Clinical Clinical diagnostic criteria were defined in 1998 and updated in 2007. Certain signs and symptoms of<unk>  also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult. Radiologic Both MRI and CT scanning may show a decrease in the size of the cerebellum and pons in those with cerebellar features <unk> -C). The putamen is hypointense on T2-weighted MRI and may show an increased deposition of iron in the Parkinsonian <unk> -P) form. In<unk> -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<unk> . Pathologic Pathological diagnosis can only be made at autopsy by finding abundant GCIs on histological specimens of the central nervous<unk> . Contrary to most other synucleinopathies, which develop α-synuclein inclusions primarily in neuronal cell populations,<unk>  presents with extensive pathological α-synuclein inclusions in the cytosol of oligodendrocytes (glial cytoplasmic inclusions), with limited pathology in neurons.<unk>  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<unk>  patients. Histopathological investigation on six cases of pathologically confirmed<unk> , 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 concluded that protein misfolding cyclic amplification could be used to distinguish between two progressive neurodegenerative diseases, Parkinson’s disease and<unk> , being the first process to give an objective diagnosis of<unk>  instead of just a differential diagnosis. Classification<unk>  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<unk> s presented. These terms were discontinued by consensus in 1996 and replaced with<unk>  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: Historical Name Characteristics Modern name and abbreviation Striatonigral degeneration predominating Parkinson's-like symptoms<unk> -P, "p" = parkinsonian subtype Sporadic olivopontocerebellar atrophy (OPCA) characterized by progressive ataxia (an inability to coordinate voluntary muscular movements) of the gait and arms and dysarthria (difficulty in articulating words)<unk> -C, "c" = cerebellar dysfunction subtype Shy–Drager syndrome characterized by Parkinsonism plus a more pronounced failure of the autonomic nervous<unk> . No modern equivalent – this terminology fell out of favour and was not specified in the 2007 consensus paper. The earlier consensus of 1998 referred to<unk> -A, "a" = autonomic dysfunction subtype but this subtype is no longer used. 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<unk> , based on the predominant symptoms of the disease at the time of evaluation. These are: *<unk>  with predominant parkinsonism <unk> -P) - defined as<unk>  where extrapyramidal features predominate. It is sometimes termed striatonigral degeneration, a parkinsonian variant. *<unk>  with cerebellar features <unk> -C) - defined as<unk>  in which cerebellar ataxia predominates. It is sometimes termed sporadic olivopontocerebellar atrophy.
Multiple system atrophy
Pure autonomic failure
Progressive supranuclear palsy
Tropical ataxic neuropathy
Low pressure hydrocephalus
Spinal and bulbar muscular atrophy
Lewy body dementias
Amyotrophic lateral sclerosis