The Four Atypical Parkinsonism Disorders

This section compares the four atypical parkinsonism disorders:

These diseases are frequently mistaken for each other and for Parkinson’s Disease, Alzheimer’s Disease, stroke, and other neurological conditions. To some extent, we address the questions “If it’s not Alzheimer’s Disease, what is it?” and “If it’s not Parkinson’s Disease, what is it?”

Excellent organizations focus on each of these atypical parkinsonism disorders.  We list these organizations on our pages dedicated to each disorder.  Brain Support Network casts a wider net, describing and comparing the four disorders and their subtypes.

Given our extensive experience with brain donation, we know that the diagnostic accuracy of these disorders is low.  We know the diagnosis before the brain is delivered for autopsy and we learn the definitive diagnosis by the neuropathologist after autopsy.  Accuracy hovers around 50%, even for diagnoses delivered by expert neurologists.

These disorders are rare, difficult to diagnose, and moving targets as new subtypes are described.  One of BSN’s missions is to sketch the landscape so that laypeople can have meaningful discussions with medical providers and can serve as effective advocates.

Terminology

To be diagnosed with Parkinson’s Disease, someone must have two of four symptoms: rigidity, bradykinesia (slow movement), tremor, or postural instability. In addition, someone must have a robust response to levodopa therapy, the standard medication of Parkinson’s Disease. And other explanations for symptoms—such as stroke, antipsychotic medication, or atypical parkinsonism disorders—must be excluded.

Parkinsonism Symptoms

A key term in the atypical parkinsonism field is parkinsonism. Parkinsonism is a term that refers to Parkinson’s Disease-like symptoms; in other words, rigidity, bradykinesia, tremor, or postural instability. The most common parkinsonism condition is Parkinson’s Disease.

If someone has an atypical parkinsonism, Parkinson’s Plus, or a parkinsonism syndrome, this means that the person has parkinsonism but not Parkinson’s Disease. Generally, this means that there is not a robust response to levodopa therapy. Many movement disorder specialists give someone suspected of having an atypical parkinsonism disorder a “challenge” dose of levodopa. If there is no response or the response is minimal, this is further evidence that the person has an atypical diagnosis, rather than “typical” Parkinson’s Disease.

The Plus term in Parkinson’s Plus refers to the fact that the atypical parkinsonism disorders have symptoms on top of parkinsonism symptoms. The term Parkinson’s Plus has gone out of fashion because these diseases don’t always look like Parkinson’s. They might look more like Alzheimer’s Disease, frontotemporal dementia, or stroke.

To be diagnosed with Alzheimer’s Disease, someone must have progressive dementia including memory loss. Alzheimer’s Disease is the most common type of dementia in both the elderly and middle-aged.

Dementia Symptoms

What is dementia? Dementia is decline in memory and thinking skills so severe that it impedes normal life. There must be problems in two or more domains such as memory, judgment, language/communication, perception/visuospatial skills, and attention. There may be impairment in social functioning, the ability to function at work, the ability to perform activities of daily living (bathing, grooming, dressing, toileting, self-feeding, ambulating/transferring), or the ability to perform tasks of independent living (grocery shopping, cooking, paying bills, maintaining a checkbook, housekeeping, taking medications as prescribed, using the telephone, etc.). Dementia is not a specific disease. The terms dementia and Alzheimer’s are often used synonymously but this is incorrect. Nor is dementia a part of normal aging.

A change in cognition and memory between normal aging and dementia is called cognitive impairment. Cognitive impairment can be mild, moderate, or severe. Some number of those with cognitive impairment develop dementia.

Depending on whom you ask, Lewy Body Dementia is either the second or third most common type of dementia in the elderly. (Alzheimer’s is the most common and vascular dementia is thought by many to be the second-most common.)   Dementia symptoms seen in LBD are very different from dementia symptoms seen in Alzheimer’s Disease and other dementia types.

