Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide

Figures & data

Figure 1 This is an EEG of a 5-year-old girl with Lennox-Gaustaut syndrome showing generalized spike-and-wave discharges. The frequency of spike-and-wave activity is <2.5 Hertz.

Figure 2 This is an EEG of a 8-year-old boy with Lennox-Gaustaut syndrome demonstrating paroxysmal fast activity during sleep. There were no observable clinical changes noted during the discharge.

Table 1 Methodological features of randomized, double-blind controlled trials of adjunctive drug treatment for Lennox-Gaustaut syndromea

	Felbamate	Lamotrigine	Topiramate	Rufinamide
Number of patients	73	169	98	138
Age range (years)	4–36	3–25	2–29	4–36
EEG criteria	SSW	SSW	SSW	SSW
Number of seizures per month	90	15	60	>90
Seizure frequency determination	Diaryb	Diary	Diary	Diary
AEDs	1–2	1–3	1–2	1–3
Time course (weeks)
Baseline	4	4	4	4
Titration	2	6	3	2
Maintenance	8	10	8	10

^a Only studies that showed a significant reduction in seizures are presented. Data from derived from Glauser et al⁶ and Hancock and Cross.³¹

^b This study also used video EEG.

Abbreviations: AEDs, antiseizure drugs; EEG, electroencephalogram; SSW, diffuse slow spike-and-wave complexes.

Table 2 Overview of key seizure outcomes of randomized, double-blind, controlled trials of adjunctive drug treatment for Lennox-Gaustaut syndromea

Study	Outcomes vs Placebo
Felbamate	Complete cessation of seizures  10.8% vs 2.7% (p = 0.2, RR = 3.9, CI = 0.5–33.2)
	Complete cessation of atonic seizures  17.9% vs 0% (p = 0.1, RR = 5.7, CI = 0.5–49.8)
	Complete cessation of tonic-clonic seizures  43.7% vs 7.7% (p = 0.08, RR = 5.7, CI = 0.8–40.5)
	Mean change in total seizure frequency  19% vs 4% (p = 0.002)
Lamotrigine	Mean reduction in drop attacks  34% vs 9%
	Responder rateb for drop attacks
	Responder rateb for tonic-clonic seizures  43.3% vs 20.3% (RR = 2.1, CI = 2.0–3.8)
	Responder rateb for total seizures  33.3% vs 15.7% (RR = 2.1, CI = 2.0–3.8)
	Mean change in total seizure frequency  32% vs 9% (increase)
Topiramate	Mean change in drop attacks  14.8% vs 5.1% (increase) (p = 0.04)
	Complete cessation of drop attacks  2.2% vs 0% (RR = 3.3, CI = 0.1–7.8)
	Responder rateb for drop attacks  45.6% vs 20.0% (RR = 2.9, CI = 0.8–10.2 for ≥75% reduction, RR = 2.0, CI = 0.9–4.6 for 50%–74% reduction)
	Mean reduction in total seizures  20.6% vs 8.8% (p = 0.037)
Rufinamide	Median reduction of tonic-atonic seizures  42.5% vs 1.4% (p < 0.0001)
	Responder rateb for tonic-atonic seizures  42.5% vs 16.7% (p = 0.0020)
	Median reduction in total seizures  32.7% vs 11.7% (p = 0.0015)
	Patients with improvement in seizure frequency  53.4% vs 30.6% (p = 0.0041)

^a Only studies that showed a significant reduction in seizures are reported. Data from Cochrane review³¹ and Glauser et al.⁶

^b Responder rate defined as % patients achieving at least 50% reduction from baseline in seizure frequency.

Abbreviations: CI, confidence interval; RR, relative risk.

Figure 3 The molecular structure of rufinamide (1-[(2,6-difluorophenyl) methyl]-1 hydro-1,2,3-triazole-4 carboxamide). Rufinamide is a triazole derivative.

GlauserTKlugerGSachdeoRKraussGPerdomoCArroyoSRufinamide for generalized seizures associated with Lennox-Gastaut syndromeNeurology200870211950195818401024

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HancockECrossHTreatment of Lennox-Gastaut syndromeCochrane Database Syst Rev20033CD00327712917958

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