Clinical Clinical diagnostic criteria were defined in 1998 and updated in 2007 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
cerebellar ataxia, leading to clumsiness in body movements, veering from midline when walking, wide-based stance, and falls without signs of
paralysis or weakness. Clinical presentation can vary greatly between patients, but mostly affects speech, balance and walking. Other possible neurological problems include
spasmodic dysphonia,
hypertonia,
hyperreflexia, rigidity,
dysarthria,
dysphagia and neck
dystonic posture. 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
glial
cytoplasmic
inclusions (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
cerebellum,
pons, and
inferior olivary nucleus. 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) and MSA, with which it is primarily associated. MSA presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons. rather than the brainstem, limbic and cortical regions typically effected in Lewy inclusion diseases. 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. 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.
Classification 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. Other synucleinopathies include Parkinson's disease, the
Lewy body dementias, 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. 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. 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:
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==