Malformations of cortical development (MCDs) and epilepsy: Experience from a tertiary care center in south India

IntroductionMalformations of cortical development (MCDs) are increasingly recognized as important cause of epilepsy, especially refractory epilepsy. In developing countries like India, where the facilities for sophisticated imaging are not easily accessible to all, the prevalence and the types of cortical malformations are largely unknown. Hence this preliminary study has been undertaken to examine the relation between epilepsy and malformations of cortical development in a resource-limited setting.AimsTo study various types of malformations of cortical development (MCDs) associated with epilepsy and to correlate with their clinical semiology.Settings and designThe study was conducted in a tertiary care neurological center in south India. Cohort included all patients with epilepsy associated with cortical malformation on neuroimaging.Methods and materialsNeuroimaging data of all patients with epilepsy were evaluated for a 5-year period from 1998 to 2003, for the presence of cortical malformations. The case records of those patients with cortical malformations were taken from the medical records department and the clinical and electrophysiological data were analyzed.ResultsWe are reporting 34 cases of MCDs evaluated during the 5-year period. The mean age of the cohort was 15.1 (±12.2) years, with a range from 3 months to 45 years and 52.9% were males. Mean age at seizure onset was 7.2 years (±7.8), with a mean duration of seizure of 8.1 years (±7.7). Delayed motor and mental milestones were present in 15 patients (44.1%) and positive family history of seizure/epilepsy was seen in 9 patients (26.5%). Cortical malformations were most often associated with partial seizures (19/34, 55.9%). The most common type of seizure was complex partial seizure, seen in 12 patients (35.3%). Majority had very frequent, uncontrolled seizures with 16 (47.1%) patients having a seizure frequency of more than one per day. Heterotopias were seen in 14 patients (41.2%), in isolation in 5 (14.7%) patients and in combination with other malformations in 9 (26.5%) patients. Pachygyria was present as an isolated anomaly in five (14.7%) patients and combined with other abnormalities in eight (23.5%) patients. Cortical dysplasia was seen in 5 (14.7%) patients, hemimegalencephaly in two patients, polymicrogyria in two patients, lissencephaly and schizencephaly were seen in one patient each. EEG demonstrated focal epileptiform discharges in 59.1%, while generalized epileptiform discharges were seen in 22.7% of patients. Twenty-seven out of 34 (79.4%) patients had refractory/difficult to treat epilepsy.ConclusionsMalformations of cortical development are a heterogenous group of disorders, associated with developmental delay and refractory seizures but seizures usually do not have pathognomonic semiologic features. Possibility of MCDs should be considered during the evaluation of refractory epilepsy cases.     

A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy

OBJECTIVE: To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double-blind, sham-controlled trial. METHODS: Twenty-one patients with malformations of cortical development and refractory epilepsy underwent five consecutive sessions of low-frequency rTMS, either sham or active (1Hz, 1,200 pulses), focally targeting the malformations of cortical development. The number of epileptiform discharges in the electroencephalogram and the number of clinical seizures were measured before (baseline), immediately after, as well as 30 and 60 days after rTMS treatment. RESULTS: rTMS significantly decreased the number of seizures in the active compared with sham rTMS group (p < 0.0001), and this effect lasted for at least 2 months. Furthermore, there was a significant decrease in the number of epileptiform discharges immediately after (p = 0.01) and at week 4 (p = 0.03) in the active rTMS group only. There were few mild adverse effects equally distributed in both groups. The preliminary cognitive evaluation suggests improvement in some aspects of cognition in the active rTMS group only. INTERPRETATION: Noninvasive brain stimulation for epilepsy may be an alternative treatment for pharmaco-resistant patients with clearly identifiable seizure foci in the cortical convexity and who are not eligible for surgical treatment.     

When is a postoperative seizure equivalent to “epilepsy recurrence” after epilepsy surgery?

