Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease

Abstract

Background and purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: predictive factor; prognosis; signs and symptoms; sporadic Creutzfeldt−Jakob disease.

Figure 1

Cumulative incidences of clinical signs and symptoms. Cumulative incidence plots of (a) akinetic mutism; (b) myoclonus, pyramidal dysfunction and extrapyramidal dysfunction; and (c) psychiatric symptoms, cerebellar disturbance and visual disturbance.

Figure 2

Stratified cumulative incidence of akinetic mutism based on prognostic factors. Stratified cumulative incidence of akinetic mutism based on the presence of cerebellar disturbance and/or psychiatric symptoms at diagnosis.

Figure 3

Schematic description of regression analysis results showing typical sequences of sign and symptom development. For signs or symptoms A (e.g. cerebellar disturbance) and B (e.g. myoclonus), solid arrows from A to B indicate that the A at diagnosis was identified as a prognostic factor by multivariate regression analyses for the time to onset of B. Dashed arrows from C (e.g. myoclonus) to D (e.g. akinetic mutism) indicate that the C at diagnosis was identified as a potential prognostic factor by univariate regression analyses for the time to onset of D.