Adult-onset Neuronal Intranuclear Inclusion Disease Research Articles

Clinical Features of Adult-Onset Neuronal Intranuclear Inclusion Disease: A Multi-Centre Study in China

Background: The full clinical spectrum of neuronal intranuclear inclusion disease (NIID) and its relationship with genotype have not been documented. We aimed to identify the clinical, neuroimaging, and genetic features of adult-onset NIID. Methods: An adult-onset NIID registry was launched in multiple centres throughout China. Clinical data, routine brain magnetic resonance imaging, and skin pathologies were evaluated. Arterial spin labelling magnetic resonance imaging and electrophysiological studies were conducted. Repeat-primed and amplicon length polymerase chain reaction were used to screen (GGC)n repeat expansions in the 5’ untranslated region of the NOTCH2NLC gene. Findings: In total, 134 adult-onset patients with NIID (66% female) from 72 clinical centres were included; 23 cases were familial. The mean age of onset was 56·9±9·4 years. The median disease duration was 4 (IQR 2–9) years. Adult-onset NIID was divided into three subtypes based on primary manifestations: dementia-dominant type (n=65), parkinsonism-dominant type (n=19), and episodic neurogenic event-dominant type (n=45). Among the patients, 90·5% presented with mild demyelinating polyneuropathy. All patients presented with high intensities along the corticomedullary junction on diffusion-weighted imaging, and 53·7% of them presented with abnormal hyperintensity in the paravermal area on T2/fluid-attenuated inversion recovery images. Cerebral blood flow in the whole brain was lower and that in globus pallidus was higher in patients with NIID than in healthy controls. (GGC) n repeat number in the 5’-untranslated region of the NOTCH2NLC gene ranged from 82 to 173 repeats. A significant inverse correlation between (GGC) n repeat number and age of onset was observed (r=–0·203, p=0·018). Interpretation: This study provides a novel classification of adult-onset NIID for clinical application. Decreased cerebral perfusion may underpin the pathogenesis of NIID and highlight the potential of perfusion modulation therapy. (GGC) n repeat number was inversely correlated with the age of onset, and the pathogenetic effect may have a cumulative effect. Funding: None Declaration of Interest: We declare no competing interests. Ethical Approval: This study was approved by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University, and adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all individuals or their authorised surrogates at enrolment.

Adult-onset neuronal intranuclear inclusion disease, with both stroke-like onset and encephalitic attacks: a case report

BackgroundNeuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, the clinical manifestations of which are complex and easily misdiagnosed. NIID clinical characteristics are varied, affecting the central and peripheral nervous systems and autonomic nerves. In this study, we present an NIID case with both stroke-like onset and encephalitic attacks, which is a rare case report.Case presentationA 68-year-old Chinese female presented with sudden aphasia and limb hemiplegia as the first symptoms, as well as fever, cognitive impairment and mental irritability from encephalitic attacks. During hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity from diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. Electrophysiological tests revealed the main site of injury was at the myelin sheath in the motor nerves. A skin biopsy revealed eosinophilic spherical inclusion bodies in the nuclei of small sweat gland cells, fibroblasts and fat cells, whilst immunohistochemistry revealed that p62 and ubiquitin antibodies were positive. From genetic analyses, the patient was not a carrier of the fragile X mental retardation 1 (FMR1) permutation, but repeated GGC sequences in the NOTCH2NLC gene confirmed an NIID diagnosis. Through antipsychotic and nutritional support therapy, the patient’s symptoms were completely relieved within 3 weeks.ConclusionsThis report of an NIID case with both stroke-like onset and encephalitic attacks provides new information for NIID diagnoses, and a comprehensive classification of clinical characteristics.

