauma patients. However, recent evidence available through freedom of information legislation was reviewed in the British Journal of Anaesthesia,[37] which has suggested that this story was grossly exaggerated. Of the 344 wounded that were admitted to the Tripler Army Hospital only 13 did not survive and it is unlikely that thiopentone overdose was responsible for more than a few of these.
Thiopental is still rarely used as a recreational drug, usually stolen from veterinarians or other legitimate users of the drug; however, more common sedatives such as benzodiazepines are usually preferred as recreational drugs, and abuse of thiopental tends to be uncommon and opportunistic.[citation needed]
Communication channel between Washington and Moscow to be suspended immediately
Russia has said it will treat US warplanes operating in parts of Syria where its air forces are also present as “targets” amid a diplomatic row caused by the downing of a Syrian jet.
The country’s defence ministry said it would track US-led coalition aircraft with missile systems and military aircraft, but stopped short of saying it would shoot them down.
A hotline set up between Russia and the US to prevent mid-air collisions will also be suspended.
“All kinds of airborne vehicles, including aircraft and UAVs of the international coalition detected to the west of the Euphrates River will be tracked by the Russian SAM systems as air targets,” the Russian Defence Ministry said in a statement.
The warning comes after a US F-18 Super Hornet shot down a Syrian army SU-22 jet on Sunday in the countryside southwest of Raqqa – the first such downing of a Syrian jet by the US since the start of the country’s civil war in 2011.
Washington said the jet had dropped bombs near US-backed forces but Damascus said the plane was downed while flying a mission against Isis militants.
Russia’s defence ministry said the suspension of its communication line with the Americans would begin immediately.
The US did not use its hotline with Russia ahead of the downing of the Syrian government warplane, said the ministry, which accused the US of a “deliberate failure to make good on its commitments” under the deconfliction deal.
“The shooting down of a Syrian Air Force jet in Syria’s airspace is a cynical violation of Syria’s sovereignty,” the ministry said.
“The US’ repeated combat operations under the guise of ‘combating terrorism’ against the legitimate armed forces of a UN member-country are a flagrant violation of international law and an actual military aggression against the Syrian Arab Republic.”
Theresa May appealed to Russia to continue the use of “deconfliction” measures over the skies of Syria to reduce the risk of misunderstandings in what is a crowded airspace.
Russia, which has been providing air cover for Syria’s President, Bashar al-Assad, since 2015, has an agreement with the US aimed at preventing incidents involving either country’s warplanes engaged in operations in Syria.
Downing the jet was akin to “helping the terrorists that the US is fighting against”, Sergei Ryabkov, Russia’s deputy foreign minister, said.
A statement released by US Central Command on Sunday said the Syrian jet was “immediately shot down… in accordance with rules of engagement and in collective self-defence of Coalition partnered forces”.
“The Coalition’s mission is to defeat Isis in Iraq and Syria. The Coalition does not seek to fight Syrian regime, Russian, or pro-regime forces partnered with them, but will not hesitate to defend Coalition or partner forces from any threat,” it added.
“The Coalition presence in Syria addresses the imminent threat Isis in Syria poses globally. The demonstrated hostile intent and actions of pro-regime forces toward Coalition and partner forces in Syria conducting legitimate counter-Isis operations will not be tolerated.”
BEIRUT (AP) — Russia on Monday threatened aircraft from the U.S.-led coalition in Syrian-controlled airspace and suspended a hotline intended to avoid collisions in retaliation for the U.S. military shooting down a Syrian warplane.
The U.S. said it had downed the Syrian jet a day earlier after it dropped bombs near the U.S.-backed Syrian Democratic Forces conducting operations against the Islamic State group, adding that was something it would not tolerate.
The downing of the warplane — the first time in the six-year conflict that the U.S. has shot down a Syrian jet — came amid another first: Iran fired several ballistic missiles Sunday night at IS positions in eastern Syria in what it said was a message to archrival Saudi Arabia and the United States.
The developments added to already-soaring regional tensions and reflect the intensifying rivalry among the major players in Syria’s civil war that could spiral out of control just as the fight against the Islamic State group in its stronghold of Raqqa is gaining ground.
Russia, a key ally of Syrian President Bashar Assad, called on the U.S. military to provide a full accounting as to why it decided to shoot down the Syrian Su-22 bomber.
The U.S. military confirmed that one of its F-18 Super Hornets shot down a Syrian jet that had dropped bombs near the U.S. partner forces SDF. Those forces, which are aligned with the U.S. in the campaign against the Islamic State group, warned Syrian government troops to stop their attacks or face retaliation.
The Russian Defense Ministry said in a statement that as of Monday, all coalition jets and drones flying west of the Euphrates River will be tracked as potential targets.
Areas of northern Syria west of the Euphrates were controlled by IS before Syrian government forces captured most of them in recent months. The Russians, who have been providing air cover for Assad’s forces since 2015, appear to want to avoid further U.S. targeting of Syrian warplanes or ground troops that have come under U.S. attack in eastern Syria recently.
It was the second time Russia suspended a hotline intended to minimize incidents with the U.S. in Syrian airspace. In April, Russia briefly suspended cooperation after the U.S. military fired 59 missiles at a Syrian air base following a chemical weapons attack that Washington blamed on the Assad government.
Gen. Joseph Dunford, chairman of the Joint Chiefs of Staff, said Washington is working to re-establish communications aimed at avoiding mishaps involving U.S. and Russian air operations in Syria.
Speaking in Washington, the top U.S. military officer said the two sides were in delicate discussions to lower tensions.
“The worst thing any of us could do right now is address this with hyperbole,” Dunford said.
Viktor Ozerov, chairman of the defense and security committee at the upper chamber of Russian parliament, described his Defense Ministry’s statement as a warning.
“I’m sure that because of this, neither the U.S. nor anyone else will take any actions to threaten our aircraft,” he told the state-owned RIA Novosti news agency. “That’s why there’s no threat of direct confrontation between Russia and American aircraft.”
Ozerov insisted that Russia will be tracking the coalition’s jets, not shooting them down, but he added that “a threat for those jets may appear only if they take action that pose a threat to Russian aircraft.”
Iran said the missile strike by its powerful Revolutionary Guard hit Syria’s eastern city of Deir el-Zour on Sunday night and was in retaliation for two attacks in Tehran earlier this month that killed 17 people and were claimed by the Islamic State group.
It appeared to be Iran’s first missile attack abroad in over 15 years and its first in the Syrian conflict, in which it has provided crucial support to Assad. The muscle-flexing comes amid the worsening of a long-running feud between Shiite powerhouse Iran and Saudi Arabia, with supports Syrian rebels and has led recent efforts to isolate the Gulf nation of Qatar.
“The Saudis and Americans are especially receivers of this message,” Gen. Ramazan Sharif of the Revolutionary Guard told Iranian state TV in an interview.
It also raised questions about how U.S. President Donald Trump’s administration, which had previously put Iran “on notice” for its ballistic missile tests, will respond. Israel also is concerned about Iran’s missiles and has deployed a multilayered missile-defense system.
The missile attack came amid recent confrontations in Syria between U.S.-backed forces and Iranian-backed pro-government factions. The U.S. recently deployed a truck-mounted missile system in Syria as Iranian-backed forces cut off the advance of the U.S.-supported rebels along the Iraqi border.
Iranian officials threatened more strikes. Former Guard chief Gen. Mohsen Rezai wrote on Twitter: “The bigger slap is yet to come.”
U.S.-backed opposition fighters said Assad’s forces have been attacking them in the northern province of Raqqa and warned that if such attacks continue, the fighters will take action.
Clashes between Syrian troops and the SDF would escalate tensions and open a new front line in the many complex battlefields of the civil war, now in its seventh year. Clashes between the Kurdish-led SDF and Syrian forces have been rare and some rebel groups have even accused them of coordinating on the battlefield.
Both sides are battling the Islamic State group, with SDF fighters focusing on their march into the northern city of Raqqa, which the extremist group has declared to be its capital.
Syrian government forces have also been attacking IS in northern, central and southern parts of the country, seizing 25,000 square kilometers (9,600 square miles) and reaching the Iraqi border for the first time in years.
SDF spokesman Talal Sillo said the government wants to thwart the SDF offensive to capture Raqqa. He said government forces began attacking the SDF on Saturday, using warplanes, artillery and tanks in areas that SDF had liberated from IS.
Sillo also warned that if “the regime continues in its offensive against our positions in Raqqa province, this will force us to retaliate with force.”
The Britain-based Syrian Observatory for Human Rights, which tracks Syria’s war, said government forces expanded their presence in Raqqa province by capturing from IS the town of Rasafa.
___
Vasilyeva reported from Moscow. Associated Press writers Nasser Karimi in Tehran and Jon Gambrell in Dubai, United Arab Emirates, contributed.
http://hosted2.ap.org/APDefault/*/Article_2017-06-19-Syria/id-371357b2c20e4aaa982d07da071a7f7a
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Part III of the undercover Project Veritas Action investigation dives further into the back room dealings of Democratic politics. It exposes prohibited communications between Hillary Clinton’s campaign, the DNC and the non-profit organization Americans United for Change. And, it’s all disguised as a duck. In this video, several Project Veritas Action undercover journalists catch Democracy Partners founder directly implicating Hillary Clinton in FEC violations. “In the end, it was the candidate, Hillary Clinton, the future president of the United States, who wanted ducks on the ground,” says Creamer in one of several exchanges. “So, by God, we would get ducks on the ground.” It is made clear that high-level DNC operative Creamer realized that this direct coordination between Democracy Partners and the campaign would be damning when he said: “Don’t repeat that to anybody.” The first video explained the dark secrets and the hidden connections and organizations the Clinton campaign uses to incite violence at Trump rallies. The second video exposed a diabolical step-by-step voter fraud strategy discussed by top Democratic operatives and showed one key operative admitting that the Democrats have been rigging elections for fifty years. This latest video takes this investigation even further.
First video: https://www.youtube.com/watch?v=5IuJG…
Second video: https://www.youtube.com/watch?v=hDc8P…
Part III of the undercover Project Veritas Action investigation dives further into the back room dealings of Democratic politics. It exposes prohibited communications between Hillary Clinton’s campaign, the DNC and the non-profit organization Americans United for Change. And, it’s all disguised as a duck. In this video, several Project Veritas Action undercover journalists catch Democracy Partners founder directly implicating Hillary Clinton in FEC violations. “In the end, it was the candidate, Hillary Clinton, the future president of the United States, who wanted ducks on the ground,” says Creamer in one of several exchanges. “So, by God, we would get ducks on the ground.” It is made clear that high-level DNC operative Creamer realized that this direct coordination between Democracy Partners and the campaign would be damning when he said: “Don’t repeat that to anybody.” The first video explained the dark secrets and the hidden connections and organizations the Clinton campaign uses to incite violence at Trump rallies. The second video exposed a diabolical step-by-step voter fraud strategy discussed by top Democratic operatives and showed one key operative admitting that the Democrats have been rigging elections for fifty years. This latest video takes this investigation even further.
Project Veritas Action Founder James O’Keefe brings you more Hillary shockers.
Citing a Democratic operative’s confirmation of a chain of command that runs directly from Hillary Clinton’s campaign to agents who “execute … on the ground,” the activists at Project Veritas are asking the Federal Election Commission to investigate a “criminal conspiracy.’
The filing of the complaint with the federal agency follows the release earlier this week of two videos in which Democrats explain how they can attempt to change the outcome of the election through apparently fraudulent means, such as having people travel across state lines to vote illegally.
The complaint follows the filing of a another complaint with the FEC, by the Public Interest Legal Foundation, a nonprofit organization “dedicated to protect the right to vote, preserve the constitutional framework of American elections, and educate the public on the issue of election integrity.”
Both cite the evidence in the videos released by James O’Keefe’s Project Veritas.
The videos have resulted already in two Democratic operatives who appeared on them losing their jobs.
Editor’s Note: Be aware of offensive language throughout videos and in quotes from videos.
One is Scott Foval, who had worked for People for the American Way, a George Soros-funded group, and more recently with Americans United for Change.
In the video, he said: “You know what? We’ve been busing people in to deal with you f—ing a—–es for 50 years, and we’re not going to stop now.”
Also, he said he and his agents are “starting anarchy” by creating “conflict engagement … in the lines at Trump rallies.”
Also now out of work is Bob Creamer, founder and partner of Democracy Partners, and husband of Rep. Jan Schakowsky, D-Ill.
Foval credited Creamer with coming up with a number of ideas and strategies to enhance Democrats’ standing among voters.
The new complaint from O’Keefe’s organization explained his journalists “have uncovered a criminal conspiracy where, in the words of Scott Foval, ‘The way that works is: The [Clinton] campaign pays DNC, DNC pays Democracy Partners, Democracy Partners pays The Foval Group, The Foval group goes and executes … on the ground.’
The complaint states: “This has been done in a manner to evade federal election laws and violating coordinated expenditure rules.”
It is supplemented with pages of evidence.
“The criminal conspiracy involves the knowing and willful creation of coordinated expenditures from prohibited corporate sources. As is detailed numerous times in the Veritas transcript, attached as EXHIBIT A, the supposedly independent speech and actions of third-party groups were directed, controlled, or puppeteered by HFA or the DNC.
“Indeed, the record establishes not just simple violations of the FECA’s coordination provisions, but ongoing knowing and willful evasion of federal election law requirements through a complicated scheme. Because this conspiracy involves large numbers of employees, heightened travel, production, and distribution costs and because of the nationwide scale of the operation, upon information and belief, this triggers criminal penalties.”
One result of the six-month undercover investigation is that “the supposedly spontaneous and independent protests occurring at Donald Trump events nationwide were controlled and directed by Democratic Party operatives.”
“The commission should find reason to believe that Hillary for America and other named respondents have violated 52 U.S.C. [paragraph] 30101, et seq, and conduct an immediate investigation,” the complaint explains. “Because of the weighty public interest at stake here, it should do so within 120 days of the filing of this complaint … the complainants request that the FEC impose sanctions appropriate to these violations and take further action as may be appropriate, including referring the matter to the Department of Justice for a criminal investigation.”
Foval explains the subterfuge.
“We can hire any demo that we want. We use the same mechanism to recruit them that we do to make focus groups. … We have to be really careful. Um, because, what we don’t need is for it to show up on CNN that the DNC paid ‘x’ people to … that’s not gonna happen. We need to keep it, you know, I hate to use the Beyonce term, ‘partition,’ but we need to keep the partition. That’s as gay as I’ll get.”
The previous complaint from PILF was over the same events.
When the videos appeared, former House Speak Newt Gingrich also raised questions about the apparent disdain for the law.
“Where is the FBI, why is the FBI not investigating this?” the former House speaker asked during an appearance on Fox News on Tuesday, BizPacReview reported. “You have a deliberate willful effort to foment violence, to break up a presidential campaign [and] to intimidate voters.”
The PILF complaint, directed to the office of the general counsel for the FEC in Washington, names Hillary for America, the DNC, Democracy Partners, Americans United for Change and others.
“This complaint is based on information and belief that respondents have engaged in public communications, campaign activity, targeted voter registration drives, and other targeted GOTV activity … at the request, direction, and approval of the Hillary for America campaign committee and the Democratic National committee in violation of 11 C.F.R. 109.20 and 11 C.F.R. 114.4(d)(2) and (3).”
The activities, the complaint says, “potentially registered persons who were not citizens.” They also illegally coordinated political maneuvers between a candidate’s committee and groups that are supposed to be operating independently, the complaint charges.
That puts them in violation of Federal Election Campaign Act of 1971, the complaint contends.
Sen. Ted Cruz, R-Texas, said on Twitter, according to the Washington Examiner, that multiple visits to the White House by a “voter fraud operative” merits “a serious criminal investigation.”
Talk-radio icon Rush Limbaugh said the evidence is worrisome.
“Every Trump rally would feature none of this [violence] unless the Democrats were paying for it. I think it’s a big deal, folks. The media is complicit. They know who these people are. … They’re in on it. They’re part of the game. … None of it’s organic. None of it’s natural. None of it’s real. Every bit of it is bought and paid for.
“[Democrats] can’t leave elections to chance because they know that, despite the way it may look, the majority of Americans would not support them if they knew who they are.”
Foval said he works backward in his thinking. He first speculates how a charge of voter fraud could be proven, and then he manipulates circumstances and events to avoid those tactics.
He talked about bringing voters from one state to another to vote illegally.
Hiring a bus could be used as evidence of conspiracy, he noted, so people would need to drive their own cars, or better yet, rentals.
There also was a discussion about using local addresses for illegal voters.
He said what needs to happen is to “implement the plan on a much bigger scale.”
“You implement a massive change in state legislatures and in Congress. So you aim higher for your goals, and you implement it across every Republican-held state.”
In Monday’s video, Creamer confirmed, “The campaign is fully in it.”
Project Veritas says the actions are “behind-the-scenes shady practices with consequences most Americans have seen on national television at Donald Trump campaign rallies across the country.”
“What the media hasn’t reported is that the Clinton campaign and Democratic National Committee has been directing these activities with, at very best, a very thin veil of plausible deniability.”
Commented Foval at one point, “I’m saying we have mentally ill people, that we pay to do s—, make no mistake. Over the last 20 years, I’ve paid off a few homeless guys to do some crazy stuff, and I’ve also taken them for dinner, and I’ve also made sure they had a hotel, and a shower. And I put them in a program. Like I’ve done that. But the reality is, a lot of people especially our union guys. A lot of our union guys … they’ll do whatever you want. They’re rock and roll. When I need to get something done in Arkansas, the first guy I call is the head of the AFL-CIO down there, because he will say, ‘What do you need?’ And I will say, ‘I need a guy who will do this, this and this.’ And they find that guy. And that guy will be like, ‘Hell yeah, let’s do it.’”
Last week, O’Keefe reported his Twitter account was shut down as he was releasing reports on voter fraud.
In one video he released last week, a Clinton staffer confessed that ripping up voter registration forms – if they are for Republicans – is “fine.”
The video also revealed a sexist atmosphere inside the Clinton campaign in which another staffer boasts he would probably have to “grab a–” twice before he’d even be reprimanded. It underscores the double standard by Democrats who have been critical of the 11-year-old recording of Donald Trump making lewd remarks about women.
In the video, both Wylie Mao, a field organizer for the Clinton campaign and the Democratic Party of Florida in West Palm Beach, and Trevor Lafauci, a Clinton campaign staffer, agree that ripping up registration forms from Republicans should be “fine.”
“If I rip up completed VR forms, like 20 of them, I think I’ll just get reprimanded. I don’t think I would get fired,” Mao said.
Lafauci, after being told that someone else ripped up Republican registration forms, said, “Yeah, that should be fine.”
When Project Veritas journalists confronted both Mao and Lafauci about the comments they made on camera, they “refused to answer and walked away,” the organization said.
O’Keefe previously released an undercover video of Alan Schulkin, the New York Democratic commissioner of the Board of Elections, confirming there is widespread fraud.
In the video, he is heard disclosing that organizers use buses to haul people from poll to poll to vote.
“Yeah, they should ask for your ID. I think there is a lot of voter fraud,” he said in the video, which was recorded some months ago.
http://www.wnd.com/2016/10/okeefe-complaint-to-fec-cites-dems-criminal-conspiracy/#y15gwzlJcyR5tBzu.99
[yotuube=https://www.youtube.com/watch?v=olH1qXW2w4M]
Tribute to the Visegrad Four countries: Poland, Hungary, Czech Republic and Slovakia. Often in the West we hear of “Europeans values”, “Western values”. Those values that are touted as “European” and “Western” by Leftist are anything but. The value of self-hate is a value of the far-left imposed on Europe over the last half-century. Those aren’t our real European values nor representative of our ancient cultures. It is manipulation and deceit to say they are.
Hillary Clinton has aligned herself closely with a vision for America laid out by her benefactor — left-wing financier George Soros, who talks of “international governance,” more open borders, increased Muslim immigration and diminished U.S. global power.
The phrase “American exceptionalism” is not part of his agenda. He wrote in 1998: “The sovereignty of states must be subordinated to international law and international institutions.”
