Resective surgery in tuberous Sclerosis complex, from Penfield to 2018: A critical review.

Medically treated patients suffering from tuberous sclerosis complex (TSC) have less than 30% chance of achieving a sustained remission. Both the international TSC consensus conference in 2012, and the panel of European experts in 2012 and 2018 have concluded that surgery should be considered for medically refractory TSC patients. However, surgery remains currently underutilized in TSC. Case series, meta-analyses and guidelines all agree that a 50 to 60% chance of long-term seizure freedom can be achieved after surgery in TSC patients and a presurgical work-up should be done as early as possible after failure of two appropriate AEDs. The presence of infantile spasms, the second most common seizure type in TSC, had initially been a barrier to surgical planning but is now no longer considered a contraindication for surgery in TSC patients. TSC patients undergoing presurgical evaluation range from those with few tubers and good anatomo-electro-clinical correlations to patients with a significant "tuber burden" in whom the limits of the epileptogenic zone is much more difficult to define. Direct surgery is often possible in patients with a good electro-clinical and MRI correlation. For more complex cases, invasive monitoring is often mandatory and bilateral investigations can be necessary. Multiple non-invasive tools have been shown to be helpful in determining the placement of these invasive electrodes and in planning the resection scheme. Additionally, at an individual level, multimodality imaging can assist in identifying the epileptogenic zone. Increased availability of investigations that can be performed without sedation in young and/or cognitively impaired children such as MEG and HR EEG would most probably be of great benefit in the TSC population. Of those selected for invasive EEG, rates of seizure freedom following surgery are close to cases where invasive monitoring is not required, strengthening the important and efficient role of intracranial investigations in drug-resistant TSC associated epilepsy.

STAG2 microduplication in a patient with eyelid myoclonia and absences and a review of EMA-related reported genes.

Xq25 microduplication involving exclusively STAG2 is a new distinctive cohesinopathy including mild to moderate intellectual disability, speech delay and facial dysmorphism. Seizures seem to be scarce, but detailed seizure type descriptions are missing. We report the case of an 8-year-old boy with mild intellectual disability and eyelid myoclonia with onset at age of 3 years, initially misinterpreted as tics. An ictal VIDEO-EEG documented eye closure elicited generalized 3 Hz spike-waves or polyspike-waves concomitant to eyelid myoclonia, sometimes associated to brief clinically observable absences. Intermittent photic stimulation revealed a photoparoxysmal response. Array CGH identified a 199 kb copy number gain in Xq25 including the whole STAG2 gene, inherited from his asymptomatic mother. To the best of our knowledge, this is the first case of STAG2 encephalopathy fulfilling all electroclinical criteria for epilepsy with eyelid myoclonia and absences (EMA), formally named Jeavons syndrome (JS). As for other Genetic Generalized Epilepsy syndromes, EMA/JS usually occurs in normally developing children. Intellectual disability of variable degree is occasionally reported. On the background of other genes responsible for Developmental and Epileptic Encephalopathies, linked to specific generalized seizure types or seizure combinations, we discuss the contribution of pathogenic variants in CHD2, SYNGAP1 and some other genes as, RORB, NEXMIF and KCNB1 to this peculiar EMA phenotype.

Absence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC).

Alternating hemiplegia of childhood (AHC) is a rare neuropediatric disorder classically characterized by episodes of hemiplegia developing in the first months of life, various non-epileptic paroxysmal events and global neurological impairment. If the etiology is unresolved, the disorder is highly suspected to be monogenic with DE NOVO autosomal dominant mutations. A missense mutation in the SLC2A1 gene encoding the facilitative glucose transporter-1 (GLUT1) was recently described in a child fulfilling the existing criteria for the diagnosis of AHC, with the exception of age at onset, thus suggesting a clinical overlap between AHC and GLUT1 deficiency syndrome due to SLC2A1 mutations. We have studied a cohort of 23 patients to investigate whether patients with classical AHC harbor SLC2A1 mutations. Automated Sanger sequencing and MLPA analyses failed to detect any SLC2A1 mutations in the 23 patients analyzed, thus excluding mutations of this gene as a frequent cause of classical AHC.

Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients.

