Unusually Short Lucid Interval with Delayed Post-hypoxic Leukoencephalopathy: A Case Report

Case Diagnosis: Delayed post-hypoxic leukoencephalopathy secondary to drug overdose

Case Description or Program Description: A 25-year-old female with history of mood disorder, autoimmune thyroiditis, and multisubstance abuse became altered after inhaling fentanyl. Paramedics found her obtunded with normal respirations despite 4 naloxone doses. In the emergency department, she had a Glasgow Coma Scale of 7 and dystonic posturing. Computed tomography (CT) head and angiography were unremarkable. After 3 hours, she improved to follow commands and converse. Urine drug screen was positive for cannabinoids, benzodiazepines, and opiates. Initial workup ruled out electrolyte abnormalities, hypoglycemia, and other toxins (e.g., carbon monoxide, ammonia). By day 1, she recovered to baseline except for slowed speech and fatigue. Magnetic resonance imaging (MRI) showed Fluid-Attenuated Inversion Recovery (FLAIR) hyperintensities in bilateral caudate nuclei. On day 5, she awoke unable to follow commands with new decerebrate posturing and akinetic mutism.

Setting: Tertiary care hospital

Assessment/Results: Repeat CT head showed mild cerebral edema from increased sulcal effacement. Multiple electroencephalograms suggested encephalopathy with diffuse beta frequency activity. MRI brain on day 6 showed new FLAIR signal with corresponding restrictive diffusion in bilateral striata and cortex suggestiing hypoxic ischemic injury. Extensive infectious disease and autoimmune workup were only consistent with patient’s known autoimmune thyroiditis. By day 14, MRI brain showed FLAIR signal progression and diffusion restriction involving the splenium, bilateral precentral, parietal, and occipital gyri, and putamen. By 3 weeks, she remained minimally conscious minus, so amantadine was initiated prior to discharge.

Discussion (relevance): This is a unique case of delayed post-hypoxic leukoencephalopathy (DPHL) after drug overdose with a short lucid interval of 4 days. DPHL diagnosis is based on clinical features of parkinsonism or akinetic-mutism, a lucid interval of 7 to 21 days, pathognomonic MRI T2 hyperintensities of cerebral white matter and some deep grey matter structures, and negative other encephalopathy workup.

Conclusions: DPHL is a rare consequence of drug overdose.