How a Common Antibiotic Nearly Hijacked a Coma Prognosis After Cardiac Arrest

In the high-stakes world of neurocritical care, few decisions carry as much weight as predicting whether a comatose patient will ever wake up after cardiac arrest. A remarkable case report published in the journal Neurocritical Care by a team at the University of Virginia School of Medicine now illustrates just how easily those predictions can go wrong when treatable neurotoxicity hides inside the clinical picture. The report follows a 42-year-old woman who survived a cardiac arrest, appeared destined for a devastating outcome based on myoclonic jerks and an unreactive brain, and then made a near-complete neurological recovery once her care team identified a surprising culprit: cefepime, one of the most widely used hospital antibiotics in the world.

The story began with an elective abdominal operation in a patient whose medical history was already extraordinarily complex. She carried a diagnosis of VACTERL association, a congenital syndrome involving vertebral defects, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies, and limb abnormalities, and she had undergone multiple reconstructive surgeries as well as treatment for advanced gynecologic cancer. The planned exploratory laparotomy included removal of both ovaries and fallopian tubes, lysis of adhesions, repair of a small bowel leak, and placement of a temporary ureteral stent. For eight days her recovery proceeded uneventfully. Then, during a failed attempt to place a nasogastric tube for a suspected ileus, she suffered a pulseless electrical activity arrest. After eight minutes of cardiopulmonary resuscitation, her heartbeat returned, she was intubated and sedated, and surgeons re-entering her abdomen found frank pus. Septic shock was diagnosed as the likely cause of the arrest, and broad-spectrum antibiotics were started.

The neurological trouble surfaced on postoperative day 9, when abnormal movements concerning for seizure appeared during an attempt to wean her sedation. Neurologists ordered continuous electroencephalography, which recorded unreactive theta slowing consistent with severe encephalopathy, along with myoclonic movements that occurred without any evolving electrographic seizure activity. The official interpretation described findings consistent with postanoxic myoclonus, a phenomenon long regarded as an ominous sign after cardiac arrest. On examination the patient was comatose, her pupillary reflexes were the only preserved brainstem findings, and she exhibited severe stimulus-induced generalized myoclonus. Laboratory markers told a mixed story: elevated liver enzymes and troponin suggested ongoing hypoperfusion, but neuron-specific enolase, a blood biomarker of neuronal injury, remained reassuringly low at 16, 14, and 15 nanograms per milliliter over the first three days after the arrest. Head computed tomography showed nothing abnormal, and magnetic resonance imaging was scheduled three to five days after the arrest in keeping with neuroprognostication guidelines.

What followed was a cascade of findings that failed to converge on the grim prognosis the early exam had implied. Bacteremia from Enterobacter was confirmed on day 10, prompting broader antibiotics. Brain MRI on day 11, three days after the arrest, revealed no cerebral ischemia at all, an outcome that directly contradicted the expected signature of severe hypoxic-ischemic injury. By day 13, nurses were reporting violent stimulus-induced myoclonus accompanied by autonomic changes that demanded repeated midazolam boluses every four hours, and her mental status did not improve even after propofol sedation was withdrawn. When neurology was reconsulted on day 15, the team recognized that none of the highly reliable predictors of poor outcome had actually been met, raising the possibility that a reversible metabolic or iatrogenic process was obscuring the true picture. Laboratory review then uncovered worsening acute kidney injury, a pivotal clue.

A repeat EEG changed the diagnostic landscape. This time it captured centrally predominant spikes time-locked to the clinical myoclonic jerks, a pattern the consulting team interpreted as cortical myoclonus with potential epileptogenicity, in contrast to the earlier recording that had suggested a subcortical origin without cortical spikes. Repeat MRI remained unchanged, deepening the puzzle. The case report uses this evolution to highlight a fundamental problem in post-arrest neurology: myoclonus can arise from the cortex or the subcortex, and the two are notoriously difficult to disentangle. Cortical myoclonus is classically associated with single midline or parasagittal EEG spikes against a continuous background, thought to reflect bilateral motor strip involvement transmitted through the corpus callosum. Subcortical posthypoxic myoclonus, by contrast, has been conceptualized as reticular reflex myoclonus, a stimulus-sensitive phenomenon arising from the medulla oblongata. In practice, EEG findings in subcortical myoclonus may be absent or nonspecific, movement artifacts contaminate recordings, electromyography leads that would help localize the jerk are often not used, and no clinical examination can reliably separate the two categories. Recent studies have even reported similar rates of favorable outcomes between the groups, eroding confidence in the dichotomy itself.