INTRODUCTION: Mutations in the voltage-gated sodium channel SCN1A gene are the main genetic cause of Dravet syndrome (previously called severe myoclonic epilepsy of infancy or SMEI). OBJECTIVE: To characterise in more detail the mutation spectrum associated with Dravet syndrome. METHODS: A large series of 333 patients was screened using both direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Non-coding regions of the gene that are usually not investigated were also screened. RESULTS: SCN1A point mutations were identified in 228 patients, 161 of which had not been previously reported. Missense mutations, either (1) altering a highly conserved amino acid of the protein, (2) transforming this conserved residue into a chemically dissimilar amino acid and/or (3) belonging to ion-transport sequences, were the most common mutation type. MLPA analysis of the 105 patients without point mutation detected a heterozygous microrearrangement of SCN1A in 14 additional patients; 8 were private, partial deletions and six corresponded to whole gene deletions, 0.15-2.9 Mb in size, deleting nearby genes. Finally, mutations in exon 5N and in untranslated regions of the SCN1A gene that were conserved during evolution were excluded in the remaining negative patients. CONCLUSION: These findings widely expand the SCN1A mutation spectrum identified and highlight the importance of screening the coding regions with both direct sequencing and a quantitative method. This mutation spectrum, including whole gene deletions, argues in favour of haploinsufficiency as the main mechanism responsible for Dravet syndrome.

Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy - A systematic review of the literature using lacosamide as an example.

Extrapolation of efficacy data from adults to children is accepted for focal epilepsy - the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.

[Epilepsy surgery in children: from a multidisciplinary network to the creation of an expertise and care centre]. / Chirurgie des épilepsies de l'enfant: du fonctionnement en réseau à la création d'un centre d'expertise et de soins.

We report on the experience of a network created in 1994 to evaluate children with drug-resistant epilepsies who are candidates for surgical treatment. The network includes epilepsy units from several university hospitals in France that decided to share not only their clinical expertise to better respond to the need for a multidisciplinary approach of epilepsy surgery in children, but also all the technical and human resources available in the various teams. This mode of operation has certainly provided concrete proof of its efficacy since it undoubtedly facilitated, and even accelerated, access to optimal presurgical evaluation and epilepsy surgery for hundreds of children. However, after 10 years of this very enriching practice it became evident that our approach was certainly necessary but not sufficient. It is estimated that every year in France nearly 500 children are candidates for surgical treatment, and following a presurgical evaluation, 50% of them could be operated on. Today, only 150-200 children have access to a presurgical evaluation every year. This is a highly paradoxical situation since, even if the human suffering component that such a situation generates is set aside, the direct and indirect life-time costs for every 100 nonoperated patients is estimated at 40 million euros. As a result of our cumulated experience, in 2004 we proposed a different operating model with the creation of an expertise center that will combine not only medical care services provided by a fully equipped multidisciplinary team, but also a pole of applied clinical and fundamental research, a medicosocial center managed by a lay association and an industrial development pole. The project has been recently validated by the Ministry of Health and is supported by a number of national and regional institutions. The Institute for Children and Adolescents with Epilepsy--IDEE--is designed to accelerate diagnostic procedures and, when indicated, access to optimal presurgical evaluation, while also serving as a model for a medical and economic evaluation of epilepsy care in children.

[Medicoeconomic assessment of epilepsy surgery in adults with medically intractable partial epilepsy. Three-year outcomes from a multicenter French cohort]. / Evaluation médicoéconomique de la chirurgie des épilepsies partielles pharmacorésistantes de l'adulte. Résultats à trois ans d'une étude prospective multicentrique française.

PURPOSE: To compare resective surgery and medical therapy in a cost-effectiveness analysis in a multicenter cohort of adult patients with partial intractable epilepsy. POPULATION AND METHODS: Adult patients with partial, medically intractable, potentially operable epilepsy were eligible and followed every year over five years. Effectiveness was defined as one year without seizure. The long-term costs and effectiveness were extrapolated over the patients' lifetime with a Markov model. Productivity (indirect costs) and quality of life (QOLIE-31, SEALS) were also assessed. Changes before and after surgery were compared between the two groups. RESULTS: Two hundred and eighty-nine patients were included (119 with surgery, 161 medically treated, six not eligible, three lost to follow-up). One year after surgery, 81% of the patients were seizure-free; at two and three years, this rate was 78%. In the medical group, these rates were 10, 18, and 15%, respectively. The cost of the explorations was euro 8464; including surgery, it was euro 19,700. In the medical group, the average annual direct costs were between 3500 and euro 6000. At two years after surgery, the annual direct cost decreased to euro 2768, at three years, it was euro 1233, predominately antiepileptic drug costs. Surgery became cost-effective between seven and eight years. In the surgical group, all the quality-of-life scores improved at one year after surgery and were stable during the second and third years. CONCLUSION: Surgical therapy was cost-effective at the middle term even though indirect costs were not considered.

