Clinical studyCephalosporin-related neurotoxicity: Metabolic encephalopathy or non-convulsive status epilepticus?
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.
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