Purpose: Up to one‐half of epilepsy surgery patients will have at least one seizure after surgery. We aim to characterize the prognosis following a first postoperative seizure, and provide criteria allowing early identification of recurrent refractory epilepsy. Methods: Analyzing 915 epilepsy surgery patients operated on between 1990 and 2007, we studied 276 who had ≥1 seizure beyond the immediate postoperative period. The probability of subsequent seizures was calculated using survival analysis. Patients were divided into seizure‐free (no seizures for ≥1 year) and refractory (persistent seizures) and analyzed using multivariate regression analysis. Results: After a first seizure, 50% had a recurrence within 1 month and 77% within a year before the risk slowed down to additional 2–3% increments every two subsequent years. After a second seizure, 50% had a recurrence within 2 weeks, 78% within 2 months, and 83% within 6 months. Having both the first and second seizures within six postoperative months [odds ratio (OR) 4.04; 95% confidence interval (CI) 2.05–8.40; p = 0.0001], an unprovoked initial recurrence (OR 3.92; 95% CI 2.13–7.30; p < 0.0001), and ipsilateral spikes on a 6‐months postoperative electroencephalography (EEG) (OR 2.05; 95% CI 1.10–3.88; p = 0.025) predicted a poorer outcome, with 95% of patients who had all three risk factors becoming refractory. All patients with cryptogenic epilepsy and recurrent seizures developed refractoriness. Discussion: Seizures will recur in most patients who present with their first postoperative event, with one‐third eventually regaining seizure‐freedom. Etiology and early and unprovoked postoperative seizures with epileptiform activity on EEG at six postoperative months may predict recurrent medical refractoriness.     

Callosotomy and subsequent surgery for children with refractory epilepsy

Callosotomy has been considered as a palliative therapy for refractory epilepsy patients with non-focal onset seizures. Residual partial seizures and unilateral epileptiform discharges on electroencephalography (EEG) are sometimes observed after callosotomy. These findings suggest that some patients may be candidates for subsequent resective surgery. Of 149 children who received a callosotomy, resective/disconnective surgery was subsequently performed in 19 patients. Most patients had generalized seizures and epileptiform discharges on EEG before callosotomy. Two-third had normal neuroimaging studies at initial presurgical evaluation. After callosotomy, ictal symptoms evolved into asymmetric features suggesting partial onset seizures. Post-callosotomy EEG showed completely lateralized or localized epileptiform discharges responsible for residual partial seizures in 16 of 19 patients. Fifteen patients underwent resective surgery of the unilateral frontal lobe, and the remaining received hemispherotomy or posterior quadrantectomy. After subsequent surgery, favorable seizure outcomes were obtained in 11 patients (57.9%). Favorable seizure outcomes may be achieved with callosotomy and subsequent surgery in selected patients who are not candidates for a conventional resective surgery at initial presurgical evaluation.     

Does Hyperventilation Elicit Epileptic Seizures?

PURPOSE: Voluntary hyperventilation has been advocated for many decades as an "activating" procedure to provoke clinical seizures and epileptiform discharges in subjects with suspected epilepsy who undergo standard EEG recordings. This study was undertaken to determine the effects of hyperventilation in patients with proven epilepsy. METHODS: We examined the records of 433 consecutive patients with proven epilepsy, as documented by long-term video-EEG studies. The patients underwent 5 min of voluntary hyperventilation during standard EEG recordings. All EEGs were interpreted by board-certified electroencephalographers. The patients ranged in age from 10 to 64 years; 384 (88.7%) had localization-related and 48 (11.3%) generalized epilepsy syndromes. RESULTS: Hyperventilation was associated with a clinical seizure in two (0.46%) of the subjects (partial seizures in both cases). Interictal epileptiform discharges were interpreted as showing in increase in frequency during hyperventilation in 19 (4.4%) patients, when compared with the baseline EEG. CONCLUSIONS: Voluntary hyperventilation in patients with unequivocal epilepsy is rarely associated with either clinical seizures or an increase in frequency of epileptiform discharges.     

Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures

Purpose: The aim of the present study was to investigate the correlation between epileptiform discharges on EEGs after febrile seizures and the prognosis of patients in terms of the development of epilepsy and recurrence of febrile seizures. This study also evaluated the characteristics of epileptiform discharges and EEG changes on follow-up examination. Methods: This study consisted of 36 children who presented to our hospital with febrile seizures and whose electroencephalograms (EEG) showed epileptiform discharges. The development of epilepsy and the recurrence of febrile seizures were compared between the study group (n = 36) and the control group (n = 87), which included children with febrile seizure but with normal EEG findings. Results: No significant correlation was detected between the recurrence rate of febrile seizures in patients with normal EEG (23 out of 87, 26.4%) findings and that of patients whose EEGs showed epileptiform discharges (12 out of 36, 33.3%) [adjusted OR 0.67 (0.26–1.68)]. However, 9 (25.0%) out of 36 patients with epileptiform discharges on EEG had epilepsy compared to 2 patients (2.3%) in the control group. The correlation was statistically significant [crude OR 10.88 (2.47–47.88) and adjusted OR 8.75 (1.49–51.6)]. Conclusion: Epileptiform discharges on the EEGs of patients with febrile seizures are important predictive risk factors of the development of epilepsy.     

