Surgical outcome and prognostic factors of pediatric epilepsy caused by cortical dysplasia

Objects We analyzed 30 patients with cortical dysplasia (CD) and epilepsy to evaluate the clinical characteristics and surgical outcome of both epilepsy control and neurocognition.Materials and methods The mean ages at seizure onset and at the time of the operation were 3.6 years (range, 1 month–12.6 years) and 10.3 years (range, 1.5–18.3 years), respectively. The mean follow-up period was 3.2 years (range, 1–5.3 years). ¹⁸FDG-positron emission tomography was the most sensitive and magnetic resonance imaging was the most specific in localizing the lesion. Developmental/intellectual delay was predominant in the early-onset group (n=18, seizure onset <3 years), with intelligence tending to be normal in the late-onset group (n=12, seizure onset ≥3 years). Mild CD predominated in the late-onset epilepsy group and moderate or severe CD in the early-onset group (p=0.005). The surgical success rate of epilepsy control was 87%. A better outcome was obtained if the lesion was confined to the temporal lobe. School performance was favorable in 43%. The age at seizure onset and preoperative developmental/intellectual delay were the important prognostic factors in school performance as well as the epilepsy control. A total of 77% of patients had relatively good social adaptation. Successful epilepsy control and good school performance were affirmative conditions precedent to social adaptation.Conclusions Due to the favorable control of epilepsy and its effect on school performance and social adaptation, surgical treatment is strongly recommended for cortical dysplasia and intractable epilepsy.     

Intraoperative ultrasound to define focal cortical dysplasia in epilepsy surgery

Focal cortical dyplasia (FCD) is a frequent cause of medication-resistant focal epilepsy. Patients with FCD may benefit from epilepsy surgery. However, it is difficult to intraoperatively define lesion boundaries. In this case report we present a novel tool to identify FCD intraoperatively. A patient with frontal lobe epilepsy underwent resection of a left frontomesial FCD. Image guidance was achieved by intraoperative ultrasound, which depicted the lesion with a higher resolution than preoperative MRI. Postoperatively the patient remained seizure free. Intraoperative ultrasound may be helpful in identifying and targeting subtle epileptogenic lesions, which are difficult to visualize.     

Risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia

Objective

The purpose of this study was to identify the risk factors of cognitive impairment in pediatric epilepsy patients with focal cortical dysplasia (FCD).

Surgical outcome and predictive factors in adult patients with intractable epilepsy and focal cortical dysplasia

OBJECTIVES: To determine the surgical outcome and prognostic factors in adult patients with intractable epilepsy and focal cortical dysplasia (FCD). MATERIALS AND METHODS: We retrospectively studied the operative outcome in 21 consecutive adult patients with FCD who underwent surgical treatment for intractable partial epilepsy. RESULTS: The mean age at surgery was 32.7 years (range, 18-58 years). The median post-operative follow-up was 2.5 years. The FCD was extratemporal in 11 patients, involved the temporal lobe in 10 patients, and was multilobar in eight patients. Eleven patients (52%) were rendered seizure-free, four patients (19%) had >95% reduction in seizures, and two patients (10%) had an 80-94% reduction in seizures. A seizure-free outcome was associated with shorter duration of epilepsy (P = 0.02). CONCLUSION: Adult patients with FCD may be candidates for surgical treatment of intractable partial epilepsy. Most individuals have neocortical, extrahippocampal seizures and approximately 50% of patients are rendered seizure-free.     

皮质发育不良性癫痫的超微形态学观察

目的 探讨伴皮质发育不良的难治性癫痫脑组织的超微形态学改变与癫痫发病机制的关系.方法 回顾性分析7例患者的临床资料,对其手术切除的标本进行电镜观察.结果 伴皮质发育不良的难治性癫痫主要发生在巨脑回畸形、灰质异位、皮层发育不良及结构紊乱,电镜下表现为神经组织变性,神经元减少或增多,星形细胞肿胀,突触数苗改变,突触前终末兴奋性递质小泡增多.结论 伴皮质发育不良的难治性癫痫患者脑组织发生了大脑皮质神经元形态异常,固缩变性,皮质结构紊乱,神经毡内突触数量及结构的改变.     

