What is Multiple System Atrophy?

Jul 29

Multiple System Atrophy, or MSA, is a rare progressive neurodegenerative disease that results in neuronal cell death and degeneration in the brain and spinal cord. It mainly affects the autonomic nervous system. Our autonomic nervous system (or ANS) is responsible for controlling critical automatic bodily functions, including regulation of heart rate, blood pressure, respiration, and digestion. The autonomic system degenerates in multiple system atrophy, leading to an array of negative symptoms.

How Common is Multiple System Atrophy?

MSA is present in 15,000 to 50,000 people in the United States. It affects men and women of all racial and ethnic groups (3).

What Causes Multiple System Atrophy?

The cause of MSA is still poorly understood, but researchers have identified the buildup of a misfolded protein called alpha-synuclein in oligodendrocytes (1). Oligodendrocytes are supporting cells that create a protective layer around our neurons called a myelin sheath. Myelin allows nerves to transmit information rapidly and efficiently. Alpha-synuclein protein stops the ability of our nervous system to lay a protective coating on our neurons, leaving them unprotected and vulnerable to early cell death. The same protein is present in Parkinson’s disease, but in Parkinson’s the alpha synuclein accumulates in dopamine producing neurons. Therefore, both diseases are often referred to as alpha synucleinopathies (3). A risk factor for these diseases is variations in the gene SCNA, which provides instructions for the creation of alpha-synuclein (19).

What are the Early Symptoms of Multiple System Atrophy?

Early symptoms of MSA look very similar to Parkinson’s disease:

Loss of coordination

Slowness of movement, tremor, or rigidity
Slow or slurred speech and/or quiet, quivering voice
Fainting/lightheadedness due to orthostatic hypotension
Difficulty chewing or swallowing
Loss of bowel and bladder control

MSA is classified in two different categories, depending on the more prominent symptoms presenting in the individual (3):

The Parkinsonian type (MSA-P), with primary characteristics similar to Parkinson’s disease with slowness of movements, tremor, shuffling gait, balance problems and autonomic nervous system dysfunction
The cerebellar type (MSA-C), with primary characteristics similar to cerebellar disorders featuring ataxia (problems with balance and coordination), difficulty with swallowing, changes to the voice and abnormal eye movements

What are the Later Symptoms of Multiple System Atrophy?

Although similar, MSA does tend to progress more rapidly than Parkinson’s disease. Later symptoms of MSA include:

Contractures in the hands or limbs (muscles or tendons around joints shorten and prevent ease of movement).
Pisa syndrome, an abnormal posture where the person appears to be always leaning to one side (like the Leaning Tower of Pisa)
Antecollis, where the head drops down as the neck bends forward
Sighing or gasping uncontrollably, as respiratory control changes
Sleep disorders
Anxiety or depression
Dysautonomia, which is a disturbance in our ANS making it hard to control our automatic functions like regulating our heart rate, sending blood where it needs to go against gravity, creating an erection, producing adequate amounts of sweat or controlling our bowel and bladder (20).

How Does Multiple System Atrophy Affect the Brain?

The presence of alpha-synuclein proteins creates an opportunity for neuron cell death in regions where the proteins are present. Cells require blood, which carries oxygen and glucose to them, as well as stimulation in order to survive. As alpha-synuclein prevents the supportive oligodendrocytes from creating the protective fatty myelin sheath around cells, the cells begin to die as they lose appropriate levels of stimulation, as well as access to the fuel they require (1).

