Kratom Neurotoxicity

Background:

• Kratom (Mitragyna speciosa) is an over-the-counter, herbal, opioid-like substance with stimulant properties at lower doses and analgesic properties at higher doses that is not currently regulated by the US Food and Drug Administration.
• In 2018–2019, it was estimated to be used by 0.8% of the adult US population.
• There are no standardized assays to detect kratom on drug screening.
• Kratom stimulates µ opioid receptors and is more potent than morphine, oftentimes used as an opiate withdrawal agent.
• Long-term misuse of kratom may present with nonfocal neuropathies, seizures, hepatotoxicity, and rhabdomyolysis.

Clinical Presentation:

• Presenting symptoms reported in the literature include nondermatomal sensory and motor neuropathies, ataxia, seizures, hepatotoxicity, and rhabdomyolysis.
• Symptoms are more frequent and severe with higher doses of kratom abuse and typically gradually improve following cessation.
• Kratom has been demonstrated to cross the placenta leading to fetal death or postnatal withdrawal.

Key Diagnostic Features:

• On MRI of the brain, kratom abuse typically presents with symmetric T1 signal hyperintensity involving the globi pallidi, subthalamic nuclei, and cerebral peduncles.
• These signal changes have been shown to resolve following cessation of kratom use.

Differential Diagnoses:

• Chronic liver disease: The hepatobiliary system is responsible for excretion of copper and manganese, which can pathologically accumulate in the setting of chronic liver disease. This patient’s laboratory analysis demonstrated normal hepatic function.
• Wilson disease: Abnormal copper accumulation in this disease can deposit in the basal ganglia and result in T1 signal hyperintensity. T2 signal hyperintensity involving the putamina is also often seen, unlike this case.
• Total parenteral nutrition: These patients are at risk for manganese deposition in the basal ganglia, which can render an identical imaging appearance to this case.
• Gadolinium deposition: Recurrent exposure to gadolinium-based contrast agents has been associated with progressive T1 signal hyperintensity in the globi pallidi, thalami, pons, and dentate nuclei. This patient had no history of prior gadolinium administration.

Treatment:

• Patients should be screened for concomitant metabolic derangements such as electrolyte abnormalities and liver and kidney dysfunction.
• Cessation of kratom consumption should be encouraged.
• Careful monitoring of and treatment for withdrawal symptoms is important, particularly in those seriously abusing the substance.