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Progressive supranuclear palsy
A rare late-onset neurodegenerative disease characterized by supranuclear gaze palsy, postural instability, progressive rigidity, and mild dementia.
ORPHA:683Classification level: Disorder
Prevalence is conservatively estimated at about 1/16,600.
PSP usually manifests during the sixth or seventh decade of life. Five clinical variants have been described with clinicopathological correlations: Classical PSP (Richardson's syndrome), and four atypical variants of PSP including 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) (see these terms). Richardson's syndrome is the most common clinical variant and manifests with a lurching gait, falls due to postural instability, cognitive impairment and slowing of vertical saccadic eye movements. Progressively patients develop other problems such as problems in speech and eventually a supranuclear gaze palsy and difficulties in swallowing. PSP-Parkinsonism (PSP-P) is characterized by prominent early parkinsonism (tremor, limb bradykinesia, axial and limb rigidity) rather than falls and cognitive change. Over the years, patients ultimately develop clinical features characteristic of Richardson's syndrome. PSP-Pure akinesia with gait freezing (PSP-PAGF) is characterized by progressive freezing of gait, speech and writing early in the course of the disease. Later, axial rigidity, and facial immobility can occur, and supranuclear downgaze paresis may emerge after a decade. PSP-corticobasal syndrome (PSP-CBS) is characterized by progressive, asymmetric dyspraxia, limb rigidity, bradykinesia and progressive postural instability. PSP-progressive non fluent aphasia (PSP-PNFA) is characterized by speech anomalies (apraxia of speech, agrammatism, phonemic errors). Motor symptoms appear later in the course of the disease. PSP is characterized neuropathologically 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 five clinical variants.
PSP is a 4R tauopathy composed of a preponderance of four-repeat (exon 10 positive) 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). The factors that initiate tau-neurodegeneration are unknown.
Diagnosis is based on the clinical picture and neuropsychological evaluation.
Differential diagnosis includes Parkinson disease and other atypical parkinsonian disorders (APD) such as multiple system atrophy and corticobasal degeneration (see these terms). Similar eye movement abnormalities can occur in Niemann-Pick disease type C and Whipple's disease (see these terms).
Management and treatment
There is no treatment curing the disease. Some drugs, depending on the clinical variant, reduce morbidity and improve quality of life (e.g., levodopa responsiveness of patients with PSP-Parkinsonism). Amantadine may improve gait freezing, and other anticholinergic medications occasionally improve voice and speech disturbance.
Progressively, patients become wheel-chair dependant due to the frequent falls. Difficulties in breathing and swallowing, and infections are the main causes of death, generally 6-12 years after onset of the disease.