Multiple system atrophy (MSA) is a rare

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

characterized by

tremor A tremor is an involuntary, somewhat rhythmic muscle contraction and relaxation involving neural oscillations, oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the h ...

slow movement Slow movement may refer to: *Slow movement (music) A slow movement is a form in a multi-Movement (music), movement musical piece. Generally, the second movement of a piece will be written as a slow movement, although composers occasionally write ...

, muscle rigidity,

postural instability A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness, or wooziness, or having a sensation of movement, spinning, or floating. Balance ...

(collectively known as

parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

autonomic dysfunction Dysautonomia, autonomic failure, or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This condition may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and b ...

and

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

. This is caused by progressive degeneration of

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s in several parts of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

including the

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

inferior olivary nucleus The inferior olivary nucleus (ION) is a structure found in the medulla oblongata underneath the superior olivary nucleus.Gado, Thomas A. Woolsey; Joseph Hanaway; Mokhtar H. (2003). The brain atlas a visual guide to the human central nervous syste ...

, and

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

. MSA was first described in 1960 by

Milton Shy Milton may refer to: Names * Milton (surname), a surname (and list of people with that surname) ** John Milton (1608–1674), English poet * Milton (given name) Places Australia * Milton, New South Wales * Milton, Queensland, a suburb o ...

and

Glen Drager A glen is a valley, typically one that is long and bounded by gently sloped concave sides, unlike a ravine, which is deep and bounded by steep slopes. The word is Goidelic in origin: ''gleann'' in Irish and Scottish Gaelic, ''glion'' in Manx. ...

and was then known as Shy–Drager syndrome. Many people affected by MSA experience dysfunction of the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

, which commonly manifests as

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

impotence Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

, loss of sweating,

dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

and

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include urinary incont ...

and

incontinence Incontinence or Incontinent may refer to: * Urinary incontinence, the most commonly occurring type of incontinence, the involuntary excretion of urine *Fecal incontinence Fecal incontinence (FI), or in some forms, encopresis, is a lack of con ...

Palsy Palsy is a medical term which refers to various types of paralysisDan Agin, ''More Than Genes: What Science Can Tell Us About Toxic Chemicals, Development, and the Risk to Our Children'' (2009), p. 172. or paresis, often accompanied by weakness and ...

of the

vocal cords In humans, the vocal cords, also known as vocal folds, are folds of throat tissues that are key in creating sounds through Speech, vocalization. The length of the vocal cords affects the pitch of voice, similar to a violin string. Open when brea ...

is an important and sometimes initial clinical manifestation of the disorder. A

prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...

of the

alpha-synuclein Alpha-synuclein (aSyn) is a protein that in humans is encoded by the ''SNCA'' gene. It is a neuronal protein involved in the regulation of synaptic vesicle trafficking and the release of neurotransmitters. Alpha-synuclein is abundant in the brai ...

protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with those affected first showing symptoms at the age of 50–60 years. MSA often presents with some of the same symptoms as

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

. However, those with MSA generally show little response to the

dopamine agonist A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like ...

s used to treat Parkinson's disease and only about 9% of MSA patients with tremor exhibit a true parkinsonian pill-rolling tremor. MSA is distinct from

multisystem proteinopathy Multisystem proteinopathy (MSP) is a dominantly inherited, pleiotropic, degenerative disorder of humans that can affect muscle, bone, and/or the central nervous system. MSP can manifest clinically as classical amyotrophic lateral sclerosis (ALS), ...

, a more common muscle-wasting syndrome. MSA is also different from

multiple organ dysfunction syndrome Multiple organ dysfunction syndrome (MODS) is altered organ function in an acutely ill patient requiring immediate medical intervention. There are different stages of organ dysfunction for certain different organs, both in acute and in chronic ...

, sometimes referred to as multiple organ failure, and from multiple organ system failures, an often-fatal complication of

septic shock Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...

and other severe illnesses or injuries.

Signs and symptoms

MSA is characterized by the following: Autonomic and at least one Motor (clinically established MSA criteria 2022) *

: Post-void urinary residual volume ≥100 mL (usually by ultrasound); Unexplained urinary urge incontinence; or Neurogenic orthostatic hypotension (≥20/10 mmHg blood pressure drop) within 3 minutes (usually by head‐up tilt) *

(

muscle rigidity Hypertonia is a term sometimes used synonymously with ''spasticity'' and ''rigidity'' in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate ...

and slow movement: MSA-P) *

cerebellar ataxia Cerebellar ataxia is a form of ataxia originating in the cerebellum. Non-progressive congenital ataxia (NPCA) is a classical presentation of cerebral ataxias. Cerebellar ataxia can occur as a result of many diseases and may present with symptoms ...

