Neuropsychological assessment in pediatric epilepsy surgery: A French procedure consensus.

Neuropsychological assessment is a mandatory part of the pre- and post-operative evaluation in pediatric epilepsy surgery. The neuropsychology task force of the ILAE - French Chapter aims to define a neuropsychological procedure consensus based on literature review and adapted for French practice. They performed a systematic review of the literature published between 1950 and 2023 on cognitive evaluation of individuals undergoing presurgical work-up and post-surgery follow-up and focused on the pediatric population aged 6-16. They classified publications listed in the PubMed database according to their level of scientific evidence. The systematic literature review revealed no study with high statistical power and only four studies using neuropsychological scales in their French version. Afterwards, the experts defined a neuropsychological consensus strategy in pediatric epilepsy surgery according to the psychometric determinants of cognitive tests, specificity of epilepsy, surgery context, French culture and literature reports. A common French neuropsychological procedure dedicated to pediatric epilepsy surgery is now available. This procedure could serve as a guide for the pre- and post-surgical work-up in French centers with pediatric epilepsy surgery programs. The main goal is to anticipate the functional risks of surgery, to support the postoperative outcome beyond the seizure-related one, while taking into consideration the plasticity and vulnerability of the immature brain and allowing the possibility of collaborative studies.

Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

French neuropsychological procedure consensus in epilepsy surgery.

INTRODUCTION: Neuropsychological assessment is an integral component of the surgical procedure in patients with epilepsy. As no French consensus for neuropsychological assessment was available, the main goal of this work was to define French neuropsychological procedure consensus in regard to literature review. METHOD: A panel of expert in neuropsychology was created within the framework of the French League Against Epilepsy. A systematic search of publications from 1950 to 2017 listed in PubMed database was conducted leading to a classification of articles according to their level of scientific evidence. French neuropsychological procedure consensus was then carried out with an expert panel of expert. RESULTS: Low scientific evidence of neuropsychological data was reported. A panel of expert proposed a comprehensive neuropsychological assessment procedure including the exploration of intellectual efficiency, long-term memory, short-term and working memory, attention, executive functions, processing speed and motor skills, language, visual processing, praxis, psychobehavioral, and social cognition. DISCUSSION: A common procedure for assessing cognitive and psychobehavioral function is now available in patients with epilepsy undergoing surgical evaluation have been established, they may help to improve the quality of care and the patient experience. This work highlights the need of furthers investigations and the necessity to develop specific tools with normative data.

Temporal lobe epilepsy in infants and children.

Clinical expression of temporal lobe seizures is different with a more diverse and more extensive etiology in infants and children than it is in adults. It is dominated by cortical dysplasia, low-grade tumors and perinatal damage. Hippocampal sclerosis, although less frequent, exists in children usually as a dual pathology associated with ipsilateral neocortical lesions. The clinical semiology of temporal seizures is more varied, and sometimes misleading. Motor features including tonic, clonic or myoclonic behaviors, and infantile spasms predominate in infants. Classical complex partial seizures with behavioral arrest and automatisms, as well as lateralizing signs are rare and occur mostly with onset after the age of two years. Interestingly, aura, emotional, and autonomic signs seem to be independent on the brain maturation process. Moreover, the neuropsychological profile varies according to age of onset and duration, lateralization of the focus and etiology. Quality of care benefits from individual cognitive assessment for memory and emotional processes.

Outcome of surgery in children with focal cortical dysplasia younger than 5 years explored by stereo-electroencephalography.