Expanding the clinical spectrum of adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a heterogeneous neurodegenerative disease with multiple clinical subtypes. Recent breakthroughs on neuroimaging, skin biopsy and genetic testing have facilitated the diagnosis. We aim to investigate the clinical characteristics of Chinese NIID patients to further refine the spectrum. We analyzed the clinical features of 25 NIID patients from 24 unrelated families and performed skin biopsy and/or sural nerve biopsy on 24 probands. Repeat-primed PCR and fluorescence amplicon length PCR were conducted to detect GGC repeats of NOTCH2NLC. Onset age ranged from 24 to 72years old, and the disease duration ranged from 12h to 25years with the mode of onset characterized as acute, recurrent or chronic progressive type. Tremor was a common phenotype, often observed in the early stages, next to dementia and paroxysmal encephalopathy. Symptoms infrequently reported such as oromandibular dystonia, recurrent vomiting, dizziness and headache of unknown origin, as well as pure peripheral neuropathy were also suggestive of NIID. Reversible leukoencephalopathy following encephalitic episodes and the absence of apparent DWI abnormality were noticed. Two genetically confirmed NIID patients failed to be identified intranuclear inclusions, and one patient was simultaneously found significant mitochondrial swelling and fingerprint profiles depositing in lysosomes. All the patients were identified abnormal GGC repeats of NOTCH2NLC. We identify some atypical clinicopathological features and consider that pathological examinations combined with genetic testing is the gold standard for diagnosis. Whether lysosomal and mitochondrial dysfunction is involved in the pathogenesis of NIID deserves further study.

Teaching Video NeuroImages: A Triad of Tremor, Ataxia, and Cognitive Impairment

A 67-year-old woman presented with a 2-year history of forgetfulness and unsteadiness. She scored 17 on the Montreal Cognitive Assessment. She had tremor of head and upper limbs (video 1) since early adulthood, which was diagnosed as essential tremor. Brain MRI showed leukoencephalopathy and high signal intensity along the corticomedullary junction on diffusion-weighted images (figure 1). The diagnosis of adult-onset neuronal intranuclear inclusion disease (NIID) was confirmed by skin biopsy showing eosinophilic intranuclear inclusions (figure 2).1 NIID is a clinically heterogeneous rare neurodegenerative disease.2 Its characteristic MRI pattern should prompt confirmation of the diagnosis by skin biopsy.

Cognitive profiles in adult-onset neuronal intranuclear inclusion disease: a case series from the memory clinic.

This study aimed to analyze the characteristics of cognitive impairment in adult-onset neuronal intranuclear inclusion disease (NIID). Seven patients with adult-onset NIID were collected consecutively from the memory clinic of Xuanwu hospital from February to December 2019. These cases were diagnosed with skin biopsy triggered by DWI high-intensity signals in corticomedullary junction on brain MRI. We used a battery of neuropsychological scales to detect the patient's performance in each cognitive domain, and made a detailed analysis on the characteristics of cognitive impairment. All seven cases had cognitive impairment, and four of them had met the criteria for dementia. The scores of Montreal Cognitive Assessment and Frontal Assessment Battery were abnormal in all patients. The executive dysfunction was confirmed by the abnormal scores of Trail Making Test (5/7, 71%) and Clock Drawing Test (4/7, 57%). Bad performance in Auditory Verbal Learning Test (6/7, 86%) demonstrated that the memory was also a very commonly impaired cognitive domain. The low score on the animal fluency (4/7, 57%), Boston Naming Test (3/7, 43%), and Pentagon and Cube Copying Test (4/7, 57%) indicated that the language and visuospatial skills were also impaired. Fazekas scores were significantly correlated to the global cognition, executive and language functions (r = 0.788-0.906, P < 0.05). There is obvious impairment in multiple cognitive domains in adult-onset NIID, and both the executive dysfunction and memory deficit are very common. Leukoencephalopathy may be the main course of cognitive impairment in adult-onset NIID.

