Atypical Parkinsonism

What is “typical” Parkinson’s disease?

Parkinson’s disease is a progressive brain disorder which usually produces some combination of the following symptoms: 1. tremor at rest, 2. slowed movement, 3. stiffness or rigidity of muscles, 4. unsteadiness when standing or walking, and 5. “freezing”, or sudden loss of ability to move (as if the feet are “glued” to the floor). Parkinson’s disease (PD) results from dying off (degeneration) of certain nerve cells found in a deep part of the brain (brainstem) called the substantia nigra. The reason for the cell death is unknown. These cells produce a neuro¬transmitter chemical called dopamine. It is the depletion of dopamine in the brain that results in symptoms of PD. Initially, Parkinson’s symptoms improve with dopamine replacement in the form of levodopa (Sinemet). Although the nerve cells in the substantia nigra, which make dopamine, are dying, the nerve cells in the basal ganglia (striatum), which are normally stimulated by dopamine, have well preserved dopamine receptors and are therefore still responding to dopamine. The cornerstone of medical treatment of PD is administration of levodopa, which is taken up and converted into dopamine by the brain.

What is “atypical” parkinsonism and how is it differentiated from PD?

Parkinsonism refers to a set of symptoms typically seen in Parkinson’s disease, but caused by other disorders. Atypical parkinsonism includes a variety of neurological disorders in which patients have some clinical features of PD, but the symptoms are caused not only by cell loss in the substantia nigra (the brain area most affected in classic PD), but also by additional degeneration of cells in the parts of the nervous system that normally contain dopamine receptors (striatum). In other words, the patients look like they have PD, but the cause of their symptoms is different from that of classic PD. Patients with atypical parkinsonism have symptoms similar to PD, including resting tremors, slowed movement, stiffness, gait difficulty and postural instability, but in addition have symptoms and signs that are not typically present in PD, hence the term “Parkinsonism plus syndrome”. The additional problems may include inability to look up and down (vertical gaze palsy) and early postural instability, such as seen in progressive supranuclear palsy (PSP), the most common form of atypical parkinsonism. The second most common form of atypical parkinsonism is multiple system atrophy (MSA), previously also referred to as Shy-Drager syndrome or olivopontocerebellar atrophy. Patients with MSA are typically distinguished from those with PD by the presence of autonomic features such as unstable blood pressure which falls drastically upon standing (orthostatic hypotension), early disturbance of sexual, bladder, and bowel dysfunction, reddish-bluish discoloration of skin (e.g. the “cold hand” sign), and marked sleep disturbance (e.g. acting out of dreams and sleep apnea). Other typical features of MSA include forward head tilt (anterocollis) or a body tilt when sitting (pisa sign), loss of coordination, and rapidly progressive course with inability to ambulate usually within the first 3-5 years after onset. Another common cause of atypical parkinsonism is “vascular parkinsonism” caused by multiple, usually very minute, strokes. These patients usually have more symptoms in the lower extremities (lower body parkinsonism) with walking difficulties, balance problems and falls. Other forms of atypical parkinsonism are Dementia with Lewy bodies (DLB) and cortico-basal ganglionic degeneration (CBD). Patients with DLB have, in addition to the parkinsonian features, early dementia (preceding or co-occurring with the parkinsonian symptoms), visual hallucinations (seeing people, animals or objects that are not real), their symptoms fluctuating, with “good days” and “bad days”. Patients with CBD usually present with asymmetric stiffness, apraxia (inability to carry out learned purposeful movements), alien limb (the hand or the leg seem to have “a mind of their own”), and limb dystonia (abnormal sustained muscle contractions causing abnormal postures and twisting). Poor or no response to levodopa is common feature to all forms of atypical parkinsonism.

In contrast to typical PD, in which dopamine receptors are spared, patients with atypical parkinsonian disorders have lost their dopamine receptors and therefore they do not respond to levodopa as well as those with typical PD. This can be demonstrated by special imaging such as positron emission tomography (PET). MRI may be also helpful in differentiating PD from atypical parkinsonism.

What causes atypical parkinsonism?

