Reduction of seizure frequency after epilepsy surgery in a patient with STXBP1 encephalopathy and clinical description of six novel mutation carriers

Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syndrome, nonsyndromic EE with onset in the first year, and Lennox‐Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dysplasia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities.     

Long-Term Outcomes of Hemispheric Disconnection in Pediatric Patients with Intractable Epilepsy

Background and Purpose

Hemispherectomy reportedly produces remarkable results in terms of seizure outcome and quality of life for medically intractable hemispheric epilepsy in children. We reviewed the neuroradiologic findings, pathologic findings, epilepsy characteristics, and clinical long-term outcomes in pediatric patients following a hemispheric disconnection.

Methods

We retrospectively studied 12 children (8 males) who underwent a hemispherectomy at Asan Medical Center between 1997 and 2005. Clinical, EEG, neuroradiological, and surgical data were collected. Long-term outcomes for seizure, motor functions, and cognitive functions were evaluated at a mean follow-up of 12.7 years (range, 7.6-16.2 years) after surgery.

Results

The mean age at epilepsy onset was 3.0 years (range, 0-7.6 years). The following epilepsy syndromes were identified in our cohort: focal symptomatic epilepsy (n=8), West syndrome (n=3), and Rasmussen''s syndrome (n=1). Postoperative histopathology of our study patients revealed malformation of cortical development (n=7), encephalomalacia as a sequela of infarction or trauma (n=3), Sturge-Weber syndrome (n=1), and Rasmussen''s encephalitis (n=1). The mean age at surgery was 6.5 years (range, 0.8-12.3 years). Anatomical or functional hemispherectomy was performed in 8 patients, and hemispherotomy was performed in 4 patients. Eight of our 12 children (66.7%) were seizure-free, but 3 patients with perioperative complications showed persistent seizure. Although all patients had preoperative hemiparesis and developmental delay, none had additional motor or cognitive deficits after surgery, and most achieved independent walking and improvement in daily activities.

Conclusions

The long-term clinical outcomes of hemispherectomy in children with intractable hemispheric epilepsy are good when careful patient selection and skilled surgical approaches are applied.     

Long-term developmental outcome in patients with West syndrome after epilepsy surgery

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.     

Surgical management of cortical dysplasia in infancy and early childhood

Purpose: To describe operative procedures, seizure control and complications of surgery for cortical dysplasia (CD) causing intractable epilepsy in infancy and early childhood. Methods: Fifty-six consecutive children (less than 6 years old) underwent resective epilepsy surgery for CD from December 2000 to August 2011. Age at surgery ranged from 2 to 69 months (mean 23 months) and the follow-up was from 1 to 11 years (mean 4 years 4 months). Results: Half of the children underwent surgery during infancy at an age less than 10 months, and the majority (80%) of these infants needed extensive surgical procedures, such as hemispherotomy and multi-lobar disconnection. Seizure free (ILAE class 1) outcome was obtained in 66% of the cases (class 1a; 55%): 85% with focal resection (n = 13), 50% with lobar resection (n = 18), 71% with multilobar disconnection (n = 7) and 67% with hemispherotomy (n = 18). Peri-ventricular and insular structures were resected in 23% of focal and 61% of lobar resections. Repeated surgery was performed in 9 children and 5 (56%) became seizure free. Histological subtypes included hemimegalencephaly (16 patients), polymicrogyria (5 patients), and FCD type I (6 patients), type IIA (19 patients), type IIB (10 patients). Polymicrogyria had the worst seizure outcome compared to other pathologies. Surgical complications included 1 post-operative hydrocephalus, 1 chronic subdural hematoma, 2 intracranial cysts, and 1 case of meningitis. No mortality or severe morbidities occurred. Conclusions: Early surgical intervention in children with CD and intractable seizures in infancy and early childhood can yield favorable seizure outcome without mortality or severe morbidities although younger children often need extensive surgical procedures.     

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open-label extension study

Objective

This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox–Gastaut syndrome (LGS).

Methods

Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months.

Results

As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2–4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was −28.6% over the entire OLE (n = 241) and −50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was −45.9% (n = 192, p = .0038). Generalized tonic–clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%–44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%–41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed.

Significance

Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.     

