A multimodal imaging features of the brain in adult-onset neuronal intranuclear inclusion disease

Abstract

Dear Editor, Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder, with highly variable clinical manifestations such as cerebellar ataxia, neuropathy, and cognitive dysfunction [1], which was characterized pathologically by eosinophilic hyaline intranuclear inclusions in the central and autonomic neurons [2]. However, skin biopsy reveals intranuclear inclusions in somatic cells had been discovered in recent years [3]. Additionally, high signal intensity in the corticomedullary junction on diffusion-weighted imaging (DWI) had been found in NIID patients with leukoencephalopathy diagnosed by a skin biopsy [1]. However, the metabolic alterations of the brain in NIID patients have never been reported. We herein report the case of an adultonset NIID patient with cognitive dysfunction along withmultimodal imaging features of the brain, including MRIs findings and the metabolic alterations of the brain. A 67-year-old woman was referred to our hospital with dementia and gait disturbance. She had a 4-year history of dizziness and gradually developed forgetfulness. Two years later, her movement slowed down accompanied with anesthesia. Ten months before admission, gait disturbance occurred. She had a past medical history of hypertension, with no family history of dementia. Neurological examination revealed dementia, Mini-Mental State Examination (MMSE) with a score of 9/30, and Montreal Cognitive Assessment (MoCA) with a score of 6/30, which were much worse than 2 years ago (MMSE 20/30, MoCA 18/30, data from the previous hospital). Additionally, neurological examination showed diminished reflexes in the four limbs, bradykinesia, gait disturbance, and impairment of postural reflexes, but the muscle testing was normal. She showed relatively slowed sensory nerve conductive velocities (NCVs) in the median nerves and ulnar nerves, so as the motor NCVs. The results of NCVs indicated that she had neuropathy. Laboratory tests showed normal including vitamin B12, thiamine, and thyroid hormone. According to the cerebrospinal fluid examination, we found the cell counts, levels of protein, and glucose were normal. Magnetic resonance imaging (MRI) demonstrated cerebral white matter hyperintensity on fluid-attenuated inversion recovery (FLAIR) images, white matter tracts lesions on diffusion tensor imaging (DTI), and hyperintensity of the corticomedullary junction on DWI (Fig.1). A review of her MRI/CT in the past 4 years showed the white matter lesions gradually worsened (Fig.1). Brain magnetic resonance spectroscopy (MRS) revealed a decreased ratio of Nacetylaspartate/creatine (NAA/Cr). Positron emission t omog r aphy / c ompu t e d t omog r aphy w i t h 18F fluorodeoxyglucose positron emission tomography/ computed tomography (F-FDG PET/CT) showed glucose hypometabolism in bilateral cerebral hemisphere, especially the frontoparietal cortex. A skin biopsy of the left leg showed ubiquitin-positive intranuclear inclusions in the fibroblasts, adipocytes, and sweat gland cells (Fig. 2). These findings confirmed that the patient had NIID. NIID is a rare neurodegenerative disorder, until 2000s, only 30 cases were reported; thus, it had been a pathologic entity diagnosed by autopsy histological examination. However, skin biopsy was useful for antemortem diagnosis of NIID, discovered in recent years, based on nuclear inclusions in sweat gland cells, fibroblasts, and adipocytes in cutaneous Yajing Liu and Jiancong Lu contributed equally to this work.