Peripheral nerve involvement in a family with neuronal intranuclear inclusion disease: a case report

Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by a broad spectrum of clinical manifestations, including progressive dementia, limb weakness, cerebellar ataxia, and autonomic dysfunction. Peripheral nerve involvement is a recognized clinical feature of NIID and may be prominent in patients with NOTCH2NLC GGC repeat expansions. Case presentation We report a familial case of NIID with prominent peripheral nerve involvement in a 48-year-old woman. The patient developed asymmetric limb weakness, sensory deficits on neurological examination, and postural tremor without the characteristic corticomedullary junction hyperintensity on diffusion-weighted imaging. Myasthenia gravis and anxiety-related episodes were initially considered during the diagnostic evaluation, but subsequent investigations supported a diagnosis of NIID. Nerve conduction studies revealed reduced conduction velocities in multiple motor and sensory nerves, raising suspicion of NIID. The diagnosis was confirmed by identification of a NOTCH2NLC GGC repeat expansion and skin biopsy showing intranuclear inclusions. Family screening identified additional NOTCH2NLC GGC repeat-expansion carriers, including the proband’s younger brother, who showed electrophysiological abnormalities suggestive of subclinical peripheral nerve involvement despite the absence of overt neurological symptoms. Conclusion NIID may exhibit substantial phenotypic heterogeneity and may present with prominent peripheral nerve involvement even in the absence of characteristic corticomedullary DWI abnormalities. Electrophysiological abnormalities may also be detected in clinically asymptomatic expansion carriers. Although this observation is based on a single family and has limited representativeness, it provides a rationale for further evaluation in larger cohorts.