Various indications for a modified Atkins diet in intractable childhood epilepsy

Purpose: We reviewed retrospectively our experiences with children with intractable epilepsy who were indicated for a modified Atkins diet (MAD). Methods: Twenty children (8 female, 12 male) who were aged 2–17 years with intractable epilepsy and tried the MAD between September 2008 and December 2010 were enrolled. Outcome measures included seizure frequency, adverse reactions and tolerability of the diet. Results: Finally 9 patients maintained the MAD with favorable seizure outcomes (a reduction of seizure frequency by over 50%) or successfully completed the diet therapy. Two patients who required a long-term trial of the diet therapy respectively due to Leigh’s syndrome and uncategorized mitochondrial cytopathy derived from cytochrome c oxidase defect, respectively, successfully maintained the diet treatment without any significant complications. In 7 patients, the ketogenic diet (KD) was not only effective but also too restrictive or caused serious unwanted events. Five of them maintained the seizure outcome previously achieved by the KD with the MAD. Ten patients began the MAD because they were reluctant to start the KD. Unfortunately, only 2 patients maintained the MAD with favorable seizure outcomes. One patient who chose the MAD to bridge the KD and complete discontinuation of the treatment successfully completed the diet therapy. Conclusion: A long-term treatment with the MAD was well tolerated. Moreover, the MAD can successfully substitute the classic KD in patients who showed improvement in seizure outcomes by the KD but could not tolerate it.     

Our Experience with Pediatric Epilepsy Surgery Focusing on Corpus Callosotomy and Hemispherotomy

Summary:  Purpose: In pediatric patients with intractable epilepsy, surgical intervention should be considered in terms of seizure control and prevention of neuronal deterioration. We present our experience with pediatric epilepsy surgery, focusing on corpus callosotomy and hemispherotomy.
Methods: A total of 257 pediatric patients underwent epilepsy surgeries during the last decade in our clinic. The two most common surgical procedures were corpus callosotomy and hemispherotomy. The surgical outcomes of the patients undergoing these operations were analyzed with regard to seizure outcomes and surgical complications.
Results: Corpus callosotomy proved to be extremely effective in controlling drop attacks, especially when the callosum was totally sectioned. Postoperative improvement of psychomotor function also was noticeable in >70% of the cases. In patients who underwent hemispherotomy, the etiology of unilateral hemispheric lesions was closely related to surgical results, with cases of hemimegalencephaly having the worst seizure outcome and most frequent surgical complications. Incomplete section of the callosum, one of the most important causes of residual seizures, was found in three cases.
Conclusions: In pediatric epilepsy surgery, corpus callosotomy is very effective in abolishing drop attacks and improving postoperative psychomotor function. For hemispherotomy, cases of hemimegalencephaly had the worst seizure control and surgical complications. Incomplete section of the corpus callosum should be carefully evaluated as a cause of surgical failure.     

Transient focal cortical increase of interictal glucose metabolism in Sturge-Weber syndrome: implications for epileptogenesis

Purpose: To investigate clinical correlates and longitudinal course of interictal focal cortical glucose hypermetabolism in children with Sturge‐Weber syndrome (SWS). Methods: Fluorodeoxyglucose positron emission tomography (FDG‐PET) scans of 60 children (age range 3 months to 15.2 years) with Sturge‐Weber syndrome and epilepsy were assessed prospectively and serially for focal hypo‐ or hypermetabolism. Thirty‐two patients had two or more consecutive PET scans. Age, seizure variables, and the occurrence of epilepsy surgery were compared between patients with and without focal hypermetabolism. The severity of focal hypermetabolism was also assessed and correlated with seizure variables. Key Findings: Interictal cortical glucose hypermetabolism, ipsilateral to the angioma, was seen in nine patients, with the most common location in the frontal lobe. Age was lower in patients with hypermetabolism than in those without (p = 0.022). In addition, time difference between the onset of first seizure and the first PET scan was much shorter in children with increased glucose metabolism than in those without (mean: 1.0 vs. 3.6 years; p = 0.019). Increased metabolism was transient and switched to hypometabolism in all five children where follow‐up scans were available. Focal glucose hypermetabolism occurred in 28% of children younger than the age of 2 years. Children with transient hypermetabolism had a higher rate of subsequent epilepsy surgery as compared to those without hypermetabolism (p = 0.039). Significance: Interictal glucose hypermetabolism in young children with SWS is most often seen within a short time before or after the onset of first clinical seizures, that is, the presumed period of epileptogenesis. Increased glucose metabolism detected by PET predicts future demise of the affected cortex based on a progressive loss of metabolism and may be an imaging marker of the most malignant cases of intractable epilepsy requiring surgery in SWS.     

