Symptomatic and Treatment Approaches for Multiple System Atrophy

MSA Symptomology and Therapeutic Approaches

Multiple System Atrophy (MSA) is a rapidly progressive neurodegenerative disorder that affects fewer than 50,000 individuals in the United States, making it relatively rare. This condition is characterized by a combination of autonomic dysfunction, motor impairment, and severe disability over time.

Symptoms and Progression

MSA symptoms usually begin during a person's middle age and may resemble those of Parkinson's disease, including a lack of coordination, slow movements, stiffness or tremors, lightheadedness or fainting, a quivering, croaky voice, and bladder control difficulties. People start with more prominent symptoms in one of the following areas: balance and coordination, tremors and stiffness, or autonomic symptoms.

As the disease progresses, individuals may experience worsening motor symptoms such as rigidity, gait disturbances, speech and swallowing difficulties. Autonomic failure, including orthostatic hypotension and urinary dysfunction, also becomes more pronounced. Severe dysphagia and respiratory issues may develop in later stages, increasing the risk of pneumonia.

MSA has heterogeneous clinical subtypes, mainly MSA-P (predominantly parkinsonian features) and MSA-C (predominantly cerebellar ataxia). Neurodegeneration involves alpha-synuclein deposits primarily in oligodendroglia and widespread brain regions, leading to deterioration in brain glucose metabolism and dopaminergic dysfunction.

Treatment and Life Expectancy

Unfortunately, there is currently no cure or definitive disease-modifying therapy for MSA. Treatments are mainly symptomatic and supportive, focusing on managing autonomic symptoms, using dopaminergic drugs for parkinsonism symptoms (although response is usually poor), and offering physical therapy, speech/swallowing therapy, and bladder management.

Experimental therapies targeting neuroinflammation and immune activation are under investigation, such as intranasal foralumab, which aims to reduce microglial activation and may slow progression.

The prognosis for MSA is poor, with a median survival of approximately 6 to 9 years from symptom onset. Rapid progression and the onset of autonomic failure contribute to shortened life expectancy. Biomarkers such as plasma neurofilament light chain (NfL) levels correlate with progression and mortality risk.

In summary, MSA is a rapidly progressing neurodegenerative disease causing severe motor and autonomic disability with a median survival under a decade, treated mainly symptomatically while new therapeutic strategies are under investigation.