Atypical Parkinsonism

Atypical Parkinsonisms

Atypical parkinsonism, or "Parkinson's Plus," refers to conditions that have symptoms similar to Parkinson's. These symptoms — tremor, slowness and stiffness — are called "parkinsonism." People with atypical parkinsonism may look like they have Parkinson's, but they often have additional symptoms that are not common in Parkinson's. Their symptoms may progress more quickly and benefit less from Parkinson's medications.

As with Parkinson's, diagnosis of each of these conditions is based on a person's medical history and a doctor's examination. There are no blood or imaging tests to diagnose them. Because they look like Parkinson's, especially in the early years, they may be misdiagnosed as Parkinson's disease.

Currently, there are no therapies to slow or stop progression of these conditions, but treatments can ease symptoms. 

Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) causes movement problems such as tremor, slowness and stiffness and significant thinking and memory problems (dementia). DLB dementia affects thinking more than memory, and people have difficulty processing information, following steps in a process and seeing things in three dimensions to make a mental picture of their surroundings. In DLB, dementia and movement symptoms typically come on at the same time or within a year of each other.

DLB is related to Parkinson’s disease dementia (PDD), which also causes dementia and movement symptoms. People with PDD first show movement symptoms and, after many years or decades of living with Parkinson’s, develop dementia. Because DLB and PDD share symptoms and brain cell changes (misfolded alpha-synuclein protein clumps called Lewy bodies), doctors and researchers group them under the umbrella term Lewy body dementia. After Alzheimer's disease, Lewy body dementia is the second most common cause of neurodegenerative (progressive) dementia.

In addition to dementia and movement problems, Lewy body dementia can cause:

• Visual hallucinations (seeing things that aren't there) and delusions (false, often paranoid, beliefs)
• Fluctuating attention and alertness (“with it” one day and “out of it” the next”)
• Acting out dreams (REM sleep behavior disorder) and other sleep problems
• Mood changes, such as depression or anxiety
• Behavioral changes, such as agitation or aggression
• Loss of motivation (apathy)
• Blood pressure changes

Researchers are working out exactly why Lewy body dementia occurs. Genetics, environmental factors and aging all likely play a role.

Multiple System Atrophy

Multiple system atrophy (MSA) causes movement symptoms and affects the network of nerves — the autonomic nervous system — that controls blood pressure, digestion and other involuntary processes. Symptoms of MSA include, to varying degrees:

• Slowness, stiffness, and walking and balance problems
• Clumsiness and incoordination
• Slurred speech
• Low blood pressure, constipation and bladder problems
• Difficulty controlling emotions (laughing or crying at inappropriate times)
• Acting out dreams (REM sleep behavior disorder)
• Breathing problems, especially at night

The exact cause of MSA is not yet known. As in Parkinson's disease and Lewy body dementia, clumps of the protein alpha-synuclein are seen in brain cells, but they are in the support (glial) cells rather than the nerve cells. Researchers are investigating these clumps to find out more about the disease and how to slow or stop it.

Corticobasal Degeneration

Corticobasal degeneration (CBD) causes movement, memory and thinking (cognitive), and behavioral symptoms. Movement symptoms typically start in one hand, arm or leg and later may involve other parts of the body. Symptoms include:

• Slowness and stiffness
• Dystonia (muscle contractions causing abnormal postures such as an inward turned hand )
  Read more about dystonia
• Myoclonus (rapid muscle jerks)
• Difficulty paying attention or concentrating, or other cognitive changes 
• Language problems, such as trouble finding words or speaking in full sentences
• Behavioral changes, such as acting or speaking crudely

When the arm is involved, a person may be unable to control it, even though they know what they want to do and have the muscle strength to do so. For example, they may have trouble combing their hair or turning a key in a lock. Sometimes the arm may even move on its own; this is called "alien limb syndrome." CBD also may eventually lead to walking and balance problems.

