Hashimoto’s encephalopathy associated with an elevated intrathecal IgG4 level

Abstract

Hashimoto’s encephalopathy is a steroid-responsive encephalopathy associated with the existence of anti-thyroid antibodies, which is characterized by various neuropsychiatric symptoms [2, 4, 6]. Autoimmune mechanisms are thought to play a pathogenic role in the disorder due to its association with other autoimmune disorders and response to steroid therapy; however the pathological mechanism underlying the disease has not been completely elucidated. We herein report a patient who manifested with steroid-responsive progressive memory disturbance, cerebellar ataxia and dystonia associated with an elevated immunoglobulin G4 (IgG4) level in both the serum and cerebrospinal fluid (CSF). The patient was a 60-year-old Japanese male who presented with a 6-month history of progressive gait disturbance. He developed memory disturbance and involuntary movements of his face and neck 2 months after presentation. There were no vascular risk factors, such as hypertension, diabetes mellitus or dyslipidemia. A neurological examination revealed cerebellar ataxia and grimacing face with cervical dystonia. Neuropsychological assessments revealed that the Mini-Mental State Examination score was 26 and the Frontal Assessment Battery score was 14, which was normal compared to age-matched normal subjects. Laboratory tests showed a high titer of anti-thyroglobulin antibodies (213 IU/ml; normal, \100) while the titer of anti-thyroid peroxidase antibodies in the serum was negative. The results of routine blood tests, the levels of antinuclear and anti-DNA antibodies, anti-SS-A/Ro, antiSS-B/La antibodies, anti-gliadin antibodies, anti-glutamic acid decarboxylase antibodies, myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA), proteinase-3ANCA, anti-voltage-gated potassium channel antibodies, angiotensin-converting enzyme, T3, T4, TSH and serum B12 and B1were all normal. The serum IgG concentration was 1,310 mg/dl (normal 870–1,600), while the serum IgG4 concentration was elevated (298 mg/dl; normal, 4.8–105) (Table 1). A CSF analysis revealed pleocytosis (21/ll: mononuclear cells 20/ll, polymorphonuclear cells 1/ll) and an elevated protein level of 143 mg/dl. Additional testing of the CSF found elevated levels of IgG (24.6 mg/dl; normal: 0.9–5.5) and IgG4 (3.5 mg/dl; normal: not detected) (Table 1). The IgG index in the patient was 0.79 (normal: 0.33–0.60), while the IgG4 index was 0.65. No oligoclonal bands were detected in the CSF. A cytological examination of the CSF showed no plasma cells, and a CSF culture revealed no infectious pathogens. The results of electroencephalography were normal. A brain magnetic resonance imaging (MRI) study revealed symmetrical periventricular high signal intensity on T2-weighted images and fluid attenuated inversion recovery (FLAIR) images (Fig. 1a). Gadolinium-enhanced T1-weighted images showed no contrast enhancement in the dura mater. There were no findings suggesting cerebral vasculitis or atherosclerosis on MR angiography. Wholebody CT imaging showed no malignancy or complications of IgG4-related disease, such as pancreatitis, retroperitoneal fibrosis or interstitial pneumonia. Esophago-gastroduodenoscopy and colonoscopy showed no malignancy. Y. Hosoi S. Kono (&) T. Konishi H. Miyajima First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu 431-3192, Japan e-mail: satokono@hama-med.ac.jp