Improvement of intractable childhood epilepsy following acute viral infection

In this study, we report 11 patients with intractable childhood epilepsy that improved following acute viral infection. The patients were 8 boys and 3 girls. Six of the 11 children were diagnosed as West syndrome (5 of the symptomatic type and 1 of the cryptogenic type). The remaining 5 children were myoclonic seizures. The patients became seizure free within 6 days following acute viral infections without an exchange or addition of antiepileptic drugs (AEDs). The types of acute viral infections were Exanthema subitum (Roseola infantum) in 5 patients, Rotavirus gastroenteritis in 2 patients, Measles infection in 2 patients, Herpetic stomatitis in 1 patient and Common cold in the remaining patient. Salaam seizures and/or tonic spasms disappeared within 6 days after the onset of viral infections, and hypsarrhythmia evolved to localized spikes on electroencephalography (EEG) in the patients with West syndrome. Epileptic seizures disappeared rapidly and EEG gradually normalized or improved in patients with myoclonic seizures. Four patients became seizure free for 5 years to 20 years. In 6 patients, seizures relapsed within 14 days to 1 month after the disappearance of seizures. One child remained seizure free for 12 months after viral infection. Common factors in 4 children who were continuously seizure free include (1) normal or almost normal findings of brain CT/MRI, (2) normal development prior to the onset of epileptic seizures, and (3) a short time interval between the onset of seizures and the acute viral infection. We propose several hypotheses including an immunological effect for the improvement of intractable childhood epilepsy following acute viral infection. Further study may provide important information concerning the mechanism of seizure control and the applicable to treatment for intractable childhood epilepsy.     

胼胝体全段一期切开治疗癫疒间性脑病

目的探索胼胝体全段一期切开的安全性,观察该术式治疗癫疒间性脑病的有效性。方法回顾性分析我科手术治疗的37例癫疒间性脑病的临床资料。经临床症状学、神经电生理学、神经影像和神经心理学综合评估后,于全麻下额部切口、经前纵裂入路显微镜下一期切开胼胝体全段。依Engel分级标准评判手术效果。结果随访18～34个月,Engel-Ⅰ级3例,Engel-Ⅱ级25例,Engel-Ⅲ级7例,Engel-Ⅳ级2例,手术总有效率达75.7%。跌倒发作、强直发作、痉挛发作和强直-阵挛发作的有效率分别为86.2%、77.5%、61.6%和40.8%。14例患者出现不同程度的手术后并发症,缄默11例、轻偏瘫7例、颅内感染1例。其中13例患者分别在出院时和出院后1月内痊愈,1例患者仍遗留轻偏瘫。结论胼胝体全段一期切开安全、微创,无新发并发症;它能有效减少癫疒间性脑病的癫疒间发作频率、减轻发作程度。     

Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience

PURPOSE: To evaluate the efficacy and safety of zonisamide (ZNS) as long-term adjunctive therapy in children with Lennox-Gastaut syndrome (LGS). METHOD: We evaluated the seizure frequency, cognitive outcomes, and side effects of 62 LGS patients maintained on ZNS for at least 12 months in three tertiary centers. RESULTS: Of the 62 LGS patients maintained on ZNS, 3 (4.8%) had 100% seizure control; 14 (22.6%) had >75% to <100% reduction in seizure frequency; 15 (24.2%) had >50% to <75% reduction in seizure frequency; 6 (9.7%) had >0% to <50% reduction in seizure frequency, and 24 (38.7%) had no seizure reduction. Seizure outcomes were not related to seizure types or etiologies. Adverse events included somnolence and anorexia, but all were transient and successfully managed by careful follow-up. CONCLUSION: Our results indicate that adjunctive treatment with ZNS is safe and effective in pediatric LGS patients.     

