目的:本研究旨在全面分析局灶性皮质发育不良(FCD)患者的临床特征,并确定与耐药性癫痫(DRE)相关的差异表达基因。
方法:于2019年7月至2022年6月进行回顾性调查,涉及40例与FCD相关的DRE患儿。随后进行随访以评估手术后的结果。转录组测序和定量逆转录聚合酶链反应(qRT-PCR)用于检查FCD和对照组之间的差异基因表达。
结果:在纳入研究的40名患者中,以双侧强直阵挛性发作(13/40,32.50%)和癫痫性痉挛(9/40,22.50%)为主要发作类型。磁共振成像(MRI)显示额叶(22/40,55%)和颞叶(12/40,30%)频繁受累。在MRI结果阴性的情况下(13/13,100%),正电子发射断层扫描/计算机断层扫描(PET-CT)扫描显示低代谢病变。融合MRI/PET-CT图像显示,与单纯PET-CT相比,病变减少40.74%(11/27)。而59.26%(16/27)的结果与PET-CT检查结果一致。在26例中发现了II型FCD,和FCDI型13例。在最后一次随访中,38例患者的处方平均为1.27±1.05抗癫痫药物(ASM),两名患者停止治疗。术后随访23.50个月,75%(30/40)的患者取得EngelⅠ类结局。转录组测序和qRT-PCR分析确定了几个主要与纤毛相关的基因,包括CFAP47,CFAP126,JHY,RSPH4A,SPAG1
结论:本研究强调,在FCD引起的DRE患者中,局灶性至双侧强直-阵挛性癫痫发作是最常见的癫痫发作类型。手术干预主要针对额叶和颞叶的病变。FCD相关DRE患者在手术后控制癫痫发作方面表现出良好的预后。确定的基因,包括CFAP47,CFAP126,JHY,RSPH4A,和SPAG1,可以作为FCD的潜在生物标志物。
结论:本研究旨在全面评估受局灶性皮质发育不良影响的个体的临床数据,并分析来自脑组织的转录组数据。我们发现,双侧强直阵挛性癫痫发作是耐药癫痫患者中最常见的癫痫发作类型。在手术治疗的情况下,额叶和颞叶是病变的主要部位。此外,局灶性皮质发育不良诱导的耐药癫痫患者在手术后控制癫痫发作方面预后良好.CFAP47,CFAP126,JHY,RSPH4A,和SPAG1已成为局灶性皮质发育不良发展的潜在致病基因。
OBJECTIVE: This study aims to comprehensively analyze the clinical characteristics and identify the differentially expressed genes associated with drug-resistant epilepsy (DRE) in patients with focal cortical dysplasia (FCD).
METHODS: A retrospective investigation was conducted from July 2019 to June 2022, involving 40 pediatric cases of DRE linked to FCD. Subsequent follow-ups were done to assess post-surgical outcomes. Transcriptomic sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to examine differential gene expression between the FCD and control groups.
RESULTS: Among the 40 patients included in the study, focal to bilateral tonic-clonic seizures (13/40, 32.50%) and epileptic spasms (9/40, 22.50%) were the predominant seizure types. Magnetic resonance imaging (MRI) showed frequent involvement of the frontal (22/40, 55%) and temporal lobes (12/40, 30%). In cases with negative MRI results (13/13, 100%), positron emission tomography/computed tomography (PET-CT) scans revealed hypometabolic lesions. Fused MRI/PET-CT images demonstrated lesion reduction in 40.74% (11/27) of cases compared with PET-CT alone, while 59.26% (16/27) yielded results consistent with PET-CT findings. FCD type II was identified in 26 cases, and FCD type I in 13 cases. At the last follow-up, 38 patients were prescribed an average of 1.27 ± 1.05 anti-seizure medications (ASMs), with two patients discontinuing treatment. After a postoperative follow-up period of 23.50 months, 75% (30/40) of patients achieved Engel class I outcome. Transcriptomic sequencing and qRT-PCR analysis identified several genes primarily associated with cilia, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1.
CONCLUSIONS: This study highlights focal to bilateral tonic-clonic seizures as the most common seizure type in patients with DRE due to FCD. Surgical intervention primarily targeted lesions in the frontal and temporal lobes. Patients with FCD-related DRE showed a promising prognosis for seizure control post-surgery. The identified genes, including CFAP47, CFAP126, JHY, RSPH4A, and SPAG1, could serve as potential biomarkers for FCD.
CONCLUSIONS: This study aimed to comprehensively evaluate the clinical data of individuals affected by focal cortical dysplasia and analyze transcriptomic data from brain tissues. We found that focal to bilateral tonic-clonic seizures were the most prevalent seizure type in patients with drug-resistant epilepsy. In cases treated surgically, the frontal and temporal lobes were the primary sites of the lesions. Moreover, patients with focal cortical dysplasia-induced drug-resistant epilepsy exhibited a favorable prognosis for seizure control after surgery. CFAP47, CFAP126, JHY, RSPH4A, and SPAG1 have emerged as potential pathogenic genes for the development of focal cortical dysplasia.