Acute Toxic Leukoencephalopathy Due to use of Tramadol, Diagnosis, and Treatment

Sir, Acute toxic leukoencephalopathy (TLE) is a rare neurological diagnosis presented with multiple medications, including opioids, in less than 8% of patients.[1] Cases have been reported with morphine, methadone, buprenorphine, heroin, and oxycodone,[2] but there are no reports with atypical tramadol-type opioids. It has diverse clinical presentations related to the severity of imaging changes on magnetic resonance images (MRI) or computed tomography (CT).[1] This case is the first documented report, which creates a basis for future research and vigilance of toxicity with this drug type. This case presents a 26-year-old male patient who ingested an entire bottle of tramadol (1000 mg) while being tattooed. After this consumption, he became somnolent and suffered a generalized seizure associated with moderate head trauma and emesis. He arrived at the emergency department of a national university hospital with an altered state of consciousness, miotic pupils, and respiratory distress, without mobility of limbs or sphincter control. Treatment was initiated with fluid resuscitation, vasopressor support, orotracheal intubation, administration of naloxone, and transfer to the intensive care unit (ICU). Brain CT scan revealed multiple intraparenchymal hemorrhagic contusions in the left frontal and temporal lobes and biparietal region, probably related to cranioencephalic trauma. Due to the image findings, the neurosurgery department considered that the patient was not a candidate for surgical intervention and was left under neurological observation in the ICU. After 3 weeks of hospitalization in the ICU, the neurological state remained stationary with deteriorated consciousness and abnormal movements, with difficult wind out of mechanical ventilation. Therefore, the neurology department requested a brain MRI, which reported diffuse hyperintensities of the bilateral white matter and subcortical hemorrhages related to acute TLE associated with opioid intake [Figure 1]. It was considered in the multidisciplinary team of management that these findings explained the patient's neurological state. During the ICU observation, multiple complications appeared, including pneumonitis secondary to bronchial aspiration, acute renal failure after rhabdomyolysis related to the seizures, and several systemic infections, which prolonged the ICU stay. Since the transfer to the ICU, the patient was assessed by the physical medicine and rehabilitation department, which initiated early neurological rehabilitation to improve functionality and reduce complications secondary to prolonged bedridden through positioning orthoses and interventions by physical therapy, occupational therapy, and phonoaudiology.Figure 1: Cranial CT findings: (a) trasversal cut; (b) coronal cut; (c) sagital cutAfter 30 days in the ICU, it was possible to wind out mechanical ventilation support, and the patient was transferred to general hospitalization. During the follow-up, neurological sequelae were found secondary to the cortical injury and the prolonged stay in the ICU, including muscular atrophy, quadriplegia, and dysphagia. A progressive strength recovery was obtained through the neurorehabilitation process, especially in the upper right limb, which facilitated palmar grasping. After 59 days of hospitalization, the patient was discharged to a home care plan, with outpatient follow-up by psychiatry, psychology, neurology, and physical medicine and rehabilitation to define changes in rehabilitation goals, the need for mobility assistance devices, and the necessary adjustments in their home and social environment to guarantee comprehensive and multidisciplinary care in this complex clinical scenery. TLE is a rare neurological entity that affects brain white matter due to exposure to a neurotoxic agent.[2] Different drugs and substances such as chemotherapeutics, immunosuppressants, opioids, environmental agents, and cocaine have been associated with this syndrome.[3] The clinical presentation is diverse in symptoms and severity, including altered mental and psychomotor status, anxiety, visual deficit, and in more severe cases, coma and death[4] [Table 1].Table 1: Clinical and imaging findings according to severityAccording to the clinical severity, reversible and nonreversible changes are found in the brain. In addition, there may be an increase in intracerebral pressure, acute hydrocephalus, and herniation, which, if not intervened, might lead to neurological sequelae.[2] Diagnostic images are essential to confirm the diagnosis and propose treatment in the emergency services. MRI is the image of choice, in which symmetric and diffuse hyperintensity of white matter in T2 are found.[1-3] CT scan shows diffuse hypodensities of white matter and areas of necrosis in severe cases with normal scans in milder ones; it might be an option in hospitals that do not have MRI[3] [Table 1]. Opioids are a rare cause, but adverse events have risen with the worldwide increase of recreational use and dependence.[5] These drugs represent around 8% of the cases, with reports with morphine, oxycodone, methadone, heroin, and buprenorphine.[1] Tramadol is an atypical opioid with action on MU opioid receptors and inhibits serotonin and norepinephrine reuptake.[6] It is an excellent therapeutic option in moderate pain, but in high doses generates all systemic and neurological complications of other opioid drugs.[7] This case is the first report of TLE in the literature related to tramadol; previous cases of toxicity reported convulsive symptoms and reversible serotonergic manifestations, with infrequent changes on MRI.[8] These new findings incentivize clinicians to search for a broader set of signs, symptoms, and imaging findings in patients with tramadol overdose. The importance of multidisciplinary care is also highlighted in this case, in which a team of neurologists, physiatrists, neurosurgeons, and intensivists helps to improve functional and clinical outcomes. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.