Delayed Leukoencephalopathy: Three Case Reports and a Literature Review

Abstract

Background: Delayed leukoencephalopathy (DL) is a rare entity associated with cerebral hypoxia and heroin consumption. We describe the clinical course of three cases of DL due to non-heroin drug use. Material and methods:We describe the cases of three DL patients admitted to our hospital in 2012. Discussion: These cases contribute to the aetiological spectrum of DL since multifactorial causes could account for the clinical symptoms. LEARNING POINTS• Substances toxic to the CNS can damage the CNS directly (direct toxicity) or by depressing the respiratory centre (cerebral hypoxia).• As clinical manifestations can appear after a time lag, we recommend a period of initial monitoring.• Histological and radiological findings can contribute to better understanding of the pathophysiological mechanisms and causes involved. KEYWORDS delayed leukoencephalopathy, globus pallidus, methadone BACKGROUND Delayed leukoencephalopathy (DL) is caused by structural injury to the white matter of the central nervous system (CNS), with a characteristic two-phase clinical course: recovery from an episode of low level of awareness, caused by acute or chronic neurological damage, is followed by neuropsychiatric symptoms which include cognitive and level of consciousness disorders, behavioural disorders and dysautonomy. The disorder is associated with parkinsonism when grey matter basal nuclei are involved

Methadone-induced encephalopathy: a case series and literature review

“…To date, only 8 case reports evaluating 11 patients have been published reporting delayed-onset methadone-induced leukoencephalopathy [6,10,[16][17][18][19][20], summarized in Table 5. The most frequent imaging findings in case reports of patients with DOL is bilateral cerebral white matter T2 and FLAIR hyperintensity [6,8,9,16,18,20] followed by corpus callosum [9,16] and globus pallidus [8] involvement. This is in keeping with our observation of bilateral cerebral white matter hyperintensity.…”

“…Patients with persistent neurological deficits in their first admission were categorized to have AOE based on their MRI changes. Those who had been discharged after either complete or partial recovery from acute intoxication, but then deteriorated with neurological signs or symptoms within several days or weeks necessitating readmission were considered to have DOL [7][8][9]. The most prevalent delayed symptoms included psychotic delirium, fluctuating state of consciousness, depression, apathy, and bizarre behaviors [9][10][11][12][13].…”

“…AOE presents with MRI abnormalities within the first admission of the patient. DOL, however, manifests with abnormalities detected on MRI in patients who have initially responded to treatment (complete resolution of symptoms), but are then readmitted after a period of lucidity (usually days to weeks post the primary event) with neurological or psychiatric deterioration [7][8][9][10].…”

“…AOE is one of the severe neurologic complications of methadone intoxication, that has previously been associated with carbon monoxide and heroin toxicities [7,8]. To date, eight case reports have been published reporting AOE associated with methadone toxicity, ages ranging from 22month-old to 65 years old [1,4,5,[11][12][13][14][15][16].…”

“…Other case studies have reported a range of DOL symptoms, including disorientation, paranoid and bizarre behavior, and severe progressive cognitive decline with bilateral cerebral white matter hyperintensities. MRI changes in these case reports have included diffuse abnormal T2 and FLAIR signals in the corona radiate, centrum semiovale and subcortical white matter throughout all lobes, and signal abnormalities in temporomesial, substantia nigra, and basal ganglia [6,8,9,12,13,[17][18][19][20][21]. The aim of our study was to identify and describe the pattern of neurological deficits and associated brain magnetic resonance imaging (MRI) changes in methadone-poisoned patients.…”