Upbeat nystagmus as the initial clinical sign of Creutzfeldt-Jakob disease

Background: Ocular motor disorders (such as horizontal nystagmus, saccadic pursuit, gaze deviations, and pathological saccades) have been reported in patients with Creutzfeldt-Jakob disease (CJD). We report on a patient with autopsy-proven CJD who complained of dizziness and presented with upbeat nystagmus (UBN) as the initial clinical sign.

Case report: The 68-year-old man was admitted with a one-week history of dizziness and unsteadiness. The neuro-ophthalmological examination revealed an upbeat nystagmus, associated with a diminished downward optokinetic nystagmus and a slightly saccadic pursuit. The subjective visual vertical was tilted to the left (binocular 6.0 degrees) and there was an ocular torsion to the left (left eye: excyclotropia 15 degrees, right eye: excyclotropia 2 degrees). The initial MRI, EEG, and electronystagmogram were normal. Within 3 weeks after admission the patient developed a progressive cerebellar syndrome and a left-sided hemiparesis. Impaired attention and visuoconstruction were found one week after admission. Two weeks later the patient showed a severe dementia. The repeated MRI revealed hyperintensities in the left parietal and occipital cortex, which closely corresponded to hypometabolic areas in the PET scan. A spinal tap was positive for 14–3-3 protein and showed increased neuron-specific enolase and protein S-100B. The EEG revealed a slowing of the baseline rhythm, a periodic pattern, and a continuous slowing over the left hemisphere. The patient died five weeks after the first appearance of the symptoms. Neuropathology and genetics: A Western blot and sequencing of the prion protein gene (PRNP) showed that the patient was homozygous for methionine at codon 129 of PRNP and had PrP-Sc type 1 (MM1 [methionine-methionine] -type). Microscopic examination revealed moderate spongiform changes in the cerebral cortex, basal ganglia, and cerebellum with neuronal loss and proliferation of astrocytes. The brainstem did not show prominent pathological changes.

Discussion: So far UBN, especially as the initial clinical sign, has not been described in CJD. UBN is associated mainly with lesions in the brainstem and the medulla. There is, however, also evidence that the cerebellum is involved. The neuropathological findings indicating a major involvement of the cerebellum in our patient agree with a cerebellar cause of UBN. In conclusion, CJD may initially manifest with dizziness and an ocular motor disorder such as UBN.