Levetiracetam may prevent acute seizures in intracerebral hemorrhage: Lancet

France: In cases of intracerebral hemorrhage, levetiracetam may be useful in preventing acute seizures, states a recent study published in The Lancet Neurology.

Bleeding inside the brain tissue eventually results in intracerebral hemorrhage, a potentially fatal form of stroke. Acute seizures may lead to worse neurological consequences and hemorrhage that spreads. When subclinical seizures are identified by continuous EEG, the occurrence of early seizures within 7 days after stroke initiation following intracerebral hemorrhage reaches 30%.

Current guidelines do not suggest prophylactic anti-seizure treatment in patients with intracerebral hemorrhage, so neuroscientists from Lyon Neuroscience Research Centre, Fleyriat Hospital, and Saint Etienne University Hospital sought to determine whether preventive levetiracetam would minimize the risk of acute seizures in these patients.

For this purpose, the researchers conducted a phase 3 double-blind, randomized, placebo-controlled PEACH trial across three-stroke hospitals in France. The patients were randomized in the ratio of 1:1 to receive levetiracetam 500 mg intravenously every 12 hours or a matching placebo if they reported with a non-traumatic intracerebral hemorrhage within 24 hours of the onset. Six weeks of treatment were given. Within 24 hours after admission, a continuous EEG was commenced, and 48 hours of data were collected.

The main outcome was the incidence of at least one clinical seizure in 72 hours of inclusion or at least one electrographic seizure noted on ongoing EEG, both of which were evaluated in the modified intention-to-treat population, which included all patients who were randomized to treatment and who underwent continuous EEG.

Key findings of the study:

 A clinical or electrographic seizure was noted in 3 (16%) of the 19 patients in the levetiracetam group in the first 72 hours, compared to 10 (43%) of the 23 patients in the placebo group.

 13% of the patients who got levetiracetam experienced depression, compared to 15%) of the individuals who received a placebo.

 8% of the patients reported having anxiousness, compared to 4% of patients.

 In the levetiracetam group compared to the placebo group, headache, pain, and falls were the most frequent therapy-emergent adverse events.

 The two significant adverse events that occurred most frequently were severe pneumonia (9% vs. 8%) and neurological decline brought on by intra-cerebral hemorrhage (4% vs. 16%). In neither group was recorded mortality attributed to the treatment.

The researchers conclude, "Levetiracetam might be effective in preventing acute seizures in intracerebral hemorrhage."

The researchers add that there is a need for larger studies to determine whether seizure prophylaxis improves functional outcomes in intra-cerebral hemorrhage patients.

REFERENCE

Peter-Derex L, Philippeau F, Garnier P, André-Obadia N, Boulogne S, Catenoix H, Convers P, Mazzola L, Gouttard M, Esteban M, Fontaine J, Mechtouff L, Ong E, Cho TH, Nighoghossian N, Perreton N, Termoz A, Haesebaert J, Schott AM, Rabilloud M, Pivot C, Dhelens C, Filip A, Berthezène Y, Rheims S, Boutitie F, Derex L. Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2022 Sep;21(9):781-791. doi: 10.1016/S1474-4422(22)00235-6. PMID: 35963261.