PURPOSE: Focal cortical dysplasia (FCD) is the most frequent etiology for drug-resistant epilepsy in young children. Complete removal of the lesion is mandatory to cure the epilepsy. Stereo-EEG (SEEG) is an excellent method to delimitate the zone to be resected in older children and adults. We studied its feasibility in younger children. METHODS: We retrospectively studied 19 children under 5 years of age who underwent SEEG between January 2009 and December 2012 and were subsequently operated on. FCD was diagnosed in all. We reviewed magnetic resonance imaging (MRI), electrophysiological and clinical data, as well as postoperative seizure outcome. We also included fluoro-deoxyglucose positron emission tomography (FDG-PET) studies, which had been systematically performed before invasive recording in 16 of the 19 children. RESULTS: The mean patient's age at the time of SEEG was 38.6 months, and the mean age at seizure onset was 8 months. Three patients had normal MRI. No SEEG-associated complications occurred. We were able to delineate the epileptogenic zone in all children, and electrode stimulation localized the motor area when necessary (12 patients). Hypometabolic areas on FDG-PET included the epileptogenic zone in 13 of the 16 children, with a lobar concordance in 9 (56 %) and the same anatomical extent in 6 (38 %). Twelve children subsequently underwent focal or sublobar resection, six had multilobar resection, and one had hemispherotomy. The etiology was FCD type 2 in 15 and FCD type 1 or type 3 in three children. Eighty-four percent of our population have remained seizure-free at a mean follow-up of 29 months (12-48 months). CONCLUSION: Although children with FCD can successfully undergo resective surgery without invasive EEG, poor seizure semiology at this age inclines to perform SEEG when the dysplastic lesion is ill-defined and/or the electroclinical correlation is unclear. In cases with normal imaging as well as with suspected huge malformations, as was the case in 52 % of our patients, we consider it to be indispensable.

Unveiling the cognitive network organization through cognitive performance.

The evaluation of cognitive functions interactions has become increasingly implemented in the cognition exploration. In the present study, we propose to examine the organization of the cognitive network in healthy participants through the analysis of behavioral performances in several cognitive domains. Specifically, we aim to explore cognitive interactions profiles, in terms of cognitive network, and as a function of participants' handedness. To this end, we proposed several behavioral tasks evaluating language, memory, executive functions, and social cognition performances in 175 young healthy right-handed and left-handed participants and we analyzed cognitive scores, from a network perspective, using graph theory. Our results highlight the existence of intricate interactions between cognitive functions both within and beyond the same cognitive domain. Language functions are interrelated with executive functions and memory in healthy cognitive functioning and assume a central role in the cognitive network. Interestingly, for similar high performance, our findings unveiled differential organizations within the cognitive network between right-handed and left-handed participants, with variations observed both at a global and nodal level. This original integrative network approach to the study of cognition provides new insights into cognitive interactions and modulations. It allows a more global understanding and consideration of cognitive functioning, from which complex behaviors emerge.

Heterotopia associated with hippocampal sclerosis: an under-recognized cause of early onset epilepsy in children operated on for temporal lobe epilepsy.

PURPOSE: The aim of this study is to report on 52 children operated on for pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology and correlation with clinical features. METHODS: Charts were retrospectively analyzed. All children underwent comprehensive clinical, electrophysiological and radiological investigations before surgery. Surgical procedures were tailored according to scalp, foramen ovale and eventually depth electrode recordings. Histopathology was compared with clinical variables (χ (2) and Fisher's exact tests). Outcome was evaluated using the Engel scale. RESULTS: Developmental tumor was found in 14 cases, malformation of cortical development (MCD) in 26, isolated hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18 patients and the main extrahippocampal lesion consisted of microscopic sub-cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical pattern: a history of febrile seizures (FS) and/or brain injury, early onset of epilepsy without latent period from FS to the first temporal seizure, and a particularly good outcome following surgery. CONCLUSION: In our pediatric temporal lobe surgery series, the prevalence for MCD and for DP was higher than in adult series. Age at seizure onset depends on pathology, and is earlier when involving the neocortex rather than only the hippocampus. We identify the association HS-HT (the most frequent DP in this series), with particular clinical features.

[Quality of life in children with epilepsy: a review]. / La qualité de vie chez l'enfant avec épilepsie: revue de la littérature.

