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.     

病灶性癫痫的手术治疗及影响其预后的因素分析

目的 探讨病灶性癫痫的手术方法，并分析影响手术预后的一些因素。方法 回顾性地分析自2001年4月～2003年4月之间在我研究所接受手术治疗的所有病灶性癫痫患者的临床资料。33例患者手术后随访时间皆在1年或1年以上。按照Engel疗效分级标准，将其分为效果满意组与不满意组，对术前临床特点、电生理情况、手术方法等因素进行分析比较。结果 手术后效果满意率为73％。下列因素与手术效果有相关性：癫痫患病时间、发作频率以及脑电图发作间期痫性放电是否局限在病灶的脑叶上。另一方面，比较发病时年龄、是否有既发全面强直阵挛性发作以及是否完全切除术中皮层脑电监测(ECoG)为阳性的皮层三个因素，两组间无显著差异。不满意组中，皮质发育不全的患者占多数。结论 对于病灶性癫痫，手术采用病灶与周围致痫灶同时切除的方法，可获得满意的效果。癫痫患病时间、发作频率以及脑电图发作间期痫性放电是否局限在病灶的脑叶上与手术的效果有一定的相关性。     

颞叶新皮质癫痫手术的疗效分析

目的分析总结颞叶新皮质癫痫患者临床特征、术前评估、手术方法和疗效。方法对36例颞叶新皮质癫痫行神经电生理、MRI,正电子发射计算断层显像计算机体层扫描（PET—CT）定位,术中皮层电极和深部电极描记,联合采用不同术式以及术后随访6个月至2年的疗效观察。结果疗效按谭启富的标准分类：Ⅰ级12例,Ⅱ级11例,Ⅲ级8例,Ⅳ级5例,Ⅴ级0例。病理报告：胶质增生23例;微小血管畸形5例;灰质异位1例,无异常发现7例。无手术致残和死亡。结论联合采取不同术式,如：行海马及杏仁核部分切除,对颞叶新皮质癫痫可达到良好的治疗效果,且无严重手术并发症。     

Lesional mesial temporal lobe epilepsy and limited resections: prognostic factors and outcome

OBJECTIVES: To evaluate the influence of clinical, investigational, surgical, and histopathological factors on postoperative seizure relief in patients with mesial temporal lobe epilepsy (MTLE) due to lesions other than ammonshornsclerosis (AHS). METHODS: Of 738 patients operated for TLE, 78 patients underwent limited resections for lesional MTLE (1990-2000). Seventy four patients with a follow up of more than one year were included. The preoperative clinical, neuropsychological, electroencephalogram, and neuroimaging characteristics were prospectively collected in a database. The histopathological material was re-examined. RESULTS: The mean follow up was 49 months. Fifty eight patients were classified as seizure free (78.4% Class I), and six as almost seizure free (8.1% Class II), grouped together as satisfactory seizure control (64 patients, 86.5%). Five patients (6.8%) were categorised in Classes III and IV, respectively. These were grouped as unsatisfactory seizure control (10 patients, 13.5%). Surgical procedures were: 32 amygdalohippocampectomies (AH), 17 partial anterior AH, 15 AH plus polar resection, seven AH plus basal resection, and three AH plus extended temporal lesionectomy. There was no mortality and 2.7% mild permanent morbidity. Seizure relief did neither differ significantly with these approaches, nor with different classes of pathological findings (43 developmental tumours, 12 glial tumours, 10 dysplasias, and nine others). Even operation of dysplasias resulted in 80% satisfactory seizure control. Seizure onset during childhood proved to be a negative predictor for seizure relief (p = 0.020). MRI revealed 73 suspected lesions (98.6%), one dysembryoplastic neuroepithelial tumour was missed, in four cases no structural abnormalities could be confirmed with histopathological exam. Additionally, multifactorial regression revealed the factors "seizure onset after 10 years of age", "presence of complex partial seizures", "absence of a neurological deficit", and a "correlating neuropsychological deficit" as predictive for satisfactory seizure control. CONCLUSIONS: "Preoperative tailoring" resulting in limit resections has proven to be safe and to provide a very good chance for satisfactory seizure relief in patients with lesional MTLE.     

