Imaging correlates of pathology in corticobasal syndrome

Whitwell, Jennifer L.; Jack, Clifford R.; Boeve, Bradley F.; Parisi, Joseph E.; Ahlskog, J. Eric; Drubach, Daniel A.; Senjem, Matthew L.; Knopman, David S.; Petersen, Ronald C.; Dickson, Dennis W.; Josephs, Keith A.

doi:10.1212/wnl.0b013e3181feb2e8

Cited by 214 publications

(238 citation statements)

References 41 publications

Supporting

Mentioning

204

Contrasting

Unclassified

Order By: Relevance

“…Studies using clinical cohorts report abnormalities consistent with the topography of clinical findings rather than reflecting specific underlying pathology. Recently described atrophy patterns in CBS associated with CBD, progressive supranuclear palsy (PSP), AD, and FTLD-TDP pathology 57 are promising but require prospective validation prior to inclusion in diagnostic criteria. Imaging can help exclude other conditions with CBS presentations, such as CJD.…”

Section: Resultsmentioning

confidence: 99%

Criteria for the diagnosis of corticobasal degeneration

et al. 2013

Self Cite

View full text Add to dashboard Cite

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset $50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype.Future validation and refinement of the proposed criteria are needed. When first described, "corticodentatonigral degeneration with neuronal achromasia" was considered a distinct clinicopathologic entity, 1 eventually termed corticobasal degeneration (CBD). 2Clinicopathologic studies have since revealed that the originally described clinical features of CBD, now called corticobasal syndrome (CBS), are often due to other pathologies. As a pathologic diagnosis, CBD is characterized by widespread deposition of hyperphosphorylated 4-repeat tau in neurons and glia, the latter as astrocytic plaques, in specific topographic areas. 3 Despite various clinical diagnostic criteria (table e-1 on the Neurology ® Web site at www.neurology.org), 4-10 the pathology of CBD is predicted antemortem in only 25% to 56% of cases.11-17 Additionally, while these clinical criteria continue to be widely applied and cited, they reflect CBS alone and not the more recently recognized behavioral presentations of CBD.

show abstract

Section: Resultsmentioning

confidence: 99%

Criteria for the diagnosis of corticobasal degeneration

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Region-of-interest (ROI) volumes were calculated for 136 cortical and basal ganglia ROIs from the Neuromorphometric Atlas (http://neuromorphometrics.com/). Our results discuss 20 of these ROIs selected based on a priori evidence implicating these regions in PSP and CBS, [1][2][3][4][5][6][7][8][9][10][11][12][13][14] in addition to 2 control regions (left and right superior temporal gyrus) and 3 brainstem ROIs (midbrain, pons, superior cerebellar peduncle) from a previously validated atlas. 25 Further details of MRI processing are given in the e-Methods.…”

mentioning

confidence: 99%

“…[2][3][4][5][6][7] In CBS, atrophy predominantly involves dorsal neocortical gray and white matter and the basal ganglia. 2,3,5,[7][8][9][10] Prior studies have identified global and regional MRI changes in PSP over the course of 1 year or longer [11][12][13][14] but shorter intervals were rarely examined and CBS was not included. The present study compared regional patterns and rates of atrophy in these two 4R tauopathies over a shorter time frame that would be more feasible for clinical trials.…”

mentioning

confidence: 99%

Progression of brain atrophy in PSP and CBS over 6 months and 1 year

et al. 2016

View full text Add to dashboard Cite

Objective: To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents.Methods: Six-and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxelbased morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial.Results: Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale.Conclusions: Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects. Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are rare neurodegenerative disorders associated with the accumulation of insoluble deposits of predominantly 4 microtubule binding domain repeat (4R) tau protein in specific brain regions, mainly in the absence of other pathogenic proteins including b-amyloid.1 Accordingly, PSP and CBD are classified as primary 4R tauopathies. There are currently no effective therapies for either disorder, but the development of new therapeutic agents that target the tau protein has led to increased interest in pursuing clinical trials in CBD and PSP, either individually or for a combined 4R tauopathy indication.

show abstract

“…Frequently, patients with CBS are found, postmortem, to have pathology of Alzheimer disease (CBS-AD), progressive supranuclear palsy (CBS-PSP), or other non-CBD pathologies. [3][4][5][6][7][8][9][10] Of the various pathologic substrates of CBS, AD is common, accounting for more than 20% of cases. 3,5,9,10 Antemortem diagnosis of CBS-AD is important, because patients may benefit from cholinesterase inhibitors or future AD-targeted treatments.…”

mentioning

confidence: 99%

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

et al. 2014

View full text Add to dashboard Cite

Objective: To use the Visual Object and Space Perception Battery (VOSP) to distinguish Alzheimer disease (AD) from non-AD pathology in corticobasal syndrome (CBS).Methods: This clinicopathologic study assessed 36 patients with CBS on the VOSP. All were autopsied. The primary dependent variable was a binary pathologic outcome: patients with CBS who had primary pathologic diagnosis of AD (CBS-AD, n 5 10) vs patients with CBS without primary pathologic diagnosis of AD (CBS-nonAD, n 5 26). We also determined sensitivity and specificity of individual VOSP subtests.

show abstract

Imaging correlates of pathology in corticobasal syndrome

Abstract: Background: Corticobasal syndrome (CBS) can be associated with different underlying patholo-

Cited by 214 publications

References 41 publications

Criteria for the diagnosis of corticobasal degeneration

Criteria for the diagnosis of corticobasal degeneration

Progression of brain atrophy in PSP and CBS over 6 months and 1 year

Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome

Contact Info

Product

Resources

About