“We need some global system of political decision-making. In short, we need a global society to support our global economy,” Mr. Soros wrote.
After the Sept. 11, 2001, al Qaeda attacks on New York City and the Pentagon, he said, “Military power is of limited use in dealing with asymmetric threats such as terrorism.”
The Clinton-Soros symbiosis came into clearer focus this month with WikiLeaks’ release of thousands of hacked emails from John Podesta, Mrs. Clinton’s campaign chairman. Mr. Soros‘ name comes up nearly 60 times.
The financial and ideological alliance is so complete that after Mr. Soros dined with Mrs. Clinton in 2014 and asked her to attend a liberal group’s fundraiser, her campaign manager, Robby Mook, wrote in an email, “I would only do this for political reasons (ie to make Soros happy).”
http://www.washingtontimes.com/news/2016/oct/20/hillary-clinton-embraces-george-soros-radical-visi/
Just as America was tossed — or did we eagerly jump — into the sexual political gutter with Bill and Hillary and Donald, there was other news breaking.At least I thought it was news. But I must warn you: Sex and sexual politics has nothing to do with it.
It’s Hillary Clinton‘s dream of an America without borders, as expressed to investors of a Brazilian bank, in comments leaked by WikiLeaks.
An America without borders, Hillary? How positively George Soros of you, Madam Secretary.
“My dream is a hemispheric common market, with open trade and open borders, sometime in the future with energy that’s as green and sustainable as we can get it, powering growth and opportunity for every person in the hemisphere,” Clinton reportedly said to investors in a paid speech she gave to Brazilian Banco Itau in 2013.
Here’s the thing about borders. If you don’t have borders, you don’t have a country. Americans are beginning to understand this. Europeans understand it now, quite clearly.
Clinton’s dream also includes a Western Hemispheric common market, like the European common market that is dissolving in chaos, fear and debt.
If that is indeed her dream, then she dreams the internationalist dream that would end America. But Americans aren’t talking about this, perhaps because there is no video involving sex and Hollywood and Trump.
I would love to hear Clinton’s explanation. Perhaps she could put it in some proper context.
Or perhaps she was merely telling the Brazilians something they wanted to hear, because they were paying her a good chunk of cash.
And if there is a way for America to maintain sovereignty without borders, Hillary might be just the one to tell us. But the Clinton campaign isn’t commenting. And reporters aren’t really pressing, preoccupied as they are by that vulgar video of a boorish Trump.
Clinton campaign spokesman Robby Mook was on one of the talk shows saying Clinton’s dreams of American open borders didn’t really mean open borders.
Mook said she meant open borders in the context of green energy for all.
Cool. But then what about her dreams of the hemispheric common market and all the people traveling to and fro across the Western Hemisphere?
So I’d like to hear Hillary Clinton tell it.
The way to deal with this would be for Clinton to release the transcripts of all her well-paid speeches, the ones to Wall Street and the one about border dreams to Banco Itau. That’s what Bernie Sanders wanted.
But that’s not happening, just like Donald Trump isn’t releasing his tax returns.
So the Clintonistas are blaming the Russians for the hacking.
It might also be true that if a hacker could hack into Clinton campaign emails, then a hacker might also have hacked into top secret emails she kept on her home brew server in violation of federal law when she was secretary of state.
But I won’t say anything, lest I be denounced as a Russian spy.
That WikiLeaks information was available just before the last Clinton-Trump debate. The moderators could have asked a question about it, but they chose not to.
They did ask about another drop from WikiLeaks, that of Clinton’s belief in holding one public position on policy for the public and another for private consideration by insiders.
Kind of like when she was secretary of state and telling America that the four dead Americans in Benghazi were killed by protesters angry about some video. And then telling her daughter and others, in private emails, that the four were killed in a terrorist attack.
In the debate, Clinton was asked if an official holding a private and a public position could be considered “two-faced.”
She said Abraham Lincoln did it. In a movie.
And now, rather than worry about divisive issues such as borders, we’re consumed by that vulgar Trump video.
Yet back when the Clintons held the White House, back when Bill used the cigar on that intern in the Oval Office, the political left protected him. And they defended Hillary for defending Bill, who had a habit of putting his hands on women when he held office.
Sex was a private matter then. It’s quite a public matter now. But then it was all a private matter, remember?
And so, after a brief bout of impeachment interruptus, the American political establishment welcomed Bill and Hillary back into the establishment fold, where wealth and near absolute power awaited them.
What’s laughable about all this is the Clintonista argument that to cleanse America of the stain of Trump, we must re-install Hillary and Bill back into the same White House that they soiled years ago.
I get all that.
Trump is a boor and Bill Clinton is a boor and Hillary is Hillary — either a loyal spouse or a cunning enabler. And politics is politics, so you’ll hate the one or forgive the other based on your preferences, or shout a pox upon them all.
But having an America with or without borders is also rather important, no?
And someone running for president might want to explain it all, in the proper context of course.
An America without borders? That’s not a dream, that’s a nightmare.
Ask the Europeans. They know.
The most frightening thing about the recent Wikileaks drop, which included excerpts of Hillary’s paid Wall St. speeches is her excitement over ending the United States as we know it.
Hillary is an extreme globalist.
She not only embraces the globalist mentality but she actually wants to end the U.S. as we know it and replace it with a “Hemispheric Government.”
No wonder Angela Merkel is her “favorite leader.”
Hillary wants to turn the United States into Germany – or worse.
LEO HOHMANN
The United Nations has cooked up a “New Urban Agenda” coming soon to a city near you.
It was unveiled this week in Quito, Ecuador, at the so-called Habitat III conference.
And part of the plan, enthusiastically embraced by Hillary Clinton, calls for unlimited migration across open borders. Migrants displaced by war, failing economies or other hardships will be seen as having “rights” in nations other than their own. Cities are seen as the key battlegrounds and the U.N. conference in Quito had a lot to say about how your city will be expected to embrace migrants of all types, from all regions of the world.
By now most Americans who follow world events are familiar with the U.N’s plan for global governance as envisioned by its “2030 Agenda for Sustainable Development,” approved by some 190 world leaders including President Obama and Pope Francis in September 2015.
This agenda includes 17 goals aimed at ending hunger, wiping out poverty and stamping out global income inequality by “transforming our world” through sweeping changes ostensibly aimed at freeing cross-border “labor mobility,” among other things.
Hillary Clinton, anointed by Obama as his successor, said in a speech to Wall Street bankers she envisions the U.S. as part of a single “hemispheric common market with free trade and open borders,” according to WikiLeaks data dumps.
In another bombshell revealed by WikiLeaks, Mrs. Clinton told Goldman Sachs bankers that Americans who want to limit immigration are “fundamentally un-American.” She has also called for a 550-percent increase in the resettlement of Syrian refugees in America – that’s 550 percent more than Obama’s vastly increased level of more than 12,000 resettled in one year.
In short, Hillary’s agenda for cities sounds an awful lot like the U.N.’s agenda for cities as laid out in the New Urban Agenda document approved this week by world leaders in Quito.
“She’s totally in line with the U.N. agenda, on board with everything they do,” says economist Patrick Wood, author of “Technocracy Rising: The Trojan Horse of Global Transformation.”
Clinton earlier this year announced her $135 billion “breaking every barrier” program to transform America’s cities.
In this plan, she makes 37 pledges promising everything from removal of blight to construction of affordable housing in areas that are currently out of the price range of refugees, immigrants, the chronically unemployed and under-employed. She intends to build on the “successes” of her husband and the Obama administration in using public-private partnerships to transform cities. Obama’s contribution in this area included his Affirmatively Furthering Fair Housing rule, which forces grant-receiving cities to infuse their low-crime suburban areas, deemed “too white,” with subsidized housing marketed to low-income renters.
This fits right in with the U.N.’s 2030 Agenda.
“She’s making a pre-announcement here that she’s going to follow the U.N. agenda,” Wood said. “She’s signaling to her fellow globalists that she’s 100 percent on board with their agenda.”
The problem that keeps globalists like Obama and Clinton up at night is how to implement the sweeping changes laid out in the U.N. 2030 Agenda last September at the global sustainability summit in New York.
That’s where Habitat III comes into play. It’s called the U.N. Conference on Housing and Sustainable Development or “Habitat III” for short. Its focus is on the world’s cities.
Largest U.N. conference ever
Habitat III was attended by a staggering 50,000 people including more than 200 mayors and another 140 city delegations
The sole purpose of this conference is to approve a 24-page document called the New Urban Agenda.
“The only purpose of the conference is to rubber stamp this document and elevate it and lift it up to the world,” said Wood. “And right now it looks like they are. Everybody. All the nations.”
In this document lies the globalists’ plans for cities. All cities. Big, small, even tiny cities. Every American who lives in a city will at some point see the fruits of the plan the U.N. has in store for the world, says Wood, an expert on global governance and the technocracy movement.
The Habitat conference convenes only once every 20 years but when it does, it leaves a trail of anti-capitalist, anti-liberty “global standards” in its wake, says Wood. These are the standards by which the U.N. wants each and every city in the world to be operated. They come packaged as “non-binding” and Congress never approves them.
Yet, somehow, the global standards coming out of the major U.N. conferences always seem to filter down to even the smallest American hamlet. How? Through federal grants. Any city that accepts federal grants will at some point be required to implement the practices that the U.N. has declared “sustainable.”
‘Inclusive’ by design, coercive by default
The buzzword in the New Urban Agenda is “inclusive” or “inclusivity.” This concept has a long history with global elites and technocrats.
The definition of “technocracy” as used by the original technocrats back 1938 was “the science of social engineering, the scientific operation of the entire social mechanism, to produce and distribute goods and services to the entire population.” That’s according to The Technocrat magazine.
“They use the word ‘entire’ twice in that definition so I’m really not surprised we see it showing up in these conferences today,” Wood said. “Their intent is to create a net that will catch 100 percent of the people.”
The word “inclusive” or “inclusivity” appear in the New Urban Agenda document no fewer than 36 times.
“There is no exclusion,” Wood says. “If you read the document, you’ll find for instance under item 6a, ‘transformative commitments,’ the statement starts out ‘leave no one behind.’”
That same phrase, leave no one behind, is in the U.N.’s 2030 Agenda.
“In fact just about everywhere you go now at the U.N. you’ll find this concept,” Wood said. “It’s a little disturbing.”
Wood says the U.N. is resurrecting an old concept that fizzled in the early days of the technocracy movement. Its time hadn’t arrived yet, back in the 1930s, but now things are different. The world is run by big data and the world is eager to embraced a set of globalized, one-world standards for everything, whether it be Common Core education standards, globalized police standards that Attorney General Loretta Lynch announced at the U.N. last fall in the form of the Strong Cities Network, or global standards for healthcare, ala Obamacare. You name it, the United Nations wants to standardize it.
The next big hurdle in the race to standardize the world is the issue of immigration.
Point 42 on page 7 of the New Urban Agenda talks about cities providing opportunities for dialogue, “paying particular attention to the potential contributions” of women and children, the elderly and disabled, “refugees and internally displaced persons and migrants, regardless of migration status, and without discrimination based on race, religion, ethnicity, or socio-economic status.”
Everyone is welcome
Wood notes that, in America, that would mean exactly what John Podesta, Clinton’s campaign manager, has already said — that anyone with a driver’s license should be allowed to vote.
“This is the way I read it,” he said. “It doesn’t matter if they’re legal or illegal, wanted or unwanted, jihadists or non-jihadists, sick or healthy. If they show up in your country, they must participate in the affairs of that country immediately, whatever country they find themselves in.”
The preamble to the New Urban Agenda says cities are the “key to tackling global challenges.”
“So these people are viewing cities as the key ingredient right now to implementing sustainable development, and they say this battle for sustainability will be won or lost in the cities.”
And the U.N. document goes on to state that this agenda is “the first step for operationalizing sustainable development in an integrated and coordinated way at the global, national, subnational, and local levels.”
In essence, it’s a roadmap to global governance where American cities will no longer get their direction from elected officials representing them on the city council, or even the state legislature, but the United Nations itself. The local councils will likely not even know that the rules they are following in order to qualify for federal grants are tied to United Nations’ standards for sustainability.
Cities committing to ‘a paradigm shift’
The document talks about cities committing to “a paradigm shift” in the way they “plan, develop and manage urban development.”
“It’s top to bottom,” Wood said. “They’re saying it’s going to be a top-down implementation. But for all the gains that sustainable development have made since 1992, there’s been a complaint that it hasn’t gone fast enough or far enough, and that it’s not inclusive enough, that some pockets have been left out. So, what they’re saying here is that this New Urban Agenda document is really, in their minds, the first step for operationalizing it. First step to making sustainable development completely operational. That’s huge.”
Wallace Henley, a journalist and former aide in the Nixon White House who went on to become a Christian pastor and who has written extensively on globalism, said the U.N. is making a full-on assault against the American system of government, which requires federalism, states’ rights and separation of powers.
“The U.N. is a glaring example of the inevitable course of bureaucracies. Like kudzu in Alabama, a tiny seed will inevitably spread until it controls the whole of a hillside,” Henley, author of “God and Churchhill,” told WND in an email.
And he, like Wood, sees Hillary Clinton in the thick of the battle, fighting on the side of the globalists, not America first.
“The leftist-progressive philosophy is the fertilizer. Agencies sprout and grow, and bring forth policy confabs like Habitat III. The conferences then produce white papers that ultimately become the source of policies,” he said. “It is a leftist-progressivist dream.”
“Sustainability” is a code word for regulatory authority, Henley said, and that is the suffocating vine that chokes out everything else.
“This meshes perfectly with the New Globalism and its dream of a world without borders. Anything can be done in the name of a ‘sustainable’ future, including the ‘humanitarian’ invasion of a sovereign state – but only if its leaders embrace the same left-progressive philosophy as the bureaucracies headquartered in New York. This makes a Hillary Clinton presidency even more foreboding,” he said.
And these “progressives” include many in the Republican Party who are now shilling for Clinton, such as House Speaker Paul Ryan and Arizona Sen. John McCain. Ryan, according to an article by Breitbart’s Julia Hahn, has been working hand in hand with the Clinton campaign for months.
“The true conservative seeks preservation of liberty-nurturing principles, and the sustenance of values that resist the control of the bureaucrats and guarantee freedom from a globalist hegemon in the form of the U.N.,” Henley said
Eric Voegelin’s 1975 book, “From Enlightenment to Revolution,” describes with amazing prescience the “line of progress” according to the revolutionaries who drive what Henley calls the New Globalism, from the local to the global, from the individual to the mass of humanity, from nation-states to a concentrated global power.
“This is the big picture of which Habitat III and its New Urban Agenda is a part.”
http://www.wnd.com/2016/10/u-n-goes-all-in-for-unlimited-migration/#jJfgd2IQ66VXRtIG.99
The future is urban and nowhere is that more true than in Bangladesh. If current rates of urbanisation continue, the country’s urban population will double by 2035. Around the Bay of Bengal, a mega city would join Dhaka to Chittagong, creating one of the world’s largest conglomerations. Whether that process produces a congested toxic unlivable mess of concrete and steel, or whether it becomes a thriving, connected, wonderful city to live in, is almost entirely down to the political and policy choices we make.
Photo: Star
This week a critical meeting in Quito, Ecuador, will look at those critical political and policy choices. The Habitat III conference to adopt a “New Urban Agenda” builds on the Habitat Agenda of Istanbul in 1996 (Habitat II).The new agenda is intended to reinvigorate the global commitment to sustainable urbanisation. The conference is expected to result in a concise, focused, forward-looking and action-oriented outcome document on making cities and human settlements equitable, prosperous, sustainable, just, equal and safe until 2030. By the middle of the century, a majority of the world’s citizens —four out of five people — could be living in towns or cities. Indeed, in the time since the Habitat Agenda was adopted, the world has become majority urban, lending extra urgency to the New Urban Agenda.
Habitat III is one of the first major global conferences to be held after the adoption of two key agreements, last year. Agenda 2030, a new development plan for the world; and a new Climate Change agreement adopted in Paris. It offers a unique opportunity to discuss the important challenge of how cities, towns and villages are planned and managed in a sustainable manner, to meet the new global agenda and climate change goals.
The New Urban Agenda, agreed upon at Habitat III in Quito, will guide the efforts around urbanisation of a wide range of actors — nation states, city and regional leaders, international development funders, UN programmes and civil society — for the next 20 years. Inevitably, this agenda will also lay the groundwork for policies and approaches that will have long lasting impact.
HABITAT I and II
Forty years later, after both Habitat I and II, there is wide consensus that towns’ and cities’ structure, form, and functionality need to change as societies change. Especially, slums and related informal settlements that have become a spontaneous form of urbanisation, consisting of a series of survival strategies by the urban poor, most borne out of poverty and exclusion.
Habitat III represents an opportunity to make concrete the ideals of Habitat II in designing policies, planning urban spaces for all, and providing affordable urban services and utilities through adopting a ‘New Urban Agenda’ this October.
Towards the New Urban Agenda
The core issues of the Habitat II Agenda — adequate housing and sustainable human settlements — remain on the table, as the number of people worldwide living in urban slums continues to grow. There is also an increasing recognition that cities have morphed into mega-regions, urban corridors and city-regions whose economic, social and political geographies defy traditional conceptions of the “city”.
Impact of the agenda
The Agenda will seek to create a mutually reinforcing relationship between urbanisation and development. Several core ideas form the ideological underpinnings of the New Urban Agenda. Democratic development and respect for human rights feature prominently in the draft agreements, as does the relationship between the environment and urbanisation.
The new agenda also places importance on establishing a global monitoring mechanism to track progress on meeting commitments. As an “agenda”, it will provide guidance to nation states, city and regional authorities, civil society, foundations, NGOs, academic researchers and UN agencies. However, this guidance is not binding. This arrangement is different from, for example, the December 2015 climate negotiations in Paris, which resulted in a legally binding agreement.
Let’s take a practical example. The new urban agenda calls for mass transit systems and to cut back our dependence on vehicles. In recent years in Dhaka, our response to traffic congestion has been to build flyovers. This has been compared to an overweight person addressing the need to lose weight by loosening their belt. You feel better at first, but it doesn’t last. The underlying issues are not addressed. The government recently broke ground on metro rail link between Uttara and the airport. With policy choices like this, we can move Dhaka to the fore of the New Urban Agenda.
The New Urban Agenda and Bangladesh
A broad range of actors in Bangladesh were involved in contributing to developing the New Urban Agenda. The Government of Bangladesh, through the Ministry of Housing and Public Works, is engaged in both the Habitat III conference and related academic discussions through various national and international forums.
It is estimated that 60 percent of Bangladesh’s GDP is produced in urban areas. Having laid out an urban vision in the 7th Five-year Plan as “compact, networked, resilient, competitive, and inclusive and smart,” Bangladesh still has considerable work ahead to meet international goals set by the New Urban Agenda. Certainly, in Bangladesh the stakes are high, since it is the third most urbanised nation in South Asia.
The ‘new urban agenda’ will clearly influence policymakers as they consider cities, urbanisation and sustainable development, and set priorities at the national levels. With the global perspectives on managing urbanisation for making cities and human settlements equitable, prosperous, sustainable, just, equal and safe, Bangladesh can finalise the long awaited national urban sector policy. And it can begin drafting a ‘New Urban Agenda’ to tackle the country’s rapid urbanisation in order to maximise the benefits of urbanisation for the people of Bangladesh.
The writers are Acting Country Director of UNDP Bangladesh and Urban Programme Specialist of UNDP Bangladesh.
http://www.ipsnews.net/2016/10/the-new-urban-agenda-what-our-cities-can-be/
This article is part of the United Nations University’s Habitat III series featuring research and commentary related to the UN Conference on Housing and Sustainable Urban Development, 17–20 October 2016 in Quito, Ecuador.
•••
For the first time in history, a majority of the global population lives in cities. The trend toward urbanisation is continuing, and by mid-century city dwellers are expected to account for two-thirds of the world’s people. Migration accounts for a significant, yet often controversial, part of this urban development. Twenty years ago at the Habitat II conference in Istanbul, urban migration was framed as a problem to be tackled. The focus at the time was on addressing the root causes of rural-to-urban migration and finding ways to minimise population movement to cities. As such, Habitat II did not go far enough to emphasise the positive contributions migrants make to urban life.
