Abstract

The aberrant GGC repeat expansion in the 5′-untranslated region of the NOTCH2NLC gene causes neuronal intranuclear inclusion disease (NIID), a progressive neurodegenerative disorder. The clinical features of NIID are highly variable and include cognitive dysfunction, peripheral neuropathy, and episodic neurogenic symptoms. The pathogenesis of episodic symptoms in NIIDs remains unknown, and histopathological studies are limited. Here, we report an autopsy case of NIID in a 32-year-old Japanese female who developed severe episodic symptoms, including hemiplegic migraine, seizures, and impaired consciousness. Her major episodic symptoms appeared at the age of 16 years and were accompanied by alternating brain edema. She developed severe episodic symptoms with right brain edema at the age of 31. She became bedridden due to irreversible brain lesions and died 1 year later from a catheter-related bloodstream infection. Neuropathological analyses revealed numerous neuronal intranuclear inclusions and white matter lesions. In addition, bizarre astrocytes with eosinophilic cytoplasmic or intranuclear inclusions were observed. GFAP immunoreactivity in the bizarre astrocytes was diminished, AQP4 showed a disorganized distribution. The histological changes observed in this case suggest an association between non-neuronal cellular disturbances and episodic neurogenic symptoms in NIIDs.

Author Details

Authors

• Kaoru Yagita¹
• Kyoko Kanazawa²
• Terunori Sano^{1, 3}
• Kunio Toda⁴
• Yuji Nakayma⁵
• Risa Kagaya⁶
• Noriko Sato⁶
• Yuji Takahashi²
• Masaki Takao¹,³

Departments

• ¹ Neuripathology Division, Department of Laboratory Medicine,
• ² Department of Neurology,
• ³ Department of Internal Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo,
• ⁴ Department of Neurology, Shin-Matsudo-Chuo-Sogo Hospital, Chiba,
• ⁵ Department of Pathology, Keio University School of Medicine, and
• ⁶ Department of Radiology, National Center of Neurology and Psychiatry, Tokyo, Japan

Address

Masaki Takao, MD, PhD
Department of Laboratory Medicine
National Center Hospital
National Center of Neurology and Psychiatry
Tokyo, Japan
Email: [email protected]

Citation