Health-related quality of life (HRQOL) is a multidimensional construct, without general agreement on the number of domains and the content of each domain. In children with epilepsy, the HRQOL evaluation includes both nonspecific aspects, such as behavioral, psychological and cognitive difficulties and the impact of a chronic pediatric illness on the child and its family and specific aspects, such as the perception of the severity of the seizures and of the undesirable effects of the antiepileptic treatments, as well as the social impact of a negative attitude toward epilepsy. The present article presents a review of the methods proposed for the assessment of HRQOL in children with epilepsy. Most methods rely on parental reports; however, there is an increasing effort to develop tools taking the child's point of view into account. HRQOL tools have often been used in clinical trials and, especially, to evaluate the surgical treatments of epilepsy. For the clinician, HRQOL tools may be a preliminary approach to the patient's problems to be interpreted in relation to the patient's medical, psychological, cognitive, social and familial context. In France, few large-scale studies on HRQOL in children with epilepsy have been conducted. We present the preliminary results of a French study based on parental reports.

[Surgical disconnection of hypothalamic hamartomas]. / Déconnexion chirurgicale des hamartomes hypothalamiques.

BACKGROUND AND PURPOSE: Surgical resection of hypothalamic hamartomas (HHs) associated with drug-resistant gelastic epilepsy carries a considerable risk of neurological and endocrine morbidity. Alternative surgical routes and techniques have therefore been proposed, especially for broadly attached lesions and for those with a third ventricular location. METHODS: We present an updated series of 43 patients (aged nine months to 34 years), operated on from 1998 through 2005 at our institution. The hamartoma was disconnected using a microsurgical pterional approach of those lesions extending from the hypothalamic floor downward into the interpeduncular cistern. When the HH presented as a paramedian mass, partly or exclusively bulging into the third ventricle, with a rather vertical plane of attachment, we chose a frameless stereotactic endoscopic technique to disconnect the lesion. In several of our patients, both methods were applied subsequently. RESULTS: Surgery-related morbidity was lower with the ventricular endoscopic technique. Twenty-one patients (50%) are seizure-free and two patients (5%) almost seizure-free, while in 17 patients (40%), there was a significant seizure reduction. Two patients (5%) had no postoperative improvement. According to the different topographic features of the HHs, for which we have recently proposed a classification into four subtypes, the intraventricularly located hamartoma had the best prognosis following endoscopic disconnection. Ten of the 12 patients (83%) with this HH location became seizure-free. CONCLUSIONS: Resection of epilepsy-related HHs can be replaced by disconnective procedures. Our results confirm their feasibility and acceptable morbidity, with particularly good seizure outcome in patients with intraventricularly located HHs.

[Long-term outcome after hemispheric disconnection]. / Evaluation à long terme des déconnexions hémisphériques.

Hemispheric disconnection has been largely proposed for patients with severe epilepsy associated with a congenital or acquired hemispheric cerebral pathology. The classical procedure of anatomical hemispherectomy was progressively abandoned by neurosurgeons in order to avoid postoperative complications since then hemispherotomy techniques have been developed. Globally, with hemispheric disconnection, the rate of patients becoming seizure-free has been between 50 and 80%. The factors affecting seizure control have not been completely elucidated, but several authors suggested that differences in etiology as well as the hemispheric disconnection technique used may partially explain this variability. The percentage of seizure-free patients is higher with hemispherotomy techniques and in the group of patients with Rasmussen encephalitis, Sturge-Weber syndrome, and vascular insults. Depending on overall long-term progression, there is an improvement compared to preoperative status even if children exhibit heterogenous abilities. The lowest scores are observed for motor skills but communication and socialization are relatively well-preserved and strongly related to the duration of epilepsy: the longer the duration, the lower the scores were. Neuropsychological outcome following hemispheric disconnection makes it possible to study the development of hemispheric specialization during infancy and to provide information on cognitive recovery. Cerebral reorganization has been proved to exist in motor and language recovery. Ipsilateral corticospinal pathways seem to be involved in the movement of hemiplegic limbs. Everyday language can be supported by both hemispheres, but there is an early hemispheric specialization of the left hemisphere according to metaphonologic abilities.

