Explorer Criteria for the diagnosis of corticobasal degeneration

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 CBDcategory 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. Neurology 2013;80:496–503 GLOSSARY AD 5 Alzheimer disease; AOS 5 apraxia of speech; CBD 5 corticobasal degeneration; CBS 5 corticobasal syndrome; CJD 5 Creutzfeldt-Jakob disease; cr-CBD 5 clinical research criteria for probable corticobasal degeneration; DLB 5 dementia with Lewy bodies; FTD 5 frontotemporal dementia; FTLD-TDP 5 frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions; GRN 5 granulin; p-CBD 5 possible corticobasal degeneration criteria; PD 5 Parkinson disease; PNFA 5 progressive nonfluent aphasia; PPA5 primary progressive aphasia;PSP5 progressive supranuclear palsy; PSPS5 progressive supranuclear palsy syndrome. When first described, “corticodentatonigral degeneration with neuronal achromasia” was considered a distinct clinicopathologic entity, eventually termed corticobasal degeneration (CBD). Clinicopathologic 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. Despite various clinical diagnostic criteria (table e-1 on the Neurology® Web site at www.neurology.org), the pathology of CBD is predicted antemortem in only 25% to 56% of cases. 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. From the University of Maryland (M.J.A., S.G.R., W.J.W.), Baltimore; University of California San Diego (I.L.), San Diego; Morton and Gloria Shulman Movement Disorders Center and the Edmond J. Safra Program in Parkinson’s Disease (A.E.L.), Toronto Western Hospital, Toronto, Canada; Edinburgh University (T.H.B.), Edinburgh, UK; Sobell Department of Movement Neuroscience (K.P.B.), Institute of Neurology, University College London, Queen Square, London, UK; University of Brescia (B.B.), Brescia, Italy; University of California San Francisco (A.L.B., S.E.L., B.L.M.), San Francisco; Mayo Clinic (D.W.D.), Jacksonville, FL; University of Pennsylvania (M.G.), Philadelphia; National Institute of Neurological Disorders and Stroke (M.H.), National Institutes of Health, Bethesda, MD; Mayo Clinic (K.A.J.), Rochester, MN; University of Western Ontario (A.K.), London, Canada; Case Western Reserve University (D.E.R.), Cleveland, OH; Neurology Service (E.T.), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS, Universitat de Barcelona, Spain; Barrow Neurological Institute (A.I.T.), Phoenix, AZ; and Hôpital de la Salpetrière (M.V.), Pierre Marie Curie Paris-6 University and CRICM UPMC/INSERM UMR_S975 CNRS UMR7225, Paris, France. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. 496 © 2013 American Academy of Neurology a 2013 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Definition and standardization of clinical diagnostic criteria for CBD are critical, especially as potential neuroprotective therapies for tauopathies emerge. In light of advances in the understanding of CBD, we used specialist consensus, brain bank cases, and a critical literature review to develop new diagnostic criteria. During this process, however, it became clear that clinicopathologic heterogeneity of CBD confounds the development of specific criteria, unlike what has been accomplished for other neurodegenerative diseases. Thus, we propose 2 sets of criteria: a narrower, more specific one for probable CBD and a broader set for possible CBD that has less specificity for CBD pathology while still representing probable tau-based pathology. METHODS Previous CBD clinical diagnostic criteria were reviewed. Invited international specialists in behavioral neurology, neuropsychology, and movement disorders met on October 14–15, 2009, and based on participants’ experience and literature reviews, clinical phenotypes were identified and CBD criteria were drafted. Subsequently, a systematic literature search and later update using MEDLINE (1950 to April 2012) and EMBASE (1980 to April 2012) identified English-language pathologically proven CBD series. Search terms included “corticobasal,” “corticobasal degeneration,” and “CBD” text word searches paired with “pathology” as a MeSH search term and text word search. Inclusion criteria were 1) a minimum of 5 pathologically proven CBD cases (chosen a priori to avoid the bias toward atypical cases from case reports) and 2) extractable data for clinical phenotype, symptoms/features, or both. Only patients with pathologically proven CBD were included. Inclusion criteria were intentionally broad to enable a large sample size and decrease the impact of ascertainment bias and variations in CBD feature reporting. Information was entered into a database including commonly reported features and those deemed relevant by the panel. Publication authors and institutions were cross-checked to prevent case duplication. Additionally, 5 centers with CBD brain bank cases provided data on published and unpublished cases. When available, the original brain bank data were abstracted rather than using the less comprehensive information from brain bank–related publications. Two overlapping sets of cases were developed: cases for which features of CBD could be extracted and cases for which information was available regarding clinical diagnosis or phenotype. Clinical features were recorded at 2 time parameters, at presentation and “ever” (during the disease course), variables for which the most consistent data could be abstracted. Presentation was a mean of 3.0 (SD 1.9) years after symptom onset in one series. When data were abstracted, features were considered as present or absent only if specifically described. While this approach carries the risk of overestimating the frequency of each feature, it was thought suitable due to the complexity of CBD and the varying degrees of detail in the retrospective data. Because of this approach, the denominator for calculating the frequency of any given clinical feature is less than the total number of cases identified, reflecting the number of cases for which that feature was reported. Finally, a literature search was conducted for clinicopathologic correlation articles including CBD subjects and cases with other proven pathologies to identify specific clinical features that might improve the accuracy of proposed CBD criteria vs other pathologic diagnoses. Results of the specialist panel, case reviews, and clinicopathologic studies were integrated into the proposed criteria. A glossary of terms is available in appendix e-1. RESULTS Previous clinical diagnostic criteria. While self-described as criteria for CBD, previous diagnostic criteria (table e-1) outline the clinical features now labeled CBS, reflecting an asymmetric movement disorders presentation combined with lateralized higher cortical features. Consideration of the role of dementia in diagnostic criteria exemplifies changes in our understanding of CBS and CBD. Previous clinical criteria excluded “early dementia” to increase diagnostic specificity, but dementia is now recognized as a presenting and predominant feature in many cases of CBD. Systematic literature review. Of 808 nonoverlapping articles identified in the systematic literature search, 37 met inclusion criteria. Clinical features were available for 103 published and 106 brain bank nonoverlapping CBD cases. Brain bank case information was provided by Mayo Clinic Rochester (22 patients, K. Josephs, personal communication, 2011), University of Western Ontario (8 patients, A. Kertesz and P. McMonagle, personal communication, 2011), University of California San Francisco (20 patients, S.E. Lee, personal communication, 2011), and Mayo Clinic Jacksonville (53 patients, D.W. Dickson, personal communication, 2011). Information on 3 unpublished cases was provided by University of Pennsylvania (P. Moore and M. Grossman, perso