Detection of anti-glutamate receptor ε2 and anti-N-methyl-d-aspartate receptor antibodies in a patient with sporadic Creutzfeldt–Jakob disease

Abstract

Creutzfeldt–Jakob disease (CJD) is the most common type of human prion disease. CJD, particularly sporadic CJD (sCJD), is not completely related to immunological responses. However, immune abnormalities such as elevated proand anti-inflammatory cytokines have been reported in patients with sCJD [1, 2], warranting investigation of the immunological aspects of this disease. Here we present an sCJD case with autoantibodies against the Nmethyl-D-aspartate (NMDA)-type glutamate receptor. A 70-year-old right-handed woman developed a hand tremor, right-predominant rigidity in the upper limbs, and Myerson’s sign. Two months later, she developed left hemineglect. Her memory, insight, and judgment were normal at that time, but dressing apraxia, acalculia, and Balint’s syndrome were observed. She developed idiopathic hyponatremia, but her cognitive impairment progressed even after treatment of the hyponatremia. She underwent tracheostomy (without mechanical ventilation) 6 months after onset. Subsequently, she developed myoclonus of the left upper limb. About 2 years after onset, she developed akinetic mutism. Her disease duration was more than 8 years. Serum anti-thyroid peroxidase, anti-thyroglobulin, and anti-voltage-gated potassium channel complex antibodies were found to be negative. The cell count was 1/mm, protein level was 63 mg/dl, 14-3-3 protein was strongly positive, and total tau protein was 8,860 pg/mL (cut-off value 1,300 pg/mL) in the cerebrospinal fluid (CSF) collected 6 months after onset. Diffusion-weighted imaging performed 7 months after onset showed widespread cortical hyperintensity (Fig. 1a), but the signal changes were less evident on fluid-attenuated inversion recovery (Fig. 1b). An electroencephalogram showed diffuse slow waves at early stages, and periodic sharp wave complexes (PSWCs) were evident about two and a half years after onset. She was homozygous for methionine at prion protein gene codon 129, and no mutations were identified. Probable sCJD was diagnosed as per the World Health Organization criteria [3]. Accordingly, she did not receive any immunotherapy. Real-time quaking-induced conversion (RT-QUIC) [4] of CSF performed later was positive for PrP, validating the diagnosis of CJD. This study has been approved by the Ethics Committee of the Tokushima University Hospital and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Immunoblot analysis, as described previously [5], detected IgG antibody to the entire NMDA-type glutamate receptor e2 molecule (GluRe2, also called NR2B) in CSF. 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