Intravenous methadone causes acute toxic and delayed inflammatory encephalopathy with persistent neurocognitive impairments

Repple J, Haessner S, Johnen A, Landmeyer NC, Schulte-Mecklenbeck A, Pawlitzki M, Wiendl H, {Meyer zu Hörste}} G

Abstract

BACKGROUND The mu-opioid agonist methadone is administered orally and used in opioid detoxification and in the treatment of moderate-to-severe pain. Acute oral methadone-use and -abuse have been associated with inflammatory and toxic central nervous system (CNS) damage in some cases and cognitive deficits can develop in long-term methadone users. In contrast, reports of intravenous methadone adverse effects are rare. CASE PRESENTATION Here, we report a patient who developed acute bilateral hearing loss, ataxia and paraparesis subsequently to intravenous methadone-abuse. While the patient gradually recovered from these deficits, widespread magnetic resonance imaging changes progressed and delayed-onset encephalopathy with signs of cortical dysfunction persisted. This was associated with changes in the composition of monocyte and natural killer cell subsets in the cerebrospinal fluid. CONCLUSION This case suggests a potential bi-phasic primary toxic and secondary inflammatory CNS damage induced by intravenous methadone.