There are probably many causes of atypical parkinsonism, but no one specific cause has been identified. There are many articles (see references) that describe some of the research into the causes of these disorders. Although it is not yet known what causes atypical parkinsonism, only one member of a family is usually affected and, therefore, these disorders are thought to be sporadic and not inherited. This is in contrast to typical PD where genetic factors seem to be quite important. The various atypical parkinsonian syndromes are classified according to the patterns of damage they produce in the nervous system, the constellation of clinical symptoms they cause, and their natural course.

What can I do to support Parkinson's research?

Because the various atypical parkinsonism diseases are relatively uncommon, it is difficult to obtain public funding for research. Therefore, research into these disorders largely depends upon private contributions, particularly from patients and families affected with the diseases. Besides financial support and willingness to participate in clinical research projects, scientists are interested in examining postmortem brains of patients who were afflicted with these disorders. To arrange for a brain donation to a qualified “brain bank”, you should contact your neurologist or the National Parkinson Foundation for further information.

Are there any support groups for patients with Atypical Parkinsonism and their families?

Patients affected with atypical parkinsonism and their families should consider joining national or local PD support groups. Membership in these organizations facilitates exchange of information and members can obtains “tips” that may be useful in coping with the physical and mental disabilities associated with these disorders. Also, many local support groups offer exercise therapy which may be helpful to some patients. With the emotional support of family members and with expert medical management guided by a knowledgeable and compassionate physician, many patients with atypical parkinsonism can lead enjoyable and productive lives.

For further information, refer to the references on a particular disease (Table 1).

Table 1. Parkinsonism Plus Syndromes: Differential Diagnosis

	PD	PSP	MSA-P	MSA-C	CBD	DLB	PDACG
Bradykinesia	+	+	+	±	+	±	+
Rigidity	+	+	+	+	+	±	+
Gait Disturbance	+	+	+	+	+	±	+
Tremor	+	-	-	±	±	-	+
Ataxia	-	-	-	+	-	-	±
Dysautonomia	±	±	±	±	-	±	±
Dementia	±	+	-	-	±	+	+
Dysarthria/ Dysphagia	±	+	+	+	+	±	+
Dystonia	±	±	±	-	+	-	-
Eyelid Apraxia	-	+	±	-	±	-	±
Limb Apraxia	-	-	-	-	+	±	-
Motor Neuron Disease	-	-	±	-	-	-	+
Myoclonus	±	-	±	±	+	±	-
Neuropathy	-	-	-	±	-	-	-
Oculomotor Deficit	-	+	-	+	+	±	±
Sleep Impairment	±	±	±	±	-	±	-
Asymmetric Findings	+	-	±	-	+	-	-
Levodopa Response	+	±	±	±	-	-	-
Levodopa Dyskinesia	+	-	±	-	-	-	-
Family History	±	-	-	-	-	-	-
Putaminal T-2 Hypo-intensity	-	±	+	+	-	-	-
Lewy Bodies	+	-	±	±	±	+	-

Abbreviations: CBD = cortical-basal ganglionic degeneration; DLB = Dementia with Lewy Bodies;
MSA-C = multiple system atrophy, predominantly cerebellar; MSA-P = multiple system atrophy, predominantly cerebellar; PD = Parkinson's disease; PDACG = parkinsonism-dementia-amyotrophic lateral sclerosis complex of Guam; PSP = progressive supranuclear palsy

Selected References

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Burn DJ. Cortical Lewy body disease. J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):175-8.
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Gilman S, Koeppe RA, Chervin RD, et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology 2003;61:29-34.
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Appendix

Society for Progressive Supranuclear Palsy
Executive Plaza III
11350 McCormick Road, Suite 906
Hunt Valley, Maryland 21031
http://www.psp.org

Other related websites:

SDS/MSA Support Group
http://www.shy-drager.com/news.htm
http://www.msaweb.co.uk
http://groups.yahoo.com/group/shydrager
http://www.emedicine.com/neuro/topic671.htm

For additional information visit http://www.bcm.edu/neurology/pdcmdc/