(Poor coordination/unsteady walking: MSA-C) A variant with combined features of MSA and

dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior change (individual), behavior, cognition, movement, and dysautonomia, regulation of automatic bodily functions. Unlike some other dementias, mem ...

may also exist. There have also been occasional instances of

frontotemporal lobar degeneration Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes. Com ...

associated with MSA.

Initial presentation

The most common first sign of MSA is the appearance of an "akinetic-rigid syndrome" (i.e. slowness of initiation of movement resembling

) 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). About 1 in 5 MSA patients experience a fall in their first year of disease. For men, the first sign can be

erectile dysfunction Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...

. Women have also reported reduced genital sensitivity.

Progression

As the disease progresses, one of three groups of symptoms predominates. These are: #

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

- slow, stiff movement, writing becomes small and spidery #

Cerebellar The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or e ...

dysfunction - difficulty coordinating movement and balance #

Autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

dysfunction - impaired automatic body functions, including one, some, or all of the following: ::* postural or

, resulting in

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...

fainting Syncope , commonly known as fainting or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...

upon standing up ::*

urinary incontinence Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a significant effect on quality of life. Urinary incontinence is common in older women ...

::*

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

::*

vocal cord In humans, the vocal cords, also known as vocal folds, are folds of throat tissues that are key in creating sounds through vocalization. The length of the vocal cords affects the pitch of voice, similar to a violin string. Open when breathing a ...

paralysis ::*

and skin ::* trouble regulating

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

due to sweating deficiency in all parts of the body ::* loud snoring, abnormal breathing or inspiratory

stridor Stridor () is an extra-thoracic high-pitched breath sound resulting from turbulent air flow in the larynx or lower in the bronchial tree. It is different from a stertor, which is a noise originating in the pharynx. Stridor is a physical sig ...

during sleep ::* other sleep disorders including

sleep apnea Sleep apnea (sleep apnoea or sleep apnœa in British English) is a sleep-related breathing disorder in which repetitive Apnea, pauses in breathing, periods of shallow breathing, or collapse of the upper airway during sleep results in poor vent ...

REM behavior disorder Rapid eye movement sleep behavior disorder or REM sleep behavior disorder (RBD) is a sleep disorder in which people act out their dreams. It involves abnormal behavior during the sleep phase with Rapid eye movement sleep, rapid eye movement (RE ...

::*

double vision Diplopia is the simultaneous perception of two images of a single object that may be displaced in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often voluntary. However, when occ ...

::* muscle twitches ::* Cognitive impairment

Genetics

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. The region in question includes the

SHC2 SHC-transforming protein 2 is a protein that in humans is encoded by the ''SHC2'' gene. Interactions SHC2 has been shown to interact with Kinase insert domain receptor Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) a ...

gene which, in mice and rats, appears to have some function in the nervous system. The authors of this study hypothesized that there may be a link between the deletion of the SHC2 and the development of MSA. A follow-up study was unable to replicate this finding in American MSA patients. The authors of the study concluded that "Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds." Another study investigated the frequency of

RFC1 Replication factor C subunit 1 is a protein that in humans is encoded by the ''RFC1'' gene. Function The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Repli ...

intronic repeat expansions, a phenomenon implicated in

CANVAS Canvas is an extremely durable Plain weave, plain-woven Cloth, fabric used for making sails, tents, Tent#Marquees and larger tents, marquees, backpacks, Shelter (building), shelters, as a Support (art), support for oil painting and for other ite ...

; a disease with a diagnostic overlap with MSA. The study concluded that these repeats were absent in pathologically confirmed MSA, suggesting an alternative genetic cause.

Pathophysiology

Multiple system atrophy can be explained as cell loss and

gliosis Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes ...

or a proliferation of

astrocyte Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of en ...

s in damaged areas of the central nervous system. This damage forms a scar which is then termed a glial scar. The presence of

inclusion bodies Inclusion bodies are aggregates of specific types of protein found in neurons, and a number of tissue (biology), tissue cells including red blood cells, bacteria, viruses, and plants. Inclusion bodies of aggregations of multiple proteins are also ...

known as Papp–Lantos bodies, in the movement, balance, and autonomic-control centres of the brain are the defining histopathologic hallmark of MSA. The major filamentous component of Papp-Lantos bodies, glial and neuronal cytoplasmic inclusions, is

. Mutations in this substance may play a role in the disease. The conformation of the alpha-synuclein is different from that of alpha-synuclein in

Lewy bodies Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside neurons affected by Parkinson's disease (PD), the Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)) ...

