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Background And Objective: Neuronal intranuclear inclusion disease (NIID) is a multifaceted disorder impacting both the central and peripheral nervous systems. This study aims to investigate the clinical and electrophysiological characteristics of peripheral neuropathy in patients with NIID.

Methods: In this cross-sectional study, patients diagnosed with NIID were prospectively recruited from multiple centers across China between October 2017 and May 2024.

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Rationale: Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease with various manifestations and high heterogeneity. Clinical characteristics, imaging, skin biopsy, and genetic testing are necessary for its diagnosis. Electromyography may also be a useful tool for diagnosing NIID.

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A male in his 20s presented with episodic headache and subsequently developed episodic unilateral weakness, dysphasia and encephalopathy. These paroxysmal episodes persisted over time with the development of background cognitive impairment and neuropsychiatric symptoms. MRI surveillance demonstrated progressive T2 hyperintensity with focal cortical oedema correlating to symptoms observed during clinical episodes.

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Objective: Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disease affecting the central and peripheral nerves. We aimed to assess the pathophysiological features of peripheral nerve dysfunction in NIID.

Methods: We observed six unrelated NIID patients through clinical records, nerve conduction studies, and multiple measures of motor nerve excitability.

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Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disease with a characteristic pathological feature of eosinophilic hyaluronan inclusions in the nervous system and internal organs. The identification of GGC-repeat expansions in the Notch 2 N-terminal like C (NOTCH2NLC) gene facilitates the accurate diagnosis of NIID. Due to its rareness and high clinical heterogeneity, the diagnosis of NIID is often delayed or missed.

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