MSA also appears to directly affect cellular energy production. Neurons make energy within specialized organelles called mitochondria, which function like factories for producing ATP, the high-energy molecule that powers most cellular reactions. CoQ10 is an important antioxidant in this process, and genetic studies have shown dysfunctional CoQ10 production in MSA. There also appears to be specific enzyme deficit that impairs energy production in the mitochondria. Collectively these lead to impaired mitochondrial function that may not be causal but likely increases the rate of neurodegeneration in MSA (21)

New studies indicate that there is a direct connection between intestinal permeability, gut bacteria, and MSA. Research shows that MSA patients have significantly different gut microbiota than healthy subjects, with increased permeability of the intestinal wall to dietary proteins and inflammatory chemicals. They also show abnormal gut bacteria, which produce endotoxins that further damage the intestinal wall and lead to oxidative stress (6). It appears that an overstimulation of the immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation. This promotes the activation of a direct neuroinflammation response that ultimately triggers the development of alpha-synuclein pathology (7).

There is an emerging body of research that supports both Parkinson’s Disease and MSA as progressive diseases that model prion-like mechanisms. Prion is short for proteinaceous infectious particle. Prions can self-transform their shape and propagate. They can be transmitted from cell to cell, between individuals, and even between animals of different species. Prions are the cause of particularly severe neurodegenerative conditions such as Mad Cow Disease.

While no research currently demonstrates that PD or MSA is a transmissible condition between individuals, there is good support that once established, both spread through the nervous system in a similar manner to prion diseases (4). There is literature to demonstrate distinct biochemical differences in the properties of each disease’s alpha-synuclein, MSA being more readily transmissible to other cells in a system than PD. In the future, this may offer possible directions for synucleinopathy diagnosis (5).

How is Multiple System Atrophy Diagnosed?

A careful medical history and thorugh neurological examination remain critical for the accurate diagnosis of MSA. Additional investigations are helpful to support the diagnosis, rule out similar conditions, and determine therapeutic strategies. Structural and and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, swallowing studies and cognitive assessments are often used to support the diagnosis.

New diagnostic tools are emerging, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, which should lead to more accurate and earlier recognition of MSA should be possible, even in the prodromal stages (21).

How is Multiple System Atrophy Usually Treated?

There is no known cure for Multiple Systems Atrophy. Most therapy focuses on controlling the various aspects of dysfunction present in MSA patients. People are generally medicated in this regard. Improving blood pressure and preventing lightheadedness or fainting may be done by increasing salt intake, wearing compression stockings and avoiding heavy meals. Botulin injections (Botox) may be utilized to control contracted muscles. Physical therapies may be used to maintain mobility, improve muscles length and tone and abnormal postures. Assistive devices may be required for stability (22).

How is the NeuroRescue Program Different?

While we cannot cure MSA, we employ a host of advanced therapies and technologies that can help improve the function of your remaining systems. By doing so, we can often help restore your mobility, reduce your tremor, improve your balance and gait, and enhance your quality of life.

Much of what happens in MSA is related to the inability to properly localize yourself in the environment. Your brain makes sense of where you are in the world through inputs from your muscles and joints, inputs from your inner ear, and inputs from your eyes. The eyes are constantly scanning the world to provide the brain with a visual map of the surrounding space. It does this with saccades, which are fast eye movements from target to target.

In order for you to move through and interact with the world, you first need to know where the world is. This requires that saccades are fast, accurate, stable, and have very quick reaction times. As the brainstem and cerebellum are involved in saccades, all of these functions break down. Saccades lose accuracy and are easy to fatigue in MSA (8).

Smooth pursuit eye movements, which involve following moving targets, are another type of eye movement demonstrating pathophysiological differences between MSA and Parkinson’s disease. Both disease processes demonstrate breakdown of these eye movements, but in different ways (10). These features can actually help distinguish between MSA and Parkinson’s disease (9).

Research shows that the breakdown in saccades seen with MSA leads to postural instability, impairs the ability to turn, and leads to freezing of gait (11). We find that by rehabilitating saccades in a very precise manner, we can often improve balance, gait, and postural stability.

Another more complicated eye movement is called an anti-saccade, where a target is presented, and a person needs to inhibit the reflex to look at the target and instead consciously choose to look in the other direction. Anti-saccades are involved in a number of executive functions, and these give rise to foundational cognitive processes. Research shows that anti-saccades break down in MSA, leading to problems with planning, reasoning, and emotional regulation (12). We find that by rehabilitating these eye movements we can often restore some of the cognitive flexibility and emotional regulation lost to this disease.

