Anne Lépine

Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome.

In order to assess the cognitive and adaptive profiles of school-aged patients with Dravet syndrome (DS), we proposed to evaluate the intelligence and adaptive scores in twenty-one 6- to 10-year-old patients with DS followed in our institution between 1997 and 2013. Fourteen patients were tested using the Wechsler Intelligence Scale for Children (WISC) and the Vineland Adaptive Behavioral Scales (VABS); 6 patients could not be tested with the WISC and were tested with the VABS only, and one was tested with the WISC only. Data regarding the epilepsy were retrospectively collected. Statistical analysis (Spearman rank order and Pearson correlation coefficient) was used to correlate early epilepsy characteristics with the cognitive and adaptive scores. Sodium channel, neuronal alpha-subunit type 1 (SCN1A) was mutated in 19 out of 21 patients. After the age of 6years, none of the DS patients had a normal intelligence quotient (IQ) using WISC (age at the testing period: mean=100±5; median=105months; mean total IQ=47±3; n=15). Only five patients had a verbal and/or a non verbal IQ of more than 60 (points). Their cognitive profile was characterized by an attention deficit, an inability to inhibit impulsive responses, perseverative responses and deficit in planning function. Administering the Vineland Adaptive Behavioral Scales in the same period, we showed that socialization skills were significantly higher than communication and autonomy skills (age at the testing period: mean=100±4; median=100months; n=20). We did not find any significant correlation between the IQ or developmental quotient assessed between 6 and 10years of age and the quantitative and qualitative parameters of epilepsy during the first two years of life in this small group of patients. Despite an overall moderate cognitive deficit in this group of patients, the Vineland Adaptive Behavioral Scales described an adaptive/behavioral profile with low communication and autonomy capacities, whereas the socialization skills were more preserved. This profile was different from the one usually found in young patients with autism and may require specific interventions.

Anti–tumor necrosis factor alpha therapy (adalimumab) in Rasmussen's encephalitis: An open pilot study

Rasmussens encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug‐resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF‐α) in RE pathophysiology.

Diagnosis and Outcome of SCN4A-Related Severe Neonatal Episodic Laryngospasm (SNEL): 2 New Cases

Mutations of SCN4A encoding the skeletal muscle sodium channel Nav 1.4 cause several types of disease, including sodium channel myotonias. The latter may be responsible for neonatal symptoms, including severe neonatal episodic laryngospasm (SNEL). Establishing the diagnosis of SCN4A-related SNEL early in the neonatal period is crucial because treatment is available that can reduce laryngospasm and improve vital and cerebral outcome. We report 2 new unrelated French patients who presented with SNEL. The first patient was initially diagnosed with laryngomalacia and underwent laryngeal surgery in the neonatal period before being diagnosed with myotonia at 14 months of age. The episodes of laryngospasm disappeared spontaneously, although occasional circumstances such as cold exposure could trigger laryngeal reactions; in addition, he developed myotonia corresponding to an adult myotonia permanens phenotype. This patient is now 24 years old and leading a normal life. The second patient was initially diagnosed with gastroesophageal reflux, then SNEL; his condition improved with carbamazepine treatment, and he is now 6 months old. The diagnostic sequence in both patients was the same: first, severe episodic apneic attacks necessitating hospitalization occurring in the first week of life; second, observation of muscle hypertrophy and peripheral hypertonia with a clear myotonic pattern on electromyogram (at 14 and 3 months of age, respectively); third, genetic testing revealing de novo SCN4A G1306E mutation. Both patients have had good therapeutic response to sodium channel blockers (carbamazepine or mexiletine).

Cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-D-aspartate receptor encephalitis: A case series.

BACKGROUND Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. METHOD We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5 years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. RESULTS Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. CONCLUSION Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population.

The role of stereoelectroencephalography (SEEG) in reevaluation of epilepsy surgery failures

Management of patients after initial epilepsy surgical failure is challenging. In this study, we report our experience in using the stereoelectroencephalography (SEEG) method in the reevaluation of patients after initial epilepsy surgical failure. We selected 28 patients examined through SEEG in our department for drug-resistant focal epilepsy following initial epilepsy surgical failure. For each patient, the residual seizure onset zone (rSOZ) as defined by SEEG was classified as either contiguous if the seizure onset zone (SOZ) was focal and close to the surgical cavity (same lobe) or noncontiguous in cases where the SOZ included site(s) distant from the surgical cavity. The rSOZ was defined according to visual analysis of SEEG traces completed by an estimation of the epileptogenicity index (EI). A second surgical procedure was performed in 12 patients (45%). A favorable outcome (Engel class I or II) was obtained in 9/12 patients (6 in Engel class I, 50%). The proportion of patients that had reoperation was higher in the contiguous group (80%) than in the noncontiguous group (22%) (p=0.02). A rSOZ localized in close relation to the initial surgical resection zone (contiguous group) was found in 10 patients (35%). Among them, 8 have since undergone reoperation, and a good outcome (Engel class I) was achieved in 5/8 (63%). A rSOZ involving a distant region from the first surgery was observed in 18 patients (65%) (noncontiguous group). Among them, only 4 have undergone reoperation, leading to a failure in 2 (Engel class III or IV) and a good outcome in 2 (IA). Ten patients had a first standard temporal lobectomy, and in 50% of these cases, the insula was involved in the rSOZ. Stereoelectroencephalography offers a unique way to evaluate the rSOZ at the individual level and thus guide further surgical decision-making. The best results are observed in patients having a focal rSOZ close to the site of the surgical resection in the first surgery.

