Delayed Post-Hypoxic Leukoencephalopathy: Case Report with a Review of Disease Pathophysiology
A 43 year old female with chronic back pain developed depression and attempted suicide with an overdose of diazepam and methadone after an argument with her husband in the evening. She intentionally consumed approximately 40 to 50 tablets of diazepam at 5 mg strength as well as an unknown quantity of methadone tablets was found the following day in an unresponsive state with a respiratory state of only 4 breaths per minute but was revived at a local hospital with the use of naloxone. Although she could awaken and answer questions appropriately, this was only transient and required a naloxone drip infusion over 24 hours; no flumazenil had been used. Her potassium was also elevated initially at 7.6 that later normalized and had a leukocytosis secondary to mild aspiration pneumonia that was successfully treated with antibiotics. She was discharged within one week in a much improved state to a psychiatric facility. After two days as in-patient for psychiatric care, she was discharged to home in a markedly improved state with a mental status that was back to her baseline and fully able to be self-sufficient without any cognitive deficits. Interview with family and friends confirmed that she was cognitively normal and fine up until 3 weeks after the event when she abruptly changed midday and seemed confused and forgetful with a rapid worsening the following day. She was first noted not be able to play cards with her family, had developed social withdrawal with a lack of personal hygiene, and became incontinent as well. She appeared very lethargic and not very interactive. After this continued for approximately 5 days without any improvement, she was evaluated at the Emergency Dept. and admitted after a CT head exam disclosed marked and diffuse hypointensity throughout the subcortical white matter (). This was later evaluated by MRI as being a confluent change throughout the entire white matter, and appeared diffusely hyperintense on both FLAIR and T2 weighted sequences (), with hyper-intensity also noted on diffusion weighted imaging. The unusual feature though was that the cerebellar white mater had been spared, and that the change was a strictly supratentorial effect () without altering signal intensity for the white matter tracts in the internal capsule and brain stem area. Using large voxels placed over the semi-centrum ovale, MR spectroscopic analysis at 1.5 Tesla showed elevated abnormal elevations in the choline and creatinine peaks with a small peak seen for lactic acid as well (). Neurological exam revealed a blunted flat affect with abnormally slow gait and left side neglect, with disorientation and very poor short term recall. As the patient had a detectable benzodiazepine level at approximately 83 ng/mL, 1.0 mg flumazenil was given in 0.2 mg increments every 30 seconds during EEG monitoring. Although background slowing improved slightly, there was a clear and definite transient neurological improvement. Serum benzodiazepine levels continued to decline from 67.9 to 32.8 ng/mL over 4 days, with modest clinical improvement in her mental status also observed. Follow-up evaluation revealed substantial improvement both clinically and radiographically, with a normal mental status and normal MR imaging of the brain within one year of the event, with normal metabolism of both the gray and white matter of the brain, as assessed by 18F-FDG PET imaging ().