In CBD, a protein called tau builds up in certain brain cells. Exactly why this protein accumulates and cells die isn't understood, but researchers are examining these mechanisms to understand the disease and find ways to target it.

Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) causes movement symptoms, eye movement problems, and memory and thinking (cognitive) changes. The main symptoms include:

• Walking and balance problems
• Falling backward
• Slurred speech and swallowing problems
• Difficulty moving the eyes down (or up), which can cause blurred vision and difficulty reading
• Mood problems, such as depression
• Behavioral changes, such as lack of motivation

As in CBD, the tau protein clumps in certain brain cells, which die. The cause of this is unknown, but researchers are looking to environmental factors and other clues.

Treatment of Atypical Parkinsonism

While no current therapy can slow or stop progression, treatment can ease symptoms of atypical parkinsonisms. Because symptoms overlap across these conditions, treatments overlap, too.

For movement symptoms, such as stiffness and slowness, doctors may prescribe levodopa. Unfortunately, if this medication does ease symptoms, its benefit may not be significant or long-lasting. In people who have dementia with Lewy bodies, levodopa may worsen hallucinations, so doctors prescribe it cautiously. For dystonia in CBD, botulinum toxin injections such as Botox or Myobloc into the muscles may be an option. For walking and balance problems, as well as falls, occupational and physical therapy are helpful. Canes and walkers may provide extra stability, though in some cases wheelchairs may be necessary.

Memory and thinking problems may be treated with medications such as Exelon (rivastigmine), Aricept (donepezil), Razadyne (galantamine) or Namenda (memantine). In DLB, these drugs also may help with behavioral changes and hallucinations.

Hallucinations in DLB, if jeopardizing safety or well-being, may need to be treated with drugs called atypical antipsychotics. These drugs are used with extreme caution because they can worsen symptoms and cause significant side effects. While no drug is FDA-approved for use in dementia, doctors sometimes use them “off label.” Options may include Nuplazid (pimavanserin), which is approved to treat hallucinations and delusions in Parkinson's disease but sometimes is used in DLB because it is less likely to worsen movement symptoms, or Clozaril (clozapine) or Seroquel (quetiapine).

Speech therapy treats speech and swallowing problems. Therapists may recommend exercises to strengthen speech and swallowing muscles, as well as diet adjustments and behavioral strategies to improve swallowing. If swallowing problems lead to weight loss or recurrent pneumonia (because of swallowing down the wrong tube, or "aspiration"), doctors may consider a feeding tube.

Doctors can use a variety of medications to ease mood, behavioral and sleep problems.

A team approach can help address the different symptoms of atypical parkinsonism. A neurologist with additional training in movement disorders, including atypical parkinsonism — a movement disorder specialist — can coordinate care and bring in other experts to round out the care team. These experts include occupational, physical and speech therapists, as well as social workers. Social workers can provide counseling and educational resources, connect you to patient and care partner support groups, and find in-home and other care services, such as long-term care facilities, when necessary. And palliative care specialists can help at any point in the course of disease. These experts can help manage troublesome symptoms, discuss current and future care goals, and coordinate communication among the entire team (patient, family and medical providers).

Ongoing Research

Researchers are looking deeper into why each of these conditions occur, which will lead to better treatments for symptoms and therapies to slow or stop progression. Some treatments in testing for Parkinson's disease, such as those targeting alpha-synuclein, also may work for the atypical parkinsonisms associated with alpha-synuclein (Lewy body dementia and MSA).

At the same time, investigators are searching for tests to diagnose these conditions. For example, The Michael J. Fox Foundation and the Tau Consortium are co-funding projects to develop brain imaging tests to visualize the alpha-synuclein and tau proteins in the living brain. (These proteins currently can only be seen in autopsied tissue.) Such tests would allow doctors to easily and accurately separate these conditions from each other and from Parkinson's. And they would help researchers ensure the right people are selected for the right trials to speed drug development.

The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson's disease and any other medical condition be made in consultation with a physician or other qualified medical professional.