Pediatric intractable epilepsy syndromes: reason for early surgical intervention

Drug-resistance in several childhood epilepsy syndromes is common, and these patients may tolerate epilepsy surgery. In this study, the surgical outcomes of 24 pediatric patients with various intractable epilepsy syndromes and three patients with tuberous sclerosis were examined at Xinqiao hospital between 1997 and 2004. The study included nine cases of Lennox-Gastaut syndrome, two cases of Rasmussen's syndrome, one case of Sturge-Weber syndrome, three cases of West syndrome, three cases of tuberous sclerosis and nine cases of mesial temporal lobe epilepsy syndrome. In each case, different surgical procedures were performed according to preoperative evaluation and ECoG. At an average of 4.5 years after surgery, 14 out of 27 patients (51.9%) had an Engel Class I outcome after surgery, and an additional eight patients (29.6%) had rare seizure (Engel ClassII). Three patients showed a significant decrease in seizure frequency (Engel Class III). The mean IQ increased from 61.4+/-12.2 to 75.0+/-11.0, and greater IQ increase was seen in patients with shorter seizure history and drug-resistance. Temporary complications were observed in four patients and there were no deaths. In conclusion, early surgical intervention in pediatric intractable epilepsy syndromes may results in a favorable outcome in a high percentage of cases and may provides an important opportunity to prevent irreversible decline in intelligence and disability.     

Long-term effectiveness of add-on perampanel in patients with Lennox–Gastaut syndrome: A multicenter retrospective study

This retrospective study assessed long-term effectiveness of add-on perampanel (PER) in patients with Lennox–Gastaut syndrome (LGS). Outcomes included time to PER failure and time to seizure relapse in responders. PER failure was defined as either discontinuation of PER or initiation of another treatment. Seizure relapse in responders was defined as occurrence of a seizure in seizure-free patients and increase of at least 50% in average monthly seizure frequency for those who were responders. Eighty-seven patients were included. Treatment failure occurred in 52 (59.8%) subjects at a median time of 12 months. Treatment failure was due to lack of efficacy in 27 (52.0%) patients, lack of tolerability in 14 (27.0%), and both reasons in 11 (21.0%). A slower titration was associated with a lower risk of PER failure compared to faster titration schedules, and the occurrence of adverse events increased the risk of treatment failure. Thirty-six patients (41.4%) were responders during a median follow-up of 11 months. Seizure relapse occurred in 13 of 36 (36.1%) patients after a median time of 21 months. The overall rate of seizure responders was 23 of 87 (26.4%) at the end of follow-up. This study provides real-world evidence on the effectiveness of PER as adjunctive treatment in LGS patients.     

West syndrome in tuberous sclerosis complex

West syndrome occurs commonly in children with tuberous sclerosis complex and is associated with a grave prognosis for cognitive and seizure outcomes. We sought to determine the epilepsy outcome of children with tuberous sclerosis complex and West syndrome and whether EEG, MRI, or steroid therapy duration were different in those whose epilepsy improved compared with those with intractable seizures. Seventeen patients with tuberous sclerosis complex and West syndrome were identified. For each patient, two sets of clinical evaluations, EEG and MRI data, and treatment information separated by at least 12 months were obtained. The patients were divided into two seizure outcome groups. EEG, MRI, and treatment data were compared between the groups. The intellectual deficiency was either severe (76%) or moderate (24%). Seizure control improved in 10 and worsened in seven, without mortality (follow-up range = 12-216 months). No significant differences in EEG background, MRI findings, or steroid treatment duration were evident between the groups. The difference in EEG-sleep approached statistical significance (P = 0.06). Our findings did not confirm reports of high mortality and poor epilepsy outcome in intellectually deficient children with West syndrome and tuberous sclerosis complex. EEG sleep was the best indicator of seizure control and approached statistical significance. The duration of steroid therapy had no influence on seizure control.     

