Progressive Supranuclear Palsy-Pure Akinesia With Gait Freezing Syndrome

PSP-Pure akinesia with gait freezing (PSP-PAGF) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.

Epidemiology

Prevalence is unknown.

Clinical description

The disease manifests during the sixth decade of life with gait difficulties (either gait slowing or uncertainty) and progressive freezing of gait, speech and writing. In the early stages of the disease, eye movements are normal but patients present with facial immobility, rapid hypophonia with blocking and rapid micrographia. Additional clinical features which are not present in the first 5 years include tremor, axial and limb rigidity, moderate bradykinesia, cognitive disturbance, eye movement abnormalities and blepharospasm. 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 globus pallidus, subthalamic nucleus, and substantia nigra. The tau pathology is less widespread compared to the other PSP sub-types.

Etiology

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. The factors that initiate tau-neurodegeneration are unknown.

Diagnostic methods

Diagnosis is based on the clinical picture.

Differential diagnosis

Differential diagnosis includes Parkinson disease, other atypical parkinsonian disorders (APD; see this term), vascular parkinsonism and normal pressure hydrocephalus.

Management and treatment

There is no treatment curing the disease. Patients do not respond to levodopa treatment.

Prognosis

Mortality is observed generally more than 10 years after onset of the disease, due to lower respiratory tract infection or trauma.