颞叶新皮层癫痫的外科治疗（附42例病例分析）

目的研究颞叶新皮层癫痫外科治疗的临床相关问题。方法42例病人术前均经128导视频EEG及MRI检查,MRI阴性者进一步行SPECT检查;对于术前无创检查难以确定致痫灶者行硬膜下电极埋藏纪录;术中利用ECoG进一步明确致痫灶的范围后进行个体化治疗。结果①本组资料中,术前MRI的病理灶定位与128导视频EEG的致痫灶定侧高度一致(P<0.05);②MRI阳性的35例中有25例致痫灶位于病灶附近,MRI阴性7例者的SPECT与术中ECoG结果完全一致;③参照Engel标准,本组病例平均随访3.6±1.1年,总有效率为88.10%,其中Ⅰ级占71.43%,Ⅱ级占16.67%;④致痫灶处理的手术方式与预后密切相关(P<0.05)。结论①颞叶新皮层癫痫的术前定位应综合考虑方可决定手术方案;②明确致痫灶仅限于颞叶新皮层时,手术不必涉及到颞叶内侧面结构,以防增加病人的致残率。     

Relationship between preoperative hypometabolism and surgical outcome in neocortical epilepsy surgery

Purpose: Fluorine‐18‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) hypometabolism has been used to localize the epileptogenic zone. However, glucose hypometabolism remote to the ictal focus is common and its relationship to surgical outcome has not been considered in many studies. We investigated the relationship between surgical outcome and FDG‐PET hypometabolism topography in a large cohort of patients with neocortical epilepsy. Methods: We identified all patients (n = 68) who had interictal FDG‐PET between 1994 and 2004 and who underwent resective epilepsy surgery with follow up for more than 2 years. The volumes of significant FDG‐PET hypometabolism involving the resected epileptic focus and its surrounding regions (perifocal hypometabolism) and those distant to and not contiguous with the perifocal hypometabolism (remote hypometabolism) were determined statistically using Statistical Parametric Mapping (voxel threshold p = 0.01, extent threshold ≥250 voxels, uncorrected cluster‐level significance p < 0.05) and were compared with magnetic resonance imaging (MRI) and clinical and demographic variables using a multiple logistic regression model to identify independent predictors of seizure outcome. Key Findings: Remote hypometabolism was present in 39 patients. Seizure freedom was 49% (19 of 39 patients) in patients with glucose hypometabolism remote from the epileptogenic zone compared to 90% (26 of 29 patients) in patients without remote hypometabolism. In 43 patients with an MRI‐identified lesion, seizure freedom was 79% (34 of 43 patients). In patients with normal MRI, cortical dysplasia was the predominant pathologic substrate. Multiple logistic regression analysis identified a larger volume of significant remote hypometabolism (p < 0.005) and absence of a MRI‐localized lesion (p = 0.006) as independent predictors of continued seizures after surgery. Significance: In patients with widespread glucose hypometabolism that is statistically significant when compared to controls, epilepsy surgery may not result in complete seizure freedom despite complete removal of the MRI‐identified lesion. The volume of significant glucose hypometabolism remote to the ictal‐onset zone may be an independent predictor of the success of epilepsy surgery.     

Prognostic factors in neocortical epilepsy surgery: multivariate analysis

PURPOSE: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery. METHODS: One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status >or=2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors. RESULTS: The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p<0.05). Multivariate analysis revealed that a focal lesion on MRI (p=0.003), correct localization by FDG-PET (p=0.007), and localized ictal onset on EEG (p=0.01) were independent predictors of a good outcome. CONCLUSIONS: The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.     

Extent of neocortical resection and surgical outcome of epilepsy: Intracranial EEG analysis

Purpose: Intracranial electroencephalography (EEG) monitoring is an important process in the presurgical evaluation for epilepsy surgery. The objective of this study was to identify the ideal resection margin in neocortical epilepsy guided by subdural electrodes. For this purpose, we investigated the relationship between the extent of resection guided by subdural electrodes and the outcome of epilepsy surgery. Methods: Intracranial EEG studies were analyzed in 177 consecutive patients who had undergone resective epilepsy surgery. We reviewed various intracranial EEG findings and resection extent. We analyzed the relationships between the surgical outcomes and intracranial EEG factors: the frequency, morphology, and distribution of ictal‐onset discharges, the propagation speed, and the time lag between clinical and intracranial ictal onset. We also investigated whether the extent of resection, including the area showing ictal rhythm and various interictal abnormalities—such as frequent interictal spikes, pathologic delta waves, and paroxysmal fast activity—influenced the surgical outcome. Results: Seventy‐five patients (42%) were seizure free. A seizure‐free outcome was significantly associated with a resection that included the area showing ictal spreading rhythm during the first 3 s or included all the electrodes showing pathologic delta waves or frequent interictal spikes. However, subgroup analysis revealed that the extent of resection did not affect the surgical outcome in lateral temporal lobe epilepsy. Conclusions: The extent of resection is closely associated with surgical outcome, especially in extratemporal lobe epilepsy. Resection that includes the area with total pathologic delta waves and frequent interictal spikes predicts a good surgical outcome.     

