New Clinical Guidelines: Distinguishing Variations of Progressive Supranuclear Palsy

A new set of clinical guidelines for the diagnosis of progressive supranuclear palsy (PSP), developed by the Movement Disorders Society (MDS) and published recently in Movement Disorders, provides very specific and sensitive criteria that allow for identification of clinical features of the disease at much earlier stages.¹ These guidelines were designed to improve the already strong specificity (95% to 100%, validated by autopsy) of the current diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke and the Society for Progressive Supranuclear Palsy (NINDS-SPSP) in 1996.² The 2017 PSP guidelines improve on the sensitivity of the NINDS-SPSP criteria, estimated at 80% to 93%^3-5 for possible PSP.

A significant amount of variation in clinical presentation has been associated with different types of PSP. The most well defined by NINDS criteria is Richardson’s syndrome, characterized by postural instability, leading to falls, and ocular motor dysfunction.^6,7 A study by Respondek et al⁷ identified a wide range of variations to the clinical symptoms on presentation that were less likely to be identified by NINDS criteria as related to PSP but were later confirmed on autopsy as variant forms of PSP. A number of studies confirmed the distinctions between PSP variations, including parkinsonism,^6-8 frontal lobe behavioral and cognitive disturbances and frontotemporal dementia,^10-13 progressive gait freezing,^14-16 corticobasal syndrome,^16-20 primary lateral sclerosis,^21,22 and cerebellar ataxia,^23-26 in addition to including the speech and language disorders nonfluent/agrammatic primary progressive aphasia and progressive apraxia of speech.^27-30 The onset of many of the variant symptoms was often later than that of primary symptoms, contributing to low sensitivity of their capture as criteria for PSP.

A systematic review of the literature published since the NINDS-SPSP guidelines by an international committee led by Günter U. Höglinger, MD, professor and chair for translational neurodegeneration at the German Center for Neurodegenerative Diseases e.V. at the Technical University of Munich in Germany, was used as the basis of evidence for the MDS update.

New Guidelines Distinctions

The 2017 MDS guidelines are highly specific, allowing for an early diagnosis of many forms of PSP by stratifying by severity of symptoms. The committee classified the most representative symptoms of PSP reported in the literature^3,4 into 4 functional domains:

·        O: Ocular motor dysfunction

·        P: Postural instability

·        A: Akinesia

·        C: Cognitive dysfunction

For each domain, the authors designated 3 corresponding sets of early clinical symptoms stratified to 3 levels of certainty (probable, possible, and suggested) for the diagnosis of PSP. The fourth level of certainty already in use is clinically definite PSP.

“The guidelines may be a bit more complex than prior guidelines for the diagnosis of PSP, since the clinical manifestation of the disease is a bit more complex than initially thought, as we had to learn over the past 20 years,” Dr Höglinger explained to Neurology Advisor.

The diagnosis of PSP at any level requires adult onset (age ≥40 years) of PSP-like symptoms that are gradually progressive and sporadic, although the recommendations suggested additional microtubule-associated protein tau testing, particularly in small families, to rule out other dementia disorders with genetic etiologies. Genetic testing and the use of fluid biomarkers were deemed not useful for the inclusive diagnosis of PSP but could be helpful to rule out alternative disorders, as were brain imaging studies.