Neuronal intranuclear inclusion disease with mental abnormality: a case report

BackgroundNeuronal intranuclear inclusion disease (NIID) is a chronic progressive neurodegenerative disease that is characterized by the discovery of eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. In this paper, we report a case of an adult-onset neuronal intranuclear inclusion disease presenting with mental abnormality in China.Case presentationA 62-year-old woman presented with mental abnormality and forgetfulness for 3 months before she was admitted to our hospital. There were prodromal symptoms of fever before she had the mental disorder. Encephalitis was first suspected, and the patient underwent lumbar puncture and brain magnetic resonance imaging (MRI). A cerebrospinal fluid (CSF) examination indicated normal pressure, a normal white blood cell count, and slightly elevated protein and glucose levels. Coxsackie B virus, enterovirus, and cytomegalovirus tests showed normal results. Bacterial culture and Cryptococcus neoformans test results were negative. The contrast-enhanced MRI of the brain was normal. The brain diffusion-weighted imaging (DWI) showed a symmetrically distributed strip-shaped hyperintensity signal of the corticomedullary junction in the bilateral frontal, parietal, and temporal lobes. We considered the diagnosis of the NIID, and therefore, skin biopsy was performed. The electron microscopy revealed that intranuclear inclusions in the nucleus of fibrocytes existed and were composed of filaments.ConclusionsNIID is a rare neurodegenerative disease with diverse clinical manifestations. In clinical work, when a patient presents with abnormal mental behavior and exhibits hyperintensity signals on DWI images of the corticomedullary junction, it is crucial to consider the diagnosis of NIID.

Clinical Characteristics of Neuronal Intranuclear Inclusion Disease-Related Retinopathy With CGG Repeat Expansions in the NOTCH2NLC Gene.

PurposeTo report the ocular characteristics of neuronal intranuclear inclusion disease (NIID)–related retinopathy with expansion of the CGG repeats in the NOTCH2NLC gene.MethodsSeven patients from six families (aged 66–81 years) diagnosed with adult-onset NIID were studied. Ophthalmologic examinations, including the best-corrected visual acuity (BCVA), Goldmann perimetry, fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), and full-field electroretinography (ERGs), were performed. The expansion of the CGG repeats in the NOTCH2NLC gene was determined.ResultsAll patients had an expansion of the CGG repeats (length approximately from 330–520 bp) in the NOTCH2NLC gene. The most common symptoms of the five symptomatic cases were reduced BCVA and night blindness. The other two cases did not have any ocular symptoms. The decimal BCVA varied from 0.15 to 1.2. Goldmann perimetry was constricted in all four cases tested; physiological blind spot was enlarged in two of the cases. The FAF images showed an absence of autofluorescence (AF) around the optic disc in all cases and also showed mild hypo-AF or extinguished AF in the midperiphery. In all cases, the OCT images showed an absence of the ellipsoid zone of the photoreceptors in the peripapillary region, and hyperreflective dots were also present between the retinal ganglion cell layer and outer nuclear layer. The macular region was involved in the late stage of the retinopathy. The full-field ERGs showed rod-cone dysfunction.ConclusionsPatients with adult-onset NIID with CGG repeats expansions in the NOTCH2NLC gene had similar ophthalmologic features, including rod-cone dysfunction with progressive retinal degeneration in the peripapillary and midperipheral regions. The primary site is most likely the photoreceptors. Because the ocular symptoms are often overlooked due to dementia and occasionally precede the onset of dementia, detailed ophthalmological examinations are important for the early diagnosis of NIID-related retinopathy.

Adult‐onset neuronal intranuclear inclusion disease showing markedly high phosphorylated tau protein levels in cerebrospinal fluid

