What is Parkinson-Plus Syndrome?
Parkinson-plus syndrome (PPS), also known as atypical parkinsonism, is a group of diseases that damage the nerves involved in movement, similar to Parkinson’s disease (PD). However, it has certain unique clinical features and causes. Like traditional Parkinson’s, PPS symptoms include apraxia (difficulty performing tasks), rigidity, bradykinesia (slow movement), tremor, and balance instability. Moreover, PPS has some unique characteristics such as early development of memory loss, hallucinations, dysautonomia (a disorder of autonomic nervous system), eye movement issues, sudden muscle jerks, complications related to the nerve pathway of the spinal cord, and a strange phenomenon known as ‘alien limb’ where one limb behaves independently of others.
Unlike Parkinson’s disease, PPS’s response to levodopa (a common treatment) is minimal, and the overall prognosis or disease outcome is generally poor. The most typical types of PPS are Lewy body dementia (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP).
Less common types of PPS include frontotemporal dementia, Pick disease, pallidonigral degeneration (a condition that affects the ability to control movements), Parkinsonian-dementia complex of Guam, Wilson disease (a rare inherited disorder that causes excessive copper buildup), and a rigid variant of Huntington disease (a genetic disorder that causes breakdown of nerve cells in the brain). This review will tackle the most common PPS conditions, focusing on their occurrence rates, causes, pathophysiology (disease processes), evaluation, and treatment options.
What Causes Parkinson-Plus Syndrome?
Most Parkinson-plus syndrome cases happen without a clear reason. We know that genetics may be involved because there are some families where multiple members have the condition. Environmental factors, or things in our surroundings, can also influence the development of this disease. However, the exact cause is still not known.
Risk Factors and Frequency for Parkinson-Plus Syndrome
Lewy Body Dementia (LBD), Multiple System Atrophy (MSA), Corticobasal Degeneration (CBD), and Progressive Supranuclear Palsy (PSP) are among some diseases that affect the brain and cause dementia. These diseases vary in how common they are, who they affect, and when they typically start.
- LBD is one of the more common causes of dementia, making up almost 30% of all cases. It’s thought to affect around 5% of people generally, with about 0.1% of the population getting diagnosed each year.
- MSA is less common, affecting between 2 to 5 people out of every 100,000. On average, people get diagnosed around 54 years old and it affects men and women equally.
- CBD affects between 0.62 to 0.92 per 100,000 people each year, and is found in around 5 to 7 out of every 100,000 people. It typically starts around 61 and 64 years old, and seems to affect more females than males.
- PSP is seen in roughly 3 to 7 people out of every 100,000. Each year, approximately 1.1 out of every 100,000 people are diagnosed.
Signs and Symptoms of Parkinson-Plus Syndrome
Parkinson-plus syndrome is an advanced form of Parkinson’s disease. It has all the usual Parkinson’s signs such as tremors, muscle rigidity, slow movement, and difficulty with balance. However, it also has additional features which may involve mental confusion, visual hallucinations, irregular body functions, spontaneous muscular spasms and unusual eye movements. This condition typically progresses quickly and doesn’t respond well to typical Parkinson’s medication. It also hampers a patient’s ability to do daily tasks and reduces overall functionality.
Lewy Body Dementia is a type of Parkinson-plus syndrome. It causes dementia which leads to attention deficits, impaired thought processing and challenges with spatial awareness. Additional symptoms can include visual hallucinations, sleep disorders, recurrent falls, irregular body functions, sensitivity to antipsychotic medication, delusions and depression. With this condition, dementia either occurs first or within a year of detecting the movement disorder.
In Multiple System Atrophy, another type of Parkinson-plus syndrome, hallmark features include slow movement paired with muscle rigidity, uncoordinated movements, irregular body functions, and sexual and urinary dysfunction. This condition takes two forms based on the main motor symptoms: one form majorly presents Parkinson’s-like symptoms (MSA-P), and the other mainly portrays uncoordinated movements, disturbed speech and difficulties with eye movements (MSA-C). As the illness progresses, the most noticeable symptoms may change. However, cognitive abilities usually remain unaffected in MSA.
Corticobasal Degeneration is another variation of Parkinson-plus syndrome, and it starts as a movement disorder that initially affects one limb. It shows symptoms like severe rigidity, spontaneous muscular spasms, odd limb movements, and difficulty in performing motor tasks. In addition, it often presents cognitive impairments such as speech difficulties, inability to plan, conceptualize and execute tasks, spatial awareness deficits, and behavioral changes.
