. 2023 Jul 6;14:1182304. doi: 10.3389/fneur.2023.1182304

Table 2.

Studies addressing the use of PER in status epilepticus.

Study	Type of study	Patients	PER treatment	SE resolution
Chen-Jul Ho et al. (82)	Retrospective, monocentric study	67 patients included; 22 received PER treatment (32.8%).	PER was given as a median 4th ASM (range 2–7) at a median of 5.45 days after SE onset (range 0.2–12.9 days).	8/22 (36.4%)
	Effectiveness criteria: Responder: seizure freedom (clinically or electrographically) within 4 days after PER administration (last ASM used), plus no relapse during hospitalization. NR: not seizure freedom within 4 days; PER was not the last ASM used; relapse during hospitalization.	Cerebrovascular diseases (8/22; 36%), head trauma (3/22; 14%), and autoimmune disorders (3/22; 14%) were the most common etiologies of SE.	Median initial dose: 2 mg (range 2–8 mg)—median maximum dose 4 mg (range 2–12 mg). Titration up to the maximum dose occurred in a median of 2 days.		More than half of the patients had a CSE (15/22; 68%).	No SAEs observed (four patients died of sepsis); no elevation in liver enzymes.
	Strzelczyk et al. (83)	Retrospective, multicentric study	1,319 patients included; 52 (3.9%) received PER treatment: one ESE (1.9%), 28 RSE (53.8%), and 23 SRSE (44.2%).		More than half of the patients had a CSE (15/22; 68%).		PER was given as a median 6th ASM (range 1–14) with a median latency from SE onset of 10 days (range 0.5–51 days).	19/52 (36.5%)
		PER response was defined as SE cessation for ≥24 h within 24 h from PER administration, without further administration of ASM or co-medications changes in the last 24 h.	Structural etiologies were the most common causes of SE (45/52; 86.5%); five patients with hypoxic SE (9.6%).		Median initial dose: 6 mg (range 2–24 mg)—median maximum dose 10 mg (range 4–24 mg): both significantly higher in NR patients.
No SAEs were observed; two patients (3.8%) experienced dizziness and drowsiness.
Alsherbini et al. (84)	Retrospective, monocentric, observational study	75 patients included and treated with PER: 31 DR (41.3%), 28 PR (37.3%), and 14 NR (18.6%).	PER was given as a median 6th ASM (range 5–7) with a median latency from SE onset of 1.8 days (range 0.9–3.3): no significant differences between DR and PR/NR.	31/75 (41.3%; median response time: 40 h [range 1–69])
	Effectiveness criteria: DR: the resolution of SE within 72 h of initiation of PER (with no additional ASMs). PR: the resolution of SE within 72 h of initiation of PER, but other ASMs were added to the treatment regimen within 12 h of PER initiation. NR: lack of resolution after PER initiation or multiple ASMs were added within 12–72 h following PER initiation.				Structural etiologies were the most common causes of SE (59/75; 78.7%).	Median initial dose: 12 mg (range 8–12 mg) – median maximum dose 12 mg (range 8–24 mg): no significant differences comparing DR and PR/NR.	More than half of the patients had an NCSE (52/75; 69.3%); DR had a higher percentage of patients with GCSE (41.9% vs. 22.7%; p = 0.08).	Seven patients (9.3%) experienced mild adverse effects: agitation (2), drowsiness (4), and liver enzyme elevation (2).
	Atsushiet al (85).	Prospective, monocentric, interventional study	22 patients included (mean age 59.5 years), all had a SE with the prominent motor phenomenon, either focal motor (8/22; 38%) or convulsive (14/22; 62%)		PER was administered after the failure of first- and second-line agents (or levetiracetam). NR patients received a third-line agent after PER.	15/22 (68%)
		PER was considered effective in case of reduction in seizures frequency within 1 h from its administration (seizure free at 24 h).	Cerebrovascular diseases (8/22; 38%), CNS tumors (4/22; 18%) and head trauma (4/22; 18%) were the most frequent etiologies of SE		Oral loading dose: 8 mg.
					No SAEs; only a few patients experienced mild adverse effects (drowsiness and dizziness).
Slew-Na Lim et al. (86)	Retrospective, monocentric, observational	373 patients included; 81 received PER treatment (21.7%).	PER was given as a median 4th ASM (range 1–7); median latency from SE onset: 100 h (range 5–1,428).	27/81 (33.3%); (median response time: 40 h [range 1–69])
	Effectiveness criteria: Responder: seizure freedom (clinically/electrographically) within 72 h after PER administration and without other ASM or anesthetics changes. NR: ambiguous classification for co-medications changes.	373 patients included; 81 received PER treatment (21.7%).			Metabolic disturbances (27/81; 33.3%), cerebrovascular diseases (22/81; 22.7%), and CNS infections (12/81; 14.8%) were the most common etiologies of SE.	Median initial dose: 4 mg (range 2–36 mg)—median maximum dose 12 mg (range 4–36 mg). Initial and maximum dose was positively and negatively associated with response rate, respectively (OR 1.27, p = 0.025 vs. OR 0.74, p = 0.022).	More than half of the patients had a CSE (58/81; 71.6%).	No SAEs were observed even in case of high off-label dosage.

ARS, acute repetitive seizures; ASM, anti-seizure medication; CSE, convulsive status epilepticus; CNS, central nervous system; DR, definite responder; ESE, electrographic status epilepticus; GCSE, generalized convulsive status epilepticus; NCSE, non-convulsive status epilepticus; NR, non-responders; PER, perampanel; PR, partial responder; RSE, refractory status epilepticus; SAEs, serious adverse events; SE, status epilepticus; SRSE, super refractory status epilepticus.