Geriatrics & Gerontology InternationalVolume 20, Issue 8 p. 793-795 LETTER TO THE EDITOR Adult-onset neuronal intranuclear inclusion disease showing markedly high phosphorylated tau protein levels in cerebrospinal fluid Shuntaro Serisawa, Shuntaro Serisawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorKentaro Hirao, Corresponding Author Kentaro Hirao kentaroh@tokyo-med.ac.jp Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan Correspondence Kentaro Hirao MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: kentaroh@tokyo-med.ac.jpSearch for more papers by this authorTomohiko Sato, Tomohiko Sato Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYusuke Ogawa, Yusuke Ogawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHidekazu Kanetaka, Hidekazu Kanetaka Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorMutsuo Enomoto, Mutsuo Enomoto Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorSoichiro Shimizu, Soichiro Shimizu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHirofumi Sakurai, Hirofumi Sakurai Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYasuhiro Sakashita, Yasuhiro Sakashita Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorShigeo Murayama, Shigeo Murayama Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorHaruo Hanyu, Haruo Hanyu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this author Shuntaro Serisawa, Shuntaro Serisawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorKentaro Hirao, Corresponding Author Kentaro Hirao kentaroh@tokyo-med.ac.jp Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan Correspondence Kentaro Hirao MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Email: kentaroh@tokyo-med.ac.jpSearch for more papers by this authorTomohiko Sato, Tomohiko Sato Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYusuke Ogawa, Yusuke Ogawa Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHidekazu Kanetaka, Hidekazu Kanetaka Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorMutsuo Enomoto, Mutsuo Enomoto Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorSoichiro Shimizu, Soichiro Shimizu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorHirofumi Sakurai, Hirofumi Sakurai Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this authorYasuhiro Sakashita, Yasuhiro Sakashita Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorShigeo Murayama, Shigeo Murayama Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanSearch for more papers by this authorHaruo Hanyu, Haruo Hanyu Department of Geriatric Medicine, Tokyo Medical University, Tokyo, JapanSearch for more papers by this author First published: 02 August 2020 https://doi.org/10.1111/ggi.13964Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume20, Issue8August 2020Pages 793-795 RelatedInformation

Clinical and pathological features in adult-onset NIID patients with cortical enhancement

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in multiple organs. On conventional MRI, high signals on diffused weight image (DWI) along the corticomedullary junction have demonstrated great diagnostic values for adult-onset NIID. However, changes of contrast MRI in the acute period of the encephalopathy-like episode have rarely been investigated. Patients with enhanced lesions were retrieved in our database including 35 patients with adult-onset NIID between October 2017 and December 2019. Conventional and contrast MRI were conducted in all patients. Standard procedures of skin biopsy were performed in all patients. Repeat-primed PCR and amplicon length PCR were used to screen the GGC expansion in the 5'UTR of the NOTCH2NLC gene. Four of 35 patients (11.4%) were identified to have a cortical enhancement in this study. The enhanced lesions were selectively spread along the surface of posterior cortex and were clinically associated with encephalopathy-like episodes. These patients had a younger age of onset, shorter duration of disease, and a higher incidence of a headache than those without enhancement. Typical p62-postive intranuclear inclusions were observed in all patients, while patient 1 simultaneously had many nuclei full of abnormal substance immunopositive to p62, as well as short-curly filament materials on electron microscopy. All patients were identified to have GGC repeat expansion in the NOTCH2NLC gene. Post-contrast MRI should be routinely performed in the adult-onset NIID patients. Some patients with adult-onset NIID showed cortical enhancement and edema along the surface of posterior cortex, indicating that dehydrate and anti-inflammatory drugs might be potential therapies for these patients.

Diagnostic indicators for adult-onset neuronal intranuclear inclusion disease.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Abnormally high signals of diffusion-weighted image (DWI) along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID. However, the DWI abnormalities usually were observed in the late stage of disease; further study might be helpful to elucidate some clinical indicators regarding the early awareness of NIID. In this study, we summarized 9 patients with NIID from multiple centers. The mean age was 60.0 ± 6.2 years. The mean duration of disease was 4.4 ± 3.2 years. The most common symptoms included cognitive impairment, episodic encephalopathy, and bladder dysfunction. Among the 6 patients with bladder dysfunction, 3 patients had the symptom prior to the development of other neurological symptoms; 5 patients needed permanent cystostomy. Isolated high DWI signals on the splenium of corpus callosum were observed in 2 patients at the early stage. The characteristic intranuclear inclusions in the skin were identified in all patients and confirmed by electron microscopy. Episodic encephalopathy or bladder dysfunction prior to other neurological symptoms were valuable diagnostic indicators for adult-onset NIID. High DWI signals on the splenium of corpus callosum might be an early indicator for the diagnosis of NIID. The immunostain of anti-ubiquitin or anti-p62 antibody was a convenient and sensitive biomarker for NIID with the background of typical phenotype with cognitive impairment and autonomic dysfunctions.

