A handful of conditions that share some aspects of Parkinson's disease plus additional symptoms may progress faster and get less benefit from medication. Much of the research into Parkinson's can be leveraged to understand and treat these 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 also 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 is no therapy to slow or stop progression of these conditions, but treatments can ease symptoms.
Lewy Body Dementia
Lewy body dementia (LBD) is a form of dementia, a broad term that describes memory or thinking problems significant enough to interfere with a person's daily life and activities. After Alzheimer's, Lewy body dementia is the second most common cause of neurodegenerative dementia.
The dementia associated with LBD typically involves difficulty planning, processing information and understanding visual details. LBD also causes a range of symptoms that gradually worsen over time:
- Hallucinations (seeing things that aren't there)
- Fluctuating attention and alertness, which may cause daytime drowsiness
- Movement problems, such as tremor, slowness, stiffness and difficulty walking
- Acting out dreams or other sleep problems
- Mood changes, such as depression or anxiety
- Behavioral changes, such as agitation
- Loss of motivation or apathy
LBD includes two different clinical conditions — Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) — that have the same underlying brain changes. People with PDD first show classic Parkinson's movement symptoms (tremor, slowness and stiffness) and many years later develop dementia and other features of LBD, such as hallucinations and fluctuating attention. In DLB, the dementia and movement symptoms occur at or around the same time, often within about a year.
In Lewy body dementia, certain brain cells accumulate misfolded alpha-synuclein protein into clumps called Lewy bodies. Researchers don't know exactly why LBD occurs, but 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, walking and balance problems
- Clumsiness and coordination problems
- Slurred speech
- Low blood pressure, constipation and bladder problems
- Difficulty controlling emotions (laughing or crying inappropriately)
- REM sleep behavior disorder (acting out dreams)
- Breathing problems, especially at night
The cause of MSA is not yet known. As in Parkinson's disease and LBD, abnormal clumps of the protein alpha-synuclein are seen in brain cells, but 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 (CBD) causes motor, 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 a turned hand )
- Myoclonus (rapid muscle jerks)
- Difficulty paying attention or concentrating, or other cognitive changes
- Language problems, such as difficulty finding words or speaking in full sentences
- Behavioral changes, such as acting or speaking crudely
When the arm is mainly involved, people 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 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 motor symptoms, eye movement problems, and memory and thinking (cognitive) changes. The main symptoms include:
- Walking and balance problems
- Falling backwards
- Slurred speech and swallowing problems
- Difficulty moving the eyes down (or up), which can cause blurred vision and difficulty reading
- Memory and thinking problems
- Mood problems, such as depression
- Behavioral changes, such as lack of motivation
As in CBD, the tau protein clumps and certain brain cells die. The cause for this is unknown, but researchers are looking to environmental and other clues.
Treatment of Atypical Parkinsonism
Treatments for atypical parkinsonism ease symptoms. Currently, there are no therapies to slow or stop progression of these conditions. Because symptoms overlap among many of these conditions, treatments overlap, too.
For motor symptoms, such as stiffness and slowness, doctors may prescribe levodopa. Unfortunately, if the medication does ease symptoms, these benefits often aren't significant or longlasting. People with Lewy body dementia need to be especially careful with levodopa as it can worsen visual hallucinations. 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) or Razadyne (galantamine). In Lewy body dementia, these drugs also may help with behavioral problems and hallucinations.
LBD hallucinations, if upsetting, may be treated with drugs called atypical antipsychotics. These must be used cautiously as they can worsen symptoms and cause side effects. Options may include Nuplazid (pimavanserin), which is approved to treat visual hallucinations and delusions (false, often paranoid, beliefs) in Parkinson's disease, or Clozaril (clozapine) or Seroquel (quetiapine).
Speech therapy treats speech and swallowing problems. Speech therapists 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 you swallow down the wrong tube, or "aspirate"), your doctor may recommend a feeding tube.
Doctors use a variety of medications to ease mood, behavioral and sleep problems.
A team approach can help ensure that the varied symptoms of atypical parkinsonism are properly managed. A neurologist with extra 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 educational resources, connect to patient and care partner support groups, and find in-home and other care services, such as long-term care facilities, when necessary. Palliative care doctors also may be consulted at any point during the course of the disease. These specialists not only help manage symptoms, but can discuss current and future care goals, and coordinate communication among the entire team (patient, family and medical providers).
Researchers are looking into why each of these conditions occur, which will lead to better treatments for the symptoms and therapies to slow or stop progression. Some treatments in testing for Parkinson's disease, such as those targeting alpha-synuclein, may also work for the atypical parkinsonisms associated with alpha-synuclein (LBD 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 protein and the tau protein in the living brain. 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.
Register for Fox Trial Finder to be matched with recruiting atypical parkinsonism trials in your area.