Screening for depression in youth with epilepsy: The NDDI-E-Y

To The Editors: We read with interest the 2016 Epilepsia article by Wagner and colleagues validating the revised 12‐item screening tool for depression in youth with epilepsy: the Neurological Disorders Depression Inventory‐Epilepsy for Youth (NDDI‐E‐Y), and the 2017 Epilepsia article by the same team comparing NDDI‐E‐Y with the Neuro QOL‐SF. We commend the authors for this initiative, which is in line with the International League Against Epilepsy (ILAE) recommendations for routine screening for major depressive disorder (MDD) in epilepsy. Appropriate screening tools are crucial given the symptomatic overlap with the effects of antiepileptic drugs; this diagnostic challenge led to the development of the NDDI‐E for adults with epilepsy, a 6‐item questionnaire with robust psychometric properties across languages and populations. The NDDI‐E was thus a logical basis for the 12‐item NDDI‐E‐Y that aims at screening for MDD in 12‐ to 17‐year‐olds. We wished to validate this instrument in a group of 98 French patients using standard methodology, following our previous experience of validating screening instruments in French 7–9 and using methodology equivalent to that of Wagner et al, comparing NDDI‐E‐Y scores to the Childrens Depression Inventory (CDI). Our group was similar in size and demographics (age range 11‐17 years, mean 15; F 55%). According to the 2016 article of Wagner et al, the 12‐item NDDI‐E‐Y is scored from 0 to 3, giving a maximum possible of 36 if the patient scores 3 for all 12 items. It is therefore surprising that the authors found a cutoff of 32/36 as a suitable screening level, since this represents the highest percentile and would indicate nonnormal distribution of responses, with a possible ceiling effect. For the NDDI‐E in adults, scored from 1 to 4, the maximum possible is 24 and cutoff ranged from 11 to 16 across all studies, and is thus the middle range. For the NDDI‐E‐Y, our study in French youth with epilepsy found a cutoff of 11/ 36 (sensitivity 100% [95% confidence interval (CI) 83.9100.0]; specificity 83.1% [95% CI 72,9-90,7]; positive predictive value 61.8% [95% CI 43,3; -78,1]; negative predictive value 100% [95% CI 94.4; 100.0]), markedly lower than Wagner et als cutoff of 32/36. Indeed, no subject in our cohort reached a score of 32/36. This observed discrepancy in cutoff is difficult to explain by population factors, since prevalence of possible MDD according to CDI scores was similar, or by cultural‐linguistic differences, since previous multilanguage comparisons of NDDI‐E showed only mild variation. We therefore suggest that the NDDI‐E‐Y should be retested rapidly in a separate population to check validity of the proposed cutoff. Testing a new population is essential, as both recent publications on the NDDI‐E‐Y appear to have used the same 99 subjects according to the data provided. In addition, the 2017 paper surprisingly refers to the “11‐item NDDI‐E‐Y,” whereas their 2016 study was based on a 12‐item NDDI‐E‐Y, without explanation for this change. We would be grateful if the authors could present the distribution of responses for the total score and for each item, as is traditional in psychometric validation (Figure S1A,B). Further studies seem essential and urgent: Screening requires reliable and accurate cutoff scores, and an instrument with an overly elevated cutoff score would risk missing cases of MDD.

Epileptogenic networks in nodular heterotopia: A stereoelectroencephalography study

Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings.

CL056 - Association diabète de type 1 et épilepsie chez l’enfant

L’epilepsie est 2 a 3 fois plus frequente chez les enfants diabetiques de type 1. Cette association non fortuite a deja ete rapportee cependant son origine demeure inconnue : genetique, immunitaire… Nous presentons une serie de 10 cas suivis de facon retrospective afin de decrire les diverses manifestations epileptiques et diabetiques de ces patients et leurs caracteristiques electro-cliniques. La majorite des patients ont une epilepsie des regions centrales, avec des crises prolongees, voire dans un cas une epilepsie partielle continue revelatrice du diabete. Les autoanticorps anti-GAD retrouves dans la majorite des diabete de type 1, ont ete suggeres pour etre le lien entre l’epilepsie et le diabete de type 1. En effet, la GAD est retrouvee dans les cellules beta du pancreas mais c’est aussi une enzyme clef dans la synthese du GABA qui est le principal neurotransmetteur inhibiteur dans le systeme nerveux central. Le dysfonctionnement de la GAD cerebrale pourrait perturber la synthese du GABA et expliquer la plus grande frequence de l’epilepsie chez les patients diabetiques.

P310 - Phénomènes paroxystiques dans les encéphalites avec anticorps anti récepteur NMDA

Les encephalites avec anticorps anti-recepteur NMDA sont caracterisees par l’installation sub-aigue de troubles psychiatriques, d’alteration de la conscience et mouvements anormaux paroxystiques. Les anticorps diriges contre les recepteurs NMDA sont retrouves dans le LCR des patients, parfois egalement dans le serum. La presence de crises d’epilepsie est classiquement rapportee, mais leur caracterisation electro-clinique est peu decrite. Nous rapportons les observations de deux patientes de 10 et 14 ans avec une telle encephalite chez qui nous decrivons les caracteristiques electro-cliniques, l’imagerie morphologique et fonctionnelle, les donnees neuropsychologiques et l’evolution sous traitement specifique. Une des patientes presentait des phenomenes paroxystiques, initialement pris pour des crises ayant pu etre enregistres en video-EEG. Il s’agit de phenomenes dystoniques axiaux et oro faciaux paroxystiques prolonges, avec cyanose, mais dont l’origine epileptique a pu etre exclue. Ainsi, les «crises» rapportees chez les patients avec encephalite a anticorps anti-NMDA ne sont pas toutes de nature epileptique. L’existence de phenomenes dystoniques paroxystiques non epileptiques doit etre connue. Leur reconnaissance peut permettre une meilleure prise en charge therapeutique symptomatique.