Prognostic factors for surgery of neocortical temporal lobe epilepsy.

OBJECTIVES: In the current classification of epilepsies two forms of temporal lobe epilepsy (TLE) were included: mesial and lateral (neocortical) TLE. We aimed at identifying prognostic factors for the surgical outcome of lesional neocortical TLE. METHODS: We included consecutive patients who had undergone presurgical evaluation including ictal video-EEG and high-resolution MRI, who had TLE due to neocortical lateral epileptogenic lesions, who had a lesionectomy and who had >2-year follow-up. RESULTS: There were 29 patients who met the inclusion criteria. Twenty of them became postoperatively seizure-free. Patients' mean age was 34.8+/-9 years (range 18-52). The age at epilepsy onset was 20.1+/-8 years. We found that left-sided surgery (p=0.048) and focal cortical dysplasia (FCD) on MRI (p=0.005) were associated with non-seizure-free outcome, while lateralized/localized EEG seizure pattern (p=0.032), tumors on the MRI (p=0.013), and a favorable seizure situation at the 6-month postoperative evaluation were associated with 2-year postoperative seizure-freedom (p<0.001). Multivariate analysis indicated that the side of surgery was not an independent predictor. CONCLUSION: More than two-thirds of the patients with neocortical TLE became seizure-free postoperatively. Lateralized/localized EEG seizure pattern and tumors on the MRI were associated with postoperative seizure-freedom, while FCD were associated with a poor outcome. The 6-month postoperative outcome is a reliable predictor for the long-term outcome.     

Relationship of flumazenil and glucose PET abnormalities to neocortical epilepsy surgery outcome.

BACKGROUND: Cortical areas showing abnormal glucose metabolism and [(11)C]flumazenil (FMZ) binding are commonly seen on PET scans of patients with intractable partial epilepsy, but it is unclear whether these must be totally resected to achieve seizure control. OBJECTIVE: To analyze whether the extent of cortex showing 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) or FMZ PET abnormalities correlates with the outcome of resective epilepsy surgery. METHODS: Cortical FDG and FMZ PET abnormalities in 15 young patients (mean age, 12.2 +/- 7.0 years) with intractable partial epilepsy of neocortical origin were marked as regions with abnormal asymmetry using an objective semiautomated software package. These marked regions were then projected and measured on the brain surface reconstructed from the coregistered high-resolution MRI. Following cortical resection, the size of nonresected cortex with preoperative PET abnormalities was also measured (calculated separately for marked areas in the lobe of seizure onset as defined by long-term video EEG monitoring, and in remote cortical areas). Extent of preoperative PET abnormalities and postoperative nonresected cortex abnormalities on PET were correlated with outcome scores. RESULTS: Large preoperative FMZ PET abnormalities were associated with poor outcome (r = 0.57; p = 0.025). Larger areas of nonresected cortex with preoperative FMZ PET abnormalities in the lobe of seizure onset were also associated with worse outcome in the whole group (r = 0.66; p = 0.007) as well as in patients with extratemporal resection (r = 0.73; p = 0.007), and in those with no lesion on MRI (r = 0.60; p = 0.049). Patients with seizure-free outcome had significantly smaller nonresected cortex with preoperative FMZ PET abnormalities than those who continued to have seizures (p = 0.022). No significant correlations between nonresected FDG PET abnormalities and surgical outcome were found. CONCLUSIONS: Extensive cortical abnormalities on FMZ PET predict poor outcome in neocortical epilepsy surgery. Resection of FMZ abnormalities in the lobe of seizure onset is associated with excellent outcome even in the absence of a structural lesion. In contrast, although FDG PET abnormalities regionalized the epileptogenic area, their size was not related to the extent of epileptogenic tissue to be removed.     