Role of valproate across the ages. Treatment of epilepsy in children.

In June 2005 a team of experts participated in a workshop with the objective of reaching agreement on the place of valproate use in the treatment of paediatric epilepsy patients. A general "consensus of the meeting" was that the initiation of antiepileptic drug (AED) treatment should be based on a seizure-syndromic approach in children. Participants of the meeting also agreed that valproate is currently the AED with the broadest spectrum across all types of seizures and syndromes. Its superiority has been shown over almost 40 years of clinical experience. The best results are seen in idiopathic generalized epilepsy with or without photosensitivity, idiopathic focal and symptomatic generalized tonic-clonic seizures (GTCS). Evidence supports the use of valproate, ethosuximide and lamotrigine in absence epilepsies and the use of carbamazepine, lamotrigine, oxcarbazepine, phenytoin, topiramate, valproate and phenobarbital for primary GTCS. For new AEDs trials have been undertaken to define their therapeutic role but studies comparing their role to 'old' broad-spectrum drugs in specific syndromes are missing. Experts concluded that intravenous (i.v.) valproate is a useful agent in the treatment of non-convulsive status epilepticus (SE). There is an easy transition to oral treatment following i.v. valproate use. The discussion also concluded that, despite the lack of studies, valproate is an interesting, underutilized alternative in convulsive SE but more controlled studies are needed. The side effects of valproate use are well documented. Its effect on cognition and behaviour is more favourable than many of the other AEDs which is an important consideration in children. Overall, the clinical consensus of the meeting was that valproate's well established therapeutic properties far outweigh the negative side effects. Contraindication or withdrawal should be assessed individually.

[Aicardi-Goutieres syndrome: an oft unrecognised familial early-onset encephalopathy]. / Le syndrome d'Aicardi-Goutières: une maladie neurologique infantile, à transmission familiale, encore méconnue.

INTRODUCTION: Aicardi-Goutieres syndrome, first described in 1984, is a progressive infantile familial encephalopathy featuring cerebral calcifications, mainly of the basal ganglia, cerebral white matter abnormalities and cerebrospinal fluid lymphocytosis. Most of the patients present with severe developmental retardation, microcephaly, abnormal eye movements, pyramidal tract signs, and prominent dystonic movements. An elevated level of interferon-alpha in the CSF is a constant feature, particularly during the first stages of the disease course. One locus has been mapped on chromosome 3p21 in about half of the families so far studied. PATIENTS: and results. We report two new French cases and discuss the limits of the clinical syndrome, the differential diagnosis and issues raised by the pathophysiological mechanisms involved. The major concern is to separate this condition from intrauterine infections because of the genetic and therapeutic consequences. A number of other questions remain unanswered. For example, we still do not know today at what age the absence of features like CSF lymphocytosis, and possibly absence of calcifications, rules out the diagnosis of the condition. The origin of the vasculitis lesions is not known, but seems to be related to dysregulation of interferon production and secretion. CONCLUSION: Currently about 75 patients have been reported, even though many more probably exist. The study of this syndrome can contribute to the understanding of some mechanisms of CNS calcification and in a broader perspective to that of chronic encephalopathies with dysregulation of immune mechanisms.

Sturge-Weber syndrome: indications and results of surgery in 20 patients.

OBJECTIVE: To discuss the indications and timing for resective surgery in patients with Sturge-Weber syndrome (SWS) and medication-resistant epilepsy. BACKGROUND: SWS that causes epilepsy severe enough to merit surgery is rare. Because of the variable natural history of the disease, it is difficult to establish clear-cut indications for surgery and prospective studies are not feasible. Attitudes of clinicians and surgeons remain variable. METHODS: The authors assessed the presurgical epilepsy profile, criteria for surgery, monitoring techniques, and the postoperative outcome of epilepsy in all patients with SWS consecutively admitted between 1972 and 1990 to two referral centers (Paris and Montreal) and underwent surgery for intractable seizures. RESULTS: All 20 patients had a minimal postoperative follow-up of 4 years and all but one are still followed by one of the authors. One patient had a callosotomy, five underwent hemispherectomy, and 14 had cortical resection. Despite variability in the age at onset of seizures (range: 2 months to 12 years), age at operation (range: 8 months to 34 years) and surgical methods, almost all patients benefited from surgery. Visually guided complete resection of the pial angioma and underlying cortex, whenever possible, seemed sufficient; results were no better with intraoperative corticography. In children with previous hemiparesis, hemispherectomy proved particularly effective: all five became seizure free. None of the patients showed any aggravation of cognitive impairment following surgery; none of those who were operated on early presented with severe mental retardation, and 13 of 20 became seizure free. CONCLUSION: Although the natural history of SWS is imperfectly known, increasing duration of seizures and of postictal deficits, increase in atrophy or of calcified lesions or both, are indicative of its progressive nature. Despite the expected heterogeneity that renders formal comparison of the various approaches difficult, the current study provides new evidence to support early surgery in patients with SWS and drug-resistant epilepsy. The authors' results suggest that lesionectomy is a good approach, provided that the pial angioma is unilateral and the resection can be complete.