Lastly, Progressive Supranuclear Palsy is another form where it has a classic type known as Richardson syndrome. The major sign is difficulty with eye movements where patients aren’t able to move eyes vertically, focus on objects, or control their eyelids. Additional symptoms include unbalanced body posture leading to fall often, swallowing difficulties, speech articulation problems, cognitive problems, and sleep irregularities. This condition can also take different forms based on the predominant symptoms.
Testing for Parkinson-Plus Syndrome
In Parkinson-plus syndrome, your doctor will follow a range of diagnostic tests like lab tests and imaging studies to help rule out other similar conditions. However, most of the time, these test results cannot conclusively diagnose Parkinson-plus syndromes.
Lewy Body Dementia (LBD) is one of the conditions under Parkinson-plus syndrome. Here, the patient’s mental state is first assessed through tests like the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA). Blood tests are also done, and brain scans are taken using techniques like CT or MRI. These tests can show generalized brain atrophy and white matter lesions, pronounced cortical atrophy (which is the loss of nerve cells in the brain), and reduced blood flow, mostly in the back of the brain.
Biomarkers can also help diagnose LBD. These include reduced dopamine transporter uptake in the basal ganglia (the part of the brain responsible for movement coordination) seen on PET or SPECT scans, low uptake of MIBG myocardial scintigraphy (a heart imaging test), and certain findings from sleep studies.
In Multiple System Atrophy (MSA), another Parkinson-plus syndrome, diagnosis is made based on observable patient symptoms as laboratory and imaging results are non-specific. Neuroimaging techniques like MRI can help rule out other conditions and may show signs of brain atrophy. A definite diagnosis of MSA can only be confirmed during autopsy where neurodegenerative changes are identified in the brain.
Corticobasal Degeneration (CBD), another condition, does not have any established biological markers for diagnosis. Several tests like blood, urine, and cerebrospinal fluid (CSF) analyses, vitamin B12, thyroid function tests, and others are done to rule out other conditions causing similar symptoms. Brain scans may reveal asymmetric atrophy of the frontal and parietal lobes, although this is not specific to CBD.
For Progressive Supranuclear Palsy (PSP), another Parkinson-plus syndrome, diagnosis is done by ruling out other conditions. Although it’s not diagnostic, neuroimaging can provide useful information. For example, a hummingbird sign or penguin silhouette sign in the MRI is indicative of this condition. PET scans can also reveal decreased metabolism in certain brain regions. In addition, sleep studies can show abnormalities like lower total sleep time, loss of REM sleep, and increased awakenings in patients with PSP.
Treatment Options for Parkinson-Plus Syndrome
If you have a condition known as Parkinson-Plus Syndromes (PPS), unfortunately there isn’t a cure-all or disease-changing treatment available. The main aim of treatment is to provide relief from symptoms and improve your life’s quality. For some patients, a medication called levodopa can help improve Parkinson-like symptoms. Other meds that might provide some relief include selegiline, amantadine, and dopamine receptor agonists.
For managing tremors, your doctor might suggest medications like propranolol, clonazepam, topiramate, and gabapentin. Anticholinergics and baclofen may also be useful. Aside from medications, therapies such as physical therapy, occupational therapy, and speech therapy can play a significant role. Physical therapists guide you through different exercises to improve movement, while occupational therapists can help you manage daily activities more easily. A speech therapist can evaluate and aid with swallowing difficulties, and dietitians are there to assist with planning proper nutrition. For patients in advanced stages, palliative care focused on comfort and safety, and limiting stress for both the patient and caregivers is an important part of treatment.
Additionally, therapies like music and expressive arts can help improve mood and wellbeing. There are also various treatments and therapies that are specific to individual PPS diseases.
In Lewy Body Dementia (LBD), medications that improve cognitive or behavioral symptoms may be used, such as cholinesterase inhibitors or memantine. Antipsychotics may be used for severe behavioral symptoms. Levodopa could be tried to help with disabling parkinsonism symptoms, though its effects are usually limited. A type of sleep disorder common in LBD, called REM sleep behavior disorder, is usually managed with melatonin or clonazepam. Anxiety issues and other behaviors can be managed with the help of mental health counselors.
If you have Multiple System Atrophy (MSA), botulinum toxin injections might be done to relieve certain type of muscle contractions. For chronic low blood pressure from autonomic dysfunction, fludrocortisone acetate or midodrine can improve the condition. Similarly as with LBD, REM sleep behavior disorder is typically treated with melatonin or clonazepam.
In Corticobasal Degeneration (CBD), problematic muscle contractions can be treated with botulinum toxin to improve function in the affected limb. Clonazepam is usually used for treating sudden involuntary muscle spasms, and medications such as donepezil or rivastigmine can be used for cognitive difficulties.