Temporo-mesial extraventricular neurocytoma and cortical dysplasia in focal temporal lobe epilepsy

We describe a 17-year-old boy with a left extraventricular temporo-mesial neurocytoma associated with cortical dysplasia causing focal pharmacoresistant temporal lobe epilepsy. He presented with a long history of medically refractory, temporal complex partial seizures. MRI showed a left temporo-mesial lesion suspect to be a low-grade tumor. Based on the pre-operative non-invasive neurophysiological studies, the patient underwent a left tailored temporal antero-mesial resection. Histopathological examination showed an extraventricular neurocytoma associated with architectural dysplasia (Type 1a) of the temporal pole. The patient was seizure-free at 2 years follow-up. Extraventricular neurocytomas must be considered in the differential diagnosis of the plethora of low-grade tumors associated with focal epilepsy that typically involve the temporal lobe, and are frequently associated with focal cortical dysplasia.     

Taylor’s focal cortical dysplasia increases the risk of sleep‐related epilepsy

Purpose: To analyze the topography of the epileptogenic zone (EZ) and the etiologic substrate as risk factors for sleep‐related focal epilepsy. Methods: Three hundred three patients (172 males and 131 females, mean age at surgery 25.6 ± 13.1 years), who were seizure‐free after resective surgery for drug‐resistant focal epilepsy, were retrospectively reviewed. Statistical analysis was conducted to evaluate the risk of presenting sleep‐related epilepsy (SRE) against topography of resection (assumed to correspond or to include the EZ) and results of histology. Results: Thirty‐nine patients (12.8%) presented with an SRE. At bivariate analysis, a higher frequency of SRE was associated with a frontal lobe EZ (p = 1.94 × 10^?9) and Taylor’s FCD (TFCD, p = 2.20 × 10^?16), whereas architectural FCD (p = 0.00977), ganglioglioma (p = 0.02508), and mesial temporal sclerosis (p = 2.47 × 10^?5) were correlated with a reduced frequency of SRE. Multivariate analysis demonstrated that the only variable significantly associated with SRE was the presence of a TFCD, which increased 14‐fold the risk of SRE [p = 1.66 × 10^?10; risk ratio (RR) = 14.44]. Discussion: In this study, we have demonstrated a significant and strong association between SRE and TFCD in a select population of patients with drug‐resistant focal epilepsy submitted to surgical resection of the EZ. Although our results cannot be applied to the entire spectrum of SRE, the presence of TFCD as the underlying etiology should be considered when evaluating patients with SRE, because surgery can provide excellent results on seizures in these cases.     

局限性脑皮质发育不良继发顽固性癫痫的手术治疗

目的 探讨局限性脑皮质发育不良（FCD）的诊断、影像学和电生理学特点，以及手术治疗的策略与方法。方法 1996年6月至2003年12月在意大利米兰NiguardaCa’Granda医院手术治疗的442例癫痫患者中，根据该中心提出的FCD病理学分类标准，对81例诊断为FCD的病例进行回顾性研究。其中皮层组织结构发育异常（AD）42例、细胞组织结构发育异常（CD）12例、Taylor脑皮质发育不良（TFCD）27例。患者术前均行MRI、VEEG检查，61％的患者还接受了立体脑电图检查（SEEG）。结果 术前MRI检查阳性率65％。癫痫术后随访1年以上总治愈率为54％（Engle Ia），其中AD组为49％、CD组45％、TFCD组69％。FCD病理分型的不同与癫痫发作频率、致痫灶部位以及手术效果有关。AD组致痫灶常见于颞叶，癫痫发作次数少于CD和TFCD组。而TFCD常发生于颞叶以外的部位，SEEG发作间期显示有典型的放电节律，且手术愈后较好。结论 该分类标准简单且易于操作，对分析临床表现与判定手术效果有指导意义。SEEG技术在研究FCD，特别是TFCD电生理特征有独特的优势，并为术前准确定位致痫灶范围、保证手术效果提供了重要保障。     

Pigmented ganglioglioma in a patient with chronic epilepsy and cortical dysplasia

We report a rare case of a 22-year-old woman with biopsy-proven pigmented ganglioglioma. The patient initially underwent a right temporal lobectomy for intractable seizures at the age of 9 and remained seizure free for several years but subsequently developed complex partial seizures. Due to enhancement of a left mesial occipital lesion on preoperative MRI of the brain, the patient underwent a left subdural electrode placement and simultaneous biopsy of the left mesial occipital lesion. Biopsy results revealed a rare pigmented ganglioglioma, World Health Organization Grade I. The seizure focus was identified in the left mesial occipital lobe and the patient underwent tumor resection. An extensive literature search revealed that our patient is the fourth case of pigmented ganglioglioma described in the literature and was positive for BRAF V600E mutation by molecular studies.     