The legacy of this framing of urban migration has had lasting impacts that have reinforced the socio-economic and spatial marginalisation of migrants (and subsequent generations) in a number of cities, from Paris to Delhi. In the preparations for Habitat III, to be held in Quito from 17–20 October 2016, an issue paper on migrants and refugees points out that “the generic urbanisation model” over the past decades has “fostered segregation over integration”.
The adoption of the New Urban Agenda in Quito will bring in a new narrative on urban migration that centres on promoting migrants’ inclusion in cities and upholding their rights. States, local authorities, intergovernmental and civil society organisations can use this opportunity to collectively develop urban policies that reflect this narrative. More than half of the world’s population now lives in urban areas, and continuing migration is central to urbanisation processes — both in terms of internal migration (movement within the same country) and of international migration (be it voluntary or forced, bearing in mind that the line between the two is increasingly blurred).
“Migration is clearly an urban phenomenon, and especially so in this time of unprecedented global displacement.”
As the above issue paper notes, some 60% of the world’s refugees (and 80% of internally displaced persons) now live in urban areas rather than in camps. Cities, large and small, are where migrants seek to build their livelihoods, futures, and networks, pursue opportunities, and realise their aspirations.
Migration is thus very clearly an urban phenomenon, and especially so in this time of unprecedented global displacement. Even as states reinforce their borders, with security, fences, and walls, cities are opening themselves up to new arrivals. This is why the New Urban Agenda is so relevant to the global debates that are taking place about migration.
Where states are failing to honour the rights and dignity of migrants and refugees, cities in many parts of the world are acting in concrete ways to receive them, provide them with basic services, and find ways to include them in the everyday fabric of the city (including those without documents). This effort offers potential to transform the discourse and politics of migration by recognising the rich social, cultural, and economic contributions of migrants to urban life, while allowing us to imagine the possibilities for migrants to feel a sense of belonging at an urban level.
In New York City, for example, all migrants — regardless of their status — are eligible for an IDNYC (identification card) giving them access to many services in the city. The municipality of Sao Paulo, meanwhile, has created a municipal migration policy developed in accordance with the principles of human rights and non-discrimination, and drawing upon the voices of migrants through participative consultations. And cities in Germany are making novel uses of urban space and infrastructure to house recent arrivals of migrants and refugees, while volunteer-led projects among urban citizenshave emerged over the past year to foster a culture of welcome that, if cultivated in the long term, can lead to sustained forms of inclusion.
“We must also be aware that not all cities are powerful actors with the freedom to make and implement decisions.”
But lest we romanticise this ideal of welcoming cities, it is important to acknowledge that significant challenges remain for migrants in a number of cities: precarious work; language barriers; difficulties in accessing health, education, and justice; poor environmental health conditions and insecure housing; and discrimination.
We must also be aware that not all cities are powerful actors with the freedom to make and implement decisions. Some municipal governments remain poorly resourced and depend upon restrictive state-level policy directives — the experiences of urban refugees in Bangkok who live in a state of limbo and invisibility is a case in point. This is a reminder of the importance of multi-level governance that connects the grassroots and local levels to the national, regional, and global levels. If migration is well-managed throughout all levels, migrants are more likely to have the resources to sustain their livelihoods and the opportunities to make valuable, enduring, and creative contributions.
The New Urban Agenda is grounded in the Universal Declaration of Human Rights, and the need to take a human rights-based approach to migration has thus been recognised, far more than in the past. The draft Agenda includes commitments to support refugees, internally displaced persons, and migrants regardless of their migration status. Yet if the New Urban Agenda is based on a vision of “cities for all”, we need further clarity as to how these lofty statements will translate into practical and implementable projects and policies for social and spatial inclusion that take migration and displacement into consideration.
On this point, the New Urban Agenda remains vague. The points raised during the urban dialogues and thematic consultations in the run-up to Habitat III, which are intended to gather input from diverse stakeholders and citizens in the shaping of the Agenda, call on local and national authorities to include migration as a transversal feature of urban planning, and to promote the civic participation of migrants across urban spaces and institutions.
Indeed, we should see Habitat III as the starting point for developing and implementing inclusive policies and the sharing of good practices on these issues. In this particular moment of time — when the world’s attention is fixed on migration — it is vital that we shape our cities to be inclusive, convivial, and progressive places that embrace cultural pluralism and diversity as a hallmark of sustainable urban development.
“Power tends to corrupt, and absolute power corrupts absolutely. .”
~John Emerich Edward Dalberg-Acton, 1st Baron Acton
~
Isn’t it rich?
Are we a pair?
Me here at last on the ground,
You in mid-air..
Where are the clowns?
Isn’t it bliss?
Don’t you approve?
One who keeps tearing around,
One who can’t move…
Where are the clowns?
Send in the clowns.
Just when I’d stopped opening doors,
Finally knowing the one that I wanted was yours.
Making my entrance again with my usual flair
Sure of my lines…
No one is there.
Don’t you love farce?
My fault, I fear.
I thought that you’d want what I want…
Sorry, my dear!
And where are the clowns
Send in the clowns
Don’t bother, they’re here.
Isn’t it rich?
Isn’t it queer?
Losing my timing this late in my career.
And where are the clowns?
There ought to be clowns…
Well, maybe next year.
Hillary Clinton’s medical history – and her tendency to keep personal and medical information far from view – is coming in for new scrutiny following revelations that the candidate got diagnosed with pneumonia Friday in advance of her stumble in New York.
Clinton’s stumble, caught on camera Sunday after she had to leave Sept. 11th anniversary memorial services after about an hour and a half, was the latest in a line of health spats that have made it into the news during her career.
‘Antibiotics can take care of pneumonia. What’s the cure for an unhealthy penchant for privacy that repeatedly creates unnecessary problems?’ asked President Obama’s former message guru David Axelrod in a tweet Monday – a message promptly retweeted by Trump‘s campaign manager Kellyanne Conway.
Below is a compilation of Clinton’s ailments and health incidents that have entered the public record:
Clinton’s medical history – and her tendency to keep personal and medical information far from view – is coming in for new scrutiny following revelations that the candidate got diagnosed with pneumonia Friday
Hillary’s dramatic collapse in New York on Sunday is prompting new examination of her health – as well as how her aides have closely guarded information
1998 Blood Clot
Clinton’s first known blood clot occurred in 1998, while she was still first lady.
Clinton experienced symptoms while attending a fundraiser for Sen. Charles Schumer of New York, who would soon become her Senate home-state colleague. Her right foot swelled up to the point where she couldn’t put on her shoe.
Clinton got quietly taken to the National Naval Medical Center in Bethesda for treatment at the time. She was found to have ‘a big clot’ blood clot behind her knee, Clinton wrote in her memoir, ‘Living History.’
She called it ‘the most significant health scare I’ve ever had,’ the Washington Post noted.
According to her physician, Mt. Kisco physician, Lisa Bardack, Clinton was advised at the time to take Lovenox, described as a short-acting blood thinner, when she took flights. The meds were discontinued when she went on Coumadin.
2009 Blood Clot
Clinton had a second blood clot incident in 2009. The episode was described by her doctor in a 2015 letter.
The doctor didn’t provide a detailed description of the event. Rather, she wrote that Clinton’s ‘past medical history is notable for a deep vein thrombosis in 1998, 2009 and a concussion in 2012.
Clinton takes a daily blood thinning medication for her deep vein thrombosis.
Clinton, a frequent flier whose staff catalogued her pursuit of the overall mileage record as secretary of state, may have exacerbated the problem through her extensive air travel.
Frequent jet travel can exacerbate blood clots, which is why some people make sure to walk around the cabin on long flights
2009 Elbow Fracture
Clinton had to work from home for a while after she fractured her elbow during a fall in 2009, CNN recounted. She fell at the State Department on the way to the White House, and went to George Washington University hospital for treatment.
She underwent a two-hour surgical procedure.
‘She is working from home. She is already taking some calls, and I’m sure starting to learn the limits of movement – how well you can text with one arm in a sling,’ quipped then spokesman P.J. Crowley at the time, in an early reference to Clinton’s communications habits.
Clinton was pictured wearing a sling emblazoned with the seal of the State Department when she returned to work. She also was photographed providing left-handed hand shake with a visiting Palestinian dignitary owing to her condition. She has showed no visible signs of lingering problems related to the injury.
HARD KNOCKS: Clinton got a fractured elbow in 2009, but still managed to negotiate with Hondouran leaders, and, according to her spokesman, text with one hand
2012 Blood Clot and Concussion
Clinton got a bad stomach bug and fainted at her home in Washington in 2012, an event that led her to get a concussion. Information about what exactly had happened emerged only slowly over time.
As her doctor put it, ‘In December 2012, Mrs. Clinton suffered a stomach virus after traveling, became dehydrated, fainted and sustained a concussion.’
The then-secretary of state wasn’t seen in public between Dec. 7th and when she left the hospital in New York January 2, 2013.
Clinton experienced ‘double vision for a period of time and benefited from wearing glasses with a Fresnel Prism,’ a special corrective lens, her doctor wrote in a letter voluntarily released to the media in 2015 as part of Clinton’s presidential campaign. Her concussion ‘resolved within two months,’ Bardack wrote.
In 2014, Bill Clinton revealed that the injury ‘required six months of very serious work to get over.’ The former president called it a ‘terrible concussion’
Clinton was diagnosed with a blood clot in the brain, transverse sinus venous thrombosis, and began anticoagulation therapy, her doctor wrote.
Clinton had to work from home and postpone planned testimony before a House Benghazi committee.
Clinton leaves New York Presbyterian Hospital with husband Bill and daughter Chelsea on January 2, 2013. The secretary of state, had not been seen in public since Dec. 7
Hypothyroidism
Clinton also suffers from Hypothyroidismrefers to an under-active thyroid gland, resulting in a lack of important hormones.
Clinton’s doctor identified the condition in her 2015 letter, but did not state for how long Clinton has suffered from the condition. She takes a medication called Armour Thyroid.
Allergies
Clinton suffers from ‘seasonal allergies,’ according to her physician. It isn’t known for how long she has suffered from allergies, although Clinton herself has cited her allergies when she has developed a cough – including on-stage during public events.
Her doctor states that Clinton is taking antihistamines, which treat the effects of allergies.
2016 Collapse and Pneumonia Diagnosis
Clinton had to leave a Sept. 11th service in New York early after spending 90 minutes at the ceremony. Her staff first cited heat and exhaustion, then ultimately revealed that Clinton had been diagnosed in pneumonia on Friday.
Clinton campaign spokesman Brian Fallon did not reveal what type of pneumonia Clinton has during a Monday interview on MSNBC, but said Clinton would be putting out more medical information.
‘She was put on antibiotics and advised to rest and modify her schedule,’ said Bardack in a statement released at the end of the day. While attending the event, ‘she became overheated and dehydrated. I have just examined her and she is now re-hydrated and recovering nicely.’
Hours after Clinton was taken away from the Sept. 11th ceremony, her office released a doctor’s statement. ‘Secretary Clinton has been experiencing a cough related to allergies. On Friday, during follow-up evaluation of her prolonged cough, she was diagnosed with pneumonia. She was put on antibiotics, and advised to rest and modify her schedule. While at this morning’s event, she became overheated and dehydrated. I have just examined her and she is now rehydrated and recovering nicely,’ Clinton’s doctor, Lisa Bardack, said in a written statement Sunday.’
‘There’s no other undisclosed condition. The pneumonia is the extent of it,’ Clinton campaign spokesman Brian Fallon told MSNBC.
Fallon also acknowledged: ‘I think in retrospect we could have handled it better in terms of providing more information more quickly.’
Campaign manager Robby Mook, speaking of the 90 minute delay before the press was told Clinton’s status after she left the New York event, said Monday: ‘We wish that that had been a lot shorter and that’s on us.’
Clinton herself tweeted Monday: ‘Thanks to everyone who’s reached out with well wishes! I’m feeling fine and getting better,’ signing the missive with the letter ‘H.’
Clinton had to shake with her left hand following her 2009 injury. She is pictured here with Palestinian Authority Salam Fayyad
Clinton campaigned in New York in June along with aide Huma Abedin. She was diagnosed with pneumonia Friday, according to her office
Clinton is 68 and would be 69 when she assumed office, second to Ronald Reagan in age taking office. Donald Trump is 70, and has released few details about his medical background.
‘She participates in a healthy lifestyle and has had a full medical evaluation, which reveals no evidence of additional medical issues or cardiovascular disease. Her cancer screening evaluations are all negative. She is in excellent physical condition and fit to serve as President of the United States,’ her doctor wrote.
The letter released by Clinton’s physician details her 2012 concussion and double vision
Clinton was a ‘healthy-appearing female’ during her last examination, according to Dr. Lisa Bardack
| Parkinson’s disease | |
|---|---|
| idiopathic or primary parkinsonism, hypokinetic rigid syndrome, paralysis agitans | |
.png)
Illustration of Parkinson’s disease by William Richard Gowers, which was first published in A Manual of Diseases of the Nervous System (1886)
|
|
| Classification and external resources | |
| Specialty | Neurology |
| ICD–10 | G20, F02.3 |
| ICD–9-CM | 332 |
| OMIM | 168600556500 |
| DiseasesDB | 9651 |
| MedlinePlus | 000755 |
| eMedicine | neuro/304neuro/635 in young pmr/99 rehab |
| MeSH | D010300 |
| GeneReviews | |
Parkinson’s disease (PD) is a long term disorder of the central nervous system that mainly affects the motor system.[1] The symptoms generally come on slowly over time. Early in the disease, the most obvious are shaking, rigidity, slowness of movement, and difficulty with walking.[1]Thinking and behavioral problems may also occur.Dementia becomes common in the advanced stages of the disease. Depression and anxiety are also common occurring in more than a third of people with PD.[2] Other symptoms include sensory, sleep, and emotional problems.[1][2] The main motor symptoms are collectively called “parkinsonism“, or a “parkinsonian syndrome”.[3][4]
The cause of Parkinson’s disease is generally unknown, but believed to involve both genetic and environmental factors. Those with a family member affected are more likely to get the disease themselves[4] There is also an increased risk in people exposed to certain pesticides and among those who have had prior head injuries while there is a reduced risk in tobacco smokers and those who drink coffee or tea.[4][5] The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain. This results in not enough dopamine in these areas.[1] The reason for this cell death is poorly understood but involves the build-up ofproteins into Lewy bodies in the neurons.[4] Diagnosis of typical cases is mainly based on symptoms, with tests such as neuroimaging being used to rule out other diseases.[1]
There is no cure for Parkinson’s disease.[1] Initial treatments is typically with the antiparkinson medicationlevodopa, with dopamine agonists being used once levodopa becomes less effective. As the disease progresses and neurons continue to be lost, these medications become less effective while at the same time they produce acomplication marked by involuntary writhing movements.[2] Diet and some forms of rehabilitation have shown some effectiveness at improving symptoms.[6][7]Surgery to place the microelectrodes for deep brain stimulation has been used to reduce motor symptoms in severe cases where drugs are ineffective.[1] Evidence for treatments for the non-movement-related symptoms of PD, such as sleep disturbances and emotional problems, is less strong.[4]
In 2013 PD was present in 53 million people and resulted in about 103,000 deaths globally.[8][9] Parkinson’s disease typically occurs in people over the age of 60, of which about one percent are affected.[1][10] Males are more often affected than females.[4] When it is seen in people before the age of 40 or 50, it is called young onset PD.[11] The average life expectancy following diagnosis is between 7 and 14 years.[2] The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy, in 1817.[12][13] Public awareness campaigns include World Parkinson’s Day (on the birthday of James Parkinson, 11 April) and the use of a red tulip as the symbol of the disease.[14] People with parkinsonism who have increased the public’s awareness of the condition include actor Michael J. Fox, Olympic cyclist Davis Phinney, and late professional boxer Muhammad Ali.[15][16][17]
The term parkinsonism is used for a motor syndrome whose main symptoms are tremor at rest, stiffness, slowing of movement and postural instability. Parkinsonian syndromes can be divided into four subtypes, according to their origin:
Parkinson’s disease is the most common form of parkinsonism and is usually defined as “primary” parkinsonism, meaning parkinsonism with no external identifiable cause.[19][20] In recent years several genes that are directly related to some cases of Parkinson’s disease have been discovered. As much as this conflicts with the definition of Parkinson’s disease as an idiopathic illness, genetic parkinsonism disorders with a similar clinical course to PD are generally included under the Parkinson’s disease label. The terms “familial Parkinson’s disease” and “sporadic Parkinson’s disease” can be used to differentiate genetic from truly idiopathic forms of the disease.[21]
Usually classified as a movement disorder, PD also gives rise to several non-motor types of symptoms such as sensory deficits,[22] cognitive difficulties, and sleep problems. Parkinson plus diseases are primary parkinsonisms which present additional features.[19] They include multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies.[19][23]
In terms of pathophysiology, PD is considered a synucleiopathy due to an abnormal accumulation of alpha-synuclein protein in the brain in the form of Lewy bodies, as opposed to other diseases such as Alzheimer’s disease where the brain accumulates tau protein in the form of neurofibrillary tangles.[24] Nevertheless, there is clinical and pathological overlap between tauopathies and synucleinopathies. The most typical symptom of Alzheimer’s disease, dementia, occurs in advanced stages of PD, while it is common to find neurofibrillary tangles in brains affected by PD.[24]
Dementia with Lewy bodies (DLB) is another synucleinopathy that has similarities with PD, and especially with the subset of PD cases with dementia. However, the relationship between PD and DLB is complex and still has to be clarified.[25] They may represent parts of a continuum or they may be separate diseases.[25]
Parkinson’s disease affects movement, producing motor symptoms.[18] Non-motor symptoms, which include autonomic dysfunction, neuropsychiatric problems (mood, cognition, behavior or thought alterations), and sensory and sleep difficulties, are also common. Some of these non-motor symptoms are often present at the time of diagnosis and can precede motor symptoms.[18]
Four motor symptoms are considered cardinal in PD: tremor, rigidity, slowness of movement, and postural instability.[18]
Tremor is the most apparent and well-known symptom.[18] It is the most common; though around 30% of individuals with PD do not have tremor at disease onset, most develop it as the disease progresses.[18] It is usually a rest tremor: maximal when the limb is at rest and disappearing with voluntary movement and sleep.[18] It affects to a greater extent the most distal part of the limb and at onset typically appears in only a single arm or leg, becoming bilateral later.[18] Frequency of PD tremor is between 4 and 6 hertz (cycles per second). A feature of tremor is pill-rolling, the tendency of the index finger of the hand to get into contact with the thumb and perform together a circular movement.[18][28]The term derives from the similarity between the movement of people with PD and the earlier pharmaceutical technique of manually making pills.[28]
Hypokinesia (slowness of movement) is another characteristic feature of PD, and is associated with difficulties along the whole course of the movement process, from planning to initiation and finally execution of a movement.[18] Performance of sequential and simultaneous movement is hindered.[18] Bradykinesia is commonly a very disabling symptom in the early stages of the disease.[19] Initial manifestations are problems when performing daily tasks which require fine motor control such as writing, sewing or getting dressed.[18] Clinical evaluation is based on similar tasks such as alternating movements between both hands or both feet.[19] Bradykinesia is not equal for all movements or times. It is modified by the activity or emotional state of the subject, to the point that some people are barely able to walk yet can still ride a bicycle.[18] Generally people with PD have less difficulty when some sort of external cue is provided.[18][29]
Rigidity is stiffness and resistance to limb movement caused by increased muscle tone, an excessive and continuous contraction of muscles.[18] In parkinsonism the rigidity can be uniform (lead-pipe rigidity) or ratchety (cogwheel rigidity).[18][19][30][31] The combination of tremor and increased tone is considered to be at the origin of cogwheel rigidity.[32]Rigidity may be associated with joint pain; such pain being a frequent initial manifestation of the disease.[18] In early stages of Parkinson’s disease, rigidity is often asymmetrical and it tends to affect the neck and shoulder muscles prior to the muscles of the face and extremities.[33] With the progression of the disease, rigidity typically affects the whole body and reduces the ability to move.
