title: Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease.
abstract: Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset.
  
  
  
  The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms.
  
  
  
  Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance.
  
  
  
  The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease.
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Nakatani
authors.affiliation: Department of Health Crisis Management, National Institute of Public Health, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanatani
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Teramukai
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kono
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitamoto
authors.affiliation: National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000405:Akinetic Mutism / Q000453:epidemiology / Q000209:etiology; D002526:Cerebellar Diseases / Q000150:complications / Q000453:epidemiology; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D018450:Disease Progression; D004569:Electroencephalography; D005260:Female; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000453:epidemiology; D008875:Middle Aged; D009207:Myoclonus / Q000453:epidemiology / Q000209:etiology; D011237:Predictive Value of Tests; D011379:Prognosis
keywords: predictive factor; prognosis; signs and symptoms; sporadic Creutzfeldt−Jakob disease