Classic Progressive Supranuclear Palsy Syndrome
Classical progressive supranuclear palsy, also known as Richardson's syndrome, is the most common clinical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease characterized by postural instability, progressive rigidity, supranuclear gaze palsy and mild dementia.
The prevalence is conservatively estimated at about 1/16,600.
PSP usually manifests during the sixth or seventh decade of life with postural instability and falls, slowing of vertical saccadic eye movements and cognitive slowing. Progressively patients develop other eye abnormalities (dry and red eyes, blurred vision, spontaneous involuntary eyelid closure, photophobia), a dysexecutive cognitive syndrome with impulsivity, problems in speech (slow speech) and a supranuclear gaze palsy and difficulties in swallowing. The disease is characterized neuropathologically by gliosis with astrocytic plaques, accumulation of tau-immunoreactive neurofibrillary tangles and neuronal loss in specific brain areas, especially in the subthalamic nucleus and the substantia nigra.
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 tauopathy extends progressively along neuron-to-neuron connections from the brain stem to the striatum, then the frontal motor area, and later to most other neocortical areas. 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). Rarely mutations of MAPT can produce a similar clinicopathological syndrome. 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. Classical PSP patients do not respond to levodopa treatment. 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 4-8 years after onset of the disease.