Postural instability is typical in the late stages of the disease, leading to impaired balance and frequent falls,[34] and secondarily to bone fractures.[18] Instability is often absent in the initial stages, especially in younger people.[19] Up to 40% may experience falls and around 10% may have falls weekly, with the number of falls being related to the severity of PD.[18]
Other recognized motor signs and symptoms include gait and posture disturbances such as festination (rapid shuffling steps and a forward-flexed posture when walking),[18] speech and swallowing disturbances including voice disorders,[35]mask-like face expression or small handwriting, although the range of possible motor problems that can appear is large.[18]
Parkinson’s disease can cause neuropsychiatric disturbances which can range from mild to severe. This includes disorders of speech, cognition, mood, behaviour, and thought.[18]
Cognitive disturbances can occur in the early stages of the disease and sometimes prior to diagnosis, and increase in prevalence with duration of the disease.[18][36] The most common cognitive deficit in affected individuals is executive dysfunction, which can include problems with planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, working memory, and selecting relevant sensory information.[36][37] Fluctuations in attention, impaired perception and estimation of time, slowed cognitive processing speed are among other cognitive difficulties.[36][37] Memory is affected, specifically in recalling learned information.[36] Nevertheless, improvement appears when recall is aided by cues.[36] Visuospatial difficulties are also part of the disease, seen for example when the individual is asked to perform tests of facial recognition and perception of the orientation of drawn lines.[36][37]
A person with PD has two to six times the risk of dementia compared to the general population.[18][36] The prevalence of dementia increases with duration of the disease.[36] Dementia is associated with a reducedquality of life in people with PD and their caregivers, increased mortality, and a higher probability of needing nursing home care.[36]
Behavior and mood alterations are more common in PD without cognitive impairment than in the general population, and are usually present in PD with dementia. The most frequent mood difficulties are depression,apathy and anxiety.[18] Establishing the diagnosis of depression is complicated by symptoms that often occur in Parkinson’s including dementia, decreased facial expression, decreased movement, a state of indifference, and quiet speech.[38]Impulse control behaviors such as medication overuse and craving, binge eating, hypersexuality, or pathological gambling can appear in PD and have been related to the medications used to manage the disease.[18][39]Psychotic symptoms—hallucinations or delusions—occur in 4% of people with PD, and it is assumed that the main precipitant of psychotic phenomena in Parkinson’s disease is dopaminergic excess secondary to treatment; it therefore becomes more common with increasing age and levodopa intake.[40][41]
In addition to cognitive and motor symptoms, PD can impair other body functions.
Sleep problems are a feature of the disease and can be worsened by medications.[18] Symptoms can manifest as daytime drowsiness, disturbances in REM sleep, or insomnia.[18] A systematic review shows that sleep attacks occur in 13.0% of patients with Parkinson’s disease on dopaminergic medications.[42]
Alterations in the autonomic nervous system can lead to orthostatic hypotension (low blood pressure upon standing), oily skin and excessive sweating, urinary incontinence and altered sexual function.[18]Constipationand gastric dysmotility can be severe enough to cause discomfort and even endanger health.[6] PD is related to several eye and vision abnormalities such as decreased blink rate, dry eyes, deficient ocular pursuit(eye tracking) and saccadic movements (fast automatic movements of both eyes in the same direction), difficulties in directing gaze upward, and blurred or double vision.[18][43] Changes in perception may include an impaired sense of smell, sensation of pain and paresthesia (skin tingling and numbness).[18] All of these symptoms can occur years before diagnosis of the disease.[18]
Parkinson’s disease in most people is idiopathic (having no specific known cause). However, a small proportion of cases can be attributed to known genetic factors. Other factors have been associated with the risk of developing PD, but no causal relationships have been proven.
A number of environmental factors have been associated with an increased risk of Parkinson’s including: pesticide exposure, head injuries, and living in the country or farming.[44][45] Rural environments and the drinking of well water may be risks as they are indirect measures of exposure to pesticides.[46][47]
Implicated agents include insecticides, primarily chlorpyrifos and organochlorines[48] and pesticides, such as rotenone or paraquat, and herbicides, such as Agent Orange andziram.[46][47][49][50]Heavy metals exposure has been proposed to be a risk factor, through possible accumulation in the substantia nigra; however, studies on the issue have been inconclusive.[46]
PD traditionally has been considered a non-genetic disorder; however, around 15% of individuals with PD have a first-degree relative who has the disease.[19] At least 5% of people are now known to have forms of the disease that occur because of a mutation of one of several specific genes.[51]
Mutations in specific genes have been conclusively shown to cause PD. These genes code for alpha-synuclein (SNCA), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or dardarin), PTEN-induced putative kinase 1 (PINK1), DJ-1 and ATP13A2.[21][51] In most cases, people with these mutations will develop PD. With the exception of LRRK2, however, they account for only a small minority of cases of PD.[21] The most extensively studied PD-related genes are SNCA and LRRK2. Mutations in genes including SNCA, LRRK2 and glucocerebrosidase (GBA) have been found to be risk factors for sporadic PD. Mutations in GBA are known to cause Gaucher’s disease.[51]Genome-wide association studies, which search for mutated alleles with low penetrance in sporadic cases, have now yielded many positive results.[52]
The role of the SNCA gene is important in PD because the alpha-synuclein protein is the main component of Lewy bodies.[51]Missense mutations of the gene (in which a singlenucleotide is changed), and duplications and triplications of the locus containing it have been found in different groups with familial PD.[51] Missense mutations are rare.[51] On the other hand, multiplications of the SNCA locus account for around 2% of familial cases.[51] Multiplications have been found in asymptomatic carriers, which indicate that penetrance is incomplete or age-dependent.[51]
The LRRK2 gene (PARK8) encodes a protein called dardarin. The name dardarin was taken from a Basque word for tremor, because this gene was first identified in families from England and the north of Spain.[21]Mutations in LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases.[21][51] There are many mutations described in LRRK2, however unequivocal proof of causation only exists for a few.[51]
Several Parkinson-related genes are involved in the function of lysosomes, organelles that digest cellular waste products. It has been suggested that some forms of Parkinson may be caused by lysosome dysfunctions that reduce the ability of cells to break down alpha-synuclein.[53]
The basal ganglia, a group of brain structures innervated by the dopaminergic system, are the most seriously affected brain areas in PD.[54] The main pathologicalcharacteristic of PD is cell death in the substantia nigra and, more specifically, the ventral (front) part of the pars compacta, affecting up to 70% of the cells by the time death occurs.[21]
Macroscopic alterations can be noticed on cut surfaces of the brainstem, where neuronal loss can be inferred from a reduction of neuromelanin pigmentation in the substantia nigra and locus coeruleus.[55] The histopathology (microscopic anatomy) of the substantia nigra and several other brain regions shows neuronal loss and Lewy bodies in many of the remaining nerve cells. Neuronal loss is accompanied by death of astrocytes (star-shaped glial cells) and activation of the microglia (another type of glial cell). Lewy bodies are a key pathological feature of PD.[55]
The primary symptoms of Parkinson’s disease result from greatly reduced activity of dopamine-secreting cells caused by cell death in the pars compacta region of thesubstantia nigra.[54]
There are five major pathways in the brain connecting other brain areas with the basal ganglia. These are known as the motor, oculo-motor, associative, limbic and orbitofrontalcircuits, with names indicating the main projection area of each circuit.[54] All of them are affected in PD, and their disruption explains many of the symptoms of the disease since these circuits are involved in a wide variety of functions including movement, attention and learning.[54] Scientifically, the motor circuit has been examined the most intensively.[54]
A particular conceptual model of the motor circuit and its alteration with PD has been of great influence since 1980, although some limitations have been pointed out which have led to modifications.[54] In this model, the basal ganglia normally exert a constant inhibitory influence on a wide range of motor systems, preventing them from becoming active at inappropriate times. When a decision is made to perform a particular action, inhibition is reduced for the required motor system, thereby releasing it for activation. Dopamine acts to facilitate this release of inhibition, so high levels of dopamine function tend to promote motor activity, while low levels of dopamine function, such as occur in PD, demand greater exertions of effort for any given movement. Thus, the net effect of dopamine depletion is to produce hypokinesia, an overall reduction in motor output.[54] Drugs that are used to treat PD, conversely, may produce excessive dopamine activity, allowing motor systems to be activated at inappropriate times and thereby producing dyskinesias.[54]
There is speculation of several mechanisms by which the brain cells could be lost.[57] One mechanism consists of an abnormal accumulation of the protein alpha-synucleinbound to ubiquitin in the damaged cells. This insoluble protein accumulates inside neurones forming inclusions called Lewy bodies.[21][58] According to the Braak staging, a classification of the disease based on pathological findings, Lewy bodies first appear in the olfactory bulb, medulla oblongata and pontine tegmentum, with individuals at this stage being asymptomatic. As the disease progresses, Lewy bodies later develop in the substantia nigra, areas of the midbrain and basal forebrain, and in a last step theneocortex.[21] These brain sites are the main places of neuronal degeneration in PD; however, Lewy bodies may not cause cell death and they may be protective.[57][58] In people with dementia, a generalized presence of Lewy bodies is common in cortical areas. Neurofibrillary tangles and senile plaques, characteristic of Alzheimer’s disease, are not common unless the person is demented.[55]
Other cell-death mechanisms include proteosomal and lysosomal system dysfunction and reduced mitochondrial activity.[57] Iron accumulation in the substantia nigra is typically observed in conjunction with the protein inclusions. It may be related to oxidative stress, protein aggregation and neuronal death, but the mechanisms are not fully understood.[59]
A physician will diagnose Parkinson’s disease from the medical history and a neurological examination.[18] There is no lab test that will clearly identify the disease, but brain scans are sometimes used to rule out disorders that could give rise to similar symptoms. People may be given levodopa and resulting relief of motor impairment tends to confirm the diagnosis. The finding of Lewy bodies in the midbrain on autopsy is usually considered proof that the person had Parkinson’s disease. The progress of the illness over time may reveal it is not Parkinson’s disease, and some authorities recommend that the diagnosis should be periodically reviewed.[18][60]
Other causes that can secondarily produce a parkinsonian syndrome are Alzheimer’s disease, multiple cerebral infarction and drug-induced parkinsonism.[60]Parkinson plus syndromessuch as progressive supranuclear palsy and multiple system atrophy must be ruled out.[18] Anti-Parkinson’s medications are typically less effective at controlling symptoms in Parkinson plus syndromes.[18] Faster progression rates, early cognitive dysfunction or postural instability, minimal tremor or symmetry at onset may indicate a Parkinson plus disease rather than PD itself.[61] Genetic forms are usually classified as PD, although the terms familial Parkinson’s disease and familial parkinsonism are used for disease entities with an autosomal dominant or recessive pattern of inheritance.[19]
Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process, especially in the early stages of the disease. The most widely known criteria come from the UK Parkinson’s Disease Society Brain Bank and the U.S. National Institute of Neurological Disorders and Stroke.[18] The PD Society Brain Bank criteria require slowness of movement (bradykinesia) plus either rigidity, resting tremor, or postural instability. Other possible causes of these symptoms need to be ruled out. Finally, three or more of the following features are required during onset or evolution: unilateral onset, tremor at rest, progression in time, asymmetry of motor symptoms, response to levodopa for at least five years, clinical course of at least ten years and appearance of dyskinesias induced by the intake of excessive levodopa.[18]Accuracy of diagnostic criteria evaluated at autopsy is 75–90%, with specialists such as neurologists having the highest rates.[18]
Computed tomography (CT) and conventional magnetic resonance imaging (MRI) brain scans of people with PD usually appear normal.[62] These techniques are nevertheless useful to rule out other diseases that can be secondary causes of parkinsonism, such as basal ganglia tumors, vascular pathology and hydrocephalus.[62] A specific technique of MRI, diffusion MRI, has been reported to be useful at discriminating between typical and atypical parkinsonism, although its exact diagnostic value is still under investigation.[62] Dopaminergic function in the basal ganglia can be measured with different PET and SPECTradiotracers. Examples are ioflupane (123I) (trade name DaTSCAN) and iometopane (Dopascan) for SPECT or fluorodeoxyglucose (18F)[62] and DTBZ[63] for PET. A pattern of reduced dopaminergic activity in the basal ganglia can aid in diagnosing PD.[62]
Exercise in middle age reduces the risk of Parkinson’s disease later in life.[7]Caffeine also appears protective with a greater decrease in risk occurring with a larger intake of caffeinated beverages such as coffee.[64]Although tobacco smoke causes adverse health effects, decreases life expectancy and quality of life, it may reduce the risk of PD by a third when compared to non-smokers.[46] The basis for this effect is not known, but possibilities include an effect of nicotine as a dopamine stimulant.[46][65] Tobacco smoke contains compounds that act as MAO inhibitors that also might contribute to this effect.[66]
Antioxidants, such as vitamins C and D, have been proposed to protect against the disease but results of studies have been contradictory and no positive effect has been proven.[46] The results regarding fat and fatty acids have been contradictory, with various studies reporting protective effects, risk-increasing effects or no effects.[46] Also, there have been preliminary indications of a possible protective role of estrogens and anti-inflammatory drugs.[46]
There is no cure for Parkinson’s disease, but medications, surgery, and multidisciplinary management can provide relief from the symptoms. The main families of drugs useful for treating motor symptoms are levodopa (usually combined with a dopa decarboxylase inhibitor or COMT inhibitor which does not cross the blood–brain barrier), dopamine agonists and MAO-B inhibitors.[67] The stage of the disease determines which group is most useful. Two stages are usually distinguished: an initial stage in which the individual with PD has already developed some disability for which he needs pharmacological treatment, then a second stage in which an individual develops motor complications related to levodopa usage.[67] Treatment in the initial stage aims for an optimal tradeoff between good symptom control and side-effects resulting from improvement of dopaminergic function. The start of levodopa (or L-DOPA) treatment may be delayed by using other medications such as MAO-B inhibitors and dopamine agonists, in the hope of delaying the onset of dyskinesias.[67] In the second stage the aim is to reduce symptoms while controlling fluctuations of the response to medication. Sudden withdrawals from medication or overuse have to be managed.[67] When medications are not enough to control symptoms, surgery, and deep brain stimulation can be of use.[68] In the final stages of the disease, palliative care is provided to improve quality of life.[69]
Levodopa has been the most widely used treatment for over 30 years.[67] L-DOPA is converted into dopamine in the dopaminergic neurons by dopa decarboxylase.[67] Since motor symptoms are produced by a lack of dopamine in the substantia nigra, the administration of L-DOPA temporarily diminishes the motor symptoms.[67]
Only 5–10% of L-DOPA crosses the blood–brain barrier. The remainder is often metabolized to dopamine elsewhere, causing a variety of side effects including nausea, dyskinesias and joint stiffness.[67]Carbidopaand benserazide are peripheral dopa decarboxylase inhibitors,[67] which help to prevent the metabolism of L-DOPA before it reaches the dopaminergic neurons, therefore reducing side effects and increasingbioavailability. They are generally given as combination preparations with levodopa.[67] Existing preparations are carbidopa/levodopa (co-careldopa) and benserazide/levodopa (co-beneldopa). Levodopa has been related to dopamine dysregulation syndrome, which is a compulsive overuse of the medication, and punding.[39] There are controlled release versions of levodopa in the form intravenous and intestinal infusions that spread out the effect of the medication. These slow-release levodopa preparations have not shown an increased control of motor symptoms or motor complications when compared to immediate release preparations.[67][70]
Tolcapone inhibits the COMT enzyme, which degrades dopamine, thereby prolonging the effects of levodopa.[67] It has been used to complement levodopa; however, its usefulness is limited by possible side effects such as liver damage.[67] A similarly effective drug, entacapone, has not been shown to cause significant alterations of liver function.[67] Licensed preparations of entacapone contain entacapone alone or in combination with carbidopa and levodopa.[67]
Levodopa preparations lead in the long term to the development of motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication.[67] When this occurs a person with PD can change from phases with good response to medication and few symptoms (“on” state), to phases with no response to medication and significant motor symptoms (“off” state).[67] For this reason, levodopa doses are kept as low as possible while maintaining functionality.[67] Delaying the initiation of therapy with levodopa by using alternatives (dopamine agonists and MAO-B inhibitors) is common practice.[67] A former strategy to reduce motor complications was to withdraw L-DOPA medication for some time. This is discouraged now since it can bring dangerous side effects such as neuroleptic malignant syndrome.[67] Most people with PD will eventually need levodopa and later develop motor side effects.[67]
Several dopamine agonists that bind to dopaminergic post-synaptic receptors in the brain have similar effects to levodopa.[67] These were initially used for individuals experiencing on-off fluctuations and dyskinesias as a complementary therapy to levodopa; they are now mainly used on their own as an initial therapy for motor symptoms with the aim of delaying motor complications.[67][71] When used in late PD they are useful at reducing the off periods.[67] Dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine and lisuride.
