Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease

Abstract

Clinical presentations of Creutzfeldt-Jakob disease (CJD) can be mimicked by those of immune-mediated encephalopathies, including limbic encephalitis with anti-voltagegated potassium channel (VGKC) complex antibodies [1, 2]. To date, anti-VGKC complex antibodies have been reported to be negative in CJD [1], thereby regarded as important to differentiate non-CJD dementia from CJD [3]. Here we report a patient with definite CJD who had serum anti-VGKC complex antibodies. A 60-year-old seaman acutely presented with blurred vision, disturbance in depth perception and light discrimination, difficulty recalling Chinese characters, and right-left disorientation. An ophthalmologist found no abnormality in his eyes. Two months later, he underwent a brain magnetic resonance imaging including diffusionweighted imaging, which showed hyperintensity signals in the bilateral occipital and parietal cortices. Neurologically, there were object agnosia, left hemineglect, dressing apraxia, Gerstmann syndrome, ideomotor apraxia, and instant memory disturbance. He also developed visual hallucinations such as flaming fire, and got agitated. Three months after onset, he got confused after taking one tablet of zolpidem and was admitted to a psychiatric department. Neurological examination on admission demonstrated the following findings: fluctuating levels of consciousness, difficulty in word recall, extinction; visual disturbance, poor pursuit eye movement, mild dysarthria; increased muscle tonus and myoclonus predominantly in the left; Myerson sign, snout reflex, increased jaw jerk and deep tendon reflexes predominantly in the left, bilateral Babinski and Chaddock signs; and he was bedridden. Serum antinuclear, anti-thyroid peroxidase, anti-thyroglobulin antibodies were negative and sodium levels were normal. No malignant tumors were found. Cell count was 2/mm, protein level was 27 mg/dl, 14-3-3 protein was positive, and total tau protein level was 3,420 pg/ml (cut-off value, 1,300 pg/ml) in the cerebrospinal fluid. Initial electroencephalography revealed slow waves, and periodic sharp wave complexes were present 23 weeks after onset. The analysis of PRNP revealed a substitution of methionine to arginine at codon 232. He received no immunotherapy. He died 8.5 months after onset and underwent necropsy of the left parietotemporal lobe. Neuropathological examination revealed neuronal loss, spongiform change, gemistocytic astrocytosis (Fig. 1a), and synaptic deposition of PrP (Fig. 1b) in the cerebral cortex, confirming the diagnosis of definite CJD. Western-blot analysis showed type 1 PrP. The titer of anti-VGKC complex antibodies, measured with radioimmunoassay using rabbit brain homogenates and K. Fujita (&) Y. Izumi R. Kaji Department of Clinical Neuroscience, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan e-mail: kof@clin.med.tokushima-u.ac.jp