[Epilepsy surgery during infancy and early childhood in France]. / Chirurgie de l'épilepsie de l'enfant et du nourrisson en France.

BACKGROUND AND PURPOSE: We present the epilepsy surgery activity in infants and children at the Fondation Rothschild Hospital, the main center dedicated to this activity in France. METHOD: A prospective study was conducted from 2003 to 2007 based on three populations: (1) children selected as candidates for surgery, (2) children undergoing presurgical evaluation and (3) children undergoing surgical procedures for epilepsy. RESULTS: Children selected as candidates for surgery: 304 children were referred and discussed by our multidisciplinary staff. They came from Paris and its suburbs (40%), the provinces (43%) or from other countries (14%). Sixty-one percent of them were included in our surgery program and 24% were excluded. Sixty-one percent of them were under 10 years of age. Children undergoing presurgical evaluation: 296 children were recorded: 140 EEG (47%), 46 with foramen ovale electrodes (16%) and 110 with invasive recording techniques (37%). Seventy percent of these children were under 10 years of age. Children undergoing surgical procedures: 316 children underwent surgery; 68% of them were under 10 years of age. The surgical procedures were focal resection (136 children), vertical parasagittal hemispherotomy (77 children), resection and or disconnection for hypothalamic hamartoma (69 children) and 34 had palliative surgery (callosotomy or vagal nerve stimulation). CONCLUSION: Eighty to 100 children undergo surgery each year in our department for drug-resistant partial epilepsy; 70% of them are less than 10 years of age. This activity is part of a network of pediatric neurologists who are deeply involved in treatment of severe epilepsy in children.

[Electrophysiological investigations in childhood epilepsy surgery]. / Explorations électroencéphalographiques préchirurgicales de l'enfant.

Epilepsy surgery in children is a functional surgery: its goal is to perform the resection of the epileptic brain tissue while sparing the eloquent cortex. Prolonged scalp video-EEGs allow recording of all types of seizures and play a crucial role in localizing the epileptogenic zone. Furthermore, EEG data correlation with clinical and radiological findings provides a guide for the surgical strategy: either resection without further investigations or an invasive recording procedure. In prehemispherotomy evaluation, EEG recordings confirm that limited resections are not indicated and demonstrate that the opposite hemisphere is not involved. If invasive recordings are needed, they consist in foramen ovale electrode insertion, which provides valuable information in mesial temporal lobe epilepsy, stereoelectroencephalography for children older than two years, and subdural grids associated with depth electrodes in infants or when the eloquent areas need to be carefully investigated. Such investigations allow tailoring surgery to each child.

[Epilepsy surgery in France]. / La chirurgie de l'épilepsie en France Evaluation de l'activité

