Multiple system atrophy is a very rare progressive neurological disorder that affects multiple areas of the brain, including areas controlling the autonomic nervous system, cerebellum and basal ganglia.1 MSA was previously termed as Shy Drager syndrome, which predominantly encompassed symptoms of autonomic nervous system dysfunction. It is usually adult onset disorder affecting individuals after 30 years of age.
MSA is grouped under two categories based on the predominant symptoms at the time of presentation, namely, MSA-P (striatonigral degeneration) in which Parkinsonism symptoms predominate and MSA-C (sporadic olivopontocerebellar atrophy) in which cerebellar ataxia predominates. The autonomic failure is present in both the phenotypes.
What Causes Multiple System Atrophy?
The exact cause of multiple system atrophy is still unknown.1 It is a random disease, i.e., it affects adults sporadically. Although, there have been suggestions of several environmental and genetic factors, more research is needed in this area. There have been many theories regarding multiple system atrophy, including a history of trauma, pesticide exposure and autoimmune mechanism, but neither has been supported by solid evidence.
Initially, it was assumed that the damage of gray matter led to multiple system atrophy; however, the presence of oligodendroglial glial cytoplasmic inclusions confirmed the damage of white matter. It is characterized by progressive loss of nerve cells at multiple sites in the brain. There are extensive areas of myelin sheath degeneration, which might play an important role in the pathogenesis of multiple system atrophy. Glial cytoplasmic inclusions (GCIs) are characteristic of the disease. In this, the damaged area of the central nervous system is proliferated by astrocytes (star shaped cells found in the CNS), which leads to scar formation in the affected areas. The specific protein associated with GCIs is alpha-synuclein, which plays a central role in the development of multiple system atrophy. The over expression of alpha-synuclein has a toxic effect on the brain and associated MSA. The accumulation of alpha-synuclein is also seen in other neurological disorders, such as Parkinson’s disease, pure autonomic failure and Lewy body dementia. These are collectively termed as synucleinopathies.
Generally in multiple system atrophy, the degeneration of central nervous system includes:
Areas that are involved in the autonomic nervous system: These include neuronal loss in intermediolateral cell columns and Onuf’s nucleus in the spinal cord. It is related to orthostatic hypotension in MSA cases.
Striatonigral degeneration: This area of the brain (substantia nigra and striatum) is responsible for movements and balance.2 When the nerve is damaged, there is disruption of communication between nerve cells. This is related to parkinsonian symptoms, such as bradykinesia, tremors, rigidity and postural instability
Olivopontocerebellar atrophy: It refers to specific areas of the brain known as olives, pons and cerebellum.3 Inferior olives are two round structures located in medulla, which forms the lowest part of brainstem. Pons forms an important part of brainstem containing neuronal pathways between cerebrum, cerebellum and spinal cord. It helps in transmission of messages between these structures. Cerebellum is the part of brain that helps in coordinating voluntary movement along with controlling balance and posture. The damage to olivopontocerebellar portion of central nervous system leads to gait ataxia, limb ataxia, ataxia dysarthria along with oculomotor dysfunction.
Multiple System Atrophy Symptoms
The symptoms include orthostatic hypotension, incomplete bladder emptying, –urinary incontinence, erectile dysfunction, rigidity, tremors, bardykinesia, postural instability, ataxia, oculomotor dysfunction, disproportionate antecollis (forward bending of the neck), anterior flexion of the spine, lateral flexion of the spine, orofacial dystonia, contractures of hands and feet, snoring, dysarthria, dysphonia, increased sighs, cold hands and feet, jerky postural or action tremors and pathological laughter or crying.
The symptoms associated with multiple system atrophy are rapidly progressive in nature, so that within 5-10 years the person may become unable to walk on their own and may require wheelchair, and may lose their ability to speak and swallow leading to severe respiratory complications. Life threatening complications include aspiration pneumonia, deep vein thrombosis and pulmonary embolism.
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