Case Presentation: Mr. B, a 72-year-old male with a history of polysubstance use and hypertension, presented to the ED with altered mental status, unresponsive to naloxone. Vital signs were stable (BP 104/62), but he exhibited impaired repetition and naming, bilateral tremors, and weakness of the left wrist and hand. Urine toxicology was positive for cocaine. Given an unknown last known well, a code stroke was activated.

CT head and angiogram revealed no acute intracranial abnormalities. However, MRI demonstrated restricted diffusion involving the bilateral cerebellar hemispheres, basal ganglia, and hippocampi.

Based on the imaging and confirmed cocaine use, the patient was diagnosed with CHANTER syndrome (Cerebellar, Hippocampal, and Basal Nuclei Transient Edema with Restricted Diffusion): a recently described toxidrome associated with cocaine and opioid use.

Pathophysiology: Cocaine-induced neurotoxicity may result from elevated synaptic dopamine levels, which upregulate the production of reactive oxygen species, causing oxidative stress and neuronal injury. Furthermore, cocaine and opioids can induce mitochondrial dysfunction, particularly in metabolically active gray matter structures. OPRM1 gene polymorphisms may additionally play a role in CHANTER pathogenesis.

Clinical and Radiologic Features: Patients typically present with encephalopathy, accompanied by MRI findings of restricted diffusion and edema localized to the cerebellum, hippocampi, and basal ganglia. Importantly, CHANTER primarily affects gray matter structures, differentiating it from posterior reversible encephalopathy syndrome and heroin-associated spongiform leukoencephalopathy, which involve white matter.

Management and Prognosis: Management of CHANTER is supportive, with interventions managing complications like cerebral edema and hydrocephalus. Prognosis is variable, ranging from full recovery to persistent cognitive deficits or death. Imaging abnormalities may resolve within several weeks, highlighting the importance of early recognition and supportive care.

CHANTER is a newly recognized toxidrome that may cause persistent neurologic deficits. Additional research is needed to better characterize its epidemiology, substance-specific risk factors, clinical course, and potential therapeutic interventions.