The Heidenhain variant of Creutzfeldt-Jakob disease

Objective: To investigate whether typical neuropathological and radiologica l findings can be identified in patients with the clinical diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease (CJD). Design: Case study. The clinical symptoms, neuropathological findings, elec troencephalograms, magnetic resonance images, and cerebrospinal fluid sampl es of 14 Heidenhain cases were evaluated. Neuropathological changes were co mpared with those in a group of 14 patients with ataxia as the leading clin ical sign. Setting: A university hospital, base of the German National Creutzfeldt-Jak ob Disease Surveillance Study. Patients: Medical records of 169 neurologically examined patients with pros pectively classified and neuropathologically confirmed CJD were analyzed. Main Outcome Measures: Difference in neuropathological and radiological fin dings between patients with the Heidenhain variant and other patients with CJD. Results: Of 169 patients with confirmed CJD, 20% showed characteristic clin ical findings such as blurred vision, visual field restriction, metamorphop sia, or cortical blindness. Disease course of the Heidenhain group, as comp ared with the group of all patients with definite CJD, was significantly sh orter (5.7 months vs 7.5 months; P =.02, t test). Neuropathological examina tion of patients with the Heidenhain variant showed most pronounced changes in the occipital lobe but less damage in the cingulate gyrus and basal gan glia compared with 14 patients with CJD who had ataxia as the leading clini cal sign. Eleven (92%) of 12 genetically analyzed Heidenhain cases were hom ozygous for methionine at codon 129 of the prion protein gene (PRNP). In 9 of 9 cases, the 14-3-3 protein was present. In 7 (78%) of 9 cases, the leve l of neuron-specific enolase was elevated, with a concentration above 35 ng /mL. Periodic sharp-wave complexes were observed in 11 (78%) of the 14 case s. In 7 (63%) of 11 patients, magnetic resonance images showed symmetric hy perintensities in the basal ganglia in the T-2- and proton-weighted sequenc e. In 4 of 11 cases the T-2- and proton density-weighted images showed a pr onounced signal increase confined to the gray matter of the occipital and v isual cortex. Isolated atrophy of the visual cortex was noticeable in 2 of 11 cases. Conclusions: The clinical presentation of the Heidenhain variant of CJD was shown to correlate with the neuropathological findings of gliosis and nerv e cell loss. In patients with visual disorders of unclear origin and signs of dementia, the differential diagnosis of a Heidenhain variant of CJD must be taken into consideration.