Vagus nerve stimulation vs. corpus callosotomy in the treatment of Lennox–Gastaut syndrome: A meta-analysis

PurposeLennox–Gastaut syndrome (LGS) is an epileptogenic disorder that arises in childhood and is typically characterized by multiple seizure types, slow spike-and-wave complexes on EEG and cognitive impairment. If medical treatment fails, patients can proceed to one of two palliative surgeries, vagus nerve stimulation (VNS) or corpus callosotomy (CC). Their relative seizure control rates in LGS have not been well studied. The purpose of this paper is to compare seizure reduction rates between VNS and CC in LGS using meta-analyses of published data.MethodsA systematic search of Pubmed, Ovidsp, and Cochrane was performed to find articles that met the following criteria: (1) prospective or retrospective study, (2) at least one patient diagnosed with Lennox–Gastaut syndrome, and (3) well-defined measure of seizure frequency reduction. Seizure reduction rates were divided into seizure subtypes, as well as total seizures, and categorized as 100%, >75%, and >50%. Patient groups were compared using chi-square tests for categorical variables and t-test for continuous measures. Pooled proportions with 95% confidence interval (95% CI) of seizure outcomes were estimated for total seizures and seizure subtypes using random effects methods.Results17 VNS and 9 CC studies met the criteria for inclusion. CC had a significantly better outcome than VNS for >50% atonic seizure reduction (80.0% [67.0–90.0%] vs. 54.1% [32.1–75.4%], p < 0.05) and for >75% atonic seizure reduction (70.0% [48.05–87.0%] vs. 26.3% [5.8–54.7%], p < 0.05). All other seizure types, as well as total number of seizures, showed no statistically significant difference between VNS and CC.ConclusionsCC may be more beneficial for LGS patients whose predominant disabling seizure type is atonic. For all other seizure types, VNS offers comparable rates to CC.     

Treatment of Lennox-Gastaut syndrome: overview and recent findings

Lennox-Gastaut syndrome (LGS) is a rare, age-related syndrome, characterized by multiple seizure types, a specific electro-encephalographic pattern, and mental regression. However, published data on the etiology, evolution, and therapeutic approach of LGS are contradictory, partly because the precise definition of LGS used in the literature varies. In the most recent classification, LGS belongs to the epileptic encephalopathies and is highly refractory to all antiepileptic drugs. Numerous treatments, medical and non-medical, have been proposed and results mostly from open studies or case series have been published. Sometimes, patients with LGS are included in a more global group of patients with refractory epilepsy. Only 6 randomized double-blind controlled trials of medical treatments, which included patients with LGS, have been published. Overall, treatment is rarely effective and the final prognosis remains poor in spite of new therapeutic strategies. Co-morbidities need specific treatment. This paper summarizes the definition, diagnosis and therapeutic approach to LGS, including not only recognized antiepileptic drugs, but also “off label” medications, immune therapy, diet, surgery and some perspectives for the future.     

Long-term seizure and behavioral outcomes after corpus callosotomy

Outcomes of corpus callosotomy (CC) have been mainly focused on seizures. The present study aimed to evaluate the long-term effects of CC on adaptive behaviors and caregivers' satisfaction in addition to seizures and to identify clinical predictors of postsurgical outcomes. Medical records of 26 patients (mean age at study time: 40 years, mean follow-up: 14 years) with childhood-onset epilepsy who underwent anterior or 2-stage complete CC were reviewed. A structured questionnaire was submitted to caregivers asking about relative changes in different seizure types, behavioral functions, and satisfaction with the postoperative outcomes. Formal neuropsychological assessment was carried out in a subgroup of patients. Selected clinical variables including age at surgery, extent of callosal section, length of follow-up, epilepsy syndrome, and presurgical cognitive level were submitted to multiple regression analysis. At the last follow-up visit, a reduction greater than 50% was observed mainly for drop attacks (65% of patients), followed by generalized tonic-clonic seizures (53%), and complex partial seizures (50%). No presurgical variables were significantly associated with seizure outcome. After surgery, more than half of patients showed attention enhancement, which was related to drop seizure improvement. Early age at surgery was associated with better behavioral regulation; complete CC slightly worsened language abilities. Satisfaction with surgery outcomes was expressed by 73% of caregivers and was dependent on drop seizure reduction and improvements in activities of daily living. A long-term positive psychosocial outcome is likely after CC also in severely disabled patients, especially if surgery is performed early.     

