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Atypical progressive supranuclear palsy syndrome
A group of clinical syndromes associated with underlying PSP-tau pathology, that do not conform to the classic presentation of PSP (Richardson syndrome), a rare late-onset neurodegenerative disease. The group comprises PSP-Parkinsonism (PSP-P), PSP-Pure akinesia with gait freezing (PSP-PAGF), PSP-corticobasal syndrome (PSP-CBS) and PSP-progressive non fluent aphasia (PSP-PNFA).
ORPHA:99750Classification level: Subtype of disorder
PSP-P is characterized by early parkinsonism, including limb bradykinesia, axial and limb rigidity and, in some patients, tremor, with some response to dopaminergic medications. The improvement with medication often diminishes and patients usually go on to develop clinical features characteristic of classical PSP. PSP-PAGF is characterized by progressive gait freezing, speech and writing difficulties, facial immobility and ultimately blepharospasm with occasionally supranuclear downgaze paresis. PSP-CBS is characterized by progressive asymmetric dyspraxia, limb rigidity, bradykinesia, and progressive postural instability. PSP-PNFA is characterized by speech anomalies (apraxia of speech, agrammatism, phonemic errors). Motor disturbances may occur later. Neuropathologically, all forms are characterized by neuronal loss, gliosis with astrocytic plaques and accumulation of tau-immunoreactive neurofibrillary tangles in specific brain areas. The differences in the rate and areas of accumulation of phosphorylated tau protein correlate with the clinical variants of PSP-tau pathology.
PSP is a 4R tauopathy composed of a preponderance of four-repeat tau isoforms and a characteristic biochemical profile (doublet tau 64 and tau 69). The MAPT H1-clade specific sub-haplotype, H1c, is a risk factor for this disease. PSP is also characterized by deficits in several neurotransmitter systems (e.g., dopaminergic, cholinergic, gabaergic).