We report here the results of the first survey on epilepsy surgery activity in France. Data from a questionnaire sent to 17 centers practicing epilepsy surgery were analyzed. All centers responded; however, all items were not completely documented. Over 50 years, more than 5000 patients have been operated on for drug-resistant epilepsy and more than 3000 patients underwent some invasive monitoring, most often SEEG. Currently, nearly 400 patients (including more than 100 children) are operated on yearly for epilepsy in France. Over a study period varying among centers (from two to 20 years; mean, 9.5 years), results from more than 2000 patients including one-third children were analyzed. Important differences between adults and children, respectively, were observed in terms of location (temporal: 72% versus 4.3%; frontal: 12% versus 28%; central: 2% versus 11%), etiology (hippocampal sclerosis: 41% versus 2%; tumors 20% versus 61%); and procedures (cortectomy: 50% versus 23%; lesionectomy: 8% versus 59%), although overall results were identical (seizure-free rates following temporal lobe surgery: 80.6% versus 79%; following extratemporal surgery: 65.9% versus 65%). In adults, the best results were observed following temporomesial (TM) resection associated with hippocampal sclerosis or other lesions (class I: 83% and 79%, respectively), temporal neocortical (TNC) lesional (82%), while resections for cryptogenic temporal resections were followed by 69% (TM) and 63% (TNC) class I outcome. Extratemporal lesional resections were associated with 71% class I outcome and cryptogenic 43%. In children, the best results were obtained in tumor-associated epilepsy regardless of location (class I: 80%). A surgical complication occurred in 8% after resective surgery - with only 2.5% permanent morbidity - and 4.3% after invasive monitoring (mostly hemorrhagic). Overall results obtained by epilepsy surgery centers were in the higher range of those reported in the literature, along with a low rate of major surgical complications. Growing interest for epilepsy surgery is clearly demonstrated in this survey and supports further development to better satisfy the population's needs, particularly children. Activity should be further evaluated, while existing epilepsy surgery centers as well as healthcare networks should be expanded.

Long term response to steroid therapy in Rasmussen encephalitis.

Rasmussen encephalitis (RE) is a severe and progressive focal epilepsy of unknown origin that leads to deterioration of motor and cognitive function. In a previous study, we described positive effect of high doses of steroids during the first year after the onset of RE. The objective of this study was to evaluate this therapy at long term. We reviewed 11 patients (7 girls and 4 boys) with RE of the right hemisphere (7) and the left (4) at a follow-up of 9+/-2 years. Age at onset of RE ranged from 2 to 14 years. Six patients had no benefit from steroid therapy and underwent hemispherotomy. Five had significant reduction of seizure frequency with disappearance of epilepsia partialis continua, and improved motor function. Of these, two died of unexpected sudden death 5 and 7 years after seizure control. Two others with initial response experienced progressive recurrence of seizures 1 to 4 years after the end of steroid therapy and required hemispherotomy. Finally, only one patient exhibited total cessation of seizures with steroids for 3 years, but seizures progressively recurred although the frequency was moderate. Our data confirm that although steroid treatment can be useful when given early in the course of RE, long term relapse can occur among the good responders requiring delayed hemispheric disconnection.

[Recent advances in pathogenic concepts and therapeutic strategies in Rasmussen's encephalitis]. / Avancées actuelles sur les concepts pathogéniques et thérapeutiques de l'encéphalite de Rasmussen.

Rasmussen's encephalitis (RE) is a rare inflammatory brain disease mainly affecting children and characterised by intractable epilepsy involving a single hemisphere that undergoes progressive atrophy. RE is characterized by refractory focal seizures, often associated with epilepsia partialis continua, progressive unilateral motor defect, slow EEG activity over the entire contralateral hemisphere, with focal white matter hyperintensity and insular cortical atrophy on neuroimaging. Surgical exclusion of the affected hemisphere is the only treatment that interrupts progression of the disease. Pathogenic concepts have considered viruses, autoimmune antibodies and autoimmune cytotoxic T lymphocytes that might contribute to the initiating or perpetuating events in the central nervous system. Based on these concepts, different therapeutic strategies have been pursued, such as antiviral agents, plasmapheresis, immuno-adsorption, immunosuppression or immunomodulation with intravenous immunoglobulins. However, due to the lack of large studies, to date there is no established therapeutic strategy for this devastating condition. In this review, we give an overview of the current state of immunopathogenic concepts for Rasmussen's encephalitis and discuss the different therapeutic options for future perspectives.

Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes.

