LAUSR

Dear Editor, Neuronal intranuclear inclusion disease (NIID) is a progressive and fatal neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions [1]. The symptoms of NIID are variable and can be easily missed. Recent research has brought increased awareness to NIID due to a characteristic high-intensity signal in the corticomedullary junction (CMJ) in diffusion-weighted imaging (DWI) [2], the detection of intranuclear inclusions by skin biopsy [3], and the repeated amplification of GGC sequences in the 5′-untranslated region (5′UTR) of the NOTCH2NLC (Notch 2 N-terminal like C) gene [4]. Here, we report one case of NIID without a high-intensity signal in CMJ in DWI. The case is presented here to raise awareness of presentations of this disease which lack the typical imageological characteristics of NIID. A 67-year-old woman was admitted to our hospital with fever, apathy, hemiplegia, and convulsion. At the age of 55, she underwent suprapubic cystostomy due to urinary retention and recurrent urinary tract infection for more than 10 years. At 60 years of age, she developed headaches, forgetfulness, abnormal behaviours, and visual hallucinations, which showed a relapsing-remitting form, and was misdiagnosed with ‘viral or autoimmune encephalitis’. More recently, she developed a fever of over 38.5 °C, dementia, hemiplegia, epilepsy, and convulsion. She had a past medical history of hypertension, but no family history of neurological diseases. On admission, neurological examination revealed dysarthria, abnormalities in ocular movements such as slow saccade and miosis, hypokinesia, and muscle strength at grade 4 of the left limbs, absent tendon reflexes, and pathologic reflexes. Dementia and aphasia were particularly prominent, and the patient failed to complete any cognitive scales. Urinalysis revealed the presence of leukocytes, erythrocytes, and protein in the patient’s urine. The results of cerebrospinal fluid examination and electrocardiogram were normal. Brain magnetic resonance imaging (MRI) demonstrated the hyperintensity of periventricular white matter on fluidattenuated inversion recovery (FLAIR), T2-weighted images, and ADC map, with diffuse brain atrophy, but without hyperintensity of the corticomedullary junction in DWI (Fig. 1a). Electroencephalography showed abnormal activity with a number of slow waves in the bilateral anterior brain. Skin biopsy was performed and the tissue was taken from 10 cm superior to the lateral malleolus and sectioned at a thickness of 6 mm on the left leg. Haematoxylin and eosin staining showed eosinophilic intranuclear inclusions in sweat gland cells (Fig. 1b), which were immunopositive for ubiquitin and P62. The patient showed 88 repeats of GGC amplification in the 5′UTR of the NOTCH2NLC gene by repeatprimed PCR (RP-PCR) (Fig. 1c) and did not carry the fragile X mental retardation 1 (FMR1) premutation. Among healthy subjects, the number of GGC repeats of the NOTCH2NLC Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-020-04385-7) contains supplementary material, which is available to authorized users.