The most common type of Progressive Supranuclear Palsy, called Richardson’s Syndrome, includes cognitive impairment and dementia as symptoms.  Many people with Corticobasal Degeneration also have cognitive impairment or dementia symptoms.

LBD, PSP, and CBD are examples of non-Alzheimer’s dementias.  However, while those with MSA may experience mild cognitive impairment, dementia is an exclusionary criterion for Multiple System Atrophy.  Generally if dementia symptoms are present in someone diagnosed with MSA, we should question the MSA diagnosis.  An alternative diagnosis might be Lewy Body Dementia (also known as Parkinson’s Disease Dementia or Dementia with Lewy Bodies).

Certainly, someone can have multiple disorders, which complicates the clinical diagnosis.  LBD frequently co-occurs with Alzheimer’s Disease. AD co-occurs with PSP in about 30% of all cases at the Mayo Clinic Jacksonville Brain Bank. And, although unusual, someone with MSA can also have Alzheimer’s Disease.

Atypical Parkinsonism Disorders – Three Good Overviews

Brain Support Network is focused on four atypical parkinsonism disorders: LBD, PSP, MSA, and CBD. Here are links to three excellent overviews of these conditions from Parkinson’s Disease organizations:

Atypical Parkinsonism by Lawrence I. Golbe, MD, Professor of Neurology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ.  Published in The American Parkinson Disease Association Winter 2008 Newsletter

Atypical Parkinsonism by Michael J. Fox Foundation, un-dated.

Atypical Parkinsonism by Parkinson’s Disease Foundation, Chicago, IL, 2008

Comparing Disorders and Subtypes

The following table provides a brief summary of the differences among atypical parkinsonism disorders.  Most exhibit parkinsonism symptoms; some exhibit dementia symptoms; each is identified by specific mis-folded proteins visible in the brain upon autopsy.

Atypical parkinsonism disorders are difficult to diagnose because (a) there is no chemical test of blood or tissue, (b) there is no imaging test, and (c) the various disorders have similar symptoms and even share symptoms with non-parkinsonism disorders.

When a Board-certified neurologist delivers a diagnosis for any of the four atypical [arkinsonism disorders, the probability that the diagnosis is incorrect is approximately 50%. The only way to definitively diagnose an atypical parkinsonism disorder is by postmortem microscopic analysis of brain tissue.

Atypical Parkinsonism DisorderParkinsonism
Symptoms?
Dementia
Symptoms?
Protein Pathology
Lewy Body Dementia (LBD)OftenAlwaysAlpha-synuclein (Lewy bodies)
Progressive Supranuclear Palsy (PSP)AlwaysOftenTau
Multiple System Atrophy (MSA)AlwaysNeverAlpha-synuclein
Corticobasal Degeneration (CBD)OftenOftenTau

All four disorders have “subtypes” that may differ subtly in pathology distribution or reflect distinct clinical symptoms documented before death. The medical profession is not unanimous in its embrace of the listed subtypes because different researchers report different groups of subtypes.

Atypical Parkinsonism DisorderSub-types
Lewy Body Dementia (LBD)(1) Parkinson’s disease dementia (PDD) – parkinsonism symptoms are primary
(2) Dementia with Lewy bodies (DLB) – dementia symptoms are primary
(3) Dementia with Lewy bodies (DLB) – psychiatric symptoms are primary
Progressive Supranuclear Palsy (PSP)(1) Richardson’s syndrome (“classic PSP”)
(2) PSP-Parkinsonism (PSP-P)
Multiple System Atrophy (MSA)(1) Parkinsonian subtype (MSA-P)
(2) Cerebellar dysfunction subtype (MSA-C)
Corticobasal Degeneration (CBD)(1) Corticobasal Syndrome (CBS)
(2) Frontal Behavioral-spatial Syndrome
(3) Nonfluent/Agrammatic Variant, a type of Primary Progressive Aphasia (PPA)
(4) Progressive Supranuclear Palsy Syndrome