Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis

Neuronal intranuclear inclusion disease (NIID) is a rare autosomal-dominant, progressive neurodegenerative condition 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 10-y...

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Main Authors: Wan Zhu, Tiansi Liu, Xinran Yu, Min Peng, Jinghan Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1650420/full
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author Wan Zhu
Tiansi Liu
Tiansi Liu
Xinran Yu
Min Peng
Min Peng
Jinghan Hu
Jinghan Hu
author_facet Wan Zhu
Tiansi Liu
Tiansi Liu
Xinran Yu
Min Peng
Min Peng
Jinghan Hu
Jinghan Hu
author_sort Wan Zhu
collection DOAJ
description Neuronal intranuclear inclusion disease (NIID) is a rare autosomal-dominant, progressive neurodegenerative condition 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 10-year history of headaches, whose older sister had been diagnosed with NIID 1 year earlier through genetic testing and a skin biopsy. Recently, the patient developed dizziness and vomiting. Although symptomatic treatment reduced incidents of 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 revealed 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 detected positive anti-contactin-associated protein-like 2 (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 dual disease coexistence.
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publisher Frontiers Media S.A.
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spelling doaj-art-f82ec633f6c04523a40efcc4903394c62025-08-26T04:13:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16504201650420Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitisWan Zhu0Tiansi Liu1Tiansi Liu2Xinran Yu3Min Peng4Min Peng5Jinghan Hu6Jinghan Hu7Kunming University of Science and Technology, Affiliated Hospital, People’s Hospital of Wenshan Prefecture, Department of Radiology, Wenshan, ChinaKunming University of Science and Technology, Affiliated Hospital, People’s Hospital of Wenshan Prefecture, Department of Neurology, Wenshan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaKunming University of Science and Technology, Affiliated Hospital, People’s Hospital of Wenshan Prefecture, Department of Radiology, Wenshan, ChinaKunming University of Science and Technology, Affiliated Hospital, People’s Hospital of Wenshan Prefecture, Department of Neurology, Wenshan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaKunming University of Science and Technology, Affiliated Hospital, People’s Hospital of Wenshan Prefecture, Department of Neurology, Wenshan, ChinaThe Affiliated Hospital of Kunming University of Science and Technology, Kunming, ChinaNeuronal intranuclear inclusion disease (NIID) is a rare autosomal-dominant, progressive neurodegenerative condition 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 10-year history of headaches, whose older sister had been diagnosed with NIID 1 year earlier through genetic testing and a skin biopsy. Recently, the patient developed dizziness and vomiting. Although symptomatic treatment reduced incidents of 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 revealed 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 detected positive anti-contactin-associated protein-like 2 (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 dual disease coexistence.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1650420/fullanti-CASPR2 antibody encephalitisautoimmune encephalitisMorvan syndromeneuronal intranuclear inclusion diseaseNOTCH2NLC
spellingShingle Wan Zhu
Tiansi Liu
Tiansi Liu
Xinran Yu
Min Peng
Min Peng
Jinghan Hu
Jinghan Hu
Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
Frontiers in Immunology
anti-CASPR2 antibody encephalitis
autoimmune encephalitis
Morvan syndrome
neuronal intranuclear inclusion disease
NOTCH2NLC
title Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
title_full Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
title_fullStr Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
title_full_unstemmed Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
title_short Dual diagnosis at the neuro-immune interface: a case report of neuronal intranuclear inclusion disease with acute anti-CASPR2 encephalitis
title_sort dual diagnosis at the neuro immune interface a case report of neuronal intranuclear inclusion disease with acute anti caspr2 encephalitis
topic anti-CASPR2 antibody encephalitis
autoimmune encephalitis
Morvan syndrome
neuronal intranuclear inclusion disease
NOTCH2NLC
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1650420/full
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