Neuronal intranuclear inclusion disease with mental abnormality: a case report

Abstract Background Neuronal 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 presentation A 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. Conclusions NIID 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.

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Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case

BMC Neurology ◽

10.1186/s12883-021-02306-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Atsuhiko Sugiyama ◽

Takahiro Takeda ◽

Mizuho Koide ◽

Hajime Yokota ◽

Hiroki Mukai ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Repeat Expansion ◽

Cerebellar Hemisphere ◽

Intranuclear Inclusions ◽

Intranuclear Inclusion ◽

Neuronal Intranuclear Inclusion ◽

Lateral Sclerosis

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. Case presentation A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. Conclusions We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

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The Value of NOTCH2NLC Gene Detection and Skin Biopsy in the Diagnosis of Neuronal Intranuclear Inclusion Disease

Frontiers in Neurology ◽

10.3389/fneur.2021.624321 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jie Pang ◽

Jing Yang ◽

Yanpeng Yuan ◽

Yuan Gao ◽

Changhe Shi ◽

...

Keyword(s):

Skin Biopsy ◽

Clinical Manifestations ◽

Asian Population ◽

Diagnostic Value ◽

Gene Detection ◽

Intranuclear Inclusion ◽

Mri Findings ◽

Corticomedullary Junction ◽

Repeat Expansions ◽

Neuronal Intranuclear Inclusion

The clinical manifestations of neuronal intranuclear inclusion disease (NIID) are heterogeneous, and the premortem diagnosis is mainly based on skin biopsy findings. Abnormal GGC repeat expansions in NOTCH2NLC was recently identified in familial and sporadic NIID. The comparison of diagnostic value between abnormal GGC repeat expansions of NOTCH2NLC and skin biopsy has not been conducted yet. In this study, skin biopsy was performed in 10 suspected adult NIID patients with clinical and imaging manifestations, and GGC repeat size in NOTCH2NLC was also screened by repeat primed-PCR and GC-rich PCR. We found that five cases had ubiquitin-immunolabelling intranuclear inclusion bodies by skin biopsy, and all of them were identified with abnormal GGC repeat expansions in NOTCH2NLC, among whom four patients showed typical linear hyperintensity at corticomedullary junction on DWI. Five (5/10) NIID patients were diagnosed by combination of NOTCH2NLC gene detection, skin biopsy or combination of NOTCH2NLC, and typical MRI findings. The diagnostic performance of NOTCH2NLC gene detection was highly consistent with that of skin biopsy (Kappa = 1). The unexplained headache was firstly reported as a new early phenotype of NIID. These findings indicate that NOTCH2NLC gene detection is needed to be a supplement in the diagnose flow of NIID and also may be used as an alternative method to skin biopsy especially in Asian population.

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Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation

BMC Neurology ◽

10.1186/s12883-021-02367-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Danhua Zhao ◽

Sha Zhu ◽

Qinlan Xu ◽

Jianwen Deng ◽

Zhaoxia Wang ◽

...

Keyword(s):

Neurodegenerative Disorder ◽

Brain Magnetic Resonance Imaging ◽

Vestibular Migraine ◽

Sweat Glands ◽

Intranuclear Inclusion ◽

Case Presentation ◽

Disturbance Of Consciousness ◽

Corticomedullary Junction ◽

Electrophysiological Studies ◽

Neuronal Intranuclear Inclusion

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder characterized by dementia, tremor, episodic encephalopathy and autonomic nervous dysfunction. To date, vestibular migraine (VM)-like attack has never been reported in cases with NIID. Here, we describe an 86-year-old patient with NIID who presented with recurrent vertigo associated with headache for more than 30 years. Case presentation An 86-year-old Chinese woman with vertigo, headache, weakness of limbs, fever, and disturbance of consciousness was admitted to our hospital. She had suffered from recurrent vertigo associated with headache since her 50 s,followed by essential tremor and dementia. On this admission, brain magnetic resonance imaging revealed high intensity signals along the corticomedullary junction on diffusion weighted imaging (DWI). Peripheral neuropathy of the extremities was detected through electrophysiological studies. We diagnosed NIID after detecting eosinophilic intranuclear inclusions in the ductal epithelial cells of sweat glands and identifying an abnormal expansion of 81 GGC repeats in the 5’UTR of NOTCH2NLC gene. Conclusions VM-like attack may be associated with NIID.

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An unusual Neuronal Intranuclear Inclusion Disease with Chief Complaint of Autonomic Dysfunction

10.21203/rs.2.1814/v2 ◽

2019 ◽

Author(s):

Xiaoyun Liu ◽

Xiaohui Liu ◽

Yifeng Du ◽

Chunxia Li ◽

Cuicui liu ◽

...

Keyword(s):

Brain Magnetic Resonance Imaging ◽

Intranuclear Inclusions ◽

Resonance Imaging ◽

Dominant Group ◽

Intranuclear Inclusion ◽

Case Presentation ◽

Level Of Consciousness ◽

Recurrent Vomiting ◽

Neuronal Intranuclear Inclusion ◽

Magnetic Resonance Imaging Mri

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a recently defined disease entity of progressive neurodegenerative disease with characterizations of eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. The sporadic adult-onset NIID cases were previous described as ‘dementia dominant group’. Here we present a NIID case manifested prominently with recurrent vomiting. Case presentation A 60-year-old women present with paroxysmal vomiting, hypertention and decreased level of consciousness for 3 years. She was diagnosed with NIID based on history, clinical features, brain magnetic resonance imaging(MRI), skin biopsy. Conclusion Autonomic symptoms may manifest as the initial and predominant presentation of NIID. This case presentation may extend the spectrum of NIID and may give new insights in exploring the pathogenic mechanisms of NIID.

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

BMC Neurology ◽

10.1186/s12883-021-02164-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Huang ◽

Ge Jin ◽

Qun-ling Zhan ◽

Yun Tian ◽

Lu Shen

Keyword(s):

Case Report ◽

Clinical Characteristics ◽

Spherical Inclusion ◽

Clinical Manifestations ◽

Brain Magnetic Resonance Imaging ◽

High Signal ◽

Autonomic Nerves ◽

Intranuclear Inclusion ◽

Main Site ◽

Neuronal Intranuclear Inclusion

Abstract Background Neuronal 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 presentation A 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. Conclusions This 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.

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