Dopamine agonists produce significant, although usually mild, side effects including drowsiness, hallucinations, insomnia, nausea, and constipation.[67] Sometimes side effects appear even at a minimal clinically effective dose, leading the physician to search for a different drug.[67] Compared with levodopa, dopamine agonists may delay motor complications of medication use but are less effective at controlling symptoms.[67]Nevertheless, they are usually effective enough to manage symptoms in the initial years.[19] They tend to be more expensive than levodopa.[19] Dyskinesias due to dopamine agonists are rare in younger people who have PD, but along with other side effects, become more common with age at onset.[19] Thus dopamine agonists are the preferred initial treatment for earlier onset, as opposed to levodopa in later onset.[19] Agonists have been related to impulse control disorders (such as compulsive sexual activity and eating, and pathological gambling and shopping) even more strongly than levodopa.[39]
Apomorphine, a non-orally administered dopamine agonist, may be used to reduce off periods and dyskinesia in late PD.[67] It is administered by intermittent injections or continuous subcutaneous infusions.[67] Since secondary effects such as confusion and hallucinations are common, individuals receiving apomorphine treatment should be closely monitored.[67] Two dopamine agonists that are administered through skin patches (lisuride and rotigotine) and are useful for people in the initial stages and possibly to control off states in those in the advanced state.[70]
MAO-B inhibitors (safinamide, selegiline and rasagiline) increase the level of dopamine in the basal ganglia by blocking its metabolism. They inhibit monoamine oxidase B (MAO-B) which breaks down dopamine secreted by the dopaminergic neurons. The reduction in MAO-B activity results in increased L-DOPA in the striatum.[67] Like dopamine agonists, MAO-B inhibitors used as monotherapy improve motor symptoms and delay the need for levodopa in early disease, but produce more adverse effects and are less effective than levodopa. There are few studies of their effectiveness in the advanced stage, although results suggest that they are useful to reduce fluctuations between on and off periods.[67] An initial study indicated that selegiline in combination with levodopa increased the risk of death, but this was later disproven.[67]
Other drugs such as amantadine and anticholinergics may be useful as treatment of motor symptoms. However, the evidence supporting them lacks quality, so they are not first choice treatments.[67] In addition to motor symptoms, PD is accompanied by a diverse range of symptoms. A number of drugs have been used to treat some of these problems.[72] Examples are the use of quetiapine for psychosis, cholinesterase inhibitors for dementia, and modafinil for daytime sleepiness.[72][73] A 2010 meta-analysis found that non-steroidal anti-inflammatory drugs (apart from aspirin), have been associated with at least a 15 percent (higher in long-term and regular users) reduction of incidence of the development of Parkinson’s disease.[74]
Treating motor symptoms with surgery was once a common practice, but since the discovery of levodopa, the number of operations declined.[75] Studies in the past few decades have led to great improvements in surgical techniques, so that surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient.[75] Surgery for PD can be divided in two main groups: lesional and deep brain stimulation (DBS). Target areas for DBS or lesions include the thalamus, the globus pallidus or the subthalamic nucleus.[75]Deep brain stimulation (DBS) is the most commonly used surgical treatment, developed in the 1980s by Alim-Louis Benabid and others. It involves the implantation of a medical device called a neurostimulator which sends electrical impulses to specific parts of the brain. DBS is recommended for people who have PD with motor fluctuations and tremor inadequately controlled by medication, or to those who are intolerant to medication, as long as they do not have severe neuropsychiatric problems.[68] Other, less common, surgical therapies involve intentional formation of lesions to suppress overactivity of specific subcortical areas. For example, pallidotomy involves surgical destruction of the globus pallidus to control dyskinesia.[75]
Exercise programs are recommended in people with Parkinson’s disease.[7] There is some evidence that speech or mobility problems can improve with rehabilitation, although studies are scarce and of low quality.[76][77] Regular physical exercise with or without physiotherapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life.[77] When an exercise program is performed under the supervision of a physiotherapist, there are more improvements in motor symptoms, mental and emotional functions, daily living activities, and quality of life compared to a self-supervised exercise program at home.[78] In terms of improving flexibility and range of motion for people experiencing rigidity, generalized relaxation techniques such as gentle rocking have been found to decrease excessive muscle tension. Other effective techniques to promote relaxation include slow rotational movements of the extremities and trunk, rhythmic initiation, diaphragmatic breathing, and meditation techniques.[79] As for gait and addressing the challenges associated with the disease such as hypokinesia (slowness of movement), shuffling and decreased arm swing; physiotherapists have a variety of strategies to improve functional mobility and safety. Areas of interest with respect to gait during rehabilitation programs focus on but are not limited to improving gait speed, the base of support, stride length, trunk and arm swing movement. Strategies include utilizing assistive equipment (pole walking and treadmill walking), verbal cueing (manual, visual and auditory), exercises (marching and PNF patterns) and altering environments (surfaces, inputs, open vs. closed).[80] Strengthening exercises have shown improvements in strength and motor function for people with primary muscular weakness and weakness related to inactivity with mild to moderate Parkinson’s disease. However, reports show a significant interaction between strength and the time the medications was taken. Therefore, it is recommended that people with PD should perform exercises 45 minutes to one hour after medications when they are at their best.[81] Also, due to the forward flexed posture, and respiratory dysfunctions in advanced Parkinson’s disease, deep diaphragmatic breathing exercises are beneficial in improving chest wall mobility and vital capacity.[82] Exercise may improve constipation.[6]
One of the most widely practiced treatments for speech disorders associated with Parkinson’s disease is the Lee Silverman voice treatment (LSVT).[76][83] Speech therapy and specifically LSVT may improve speech.[76]Occupational therapy (OT) aims to promote health and quality of life by helping people with the disease to participate in as many of their daily living activities as possible.[76] There have been few studies on the effectiveness of OT and their quality is poor, although there is some indication that it may improve motor skills and quality of life for the duration of the therapy.[76][84]
Palliative care is specialized medical care for people with serious illnesses, including Parkinson’s. The goal of this speciality is to improve quality of life for both the person suffering from Parkinson’s and the family by providing relief from the symptoms, pain, and stress of illnesses.[85] As Parkinson’s is not a curable disease, all treatments are focused on slowing decline and improving quality of life, and are therefore palliative in nature.[86]
Palliative care should be involved earlier, rather than later in the disease course.[87][88] Palliative care specialists can help with physical symptoms, emotional factors such as loss of function and jobs, depression, fear, and existential concerns.[87][88][89]
Along with offering emotional support to both the patient and family, palliative care serves an important role in addressing goals of care. People with Parkinson’s may have many difficult decisions to make as the disease progresses such as wishes for feeding tube, non-invasive ventilator, and tracheostomy; wishes for or against cardiopulmonary resuscitation; and when to use hospice care.[86] Palliative care team members can help answer questions and guide people with Parkinson’s on these complex and emotional topics to help them make the best decision based on their own values.[88][90]
Muscles and nerves that control the digestive process may be affected by PD, resulting in constipation and gastroparesis (food remaining in the stomach for a longer period than normal).[6] A balanced diet, based on periodical nutritional assessments, is recommended and should be designed to avoid weight loss or gain and minimize consequences of gastrointestinal dysfunction.[6] As the disease advances, swallowing difficulties (dysphagia) may appear. In such cases it may be helpful to use thickening agents for liquid intake and an upright posture when eating, both measures reducing the risk of choking. Gastrostomy to deliver food directly into the stomach is possible in severe cases.[6]
Levodopa and proteins use the same transportation system in the intestine and the blood–brain barrier, thereby competing for access.[6] When they are taken together, this results in a reduced effectiveness of the drug.[6] Therefore, when levodopa is introduced, excessive protein consumption is discouraged and well balanced Mediterranean diet is recommended. In advanced stages, additional intake of low-protein products such as bread or pasta is recommended for similar reasons.[6] To minimize interaction with proteins, levodopa should be taken 30 minutes before meals.[6] At the same time, regimens for PD restrict proteins during breakfast and lunch, allowing protein intake in the evening.[6]
Repetitive transcranial magnetic stimulation temporarily improves levodopa-induced dyskinesias.[91] Its usefulness in PD is an open research topic,[92] although recent studies have shown no effect by rTMS.[93]Several nutrients have been proposed as possible treatments; however there is no evidence that vitamins or food additives improve symptoms.[94] There is no evidence to substantiate that acupuncture and practice of Qigong, or T’ai chi, have any effect on the course of the disease or symptoms. Further research on the viability of Tai chi for balance or motor skills are necessary.[95][96][97]Fava beans and velvet beans are natural sources of levodopa and are eaten by many people with PD. While they have shown some effectiveness in clinical trials,[98] their intake is not free of risks. Life-threatening adverse reactions have been described, such as the neuroleptic malignant syndrome.[99][100]
Global burden of Parkinson’s disease, measured in disability-adjusted life years per 100,000 inhabitants in 2004
|
no data
< 5
5–12.5
12.5–20
20–27.5
27.5–35
35–42.5
|
42.5–50
50–57.5
57.5–65
65–72.5
72.5–80
> 80
|
PD invariably progresses with time. A severity rating method known as the Unified Parkinson’s Disease Rating Scale (UPDRS) is the most commonly used metric for clinical study. A modified version known as the MDS-UPDRS is also sometimes used. An older scaling method known as the Hoehn and Yahr scale (originally published in 1967), and a similar scale known as the Modified Hoehn and Yahr scale, have also been commonly used. The Hoehn and Yahr scale defines five basic stages of progression.
Motor symptoms, if not treated, advance aggressively in the early stages of the disease and more slowly later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and be bedridden after ten years.[101] However, it is uncommon to find untreated people nowadays. Medication has improved the prognosis of motor symptoms, while at the same time it is a new source of disability because of the undesired effects of levodopa after years of use.[101] In people taking levodopa, the progression time of symptoms to a stage of high dependency from caregivers may be over 15 years.[101] However, it is hard to predict what course the disease will take for a given individual.[101] Age is the best predictor of disease progression.[57] The rate of motor decline is greater in those with less impairment at the time of diagnosis, while cognitive impairment is more frequent in those who are over 70 years of age at symptom onset.[57]
Since current therapies improve motor symptoms, disability at present is mainly related to non-motor features of the disease.[57] Nevertheless, the relationship between disease progression and disability is not linear. Disability is initially related to motor symptoms.[101] As the disease advances, disability is more related to motor symptoms that do not respond adequately to medication, such as swallowing/speech difficulties, and gait/balance problems; and also to motor complications, which appear in up to 50% of individuals after 5 years of levodopa usage.[101] Finally, after ten years most people with the disease have autonomic disturbances, sleep problems, mood alterations and cognitive decline.[101] All of these symptoms, especially cognitive decline, greatly increase disability.[57][101]
The life expectancy of people with PD is reduced.[101]Mortality ratios are around twice those of unaffected people.[101] Cognitive decline and dementia, old age at onset, a more advanced disease state and presence of swallowing problems are all mortality risk factors. On the other hand, a disease pattern mainly characterized by tremor as opposed to rigidity predicts an improved survival.[101] Death from aspiration pneumonia is twice as common in individuals with PD as in the healthy population.[101]
In 2013 PD resulted in about 103,000 deaths globally, up from 44,000 deaths in 1990.[8] The death rate increased from an average of 1.5 to 1.8 per 100,000 during that time.[8]
Deaths from Parkinson disease per million persons in 2012
PD is the second most common neurodegenerative disorder after Alzheimer’s disease and affects approximately seven million people globally and one million people in the United States.[34][46] The proportion in a population at a given time is about 0.3% in industrialized countries. PD is more common in the elderly and rates rises from 1% in those over 60 years of age to 4% of the population over 80.[46] The mean age of onset is around 60 years, although 5–10% of cases, classified as young onset PD, begin between the ages of 20 and 50.[19] PD may be less prevalent in those of African and Asian ancestry, although this finding is disputed.[46] Some studies have proposed that it is more common in men than women, but others failed to detect any differences between the two sexes.[46] The number of new cases per year of PD is between 8 and 18 per 100,000 person–years.[46]
Many risk factors and protective factors have been proposed, sometimes in relation to theories concerning possible mechanisms of the disease, however, none have been conclusively related to PD by empirical evidence. When epidemiological studies have been carried out in order to test the relationship between a given factor and PD, they have often been flawed and their results have in some cases been contradictory.[46] The most frequently replicated relationships are an increased risk of PD in those exposed to pesticides, and a reduced risk in smokers.[46]
Several early sources, including an Egyptianpapyrus, an Ayurvedic medical treatise, the Bible, and Galen‘s writings, describe symptoms resembling those of PD.[102] After Galen there are no references unambiguously related to PD until the 17th century.[102] In the 17th and 18th centuries, several authors wrote about elements of the disease, including Sylvius,Gaubius, Hunter and Chomel.[102][103][104]
In 1817 an English doctor, James Parkinson, published his essay reporting six cases of paralysis agitans.[14]An Essay on the Shaking Palsy described the characteristic resting tremor, abnormal posture and gait, paralysis and diminished muscle strength, and the way that the disease progresses over time.[12][105] Early neurologists who made further additions to the knowledge of the disease include Trousseau, Gowers, Kinnier Wilson and Erb, and most notably Jean-Martin Charcot, whose studies between 1868 and 1881 were a landmark in the understanding of the disease.[14] Among other advances, he made the distinction between rigidity, weakness and bradykinesia.[14] He also championed the renaming of the disease in honor of James Parkinson.[14]
In 1912 Frederic Lewy described microscopic particles in affected brains, later named “Lewy bodies“.[14] In 1919 Konstantin Tretiakoff reported that the substantia nigra was the main cerebral structure affected, but this finding was not widely accepted until it was confirmed by further studies published by Rolf Hassler in 1938.[14] The underlying biochemical changes in the brain were identified in the 1950s, due largely to the work of Arvid Carlsson on the neurotransmitter dopamine and Oleh Hornykiewicz on its role on PD.[106] In 1997, alpha-synuclein was found to be the main component of Lewy bodies by Spillantini, Trojanowski, Goedert and others.[58]
Anticholinergics and surgery (lesioning of the corticospinal pathway or some of the basal ganglia structures) were the only treatments until the arrival of levodopa, which reduced their use dramatically.[103][107]Levodopa was first synthesized in 1911 by Casimir Funk, but it received little attention until the mid 20th century.[106] It entered clinical practice in 1967 and brought about a revolution in the management of PD.[106][108] By the late 1980s deep brain stimulation introduced by Alim-Louis Benabid and colleagues at Grenoble, France, emerged as a possible treatment.[109]
The costs of PD to society are high, but precise calculations are difficult due to methodological issues in research and differences between countries.[110] The annual cost in the UK is estimated to be between 449 million and 3.3 billion pounds, while the cost per patient per year in the U.S. is probably around $10,000 and the total burden around 23 billion dollars.[110] The largest share of direct cost comes from inpatient care and nursing homes, while the share coming from medication is substantially lower.[110] Indirect costs are high, due to reduced productivity and the burden on caregivers.[110] In addition to economic costs, PD reduces quality of life of those with the disease and their caregivers.[110]
11 April, the birthday of James Parkinson, has been designated as World Parkinson’s Day.[14] A red tulip was chosen by international organizations as the symbol of the disease in 2005: it represents the James Parkinson Tulip cultivar, registered in 1981 by a Dutch horticulturalist.[111] Advocacy organizations include the National Parkinson Foundation, which has provided more than $180 million in care, research and support services since 1982,[112]Parkinson’s Disease Foundation, which has distributed more than $115 million for research and nearly $50 million for education and advocacy programs since its founding in 1957 by William Black;[113][114] the American Parkinson Disease Association, founded in 1961;[115] and the European Parkinson’s Disease Association, founded in 1992.[116]
Actor Michael J. Fox has PD and has greatly increased the public awareness of the disease.[15] After diagnosis, Fox embraced his Parkinson’s in television roles, sometimes acting without medication, in order to further illustrate the effects of the condition. He has written two autobiographies in which his fight against the disease plays a major role,[117] and appeared before the United States Congress without medication to illustrate the effects of the disease.[117]The Michael J. Fox Foundation aims to develop a cure for Parkinson’s disease.[117] Fox received an honorary doctorate in medicine from Karolinska Institutet for his contributions to research in Parkinson’s disease.[118]
Professional cyclist and Olympic medalist Davis Phinney, who was diagnosed with young onset Parkinson’s at age 40, started the Davis Phinney Foundation in 2004 to support Parkinson’s research, focusing on quality of life for people with the disease.[16][119][120]
Muhammad Ali showed signs of Parkinson’s when he was 38, but was not diagnosed until he was 42, and has been called the “world’s most famous Parkinson’s patient”.[17] Whether he had PD or a parkinsonismrelated to boxing is unresolved.[121][122]
There is little prospect of significant new PD treatments in the near future.[123] Currently active research directions include the search for new animal models of the disease and studies of the potential usefulness of gene therapy, stem cell transplants and neuroprotective agents.[57]
PD is not known to occur naturally in any species other than humans, although animal models which show some features of the disease are used in research. The appearance of parkinsonian symptoms in a group of drug addicts in the early 1980s who consumed a contaminated batch of the synthetic opiateMPPP led to the discovery of the chemical MPTP as an agent that causes a parkinsonian syndrome in non-human primates as well as in humans.[124] Other predominant toxin-based models employ the insecticide rotenone, the herbicideparaquat and the fungicide maneb.[125] Models based on toxins are most commonly used in primates. Transgenic rodent models that replicate various aspects of PD have been developed.[126] Using the neurotoxin 6-hydroxydopamine, also known as 6-OHDA, it creates a model of Parkinson’s disease in rats by targeting and destroying dopaminergic neurons in the nigrostriatal pathway when injected into the substantia nigra.[127]
Gene therapy typically involves the use of a non-infectious virus (i.e., a viral vector such as the adeno-associated virus) to shuttle genetic material into a part of the brain. The gene used leads to the production of anenzyme that helps to manage PD symptoms or protects the brain from further damage.[57][128] In 2010 there were four clinical trials using gene therapy in PD.[57] There have not been important adverse effects in these trials although the clinical usefulness of gene therapy is still unknown.[57] One of these reported positive results in 2011,[129] but the company filed for bankruptcy in March 2012.[130]
Investigations on neuroprotection are at the forefront of PD research. Several molecules have been proposed as potential treatments.[57] However, none of them have been conclusively demonstrated to reduce degeneration.[57] Agents currently under investigation include anti-apoptotics (omigapil, CEP-1347), antiglutamatergics, monoamine oxidase inhibitors (selegiline, rasagiline), promitochondrials (coenzyme Q10, creatine), calcium channel blockers (isradipine) and growth factors (GDNF).[57] Preclinical research also targets alpha-synuclein.[123] A vaccine that primes the human immune system to destroy alpha-synuclein, PD01A (developed by Austrian company, Affiris), has entered clinical trials in humans.[131]
Since early in the 1980s, fetal, porcine, carotid or retinal tissues have been used in cell transplants, in which dissociated cells are injected into the substantia nigra in the hope that they will incorporate themselves into the brain in a way that replaces the dopamine-producing cells that have been lost.[57] Although there was initial evidence ofmesencephalic dopamine-producing cell transplants being beneficial, double-blind trials to date indicate that cell transplants produce no long-term benefit.[57] An additional significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias.[132]Stem cell transplants are a recent research target, because stem cells are easy to manipulate and stem cells transplanted into the brains of rodents and monkeys have been found to survive and reduce behavioral abnormalities.[57][133]Nevertheless, use of fetal stem cells is controversial.[57] It has been proposed that effective treatments may be developed in a less controversial way by use of induced pluripotent stem cells taken from adults.[57]
| Multiple sclerosis | |
|---|---|
| disseminated sclerosis, encephalomyelitis disseminata | |
Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100
|
|
| Classification and external resources | |
| Specialty | Neurology |
| ICD–10 | G35 |
| ICD–9-CM | 340 |
| OMIM | 126200 |
| DiseasesDB | 8412 |
| MedlinePlus | 000737 |
| eMedicine | neuro/228oph/179emerg/321pmr/82radio/461 |
| Patient UK | Multiple sclerosis |
| MeSH | D009103 |
| GeneReviews | |
Multiple sclerosis (MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged.[1] This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems.[2][3][4] Specific symptoms can include double vision, blindness in one eye, muscle weakness, trouble with sensation, or trouble with coordination.[1] MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms).[5] Between attacks, symptoms may disappear completely; however, permanent neurological problems often remain, especially as the disease advances.[5]
While the cause is not clear, the underlying mechanism is thought to be either destruction by the immune system or failure of the myelin-producing cells.[6] Proposed causes for this include genetics and environmental factors such as being triggered by a viral infection.[3][7] MS is usually diagnosed based on the presenting signs and symptoms and the results of supporting medical tests.[8]
There is no known cure for multiple sclerosis.[1] Treatments attempt to improve function after an attack and prevent new attacks.[3] Medications used to treat MS, while modestly effective, can have side effects and be poorly tolerated. Physical therapy can help with people’s ability to function.[1] Many people pursue alternative treatments, despite a lack of evidence.[9] The long-term outcome is difficult to predict, with good outcomes more often seen in women, those who develop the disease early in life, those with a relapsing course, and those who initially experienced few attacks.[10]Life expectancy is on average 5 to 10 years lower than that of an unaffected population.[2]
Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system.[11] In 2013, about 2.3 million people were affected globally with rates varying widely in different regions and among different populations.[12][13] That year about 20,000 people died from MS, up from 12,000 in 1990.[14] The disease usually begins between the ages of 20 and 50 and is twice as common in women as in men.[15] MS was first described in 1868 by Jean-Martin Charcot.[16] The name multiple sclerosis refers to the numerous scars (sclerae—better known as plaques or lesions) that develop on the white matter of the brain and spinal cord.[16] A number of new treatments and diagnostic methods are under development.[17]
A person with MS can have almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common.[2] The specific symptoms are determined by the locations of the lesions within the nervous system, and may include loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness, muscle weakness, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia);problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties, among others.[2] Difficulties thinking and emotional problems such as depression or unstable mood are also common.[2]Uhthoff’s phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte’s sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS.[2] The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as the multiple sclerosis functional composite being increasingly used in research.[18][19][20]
The condition begins in 85% of cases as a clinically isolated syndrome (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the previous difficulties.[8] The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10-15% of cases).[15] A combination of these two patterns may also occur[5] or people may start in a relapsing and remitting course that then becomes progressive later on.[15] Relapses are usually not predictable, occurring without warning.[2] Exacerbations rarely occur more frequently than twice per year.[2] Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer.[21] Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk.[2]Stress may also trigger an attack.[22] Women with MS who become pregnant experience fewer relapses; however, during the first months after delivery the risk increases.[2] Overall, pregnancy does not seem to influence long-term disability.[2] Many events have been found not to affect relapse rates including vaccination, breast feeding,[2] physical trauma,[23] and Uhthoff’s phenomenon.[21]
The cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as infectious agents.[2]Theories try to combine the data into likely explanations, but none has proved definitive. While there are a number of environmental risk factors and although some are partly modifiable, further research is needed to determine whether their elimination can prevent MS.[24]
MS is more common in people who live farther from the equator, although exceptions exist.[2][25] These exceptions include ethnic groups that are at low risk far from the equator such as the Samis, Amerindians, Canadian Hutterites, New Zealand Māori,[26] and Canada’s Inuit,[15] as well as groups that have a relatively high risk close to the equator such as Sardinians,[15] inland Sicilians,[27]Palestinians and Parsis.[26] The cause of this geographical pattern is not clear.[15] While the north-south gradient of incidence is decreasing,[25] as of 2010 it is still present.[15]
MS is more common in regions with northern European populations[2] and the geographic variation may simply reflect the global distribution of these high-risk populations.[15] Decreased sunlight exposure resulting in decreased vitamin D production has also been put forward as an explanation.[28][29][30] A relationship between season of birth and MS lends support to this idea, with fewer people born in the northern hemisphere in November as compared to May being affected later in life.[31] Environmental factors may play a role during childhood, with several studies finding that people who move to a different region of the world before the age of 15 acquire the new region’s risk to MS. If migration takes place after age 15, however, the person retains the risk of his home country.[2][24] There is some evidence that the effect of moving may still apply to people older than 15.[2]
MS is not considered a hereditary disease; however, a number of genetic variations have been shown to increase the risk.[32] Some of these genes appear to have higher levels of expression in microglial cells than expected by chance.[33] The probability of developing the disease is higher in relatives of an affected person, with a greater risk among those more closely related.[3] In identical twins both are affected about 30% of the time, while around 5% for non-identical twins and 2.5% of siblings are affected with a lower percentage of half-siblings.[2][3][34] If both parents are affected the risk in their children is 10 times that of the general population.[15] MS is also more common in some ethnic groups than others.[35]
Specific genes that have been linked with MS include differences in the human leukocyte antigen (HLA) system—a group of genes on chromosome6 that serves as the major histocompatibility complex (MHC).[2] That changes in the HLA region are related to susceptibility has been known since the 1980s,[36] and additionally this same region has been implicated in the development of other autoimmune diseases such as diabetes type I and systemic lupus erythematosus.[36] The most consistent finding is the association between multiple sclerosis and alleles of the MHC defined as DR15 and DQ6.[2] Other loci have shown a protective effect, such as HLA-C554 and HLA-DRB1*11.[2] Overall, it has been estimated that HLA changes account for between 20 and 60% of the genetic predisposition.[36] Modern genetic methods (genome-wide association studies) have discovered at least twelve other genes outside the HLA locus that modestly increase the probability of MS.[36]
Many microbes have been proposed as triggers of MS, but none have been confirmed.[3] Moving at an early age from one location in the world to another alters a person’s subsequent risk of MS.[7] An explanation for this could be that some kind of infection, produced by a widespread microbe rather than a rare one, is related to the disease.[7]Proposed mechanisms include the hygiene hypothesis and the prevalence hypothesis. The hygiene hypothesis proposes that exposure to certain infectious agents early in life is protective, the disease being a response to a late encounter with such agents.[2] The prevalence hypothesis proposes that the disease is due to an infectious agent more common in regions where MS is common and where in most individuals it causes an ongoing infection without symptoms. Only in a few cases and after many years does it cause demyelination.[7][37] The hygiene hypothesis has received more support than the prevalence hypothesis.[7]
Evidence for a virus as a cause include: the presence of oligoclonal bands in the brain and cerebrospinal fluid of most people with MS, the association of several viruses with human demyelination encephalomyelitis, and the occurrence of demyelination in animals caused by some viral infection.[38]Human herpes viruses are a candidate group of viruses. Individuals having never been infected by the Epstein–Barr virus are at a reduced risk of getting MS, whereas those infected as young adults are at a greater risk than those having had it at a younger age.[2][7] Although some consider that this goes against the hygiene hypothesis, since the non-infected have probably experienced a more hygienic upbringing,[7] others believe that there is no contradiction, since it is a first encounter with the causative virus relatively late in life that is the trigger for the disease.[2] Other diseases that may be related include measles, mumps and rubella.[2]
Smoking has been shown to be an independent risk factor for MS.[28]Stress may be a risk factor although the evidence to support this is weak.[24] Association with occupational exposures and toxins—mainly solvents—has been evaluated, but no clear conclusions have been reached.[24]Vaccinations were studied as causal factors; however, most studies show no association.[24] Several other possible risk factors, such as diet andhormone intake, have been looked at; however, evidence on their relation with the disease is “sparse and unpersuasive”.[28]Gout occurs less than would be expected and lower levels of uric acid have been found in people with MS. This has led to the theory that uric acid is protective, although its exact importance remains unknown.[39]
The three main characteristics of MS are the formation of lesions in the central nervous system (also called plaques), inflammation, and the destruction of myelin sheaths of neurons. These features interact in a complex and not yet fully understood manner to produce the breakdown of nerve tissue and in turn the signs and symptoms of the disease.[2] Additionally, MS is believed to be an immune-mediated disorder that develops from an interaction of the individual’s genetics and as yet unidentified environmental causes.[3] Damage is believed to be caused, at least in part, by attack on the nervous system by a person’s own immune system.[2]
The name multiple sclerosis refers to the scars (sclerae – better known as plaques or lesions) that form in the nervous system. These lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia, and spinal cord, or white matter tracts close to the lateral ventricles.[2] The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved.[3]
To be specific, MS involves the loss of oligodendrocytes, the cells responsible for creating and maintaining a fatty layer—known as the myelin sheath—which helps the neurons carry electrical signals (action potentials).[2] This results in a thinning or complete loss of myelin and, as the disease advances, the breakdown of the axons of neurons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals.[3] A repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes are unable to completely rebuild the cell’s myelin sheath.[40] Repeated attacks lead to successively less effective remyelinations, until a scar-like plaque is built up around the damaged axons.[40] These scars are the origin of the symptoms and during an attack magnetic resonance imaging (MRI) often shows more than ten new plaques.[2] This could indicate that there are a number of lesions below which the brain is capable of repairing itself without producing noticeable consequences.[2] Another process involved in the creation of lesions is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons.[2] A number of lesion patterns have been described.[41]
Apart from demyelination, the other sign of the disease is inflammation. Fitting with an immunological explanation, the inflammatory process is caused by T cells, a kind oflymphocyte that plays an important role in the body’s defenses.[3] T cells gain entry into the brain via disruptions in the blood–brain barrier. The T cells recognize myelin as foreign and attack it, explaining why these cells are also called “autoreactive lymphocytes”.[2]
The attack of myelin starts inflammatory processes, which triggers other immune cells and the release of soluble factors like cytokines and antibodies. Further breakdown of the blood–brain barrier in turn causes a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins.[3] Inflammation can potentially reduce transmission of information between neurons in at least three ways.[2] The soluble factors released might stop neurotransmission by intact neurons. These factors could lead to or enhance the loss of myelin, or they may cause the axon to break down completely.[2]
The blood–brain barrier is a part of the capillary system that prevents the entry of T cells into the central nervous system. It may become permeable to these types of cells secondary to an infection by a virus or bacteria. After it repairs itself, typically once the infection has cleared, T cells may remain trapped inside the brain.[3]Gadolinium cannot cross a normal BBB and, therefore, Gadolinium-enhanced MRI is used to show BBB breakdowns.[42]
Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing.[8] It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.[2][43] The McDonald criteria, which focus on clinical, laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis[13] with the Schumacher and Poser criteria being of mostly historical significance.[44] While the above criteria allow for a non-invasive diagnosis, some state that the only definitive proof is an autopsy or biopsy where lesions typical of MS are detected.[2][45][46]
Clinical data alone may be sufficient for a diagnosis of MS if an individual has had separate episodes of neurological symptoms characteristic of the disease.[45] In those who seek medical attention after only one attack, other testing is needed for the diagnosis. The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine may show areas of demyelination (lesions or plaques). Gadolinium can be administeredintravenously as a contrast agent to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.[45][47] Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation in the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 75–85% of people with MS.[45][48] The nervous system in MS may respond less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined usingvisual– and sensory-evoked potentials.[49]
Several phenotypes (commonly named types), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions. In 1996, the United States National Multiple Sclerosis Society described four clinical courses.[5] This set of courses was later reviewed by an international panel in 2013, adding clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) as phenotypes, but leaving the main structure untouched.[50]
The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease.[2][8] This describes the initial course of 80% of individuals with MS.[2] When deficits always resolve between attacks, this is sometimes referred to as benign MS,[51]although people will still build up some degree of disability in the long term.[2] On the other hand, the term malignant multiple sclerosis is used to describe people with MS having reached significant level of disability in a short period.[52] The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis.[2][53] 30 to 70% of persons experiencing CIS later develop MS.[53]
Secondary progressive MS occurs in around 65% of those with initial relapsing-remitting MS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission.[2][5] Occasional relapses and minor remissions may appear.[5] The most common length of time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.[54]
The primary progressive subtype occurs in approximately 10–20% of individuals, with no remission after the initial symptoms.[8][55] It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.[5] The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in relapsing-remitting MS, around 40 years of age.[2]
Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also have clear superimposed attacks. This is the least common of all subtypes.[5]
Unusual types of MS have been described; these include Devic’s disease, Balo concentric sclerosis, Schilder’s diffuse sclerosis, and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases.[56] Multiple sclerosis behaves differently in children, taking more time to reach the progressive stage.[2] Nevertheless, they still reach it at a lower average age than adults usually do.[2]
Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting evidence.
During symptomatic attacks, administration of high doses of intravenouscorticosteroids, such as methylprednisolone, is the usual therapy,[2] with oral corticosteroids seeming to have a similar efficacy and safety profile.[57] Although, in general, effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[58] The consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis.[2]
As of 2016, nine disease-modifying treatments have been approved by regulatory agencies for relapsing-remitting multiple sclerosis (RRMS) including: interferon beta-1a, interferon beta-1b, glatiramer acetate,mitoxantrone, natalizumab, fingolimod,[59]teriflunomide,[60]dimethyl fumarate[61] and alemtuzumab.[62] Their cost effectiveness as of 2012 is unclear.[63] In May 2016 the FDA approved daclizumab for the treatment of relapsing multiple sclerosis in adults, with requirements for postmarketing studies and submission of a formal risk evaluation and mitigation strategy.[64][65]
In RRMS they are modestly effective at decreasing the number of attacks.[59] The interferons and glatiramer acetate are first-line treatments[8] and are roughly equivalent, reducing relapses by approximately 30%.[66]Early-initiated long-term therapy is safe and improves outcomes.[67][68] Natalizumab reduces the relapse rate more than first-line agents; however, due to issues of adverse effects is a second-line agent reserved for those who do not respond to other treatments[8] or with severe disease.[66] Mitoxantrone, whose use is limited by severe adverse effects, is a third-line option for those who do not respond to other medications.[8]Treatment of clinically isolated syndrome (CIS) with interferons decreases the chance of progressing to clinical MS.[2][69] Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults.[70] The role of some newer agents such as fingolimod, teriflunomide, and dimethyl fumarate, as of 2011, is not yet entirely clear.[71]
No treatment has been shown to change the course of primary progressive MS[8] and as of 2011 only one medication, mitoxantrone, has been approved for secondary progressive MS.[72] In this population tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years.[73][74]
The disease-modifying treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections).[75] Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known aslipoatrophy, may develop.[75] Interferons may produce flu-like symptoms;[76] some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes.[77] More dangerous but much less common are liver damage from interferons,[78]systolic dysfunction(12%), infertility, and acute myeloid leukemia (0.8%) from mitoxantrone,[73][79] and progressive multifocal leukoencephalopathy occurring with natalizumab (occurring in 1 in 600 people treated).[8][80]
Fingolimod may give rise to hypertension and slowed heart rate, macular edema, elevated liver enzymes or a reduction in lymphocyte levels.[71] Tentative evidence supports the short-term safety of teriflunomide, with common side effects including: headaches, fatigue, nausea, hair loss, and limb pain.[59] There have also been reports of liver failure and PML with its use and it is dangerous for fetal development.[71] Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems.[61][71] While dimethyl fumarate may lead to a reduction in the white blood cell count there were no reported cases of opportunistic infections during trials.[81][82]
Both medications and neurorehabilitation have been shown to improve some symptoms, though neither changes the course of the disease.[83] Some symptoms have a good response to medication, such as an unstable bladder and spasticity, while others are little changed.[2] For neurologic problems, a multidisciplinary approach is important for improving quality of life; however, it is difficult to specify a ‘core team’ as many health services may be needed at different points in time.[2] Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level.[84] There is limited evidence for the overall efficacy of individual therapeutic disciplines,[85][86] though there is good evidence that specific approaches, such as exercise,[87][88] and psychology therapies, in particular cognitive behavioral approaches are effective.[89]
Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined.[9] The evidence for the effectiveness for such treatments in most cases is weak or absent.[9][90] Treatments of unproven benefit used by people with MS include dietary supplementation and regimens,[9][91][92] vitamin D,[93]relaxation techniques such as yoga,[9]herbal medicine (including medical cannabis),[9][94]hyperbaric oxygen therapy,[95]self-infection with hookworms, reflexology, and acupuncture.[9][96] Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare.[9]
|
no data
<13
13–16
16–19
19–22
22–25
25–28
|
28–31
31–34
34–37
37–40
40–43
>43
|
The expected future course of the disease depends on the subtype of the disease; the individual’s sex, age, and initial symptoms; and the degree of disability the person has.[10] Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course.[10][97]
The average life expectancy is 30 years from the start of the disease, which is 5 to 10 years less than that of unaffected people.[2] Almost 40% of people with MS reach the seventh decade of life.[97] Nevertheless, two-thirds of the deaths are directly related to the consequences of the disease.[2]Suicide is more common, while infections and other complications are especially dangerous for the more disabled.[2] Although most people lose the ability to walk before death, 90% are capable of independent walking at 10 years from onset, and 75% at 15 years.[98][needs update?]
MS is the most common autoimmune disorder of the central nervous system.[11] As of 2010, the number of people with MS was 2–2.5 million (approximately 30 per 100,000) globally, with rates varying widely in different regions.[13][15] It is estimated to have resulted in 18,000 deaths that year.[99] In Africa rates are less than 0.5 per 100,000, while they are 2.8 per 100,000 in South East Asia, 8.3 per 100,000 in the Americas, and 80 per 100,000 in Europe.[13] Rates surpass 200 per 100,000 in certain populations of Northern European descent.[15] The number of new cases that develop per year is about 2.5 per 100,000.[13]
Rates of MS appear to be increasing; this, however, may be explained simply by better diagnosis.[15] Studies on populational and geographical patterns have been common[37] and have led to a number of theories about the cause.[7][24][28]
MS usually appears in adults in their late twenties or early thirties but it can rarely start in childhood and after 50 years of age.[13][15] The primary progressive subtype is more common in people in their fifties.[55] Similar to many autoimmune disorders, the disease is more common in women, and the trend may be increasing.[2][25] As of 2008, globally it is about two times more common in women than in men.[13] In children, it is even more common in females than males,[2] while in people over fifty, it affects males and females almost equally.[55]
Robert Carswell (1793–1857), a British professor of pathology, and Jean Cruveilhier (1791–1873), a French professor of pathologic anatomy, described and illustrated many of the disease’s clinical details, but did not identify it as a separate disease.[100] Specifically, Carswell described the injuries he found as “a remarkable lesion of the spinal cord accompanied with atrophy”.[2] Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836–1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels.[101][102]
The French neurologistJean-Martin Charcot (1825–1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868.[100] Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques.
The first attempt to establish a set of diagnostic criteria was also due to Charcot in 1868. He published what now is known as the “Charcot Triad”, consisting in nystagmus,intention tremor, and telegraphic speech (scanning speech)[103] Charcot also observed cognition changes, describing his patients as having a “marked enfeeblement of the memory” and “conceptions that formed slowly”.[16]
Diagnosis was based in Charcot triad and clinical observation until Schumacher made the first attempt to standardize criteria in 1965 by introducing some fundamental requirements: Dissemination of the lesions in time (DIT) and space (DIS), and that “signs and symptoms cannot be explained better by another disease process”.[103] Both requirements were later inherited by Poser criteria and McDonald criteria, whose 2010 version is currently in use.
During the 20th century theories about the cause and pathogenesis were developed and effective treatments began to appear in the 1990s.[2]
.jpg)
There are several historical accounts of people who probably had MS and lived before or shortly after the disease was described by Charcot.
A young woman called Halldora who lived in Iceland around 1200 suddenly lost her vision and mobility but, after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (1380–1433), a Dutchnun, may be one of the first clearly identifiable people with MS. From the age of 16 until her death at 53, she had intermittent pain, weakness of the legs, and vision loss—symptoms typical of MS.[104] Both cases have led to the proposal of a “Viking gene” hypothesis for the dissemination of the disease.[105]
Augustus Frederick d’Este (1794–1848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George III of the United Kingdom, almost certainly had MS. D’Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) after the funeral of a friend. During his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life.[106][107] Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (1889–1919), who maintained a detailed log of his diagnosis and struggle.[107] His diary was published in 1919 as The Journal of a Disappointed Man.[108]
There is ongoing research looking for more effective, convenient, and tolerable treatments for relapsing-remitting MS; creation of therapies for the progressive subtypes;neuroprotection strategies; and effective symptomatic treatments.[17]
During the 2000s and 2010s, there has been approval of several oral drugs that are expected to gain in popularity and frequency of use.[109] Several more oral drugs are under investigation, including ozanimod and laquinimod. Laquinimod was announced in August 2012 and is in a third phase III trial after mixed results in the previous ones.[110]Similarly, studies aimed to improve the efficacy and ease of use of already existing therapies are occurring. This includes the use of new preparations such as the PEGylatedversion of interferon-β-1a, which it is hoped may be given at less frequent doses with similar effects.[111][112] Request for approval of peginterferon beta-1a is expected during 2013.[112]
Monoclonal antibodies have also raised high levels of interest. Alemtuzumab, daclizumab, and CD20 monoclonal antibodies such as rituximab, ocrelizumab and ofatumumabhave all shown some benefit and are under study as potential treatments.[82] Their use has also been accompanied by the appearance of potentially dangerous adverse effects, the most important of which being opportunistic infections.[109] Related to these investigations is the development of a test for JC virus antibodies, which might help to determine who is at greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab.[109] While monoclonal antibodies will probably have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated with them.[109]
Another research strategy is to evaluate the combined effectiveness of two or more drugs.[113] The main rationale for using a number of medications in MS is that the involved treatments target different mechanisms and, therefore, their use is not necessarily exclusive.[113]Synergies, in which one drug improves the effect of another are also possible, but there can also be drawbacks such as the blocking of the action of the other or worsened side-effects.[113] There have been several trials of combined therapy, yet none have shown positive enough results to be considered as a useful treatment for MS.[113]
Research on neuroprotection and regenerative treatments, such as stem cell therapy, while of high importance, are in the early stages.[114] Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS.[109]
While diagnostic criteria are not expected to change in the near future, work to develop biomarkers that help with diagnosis and prediction of disease progression is ongoing.[109] New diagnostic methods that are being investigated include work with anti-myelin antibodies, and studies with serum and cerebrospinal fluid, but none of them has yielded reliably positive results.[116]
At the current time, there are no laboratory investigations that can predict prognosis. Several promising approaches have been proposed including: interleukin-6, nitric oxideand nitric oxide synthase, osteopontin, and fetuin-A.[116] Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as neurofilaments, tau, and N-acetylaspartate are under investigation.[116] Other effects include looking for biomarkers that distinguish between those who will and will not respond to medications.[116]
Improvement in neuroimaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI) carry a promise for better diagnosis and prognosis predictions, although the effect of such improvements in daily medical practice may take several decades.[109] Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, magnetization transfer, diffusion tensor, and functional magnetic resonance imaging.[117] These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values.[117] There are other techniques under development that include contrast agents capable of measuring levels of peripheralmacrophages, inflammation, or neuronal dysfunction,[117] and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion.[117] Similarly, new PET radiotracers might serve as markers of altered processes such as brain inflammation, cortical pathology, apoptosis, or remylienation.[118] Antibiodies against the Kir4.1 potassium channel may be related to MS.[119]
In 2008, vascular surgeon Paolo Zamboni suggested that MS involves narrowing of the veins draining the brain, which he referred to as chronic cerebrospinal venous insufficiency (CCSVI). He found CCSVI in all patients with MS in his study, performed a surgical procedure, later called in the media the “liberation procedure” to correct it, and claimed that 73% of participants improved.[120] This theory received significant attention in the media and among those with MS, especially in Canada.[121] Concerns have been raised with Zamboni’s research as it was neither blinded nor controlled, and its assumptions about the underlying cause of the disease are not backed by known data.[122] Also, further studies have either not found a similar relationship or found one that is much less strong,[123] raising serious objections to the hypothesis.[124] The “liberation procedure” has been criticized for resulting in serious complications and deaths with unproven benefits.[122] It is, thus, as of 2013 not recommended for the treatment of MS.[125] Additional research investigating the CCSVI hypothesis are under way.[126]
| Amyotrophic lateral sclerosis | |
|---|---|
| Lou Gehrig’s disease, Charcot disease | |
An MRI with increased signal in the posterior part of the internal capsule which can be tracked to themotor cortex consistent with the diagnosis of ALS.