. The disease probably starts with an oligodendrogliopathy. It has been proposed that the α-synuclein inclusions found in Oligodendrocytes result from the pruning and the engulfment of diseased axonal segments containing aggregated α-synuclein, i.e., of Lewy neurites

Tau proteins The tau proteins (abbreviated from tubulin associated unit) form a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintainin ...

have been found in some glial

cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...

inclusion bodies.

Diagnosis

Clinical

Clinical diagnostic criteria were defined in 1998 and updated in 2007 and in 2022. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult. Features characteristic of OPCA include progressive

, leading to clumsiness in body movements, veering from midline when walking, wide-based stance, and falls without signs of

paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...

or weakness. Clinical presentation can vary greatly between patients, but mostly affects speech, balance and walking. Other possible neurological problems include

spasmodic dysphonia Spasmodic dysphonia, also known as laryngeal dystonia, is a disorder in which the muscles that generate a person's voice go into periods of spasm. This results in breaks or interruptions in the voice, often every few sentences, which can make a p ...

hypertonia Hypertonia is a term sometimes used synonymously with ''spasticity'' and ''rigidity'' in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate ...

hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by higher brain ...

, rigidity,

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...

dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

and neck

dystonic Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. ...

posture.

Dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...

is characterized by increased pauses of irregular duration, impaired coordination of vocal pitch, prolonged syllables and an overall irregular speech rhythm. 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.

Radiologic

Both MRI and CT scanning may show a decrease in the size of the cerebellum and pons in those with cerebellar features (MSA-C). The putamen is hypointense on T2-weighted MRI and may show an increased deposition of iron in the Parkinsonian (MSA-P) form. In MSA-C, a "hot cross bun" sign is sometimes found; it reflects atrophy of the pontocerebellar tracts that give T2 hyper intense signal intensity in the atrophic pons. MRI changes are not required to diagnose the disease as these features are often absent, especially early in the course of the disease. Additionally, the changes can be quite subtle and are usually missed by examiners who are not experienced with MSA.

Pathologic

Pathological diagnosis can only be made at autopsy by finding abundant

glia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

inclusion Inclusion or Include may refer to: Sociology * Social inclusion, action taken to support people of different backgrounds sharing life together. ** Inclusion (disability rights), promotion of people with disabilities sharing various aspects of lif ...

s (GCIs) on histological specimens of the central nervous system. ''Olivopontocerebellar atrophy'' can be used as a pathological term to describe degeneration of neurons in specific areas of the brain – the

pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of ...

, and

. OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia (such as the hereditary spinocerebellar ataxia known as

Machado–Joseph disease Machado–Joseph disease (MJD), also known as Machado–Joseph Azorean disease, Machado's disease, Joseph's disease or spinocerebellar ataxia type 3 (SCA3), is a rare autosomal dominantly inherited neurodegenerative disease that causes progressi ...

) and MSA, with which it is primarily associated. Contrary to most other

synucleinopathies Synucleinopathies (also called α-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucle ...

, which develop α-synuclein inclusions primarily in neuronal cell populations, MSA presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons. MSA also differs from other synucleinopathies in its regional pathological presentation, with α-synuclein positive inclusions detected predominantly in the striatum, midbrain, pons, medulla and cerebellum, rather than the brainstem, limbic and cortical regions typically effected in Lewy inclusion diseases. However, recent studies using novel, monoclonal antibodies specific for C-terminally truncated α-synuclein (αSynΔC) have now shown that neuronal α-synuclein pathology is more abundant than previously thought. 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. Histopathological investigation on six cases of pathologically confirmed MSA, using antibodies directed at a variety of α-synuclein epitopes, revealed substantial variation in α-synuclein protein deposition across both cases and brain regions within cases, providing evidence for 'strains' of aggregated conformers that may differentially promote pathological prion-like spread. In 2020, researchers at

The University of Texas Health Science Center at Houston The University of Texas Health Science Center at Houston (UTHealth Houston) is a public academic health science center in Houston, Texas, United States. It was created in 1972 by The University of Texas System Board of Regents. It is located ...

concluded that protein misfolding cyclic amplification could be used to distinguish between two progressive neurodegenerative diseases,

and multiple system atrophy, being the first process to give an objective diagnosis of Multiple System Atrophy instead of just a differential diagnosis.

