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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%  CI 1.61–2.87, 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.

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