An 82-year-old man presented to the emergency department of our hospital with a 6-month history of progressive personality change characterized by increasing irritability, aggressive outbursts, poor self-care, repetitive facial grimacing, and diminished insight. Because of his rapid decline from a normal cognitive baseline to loss of functional independence, acute hospitalization of the patient was arranged. Examination revealed disinhibition, intermittent speech arrest, and stereotyped facial movements. The Mini-Mental State Examination (MMSE) score was 27 of 30 (with mild deficits in orientation and calculation only and 3/3 on testing recall). His Frontal Assessment Battery score (FAB) was 11 of 18 with deficits in mental flexibility, motor programming, and inhibitory control. The FAB is a bedside cognitive and behavioral battery (maximum possible score, 18) consisting of 6 subtests assessing conceptualization, mental flexibility, motor programming, resistance to interference, inhibitory control, and environmental autonomy; subjects without frontal lobe dysfunction typically score 17 or 18.10 A neurodegenerative process causing frontal lobe dysfunction was initially suspected. Magnetic resonance imaging showed age-appropriate generalized atrophy only. Electroencephalography demonstrated continuous frontal slow-wave activity but no epileptiform changes despite ongoing facial movements. A facial electromyogram demonstrated no evidence of peripheral nerve hyperexcitability. Cerebrospinal fluid (CSF) was acellular but with an elevated protein level of 1316 mg/L. Serum VGKC-Ab titer was markedly elevated at 2624 pM (normal range, < 100 pM). Blood work revealed SIADH with a serum sodium level of 123 mEq/L (the conversion to millimoles per liter is 1-to-1), and subsequent testing did not reveal any alternative cause for this. Test results for paraneoplastic and thyroid autoantibodies and vasculitic markers were negative. An [18F]-fluorodeoxyglucose positron emission tomographic (FDG-PET) image of the brain (Figure) demonstrated bilateral frontal hypometabolism. Whole-body FDG-PET was negative for malignancy. A diagnosis of VGKC-Ab–associated encephalopathy with a disinhibited, dysexecutive presentation was made. Treatment consisted of prednisolone 70 mg (1 mg/kg) daily and subsequent taper. A treatment benefit was noted after 3 weeks, and within 6 weeks the behavioral syndrome, aphasia, and facial grimacing had improved to the extent that the patient was discharged to his own home, where further improvements took place. After 6 months of treatment, the MMSE score was 29 of 30, FAB score was 17 of 18, SIADH had resolved, and VGKC-Ab titer had fallen into the normal range. At this point, the patient was taking 20-mg prednisolone by mouth daily and had resumed all his premorbid self-care, household activities, and outdoors activities, including going to the grocery store and to church.