“Atypical” atypical parkinsonism: New genetic conditions presenting with features of progressive supranuclear palsy, corticobasal degeneration, or multiple system atrophy—A diagnostic guide

Stamelou, María; Quinn, Niall; Bhatia, Kailash P.

doi:10.1002/mds.25509

Cited by 110 publications

(88 citation statements)

References 210 publications

(345 reference statements)

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“…Our results reinforce previous proposals to implement a 4-step approach based on age at onset, tempo of progression, family history and associated clinical features, to improve diagnostic accuracy [6].…”

Section: Discussionsupporting

confidence: 88%

“…[6,[13][14][15][16] This was the case in approximately 5% our cohort. In some of these patients, there was a definitive genetic diagnosis, indicating the initial working diagnosis was wrong, even though they fulfilled the respective research criteria.…”

Section: Discussionmentioning

confidence: 68%

“…All these factors might contribute to the relatively high rate of misdiagnosis [1], hence hampering the identification of homogenous groups of patients for future research on the pathophysiology of, and putative neuro-protective interventions for, these disorders. Hence in a previous review article we had introduced the term "atypical" atypical parkinsonism to highlight such cases [6]. Here we are reappraising the clinical features and diagnostic outcomes of a large series of AP patients.…”

Section: Introductionmentioning

confidence: 99%

“…(therefore being referred to as "AP-look-alikes") [6]. For example, patients with Dynactin1 (DCTN1) or microtubule-associated protein tau (MAPT) mutations can present with a supranuclear gaze palsy and parkinsonism, as in PSP, although there may be additional features atypical for PSP, and also these cases might be younger at onset than classic PSP.…”

Section: Introductionmentioning

confidence: 99%

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“Atypical” atypical parkinsonism: Critical appraisal of a cohort

Hirschbichler

Erro

Ganos

et al. 2017

Parkinsonism & Related Disorders

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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“Atypical” atypical parkinsonism: Critical appraisal of a cohort

Hirschbichler

Erro

Ganos

et al. 2017

Parkinsonism & Related Disorders

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“…Early age at onset and myoclonus are suggestive of AD rather than CBD pathology. Presenilin 1 mutations may manifest as parkinsonism with relatively symmetric myoclonus, apraxia, dystonia, frontal subcortical dementia and, sometimes, seizures 60 . Balint's syndrome, Gerstmann syndrome, visual agnosia or alexia are other possible presentations 56 .…”

Section: Differential Diagnosismentioning

confidence: 99%

Cognitive dysfunction in corticobasal degeneration

Oliveira

Barcellos

Teive

et al. 2017

Arq. Neuro-Psiquiatr.

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Corticobasal degeneration (CBD) is a rare and progressive neurodegenerative disease. It was originally described as a distinct clinicopathological entity in 1967 1 and later recognized as a polymorphous disease due to its complexity. In fact, the classical set of symptoms -namely asymmetric motor features associated with higher cortical function -were found to be associated with multiple histological presentations. Furthermore, the distinctive histopathological findings of cortical and striatal neuronal deposition of tau, and glial inclusions, were also linked to a wide variety of clinical phenotypes 2 . Hence, recent literature refers to corticobasal syndrome (CBS) as the constellation of symptoms described originally, limiting CBD to the distinctive histopathological findings .The different terminology with a seemingly paradoxical intrinsic overlap between these conditions makes diagnosis challenging. For instance, only 25% to 56.25% of patients with pathologically-confirmed CBD had previously presented with symptoms of CBS 4,5,6 . On the other hand, the proportion of patients diagnosed with CBS presenting with the histologic hallmarks of CBD is highly variable, ranging from 23.8% to 100% 4,5,6,7 . Considering the enormous difficulty in accurately diagnosing CBD during life, it is clear that current ABSTRACTCorticobasal degeneration (CBD) was originally described as a distinct clinicopathological entity in 1967. Since then, different phenotypic presentations have emerged as possible manifestations of CBD histopathological findings. In addition, pathophysiological findings and the molecular basis have been delineated and several aspects of its cognitive manifestations have been clarified. Thus, not only the spectrum of what is currently designated as CBD has expanded, but overlap with other degenerative and even secondary disorders has made clinical diagnostic certainty even more challenging in the absence of specific and readily-available markers. Cognitive deficits in CBD are now recognized as a frequent initial presentation and may appear up to eight years before the motor symptoms, depending on the phenotypic variant. Characteristic cognitive features of CBD involve language deficits, visuospatial and executive dysfunctions, apraxia, and behavioral disorders. Semantic and episodic memories are usually preserved, while language is often impaired in the early stages.Keywords: dementia; cognition; corticobasal degeneration. RESUMOA degeneração corticobasal (DCB) foi originalmente descrita como uma entidade clínico-patológica distinta em 1967. Desde então, nossa compreensão sobre DCB evoluiu substancialmente. Diferentes apresentações fenotípicas emergiram refletindo possíveis manifestações das anormalidades histopatológicos da DCB. Adicionalmente, dados fisiopatológicos e moleculares foram delineados e aspectos das manifestações cognitivas foram explorados. Assim, não só o espectro do que é atualmente designado DCB foi expandido, mas a sobreposição com outras doenças degenerativas e até mesmo secundárias to...

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