Typical imaging manifestation of neuronal intranuclear inclusion disease in a man with unsteady gait:A case report

BACKGROUND Neuronal intranuclear inclusion disease(NIID)is a rare neurological degenerative disorder with diverse manifestations and inadequate awareness.Only a few cases of NIID have been reported,and typical imaging findings can provide certain clues for the diagnosis of the disease.Furthermore,skin biopsy and genetic testing are important to confirm the diagnosis.CASE SUMMARY An 84-year-old man presented to the Neurology Department of our hospital complaining of a progressive course of cognitive impairment and unsteady gait for 2 years.The symptoms gradually progressed and affected his daily life.The patient was initially diagnosed with Parkinson’s disease and vascular dementia.The patient did not respond to conventional treatment,such as dopasehydrazine.Therefore,magnetic resonance imaging(MRI)was performed.Based on the imaging findings,we suspected an NIID diagnosis.During the 3-year follow-up in our hospital,his clinical symptoms gradually progressed,and imaging findings became more significant.A high signal intensity along the corticomedullary junction persisted on MRI.Gene testing and skin biopsy were recommended in our hospital;however,the patient refused these procedures.NIID was also considered when he went to a superior hospital in Shanghai.The patient eventually agreed to undergo gene testing.This revealed abnormal GGC repeat expansions in the NOTCH2NLC gene.CONCLUSION The clinical manifestations of NIID are diverse.Patients with clinical manifestations similar to Parkinson’s disease and dementia may have NIID.

Neuronal intranuclear inclusion disease mimicking acute cerebellitis:A case report

BACKGROUND Neuronal intranuclear inclusion disease(NIID)is an unusual autosomal dominant,chronic progressive neurodegenerative disease.The clinical manifestations of NIID are complex and varied,complicating its clinical diagnosis.To the best of our knowledge,this report is the first to document sporadic adult-onset NIID mimicking acute cerebellitis(AC)that was finally diagnosed by imaging studies,skin biopsy,and genetic testing.CASE SUMMARY A 63-year-old man presented with fever,gait unsteadiness,dysarthria,and an episode of convulsion.His serum levels of white blood cells and C-reactive protein were significantly elevated.T2-weighted brain magnetic resonance imaging and fluid attenuation inversion recovery sequences showed bilateral high-intensity signals in the medial part of the cerebellar hemisphere beside the vermis.While we initially considered a diagnosis of AC,the patient’s symptoms improved significantly without special treatment,prompting our consideration of NIID.Diffusion-weighted imaging showed hyperintensity in the corticomedullary junction.Skin biopsy revealed eosinophilic inclusions positive for anti-p62 in epithelial sweat-gland cells.GGC repeat expansions in the Notch 2 N-terminal like C gene confirmed the diagnosis of NIID.CONCLUSION For patients with clinical manifestations mimicking AC,the possibility of underlying NIID should be considered along with prompt rigorous examinations.

Intranuclear inclusions in a fragile X mosaic male

Lack of the fragile X mental retardation protein leads to Fragile X syndrome(FXS)while increased levels of FMR1 mRNA,as those observed in premutation carriers can lead to Fragile X-associated tremor ataxia syndrome(FXTAS).Until recently,FXTAS had been observed only in carriers of an FMR1 premutation(55–200 CGG repeats);however the disorder has now been described in individuals carriers of an intermediate allele(45–54 CGG repeats)as well as in a subject with a full mutation with mosaicism.Here,we report on molecular and clinical data of a male FMR1 mosaic individual with full and premutation alleles.Molecular analysis of FMR1 and FMRP expression in this subject is consistent with a FXS phenotype.We observed reduced expression of FMRP in both peripheral blood and brain leading to the FXS diagnosis.In addition,a dramatic 90%depletion of both FMR1 mRNA and FMRP levels was observed in the blood,as normally observed in FXS cases,and an even greater depletion in the brain.A clinical report of this patient,at age 71,described neurodegenerative signs of parkinsonism that were likely,in retrospect,part of a FXTAS scenario as post-mortem examination shows the presence of intranuclear inclusions,the hallmark pathology of FXTAS.The findings presented in this study indicate co-morbidity for both FXS and FXTAS in this individual carrying both full and premutation FMR1 alleles.In addition,based on symptoms and pathological and molecular evidence,this report suggests the need to redefine the diagnostic criteria of FXTAS.

β-catenin in intranuclear inclusions of hepatocellular carcinoma

Aim:β-catenin activation is known to promote liver regeneration and play a role in the pathogenesis of liver cancer.Recently,we detected intranuclear inclusions(NI)in hepatocellular carcinoma(HCC)containing degenerated cell organelles and lysosomal proteins and delimited by a completely closed nuclear membrane.The presence of NI was positively associated with patient survival.The aim of the current study was to investigate a possible association between proteins of the Wnt/β-catenin pathway with NI morphology and survival.Methods:We examined NI in 72 paraffin-embedded specimens of HCC.Immunohistochemistry(IHC)and immunofluorescence(IF)were performed to investigate the content and shape of NI.β-catenin gene(CTNNB1)mutations were analyzed by next generation sequencing.Results:We detected the accumulation ofβ-catenin and glutamine synthetase(a target gene ofβ-catenin)proteins within NI.Further,we found immunopositivity for the lysine demethylase KDM2A in NI.KDM2A is known to be involved inβ-catenin degradation.We detected significant associations between the presence ofβ-catenin and autophagy-associated proteins in NI.Double-IF revealed co-localization ofβ-catenin and p62 in the same NI.Kaplan-Meier survival analysis showed that the presence of NI containing KDM2A protein accumulations displayed a significant benefit in overall survival.Conclusion:We detected accumulations ofβ-catenin and proteins associated with the Wnt/β-catenin pathway partly together with autophagy-associated proteins in the same inclusion.Our finding that KDM2A immunopositivity within NIs was associated with favorable clinical outcomes and suggests a biological significance of NI.