Shi Jie, Lin Jiuluan, Bai Jianjun, Wang Haixiang, Zhang Bingqing, Feng Qian, Sun Zhaohui, Liu Yiou, He Jing, Song Xiancheng, Wang Siyu, Liu Xiaoyan, Zhou Wenjing
Department of Neurosurgery, Epilepsy Center, Tsinghua University Yuquan Hospital, Beijing, China.
Epilepsia Open. 2025 Jun;10(3):725-735. doi: 10.1002/epi4.70014. Epub 2025 Mar 8.
To summarize the clinical features of collagen type IV alpha 1/2 chain (COL4A)1/2-related epilepsy and the seizure outcomes of patients undergoing epilepsy surgery.
We retrospectively analyzed the clinical, electroencephalography, and neuroimaging data; genetic characteristics; surgical details; and prognosis of 8 patients (4 boys) treated for COL4A1/2-related epilepsy at Tsinghua University Yuquan Hospital.
Two of the probands had COL4A1 variants and six had COL4A2 variants. Four of the variants were de novo. Prenatal abnormalities consisted of intrauterine growth retardation and ventriculomegaly. Three patients had a low birth weight, and one had perinatal retinal hemorrhage. The median age of seizure onset was 8 months, with 75% (6/8) experiencing epilepsy before age 1. Status epilepticus occurred in 38% (3/8) of patients. All patients experienced focal seizures, and 50% (4/8) had focal epileptic spasms. Hemiparesis was observed in 88% (7/8) of patients, and all 8 had developmental delays. The median number of anti-seizure drugs was 5, and all patients had drug-resistant epilepsy. Seven patients had seizures localized to one of the posterior quadrants, consistent with the magnetic resonance imaging features of blurring of the gray-white matter junction and positron emission tomography features of metabolic abnormalities. Other neuroimaging features included bilateral mild white matter abnormalities; unilateral porencephaly near the basal ganglia; ventriculomegaly; focal cerebral calcification; contralateral schizencephaly; and contralateral cortical thickening and cerebellar abnormalities. Six patients underwent unilateral posterior quadrant disconnection, five (83%) of whom had no recurrence for at least 11 months and experienced developmental improvement. No surgical complications were reported. Pathological examination revealed malformations of cortical development in all six surgical cases (five with focal cortical dysplasia [FCD] type Ia and one with FCD type II).
The results of this case series suggest that early surgical intervention in patients with COL4A1/2-related epilepsy with well-defined epileptogenic zones may improve seizure control and developmental outcomes.
In this case series of eight patients, epilepsy related to variants in the collagen type IV alpha 1/2 chain genes was characterized by drug-resistant localized seizures with an early onset, one-sided muscle weakness, and developmental delay. Neuroimaging revealed various brain abnormalities. Structural abnormalities outside the seizure-onset zone did not appear to affect surgical prognosis. Early surgical intervention in patients with well-defined seizure-onset zones improved seizure control and developmental outcomes.
总结IV型胶原α1/2链（COL4A）1/2相关癫痫的临床特征以及接受癫痫手术患者的癫痫发作结局。
我们回顾性分析了在清华大学玉泉医院接受COL4A1/2相关癫痫治疗的8例患者（4例男性）的临床、脑电图和神经影像学数据、遗传特征、手术细节及预后情况。
先证者中2例有COL4A1变异，6例有COL4A2变异。其中4种变异为新发变异。产前异常包括宫内生长迟缓及脑室扩大。3例患者出生体重低，1例有围产期视网膜出血。癫痫发作的中位年龄为8个月，75%（6/8）的患者在1岁前出现癫痫。38%（3/8）的患者发生癫痫持续状态。所有患者均有局灶性发作，50%（4/8）有局灶性癫痫性痉挛。88%（7/8）的患者观察到偏瘫，8例均有发育迟缓。抗癫痫药物的中位数量为5种，所有患者均为难治性癫痫。7例患者的癫痫发作局限于后象限之一，与磁共振成像显示的灰白质交界模糊及正电子发射断层扫描显示的代谢异常特征相符。其他神经影像学特征包括双侧轻度白质异常；基底节附近单侧脑穿通畸形；脑室扩大；局灶性脑钙化；对侧脑裂畸形；以及对侧皮质增厚和小脑异常。6例患者接受了单侧后象限离断术，其中5例（83%）至少11个月无复发且发育有改善。未报告手术并发症。病理检查显示所有6例手术病例均有皮质发育畸形（5例为Ia型局灶性皮质发育不良[FCD]，1例为II型FCD）。
本病例系列结果表明，对COL4A1/2相关癫痫且癫痫灶明确的患者进行早期手术干预可能改善癫痫控制及发育结局。
在这个包含8例患者的病例系列中，IV型胶原α1/2链基因变异相关癫痫的特点为难治性局灶性发作、起病早、单侧肌无力及发育迟缓。神经影像学显示多种脑异常。癫痫发作起始区以外的结构异常似乎不影响手术预后。对癫痫发作起始区明确的患者进行早期手术干预可改善癫痫控制及发育结局。
