Neuronal intranuclear inclusion disease with recurrent encephalitis

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by eosinophilic intranuclear inclusions in neurons and multiple visceral organs, leading to heterogeneous clinical manifestations. This case report presents two rare NIID patients with recurrent encephalitis-like episodes, periodic prolonged hospitalizations, mimicking mitochondrial encephalomyopathies.

The first patient was a 63-year-old man with a history of migraines, who experienced two episodes of acute fever, headache, motor aphasia, behavioral abnormalities, seizures, and stroke-like symptoms over a period of four years. Brain MRI revealed swelling in the temporo-occipital lobe. Cerebrospinal fluid analysis demonstrated elevated protein levels, while tests for autoimmune encephalitis antibodies and mitochondrial gene mutations were negative. The second patient was a 38-year-old man with a family history of consanguinity, who presented with recurrent episodes of fever, limb weakness, aphasia, and psychiatric disturbances, occurring numerous times over five years. A recent MRI showed swelling in the left temporo-occipital lobe, dot-like high signals in the right frontal-parietal-temporal lobe, and filamentous high signals at the corticomedullary junction. Genetic testing revealed 93 and 101 GGC repeats, respectively, in the 5' untranslated region (5' UTR) of the NOTCH2NLC gene, indicating abnormal expansion and confirming the diagnosis of NIID.

This report underscores the importance of recognizing NIID in patients with recurrent encephalitis-like presentations and highlights the diagnostic utility of genetic testing in distinguishing it from conditions like mitochondrial encephalopathies.