Malignant Cerebellar Edema Subsequent to Accidental Prescription Opioid Intoxication in Children

Abstract

We present two recent cases of toddlers who developed malignant cerebellar edema subsequent to accidental ingestion of prescription opioids. Both children presented acute neurological decline, hydrocephalus, and tonsillar herniation requiring emergent ventricular drain placement, suboccipital craniectomy, and partial cerebellectomy. Together with several other reports, these cases suggest the existence of an uncommon yet severe syndrome of acute opioid-induced malignant cerebellar edema. We hypothesize that the condition results from a combination of primary opioid receptor-mediated changes in neuronal metabolism that are exacerbated by secondary hypoxic insult. If recognized promptly, this syndrome can be treated with emergent neurosurgical intervention with good clinical outcomes. These cases also illustrate the unintended consequences and innocent victims of the spiraling prescription opioid epidemic, which will likely increase in prevalence. Recognition of this syndrome by clinicians is thus critical.

Opioid-induced toxic leukoencephalopathy: A case report and review of the literature

“…There are also patients in the literature who received only supportive care, such as the patient described by Nanan et al [12] who had similar neurologic outcomes to our patient with significant impairment. That is in contrast to Reisner et al [3], Mills et al [8], and Duran et al, [13] who also illustrated similar neurologic outcomes after undergoing more invasive neurosurgical interventions with decompressive craniotomy, and in once case cerebellectomy. Devastating neurologic outcomes or death, as described by Krinsky and Reischard et al [2], Shrot et al [5], Riascos et al [9], and Metkees et al [10], and are also described, and hoped to be mitigated by early neuro-surgical interventions as were undertaken with our patient.…”

“…There is a paucity of literature describing varying degrees of multi-organ involvement and neurologic sequelae secondary to opiate ingestion. Although children who presented with low GCS with toxic leukoencephalopathy who recovered with mild or no neurologic deficits have been described [6, 11, 12, 13, 14, 15], we believe that these patients likely presented earlier after ingestion. Earlier access to supportive care in these cases likely lessened the effects of more sustained hypoxic injury that led to worse neurologic injury and multi-organ injury in our patient.…”

“…Hyperosmolar therapies [6, 7], corticosteroids [3, 6, 8] and vasoactive infusions [6, 8, 9, 10] to maintain cerebral perfusion pressure have all been reported. Naloxone is also frequently administered [6, 7, 10, 11, 12, 13]. Surgical procedures are targeted at attenuating increased intracranial pressure [3].…”

“…Cerebellar edema, causing narrowing of 4 th ventricle, mass effect on brainstem, and mild acute hydrocephalusExternal ventricular drain transitioned to a ventriculoperitoneal shuntSuboccipital craniectomyC1 laminectomyDecompression and removal of herniated cerebellar tissue and surrounding tonsilsPersistent gross motor delayNonambulatoryProfound visual impairment with eventual recovery of tracking and discrimination18 MonthsMetkees et al (2015) [10]15 y (F)MethadoneUnconscious GCS3 miosisDiffuse nonenhancingT2 hyperintensities and restricted diffusion in the white matter of both hemispheresIntubation, inotropic support, supportive careDeathNARando et al (2016) [15]14 (M)MethadoneUnresponsiveLow attenuation in the cerebellum with no evidence of increased ICPSupportive CareAtaxia and weakness that was improving slightly at the time of dischargeNAHosseini et al (2016) [11]2y (F)OpiumUnresponsiveBilateral cerebellar white matter involvementHigh does methylprednisoloneNo residual neurologic impairment2 monthsDuran et al (2017) [13]10m (F)OxycodoneUnresponsive, slow labored breathing leading to respiratory failureSevere, bilateral cerebellar hypoattenuation with ventral displacement of the cerebellar vermis and compression of the fourth ventricles.External ventricular drain, suboccipital craniectomy, C1 laminectomy. Partial resection of cerebellumMild spasticity and internal rotation of her left leg with gait and occasional dystonic posturing of the left upper extremity.23 monthsDuran et al (2017) [13]25 m (M)Extended Release MorphineErratic breathing progressing to apnea and respiratory arrestAcute hydrocephalus and extensive, symmetric bilateral cerebellar hemispheric hypoattenuationExternal ventricular drain, suboccipital craniectomy, and C1 laminectomy with partial resection of cerebellumWide based gait and mild left lower extremity spasticity3 monthsShrot et al (2017) [5]16HeroinAltered mental status, rhabdomyolysisDiffuse symmetrical infratentorial and supratentorial white matter T2 hyperintensities on MRIUnknownPersistent vegetative stateN/AWheaton et al (2019)4 (M)OxycodoneComatose, multi-organ failureGCS 4Cerebellar edema with diffuse white matter hypodensity sparing infratentorial regions. Diffuse T2 hyperintensity of cerebral white matter, ventriculomegaly, brainstem compressionAggressive pharmacological management with induced comaSuboccipital craniectomy, c1 laminectomy, EVD…”

Lesson of the month: Oxycodone-induced leukoencephalopathy: a rare diagnosis

“…To the authors' knowledge, there are nine such cases reported in the literature (summarised in Table 1). 2,[6][7][8][9][10][11] These patients presented with varying symptoms. With opiate prescriptions on the rise, it is imperative to be aware of this clinical condition.…”