Initial Diagnoses of Patients Ultimately Diagnosed with Prion Disease

Article type: Research Article

Authors: Appleby, Brian S.^{a; b; *} | Rincon-Beardsley, Tonya D.^c | Appleby, Kristin K.^{d; e} | Crain, Barbara J.^f | Wallin, Mitchell T.^{e; g}

Affiliations: [a] Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA | [b] Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [c] School of Arts and Sciences, Advanced Academic, Programs, Biotechnology Studies, Johns Hopkins University, Baltimore, MD, USA | [d] Cleveland Clinic Center for Regional Neurology, Cleveland, OH, USA | [e] Veterans Affairs Healthcare System, Department of Neurology, Washington, DC, USA | [f] Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA | [g] Department of Neurology, Georgetown University Hospital, Washington, DC, USA

Correspondence: [*] Correspondence to: Brian Appleby, MD, University Foley Elderhealth Center, 3619 Park East Drive, Suite 211, Beachwood, OH 44122, USA. Tel.: +1 216 464 6412; Fax: +1 216 464 6403; E-mail: bsa35@case.edu.

Abstract: Background:Prion diseases are rapidly progressive neurodegenerative diseases that frequently mimic other forms of dementia making them difficult to diagnose. Objective:To explore factors associated with the initial diagnoses of cases later determined to be caused by prion disease in an attempt to recognize key clinical variables that impact the timely diagnosis of prion disease. Methods:A retrospective chart review performed at Johns Hopkins Medicine and the Department of Veterans Affairs Health Care System (1995–2008) was conducted. Ninety-two subjects with definite or probable prion disease were included in the analyses. Demographic, clinical, diagnostic test results, neuropathologic, molecular, and genetic data were collected using a standardized instrument and compared between initial diagnosis groups. Results:Cases were separated into five broad categories pertaining to their initial diagnoses: prion disease, non-prion-related dementia, psychiatric disorder, stroke, and other. The majority of cases did not receive an initial diagnosis of prion disease (n = 76, 83%). The plurality of subjects received an initial diagnosis of a non-prion disease related dementia (n = 33, 36%). Mean survival times varied between initial diagnosis groups (p = 0.042). Times to cerebrospinal fluid 14-3-3 analysis and electroencephalogram also differed between initial diagnosis groups. Conclusions:Most patients with prion disease are initially diagnosed with a non-prion disease related dementia. Several clinical features were associated with initial diagnoses including survival time, onset of specific symptoms, and times to 14-3-3 analyses and electroencephalogram. Expanding our knowledge of the various clinical presentations of prion disease, especially dementia, may aid in the earlier diagnoses of these rapidly progressive diseases.

Keywords: Creutzfeldt-Jakob disease, Creutzfeldt-Jakob syndrome, dementia, diagnosis, diagnostic errors, fatal familial insomnia, Gerstmann-Straussler-Scheinker Disease, mean survival time, phenotype, prion diseases, sporadic

DOI: 10.3233/JAD-132465

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 833-839, 2014