A case of adult-onset neuronal intranuclear inclusion disease without abnormal high-intensity signal in the corticomedullary junction in diffusion-weighted imaging

Dong, Hui; Ji, Guang; Li, Peipei; Li, Yuehong; Tian, Yun; Shen, Lu; Liu, Yaling; Song, Xueqin

doi:10.1007/s10072-020-04385-7

Cited by 12 publications

(9 citation statements)

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“…Furthermore, it was also reported in other CGG repeat expansion diseases, including fragile X-associated tremor/ataxia syndrome (FXTAS) and oculopharyngeal myopathy with leukoencephalopathy 14 32 33. In addition, we reported diffuse DWI high signal in the white matter of patients with NIID 34. High DWI signals in the corpus callosum, severe leukoencephalopathy involving the corpus callosum, middle cerebellar peduncle, paravermal area, cortical oedema with gadolinium enhancement, brain atrophy and lateral ventricle enlargement were also observed in patients with NIID, as previously reported 12 35.…”

Section: Discussionsupporting

confidence: 80%

“… 14 32 33 In addition, we reported diffuse DWI high signal in the white matter of patients with NIID. 34 High DWI signals in the corpus callosum, severe leukoencephalopathy involving the corpus callosum, middle cerebellar peduncle, paravermal area, cortical oedema with gadolinium enhancement, brain atrophy and lateral ventricle enlargement were also observed in patients with NIID, as previously reported. 12 35 Among them, high intensity in the paravermal area has rarely been reported in other patients with leukoencephalopathies, indicating it could also be a useful indicator for NIID.…”

Section: Discussionsupporting

confidence: 79%

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Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease

Tian

Zhou

Gao

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundAbnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China.MethodsPatients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.ResultsIn the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=−0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission.ConclusionsNIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 79%

Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease

Tian

Zhou

Gao

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Despite ribbon sign as a sensitive diagnostic indicator, the characteristic DWI feature appears in only 37% of all NIID patients (35). Few NIID patients manifested with mild leukoaraiosis, progressive leukoencephalopathy, brain atrophy, or focal reversible leukoencephalopathy but without highintensity signaling in the corticomedullary junction on DWI as described in previous studies (12,31,(36)(37)(38). So, except patients with certain characteristics on DWI, patients without the ribbon sign should also be followed to avoid missed diagnosis.…”

Section: Discussionmentioning

confidence: 88%

Unraveling rare form of adult-onset NIID by characteristic brain MRI features: A single-center retrospective review

Wang

Zhu

et al. 2022

Front. Neurol.

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Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with high clinical heterogeneity. Previous studies indicated that the high-intensity signals in the corticomedullary junction on diffusion-weighted imaging (DWI) on brain MRI, known as the “ribbon sign,” could serve as a strong diagnostic clue. Here we used the explorative approach to study the undiagnosed rate of adult-onset NIID in a single center in China via searching for the ribbon sign in picture archive and communication system (PACS) and report the clinical and radiological features of initially undiagnosed NIID patients.Consecutive brain MRI of 21,563 adult individuals (≥18 years) in the PACS database in 2019 from a tertiary hospital were reviewed. Of them, 4,130 were screened out using the keywords “leukoencephalopathy” and “white matter demyelination.” Next, all 4,130 images were read by four neurologists. The images with the suspected ribbon sign were reanalyzed by two neuroradiologists. Those with the ribbon sign but without previously diagnosed NIID were invited for skin biopsy and/or genetic testing for diagnostic confirmation. The clinical features of all NIID patients were retrospectively reviewed.Five patients with high-intensity in the corticomedullary junction on DWI were enrolled. Three patients were previously diagnosed with NIID confirmed by genetic or pathological findings and presented with episodic encephalopathy or cognitive impairment. The other two patients were initially diagnosed with limb-girdle muscular dystrophy (LGMD) with rimmed vacuoles (RVs) and normal pressure hydrocephalus (NPH) in one each. Genetic analysis demonstrated GGC repeat expansion in the NOTCH2NLC gene of both, and skin biopsy of the first patient showed the presence of intranuclear hyaline inclusion bodies. Thus, five of the 21,563 adult patients (≥18 years) were diagnosed with NIID. The distinctive subcortical high-intensity signal on DWI was distributed extensively throughout the lobes, corpus callosum, basal ganglia, and brainstem. In addition, T2-weighted imaging revealed white matter hyperintensity of Fazekas grade 2 or 3, atrophy, and ventricular dilation. Distinctive DWI hyperintensity in the junction between the gray and white matter can help identify atypical NIID cases. Our findings highly suggest that neurologists and radiologists should recognize the characteristic neuroimaging pattern of NIID.

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“…The inclusion criteria were as follows: (1) skin biopsy indicating intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands, (2) NOTCH2NLC gene testing showing abnormal repeated GGC premutation, and (3) detailed medical history. Finally, 63 patients met the inclusion criteria ( Chen et al, 2020 ; Dong et al, 2020 ; Guo et al, 2020 ; Ishihara et al, 2020 ; Li et al, 2020 ; Liang et al, 2020 ; Ogasawara et al, 2020 ; Okamura et al, 2020 ; Wang et al, 2020 ; Yuan et al, 2020 ; Zhang et al, 2020 , 2022 ; Cao et al, 2021 ; Deng et al, 2021 ; Huang et al, 2021 ; Kikumoto et al, 2021 ; Kotani et al, 2021 ; Pang et al, 2021 ; Tachi et al, 2021 ; Zhao et al, 2021 ; Liao et al, 2022 ; Yang et al, 2022 ). The clinical, radiological, pathological, genetic, electrophysiological features, and cerebrospinal fluid (CSF) results were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review

et al. 2022

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BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.Materials and methodsWe presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed.ResultsPatient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations.ConclusionNIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies.

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A case of adult-onset neuronal intranuclear inclusion disease without abnormal high-intensity signal in the corticomedullary junction in diffusion-weighted imaging

Cited by 12 publications

References 10 publications

Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease

Clinical features ofNOTCH2NLC-related neuronal intranuclear inclusion disease

Unraveling rare form of adult-onset NIID by characteristic brain MRI features: A single-center retrospective review

Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review

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