Clinical and prognostic features of Heidenhain variant of Creutzfeldt−Jakob disease: A retrospective case series study

Abstract

Heidenhain variant of Creutzfeldt-Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study. We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed. Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64years [range, 44-72years]) were identified. The median survival time was 22weeks (range, 5-155weeks). The median duration of isolated visual symptoms was 3weeks (range, 1-12weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p=0.005) and cortical blindness (p=0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p=0.047). Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.