Pre-surgical evaluation and surgical outcome of 41 patients with non-lesional neocortical epilepsy.

Pre-surgical evaluation and the surgical treatment of non-lesional neocortical epilepsy is one of the most challenging areas in epilepsy surgery. The aim of this study was to evaluate the surgical outcome and the diagnostic role of ictal scalp electroencephalography (EEG), interictal (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and ictal technetium-99m hexamethylpropyleneamine oxime single photon emission tomography ( (99m)Tc-HMPAO SPECT). In 41 non-lesional neocortical epilepsy patients (16 frontal lobe epilepsy, 11 neocortical temporal lobe epilepsy, seven occipital lobe epilepsy, four parietal lobe epilepsy, and three with multifocal onset) who underwent surgical treatment between December 1994 and July 1998, we evaluated the surgical outcome with a follow-up of at least 1 year. The localizing and lateralizing values of ictal scalp EEG, interictal FDG-PET, and ictal SPECT were evaluated in those patients with good surgical outcome. Ictal scalp EEG had the highest diagnostic sensitivity in the localization of epileptogenic foci (69.7% vs. 42.9% for FDG-PET and 33.3% for ictal SPECT; P= 0.027). However, no significant difference was found in the lateralization of the epileptogenic hemisphere among the three modalities (78.8% for ictal scalp EEG, 57.2% for FDG-PET, and 55.5% for ictal SPECT; P= 0.102). During a mean follow-up of 2.77 +/- 1.12 years, 33 (80.5%) showed good surgical outcome (seizure free or seizure reduction >90%), including 16 (39.0%) seizure free patients. Ictal scalp EEG was the most useful diagnostic tool in the localization of epileptogenic foci. Interictal FDG-PET and ictal SPECT were found to be useful as complementary and, sometimes, independent modalities. Many patients with non-lesional neocortical epilepsy would benefit from surgical treatment.     

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.     

Childhood absence epilepsy: evolution and prognostic factors

PURPOSE: To evaluate how diagnostic criteria influence remission rates for patients with childhood absence epilepsy (CAE) and to assess clinical and EEG parameters as predictors of outcome. METHODS: One hundred nineteen patients were diagnosed with CAE, according to International League Against Epilepsy (ILAE) classification criteria. They were subsequently evaluated according to stricter diagnostic criteria. Sixty-two subjects fulfilled these criteria as group 2; 57 did not and constituted group 1. Diagnostic parameters that prevented patients of group 1 from entering group 2, and variables such as sex, familial history of generalized epilepsy, and personal history of febrile convulsions also were tested as prognostic factors for terminal remission. RESULTS: Compared with those in group 1, patients of group 2 had significantly higher rates of seizure control (95% vs. 77%), higher rates of terminal remission (82% vs. 51%), fewer generalized tonic-clonic seizures (8% vs. 30%), and shorter mean periods of treatment (2.2 vs. 3.8 years). Significantly fewer patients were receiving polytherapy in group 2 than in group 1 (11% vs. 47%), and fewer patients had seizure relapses at antiepileptic drug discontinuation (0 vs. 22%). CONCLUSIONS: Remission rates of patients with CAE are greatly influenced by the classification criteria used for selection. Stricter diagnostic criteria allow the definition of a homogeneous group of patients with excellent prognosis. Factors predicting unfavorable prognosis were generalized tonic-clonic seizures in the active stage of absences, myoclonic jerks, eyelid myoclonia or perioral myoclonia, and EEG features atypical for CAE.     

Cognitive performance in cryptogenic epilepsy

Cognitive impairment in epilepsy has begun to gain more attention in clinical practice. There is now a considerable amount of research relating to memory functioning in epilepsy, however, few studies specifically focused on cryptogenic epilepsy. We investigated the cognitive performance in cryptogenic epilepsy patients with the aid of cognitive ability screening instrument (CASI), based on cross-sectional and longitudinal aspects. A total of 100 patients who met the diagnostic criteria of cryptogenic epilepsy were recruited from a national university hospital. The patients with normal CASI scores were compared with those with abnormal ones. We also compared the follow-up CASI score after 3 years with the previous score in all cryptogenic epilepsy patients. Thirty-six per cent of cryptogenic epilepsy patients showed cognitive impairment. The variables correlated with higher risks of cognitive impairment were lower educational status, number of seizure types, duration of seizure and polytherapy, especially in the lower educational status. The correlation between CASI and the Mini-Mental State Examination was excellent. In the follow-up study, the abnormal group showed significant improvement in total CASI score. The normal group showed no significant change. We suggest that in cryptogenic epilepsy, lower educational status remains the most important factor in determining cognitive performance. Adequate treatment with antiepileptic drugs can improve cognitive performance in previously cognitively impaired patients.     