The report also addresses the question hanging over every such case: does postanoxic myoclonus doom a patient? Historically the answer was assumed to be yes, but contemporary evidence cautions strongly against relying on myoclonus, especially within the first 48 to 72 hours after return of spontaneous circulation, to guide irreversible decisions. Early motor findings can be distorted by sedatives, metabolic derangements, and drug-induced encephalopathy, and current guidelines explicitly warn against premature prognostication, urge clinicians to exclude modifiable factors, and recommend waiting at least 72 hours before using EEG findings prognostically. Importantly, the authors note that the vertex spike-wave discharges synchronized with the patient’s jerks have been described in the literature as a characteristic EEG phenotype of Lance-Adams syndrome, a chronic and typically survivable form of posthypoxic myoclonus. Recognizing that pattern earlier, they suggest, might have reframed the entire prognostic conversation.

That reframing opened the door to the case’s most consequential insight. Among the differential diagnoses was toxic myoclonus, and the team noted that the patient’s antibiotics had recently been broadened to cefepime, a fourth-generation cephalosporin with a well-documented neurological footprint. Beta-lactam antibiotics can induce encephalopathy by antagonizing GABA-A receptors, the brain’s principal inhibitory signaling system, producing cortical hyperexcitability that manifests as myoclonus and seizures; the full mechanism of the accompanying encephalopathy remains incompletely understood. The randomized ACORN trial further strengthened the suspicion, having demonstrated greater neurological dysfunction among hospitalized adults treated with cefepime than with piperacillin-tazobactam. Critically, the patient had possessed none of the recognized risk factors for cefepime neurotoxicity when the drug was first chosen, including advanced age, renal impairment, or prolonged high-dose therapy. Only as her kidney function deteriorated did the drug’s accumulation become a credible threat, a vivid reminder that critically ill patients have rapidly shifting metabolic states that demand continual reassessment of neuroactive prescriptions.

On day 16, cefepime was discontinued and replaced with metronidazole and piperacillin-tazobactam, while valproate was initiated for symptomatic myoclonus control based on literature supporting its use in posthypoxic cortical reflex myoclonus. The response was striking. By day 17, brainstem reflexes had returned. By day 20, she opened her eyes to voice, and over the following days she progressed to full alertness and consistent command-following, although stimulus-induced myoclonus stubbornly persisted. That persistence was diagnostically decisive: it supported a final diagnosis of Lance-Adams syndrome, likely layered with a toxic-metabolic overlay of cefepime-induced neurotoxicity in the setting of acute kidney injury, rather than cefepime toxicity alone. The chronic myoclonus continued to obstruct rehabilitation, and levetiracetam restarted alongside up-titrated valproate, a commonly reported first-line strategy, produced no benefit. Clonazepam was eventually added. Her mentation, however, kept improving, and she was discharged to a rehabilitation facility awake, communicative, and bearing a diagnosis that carries a typically favorable neurological outlook rather than the devastating prognosis her first days in the ICU had suggested.

The lessons the authors distill reach well beyond this single bedside. Clinical myoclonus alone, they argue, should never be treated as a definitive marker of severe anoxic brain injury, even though myoclonic status epilepticus with truly malignant EEG patterns remains a poor prognostic sign; neuroprognostication must instead weave together evolving EEG findings, examination, neuroimaging, and evoked potentials while actively hunting for modifiable contributors such as antibiotic-associated encephalopathy. Cefepime-induced neurotoxicity, they emphasize, can worsen mental status and provoke myoclonus and seizures, and it is exceptionally easy to miss in patients who already have neurological impairment, because every new abnormality gets attributed to the original injury. And Lance-Adams syndrome, though rare, should stand in every clinician’s mind as the favorable exception among postanoxic movement disorders. For a field in which prognostic statements can drive decisions about withdrawal of life-sustaining therapy, the case is a powerful demonstration that diagnostic clarity, patience, and a willingness to question early assumptions can quite literally change the predicted future of a patient who wakes up against the odds.

Subject of Research: Neuroprognostication after cardiac arrest complicated by postanoxic myoclonus and antibiotic-induced neurotoxicity

Article Title: Neurotoxicity in Neuroprognostication: The Importance of Differential Diagnostic Clarity

Article References: Tocco, E., Gruccio, P., Davidow, J., & Graziano, A. (2026). Neurotoxicity in Neuroprognostication: The Importance of Differential Diagnostic Clarity. Neurocritical Care. https://doi.org/10.1007/s12028-026-02654-5

Image Credits: AI Generated

DOI: 10.1007/s12028-026-02654-5

Keywords: neuroprognostication, cardiac arrest, postanoxic myoclonus, Lance-Adams syndrome, cefepime neurotoxicity, electroencephalography, encephalopathy, septic shock, myoclonus, neurocritical care, beta-lactam antibiotics, GABA-A receptors