Classification

MSA is one of several

neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

diseases known as

: they have in common an abnormal accumulation of

protein in various parts of the brain. Other synucleinopathies include Parkinson's disease, the

Lewy body dementia Lewy body dementia (LBD) is an umbrella term for two similar and common subtypes of dementia: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The ...

s, and other more rare conditions.

Old terminology

Historically, many terms were used to refer to this disorder, based on the predominant systems presented. These terms were discontinued by consensus in 1996 and replaced with MSA and its subtypes, but awareness of these older terms and their definitions is helpful to understanding the relevant literature prior to 1996. These include striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and

Shy–Drager syndrome Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia. This is caused by progre ...

. A table describing the characteristics and modern names of these conditions follows: The term ''olivopontocerebellar atrophy'' was originally coined by

Joseph Jules Dejerine Joseph Jules Dejerine (3 August 1849 – 26 February 1917) was a French neurologist. Early life and education Dejerine was born to French parents in Geneva, Switzerland, where his father was a carriage proprietor. During the Franco-Prussian War ...

and André Thomas. It was subdivided as: Non-hereditary diseases formerly categorized as olivopontocerebellar atrophy have were reclassified as forms of MSA as well as to four hereditary types, that have been currently reclassified as four different forms of

spinocerebellar ataxia Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of ...

Current terminology

The current terminology and diagnostic criteria for the disease were established at a 2007 conference of experts and set forth in a position paper. This Second Consensus Statement defines two categories of MSA, based on the predominant symptoms of the disease at the time of evaluation. These are: * MSA with predominant parkinsonism (MSA-P) - defined as MSA where extrapyramidal features predominate. It is sometimes termed striatonigral degeneration, a parkinsonian variant. * MSA with cerebellar features (MSA-C) - defined as MSA in which cerebellar ataxia predominates. It is sometimes termed sporadic olivopontocerebellar atrophy.

Management

Supervision

Ongoing care from a

neurologist Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the ...

specializing in

movement disorders Movement disorders are clinical syndromes with either an excess of movement or a paucity of voluntary and involuntary movements, unrelated to weakness or spasticity. Movement disorders present with extrapyramidal symptoms and are caused by basal ...

is recommended, because the complex symptoms of MSA are often not familiar to less-specialized neurologists.

Hospice Hospice care is a type of health care that focuses on the palliation of a terminally ill patient's pain and symptoms and attending to their emotional and spiritual needs at the end of life. Hospice care prioritizes comfort and quality of life b ...

/homecare services can be very useful as disability progresses.

Drug therapy

Levodopa Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...

(L-Dopa), a drug used in the treatment of Parkinson's disease, improves parkinsonian symptoms in a small percentage of MSA patients. A recent trial reported that only 1.5% of MSA patients experienced any improvement at all when taking levodopa, their improvement was less than 50%, and even that improvement was a transient effect lasting less than one year. Poor response to L-Dopa has been suggested as a possible element in the differential diagnosis of MSA from Parkinson's disease. The drug

riluzole Riluzole is a medication used to treat amyotrophic lateral sclerosis (ALS) and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Ril ...

is ineffective in treating MSA or PSP.

Rehabilitation

Management by rehabilitation professionals including

physiatrist Physical medicine and rehabilitation (PM&R), also known as physiatry, and outside the United States as physical and rehabilitation medicine (PRM), is a branch of medicine that aims to enhance and restore functional ability and quality of life ...

s, physiotherapists, occupational therapists, speech therapists, and others for difficulties with walking/movement, daily tasks, and speech problems is essential.

Physiotherapist Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

s can help to maintain the patient's mobility and will help to prevent

contractures In pathology, a contracture is a shortening of muscles, tendons, skin, and nearby soft tissues that causes the joints to shorten and become very stiff, preventing normal movement. A contracture is usually permanent, but less commonly can be temp ...