Is the underlying cause of epilepsy a major prognostic factor for recurrence?

BACKGROUND: We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region. METHODS: A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy. RESULTS: Seizure control (>1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS. CONCLUSIONS: In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

Gilles de la Tourette syndrome.

The study of childhood movement disorders is still in an early stage. Tics and related disorders are recognized as one of the most common movement disorders. This contribution reviews the main clinical, epidemiological, pathophysiological, and treatment issues on tics and Gilles de la Tourette syndrome. Although these disorders are not life threatening, they may be psychologically or functionally disabling. Early diagnosis and special management permit the alleviation of symptoms.

Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME.

Disruption of the function of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24, a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore, a candidate locus for at least some forms of IGE. We report corrected cDNA sequences and extended open reading frames for the mouse jerky and human JRK/JH8 genes, which add 48 amino acids to the N-terminus of the Jerky protein and which extends the region of homology with the N-terminal DNA-binding domain of the centromere-binding protein, CENP-B. Systematic sequencing of the coding region of the extended JRK/JH8 gene identified single nucleotide polymorphisms that define three haplotypes, which were used for association studies in patients with idiopathic generalized epilepsy. We report one subject with childhood absence epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a unique de novo mutation that results in a non-conservative amino acid change at a potential protein glycosylation site. Familial analysis supports a causal role for this mutation in the disease.

Multicentre clinical evaluation of vigabatrin (Sabril) in mild to moderate partial epilepsies. French Neurologists Sabril Study Group.

Vigabatrin (VGB) has been shown through several studies to be safe and effective as add-on therapy, particularly for the treatment of partial seizures in patients with severe epilepsies followed for years in hospital-based clinics. We now report additional clinical experience with VGB arising from an open trial of add-on VGB therapy in patients with relatively few seizures followed by qualified neurologists in private practice (the French Neurologists Sabril Study Group). VGB was administered to 397 patients aged 12-74 years (mean age = 37.5 +/- 13.8 years) who presented with no more than seven partial seizures of any type per month during a 3-month baseline period (mean number of seizures = 3.7 +/- 1.9/month). Simple partial seizures were reported in 121 (30.5%) patients, complex partial seizures in 282 (71.0%) and seizures with secondary generalization were reported in 111 (28.0%). The mean number of associated antiepileptic drugs (AEDs) was 1.9 +/- 0.9 and the mean dose of VGB was 2.21 +/- 0.64 g/day. Following introduction of VGB, 53 (13.4%) became seizure-free and remained so during the whole trial. During the fourth month of treatment, 158 patients (39.8%) had no seizures at all and a further 69 (17.4%) had their seizure frequency reduced by more than 50%. Secondary generalization was controlled during the whole period of treatment in 55 out of 97 patients (56.7%), 17 of which remained free of all types of partial seizures. VGB showed a good tolerability profile; adverse experiences more frequently reported were drowsiness and sleep disturbances. No action was necessary in the great majority of cases; the dose was reduced in 26 (6.5%) and VGB was discontinued in 32 (8%) patients. These data provide additional evidence that VGB can be used safely early on to treat patients with mild to moderate partial epilepsies. Secondary generalization was controlled in the majority of patients. Factors associated with the everyday clinical use of VGB, that resulted from a series of organized meetings with the investigators, are discussed.

Gabapentin add-on therapy with adaptable dosages in 610 patients with partial epilepsy: an open, observational study. The French Gabapentin Collaborative Group.

