This is an overview of Atypical Parkinsonism written by our friend Dr. Golbe. Of course covering five disorders in a two-page document means that lots of information is left out, including subtleties and exceptions. But overall, I think this is a reasonably good overview of these disorders. (The first four disorders are in our local support group. Vascular Parkinsonism is not; I know nothing about it.) I read about this article on an MSA-related Yahoo!Group today. Unfortunately the newsletter isn’t available online yet so there’s nothing to link to; for future reference the APDA’s website is apdaparkinson.org.
by Lawrence I. Golbe, MD, Professor of Neurology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ
The American Parkinson Disease Association Winter 2008 Newsletter
You may have been told by your doctor that you have not Parkinson’s disease but “atypical parkinsonism,” “Parkinson’s-plus” or “Parkinson’s syndrome.” Confused?
What is “Parkinson’s syndrome”?
A “syndrome” is a group of signs and symptoms that often occur together and may be caused by any of a variety of diseases. A “disease” is an abnormal process, usually with a specific cause. For example, the syndrome called the “flu,” which includes fever, muscle aches, cough and headache, can be the result of any of several diseases, only one of which is an infection by the influenza virus.
Similarly, a combination of slowness, muscle rigidity, tremor and impaired balance is a syndrome called “Parkinson’s syndrome” or just “parkinsonism.” The disease that most commonly causes it is “Parkinson’s disease” (PD). PD is strictly defined as parkinsonism associated with gradual loss of certain groups of brain cells that, as they sicken, form within them microscopic balls called Lewy bodies.
Parkinsonism may also be caused by a dozen diseases other than PD. Most of these cause other signs and symptoms in addition to the parkinsonism, which is why they are also called the “Parkinson-plus disorders or the “atypical parkinsonisms.”
Progressive Supranuclear Palsy
The most common atypical parkinsonism is “progressive supranuclear palsy” or PSP. There are only about 20,000 people with PSP in the US, while there may be one million with PD. What’s “atypical” about PSP is its failure to respond to levodopa/carbidopa or other PD medications, difficulties looking up and down, an erect or even backwardly arched neck posture, and the relatively early appearance of falls, slurred speech and swallowing difficulty. Most of these features can occur in PD, but not with the intensity or frequency with which they appear in PSP. Instead of Lewy bodies, the brain cells in PSP have “neurofibrillary tangles.” While Lewy bodies are mostly made up of a protein called alpha-synuclein, neurofibrillary tangles are made of a different protein called “tau.”
Multiple System Atrophy
The next most common atypical parkinsonism is “multiple system atrophy” or MSA. In addition to parkinonism, MSA usually features the type of poor coordination and balance that arises from disorders of the cerebellum, giving some sufferers a “drunken” appearance. Other “atypical” features in most people with MSA are low blood pressure, sensations of being too hot or cold, constipation, urinary difficulties and brief episodes of shortness of breath or sleep apnea. These arise from “dysautonomia” which is a loss of brain cells that control the autonomic nervous system. The dysautonomia of MSA was called “Shy-Drager syndrome” before it was recognized in the early 1990’s as part of a specific disease that can have several forms. Like PSP, MSA causes earlier balance problems than PD and medication for PD usually has little benefit. However, there is medication for most of the dysautonomic features. In MSA, the protein that aggregates is alpha-synuclein, as in PD, but it does so in a different set of brain cells and looks different from Lewy bodies. The protein aggregates in MSA are called “glial cytoplasmic inclusions.”
The third leading atypical parkinsonism is “corticobasal degeneration” (CBD). CBD affects one side of the body first and worst. This is also true, but to a far lesser extent, for PD. For PSP and MSA, the problem is usually symmetric, with left and right sides affected nearly equally. CBD, in addition to parkinsonism, features abnormally heightened reflexes as elicited by tapping with a hammer, and small, sudden, rapid involuntary movements called myoclonus. Its most distinctive feature is apraxia, which is a loss of the ability to perform complex movements with the hands or feet. There is also difficulty with the ability to perceive the spatial features of objects. At present, no medication is effective, unfortunately, and the disorder is treated with physical therapy. In CBD, the protein that aggregates is tau, as in PSP, but it does so mostly on one side of the brain, and disproportionately in the area of the brain responsible for planning complex movement tasks, the frontal lobes.
Dementia with Lewy Bodies
“Dementia with Lewy bodies” is a parkinsonian disorder that often starts with confusion, depression or psychosis (that is, hallucinations or delusions). However, the mental symptoms appear before or together with the movement symptoms and not afterwards, as in PD. The movement difficulty may even be very mild and, as for most of the atypical parkinsonisms, tremor at rest is far less common than in PD. In DLB, the behavioral symptoms can vary greatly over periods of minutes to days and can include periods of unresponsiveness, elaborate delusions and visual hallucinations in addition to the difficulty with memory and thinking. The hallucinations of DLB can occur without levodopa or other dopamine-enhancing medications, while in PD, any hallucinations are a side effect of those medications. The parkinsonism of DLB responds to levodopa/carbidopa. The movement and behavioral symptoms can be severely and dangerously exacerbated by drugs that block dopamine such as Haldol (haloperidol), Compazine (prochlorperazine), and Reglan (metoclopramide).
Another common condition causing atypical parkinsonism is “vascular parkinsonism” or “arteriosclerotic parkinsonism.” This is the eventual result of many tiny strokes, no one of which may be large enough to cause symptoms at the time it occurs. The strokes can be seen on an MRI scaan. Over the years, the cumulative effect causes movement difficulty, especially with walking and other movement of the legs. The condition does not respond to PD medication, but its progression can often be slowed or even stopped by controlling risk factors such as high blood pressure, smoking, or high lipids. Physical therapy is helpful in dealing with the gait problem.
How Do I Tell If I Have Atypical Parkinsonism?
Atypical parkinsonism rather than PD should be suspected when someone with the parkinsonian syndrome has little or no response to a moderate dosage of levodopa/carbidopa or when there is the early appearance of falls, behavioral changes, swallowing problems, abnormal eye movements, bladder problems or lightheadedness on standing. The physician should order an MRI scan, which can show the small strokes of vascular parkinsonism, the asymmetric shrinking of corticobasal degeneration, the unusual pattern of brain shrinkage of progressive supranuclear palsy, or the abnormal pattern of iron and scarring of PSP or multiple system atrophy. Some other radiologic tests such as PET and SPECT can also be helpful in special circumstances.
While the atypical parkinsonism are more difficult to treat than PD, the good news is that they do not run in families nearly as often as PD does. While 20-25% of people with PD have some close relative with PD, fewer than 1% of those with PDP, MSA or CBD have a relative with atypical parkinsonism. For DLB and vascular parkinsonism, the fraction is slightly higher. The causes of the atypical parkinsonism are started to be worked out. As we learn more about the abnormal processes in the brain cells in these conditions, treatments that may slow, stop or even reverse their course will become possible.