Which are the causes of Multiple Systems Atrophy?

TL;DR: Multiple Systems Atrophy (MSA) is a sporadic neurodegenerative disorder caused by the abnormal accumulation of the protein alpha-synuclein within the brain's support cells, known as oligodendrocytes. While the exact trigger remains unknown, it is considered a non-hereditary condition where these protein clumps disrupt vital communication between the nervous system and various bodily functions.

What causes Multiple Systems Atrophy?

The primary mechanism in Multiple Systems Atrophy is the formation of glial cytoplasmic inclusions—clumps of misfolded alpha-synuclein protein that build up inside oligodendrocytes. These cells are responsible for insulating nerve fibers. When they malfunction, the nervous system struggles to regulate involuntary processes, leading to the hallmark symptoms of Multiple Systems Atrophy, such as orthostatic hypotension and urinary retention. Think of these protein clumps as "cellular debris" that prevents the brain from sending clear signals to the rest of the body.

Is Multiple Systems Atrophy hereditary?

Current clinical research indicates that Multiple Systems Atrophy is almost exclusively a sporadic condition. This means it is not passed down through families, and there is no single known genetic mutation that causes the disease. While researchers are studying whether certain genetic variations might slightly increase an individual's susceptibility, Multiple Systems Atrophy is not currently classified as an inherited genetic disorder.

Are there known environmental or metabolic triggers?

Scientists are actively investigating why the protein misfolding begins in Multiple Systems Atrophy patients. While no specific environmental toxin or infection has been confirmed as a direct cause, research into the etiology of Multiple Systems Atrophy focuses on several potential contributors:

• Mitochondrial dysfunction (problems with energy production in cells).


• Oxidative stress causing damage to neural pathways.


• Potential autoimmune responses or inflammatory triggers in the central nervous system.


• Disruption of the gut microbiome, which is a growing area of interest in synucleinopathies.

What is the difference between causes and risk factors?

In the context of Multiple Systems Atrophy, a "cause" would be the direct biological trigger for protein misfolding, which remains undiscovered. "Risk factors," by contrast, are associations researchers observe in patient populations, such as age of onset (typically in the 50s and 60s). Currently, the etiology of Multiple Systems Atrophy is the subject of intense global study, and the medical community emphasizes that lifestyle choices do not cause this disease.

Next steps

• Consult with a movement disorder specialist or neurologist for a formal evaluation.


• Join the 911 members at DiseaseMaps.org to share experiences and connect with others.


• Monitor for new clinical trials regarding disease-modifying therapies via NIH clinicaltrials.gov.

Medical disclaimer: This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Multiple System Atrophy.


• Orphanet: Multiple System Atrophy (ORPHA:593).


• OMIM (Online Mendelian Inheritance in Man): Multiple System Atrophy.


• The MSA Coalition: Understanding the Science of MSA.