For Progressive Supranuclear Palsy (PSP), various measures can be taken to tackle eye-related symptoms. Patients with limited eye movements can benefit from mirror-prism lenses to help with reading and performing daily activities. Issues with opening eyelids and blinking can be managed with eyelid crutches and botulinum toxin, while decreased blink rate problems can be treated with artificial tears. Wearing dark glasses can help reduce sensitivity to light.
What else can Parkinson-Plus Syndrome be?
When a doctor is diagnosing Parkinson’s disease, they must also consider other conditions that might show similar symptoms. This includes ‘Parkinson-plus’ syndromes, which are a group of neurological disorders that have symptoms similar to Parkinson’s disease but are distinct conditions. They must be considered carefully to reach the correct diagnosis.
Other potential diagnoses could include:
- Alzheimer’s Disease (AD)
- Vascular dementia (a common type of dementia caused by reduced blood flow to the brain)
- Normal pressure hydrocephalus (a condition caused by excessive cerebrospinal fluid in the brain’s cavities)
- Creutzfeldt-Jakob disease (CJD, a rare and fatal condition that affects the brain)
- Various psychiatric diseases
Sometimes, symptoms similar to Parkinson’s can also be brought on by the side effects of certain medications. Therefore, it’s important to examine the patient’s medical history, drugs they are taking, and their symptoms before diagnosing Parkinson’s disease.
What to expect with Parkinson-Plus Syndrome
Compared to the common cases of Parkinson’s Disease (PD), there are some disorders where the disease gets worse more quickly and life expectancy is shorter. These include Lewy Body Disease and Multiple System Atrophy, among others.
Lewy Body Disease is characterized by its rapid worsening of symptoms. On average, individuals living with this condition have a lifespan of about 1.8 to 9.5 years after diagnosis. They experience cognitive decline more quickly than those with Alzheimer’s, often reaching severe dementia around five years after appearance of the first symptoms. This disease does not only affects memory and thinking, but also motor skills (how they move) and emotional health, with symptoms like depression and anxiety worsening over time. In some cases, these behavioral symptoms might need the person to be admitted into a nursing home.
In Multiple System Atrophy, the disease progresses much faster compared to most cases of PD. Typical milestones of the disease include the start of autonomic dysfunction (body functions that occur involuntarily, like heartbeat or digestion) after around 2.5 years, needing a wheelchair at around 3.5 to 5 years, and being bedridden for 5 to 8 years. Generally, from diagnosis, the disease leads to death in 6 to 10 years.
Corticobasal Degeneration is another such disorder where the disease progresses quickly, often leading to death due to complications from being unable to move or swallow properly, which can lead to conditions like pneumonia and sepsis. From the appearance of the first symptoms, life expectancy is generally around 6 to 8 years but can range between 2 to 13 years.
The progression of Progressive Supranuclear Palsy is also fast, and within three to four years from when symptoms begin, patients usually need dependent care. Death usually occurs around six to nine years after the diagnosis. Some variants of this disease result in a shorter survival time than others.
Possible Complications When Diagnosed with Parkinson-Plus Syndrome
There can be several complications in Progressive Supranuclear Palsy (PPS). These complications are usually related to dementia and Parkinson’s-like symptoms. One of the issues is immobility and falls due to the Parkinson’s-like symptoms. Some people may have trouble swallowing, which can lead to serious illnesses like lung infections due to aspirated food or fluid and severe body-wide infections. Issues with the urinary tract may also cause infections.
Using medications to manage the disease can sometimes result in unwanted side effects. Also, issues with the automatic bodily functions, like heartbeat regulation, can lead to heart-related complications. Often ignored, emotional symptoms like anxiety and depression can lead to suicidal thoughts.
Common Complications Include:
- Immobility and falls
- Difficulty swallowing leading to pneumonia and severe infections
- Urinary tract infections
- Unwanted side effects of medications
- Heart complications due to issues with automatic bodily functions
- Anxiety and depression leading to suicidal thoughts
Preventing Parkinson-Plus Syndrome
Educating both patients and caregivers is extremely important when dealing with Parkinson-plus syndrome. The right information can help manage the disease better, allow patients to function in a more independent manner, and enhance the quality of life. Patients and their families should understand that conditions linked to Parkinson-plus syndrome can deteriorate rapidly. Despite this fact, there are many treatments and therapies available that can support patients’ well-being.
In such cases, healthcare professionals have a key role in providing the necessary education to cope with the disease. It’s important for patients and their families to appreciate the various symptoms of the Parkinson-plus syndrome. These can involve mental deterioration, problems with movement, alterations in behaviour, visual hallucinations, and disruption of the body’s automatic, or ‘autonomic,’ functions such as heart rate and digestion.
These conditions can lead to many complications, making it vital to focus on prevention and slowing the progression of further health problems associated with the syndrome.