Neuropsychological outcome following focal cortical removal for intractable epilepsy in children

In children, surgery for epilepsy has been recognized as a viable treatment option since publication of S. Davidson and M.A. Falconer's outcome study in 1975 [Lancet North Am Ed 5:1260-3], which demonstrated that medical outcome of children who underwent anterior temporal lobectomy paralleled that of adults. Pediatric surgical programs and the literature on medical outcome have grown considerably since that time, with surgery being offered to children with temporal but also extratemporal epilepsy foci. Comparatively little work has been conducted in the area of neuropsychological outcome. This article outlines differences in adult and pediatric outcome studies, reviews the literature on the intellectual and memory outcome in children, and discusses shortcomings of the pediatric outcome research conducted to date.     

局灶性皮质发育不良相关癫痫的诊疗进展

局灶性皮质发育不良（FCD）是临床中常见的局灶性癫痫的病理类型之一,多数FCD患者在癫痫起病后即表现出耐药性,成为难治性癫痫。2011年国际抗癫痫联盟提出了新的FCD病理分型后,让大家对FCD有了更进一步的认识。近几年随着医学检测技术、病理研究及神经影像技术的发展,针对不同病理亚型的研究使得临床医生对FCD致病机制及治疗措施的决策有了新的理解。该文综合近年相关文献,对FCD不同亚型临床特点、治疗方法及相关预后作一综述,以期为临床决策提供帮助。     

Sleep related epilepsy in focal cortical dysplasia type 2: Insights from sleep recordings in presurgical evaluation

ObjectiveTo determine the relationship between seizure onset, sleep stage and focal cortical dysplasia type 2 (FCD2) location in sleep related epilepsy (SRE).MethodsWe reviewed scalp video-EEG data of 77 patients with SRE among 130 surgically treated patients with histologically confirmed FCD2. Seizure onset was classified as occurring during NREM, REM and after arousal.ResultsSleep recordings were available for 65 patients (37 males, 7–49 years old). FCD2 was located in frontal lobe in 46 (71%) and in extra-frontal regions in 19, including the temporal lobe in 6. MRI was negative/doubtful in 35 cases. Interictal rhythmic/pseudorhythmic spike rate increased from 31% during waking to 65% during sleep. Seizure onset occurred from NREM in 46 cases (71%), mostly from stage 2, and after arousal in 14 (22%). Seizures occurring from NREM/REM sleep were significantly more frequent in frontal (89%) compared to extra-frontal location (42%), whilst arousal preceded seizure onset more often in extra-frontal (58%) compared to frontal location (7%).ConclusionsNREM seizure onset is the most common ictal pattern in SRE due to frontal FCD2 whereas preceding arousal points to extra-frontal regions.SignificanceSleep recordings may help for FCD2 localisation and suggest topography dependent impact on sleep related epileptic networks.     

Clinical and experimental studies of epilepsy associated with focal cortical dysplasia

The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.     

Low-grade focal cortical dysplasia is associated with prenatal and perinatal brain injury

Purpose: Prenatal and perinatal adverse events are reported to have a pathogenetic role in focal cortical dysplasia (FCD). However, no data are available regarding the prevalence and significance of this association. A cohort of children with significant prenatal and perinatal brain injury and histologically proven mild malformations of cortical development (mMCD) or FCD was analyzed. Methods: We retrospectively evaluated a surgical series of 200 patients with histologically confirmed mMCD/FCD. Combined historical and radiologic inclusion criteria were used to identify patients with prenatal and perinatal risk factors. Electroclinical, imaging, neuropsychological, surgical, histopathologic, and seizure outcome data were reviewed. Results: Prenatal and perinatal insults including severe prematurity, asphyxia, bleeding, hydrocephalus, and stroke occurred in 12.5% of children with mMCD/FCD (n = 25). Their epilepsy was characterized by early seizure onset, high seizure frequency, and absence of seizure control. Patients with significant prenatal and perinatal risk factors had more abnormal neurologic findings, lower intelligence quotient (IQ) scores, and slower background EEG activity than mMCD/FCD subjects without prenatal or perinatal brain injury. MRI evidence of cortical malformations was identified in 74% of patients. Most patients underwent large multilobar resections or hemispherectomies; 54% were seizure‐free 2 years after surgery. Histologically “milder” forms of cortical malformations (mMCD and FCD type I) were observed most commonly in our series. Conclusions: Surgically remediable low‐grade cortical malformations may occur in children with significant prenatally and perinatally acquired encephalopathies and play an important role in the pathogenesis of their epilepsy. Presurgical detection of dysplastic cortex has important practical consequences for surgical planning.     