A population-based study of long-term outcomes of cryptogenic focal epilepsy in childhood: cryptogenic epilepsy is probably not symptomatic epilepsy

Purpose: To compare long‐term outcome in a population‐based group of children with cryptogenic versus symptomatic focal epilepsy diagnosed from 1980 to 2004 and to define the course of epilepsy in the cryptogenic group. Methods: We identified all children residing in Olmsted County, MN, 1 month through 17 years, with newly diagnosed, nonidiopathic focal epilepsy from 1980 to 2004. Children with idiopathic partial epilepsy syndromes were excluded. Medical records were reviewed to determine etiology, results of imaging and EEG studies, treatments used, and long‐term outcome. Children were defined as having symptomatic epilepsy if they had a known genetic or structural/metabolic etiology, and as cryptogenic if they did not. Key Findings: Of 359 children with newly diagnosed epilepsy, 215 (60%) had nonidiopathic focal epilepsy. Of these, 206 (96%) were followed for >12 months. Ninety‐five children (46%) were classified as symptomatic. Median follow‐up from diagnosis was similar in both groups, being 157 months (25%, 75%: 89, 233) in the cryptogenic group versus 134 months (25%, 75%: 78, 220) in the symptomatic group (p = 0.26). Of 111 cryptogenic cases, 66% had normal cognition. Long‐term outcome was significantly better in those with cryptogenic versus symptomatic etiology (intractable epilepsy at last follow‐up, 7% vs. 40%, p < 0.001; seizure freedom at last follow‐up, 81% vs. 55%, p < 0.001). Of those who achieved seizure freedom at final follow‐up, 68% of the cryptogenic group versus only 46% of the symptomatic group were off antiepileptic medications (p = 0.01). One‐third of the cryptogenic group had a remarkably benign disorder, with no seizures seen after initiation of medication, or in those who were untreated, after the second afebrile seizure. A further 5% had seizures within the first year but remained seizure‐free thereafter. With the exception of perinatal complications, which predicted against seizure remission, no other factors were found to significantly predict outcome in the cryptogenic group. Significance: More than half of childhood nonidiopathic localization‐related epilepsy is cryptogenic. This group has a significantly better long‐term outcome than those with a symptomatic etiology, and should be distinguished from it.     

Gelastic epilepsy: symptomatic and cryptogenic cases

PURPOSE: To describe the etiology, characteristics, and clinical evolution of epilepsy in patients with gelastic seizures (GSs). METHODS: Nine patients whose seizures were characterized by typical laughing attacks were observed between 1986 and 1997. Patients were selected based on electroencephalogram (EEG) or video-EEG recordings of at least one GS and on magnetic resonance imaging (MRI) study. RESULTS: Five patients were affected by symptomatic localization-related epilepsy (LRE), with four of the patients' disorders related to a hypothalamic hamartoma (HH) and one to tuberous sclerosis (TS) without evident hypothalamic lesions. In four patients (the cryptogenic cases) MRI was negative also in these cases, clinical and EEG data suggested a focal origin of the seizures. The epileptic syndrome in the HH cases was usually drug-resistant, and was surgically treated in two of the patients. The patient with TS became seizure free with vigabatrin. In the cryptogenic cases, the ictal, clinical, and EEG semiology were similar to the symptomatic cases: the clinical evolution was variable, with patients having transient drug resistance or partial response to treatment. No cognitive defects were observed in the cryptogenic patients. None of the nine patients had precocious puberty. CONCLUSIONS: We confirm the frequent finding of HHs in GSs and further underline how GSs may also be observed in patients without MRI lesions and with normal neurologic status. In these patients, clinical and EEG seizure semiology is similar to symptomatic cases, but the clinical evolution is usually more benign.