Understanding Atypical Parkinsonism

Parkinson’s disease vs. Parkinsonism: what’s the difference?

The recent death of President George H.W. Bush, who had been diagnosed with vascular parkinsonism towards the end of his life, placed this disease in the media limelight. Generally, there is a lot of confusion about Parkinson’s disease (PD) and parkinsonism and many of you have asked me to clarify this distinction.

What is Parkinsonism?

Parkinsonism is not technically a diagnosis, but rather a set of symptoms including slowness, stiffness, tremor, and problems with walking and balance. There is a list of diseases that manifest with these parkinsonism symptoms and they include:

  1. Parkinson’s disease
  2. Drug-induced parkinsonism
  3. Vascular parkinsonism
  4. Multiple system atrophy (MSA)
  5. Dementia with Lewy bodies (DLB)
  6. Progressive supranuclear palsy (PSP)
  7. Corticobasal ganglionic degeneration (CBGD)

There are a variety of other terms that you may also hear. Atypical parkinsonism usually refers to numbers 2-7 on this list, that is, the diseases that cause parkinsonism but are not PD. “Parkinson’s plus” syndromes refers to numbers 4-7 on the list. These are diseases that are neurodegenerative (involve nerve cell loss) that present with parkinsonism but are not PD.  Lower body parkinsonism refers to a clinical syndrome in which gait and balance appear parkinsonian without parkinsonian features in the upper body. Vascular parkinsonism tends to manifest primarily in this way. It can be very confusing because there are many variations and similar-sounding diagnoses. Read on for some descriptions that might help you understand the differences among these diseases.

Because there is no available biomarker or specific test that can be performed to easily distinguish these conditions from each other, the diagnosis can sometimes be unclear, and often is in flux. That is, as the disease progresses, the diagnosis may be changed as the clinical syndrome takes on features that more fully support a particular diagnosis. In general, the atypical parkinsonian syndromes are much less responsive to PD medications as compared to PD itself. Often, it is the lack of response to medication that suggests that the diagnosis is not PD, but rather one of the atypical syndromes. The history and clinical features of each of these diseases is different and I will summarize these distinctions.

Drug-induced parkinsonism

There are a number of medications that can cause parkinsonism because they block the dopamine receptor and thereby mimic the same symptoms caused by loss of dopamine neurons in the brain, which occurs in PD. Reviewing a patient’s medications is therefore a critical step for a neurologist when seeing someone with parkinsonism. The primary treatment for this type of parkinsonism is weaning off of the offending medication, if possible.

In addition, these medications should be avoided in people with parkinsonism from other causes, such as PD, and are listed for your convenience in the table of Medications to be Avoided or Used With Caution in Parkinson’s Disease which is available for download on our website. Anti-psychotics and anti-nausea treatments make up the bulk of the problematic medications. It is important to note that there are anti-psychotics and anti-nausea medications which do not cause parkinsonism and can be used safely in people with PD.

Vascular parkinsonism

Vascular parkinsonism is thought to be due to an accumulation of small strokes in the parts of the brain that control movement. The most prominent feature usually involves a gait abnormality. Lewy bodies, the key pathological hallmark of PD, are not present in vascular parkinsonism. People with vascular parkinsonism are less likely to be responsive to Levodopa and other PD meds than people with typical PD, but some are responsive, so it is common practice to try PD meds even if vascular parkinsonism is suspected.  Treatment also focuses on preventing any further strokes with management of high blood pressure, high cholesterol, and diabetes, in addition to maximizing mobility with physical therapy.

Multiple system atrophy (MSA)

MSA manifests with parkinsonism, accompanied by prominent abnormalities in the autonomic nervous system, the system that controls that automatic functions of the body. The two automatic functions that are most typically affected are urinary and blood pressure control. This autonomic dysfunction can also be present in PD, but it often occurs earlier and in a more severe form in MSA. A clinical variant of MSA presents with dysfunction of the cerebellum, the part of the brain that controls accuracy of movement, and causes a movement problem called ataxia.

MSA can appear very similar to PD early on in the diagnosis and can even be somewhat Levodopa responsive. Like PD, MSA is associated with abnormal accumulation of alpha-synuclein, although this accumulation takes place in a different cell type in the brain than it does in PD.

Other “red flags” for MSA which make a clinician think that the diagnosis is not PD include rapid progression, prominent postural abnormalities such as tilting of the torso or flexion of the neck (this can also happen in PD, but can be more pronounced in MSA), and early dysfunction of voice and swallowing ability.

Dementia with Lewy bodies (DLB)

DLB is a neurodegenerative disease marked by early cognitive difficulties and visual hallucinations. It is sometimes difficult to distinguish this disease from Parkinson’s disease dementia (PDD). I delve deeper into this complicated topic in my blog about DLB and Parkinson’s.

Progressive supranuclear palsy (PSP)

PSP manifests with parkinsonism and is characterized by neuron loss in the brain, accompanied by deposition of the protein called Tau.

Recently, it has been recognized that there are many clinical subtypes of PSP. In the classic version there are frequent falls early in the course of the disease, often in the backwards direction, with balance difficulties developing into a key source of disability. A very characteristic feature of the classic version of the disease is the decreased ability to move the eyes voluntarily, mostly in the vertical direction.  In addition, the faces of people with PSP tend to have prominent facial folds, making the person look astonished or worried.

Other clinical subtypes include one that is indistinguishable, at least for the first number of years, from PD itself.  Other subtypes include one in which there is a very striking amount of freezing of gait (Primary Freezing of Gait), one with significant difficulty producing language (Primary progressive aphasia) and one with significant behavioral dysregulation. The diagnosis of PSP in these situations may be unclear and may only reveal itself if and when the characteristic eye movement abnormalities develop.

As the disease progresses, swallowing difficulties can be a major source of disability.

Corticobasal ganglionic degeneration (CBGD)

CBGD (also called corticobasal degeneration or CBD) is similar to PSP in that it manifests with parkinsonism accompanied by deposition of the protein Tau.

In its classic form, the disease is very asymmetric, with one side of the body, usually one arm, developing dystonia (sustained twisting movements) and myoclonus (brief, lightning-like jerks). The more affected side of the body tends to demonstrate apraxia, or an inability to use the limb productively, despite intact motor function. Like PSP, there are other clinical forms, including one with prominent difficulty producing language and one with prominent behavioral symptoms.

To complicate matters even more, the syndrome of asymmetric dystonia and myoclonus, accompanied by apraxia can be a clinical syndrome associated with brain pathologies other than CBGD. This clinical presentation is called the corticobasal syndrome and can be seen in patients with PSP, frontotemporal dementia or even Alzheimer’s disease.

Treatment for atypical Parkinsonism symptoms

Because PD medication response is poor in these syndromes, treatment focuses on symptom management – e.g. physical therapy for fall prevention, speech therapy to maximize communication, swallow therapy to prevent aspiration.

Other symptoms that can be addressed include dystonia, myoclonus, blood pressure dysfunction and urinary dysfunction.

Tips and takeaways:

  • Atypical parkinsonism is a very complicated group of diseases that are hard to diagnose. Sometimes a neurologist will change the diagnosis as new symptoms develop or become more apparent.
  • Despite the fact that these conditions typically do not respond well to medications for PD, many of the presenting symptoms can be addressed, so make sure to raise all of your concerns with your neurologist.

Support Our Mission

To support your local Understanding Atypical Parkinsonism chapter please click the button below: