What is Shy-Drager Syndrome?
Shy Drager syndrome was first identified in 1960 as a brain-related disorder that caused an unexplained drop in blood pressure when a person stands up. Over time, our understanding of this syndrome and the way we categorize it has changed. In 1998, medical experts decided to stop using the term “Shy Drager syndrome”. Instead, they grouped it under the umbrella term “Multiple System Atrophy” (MSA).
Multiple System Atrophy is further split into two categories: MSA-P and MSA-C, depending on the main symptoms the patient shows. If a person’s symptoms are more similar to Parkinson’s disease, they’re categorized as MSA-P. If their symptoms are more related to problems with the ‘cerebellum’ (a part of the brain that helps regulate and coordinate body movements), they’re categorized as MSA-C.
The name “Multiple System Atrophy” reflects the fact that certain parts of the brain shrink or ‘atrophy’ in this disorder. The main parts affected are the ‘cerebellum’, ‘pons’ (which is involved in many essential functions, including movement and sleep), and ‘putamen’ (which plays a role in movement and learning). The extent of the atrophy in these areas varies between MSA-P and MSA-C.
In the spinal cord, MSA-P and MSA-C both affect the ‘intermediolateral area’ (a part of the spinal cord that helps control involuntary actions like heart rate and digestion), ‘Onuf’s nucleus’ (which is involved in controlling some involuntary muscle movement), and the ‘vagal nucleus’ (involved in controlling the heart, digestion, and other functions).
What Causes Shy-Drager Syndrome?
The precise cause of multiple system atrophy, a rare neurological disorder, and its various forms is still unknown. Despite this, researchers have a few theories based on extensive studies. One of the most common theories points to a buildup of a type of protein called alpha-synuclein inside of cells. Lately, researchers have also started looking at the role that malfunctioning mitochondria (the powerhouses of cells), and inflammation might play in causing the disease.
Interestingly, alpha-synuclein is also found to build up inside cells in other brain disorders like Parkinson’s disease. However, in the case of multiple system atrophy, this buildup is found primarily in a type of cell called oligodendrocytes.
Continuing research suggests that this excess of alpha-synuclein might be due to it being over-produced by oligodendrocytes in affected patients, or because the cells absorb too much of it from the surrounding environment. Furthermore, studies have found that patients with multiple system atrophy often have changes, or mutations, in a gene known as COQ2. This gene is responsible for producing a compound called Coenzyme Q10 or CoQ10, a crucial part of the mitochondria’s function in producing energy.
Tissue samples taken after death (autopsy) from the brains of multiple system atrophy patients showed a severe shortage of CoQ10. However, this shortage was primarily observed in the cerebellum, a part of the brain responsible for coordinating muscle movements, suggesting that CoQ10 deficiency might be more related to a variant of multiple system atrophy that chiefly affects the cerebellum. Lastly, researchers have also found evidence to suggest that increased cellular inflammation may be a part of what causes multiple system atrophy.
Risk Factors and Frequency for Shy-Drager Syndrome
Multiple system atrophy is a condition that affects roughly 0.6 to 0.7 out of every 100,000 people each year. The types of this disease seem to be more common in specific regions: MSA-C is mostly found in Japan, while MSA-P is more frequently seen in Western countries. This condition typically starts showing symptoms in people’s sixties.
Signs and Symptoms of Shy-Drager Syndrome
Multiple System Atrophy (MSA) is a condition that affects many parts of the body. Its main symptoms and signs include motor dysfunction (movement problems), dysautonomia (issues with the autonomic nervous system that controls body functions we don’t think about, like blood pressure and heart rate), and sleep disorders. If a patient has MSA with mainly Parkinson’s disease symptoms (MSA-P), they may experience instability when standing, shaking (tremor), stiffness (rigidity), and slowed movements (bradykinesia). Both types of MSA (MSA-P and MSA with mainly cerebellar symptoms MSA-C) can cause dysautonomia, which may include problems with urination, absence of sweating (anhydrosis), and a drop in blood pressure when standing up (orthostatic hypotension). Sleep problems, including sleep apnea, noisy breathing (stridor), and irregular breathing (ataxic breathing), are also common in MSA.
- Motor dysfunction like movement problems
- Dysautonomia symptoms like urinary issues, lack of sweating, and a drop in blood pressure on standing
- Sleep disorders such as sleep apnea, noisy breathing, and irregular breathing
- Parkinsonism features (in MSA-P) including instability when standing, tremor, rigidity, and slow movement
Testing for Shy-Drager Syndrome
Multiple system atrophy (MSA) is a condition that’s quite complex to diagnose. In fact, the most accurate diagnosis can only be done after one has passed away, through an examination of brain tissue that reveals a buildup of a protein called alpha-synuclein and damage to certain brain structures. Because of this, doctors often have to base their diagnosis of MSA on a patient’s symptoms.
To make a formal diagnosis, doctors look for symptoms that start in adulthood (after the age of 30), signs of Parkinson’s disease or cerebellar ataxia, which is a type of movement disorder, problems with automatic body functions such as bladder control or heart rate, and at least one other trait common in MSA patients.
One of the ways that MSA can be differentiated from Parkinson’s disease is through the response to a medication called levodopa. If the patient doesn’t react to the medicine, it’s more likely that they have MSA. On the other hand, if they respond well to the medicine, Parkinson’s disease becomes the most likely diagnosis. This can be a helpful factor when diagnosing MSA.
