CHANTER Syndrome—Fentanyl and Cocaine Use Meets Neurotoxic Edema

A 26-year-old female with a history of bilateral anterior communicating artery stroke without residual deficits and polysubstance use presented to the ED with three days of altered mental status, weakness, and decreased sensation in her extremities. Naloxone partially improved her arousal, but motor and sensory deficits persisted. The patient reported smoking marijuana and taking illicit alprazolam. Exam findings included somnolence, intact sensation, and mild left lower extremity weakness. Urine drug screen (UDS) was positive for cannabinoids, benzodiazepines, fentanyl, and cocaine. Computed tomography (CT) head showed hypoattenuation of the cerebellar white matter with indeterminate loss of gray-white matter differentiation. Subsequent MRI showed atypical restricted diffusion in the splenium of the corpus callosum and right posterior frontal corona radiata, effacement of the 4th ventricle and suprasellar cistern, and low-lying cerebellar tonsils. A neurology consult was obtained.

The neurology consultant ultimately diagnosed the patient with cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome.

Discussion

First described in a 2019 case series,¹ CHANTER syndrome is a novel disease characterized by altered mental status along with transient cytotoxic edema of the hippocampus, cerebellum, and basal ganglia in the setting of opioid and/or cocaine use.² There is a strong association between this disease process and opioid use, possibly specific to fentanyl use potentiated by cocaine use.^1,4,6,^9,10 The rise in reported CHANTER syndrome may be due to greater awareness of this condition or due to the rising contamination of illicit drugs with fentanyl.

Post-mortem analysis of heroin users with CHANTER syndrome demonstrates hippocampal Purkinje cell loss and astroglial reactivity representative of hypoxic and neurotoxic effects;⁶ this is thought to be caused by mitochondrial or metabolic failure of neurons.¹ The relative hypoxia induced by respiratory depression with opioid use may incite this.¹Cocaine may potentiate this process by inciting neuro-inflammation and cytotoxic edema, decreasing metabolic delivery through vasoconstriction, and exposing endothelial cells to oxidative stress.⁷ Further studies are needed to fully understand the pathophysiology behind this disease process and to assess the confounding factors that impact disease progression and patient outcomes.

CHANTER syndrome presents with altered mental status, decreased level of consciousness, or neuropsychiatric symptoms in the setting of opioid use and/or cocaine use.^1,8 This condition can be difficult to diagnose clinically since these manifestations can look very similar to opioid intoxication. Failure of a patient’s mental status to return to baseline after naloxone administration or focal neurologic deficits in the absence of an alternate explanation should prompt emergency physicians to obtain neuroimaging.

The diagnosis of CHANTER syndrome requires a high degree of suspicion based on a clinical history of opioid use disorder (particularly fentanyl use), potentially with concomitant cocaine use disorder.^3–5 Since these patients present with altered mentation, it is critical for the emergency physician to obtain a collateral history from family, friends, or bystanders. UDS may support the history but has high false negative rates for fentanyl use.⁹

On CT scan, CHANTER syndrome presents with edema in the cerebellum, basal ganglia, and hippocampi. If the cerebellar edema is severe, ventriculomegaly secondary to obstructive hydrocephalus may be noted.¹⁰ MRI further characterizes this disease with demonstration of diffusion restriction in the gray matter of the aforementioned structures.¹The distinct imaging pattern differentiates CHANTER from other possible causes of toxidromes such as pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE) syndrome,¹⁰ heroin-associated spongiform leukoencephalopathy, opioid-associated amnestic syndrome, stroke, metabolic leukoencephalopathies and most commonly posterior reversible encephalopathy syndrome (PRES).^1,11 PRES can also cause edema and mass effect in the posterior fossa, but unlike CHANTER syndrome, usually impacts the white matter rather than the cortex.¹ POUNCE syndrome can look remarkably similar clinically and on imaging to CHANTER syndrome, but edema is isolated to the cerebellum and does not involve the basal nuclei or hippocampi.¹⁰

Management includes airway protection while decreasing intracranial pressure with osmotic agents such as hypertonic saline and mannitol. In patients with obstructive hydrocephalus, neurosurgical intervention via external ventricular drain (EVD) to relieve intracranial pressure may be necessary.^1,10,11 One case report describes the use of hyperbaric oxygen therapy for the treatment of CHANTER syndrome,⁸ but more data are needed.

In a case series of six patients, five patients required intubation and mechanical ventilation, and three required EVD for cerebrospinal fluid (CSF) diversion due to obstructive hydrocephalus.¹ CHANTER syndrome is associated with a wide range of outcomes, from full recovery^12,13 to severe morbidity and death.^1,11 It appears that early diagnosis and treatment are associated with improved outcomes whereas more severe and bilateral imaging findings of cytotoxic edema are a poor prognostic indicator.¹¹

Case Resolution

The patient was admitted to the Neurology and Neurosurgery ICU for further management. During her hospital stay, she had one brief generalized tonic-clonic seizure, which self-aborted. Her mental status improved over a week with supportive care and she was discharged to a skilled nursing facility with a prescription for levetiracetam and follow-up in the neurology clinic.

Conclusion

CHANTER syndrome is a rare condition consisting of cytotoxic edema of the cerebellum, hippocampus, and basal nuclei that may occur in patients who use opioids and/or cocaine, which can be fatal. Clinicians should suspect this diagnosis in patients who present with an altered level of consciousness that does not resolve with naloxone and should pursue further imaging via CT brain and possibly MRI. Substance use history and UDS analysis can be helpful for early diagnosis and management. Treatment in the ED involves airway protection and reducing cerebral edema while engaging neurology and neurosurgery early.

Dr. Johnson is an Emergency Medicine Resident at Washington University in St. Louis, St. Louis, MO@LashaundaJ_MD

Dr. Ickes is and inpatient addiction medicine and emergency medicine physician at the Department of Emergency Medicine and Psychiatry in Virginia Tech Carilion, Roanoke, VA.

Dr. Pelletier is an assistant professor of emergency medicine and assistant residency program director at the University of Missouri-Columbia in Columbia, MO. @dr.jnpelletier (Instagram), @jessicanpelletierdo (LinkedIn)

References

CHANTER Syndrome—Fentanyl and Cocaine Use Meets Neurotoxic Edema

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