Adult-Onset Neuronal Intranuclear Inclusion Disease: First Korean Case Confirmed by Skin Biopsy.

Adult-Onset Neuronal Intranuclear Inclusion Disease: First Korean Case Confirmed by Skin Biopsy.

Clinical analysis of adult-onset neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID) is characterized by eosinophilic nuclear inclusions (NI) in the nervous systems and the visceral organs. Ante-mortem diagnoses have been made by NI identification in skin biopsy samples based on characteristic corticomedullary junction (CMJ) high intensity in brain diffusion-weighted imaging (DWI). However, the clinical symptoms of NIID are variable. We analyzed 14 (10 sporadic, 4 familial) adult-onset NIID patients with clinical examination, electrophysiological study, brain MRI, cerebrospinal fluid (CSF) biomarker, and skin biopsy. The mean onset-age was 63.8 years. Initial symptoms were consciousness disturbance, memory impairment, gait disturbance, etc. The mean scores of MMSE, Japanese version of Montreal Cognitive Assessment and Frontal Assessment Battery were 20.7/30, 14.2/30 and 9.2/18, respectively. Neurological examination demonstrated hypo-areflexia, miosis and urinary dysfunction. All patients showed abnormal nerve conduction. Thirteen of 14 patients revealed high intensities of CMJ in DWI and leukoencephalopathy with ventricular dilatation and brain atrophy in MRI FLAIR images. In one patient with leukoencephalopathy, DWI high intensity was not detected. The levels of total Tau in CSF were increased in accordance with the grade of DWI high intensity. Skin biopsies from all patients demonstrated that NI immunostained with anti-ubiquitin and anti-p62 antibodies in the sweat gland cells, adipocytes and fibroblasts, were composed of filamentous structure without limiting membrane by electron microscopy. In patients with miosis and hyporeflexia with leukoencephalopathy, NIID should be considered for differential diagnosis even when DWI high intensity is negative. Total Tau in CSF will be a biomarker for progression of NIID.

Teaching NeuroImages: The zigzag edging sign of adult-onset neuronal intranuclear inclusion disease.

Teaching NeuroImages: The zigzag edging sign of adult-onset neuronal intranuclear inclusion disease.

Identifying patients with neuronal intranuclear inclusion disease in Singapore using characteristic diffusion-weighted MR images.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder described mainly in the Japanese population, with characteristic DWI abnormalities at the junction between gray and white matter. We identify possible cases of NIID in the picture archive and communication system (PACS) of a tertiary neurological referral hospital in Singapore and describe their radiological features. The neuroradiology imaging database was reviewed using keyword search of radiological reports to identify patients who had "subcortical U fibre" abnormalities on DWI. MRI were retrospectively reviewed, and those fulfilling inclusion criteria were invited for skin biopsy to detect nuclear inclusions by light and electron microscopy. Twelve Chinese patients (nine female; median age 70.5years) were enrolled. Seven patients were being assessed for dementia and five for other neurological indications. In all patients, DWI showed distinctive subcortical high signal with increased average apparent diffusion coefficient (ADC), involving frontal, parietal, and temporal more than occipital lobes; the corpus callosum and external capsule were affected in some patients. On T2-weighted images, cerebral and cerebellar atrophy and white matter hyperintensity of Fazekas grade 2 and above were seen in all patients. Three patients underwent skin biopsy; all were positive for intranuclear hyaline inclusion bodies on either p62 staining or electron microscopy, which are pathognomonic for NIID. Previously undiagnosed patients with NIID can be identified by searching for abnormalities at the junction between gray and white matter on DWI in PACS and subsequently confirmed by skin biopsy. Radiologists should recognize the distinctive neuroimaging pattern of this dementing disease.