While no single imaging test can confirm MSA, certain findings on a Magnetic Resonance Imaging (MRI) scan can support an MSA diagnosis. For example, signs of nerve cell loss in areas of the brain known as the pons, putamen, or middle cerebellar peduncle could point towards MSA.
Treatment Options for Shy-Drager Syndrome
Currently, there is no definite cure for a condition known as multiple system atrophy (MSA). However, there are ways to manage the symptoms and novel treatments are being researched that could potentially improve lives in the future. MSA is a condition with symptoms that can manifest differently in different people, and the management approach often depends on these dominant symptoms.
The symptoms that resemble Parkinson’s disease (known as parkinsonism) can be treated with several medicines, including those that increase the monoamine levels in the brain and levodopa, a medication that helps with stiffness, shaking, and difficulty starting movement. If the patient displays signs of cerebellar ataxia (a lack of muscle control or coordination), cholinergic agents (drugs that inhibit, enhance, or mimic the neurotransmitter acetylcholine) are often used.
For patients experiencing urinary and fecal incontinence, treatments can range from medications such as trospium chloride (which treats overactive bladder) and vasopressin analogs (which help the body balance water), to more physical interventions like the use of laxatives or straight catheterization (a tube inserted into the bladder to facilitate urine drainage).
Medications like midodrine and fludrocortisone have also been used to treat orthostatic hypotension, a form of low blood pressure. Physical therapy can accompany these treatments to help manage additional motor symptoms.
New therapies are being developed to prevent the accumulation of alpha-synuclein, a protein in the brain, which is often found in MSA patients. Certain antidepressant medications like sertraline and paroxetine, which belong to the selective serotonin reuptake inhibitors (SSRIs) group, show promise in blocking alpha-synuclein.
Another promising treatment is the use of stem cells, particularly derived from adipose tissue (fat). In a 2019 trial, these cells were implanted in patients with MSA, which resulted in slowing down the progression of the disease.
Other ongoing studies are looking into reducing inflammation and controlling the activity of microglia (a type of cell that supports nerve cells). One such innovation is the myeloperoxidase inhibitor verdiperstat, a drug that demonstrated promising results in animal models of MSA, with a large-scale human trial currently underway to confirm its efficacy in improving patient quality of life.
What else can Shy-Drager Syndrome be?
Multiple system atrophy, a serious condition, can appear in two main forms: one that prominently affects balance (‘cerebellar’) and one that is more similar to Parkinson’s disease (‘parkinsonian’).
When doctors are trying to diagnose this condition, they must consider a range of other similar illnesses, including:
- Parkinson’s disease
- Neurological diseases that impact the balance center of the brain (the cerebellum), like Friedreich ataxia and other spinocerebellar ataxias
- Progressive supranuclear palsy, a condition causing problems with balance, movement, vision, speech and swallowing
- Fragile X–associated tremor ataxia syndrome, a condition characterized by problems with movement and thinking abilities
- Dementia with Lewy bodies, a type of dementia that affects thinking, behavior, mood, and movement
It’s crucial for physicians to examine all these possibilities to reach an accurate diagnosis.
What to expect with Shy-Drager Syndrome
The outlook for patients diagnosed with multiple system atrophy, a rare neurological disorder, isn’t very good, with an average life expectancy of 6 to 10 years after the diagnosis. Generally, if a patient is older at the time they are diagnosed, their survival rate tends to be lower.
Several characteristics have been linked to increased mortality (chances of death) after diagnosis. These include patients frequently falling, being female, and experiencing significant autonomic symptoms. Autonomic symptoms refer to problems with involuntary bodily functions like blood pressure, heart rate, sweating and bowel and bladder control.
Possible Complications When Diagnosed with Shy-Drager Syndrome
The complications of multiple system atrophy (MSA) are quite undesirable and stem directly from a problematic nervous system. A common complaint is sleep disruption, often due to sleep apnea or stridor, which is a high-pitched wheezing sound caused by disrupted airflow. Following recurrent falls due to poor balance or low blood pressure when standing up, patients may suffer from encephalopathy, which is brain damage or disease. Speech and breathing problems can also occur as the illness progresses and results in vocal cord paralysis. Lastly, difficulties swallowing can lead to a severe lung infection known as aspiration pneumonia.
The complications include:
- Disturbed sleep patterns as a result of sleep apnea or stridor
- Encephalopathy due to repeated falls from poor balance or orthostatic hypotension
- Significant speech and breathing difficulties due to vocal cord paralysis
- Aspiration pneumonia from increased swallowing abnormalities
Preventing Shy-Drager Syndrome
The disease Multiple System Atrophy, or MSA, is interesting because its behavior seems similar to many other brain diseases. This means it’s crucial for doctors to conduct thorough examinations, checking carefully for other diseases that look like MSA before confirming the diagnosis. A particular drug called levodopa can be useful at this stage. Not only does it help treat the symptoms of MSA, but it can also speed up the process of identifying the disease.
There is also a need for swift decision-making as MSA decreases life expectancy and treatment options are limited. Therefore, it’s important right from the beginning, to talk about and plan for the end-of-life care alongside regular treatment. It is also necessary to help patients set realistic expectations regarding their treatment outcomes.