.
Instructing patients in

gait training Gait training or gait rehabilitation is the act of learning how to walk, either as a child, or, more frequently, after sustaining an injury or disability. Normal human gait is a complex process, which happens due to co-ordinated movements of the wh ...

will help to improve their mobility and decrease their risk of falls. A physiotherapist may also prescribe

mobility aid A mobility aid is a device designed to assist individuals with impaired movement. These devices help people walk, maintain balance, or get around more easily. Mobility aids include walking supports like canes, crutches, and walkers for those w ...

s such as a cane or a walker to increase the patient's safety.

Speech therapist Speech is the use of the human voice as a medium for language. Spoken language combines vowel and consonant sounds to form units of meaning like words, which belong to a language's lexicon. There are many different intentional speech acts, suc ...

s may assist in assessing, treating and supporting speech (dysarthria) and swallowing difficulties (dysphagia). Speech changes mean that alternative communication may be needed, for example, communication aids or word charts. Early intervention of swallowing difficulties is particularly useful to allow for discussion around tube feeding further in the disease progression. At some point in the progression of the disease, fluid and food modification may be implemented.

Avoidance of postural hypotension

One particularly serious problem, the drop in blood pressure upon standing up (with risk of

and thus injury from falling), often responds to

fludrocortisone Fludrocortisone, sold under the brand name Florinef among others, is a corticosteroid used to treat congenital adrenal hyperplasia, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together wit ...

, a synthetic

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

. Another common drug treatment is the alpha-agonist

midodrine Midodrine, sold under the brand names ProAmatine and Orvaten among others, is an antihypotensive medication used to treat orthostatic hypotension (low blood pressure when standing) and urinary incontinence. It is taken oral administration, by m ...

.Multiple system atrophy (MSA)
''mayoclinic.org'', accessed 20 May 2018 Non-drug treatments include "head-up tilt" (elevating the head of the whole bed by about 10 degrees), salt tablets or increasing salt in the diet, generous intake of fluids, and pressure (elastic) stockings. Avoidance of triggers of low blood pressure, such as hot weather,

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

, and dehydration, are crucial. 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 Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

. Instruction in ankle pumping helps to return blood in the legs to the

systemic circulation In vertebrates, the circulatory system is a organ system, system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of ...

. Other preventative measures are raising the head of the bed by 8 in (20.3 cm), and the use of compression stockings and abdominal binders.

Supine hypertension

In addition to orthostatic hypotension, supine hypertension, where the BP is excessively high lying down, is a frequent problem in multiple system atrophy. Treatment of one symptom can easily aggravate the other, and supine hypertension in such patients has been linked to the same cardiovascular complications as essential hypertension.

Support

Social workers and occupational therapists can also help with coping with disability through the provision of equipment and home adaptations, services for caregivers and access to healthcare services, both for the person with MSA as well as family caregivers.

Prognosis

The average lifespan after the onset of symptoms in patients with MSA is 6–10 years. Approximately 60% of patients require a wheelchair within five years of onset of the motor symptoms, and few patients survive beyond 12 years. The disease progresses without remission at a variable rate. Those who present at an older age, those with parkinsonian features, and those with severe autonomic dysfunction have a poorer prognosis. Those with predominantly cerebellar features and those who display autonomic dysfunction later have a better prognosis.

Causes of death

The most common causes of death are

sudden death Sudden Death or Sudden death may refer to: Medical * Cardiac arrest, also known as sudden cardiac death, natural death from cardiac causes * Sudden cardiac death of athletes * Sudden infant death syndrome * Sudden unexpected death in epilepsy *Su ...

and death caused by infections, which include urinary catheterization infections,

feeding tube A feeding tube is a medical device used to provide nutrition to people who cannot obtain nutrition by mouth, are unable to swallow safely, or need nutritional supplementation. The state of being fed by a feeding tube is called gavage, enteral f ...

infections, and

aspiration pneumonia Aspiration pneumonia is a type of lung infection that is due to a relatively large amount of material from the stomach or mouth entering the lungs. Signs and symptoms often include fever and cough of relatively rapid onset. Complications may incl ...

. Some deaths are caused by

cachexia Cachexia () is a syndrome that happens when people have certain illnesses, causing muscle loss that cannot be fully reversed with improved nutrition. It is most common in diseases like cancer, Heart failure, congestive heart failure, chronic o ...

, also known as wasting syndrome.

Epidemiology

Multiple system atrophy is estimated to affect approximately 5 per 100,000 people. At autopsy, many patients diagnosed during life with Parkinson's disease are found actually to have MSA, suggesting that the actual incidence of MSA is higher than that estimate. While some suggest that MSA affects slightly more men than women (1.3:1), others suggest that the two sexes are equally likely to be affected. The condition most commonly presents in persons aged 50–60.