A Case of Adult Onset Neuronal Intranuclear Inclusion Disease

In this case of adult onset neuronal intranuclear inclusion disease (NIID), we will explore the clinical and pathological features of NIID as well as its medical imaging and histological features. The patient presented with tremor, cognitive impairment, and paroxysmal disturbance of consciousness. Diffusion-weighted imaging of cranial magnetic resonance showed high signal intensity of ribbon-like distribution at corticomedullary junction. Additionally, fibloblasts, vascular endothelial cells, and intranuclear inclusions were found on histological specimens of skin biopsy. This case suggests adult onset NIID is a disease of chronic neurological degeneration with high heterogeneity, which can be diagnosed by characteristic MRI DW1 ribbon-like high signal and eosinophilic intranuclear inclusions under electron microscopy.

MR Imaging Features of Adult-Onset Neuronal Intranuclear Inclusion Disease May Be Indistinguishable from Fragile X–Associated Tremor/Ataxia Syndrome

We have read with great interest the article by Sugiyama et al[1][1] published in the November 2017 edition of the American Journal of Neuroradiology , which described typical brain MR imaging findings in adult-onset neuronal intranuclear inclusion disease (NIID). The authors highlighted the

Two cases of sporadic adult-onset neuronal intranuclear inclusion disease preceded by urinary disturbance for many years

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease defined by the presence of eosinophilic hyaline intranuclear inclusions. The initial and main clinical feature of adult-onset NIID is predominantly dementia. We present herein 2 cases of sporadic adult-onset NIID with longstanding urinary disturbance prior to development of other neurological symptoms. Case 1: A 71-year-old woman was admitted after she lost consciousness while bathing. She presented slowly progressive bladder dysfunction starting at the age of 40. Recently, she complained of recurrent light-headedness on standing. Her neurological findings showed miosis, muscle weakness, rigidity, hyporeflexia, sensory disturbance, cerebellar ataxia, and orthostatic hypotension. Case 2: A 68-year-old man was admitted because of episodes of transient loss of consciousness. Ten years earlier, he had developed urinary dysfunction. His neurological findings revealed cognitive dysfunction, cerebellar ataxia, and hyporeflexia. Both patients had leukoencephalopathy and motor-sensory neuropathy. In both cases, diffusion-weighted imaging showed high-intensity signals in the corticomedurally junction; and skin biopsy samples revealed ubiquitin-positive intranuclear inclusions. Therefore, we made a diagnosis of adult-onset NIID. Although numerous cases of this disorder have been reported in the past, there were only a few cases showing the development of other neurological symptoms after longstanding urinary disturbance. Our cases suggest that it is worthwhile considering the possibility of NIID in cases with a long-term history of neurogenic bladder dysfunction.

An adult onset sporadic neuronal intranuclear inclusion disease case reminiscent with Fisher syndrome

A 63-year-old woman presented to our hospital with sudden symptoms of unsteadiness while walking. Based on the neurological findings, i.e., ataxia and absence of tendon reflex in the extremities accompanied by antecedent infection at the time, she was tentatively diagnosed with Fisher syndrome. Following intravenous immunoglobulin (IVIg) therapy for 5 days, her ataxic symptoms improved. Laboratory data were negative for antiganglioside antibody against GQ1b in the IgG subclass. Six months after her first admission, cognitive impairment gradually developed. She was re-admitted owing to new onset of unsteadiness while walking 1.5 years after her first admission. Diffusion-weighted brain MRI (DWI) revealed linear high-intensity signals in the region of the corticomedullary junction. Cutaneous skin biopsy revealed intranuclear inclusion bodies in sweat gland cells. Considering her family history along with the examination results, we diagnosed with adult-onset sporadic neuronal intranuclear inclusion disease (NIID). Retrospective investigation of the previous DWI obtained at the first admission had also shown slight linear high-intensity areas, suggesting that a series of events, including repeated sudden-onset transient ataxia, resulted due to NIID.

Adult-onset neuronal intranuclear inclusion disease without corticomedullary junction high intensity in brain diffusion-weighted imaging

Adult-onset neuronal intranuclear inclusion disease without corticomedullary junction high intensity in brain diffusion-weighted imaging

Involvement of TGF-β signaling-related proteins in the inclusions in adult-onset neuronal intranuclear inclusion disease

Involvement of TGF-β signaling-related proteins in the inclusions in adult-onset neuronal intranuclear inclusion disease