Progressive Supranuclear Palsy-Progressive Non-Fluent Aphasia Syndrome

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

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Drugs

(2'R,3'S)-2'-hydroxy-N-carboxy-3'-amino-5'-methyl-hexanoic,N-tert-butyl ester, 13 ester 5B-20-epoxy-1B,2a,4a,7B,9a,10a,13a-heptahydroxy-4,10-diacetate-2-benzoate-(1"S)-7,9-acrolein acetal-11(15-1)-abeotaxane, Davunetide, Humanised IgG4 monoclonal antibody against extracellular tau, Methylthioninium, N-(3-(4-(3-(diisobutylamino)propyl)piperazin -1-yl)propyl)-1H-benzo[d]imidazol-2-amine disulphate, Tilavonemab, tideglusib

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PSP-progressive non fluent aphasia (PSP-PNFA) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease. Unlike classic PSP (Richardson syndrome) patients present with an isolated speech production problem years before developing other motor features of PSP.

Epidemiology

Prevalence is unknown, and less than ten cases have been reported in the literature. PSP-PNFA probably accounts for less than 5% of all patients with PSP-tau pathology, but may account for a third of patients with PNFA (see this term) with prominent apraxia of speech.

Clinical description

The disease manifests during the sixth decade of life with speech anomalies such as apraxia of speech, agrammatism, and phonemic errors. Cognitive impairment occurs early. 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 temporal cortex and superior frontal gyrus.

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 and neuropsychological evaluation.

Differential diagnosis

Differential diagnosis includes other causes of frontotemporal dementia and in particular corticobasal degeneration, Pick's disease (see these termes) and gTDP-43 positive pathologies

Management and treatment

There is no treatment curing the disease. Patients do not respond to levodopa treatment. Communication strategies can be improved with speech therapy.

Prognosis

Disease duration is typically less than 10 years, and there may be an accelerated phase of deterioration late in the course. Most patients die in their eighth decade.