Elsevier

Journal of Clinical Neuroscience

Volume 67, September 2019, Pages 163-166
Journal of Clinical Neuroscience

Clinical study
Cephalosporin-related neurotoxicity: Metabolic encephalopathy or non-convulsive status epilepticus?

https://doi.org/10.1016/j.jocn.2019.05.035Get rights and content

Highlights

  • CRN is a toxic encephalopathy in most patients.

  • EEG in CRN characteristically reveals generalized slowing and TW.

  • Management of CRN should focus on supportive care and cephalosporin cessation.

Abstract

Metabolic encephalopathy and Non-Convulsive Status Epilepticus (NCSE) have been reported with cephalosporin use, particularly cefepime. We aimed to analyze the clinical and EEG findings in patients with cephalosporin-related neurotoxicity (CRN) at our hospital identified via the hospital EEG database, and to critically review CRN case reports in the literature. A Medline search was performed to identify CRN cases where a representative sample of EEG was provided. EEGs were analyzed using published criteria differentiating NCSE from triphasic waves (TW). Eleven patients at our hospital were identified with CRN (9 cefepime, 2 ceftriaxone): all had an encephalopathy with decreased consciousness and/or confusion. One patient had clinical seizures and 6 had multifocal myoclonus. All patients had abnormal EEGs, all with moderate to severe generalized slowing and 10 also with TW. Recovery was related to cephalosporin withdrawal rather than antiepileptic therapy. Analysis of 37 EEG samples of CRN patients reported in the literature as NCSE (30) or TW (7) revealed that most did not meet criteria for NCSE, with 33 showing TW, 1 showing generalised epileptiform discharges and 3 being uninterpretable. CRN usually produces a toxic encephalopathy rather than NCSE, and is commonly associated with triphasic waves on EEG. In most patients anti-epileptic and/or sedative drugs do not hasten clinical improvement.

Section snippets

Background

Cephalosporin-related neurotoxicity (CRN) is reported to cause both a toxic encephalopathy, and Non-Convulsive Status Epilepticus (NCSE) [1], [2], [3], [4], [5], [6]. Increased cerebral cephalosporin concentrations are thought to produce CRN via GABA-A receptor antagonism [7]. Manifestations include confusion, agitation, hallucinations, myoclonus, seizures, tremor and coma. Pre-existing CNS impairment, renal impairment and excessive dosing are predisposing factors [1], although CRN can occur

Methods

CRN was defined as an encephalopathy without other obvious cause occurring in patients receiving cephalosporin therapy. Patients were identified from a tertiary adult general hospital EEG database (2002–2016) searching patients taking cephalosporins at the time of EEG (n = 153), patients with NCSE, or both. EEGs, clinical features and investigation findings were analyzed, specifically in those patients responding to cephalosporin withdrawal, to antiepileptic therapy or to both. Medline and

Results

Eleven patients with CRN were identified at our hospital, nine treated with cefepime (median dose 4 g per day, range 2–6 g per day) and two ceftriaxone (Table 1). All had decreased conscious state and/or confusion. One patient with history of focal epilepsy and HIV infection had a single tonic-clonic seizure and 6 had multifocal myoclonus. Doses of cephalosporin were in excess of that recommended in 6 of 11 patients (55%) (5 cefepime and 1 ceftriaxone).

EEG showed moderate or severe generalised

Review of published EEGs in CRN

The 31 articles reporting CRN with 37 representative samples of EEG were analyzed. Seven patient EEGs were reported as showing TW consistent with a metabolic encephalopathy and 30 as NCSE, variously interpreted as GPEDs, PLEDs or GSW.

Three EEGs were assessed as uninterpretable, all previously reported as NCSE. Of the remaining 34 EEGs, blinded analysis was uniformly in agreement, with 1 showing ongoing generalised spike-wave/polyspike and wave, and 33 showing TW, confirmed by applying the

Discussion

CRN was initially reported as a metabolic/toxic encephalopathy with EEGs showing diffuse slowing with or without TW. However reports of CRN induced NCSE have subsequently dominated the literature, including recent review articles on antibiotic associated encephalopathies [4], [5], [6], [7], [8]. The patients identified at our hospital share clinical features with previously reported cases of CRN. Most patients had renal impairment or received an above-recommended dose of cephalosporin, most

Ethical publication statement

We the authors confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Declaration of Competing Interest

Nicholas Lawn reports grants from UCB, outside the submitted work. Dr Triplett, Dr Chan and Professor Dunne report no disclosures.

References (21)

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