Increased adverse events associated with antiepileptic drugs in anti–leucine‐rich glioma‐inactivated protein 1 encephalitis

Abstract

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti-LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti-LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti-LGI1 encephalitis.

Seizure specificities in patients with antibody‐mediated autoimmune encephalitis

“…More importantly, a study reported an unusually high frequency of severe adverse effects from AEDs in this population of patients . Indeed, half of the LGI1 patients studied in a recent report had to change their AED treatment due to adverse cutaneous drug reactions, consisting mainly of maculopapular eruptions . One patient even presented with drug rash accompanied by eosinophilia and systemic symptoms syndrome (DRESS), a potentially fatal dermatologic condition.…”

“…AEDs should be utilized as symptomatic treatment, starting with a single drug, possibly a sodium‐channel blocker (eg, carbamazepine, oxcarbazepine, eslicarbazepine acetate, lamotrigine, or lacosamide) . However, special caution is needed in rapid dosage increase of aromatic AEDs in LGI1‐Ab encephalitis, given the high incidence of cutaneous adverse effects in this population . If the first AED results are ineffective, the adjunct of a second drug with different or multiple mechanisms of action (eg, valproate) is advisable .…”

“…37 Indeed, half of the LGI1 patients studied in a recent report had to change their AED treatment due to adverse cutaneous drug reactions, consisting mainly of maculopapular eruptions. 45 One patient even presented with drug rash accompanied by eosinophilia and systemic symptoms syndrome (DRESS), a potentially fatal dermatologic condition. The underlying cause of developing such cutaneous adverse reactions probably relates to the peculiar HLA subtypes present in LGI1 patients.…”

“…[102][103][104] However, special caution is needed in rapid dosage increase of aromatic AEDs in LGI1-Ab encephalitis, given the high incidence of cutaneous adverse effects in this population. 45,104 If the first AED results are ineffective, the adjunct of a second drug with different or multiple mechanisms of action (eg, valproate) is advisable. 105 Treatment of status epilepticus requires intravenous administration and rapid drug titration, as recommend by international guidelines.…”

Neuro-psycho disorders and Hyponatremiain a Renal Carcinoma patient revealed as Anti-LGI1 Encephalitis and Renal Salt Wasting: a Case Report

“…Recently, a strong influence of a specific HLA (human leukocyte antigen) haplotype has been shown in anti-LGI1 encephalitis in Koreans [25]. In our report, the patient presented with typical features of anti-LGI1 limbic encephalitis, including cognitive defects, FBDS, hyponatremia, and had a good response to steroids and IVIG instead of antiepileptic therapy [26,27].…”