Nonconvulsive status epilepticus cases arising in connection with cephalosporins

Abstract

Cephalosporins, particularly cefepime, exert neurotoxic side effects that can lead to status epilepticus. These neurotoxic side effects include myoclonus, dystonic movements, tremor, asterixis, seizure, status epilepticus, encephalopathy, and sometimes coma. Status epilepticus, particularly nonconvulsive status epilepticus (NCSE), is a well-known but unusual complication in patients with altered renal function who were receiving treatment with intravenous cephalosporins, especially cefepime. We reviewed the clinical and electroencephalographic (EEG) characteristics of 7 patients with renal failure who developed consciousness alterations with changes in EEG activity while being treated with cephalosporins. All patients developed renal failure: six patients had chronic renal failure, one patient had acute renal failure, and two patients were administered hemodialysis. Nonconvulsive status epilepticus was observed between 2 and 8 days (average of 5.6 days) after initiation of cephalosporins. Cephalosporins are epileptogenic drugs, especially when used in excessive doses or when renal function is impaired. Critically ill patients with chronic kidney disease are particularly susceptible to cefepime neurotoxicity. Clinical and electrophysiological results of patients guide the diagnosis of NCSE by healthcare providers.

Cefepime-Induced Encephalopathy and Nonconvulsive Status Epilepticus: Dispelling an Artificial Dichotomy

“…Based on this dichotomized labeling, those deemed to have "NCSE" were more likely to receive one or more anti-seizure medication (ASM), while others labeled "encephalopathic" often just had their cefepime discontinued without additional interventions. 4,[7][8][9]11,12 Indeed, on review of prior cases outlined in Table 1, 100% of those labeled NCSE received an ASM compared to only 15% of those who were labeled as having an encephalopathy. No report prior to our case series clearly demonstrated a positive electroclinical response to ASMs (as in our case, the clinical improvements were only partial), while all earlier publications on this topic, regardless of whether they labeled the case as encephalopathy or NCSE, report resolution of the altered mentation after cefepime discontinuation.…”

“…The patients in this case series were identified prospectively by the authors, who were on EEG service at the times when the patients underwent EEG monitoring. 52/M 2 DZP ND ND 7 NCSE 11 7 39/F 6 DZP ND ND 5 NCSE 12 9 58/F 8 DZP ND ND 5 NCSE 13 9 68/F 4 DZP ND ND 5 NCSE 14 9 74/F 4 DZP, LEV ND ND 5 NCSE 15 4 74/F 7 PHE ND ND 3 NCSE 16 10 64/M 3 ND EP 17 11 57/F 10 LEV, PHE ND ND 4 NCSE 18 5 64/F 5 3 EP 19 12 68/M 7 CBZ 4 EP 20 12 85 Abbreviations: AMS, altered mental status; ASM, anti-seizure medication; CBZ, carbamazepine; CLN, clonazepam; DZP, diazepam; EEG, electroencephalogram; EP, encephalopathy; LEV, levetiracetam; LZP, lorazepam; NCSE, nonconvulsive status epilepticus; ND, not documented; PHE, phenytoin; VPA, valproate. a Patients were identified via a PubMed search for the terms "cefepime," "encephalopathy," "NCSE," and "non-convulsive status epilepticus."…”

An Emergency Medicine Perspective for Non-Convulsive Status Epilepticus Patients: Intravenous Midazolam

“…Similarly, in a single-case study by Akpınar et al (13), they used 10 mg IV diazepam as first-line therapy to terminate NCSE caused by an infection. Moreover, in a case series including 7 patients who developed NCSE due to cephalosporins, all patients were successfully treated with IV diazepam (14). Contrary to these studies, we used midazolam that was more rapid and short acting to terminate seizures of our patients compared to diazepam.…”

Cefepime-induced neurotoxicity

“…First, their EEG did not satisfy the working clinical criteria for NCSE [65]. Most of the reported cases showed transient or partial improvement of EEG after intravenous administration of benzodiazepines [13,21,44,48,70,77,83]; however, GPD with triphasic morphology can be also suppressed by intravenous benzodiazepines [43,85,86]. Immediate clinical improvement occurred exceptionally in few cases [20,76,81].…”

“…normalities, some described as CIN with TW or GPD [3,15,17,22,24,43,49,[70][71][72][73][74][75][76], whereas others reported these as CIN with NCSE [4][5][6]13,14,16,18,20,21,42,45,[77][78][79][80][81][82][83][84], depending on the author's view. Some investigators proposed that encephalopathies with GPD or severe metabolic encephalopathies with continuous epileptiform EEG abnormality are not NCSE, and that a coma with continuous generalized epileptiform discharges (coma-GED) should be differentiated from NCSE proper [67,69].…”