Correlation of EEG, neuroimaging and histopathology in an epilepsy patient with diffuse cortical dysplasia

The correlation between scalp EEG, intraoperative electrocorticogram, neuroimaging and histopathology was examined in an epileptic child with diffuse cortical dysplasia. The 6-year-old girl with moderate mental retardation had suffered from intractable complex partial and generalized epilepsies since the age of 2 years. MR images demonstrated unilateral large macrogyria/polymicrogyria and schizencephaly in the right occipital lobe. The epileptic focus was detected on the macrogyria by EEG and single photon emission tomography. However, the intraoperative electrocorticogram showed frequent spikes from the polymicrogyria and no paroxysmal activity in the macrogyria. The polymicrogyria and the macrogyric lesion were resected, using an image-guided system. The histological findings revealed that the macrogyria was covered with and separated by glial bundles. It has been reported that epileptogenicity is produced from abnormal neurons and their arrangement in cortical dysplasia; in this case, however, the major dysplastic lesion had no epileptogenicity; rather the focus might be in the polymicrogyria around the lesion. Received: 18 November 1998 Revised: 19 February 1999     

不同病理分型局部脑皮质发育不良的MRI研究

目的 探讨不同病理分型局部脑皮质发育不良(FCD)在MRI表现上的特点.方法 回顾性分析广州医学院第二附属医院自2006年5月至2010年6月收治的23例FCD患者资料.所有患者均经手术病理证实,按Palmini方法FCDⅠA、FCDⅠB、FCDⅡA、FCDⅡB4型,总结各类型患者MRI表现的特点.结果 23例患者中FCD Ⅰ A 2例,FeD Ⅰ B 6例,FCDⅡA 8例,FCDⅡB7例.FCDⅡ型中,有11例MRI表现为病灶Flair高信号,Ⅰ型中仅有2例,差异有统计学意义(P=0.039).而病灶T2高信号、白质内向脑室延伸带等表现虽然在Ⅰ、Ⅱ型间相差较大,但差异没有统计学意义(P=0.074、0.058).ⅡB型的MRI表现在灰白质分界不清、病灶T2高信号、脑沟加深、灰质增厚、白质内向脑室延伸带等方面均明显高于其他3型,差异有统计学意义(P<0.05).结论 不同病理分型FeD的MRI表现各有特点,特别是ⅡB型,其在MRI上的表现与其他3型明显不同,了解这些特点有助于FCD的早期诊断和术前评估.     

脑皮质发育不良继发顽固性癫痫的病理分型及手术治疗

目的 探讨局灶性脑发育不良(FCD)的临床特征、病理学、影像学的特点及手术疗效.方法 42例外科手术切除致痫灶并经病理证实为FCD的患者中,根据Palmini病理学分型进行分类,并对其临床特征、影像学特点及手术疗效进行回顾性分析.结果 42例患者中,按致痫灶部位分类颢叶24例、额叶14例、顶叶6例及枕叶3例,其中多脑叶5例.术前影像学检查阳性率62%.组织学分型FCDⅠA型9例,FCDⅠB型21例,FCDⅡA型5例,FCDⅡB型7例,其中以FCD Ⅰ B型最为常见,多位于颞叶且常伴有海马硬化.所有患者术后至少随访1年以上,癫痫术后治愈率FCD位于颞叶67%,颞叶以外43%(EngleⅠa).结论 FCD是难治性癫痫常见的病理学改变,其病理分型与临床特征和致痫灶部位存在相关性,为制定手术方案和判定手术效果提供了依据.     

Three-dimensional brain surface visualization for epilepsy surgery of focal cortical dysplasia

Focal cortical dysplasia (FCD) causes medically intractable seizures in 5–10% of adult epilepsy patients, but patients can become seizure free through surgical resection. The authors present the utility of three-dimensional surface visualization (3DSV) that expands on existing imaging datasets to highlight surface vasculature as a tool for achieving more successful resections in patients with FCD. In this prospective series of six patients, preoperative 3DSV was performed for planning the surgical approach to the lesion and for intraoperative guidance. Reconstructions involved volume rendering of a contrast-enhanced dataset to visualize surface venous vasculature. Postoperatively, five of the six patients had complete resections, with one patient having a subtotal resection due to proximity to crucial vasculature. We report that 3DSV is a useful tool for surgical planning, since topographical relationships between lesion location and surface vasculature landmarks are less likely to change with surgical progress.