Efficacy and tolerability of adjunctive therapy with zonisamide in childhood intractable epilepsy

Purpose: This study investigated the efficacy and safety of zonisamide (ZNS) adjunctive therapy in children with intractable epilepsy to existing antiepileptic drugs (AEDs). Methods: A clinical retrospective study was performed from 2003 to 2005 at two tertiary epilepsy centers. We reviewed the data from 163 children (107 boys and 56 girls) who experienced more than four seizures per month, whose seizures were intractable to an initial 2 or more AEDs, and could be followed up for at least 6 months after ZNS adjunctive therapy initiation. Efficacy was estimated by seizure reduction rate according to seizure types including infantile spasms, and adverse events were also measured. Results: Seventy-nine patients (48.5%) out of 163 patients experienced a reduction in seizure frequency of more than 50%, and 25 patients (15.3%) became seizure-free. The rate of seizure reduction greater than 50% in children with partial seizures was 40.5% (17/42) and in children with generalized seizures was 51.2% (62/121). Of 36 patients who manifested mainly myoclonic seizures, 20 patients (55.6%) showed a seizure reduction of more than 50% and 9 patients (25.0%) were seizure-free. Mean maintenance dosage of drug was 8.2 mg/kg/day (range 5.0-16.0 mg/kg/day). Adverse events were documented in 15 children (9.2%), including somnolence (8 patients), fatigue, and anorexia, but all were transient and successfully managed. One patient discontinued ZNS therapy due to acute pancreatitis. Conclusion: ZNS adjunctive therapy is an effective and safe treatment in various childhood intractable epilepsy.     

Aicardi Syndrome: A Longitudinal Clinical and Electroencephalographic Study

Summary: We report clinical and EEC follow-up of 6 children with Aicardi syndrome. Age at seizure onset was <3 months in 5 patients and 4 months in 1 patient. All patients had spasms, and these continued at time of follow-up in 5 patients. Five patients had seizures other than spasms which disappeared during early infancy. Bilateral independent bursts (BIBs) characteristic of Aicardi syndrome were noted in 4 patients. In 1, BIBs showed suppression-burst patterns. BIBs converted to hypsarrhythmia or multifocal spikes with a tendency to BIBs during sleep. BIBs disappeared completely during both waking and sleeping states between the ages of 3 years 1 month and 4 years 9 months. After BIB disappearance, the EEG of 1 patient showed diffuse slow spike-and-wave complexes most of which appeared asynchronously. At onset, 1 patient had early-infantile epileptic encephalopathy with suppression-burst which evolved initially into West syndrome (WS) and then Lennox-Gastaut syndrome (LGS). The other 3 children also had WS.     

Epilepsy surgery for hemispheric syndromes in infants: Hemimegalencepahly and hemispheric cortical dysplasia

Objective: Hemimegalencepahly (HME) and Hemispheric Cortical Dysplasia (HCD) are rare congenital diseases that occur with intractable epilepsy. They manifest by early epilepsy, mental retardation, hemianopsia and contralateral hemiplegia. Hemispheric disconnection (mainly anatomical hemispherectomy, peri-insular hemispherotomy, modified lateral hemispherotomy and vertical parasagittal hemispherotomy) have been reported to be efficient on seizures and also to prevent additional cognitive injury and developmental delay. Method: We reviewed literature about clinical presentation, predictors of outcome and expectation about epileptic seizures and cognitive outcome. Results: Clinical presentation and seizures outcome have been described in almost 600 children for the last thirty years. Epilepsy improved in most cases depending on the series and the follow-up duration. Percentage of seizure-free patients with HME or HCD was lower than in other groups (Rasmussen Encephalitis, Vascular Sequellae). Post-operative complications decreased with the hemispherotomy surgical procedures. EEG abnormalities on the “save” hemisphere did not negatively influence postsurgical outcome. Seizure free outcome did not seem to depend on the surgical procedure but the presence of residual insular cortex seemed to be associated with persistent postoperative seizures. Contralateral MRI abnormalities seemed to be associated with poorer prognosis for seizure free outcome and lack of cognitive improvement. Conclusion: Hemispheric disconnection remains the best treatment in order to control epileptic seizures. Hemispheric surgical procedures are safe and can be performed from the first month of life. Prospective studies of cognition are needed to emphasize benefits on long term outcome.