“Atypical” atypical parkinsonism: Critical appraisal of a cohort

Abstract

Background: Atypical parkinsonian conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and Dementia with Lewy bodies (DLB) comprise 10-15% of parkinsonian syndromes. Misdiagnosis with Parkinson disease (PD) and within the entities is common, given the absence of reliable biomarkers.However a correct diagnosis is not only important in clinical practice, but also crucial for any trial attempting to identify biomarkers or new treatments. Methods:Consecutive patients, who were either referred with a diagnosis of a particular AP by a neurologist, or where a movement disorder specialist at Queen Square considered such a diagnosis, were included and the medical records were reviewed retrospectively. We applied each set of current diagnostic research criteria to the respective cohort to see which features fit in and if there are atypical features "outside" the classic definition. Results:Sixty-nine patients were recruited clinically presenting with one of the following phenotypes: 14 MSA, 24 PSP, 19 CBS and 12 DLB. Up to 49% showed additional "atypical"features and approximately 10% eventually received an alternative diagnosis, in half of whom this was based on genetic testing. Conclusions:In a subset of our patients, despite the final diagnosis of an AP being maintained, there were additional "atypical" features. It remains to be seen if these reflect the clinical heterogeneity of APs, or should prompt a search for an alternative diagnosis. A change in terminology using phenotypic descriptors (e.g. MSA syndrome) rather than aetiological labels, as already applied for CBS, could therefore be a consideration for all the APs.

Neuropathological correlates of parkinsonian disorders in a large Dutch autopsy series

“…The clinical heterogeneity of PD is well-known, and different clinical subtypes of PD have been proposed [11,12]. Similarly, atypical parkinsonian disorders are also clinically heterogeneous entities [13].…”

Very Late‐Onset Niemann Pick Type C Disease: Example of Progressive Supranuclear Palsy Look‐Alike Disorder

“…This has led to the emerging concept of “atypical” APs. Among these, some genetic conditions might share some clinical features with the APs, and they are referred to as “AP‐look‐alikes.” Hirschbichler and colleagues reported that half of APs cases showed additional “atypical” features, and approximately 10% eventually received an alternative diagnosis.…”

“…Classical atypical parkinsonian syndromes (APs) refers to a group of disorders including progressive supranuclear palsy (PSP), multiple system atrophy, corticobasal syndrome, and dementia with Lewy bodies . Clinical and pathological heterogeneity has been reported among APs .…”

“…Classical atypical parkinsonian syndromes (APs) refers to a group of disorders including progressive supranuclear palsy (PSP), multiple system atrophy, corticobasal syndrome, and dementia with Lewy bodies . Clinical and pathological heterogeneity has been reported among APs . Additional features such as positive family history, “too‐long” stable course, and associated clinical/radiological findings may be “red flags” for APs and should direct clinicians toward alternative diagnosis and further investigations.…”

123I‐Metaiodobenzylguanidine Myocardial Scintigraphy in Discriminating Degenerative Parkinsonisms

“…In their early stage, atypical parkinsonisms may generally share the same motor phenomenology observed in PD. 4 As an additional layer of complexity, unusual clinical features (ie, “red flags”), orienting the diagnostic suspicion towards less common forms of parkinsonism, may at times be observed in early PD patients, thus challenging a prompt differential diagnosis. 5 This has important prognostic implications: atypical parkinsonisms, as compared to PD, are known to be linked to earlier disability, poorer quality of life, and decreased survival.…”