There are a host of other therapies that we engage in with our MSA patients. All of these have different functions and allow us to rehabilitate specific capacities. These range from vestibular rehabilitation to improve balance, gait, and cognition (13), to visual optokinetic stimulation to improve motor control and postural stability (14,15). They include a number of different types of electrical stimulation to improve cognition, eye movements, balance, gait, tremor, cognition, blood pressure regulation, and even swallowing (16,17,18). They even include therapies such as transcranial magnetic stimulation to improve motor function, emotional regulation and balance (19), and virtual reality exercises to improve the ability to function in the world and decrease fall risk (20).

No two Multiple System Atrophy disease presentations are alike, and the same holds true for the NeuroRescue program. A cookie-cutter approach will be doomed to fail in a condition as complicated as MSA. All of our therapy protocols are tailored to the unique needs of the individual.

How Does the NeuroRescue Program Work?

We design your unique NeuroRescue Program to be among the most comprehensive diagnostic and therapeutic protocols available today. We create individual NeuroRescue Programs based on a comprehensive analysis of every relevant neurological system and pathway, using gold-standard, cutting edge neurodiagnostic technologies and examination procedures and state-of-the-art therapies.

We begin with your Discovery Day, wherein we perform a comprehensive history of not only your condition, but your life on a timeline. This allows us to dive deeply into your case and see all of the factors that led to where you are now. It helps us uncover hidden problems and associated conditions that may be making it difficult for you to move your recovery forward.

In the case of MSA, this requires a deep dive into the gut microbiome, intestinal wall permeability, mechanisms of oxidative stress and mitochondrial failure, and many other factors that can be provoking your issues.

Our examination allows us to identify the areas and pathways of your brain that have been impacted by your MSA. We begin by precisely quantifying the function of your visual, vestibular, and proprioceptive systems through computerized analysis of your eye movements, your inner ear reflexes, and your balance in a host of different sensory conditions.

We employ technologies including Videooculography and Saccadometry to measure several classes of eye movements. We use Video Head Impulse Testing to measure the function of your inner ear, and Computerized Dynamic Posturography to assess your balance in different sensory conditions.

We use NeuroSensoryMotor Integration testing to evaluate hand-eye coordination and cognition, and Virtualis testing to assess dynamic eye tracking and perception of vertical in a virtual reality environment.

We combine all of this with a comprehensive physical and neurological examination of your sensory, motor, autonomic, and cognitive systems. We review any relevant laboratory testing, radiological imaging, and prior neurodiagnostic testing, and integrate that information with our findings.

We use this information to identify which parts of your brain are working properly, which systems are struggling, and the precise point at which your systems fatigue.

We can then design a NeuroRescue Program that is unique and specific to your brain, and yours alone. Your NeuroRescue Program works to rejuvenate and reintegrate the damaged neurons and pathways in your brain. It works to improve energy, endurance, and functional capacity within your fragile systems.

We use our technologies and procedures to not only see what we need to address, but also when it is time to stop and let you rest. We address your impaired neurological function from multiple angles of therapy, and provide metabolic support to improve neurological recovery.

While we cannot bring back neurons that have been lost to MSA, your NeuroRescue Program allows us to take the pathways that remain and maximize their efficiency and endurance. And by focusing on the integration of systems, we can do more than just get pathways working better, we can get them working together again. This gives us our best opportunity to help you live a healthy, vibrant, and fulfilling life.

Your Next Best Step:

Living with Multiple Systems Atrophy is challenging. While we cannot offer a cure for the condition, we find that with our therapies many of the symptoms can be manageable, function can be enhanced, and quality can often be significantly improved.

To see if the NeuroRescue Program is right for you, contact one of our patient care coordinators to schedule your Discovery Day.

And remember, it’s never too late to start getting better.