Dual Diagnosis at the Neuro-Immune Interface: A Case Report of Neuronal Intranuclear Inclusion Disease with Acute Anti-CASPR2 Encephalitis

Wan Zhu^1,2Tiansi Liu^1,2Xinran Yu^1,2Min Peng^1,2Jinghan Hu^1,2*

• ¹The People's Hospital Of Wenshan Prefecture, Wenshan, China
• ²Kunming University of Science and Technology School of Medicine, Kunming, China

Neuronal intranuclear inclusion disease (NIID) is a rare autosomal dominant, progressive neurodegenerative disorder characterized by complex and variable clinical manifestations that can affect multiple neurological domains. This report describes the case of a 49-year-old female patient with a ten-year history of headaches, whose elder sister had been diagnosed with NIID one year earlier through genetic testing and skin biopsy. Recently, the patient developed dizziness and vomiting. Although symptomatic treatment alleviated the vomiting, her dizziness progressively worsened. It was accompanied by lower limb weakness, gait instability, hallucinations, and abnormal sleep behaviors. Routine imaging and cerebrospinal fluid immunological and microbiological tests revealed no abnormalities. Genetic analysis detected a 130-repeat expansion in the NOTCH2NLC gene, and skin biopsy confirmed the presence of intranuclear inclusions, establishing the NIID diagnosis. However, during hospitalization, the patient's bilateral lower limb tremors, hallucinations, and abnormal sleep behaviors suggested a possible acute encephalitic process. Subsequent serum testing identified positive CASPR2 antibodies. Significant symptom improvement following treatment with immunoglobulins and steroids supported the diagnosis of coexisting acute anti-CASPR2 antibody encephalitis and NIID. This is the first reported case of such dual disease coexistence.