The objectives were to evaluate gabapentin add-on therapy in a large population under conditions close to real practice and to determine the therapeutic doses as reached with adaptable dosages. A 6-month multicentre, open-label study, involved addition of gabapentin to pre-existing treatment at the initial dosage of 1200 mg and subsequent adjustment between 900 and 2400 mg/day according to efficacy and tolerability. A study group of 610 adult patients, with partial epilepsy, persistent seizures and a median seizure frequency with a baseline of 7.2 per month were recruited; one-third had less than four seizures per month. Polypharmacy was frequent, with a mean of 2.3 concomitant drugs. After 6 months, 368 patients (62%) continued on gabapentin, at a mean dosage of 1739 mg/day with 44% of responders. On an intention-to-treat basis, median reduction in frequency was 21.2%, and the responder rate was 33.9%. The responder rate increased to 40.7% in the less severe subgroup receiving only one concomitant drug. Seventy-nine patients (13.4%) remained without seizures during the last evaluation period, versus nine (1.5%) during the baseline. Most of them had initially less than four seizures per month. The most frequent adverse effects, somnolence (29.3%), asthenia (14.6%), nausea (7.9%), ataxia (7.7%) and vertigo (7.2%), occurred rapidly after initial titration to 1200 mg/day, and were usually transitory. Weight gain (8.8%) seemed to be related to gabapentin dose. The combination of two recent drugs, vigabatrin and gabapentin, in 190 patients led to similar efficacy levels, with a tendency for more frequent somnolence and asthenia.

Hemifacial spasm or subcortical epilepsy?

A child with Goldenhar's syndrome presented at about one week of age with stereotyped, repetitive paroxysmal episodes of hemifacial contraction, suggestive of partial seizures or hemifacial spasm. Later in life he also developed independent, permanent abnormal eye and chin movements identical in rhythm to those seen in myorhythmias, suggesting involvement of the dentato-olivary pathway. MRI demonstrated a hamartomatous lesion at the level of the pontomedullary junction. We speculate that the nature of the lesion could be responsible for the partial seizures mimicking hemifacial spasm and that because of its location, this same lesion could also be implicated in the genesis of myorhythmias. The presence of a hamartomatous lesion in a region affected by the abnormal development of the first and second branchial arches is not fortuitous.

Infantile spasms and Menkes disease.

Epileptic seizures are a common feature in Menkes disease, an X-linked genetic disorder of copper metabolism. Details of type of seizures are rarely reported. We report the evolution of infantile spasms in two patients with Menkes disease and the relation with subcutaneous administration of copper-histidine.

Semiology of typical and atypical Rolandic epilepsy: a video-EEG analysis.

Since the first descriptions of Rolandic Epilepsy or benign epilepsy with centrotemporal spikes (BECTS), typical and atypical forms have been reported. Indeed, classical focal seizures are sometimes associated with various atypical ictal symptoms and cognitive or behavioural disorders. In an effort to define early clinical and EEG criteria allowing early distinction between typical and atypical forms, we recently conducted a prospective study in a cohort of children with Rolandic Epilepsy. The results of this study have been reported elsewhere. We now discuss the semiological characteristics, and comment on the video-EEG data collected during this study. Symptoms were classified into three major categories: "classical focal seizures"; "spike and wave related symptoms"; and "paraictal symptoms". Classical focal seizures constitute the electroclinical expression of the development and the propagation of a focal cortical neuronal discharge. "Spike and wave related symptoms" are brief neurological or neuropsychological phenomena having a relatively strict temporal relation with individual components of isolated focal or generalized spikes and waves. "Paraictal symptoms" consist of acquired progressive and fluctuating motor or cognitive deficits and are not directly correlated with Todd paralysis. We present detailed video-EEG material of selected cases and discuss the usefulness of such distinctions in terminology. We suggest that variability in clinical expression probably reflects the implication of different pathophysiological mechanisms, which in turn could explain differences in sensitivity to treatment. (Published with videosequences.)

[Children with drug-resistant partial epilepsy: criteria for the identification of surgical candidates]. / Les épilepsies partielles pharmaco-résistantes Quels sont les critères d'éligibilité à un traitement chirurgical chez l'enfant?

