Neuronal intranuclear inclusion disease (NIID) exhibits diverse clinical phenotypes caused by the intronic repeat expansion of NOTCH2NLC. 1,2 An acute encephalopathic episode can manifest in some patients with NIID. 3,4 Herein, we report an NIID patient harboring a de novo {(GGA) n (GGC) n } n repeat expansion in NOTCH2NLC, who developed abrupt mitochondrial encephalomyopathy, lactic acidosis, and stroke-like (MELAS)-like episode in the 15-year course clinical diagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). Case report A 31-year-old woman developed slowly progressing muscle weakness and paresthesia in all extremities. Neurologic examination at 33 years of age revealed distal dominant muscle weakness with areflexia and abnormal deep sensations in all extremities without obvious cranial nerve involvement. A nerve-conduction study revealed sensorimotor polyneuropathy in all extremities (table e-1, links.lww.com/NXG/A335). Although clinical and electrophysiologic features met the diagnostic criteria for CIDP, 5 she showed limited response to immunotherapy. At 45 years, she abruptly started experiencing headaches, nausea, and eventually, loss of consciousness. Neurologic examination revealed left conjugate eye deviation, neck stiffness, and left hemiparesis. Blood analysis revealed an elevated blood lactate/pyruvate molar ratio (lactate: 2.1 mmol/L, pyruvate: 0.022 mmol/L, molar ratio: 91, normal range <25.8). Brain MRI showed abnormal hyperintensities in the right hemisphere on diffusion-weighted images (DWIs) (figure, A) and T2weighted images (figure, B), with gadolinium enhancement not corresponding to the vascular distribution. Hyperperfusion on arterial spin labelling (figure, C), dilation of the right cerebral artery (figure, D), and elevated lactate peak on magnetic resonance spectroscopy (MRS) (figure, E) in the involved areas were also identified. She was diagnosed with MELAS and was administered IV levetiracetam, edaravone, and oral taurine. She gradually improved without residual cognitive disturbances. Neither histopathologic studies nor whole mitochondrial genome sequence analysis on muscle biopsy showed any specific findings for mitochondrial disease. At 47 years of age, a follow-up neurologic examination revealed bilateral miosis with sluggish response to light. Brain MRI revealed both gray and white matter hyperintensities on T2-weighted images corresponding to acute encephalopathic lesions (figure, F and G). However, there was no abnormal corticomedullary hyperintensity on DWI. Abdominal skin biopsy performed at 47 years of age and re-examination of the sural nerve sample at 35 years resulted in NIID diagnosis, demonstrating eosinophilic intranuclear inclusions surrounded by a halo and antiubiquitin and p62-immunoreactive intranuclear inclusions in fibroblasts, sweat gland cells (figure, H),