|
|
| Classification and external resources | |
| Specialty | Neurology |
| ICD–10 | G12.2 |
| ICD–9-CM | 335.20 |
| OMIM | 105400 |
| DiseasesDB | 29148 |
| MedlinePlus | 000688 |
| eMedicine | neuro/14emerg/24pmr/10 |
| Patient UK | Amyotrophic lateral sclerosis |
| MeSH | D000690 |
| GeneReviews | |
| Orphanet | 803 |
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease and motor neurone disease (MND), is a specific disorder that involves the death of neurons that control voluntary muscles.[1][2][3][4] Some also use motor neuron disease for a group of five conditions of which ALS is the most common.[5] ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size.[6] This results in difficulty in speaking,swallowing, and eventually breathing.[3][6]
The cause is not known in 90% to 95% of cases.[1] About 5–10% of cases are inherited from a person’s parents.[7] About half of these genetic cases are due to one of two specific genes. The diagnosis is based on a person’s signs and symptoms with testing done to rule out other potential causes.[1]
No cure for ALS is known.[1] A medication called riluzole may extend life by about two to three months.[8]Non-invasive ventilation may result in both improved quality and length of life.[9] The disease usually starts around the age of 60 and in inherited cases around the age of 50.[7] The average survival from onset to death is three to four years.[10] About 10% survive longer than 10 years.[1] Most die from respiratory failure. In much of the world, rates of ALS are unknown.[7] In Europe and the United States the disease affects about two people per 100,000 per year.[7][11]
Descriptions of the disease date back to at least 1824 by Charles Bell.[12] In 1869, the connection between the symptoms and the underlying neurological problems was first described by Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.[12] It became well known in the United States in the 20th century when in 1939 it affected the baseball player Lou Gehrig,[2] and later worldwide when physicist Stephen Hawking, diagnosed in 1963 and expected to die within two years, became famous.[13] In 2014 videos of the ice bucket challenge went viral on the Internet and increased public awareness.[14]
The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel function and the muscles responsible for eye movement are usually spared until the final stages of the disorder.[15]
Cognitive function is generally spared for most people, although some (about 5%) also develop frontotemporal dementia.[16] A higher proportion of people (30–50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Sometimes, ALS coexists in individuals who also experience dementia, degenerative muscle disorder, and degenerative bone disorder as part of a syndrome called multisystem proteinopathy.[17]Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing, sight, touch, smell, andtaste.[18]
The start of ALS may be so subtle that the symptoms are overlooked.[19] The earliest symptoms of ALS are muscle weakness and/or muscle atrophy. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.[citation needed]
About 75% of people contracting the disorder first experience weakness or atrophy in an arm or leg and this is known as “limb-onset” ALS. Awkwardness when walking or running or even tripping over or stumbling may be experienced and often this is marked by walking with a “dropped foot” which drags gently on the ground. Or if arm-onset, difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock may be experienced. Occasionally, the symptoms remain confined to one limb for a long period of time or for the duration of the illness; this is known as monomelic amyotrophy.[citation needed]
About 25% of cases begin as progressive bulbar palsy termed “bulbar-onset” ALS. Initial symptoms will mainly be of difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty in swallowing and loss of tongue mobility. A smaller proportion of people experience “respiratory-onset” ALS, where the intercostal muscles that support breathing are affected first. A small proportion of people may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms.[citation needed]
Over time, people experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski’s sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations) although twitching is not a diagnostic symptom and more of a side effect so twitching would either occur after or accompany weakness and atrophy. Around 15–45% of people experience pseudobulbar affect, a neurological disorder also known as “emotional lability”, which consists of uncontrollable laughter, crying, or smiling, attributable to degeneration of bulbar upper motor neurons, resulting in exaggeration of motor expressions of emotion.[citation needed] For ALS to be diagnosed, symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes must be present.[citation needed]
Although the order and rate of symptoms varies from person to person, most people eventually are not able to walk or use their hands and arms. They also lose the ability to speak and swallow food, while most end up on a portable ventilator, called bilevel positive airway pressure. The rate of progression can be measured using an outcome measure called the “ALS Functional Rating Scale Revised (ALSFRS-R)”, a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though the degree of variability is high and a small percentage of people have a much slower disorder, on average, patients lose about 0.9 FRS points per month. A survey-based study amongst clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful.[20] Regardless of the part of the body first affected by the disorder, muscle weakness and atrophy spread to other parts of the body as the disorder progresses. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS, symptoms typically spread to the arms before the legs.[citation needed]
Disorder progression tends to be slower in patients who are younger than 40 at onset,[21][22] are mildly obese,[23] have disorder restricted primarily to one limb, and those with primarily upper motor neuron symptoms.[24] Conversely, progression is faster and prognosis poorer in people with bulbar-onset disorder, respiratory-onset disorder, and frontotemporal dementia.[24]
The CX3CR1allelic variants have also been shown to have an effect on the disorder’s progression and life expectancy.[25]
Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die within three to five years from the onset of symptoms. In one study, the median survival time from onset to death was around 39 months, and only 4% survived longer than 10 years.[26] Newer data point to around 10% of people surviving beyond 10 years.[1] Guitarist Jason Becker has lived since 1989 with the disorder, while physicist Stephen Hawking has survived for more than 50 years, but they are considered unusual cases.[27]
Difficulty in chewing and swallowing makes eating very difficult and increases the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung functionsuch as vital capacity and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Most people with ALS die of respiratory failure or pneumonia.[7]
In late stages, the oculomotor nerve that controls the movements of the eye can be affected as can the extraocular muscles (EOMs). The eye movements remain unaffected largely until the later stages due to differences in the extraocular muscles compared to the skeletal muscles that are initially and readily affected. In the disease’s final stages, a person’s condition may resemble locked-in syndrome.[28]
About 5–10% of cases are directly inherited from a person’s parents.[7] Overall, first-degree relatives of an individual with ALS have a 1% risk of developing ALS.[29][30]
A defect on chromosome 21, which codes for superoxide dismutase, is associated with about 20% of familial cases of ALS, or about 2% of ALS cases overall.[31][32][33] This mutation is believed to be transmitted in anautosomal dominant manner, and has over a hundred different forms of mutation. The most common ALS-causing mutation is a mutant SOD1 gene, seen in North America; this is characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A-SOD1, is more slowly progressive than typical ALS, and people with this form of the disorder survive for an average of 11 years.[34]
In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD,[35] and accounts for some 6% of cases of ALS among white Europeans.[36]
The UBQLN2 gene encodes production of the protein ubiquilin 2 in the cell, which is a member of the ubiquilin family and controls the degradation of ubiquitinated proteins. Mutations in UBQLN2 interfere with protein degradation, leading to neurodegeneration and causing dominantly inherited, chromosome X-linked ALS and ALS/dementia.[37]
To date, a number of genetic mutations have been associated with various types of ALS. The currently known associations are:
| Type | OMIM | Gene | Locus | Inheritance | Remarks |
|---|---|---|---|---|---|
| ALS1 | 105400 | SOD1 | 21q22.1 | autosomal dominant (?),autosomal recessive (?) | The most common form of familial ALS |
| ALS2 | 205100 | ALS2 | 2q33.1 | autosomal recessive (?) | Juvenile-onset |
| ALS3 | 606640 | (?) | 18q21 | (?) | |
| ALS4 | 602433 | SETX | 9q34.13 | autosomal dominant (?) | |
| ALS5 | 602099 | SPG11 | 15q21.1 | autosomal recessive (?) | Juvenile onset |
| ALS6 | 608030 | FUS | 16p11.2 | (?) | |
| ALS7 | 608031 | (?) | 20p13 | (?) | |
| ALS8 | 608627 | VAPB | 20q13.3 | autosomal dominant (?) | |
| ALS9 | 611895 | ANG | 14q11.2 | (?) | |
| ALS10 | 612069 | TARDBP | 1p36.2 | autosomal dominant (?) | ALS with or without frontotemporal dementia |
| ALS11 | 612577 | FIG4 | 6q21 | (?) | |
| ALS12 | 613435 | OPTN | 10p13 | (?) | |
| ALS13 | 183090 | ATXN2 | 12q24.12 | autosomal dominant (?) | Spinocerebellar ataxia 2 |
| ALS14 | 613954 | VCP | 9p13.3 | (?) | Recent new study shows strong link in ALS mechanism[38][39] |
| ALS15 | 300857 | UBQLN2 | Xp11.21 | X-linked dominant (?) | Described in one family[37] |
| ALS16 | 614373 | SIGMAR1 | 9p13.3 | autosomal recessive (?) | Juvenile onset, very rare, described only in one family[40] |
| ALS17 | 614696 | CHMP2B | 3p11.2 | autosomal dominant (?) | Very rare, reported only in a handful of people |
| ALS18 | 614808 | PFN1 | 17p13.2 | (?) | Very rare, described only in a handful of Chinese families[41] |
| ALS19 | 615515 | ERBB4 | 2q34 | autosomal dominant (?) | Very rare, as of late 2013 described only in four people[42] |
| ALS20 | 615426 | HNRNPA1 | 12q13.13 | (?) | Very rare, as of late 2013 described only in two people[43] |
| ALS21 | 606070 | MATR3 | 5q31.2 | autosomal dominant (?) | Very rare. Formerly known as “distal myopathy type 2” (MPD2) and “vocal cord and pharyngeal dysfunction with distal myopathy” (VCPDM) |
| ALS22 | 616208 | TUBA4A | 2q35 | autosomal dominant (?) | “Amyotrophic lateral sclerosis 22 with or without frontotemporal dementia” |
| FTDALS1 | 105550 | C9orf72 | 9p21.2 | autosomal dominant (?) | “Frontotemporal dementia and/or amyotrophic lateral sclerosis type 1”. Accounts for around 6% of ALS cases among white Europeans[citation needed] |
| FTDALS2 | 615911 | CHCHD10 | 22q11.23 | autosomal dominant (?) | “Frontotemporal dementia and/or amyotrophic lateral sclerosis type 2” |
| FTDALS3 | 616437 | SQSTM1 | 5q35.3 | autosomal dominant (?) | “Frontotemporal dementia and/or amyotrophic lateral sclerosis type 3” |
| FTDALS4 | 616439 | TBK1 | 12q14.2 | autosomal dominant (?) | “Frontotemporal dementia and/or amyotrophic lateral sclerosis type 4” |
In 1993, scientists discovered that mutations in the gene (SOD1) that produces the Cu–Znsuperoxide dismutase (SOD1) enzyme were associated with around 20% of familial ALS. This enzyme is a powerfulantioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to DNA and proteins within cells. To date, over 110 different mutations in SOD1 have been linked with the disorder, some of which (such as H46R) have a very long clinical course, while others, such as A4V, are exceptionally aggressive. When the defenses against oxidative stress fail, programmed cell death (apoptosis) is upregulated.
A defect in SOD1 could be a loss or gain of function. A loss of SOD1 function could lead to an accumulation of free radicals. A gain of SOD1 function could be toxic in other ways.[44][45]
Aggregate accumulation of mutant SOD1 is suspected to play a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein folding chaperones, or other proteins.[46] Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. Critics have noted that in humans, SOD1 mutations cause only 2% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. To date, the ALS-SOD1 mice remain the best model of the disease for preclinical studies, but it is hoped that more useful models will be developed.
While moderate to severe traumatic brain injury is a risk for ALS, it is unclear if mild traumatic brain injury increases rates.[47][48]
In 1994 the National Institute for Occupational Safety and Health (NIOSH) reported a nonsignificant increase in nervous system disorders due to four cases of ALS among NFL football players. It was unclear if this was due to chance or not.[49] Another study from 2012 also found a possible increase in ALS in NFL football players.[50] An older study did not find an increased risk among high school football players.[47] A 2007 review found an increased risk among soccer players.[48] ALS may also occur more often among the US military veterans however the reason is unknown.[51] This may be due to head injury.[52]
Where no family history of the disease is present – i.e., in around 90% of cases – no cause is known for ALS. Possible associations for which evidence is inconclusive include military service, frequent drug use, and participation in contact sports.[medical citation needed]
Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the neurotransmitters in the brain. Scientists have found, compared with healthy people, people with ALS have higher levels of glutamate in their serum and spinal fluid.[32]Riluzole is currently the only FDA-approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease.
Certain studies suggested a link between sporadic ALS, specifically in athletes, and a diet enriched with branched-chain amino acids, a common dietary supplement among athletes, which cause cell hyperexcitability resembling that usually observed in people with ALS. The proposed underlying mechanism is that cell hyperexcitability results in increased calcium absorption by the cell, and thus brings about cell death of neuronal cells, which have particularly low calcium buffering capabilities.[53]
Some evidence supports superoxide dismutase 1 (SOD1) protein misfolding propagates between molecules in a similar fashion to prions.[54] Similarly, it has been proposed that incorporation of the cyanobacterial toxin β-methylamino-l-alanine (BMAA) leads to another prion-like protein misfolding propagation.[55][56]
Another very common factor associated with ALS is a lesion to the motor system in areas such as the frontotemporal lobes.[57] Lesions in these areas often show signs of early deficit, which can be used to predict the loss of motor function, and result in the spread of ALS.[57] The mechanisms of ALS are present long before any signs or symptoms become apparent.[58] Before any muscular atrophy becomes apparent during ALS, roughly one-third of the motor neurons must be destroyed.[58]
Other potential risk factors including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated, but are without consistent findings.[59][60] There is a tentative association with exposure to a number of pesticides including the organochlorine insecticidesaldrin, dieldrin, DDT, and toxaphene.[61][62][63]
The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop protein-richinclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.[37] These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1,TAR DNA binding protein (TDP-43, or TARDBP), and/or FUS.[64]
No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive.[1] Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the person and a series of tests to rule out other diseases.[1] Physicians obtain the person’s fullmedical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are worsening.[1]
Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions.[1] One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles.[1] Certain EMG findings can support the diagnosis of ALS.[1] Another common test measures nerve conduction velocity (NCV).[1] Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging (MRI) is often normal in people with early stage ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, aherniated disk in the neck, syringomyelia, or cervical spondylosis.[1]
Based on the person’s symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases, as well as routine laboratory tests.[1] In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.[1]
Viralinfectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease,[65]syphilis[66] and tick-borne encephalitis[67] can in some cases cause ALS-like symptoms.[1]Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, spinal muscular atrophy, and spinal and bulbar muscular atrophy can also mimic certain aspects of the disease and should be considered.[1]
ALS must be differentiated from the “ALS mimic syndromes” which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants.[68] Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, people should always obtain a specialist neurological opinion, so alternative diagnoses are clinically ruled out. Benign fasciculation syndrome is another condition that mimics many of the symptoms of ALS, but is accompanied by normal EMG readings and no major disablement.[citation needed]
However, most cases of ALS are readily diagnosed and the error rate of diagnosis in large ALS clinics is less than 10%.[69][70] In one study, 190 patients who met the MND/ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these patients (16%) had their diagnosis completely changed during the clinical observation development period.[71] In the same study, three patients had a false negative diagnosis, myasthenia gravis (MG), an autoimmune disease. MG can mimic ALS and other neurological disorders leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not.[72] Myasthenic syndrome, also known as Lambert-Eaton syndrome, can mimic ALS and its initial presentation can be similar to that of MG.[73][74]
Management of ALS attempts to relieve symptoms and extend life expectancy. This supportive care is best provided by multidisciplinary teams of health care professionals working with the person and their caregivers to keep them as mobile and comfortable as possible.[citation needed]
Riluzole (Rilutek) has been found to modestly improve survival.[75] It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. People taking it must be monitored for liver damage (occurring in about 10% of people taking the drug).[76] It is approved by Food and Drug Administration (US) and recommended by the National Institute for Clinical Excellence (UK). Riluzole does not reverse damage already done to motor neurons.[77]
Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl or amitriptyline may be prescribed when people with ALS begin having trouble swallowing their saliva.[15]
When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation, bilevel positive airway pressure (BiPAP), or biphasic cuirass ventilation (BCV) may be used to aid breathing. Such devices artificially inflate the person’s lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time. BCV has the added advantage of being able to assist in clearing secretions by using high-frequency oscillations followed by several positive expiratory breaths.[78] People may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheotomy, in which a plastic breathing tube is inserted directly in the person’s windpipe through an opening in the neck.[citation needed]
Persons and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the person’s quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support and have deep discussions on quality of life. Some persons under long-term tracheotomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheotomy tubes (leak ventilation) are able to speak, provided their bulbar muscles are strong enough, though in all cases speech will be lost as the disease progresses. This technique preserves speech in some persons with long-term mechanical ventilation. Other persons may be able to use a speaking valve such as a Passey-Muir speaking valve with the assistance and guidance of a speech-language pathologist.[citation needed]
External ventilation machines that use the ventilation mode of BiPAP are frequently used to support breathing, initially at night, and later during the daytime, as well. The use of BPAP (more often referred to as noninvasive ventilation, NIV) is only a temporary remedy, however, and long before BPAP stops being effective, persons should decide whether to have a tracheotomy and long-term mechanical ventilation. At this point, some persons choose palliative hospice care.[citation needed]
Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence.[79]
Occupational therapy and special equipment such as assistive technology can also enhance patients’ independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help patients remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable people to retain as much safety and independence in activities of daily living as possible.[citation needed]
People with ALS who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more
The Pronk Pops Show 858, Part 2 — Story 1: House Freedom Caucus Is Right: First Complete Clean Repeal and Then Replace Obamacare — No Three Phases/Prongs Bull — Change Your Rules or American People Will Replace You — Restore Free Market Competition In Health Insurance Sector So That Companies and Consumers Are Free of Government Mandates and Dictates Thereby Lowering Premiums and Deductibles — Freedom Works — Repeal and Replace Obamacare Now! — Videos
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Part 2 — Story 1: House Freedom Caucus Is Right: First Complete Clean Repeal and Then Replace Obamacare — No Three Phases/Prongs Bull — Change Your Rules or American People Will Replace You — Restore Free Market Competition In Health Insurance Sector So That Companies and Consumers Are Free of Government Mandates and Dictates Thereby Lowering Premiums and Deductibles — Freedom Works — Repeal and Replace Obamacare Now! — Videos
What Is Budget Reconciliation?
Video Transcript:
Led by President Donald Trump, Republicans have promised to repeal the Affordable Care Act. They have control of both houses of Congress and the White House, but they still have one big obstacle in that effort.
In the Senate, opponents could stage a filibuster — the right of the minority to try to talk a bill to death and keep senators from voting. It takes 60 votes to stop a filibuster. Republicans have a majority but only 52 seats. And Democrats say they won’t help take apart the health law they voted to pass seven years ago.
