Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that classically presents with oculomotor dysfunction (abnormal vertical eye movements), postural instability and falls, parkinsonism, and cognitive (mainly executive) dysfunction. PSP is the most frequent parkinsonian disorder after idiopathic Parkinson disease and has a relentless course, leading to death after an average of 7 years.

The diagnosis of PSP during life is clinical and relies on careful history-taking and physical examination, supported by characteristic findings on brain magnetic resonance imaging. Definitive diagnosis requires postmortem pathology. Many patients are initially diagnosed with Parkinson disease but a poor, transient, or absent response to levodopa and/or examination of eye movements can point to PSP as the correct diagnosis.

There are multiple PSP clinical phenotypes that present with varying predominant symptoms. The most common are the Richardson syndrome subtype (PSP-RS or classic PSP, also known as Steele-Richardson-Olszewski syndrome) and the parkinsonism subtype (PSP-P).

There is no disease-modifying treatment available for PSP so treatment is focused on symptomatic management and rehabilitation. A multidisciplinary team approach is recommended, with key team members including a movement disorder specialist neurologist, a physical therapist, a speech and language pathologist, an occupational therapist, and a social worker or a case manager.

PSP is a rare, sporadic neurodegenerative disease that is clinically classified as an atypical parkinsonian disorder and affects people ages 40 years or older. PSP is caused by abnormal accumulation of tau protein, which is a constituent of neural structural microtubules and is abundantly present in neurons. PSP can present with multiple clinical phenotypes depending on the site of more severe pathology and the pattern of pathology spread in the brain. By far the most common or “classic” phenotype is Richardson syndrome (PSP-RS), as first described in 1964 by Steele, Richardson, and Olszewski.[1]Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol. 1964 Apr;10:333-59. http://www.ncbi.nlm.nih.gov/pubmed/14107684?tool=bestpractice.com  This presents with slowness of vertical saccades (eye movements) progressing to vertical supranuclear gaze palsy, postural instability and falls, axial-predominant akinetic rigid parkinsonism, dysarthria, dysphagia, and frontal executive dysfunction.[2]Olfati N, Shoeibi A, Litvan I. Clinical spectrum of tauopathies. Front Neurol. 2022 Jul 14;13:944806. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329580 http://www.ncbi.nlm.nih.gov/pubmed/35911892?tool=bestpractice.com [3]Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov Disord. 2017 Jun;32(6):853-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516529 http://www.ncbi.nlm.nih.gov/pubmed/28467028?tool=bestpractice.com ​​​ Other PSP phenotypes include: the parkinsonism-predominant phenotype (PSP-P); the progressive gait freezing phenotype (PSP-PGF); the speech and language-dominant syndrome phenotype (PSP-SL); the frontal behavioral-dysexecutive syndrome phenotype (PSP-F); and the corticobasal syndrome phenotype (PSP-CBS).[3]Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: the Movement Disorder Society criteria. Mov Disord. 2017 Jun;32(6):853-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516529 http://www.ncbi.nlm.nih.gov/pubmed/28467028?tool=bestpractice.com ​