Cephalosporin-Induced Neurotoxicity: Clinical Manifestations, Potential Pathogenic Mechanisms, and the Role of Electroencephalographic Monitoring

Abstract

Objective: To review the clinical manifestations of cephalosporin-induced neurotoxicity, underlying potential mechanisms, role of electroencephalographic (EEG) monitoring, and management of neurotoxicity. Data: A PubMed search (1970–May 2006) was conducted using search terms such as cephalosporins, neurotoxicity, seizures, and status epilepticus. The search was not limited to the English language and yielded approximately 187 articles. Study Selection and Data Extraction: Several case reports and case series were included to outline the salient clinical features of cephalosporin neurotoxicity. Laboratory studies investigating the potential mechanisms were also included. Reports outlining the EEG features of cephalosporin neurotoxicity were included and the role of continuous EEG monitoring was extracted. Finally, management strategies of such neurotoxicity are discussed. Data Synthesis: Cephalosporin-induced neurotoxicity may manifest in a variety of clinical presentations, ranging from simple encephalopathy or mental status changes to myoclonus, asterixis, seizures, nonconvulsive status epilepticus, as well as coma. Patients who are elderly, those with renal insufficiency, and those with prior neurologic disease may be particularly prone to the neurotoxic effects. The main mechanism of neurotoxicity appears to involve γ-aminobutyric acid A receptor inhibition, although other mechanisms may be possible. Cephalosporin neurotoxicity may be associated with a variety of EEG manifestations. Treatment mainly involves withdrawal of the offending drug, in addition to hemodialysis in patients with renal failure, and use of benzodiazepines or other anticonvulsants in patients who develop frank status epilepticus. Neurotoxicity can be prevented in high-risk cases with dosage adjustments and monitoring of serum concentrations. Conclusions: Knowledge and awareness of the neurotoxic clinical manifestations, EEG findings, and underlying mechanisms are essential for clinicians in identifying and treating this potentially lethal but reversible complication of cephalosporin therapy. Further studies are needed to determine the most appropriate treatment paradigms for patients who develop status epilepticus as a result of cephalosporins.