PURPOSE: To analyze the relationship between craniospinal irradiation (CSI) and intellectual outcome in children with posterior fossa (PF) tumors. METHODS AND MATERIALS: A neuropsychological evaluation was performed retrospectively in 31 children, aged 5-15 years, who had received radiotherapy for PF tumors, and who had been off therapy for at least 1 year. Factors evaluated for impact on intellectual outcome were: socioeconomic status, disease presentation, histology, complications, chemotherapy, age at radiotherapy, interval between radiotherapy and testing, and radiation doses and volumes. Patients were divided into 3 subgroups according to the CSI doses (0 Gy [i.e., PF irradiation only], 25 Gy, and 35 Gy), with 11, 11, and 9 patients, respectively. RESULTS: Long-term cognitive impairment occurred in most of the patients, even after PF irradiation only. Moreover, there was a significant correlation between the full-scale IQ score (FSIQ) and the CSI dose, with mean FSIQ scores at 84.5 (SD = 14.0), 76.9 (SD = 16.6), and 63.7 (SD = 15.4) for 0 Gy, 25 Gy, and 35 Gy of CS1, respectively. A marked drop in verbal comprehension scores was noted in children who had received the higher dose. CONCLUSION: This preliminary study further supports the rationale for de-escalation of CSI doses and volumes in standard-risk PF tumors.

Dopaminergic D2 receptor SPECT imaging in Rett syndrome: increase of specific binding in striatum.

A dopamine deficiency has been implicated in Rett syndrome, a progressive encephalopathy in girls that involves movement, tonus and cognitive disorders. To test the hypothesis that striatal D2 receptors increase in number in early stages of the disease, we measured the binding potential of 123I-Iodolisuride, a specific D2 ligand, in eleven Rett children aged 4-15 yr (7.9 +/- 3.5 yr) (mean +/- s.d.) and eight control subjects aged 3.5-13 yr (8.1 +/- 3.8 yr) who exhibited other neurological disorders. Regional cerebral blood flow (rCBF) was also measured with SPECT using 133Xe. The binding potential for 123I-ILIS and D2 receptors was significantly higher in Rett (0.45) than in controls (0.23) (p < 0.01). An increase in 123I-ILIS binding due to increased rCBF in patients' striata was excluded. Our results are consistent with a higher density of D2 receptors in young patients suffering from Rett syndrome because of reduced dopaminergic neurotransmission.

Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.

Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.

No evidence for a susceptibility locus for idiopathic generalized epilepsy on chromosome 5 in families with typical absence seizures.

A recent genome-wide scan revealed suggestive evidence for two susceptibility loci for idiopathic generalized epilepsy (IGE) in the chromosomal regions 5p15 and 5q14-q22 in families with typical absence seizures. The present replication study tested the validity of the tentative IGE loci on chromosome 5. Our study included 99 multiplex families in which at least one family member had typical absence seizures. Parametric and non-parametric multipoint linkage analyses were carried out between the IGE trait and 23 microsatellite polymorphisms covering the entire region of chromosome 5. Multipoint parametric heterogeneity lod scores < -2 were obtained along chromosome 5 when a proportion of linked families greater than 50% was assumed under recessive inheritance and > 60% under dominant inheritance. Furthermore, non-parametric multipoint linkage analyses revealed no hint of linkage throughout the candidate region (P > 0.05). Accordingly, we failed to support previous evidence for common IGE loci on chromosome 5. If there is a susceptibility locus for IGE on chromosome 5 then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.

Visual agnosia after treatment of a posterior fossa ependymoma in a 16-month-old girl.

We present the clinical observation of a 16-month-old girl treated for a posterior fossa ependymoma who experienced severe and delayed visual dysfunction. She was initially treated by surgery and conventional chemotherapy. When she relapsed at age 3 years, the salvage treatment combined high-dose chemotherapy, second surgery, and local irradiation. At age 4 years, disturbed gait and dysarthric speech appeared rapidly, and she became unable to recognize objects and people. Computed tomography revealed bilateral calcifications in the cerebellum and temporal and occipital lobes but no relapse. The neuropsychologic evaluations revealed signs of visual agnosia and marked intellectual impairment. The role of the different treatment modalities in the pathogenesis of this unusual syndrome is discussed.