Instead, Republicans are vowing to use a budget procedure called “reconciliation.” It comes from a 1974 law called the Congressional Budget and Impoundment Control Act. Lots of major health laws have been passed using reconciliation, including those guaranteeing the right to emergency room care, creating the Children’s Health Insurance Plan, and allowing private plans as an alternative to traditional Medicare coverage.
Here’s how reconciliation would work. First, Congress has to pass a budget resolution.
That budget document has to be agreed on by the House and Senate, but it doesn’t go to the president for his signature.
The budget resolution does two main things. First, it sets spending targets for federal programs Congress funds every year. Those are known as appropriations.
But there are also programs funded by the federal government that don’t need annual approvals from Congress. These include tax cuts or increases and so-called entitlement programs like Medicare and Medicaid.
So the budget resolution also instructs the congressional committees in charge of those programs to propose changes in the law that would “reconcile” how much those programs cost with the targets set by the budget. This is what Republicans would use to order changes to the Affordable Care Act.
When the committees report back their proposed changes, they are assembled into a budget reconciliation bill.
In the Senate, budget reconciliation has its own special rules that make it easier to pass. Debate is strictly limited, and the bill only needs a simple majority to pass.
But there are limits, too. Budget reconciliation bills can only change things that directly impact the federal budget — either adding to or reducing federal spending.
For the Affordable Care Act, that means Congress could use budget reconciliation to eliminate spending, like the help people get to pay their premiums or funding to states to expand the Medicaid program for the poor. It can also repeal the taxes that help pay for those benefits, including the tax penalties for individuals who fail to have insurance.
But Congress can’t use reconciliation to change parts of the health law like provisions requiring insurance companies to provide certain benefits or sell coverage to people with preexisting conditions. Those don’t directly affect federal spending.
That has led insurance companies to complain that they will go broke if they still have to sell to sick people, but healthy people won’t have any incentive to get covered. In that case, they say, only sick people will buy insurance, and premiums will skyrocket.
And the new Republican Congress seems set on using the technique to take apart the health law. Whether that’s a good idea may depend on whether you favor or oppose the Affordable Care Act.
Sen. Mitch McConnell: ‘If’ The House Passes Repeal/Replace Bill, ‘I’ll Bring It Up’
Rand Paul Doesn’t Want the GOP to Fail at Obamacare Replacement Plan
Paul Ryan’s Obamacare Lite Plan with Skyrocket Prices | Rand Paul
Let’s Stop Kissing the Boots of Insurance Companies | Rand Paul
How Trump is trying to sell Republicans on the health care bill
FreedomWorks Day of Action Obamacare Repeal Rally
Watch House Freedom Caucus members speak out on health care bill
Reps. Gohmert, Meadows detail the new ObamaCare proposal
Trump makes final push for health care bill
Paul Ryan: President Trump ‘Knocked The Ball Out Of The Park’ With Capitol Visit | NBC News
Speaker Ryan on President Trump’s Visit: “We Are All-In To End This Obamacare Nightmare”
FNN: Paul Ryan’s FULL PowerPoint Presentation on American Health Care Act (Obamacare Replacement)
AWESOME!! PRESIDENT TRUMP KEEPING HIS PROMISE ON OBAMACARE REPEAL AND REPLACE
House Freedom Caucus Throws Support Behind Paul Health Care Plan
Rand Paul Unveils His Brilliant Replacement Plan for Obamacare
CSPAN | Rand Paul Answers Tough Questions on His Healthcare Plan
Rand Paul and Mark Sanford Unveil Obamacare / Affordable Care Act Replacement Bill
Rand Paul on Why He Walked Out of Obamacare Meeting
Reconciliation in Congress
Exclusive — Rand Paul: ‘Easily 35 No Votes’ Against Paul Ryan’s Obamacare 2.0, ‘I Would Predict They Pull Bill, Start Over’
by MATTHEW BOYLE
21 Mar 2017Washington, D.C.2,723
Sen. Rand Paul (R-KY) told Breitbart News exclusively on Tuesday afternoon that he expects House Speaker Paul Ryan will be forced to pull the American Health Care Act (AHCA) before a scheduled Thursday vote because Ryan will not get the votes to pass the legislation.
The AHCA has been dubbed “Obamacare Lite” by Paul — a leading conservative critic of the plan — and by other conservatives as “RyanCare,” “RINO-Care,” and “Obamacare 2.0,” since the bill does not actually fully repeal Obamacare and keeps many of the main structures that the now-former President Barack Obama installed in the healthcare system. It has come under intense scrutiny from both sides of the Republican Party — moderates and conservatives are lining up against the bill — and Ryan, despite publicly projecting confidence, cannot find the necessary 216 votes to pass the legislation.
Paul, one of the leading senators out of more than a dozen Republicans in the upper chamber criticizing the bill there, told Breitbart News in this exclusive interview he believes there are at least 35 House Republicans ready to vote against the bill in its current form. And he predicted that, unless some major changes come to the legislation between now and the scheduled vote on Thursday, Ryan will need to withdraw the bill and Republicans will have to start from scratch with a new bill and a new strategy on Obamacare.
Paul said in the in-person interview at his U.S. Senate office in the Russell Senate Office Building:
View image on Twitter
There is plenty of reason to believe that Paul is correct in predicting Ryan does not have the votes to pass this legislation and will need to pull the bill to start over. Despite overtures from President Donald Trump, the House Freedom Caucus members — and particularly its chairman Rep. Mark Meadows (R-NC) — remain steadfastly opposed to the bill.
View image on Twitter
But Breitbart News can confirm several more than that are definitely opposed to the legislation. To kill the bill, Republicans need just 21 Republicans opposed—and some are talking about holding a press conference on Wednesday or Thursday with the necessary number of House Republicans to crush RyanCare, appearing arm-in-arm in public opposition before a vote.
House GOP leadership made some last minute changes, too, which Paul — in his interview with Breitbart News — flatly said “no,” were not enough to get the bill passed. Regarding those changed, Paul said:
Paul added that Ryan would not have dragged President Trump into this awful position if he had been more open and inclusive in the process from the beginning. In effect, Paul argued as he has done before, that Ryan is hurting President Trump by doing this the way he is doing it. Paul said:
Paul would not say if Ryan will lose the confidence necessary to run the House of Representatives if this bill fails, as some have suggested. When asked if Ryan can still run the House if the bill goes down, Paul told Breitbart News that instead he thinks the bill going down would lead to real negotiations on healthcare reform. He said:
More from Sen. Rand Paul’s latest exclusive interview with Breitbart News is forthcoming.
http://www.breitbart.com/big-government/2017/03/21/exclusive-rand-paul-easily-35-no-votes-paul-ryans-obamacare-2-0-predict-pull-bill-start/
Conservative Review
Member Name Party State Liberty Score Years in DC Next Election
Track
Gary Palmer R AL-6 A 100% 2 2018
Dave Brat R VA-7 A 100% 2 2018
Mike Lee R UT A 100% 6 2022
Louie Gohmert R TX-1 A 98% 12 2018
Ted Cruz R TX A 97% 4 2018
Jim Bridenstine R OK-1 A 97% 4 2018
Justin Amash R MI-3 A 96% 6 2018
Jeff Duncan R SC-3 A 96% 6 2018
Jim Jordan R OH-4 A 96% 10 2018
Thomas Massie R KY-4 A 94% 4 2018
Benjamin Sasse R NE A 94% 2 2020
Mark Meadows R NC-11 A 94% 4 2018
Ken Buck R CO-4 A 94% 2 2018
Raul Labrador R ID-1 A 93% 6 2018
Rand Paul R KY A 92% 6 2022
Trent Franks R AZ-8 A 90% 14 2018
David Schweikert R AZ-6 A 90% 6 2018
Mark Sanford R SC-1 A 90% 3 2018
Tim Scott R SC B 89% 4 2022
Ron DeSantis R FL-6 B 87% 4 2018
Tom McClintock R CA-4 B 86% 8 2018
Scott DesJarlais R TN-4 B 85% 6 2018
Trey Gowdy R SC-4 B 85% 6 2018
Doug Lamborn R CO-5 B 85% 10 2018
Randy Weber R TX-14 B 84% 4 2018
Paul Gosar R AZ-4 B 84% 6 2018
Mo Brooks R AL-5 B 84% 6 2018
Kenny Marchant R TX-24 B 84% 12 2018
Sam Johnson R TX-3 B 82% 25 2018
Steve King R IA-4 B 81% 14 2018
John Ratcliffe R TX-4 B 81% 2 2018
Jody Hice R GA-10 B 81% 2 2018
Dana Rohrabacher R CA-48 B 80% 28 2018
Andy Harris R MD-1 B 80% 6 2018
Bill Posey R FL-8 B 80% 8 2018
John J. Duncan Jr. R TN-2 B 80% 28 2018
– See more at: https://www.conservativereview.com/scorecard#sthash.RyaYlHY1.dpuf
Freedom Caucus
Fiscal conservatism
Social conservatism[1]
29 / 435
The Freedom Caucus, also known as the House Freedom Caucus, is a congressional caucus consisting of conservative Republican members of the United States House of Representatives.[7] It was formed in 2015 by a group of Congressmen as what member Jim Jordan called a “smaller, more cohesive, more agile and more active” group of conservatives.[8]
Many members are also part of the Republican Study Committee, another conservative House group.[8][9] The caucus is sympathetic to the Tea Party movement.[10] According to its mission statement, it “gives a voice to countless Americans who feel that Washington does not represent them. We support open, accountable and limited government, the Constitution and the rule of law, and policies that promote the liberty, safety and prosperity of all Americans.”[11]
History
The origins of the caucus lie at the mid-January 2015 Republican congressional retreat in Hershey, Pennsylvania. Nine conservative active Republican members of the House began planning a new Congressional caucus separate from the Republican Study Committee and apart from the House Republican Conference. The group ultimately became the nine founding members and the first board of directors for the new caucus consisting of Republican Representatives Scott Garrett of New Jersey, Jim Jordan of Ohio, John Fleming of Louisiana, Matt Salmon of Arizona, Justin Amash of Michigan, Raúl Labrador of Idaho, Mick Mulvaney of South Carolina, Ron DeSantis of Florida and Mark Meadows of North Carolina.[12] The group debated over a name for their new caucus eventually settling on “House Freedom Caucus” (HFC) because, according to founding member Mick Mulvaney, “it was so generic and universally awful that we had no reason to be against it.” The group of nine founding members in Hershey set as a criterion for new members that they had to be willing to vote against Speaker of the United States House of Representatives John Boehner on legislation that the group opposed.[13]
During the crisis over the funding of the Department of Homeland Security in early 2015, the Caucus offered four plans for resolution, but all were rejected by the Republican leadership. One of the caucus leaders, Labrador of Idaho, said the Caucus will offer an alternative that the most conservative Republican members could support.[14][needs update]
The House Freedom Caucus was involved in the resignation of Boehner on September 25, 2015, and the ensuing leadership battle for the new Speaker.[15] Members of the Caucus who had voted against Boehner for Speaker felt unfairly punished, accusing him of cutting them off from positions in the Republican Study Committee and depriving them of key committee assignments.[not in citation given] Boehner found it increasingly difficult to manage House Republicans with the fierce opposition of the Freedom Caucus, and he sparred with House Republican members (who later created and became members of the Freedom Caucus when it was created in 2015) in 2013 over their willingness to shut down the government in order to accomplish goals such as repealing the Affordable Care Act.[13][16][not in citation given]
Initially, Kevin McCarthy, the House Majority Leader, was the lead contender, but the Freedom Caucus withheld its support.[17] However, McCarthy withdrew from the race on September 28, 2015.[18] On the same day as McCarthy’s withdrawal, Reid Ribble resigned from the Freedom Caucus saying he had joined to promote certain policies and could not support the role that it was playing in the leadership race.[19]
On October 20, 2015, Paul Ryan announced that his bid for the Speaker of the United States House of Representatives was contingent on an official endorsement by the Freedom Caucus.[20] While the group could not reach the 80% approval that was needed to give an official endorsement, on October 21, 2015, it announced that it had reached a supermajority support for Ryan.[21] On October 29, 2015, Ryan succeeded John Boehner as the Speaker of the House.[22]
On November 17, 2015, Jim Jordan was re-elected as Chairman of the caucus.[citation needed]
The group has faced backlash from the Republican Party establishment during the 2016 election cycle.[23] One of its members, Congressman Tim Huelskamp, a Tea Party Republican representing Kansas’s First District, was defeated during a primary election on August 2, 2016, by Roger Marshall.[24] GOP Establishment PACs, many of whom also opposed Donald Trump, spent nearly $2 million to defeat Huelskamp.[25]
Membership
Congressional District map for Freedom Caucus membership of the 114th Congress. Former members in light color.
Members of the House Freedom Caucus as of March 2017 include:
Former members
See also
https://en.wikipedia.org/wiki/Freedom_Caucus
It’s Rand Paul vs Paul Ryan in the battle over Obamacare — and the future of the GOP
Brandon Morse Mar 17, 2017 8:52 am
A protester wears a Repeal Obamacare button on his jacket during a Freedom Works rally Wednesday against the proposed GOP health care plan across from the U.S. Capitol in Washington, D.C. (Justin Sullivan/Getty Images)
Paul has been waging a war against the House GOP Obamacare repeal and replace plan since before it was given to the public. Calling it “Obamacare Lite,” Paul has lambasted not only the bill, but his fellow Republicans for their less-than-diligent attempts at getting rid of the unpopular health care law. This time, he turned his attention toward Ryan, who has been the bill’s primary spokesman.
“I think that Paul Ryan’s selling [Donald Trump] a bill of goods that he didn’t explain to the president, and the grassroots doesn’t want what Paul Ryan is selling,” Paul told CNN.
Paul Ryan, during an segment on CNN’s “The Lead with Jake Tapper,” fired back at the Kentucky senator, claiming that his remarks were a jab at President Donald Trump.
“Frankly, I think that’s kind of an insulting remark to the president — as if he doesn’t know what he’s doing,” Ryan said.
“We think this is a smarter way to go,” Ryan said to Tapper. “The alternative is the status quo, and the status quo is in the middle of a collapse.”
Ryan has made the case that this version of the Obamacare repeal bill is the “closest we will ever get” to repealing it.
Paul, however, believes that Trump is open to changing his mind on the health care bill, despite his prior statements of broad approval, and that it’s Republican leadership who have “dug in their heels.”
Other Republicans in Congress have joined Paul in his efforts to push a more conservative version of a repeal bill, which focuses solely on repeal, and repeal alone. Rep. Jim Jordan and Paul have both submitted versions of the bill in the Senate and the House, and has the support of conservative legislators such as Rep. Justin Amash, Sen. Mike Lee, Rep. Jeff Duncan, and Sen. Tom Cotton. This list of allies now also includes a group of moderate Republicans rattled by the recent Congressional Budget Office report.
As the battle continues between the conservatives and GOP leadership, the faith of the voters hangs in the balance, according to the conservatives. Paul believes that should the GOP pass “Obamacare Lite,” Republicans will pay for it come election time. Duncan wrote in the Daily Signal that should the bill pass, voters “will feel betrayed.”
If that is true, then winner of the struggle between Paul and Ryan may determine the GOP’s future momentum.
http://www.theblaze.com/news/2017/03/17/its-rand-paul-vs-paul-ryan-in-the-battle-over-obamacare-and-the-future-of-the-gop/
Rand Paul Unveils His Brilliant Obamacare Replacement Plan
WASHINGTON (AP) — Time for talk running out, President Donald Trump on Tuesday warned wavering House Republicans that their jobs were on the line in next year’s elections if they failed to back a GOP bill that would overhaul Barack Obama’s Affordable Care Act.
The countdown quickened toward an expected vote Thursday on legislation undoing much of the law that provided health coverage to some 20 million Americans. Trump huddled behind closed doors with rank-and-file Republicans just hours after GOP leaders unveiled changes intended to pick up votes by doling out concessions to centrists and hardliners alike.
“If we fail to get it done, fail to (meet) the promises made by all of us, including the president, then it could have a very detrimental effect to Republicans in ’18 who are running for re-election,” said Rep. Mike Conaway, R-Texas. “If it fails, then there will be a lot of people looking for work in 2018.”
Trump’s message to Republicans: “If you don’t pass the bill there could be political costs,” said Rep. Walter Jones, R-N.C.
The outlook for House passage remains dicey even with the revisions.
The GOP bill would scale back the role of government in the private health insurance market, and limit future federal financing for Medicaid. It would also repeal tax cuts on the wealthy that Democrats used to pay for Obama’s coverage expansion. Fines enforcing the Obama-era requirement that virtually all Americans have coverage would be eliminated.
The nonpartisan Congressional Budget Office estimates that 24 million fewer people will have health insurance in 2026 under the GOP bill.
Trump warned House Republicans they’d seal their political doom if they waver, with the party potentially losing majority control of the House. Still, several conservatives were steadfast in their opposition even after the session with Trump and the leadership’s changes.
“The president wouldn’t have been here this morning if they have the votes,” said Rep. Rod Blum, R-Iowa, a member of the Freedom Caucus who complained that the GOP bill leaves too much government regulation in place.
Rep. Don Bacon, R-Neb., said he was convinced to back the bill in part by Trump’s urging and the changes.
“I think a vote ‘no’ is a vote for Obamacare,” Bacon said. “We can vote for this, and continue to make it better. I intend to vote ‘yes’ Thursday.”
Speaker Paul Ryan, R-Wis., told reporters that if Republicans pass the legislation, “people will reward us. If we don’t keep our promise, it will be very hard to manage this.”
If the bill advances, prospects are uncertain in the Senate, where Republicans hold a slim majority. Six GOP senators have expressed deep misgivings including Tom Cotton of Arkansas, who said Tuesday he cannot support the House bill.
In an Associated Press interview, Senate Majority Leader Mitch McConnell, R-Ky., signaled he’d use Trump’s clout to pressure unhappy Republicans in his chamber. McConnell said he’s optimistic that in the end no Republican senator will want to be held responsible for “Obamacare’s” survival.
“I would hate to be a Republican whose vote prevented us from keeping the commitment we’ve made to the American people for almost 10 years now,” McConnell said.
The House GOP bill would dismantle Obama’s requirements that most people buy policies and that larger companies cover workers. Federal subsidies based on peoples’ incomes and the cost of insurance would end, and a Medicaid expansion to 11 million more low-income people would disappear.
Instead, the bill would provide tax credits based chiefly on age to help people pay premiums. Open-ended federal payments to help states cover Medicaid costs would be cut. Insurers could charge older consumers five times the premiums they charge younger people instead of Obama’s 3-1 limit, and would boost premiums 30 percent for those who let coverage lapse.
The latest changes to the bill by GOP leaders were largely aimed at addressing dissent that the measure would leave many older people with higher costs.
Included was an unusual approach: language paving the way for the Senate, if it chooses, to make the bill’s tax credit more generous for people age 50-64. Republicans said the plan sets aside $85 billion over 10 years for that purpose. The income tax threshold for deducting medical expenses would be lowered to 5.8 percent, from the current 10 percent.
The leaders’ proposals would accelerate the repeal of tax increases Obama imposed on higher earners, the medical industry and others.
On Medicaid, the changes would provide higher federal payments to help states care for older and disabled beneficiaries. States would be able to impose work requirements for able-bodied adults. But the bill would still limit future federal financing for Medicaid, seen by many state officials as a cost shift. Obama’s Medicaid expansion would be repealed.
In a bid to cement support from upstate New Yorkers, the revisions would also stop that state from passing on over $2 billion a year in Medicaid costs to upstate counties, though it exempts Democratic-run New York City from that protection. Local officials have complained the practice overburdens their budgets.
Democrats remain solidly opposed to the GOP repeal effort.
Rep. Chris Collins, R-N.Y., said Trump told Republicans he would campaign for them if they backed the bill.
—
Associated Press reporters Matthew Daly, Kevin Freking, Richard Lardner, Stephen Ohlemacher in Washington and Thomas Beaumont in Iowa contributed to this report.
http://hosted.ap.org/dynamic/stories/U/US_CONGRESS_HEALTH_OVERHAUL?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT&CTIME=2017-03-21-03-20-21
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