Observation on the therapeutic efficacy of ketogenic diet combined with perampanel in children with epileptic encephalopathy accompanied by sharp-slow wave activation during sleep period

doi:10.11958/20253253

Abstract

Abstract:

Objective To evaluate the therapeutic effects of ketogenic diet (KD) combined with perampanel (PER) on sleep-related spike-and-wave activity index (SWI), serum levels of central nervous system-specific protein S-100β and intellectual development in children diagnosed with epileptic encephalopathy with sleep-related spike-and-wave activation (EE-SWAS). Methods A prospective randomized controlled trial was conducted involving 99 children with EE-SWAS, and they were randomly assigned to the control group (n = 49, receiving PER monotherapy) and the experimental group (n = 50, receiving KD combined with PER). After six months of treatment, clinical efficacy, SWI, serum biomarkers including S-100β, neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF) were assessed and compared between groups. Cognitive function was evaluated using the Wechsler Intelligence Scale for Children—Fifth Edition (WISC-V). Adverse events were systematically monitored throughout the study period. Results After treatment, SWI, S-100β and NSE levels were significant reduced in both groups, and BDNF level and WISC-V scores were higher compared to those of the control group (P<0.05). SWI, S-100β and NSE levels were lower in the experimental group than those of the control group, and BDNF level and WISC-V scores were higher in the control group (P<0.05). After treatment, the total effective rate was hiter in the experimental group (96.00%) than that in the control group (79.59%, P<0.05). There was no significant difference in the incidence of adverse events during the treatment period between the two groups (12.00% vs. 16.32%，P>0.05). Conclusion The combination of KD and PER demonstrates superior therapeutic efficacy in children with EE-SWAS, effectively reducing abnormal electroencephalographic activity, modulating key neurochemical markers, supporting cognitive development and exhibiting a favorable safety.

Key words: epilepsy, S100 calcium binding protein beta subunit, Wechsler scales, ketogenic diet, perampanel, epileptic encephalopathy with sleep-wake-activated spikes, spike-wave index

CLC Number:

R742.1

Figures/Tables 5

References 18

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组别		n	年龄/岁		性别				体质量/kg		病程/月		ASMs种类
组别		n	年龄/岁		女		男		体质量/kg		病程/月		2种		≥3种
对照组		49	8.14±0.93		23（46.94）		26（53.06）		21.79±3.52		6.21±0.75		32（65.31）		17（34.69）
试验组		50	8.29±1.05		21（42.00）		29（58.00）		22.03±3.78		5.93±0.66		33（66.00）		17（34.00）
χ2或t			0.752		0.244				0.372		1.973		0.005
组别	非自限性病因分类							自限性病因		亚型
组别	结构性			遗传性		免疫性	不明	自限性病因		CSWS		LKS		SeL-ECTS		SeL-EAS
对照组	18（36.73）			10（20.41）		5（10.20）	2（4.08）	14（28.57）		26（53.06）		15（30.61）		3（6.12）		5（10.20）
试验组	17（34.00）			11（22.00）		4（8.00）	3（6.00）	15（30.00）		26（52.00）		16（32.00）		4（8.00）		4（8.00）
χ2	0.387							0.024		0.276

组别		n	年龄/岁		性别				体质量/kg		病程/月		ASMs种类
组别		n	年龄/岁		女		男		体质量/kg		病程/月		2种		≥3种
对照组		49	8.14±0.93		23（46.94）		26（53.06）		21.79±3.52		6.21±0.75		32（65.31）		17（34.69）
试验组		50	8.29±1.05		21（42.00）		29（58.00）		22.03±3.78		5.93±0.66		33（66.00）		17（34.00）
χ2或t			0.752		0.244				0.372		1.973		0.005
组别	非自限性病因分类							自限性病因		亚型
组别	结构性			遗传性		免疫性	不明	自限性病因		CSWS		LKS		SeL-ECTS		SeL-EAS
对照组	18（36.73）			10（20.41）		5（10.20）	2（4.08）	14（28.57）		26（53.06）		15（30.61）		3（6.12）		5（10.20）
试验组	17（34.00）			11（22.00）		4（8.00）	3（6.00）	15（30.00）		26（52.00）		16（32.00）		4（8.00）		4（8.00）
χ2	0.387							0.024		0.276

组别		n	SWI								S-100β/（μg/L）
组别		n	治疗前			治疗后			t		治疗前		治疗后		t
对照组		49	87.49±9.52			15.47±2.34			88.156^＊＊		1.03±0.23		0.62±0.09		22.625^＊＊
试验组		50	88.26±10.14			6.21±0.79			85.038^＊＊		0.99±0.16		0.47±0.07		42.630^＊＊
t			0.389			26.487^＊＊					1.006		9.267^＊＊
组别	BDNF/（μg/L）						NSE/（μg/L）					WISC-V评分/分
组别	治疗前			治疗后	t		治疗前	治疗后		t		治疗前		治疗后		t
对照组	5.97±0.71			7.52±0.94	22.808^＊＊		25.81±3.56	16.39±2.65		36.636^＊＊		79.36±9.28		90.77±9.51		15.539^＊＊
试验组	5.83±0.64			8.09±1.22	25.162^＊＊		26.19±3.77	14.15±2.29		44.335^＊＊		80.57±9.13		96.47±10.07		21.272^＊＊
t	1.031			2.600^＊			0.515	4.503^＊＊				0.654		2.894^＊＊

组别		n	SWI								S-100β/（μg/L）
组别		n	治疗前			治疗后			t		治疗前		治疗后		t
对照组		49	87.49±9.52			15.47±2.34			88.156^＊＊		1.03±0.23		0.62±0.09		22.625^＊＊
试验组		50	88.26±10.14			6.21±0.79			85.038^＊＊		0.99±0.16		0.47±0.07		42.630^＊＊
t			0.389			26.487^＊＊					1.006		9.267^＊＊
组别	BDNF/（μg/L）						NSE/（μg/L）					WISC-V评分/分
组别	治疗前			治疗后	t		治疗前	治疗后		t		治疗前		治疗后		t
对照组	5.97±0.71			7.52±0.94	22.808^＊＊		25.81±3.56	16.39±2.65		36.636^＊＊		79.36±9.28		90.77±9.51		15.539^＊＊
试验组	5.83±0.64			8.09±1.22	25.162^＊＊		26.19±3.77	14.15±2.29		44.335^＊＊		80.57±9.13		96.47±10.07		21.272^＊＊
t	1.031			2.600^＊			0.515	4.503^＊＊				0.654		2.894^＊＊

组别	n	显效	有效	无效	总有效
对照组	49	23（46.94）	16（32.65）	10（20.41）	39（79.59）
试验组	50	28（56.00）	20（40.00）	2（4.00）	48（96.00）
χ²					6.255^＊