难治性癫痫早期预测因素的病例对照研究

目的 探索癫痫患者易演变为难治性癫痫（refractory epilepsy,RE）的早期预测因素,为临床尽早处理RE提供理论依据。方法 收集173例诊断明确、治疗合理的癫痫患者,分为药物难治性癫痫(drug non-responsive epilepsy,DNR-EP)组（106例）和药物有效性癫痫(drug-responsiveepilepsy,DR-EP)组（67例）。通过观察癫痫患者早期临床特点,采用多因素Logistic回归分析,探索癫痫患者易发展为RE的预测因素。结果 多因素Logistic回归分析显示：初次治疗前＞10次发作（OR =4.46,95％ CI 1.60～12.40,P=0.004）、早期伴智能障碍(OR=19.87,95％ CI 3.60～ 109.78,P=0.001)、治疗后脑电图仍有癫痫波样异常（OR=7.57,95％ CI 2.54～22.56,P＜0.01）是癫痫患者易发展为RE的预测因素;而初次使用抗癫痫药物(AEDs)治疗效果良好是RE的保护因素（OR=0.05,95％ CI 0.018 ～0.139,P＜0.01）。结论 初次治疗前发作次数多、早期伴智能障碍、治疗后脑电图仍有癫痫波样异常、初次AEDs治疗效果差的癫痫患者易发展为RE。     

Epileptiform activity in the electroencephalogram of 6-year-old children of women with epilepsy

Purpose:To study the epileptiform discharges (EDs) in the electroencephalogram (EEG) of 6-8-year-old children of women with epilepsy (WWE).Results:Of the 185 children examined, 37 (20%) children (19 males, 18 females) had ED in their EEG. The EDs were generalized in 7 children, and focal in 30 children. The EDs were present in the sleep record only of 16 (43%) children and in the awake record only of 6 (16%) children. Out of the 94 children for whom seizure history was available, 7 children (7.4%) had seizures (neonatal seizures: 4, febrile seizure: 1, and single nonfebrile seizure: 2) and none had history of epilepsy or recurrent nonfebrile seizures. The odds ratio (OR) for occurrence of ED in the EEG was significantly higher for children of WWE [OR = 3.5, 95% confidence interval (CI) 2.3-6.0] when compared to the published data for age-matched children of mothers without epilepsy. There was no association between the occurrence of ED and the children''s maternal characteristics [epilepsy syndrome, seizures during pregnancy, maternal intelligence quotient (IQ)] or the children''s characteristics [antenatal exposure to specific antiepileptic drugs (AEDs), birth weight, malformations, IQ].Conclusion:Children of WWE have a higher risk of epileptiform activity in their EEG when compared to healthy children in the community though none had recurrent seizures.     

Effects of low-frequency repetitive transcranial magnetic stimulation on electroencephalogram and seizure frequency in 15 patients with temporal lobe epilepsy following dipole source localization

BACKGROUND:Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The location of epileptic foci and magnetic stimulation sites remain uncertain. The effects of rTMS on electroencephalogram and seizure remain unclear in epileptic patients following dipole source localization. OBJECTIVE: To investigate the effects of low-frequency rTMS on electroencephalogram and seizure i...     

结节性硬化症患儿癫痫预后的危险因素分析

目的探讨影响结节性硬化症(TSC)患儿进展为难治性癫痫的危险因素。方法根据近1年内有无癫痫发作及药物控制情况,将83例合并癫痫的TSC患儿分为难治性癫痫组和癫痫控制组,比较两组患儿的临床资料、脑电图(EEG)和头颅MRI检查差异,并通过多因素Logistics回归分析确定影响难治性癫痫进展的独立危险因素。结果与癫痫控制组患儿相比,难治性癫痫组患儿中,癫痫首次发作年龄<2岁、新生儿癫痫、智商评分<70、婴儿痉挛史、合并林-戈综合征、自闭症、癫痫持续状态、使用抗癫痫药物≥3种的患儿显著升高。而难治性癫痫组患儿的EEG呈全面型的患儿比例显著高于癫痫控制组,磁共振(MRI)显示皮质结节≥3个的患儿比例也显著高于癫痫控制组(P<0.001)。多因素Logistics回归分析显示癫痫首次发作年龄<2岁(OR=1.243,95%CI:1.114~1.672,P=0.036)、合并自闭症(OR=3.892,95%CI:1.241~9.351,P=0.008)和大脑皮质结节≥3个(OR=1.905,95%CI:1.101~3.288,P=0.021)是影响难治性癫痫的独立危险因素。结论癫痫首发年龄小于2岁、合并自闭症和脑皮质结节数目超过3个是影响TSC患儿难治性癫痫进展的独立危险因素,对于此类TSC患儿应早期采取干预措施以预防或延缓难治性癫痫的进展。