The majority of candidates for epilepsy surgery, in both children and adults, belong to the syndromic category of partial epilepsies. However, particularly in children, the clinical expression of epilepsy may sometimes be misleading, as paroxysmal events may present as generalized seizures although having a focal onset. The spectrum of surgical possibilities for early-onset epilepsy has tended to widen rapidly and to include not only other focal epilepsies but also more difficult types. This is because developmental lesions that are the major cause of infantile epilepsy are often poorly localized, involve extensive brain areas and require extensive operations (e.g. hemispherotomy). Surgery is also used for progressive conditions such as Rasmussen's encephalitis or Sturge-Weber syndrome. Some forms of generalized symptomatic epilepsy may also benefit from palliative surgical procedures (callosotomy in cases with repetitive drop attacks often as a manifestation of a Lennox-Gastaut syndrome). The timing of surgery partly depends on the probable effectiveness of the operation available for each particular patient. Candidates for epilepsy surgery must be identified early in the process of the disease, thus increasing the chances for a satisfactory cognitive and behavioral outcome. The decision should be taken by experienced multidisciplinary groups, that will also ensure post-operative follow-up, both in terms of medical management and psycho-social integration. Prospective studies are still needed, to evaluate the long-term cognitive evolution of children operated on early for their epilepsy and cured. Increasing evidence indicates that drug therapy is likely to fail to achieve control of the seizures when two-three of the major drugs, properly chosen by competent clinicians, have not obtained satisfactory results, i.e. full control of seizures and absence of side effects. Testing of all possible drugs is not advisable, because this process would be excessively long when surgery is a reasonable possibility. The requirements for resective surgery in children with partial drug-resistant epilepsy vary with the type of resection considered. Three basic requirements apply to almost all cases: (a) the epileptogenic area must be localized to a territory whose removal is contemplated; (b) that no other independent epileptogenic area exists in those areas that are not included in the planned resection, and (c) that any possible deficit resulting from resection must be acceptable. The current experience confirms that the complete resection of the epileptogenic area is the major condition for a satisfactory surgical result. The possibilities for resective surgery depend upon the localization of the ictal onset zone, its relationship with adjacent functional brain areas and the availability of convergent data that point to a single localization. Epilepsy surgery mandates a multidisciplinary approach that requires special skills and sophisticated instruments and materials that cannot be improvised. A global evaluation of risks and expected benefits is always required. All decisions require a close collaboration between the epilepsy team, the patient and the family. With the exception of high quality MRI and video-EEG recording of seizures, the need to perform any other complementary presurgical investigation should be evaluated on an individual basis.

[Therapeutic options provided by new antiepileptic drugs]. / Options thérapeutiques offertes par les nouveaux médicaments antiépileptiques.

The introduction on the French market of vigabatrin, gabapentin and lamotrigine has considerably diversified our conventional therapeutical schemes in epilepsies, as will be as amplified by the arrivals of topiramate, tiagabine and oxcarbazepine. Compared to the conventional drugs, these new products present more favorable pharmacokinetics, no or very weak interactions and a better tolerability, specially regarding the cognitive field. They should be used according to their spectrum of activity, function of their modes of action. In add-on trials on partial epilepsy patients all these new products have shown efficacy on partial and secondarily generalized seizures. Seizure frequency is reduced by at least 50 p. 100 in 30 to 50 p. 100 of the patients. A substantial number of patients can be rendered seizure-free with vigabatrin. Lamotrigine has a broader spectrum, as it is also efficacious on the different seizure types of generalized, symptomatic or idiopathic epilepsies. Main adverse events are non-specific central nervous system disturbances such as dizziness, drowsiness, ataxia, tremor or diplopia. More specifically, vigabatrin may induce weight gain and requires closer supervision in case of psychiatric history; lamotrigine which has also probable antidepressant properties, may induce skin rashs, rarely severe. Further data are needed for gabapentin which is now used at daily dosages which are two to three times those used in the initial studies. Gabamimetic agents may be worsening in some cases of generalized epilepsies, more specially on absence and myoclonic seizures. The most obvious benefits, some patients becoming seizure-free, are obtained in cases of intermediate severity, with a bitherapy including one of these new drugs. Developments in children are often delayed. Nevertheless the prognosis, including cognitive outcome, is considerably improved in infantile spasms with vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the latter being highly toxic. For the moment in France, authorities have limited the use of all these new antiepileptic drugs to adjunctive therapy in epilepsies resisting to conventional drugs. But recent monotherapy data show similar efficacy with better tolerability. Once the pivotal, controlled studies have enabled to obtain regulatory approval, all these compounds must undergo a large-scale evaluation phase in order to better define dosages, long-term tolerability, indications and eventual contra-indications in the various epileptic syndromes, including children.