Clinico-radiologic and Pathological Evaluation of Corticobasal Syndrome (S8.004)

Abstract

<h3>Objective:</h3> The objectives of this study were to determine the pathologic heterogeneity, the clinico-radiological findings associated with different underlying pathologies, and the positive predictive value (PPV) of current diagnostic criteria for CBD amongst patients with CBS. <h3>Background:</h3> Corticobasal syndrome (CBS) is characterized by asymmetric parkinsonism, rigidity, myoclonus, and apraxia. While originally considered primarily a motor disorder secondary to corticobasal degeneration (CBD), its effects on cognition, behavior, and language are now well-recognized - as well as its heterogenous underlying neuropathologies. <h3>Design/Methods:</h3> Clinical, neuropathologic, brain MRI and FDG-PET imaging data of patients clinically diagnosed with CBS were reviewed according to neuropathology determined at autopsy. <h3>Results:</h3> The cohort included 113 patients, 61 (54%) females. Primary neuropathologic diagnoses were: 43 (38%) CBD, 27 (23.9%) progressive supranuclear palsy (PSP), 17 (15%) Alzheimer’s disease (AD), 10 (8.8%) frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), 7 (6.2%) diffuse Lewy body disease/AD (DLBD/AD), and 9 (7.9%) with other diagnoses. CBS-AD or CBS-DLBD/AD patients were youngest at death (median [IQR]: 64[13], 64[11] years) while CBS-PSP patients were oldest (77[12.5], <i>P</i>=0.024). CBS-DLBD/AD patients had the longest disease duration (9[6] years) while CBS-other subgroup had the shortest (3[4.25], <i>P</i>=0.04). Posterior cortical signs and myoclonus were more characteristic of CBS-AD and CBS-DLBD/AD patients. Voxel-based morphometry revealed that widespread cortical loss was characteristic of CBS-AD, while CBS-CBD and CBS-PSP predominantly involved premotor regions with greater white matter loss. CBS-DLBD/AD showed atrophy in a focal parieto-occipital region, and CBS-FTLD-TDP had predominant prefrontal cortical loss. For cases with CBS-PSP pathology, midbrain/pons ratio was lowest (<i>P</i>=0.012). Of the 67 cases who met criteria for possible CBD at presentation, 27 were pathology-proven CBD cases, yielding PPV of 40.3%. <h3>Conclusions:</h3> A variety of neurodegenerative disorders can be identified in CBS patients, but clinical and regional imaging differences may aid in predicting underlying neuropathology. Biomarkers that are sensitive and specific for underlying CBD are needed. <b>Disclosure:</b> Dr. Shir has nothing to disclose. Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic. Dr. Botha has received research support from NIH. Dr. Koga has nothing to disclose. Naomi Kouri has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nestle. Dr. Petersen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech, Inc.. Dr. Petersen has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche, Inc.. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Walter Kremers has received research support from Biogen. Aivi Nguyen has nothing to disclose. Dr. Murray has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avid Radiopharmaceuticals. The institution of Dr. Murray has received research support from National Institute on Aging. The institution of Dr. Murray has received research support from Alzheimer’s Association. The institution of Dr. Murray has received research support from Chan Zuckerberg Initiative. The institution of Ross Reichard has received research support from NIH. An immediate family member of Ross Reichard has received publishing royalties from a publication relating to health care. Dr. Dickson has nothing to disclose. The institution of Dr. Graff-Radford has received research support from Biogen. The institution of Dr. Graff-Radford has received research support from Lilly. The institution of Dr. Graff-Radford has received research support from Novartis. The institution of Dr. Graff-Radford has received research support from AbbVie. Dr. Graff-Radford has received publishing royalties from a publication relating to health care. Dr. Josephs has nothing to disclose. Dr. Whitwell has nothing to disclose. Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. Dr. Graff-Radford has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. The institution of Dr. Graff-Radford has received research support from NIH.