Research

Mesenchymal

stem cell therapy Stem-cell therapy uses stem cells to treat or prevent a disease or condition. , the only FDA-approved therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone marrow or peripheral blood stem cel ...

may delay the progression of neurological deficits in patients with MSA-cerebellar type.

Notable cases

Nikolai Andrianov Nikolai Yefimovich Andrianov (; 14 October 1952 – 21 March 2011) was a Soviet and Russian gymnast. He held the record for men for the most Olympic medals at 15 (7 gold medals, 5 silver medals, 3 bronze medals) until Michael Phelps surpass ...

was a Soviet/Russian gymnast who held the record for men for the most Olympic medals at 15 (7 gold medals, 5 silver medals, 3 bronze medals) until Michael Phelps surpassed him at the 2008 Beijing Summer Olympics. * Todd J. Campbell (1956–2021), United States district judge and counsel to former Vice President Al Gore. *Singer and songwriter

Johnny Cash John R. Cash (born J. R. Cash; February 26, 1932 – September 12, 2003) was an American singer-songwriter. Most of his music contains themes of sorrow, moral tribulation, and redemption, especially songs from the later stages of his career. ...

wrote in his autobiography that he was diagnosed with Shy–Drager in 1997. * Ronald Green (1944–2012),

American-Israeli Israeli Americans () are Americans who are of full or partial Israeli descent. The Israeli-American community, while predominantly Jewish, also includes various ethnic and religious minorities reflective of Israel's diverse demographics. This c ...

basketball player *

Joseph C. Howard Sr. Joseph Clemens Howard Sr. (December 9, 1922 – September 16, 2000) was the first African American to win an election as judge for the Baltimore City Supreme Bench and was later appointed by President Jimmy Carter to be a United States district ...

(1922-2000) was the first African American to serve as a

United States district judge The United States district courts are the trial courts of the U.S. federal judiciary. There is one district court for each federal judicial district. Each district covers one U.S. state or a portion of a state. There is at least one feder ...

of the

United States District Court for the District of Maryland The United States District Court for the District of Maryland (in case citations, D. Md.) is the United States district court, federal district court whose jurisdiction is the state of Maryland. Appeals from the District of Maryland are taken ...

. *

Kenneth More Kenneth Gilbert More (20 September 1914 – 12 July 1982) was an English actor. Initially achieving fame in the comedy ''Genevieve (film), Genevieve'' (1953), he appeared in many roles as a carefree, happy-go-lucky gent. Films from this period ...

British actor, originally diagnosed with Parkinson's disease. *Chef

Kerry Simon Kerry Glen Simon (June 17, 1955 – September 11, 2015) was an American celebrity chef and restaurateur based in Las Vegas. Simon was also known by the moniker "Rock n' Roll Chef", given to him by ''Rolling Stone''. He was the executive chef ...

died from complications of MSA. *

David Colin Sherrington David Colin Sherrington FRS (5 March 1945 – 4 October 2014) was a polymer chemist whose research career was based at the University of Strathclyde. Biography David Colin Sherrington was born at Webster Street, Litherland, Liverpool on 5 M ...

FRS (1945–2014), noted polymer chemist, who was diagnosed in 2012 and died from pneumonia two years later. * Karsten Heuer (1968-2024) Canadian Biologist, Conservationist, Filmmaker and Author.

References

External links

* Medical Textbook
"Multiple System Atrophy"
edited by Gregor Wenning and Alessandra Fanciulli * {{DEFAULTSORT:Multiple System Atrophy Extrapyramidal and movement disorders Rare diseases Neurodegenerative disorders Peripheral nervous system disorders ca:Síndrome de Shy-Drager es:Síndrome de Shy-Drager pt:Síndrome de Shy-Drager ro:Sindromul Shy-Drager sl:Shy-Dragerjev sindrom

Signs and symptoms

Initial presentation

Progression

Genetics

Pathophysiology

Diagnosis

Clinical

Radiologic

Pathologic

Classification

Old terminology

Current terminology

Management

Supervision

Drug therapy

Rehabilitation

Avoidance of postural hypotension

Supine hypertension

Support

Prognosis

Causes of death

Epidemiology

Research

Notable cases

See also

References

External links