Multiple system atrophy (MSA) is a rare neurodegenerative disorder[1] characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia.
This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum.
[2] Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence.
[9] The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling Parkinson's disease) found in 62% at first presentation.
Other common signs at onset include problems with balance (cerebellar ataxia) found in 22% at first presentation, followed by genito-urinary symptoms (9%): both men and women often experience urgency, frequency, incomplete bladder emptying, or an inability to pass urine (retention).
These are:[12] One study found a correlation between the deletion of genes in a specific genetic region and the development of MSA in a group of Japanese patients.
"[clarification needed] Another study investigated the frequency of RFC1 intronic repeat expansions, a phenomenon implicated in CANVAS; a disease with a diagnostic overlap with MSA.
[40][41][42] Features characteristic of OPCA include progressive cerebellar ataxia, leading to clumsiness in body movements, veering from midline when walking, wide-based stance, and falls without signs of paralysis or weakness.
[45] Other possible neurological problems include spasmodic dysphonia, hypertonia, hyperreflexia, rigidity, dysarthria, dysphagia and neck dystonic posture.
[44] Diagnosis may be based on a thorough medical exam; the presence of signs and symptoms; imaging studies; various laboratory tests; and an evaluation of the family history.
[citation needed] Pathological diagnosis can only be made at autopsy by finding abundant glial cytoplasmic inclusions (GCIs) on histological specimens of the central nervous system.
[47] Olivopontocerebellar atrophy can be used as a pathological term to describe degeneration of neurons in specific areas of the brain – the cerebellum, pons, and inferior olivary nucleus.
[53][54] One group revealed robust α-synuclein pathology in the pontine nuclei and medullary inferior olivary nucleus upon histological analysis of neurological tissue from MSA patients.
[55] In 2020, researchers at The University of Texas Health Science Center at Houston concluded that protein misfolding cyclic amplification could be used to distinguish between two progressive neurodegenerative diseases, Parkinson's disease and multiple system atrophy, being the first process to give an objective diagnosis of Multiple System Atrophy instead of just a differential diagnosis.
[56][57] MSA is one of several neurodegenerative diseases known as synucleinopathies: they have in common an abnormal accumulation of alpha-synuclein protein in various parts of the brain.
[61] A table describing the characteristics and modern names of these conditions follows: The term olivopontocerebellar atrophy was originally coined by Joseph Jules Dejerine and André Thomas.
[citation needed] Levodopa (L-Dopa), a drug used in the treatment of Parkinson's disease, improves parkinsonian symptoms in a small percentage of MSA patients.
[citation needed] One particularly serious problem, the drop in blood pressure upon standing up (with risk of fainting and thus injury from falling), often responds to fludrocortisone, a synthetic mineralocorticoid.
[72] The patient can be taught to move and transfer from sitting to standing slowly to decrease risk of falls and limit the effect of postural hypotension.
[6] In addition to orthostatic hypotension, supine hypertension, where the BP is excessively high lying down, is a frequent problem in multiple system atrophy.