Case Report: Severe Encephalopathy with Reversible White Matter Changes After Gabapentin and Morphine Use: A Toxic-Metabolic Mimic of ADEM

Severe encephalopathy with reversible white matter changes following gabapentin and morphine use is a rare phenomenon, and even more unusual when it presents with magnetic resonance imaging (MRI) findings resembling acute disseminated encephalomyelitis (ADEM). We report the case of a 56-year-old woman who presented with coma after self-administering a high dose of gabapentin (3600 mg/day) and receiving an intramuscular dose of morphine (unknown amount) for radicular pain. On admission, the patient exhibited profound central nervous system depression accompanied by hypoglycemia, rhabdomyolysis, transaminitis, and acute kidney injury, consistent with systemic toxicity. Despite correction of metabolic disturbances and administration of naloxone, the coma persisted. This may be explained by the accumulation of neurotoxic opioid metabolites, such as morphine-3-glucuronide (M3G), particularly in the context of impaired renal function. Initial MRI demonstrated bilateral watershed infarcts, while repeat imaging revealed diffuse white matter hyperintensities not typical of ischemia. Cerebrospinal fluid (CSF) analysis showed elevated protein and lactate without pleocytosis, and extensive infectious and autoimmune investigations were negative. The clinical and radiologic course was most consistent with toxic-metabolic encephalopathy with secondary reversible leukoencephalopathy mimicking demyelination. The patient was treated with corticosteroids and gradually improved, with near-complete radiological resolution on follow-up imaging. Conclusions: This case highlights the diagnostic challenge of differentiating toxic-metabolic encephalopathy from inflammatory demyelinating disorders in adults. The clinical presentation, laboratory abnormalities, and temporal relationship to drug exposure strongly support a primary toxic-metabolic etiology related to combined gabapentin and morphine use. Although corticosteroids were administered, their independent therapeutic effect remains uncertain and may reflect the natural course of drug clearance. Clinicians should recognize that severe drug-induced neurotoxicity can mimic demyelinating disease and should be considered a leading diagnosis in similar presentations.