Optimal management of seizures associated with tuberous sclerosis complex: current and emerging options

Figures & data

Table 1 Prospective pharmacological trials for the treatment of epilepsy in TSC or IS

Agent	Trial description	Author	Year	Size	Demographic	Study design	Conclusion
ACTH	ACTH versus prednisone for IS	Hrachovy et al^Citation85	1983	24	Age 1–24 months	RCT double-blinded crossover study	Treatment response in 38% of ACTH and 29% of prednisone group
	ACTH: low versus high dose for IS	Hrachovy et al^Citation30	1994	50	Age 1–24 months	RCT double-blinded	Treatment response in 58% of low dose and 50% of high dose group (no significant difference)
	ACTH versus prednisone for IS	Baram et al^Citation86	1996	29	Age 3–21 months	RCT single-blinded	Treatment response in 87% of ACTH and 29% of prednisone group
	ACTH + MgSO4 versus ACTH monotherapy for IS	Zou et al^Citation87	2010	38	Age <12 months	RCT open-label	Treatment response in 63% of ACTH with MgSO4 and 53% of ACTH monotherapy group
Vigabatrin (VGB)	VGB versus hydrocortisone for IS secondary to TSC	Chiron et al^Citation88	1997	22	Age 1–24 months	RCT open-label crossover study	Treatment response in 100% of VGB and 45% of ACTH group VGB demonstrated greater efficacy and decreased side effect profile
	VGB versus ACTH for IS	Vigevano and Cilio^Citation89	1997	42	Age 2–9 months	RCT open-label crossover study	Treatment response in 74% of ACTH group and 48% of VGB group In the TSC subgroup, VGB demonstrated improved efficacy of seizure control, time to response, and decreased adverse events compared to ACTH
	VGB versus ACTH/valproic acid for IS	Granström et al^Citation90	1999	42	Age <12 months	Population-based study	Treatment response in 26% of VGB group ACTH and valproic acid offered to patients who did not respond to VGB
	VGB low versus high dose for IS	Elterman et al^Citation38	2001	142	Age <24 months	RCT single-blinded	Treatment response in 11% of low dose and 36% of high dose group Clinically significant improvement in TSC subgroup
Everolimus	SEGA NCT00411619 TSC patients with SEGA	Krueger et al^Citation51	2010	28	Age 3–34 years	Phase I/II open-label	Clinically relevant reduction in SEGA size, clinical and subclinical seizures Nonsignificant trend toward better quality of life measures
	EXIST-1 TSC patients with SEGA	Franz et al^Citation52	2013	117	Age 0–65 years	RCT Phase III	35% patients in the everolimus group had ≥50% reduction in SEGA volume
	Epilepsy, NCT01070316	NCT01070316	Ongoing	20 (target)	Age >24 months	Phase I/II open-label	Ongoing study Primary outcome: reduction in seizure frequency

Abbreviations: ACTH, adrenocorticotropic hormone; EXIST, Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex; IS, Infantile spasm; RCT, randomized controlled trial; SEGA, subependymal giant cell astrocytoma; TSC, tuberous sclerosis complex.

Table 2 Engel classification of seizure outcomes following surgical resection

Class I	Seizure free or no more than a few early, nondisabling seizures; or seizures upon drug withdrawal only
Class II	Disabling seizures occur rarely during a period of at least 2 years; disabling seizures may have been more frequent soon after surgery; nocturnal seizures
Class III	Worthwhile improvement; seizure reduction for prolonged periods but less than 2 years
Class IV	No worthwhile improvement; some reduction, no reduction, or worsening are possible

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