Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome

Background: Previous studies reported skin phosphorylated α-synuclein (p-syn) deposits in Parkinson’s disease (PD) patients but not in patients with parkinsonism due to tauopathies, although data on the latter are limited. Objective: We aimed to assess the presence of skin p-syn deposits in patients with clinical diagnosis of parkinsonism usually due to tauopathy and PD. Methods: We consecutively recruited 26 patients, 18 fulfilling clinical diagnostic criteria of progressive supranuclear palsy (PSP) and 8 of corticobasal syndrome (CBS), 26 patients with PD, and 26 healthy controls (HC). All subjects underwent skin biopsy to study p-syn deposits in skin nerves by immunofluorescence. Results: Skin p-syn deposits were present in only two of the PSP/CBS patients and none of the HC. Conversely, all PD patients showed p-syn deposition (p < 0.001, Chi-square). The two p-syn positive patients were diagnosed with PSP and CBS, respectively. Although clinical and MRI findings supported these diagnoses, both patients had some atypical features more typical of synucleinopathies. Conclusion: The detection of skin p-syn deposits may help in the differential diagnosis of parkinsonism. Indeed, in this study, all PD patients and only two out of 26 with a clinical diagnosis of PSP/CBS had skin p-syn deposits. Furthermore, these two patients showed clinical features that could suggest an atypical synucleinopathy presentation or a mixed pathology.

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Diffuse Lewy body disease manifesting as corticobasal syndrome

Neurology ◽

10.1212/wnl.0000000000005828 ◽

2018 ◽

Vol 91 (3) ◽

pp. e268-e279 ◽

Cited By ~ 13

Author(s):

Koji Kasanuki ◽

Keith A. Josephs ◽

Tanis J. Ferman ◽

Melissa E. Murray ◽

Shunsuke Koga ◽

...

Keyword(s):

Motor Cortex ◽

Alzheimer Disease ◽

Progressive Supranuclear Palsy ◽

Lewy Body ◽

Disease Onset ◽

Lewy Bodies ◽

Lewy Body Disease ◽

Corticobasal Syndrome ◽

Imaging Biomarkers ◽

Diffuse Lewy Body Disease

ObjectiveTo describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS).MethodsIn 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex.ResultsDLBD patients with antemortem features of CBS were significantly younger at disease onset and less likely to have REM sleep behavior disorder than DLBD cases who met clinical criteria for DLB during life. Patients with DLBD manifesting as CBS had more Lewy bodies in the motor cortex than DLBD manifesting as clinically probable DLB. Three cases had concomitant progressive supranuclear palsy and 4 cases had concomitant Alzheimer disease as probable correlates of CBS.ConclusionThe neuropathology underlying CBS is heterogeneous, including corticobasal degeneration, Alzheimer disease, and progressive supranuclear palsy. This study suggests that atypical variants of Lewy body disease with severe peri-Rolandic Lewy-related pathology can present clinically as CBS. Patients with DLBD who present as CBS tend to have an earlier age at onset and are less likely to have clinical features of DLB, such as dream enactment behavior during sleep, visual hallucinations, and levodopa-responsive parkinsonism. Future studies with biofluid or molecular imaging biomarkers for α-synuclein will permit better recognition of this uncommon pathologic substrate of CBS.

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Language disorder in progressive supranuclear palsy and corticobasal syndrome: neural correlates and detection by the MLSE screening tool

10.1101/2021.03.04.21252852 ◽

2021 ◽

Author(s):

Katie A. Peterson ◽

P. Simon Jones ◽

Nikil Patel ◽

Kamen A. Tsvetanov ◽

Ruth Ingram ◽

...

Keyword(s):

Progressive Supranuclear Palsy ◽

Cortical Thickness ◽

Screening Tool ◽

Language Disorder ◽

Short Form ◽

Temporal Cortex ◽

Primary Progressive Aphasia ◽

Corticobasal Syndrome ◽

Speech And Language ◽

Subcortical Volumes

AbstractBackgroundProgressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI).MethodsFifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke’s Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with severity of speech and language impairment.ResultsCBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen and caudate.ConclusionsThe effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.

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Parkinsonism and Related Dementias

10.1093/med/9780197512166.003.0079 ◽

2021 ◽

pp. 680-688

Author(s):

Rodolfo Savica ◽

Pierpaolo Turcano ◽

Bradley F. Boeve

Keyword(s):

Differential Diagnosis ◽

Parkinson Disease ◽

Progressive Supranuclear Palsy ◽

Frontotemporal Dementia ◽

Lewy Body ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Corticobasal Degeneration ◽

Corticobasal Syndrome ◽

Progressive Course

The differential diagnosis for dementia is wide. A slowly progressive course for parkinsonism suggests a degenerative cause and helps to narrow the differential diagnosis considerably. In patients with dementia in combination with parkinsonism (often collectively termed the parkinsonism-related dementias), the 4 most common neurodegenerative entities are 1) Lewy body dementias (which include dementia with Lewy bodies and Parkinson disease with dementia); 2) corticobasal syndrome or corticobasal degeneration; 3) Richardson syndrome or progressive supranuclear palsy; and 4) frontotemporal dementia with parkinsonism.

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