Developmental outcome of children with Robin sequence treated with the current Paris protocol.

AIM: We aimed to investigate the developmental outcome of children with Robin sequence (RS) for whom continuous positive airway pressure was the main strategy to release upper airway obstruction. METHODS: We included children with isolated RS or RS associated with Stickler syndrome who were aged 15 months to 6 years. We used the French version of the Child Development Inventory and calculated the developmental quotient (DQ) for eight different domains and the global DQ (DQ-global). We searched for determinants of risk of delay. RESULTS: Of the 87 children, for 71%, the developmental evolution was within the norm (DQ-global ≥86 or ≥-1 SD), 29% were at high risk of delay (DQ-global <86 or <-1 SD), and only 3% were at very high risk of delay (DQ-global <70 or <-2 SD). The DQs for expressive language and language comprehension were lower in our study population than the general population, but an improvement was noticed with the children's growth. CONCLUSION: Risk of a developmental delay was not greater for children with the most severe respiratory phenotype than the others. Children whose mothers had low education levels were more at risk than the others.

Autism spectrum disorder phenotype and intellectual disability in females with epilepsy and PCDH-19 mutations.

INTRODUCTION: Autism features and various degrees of cognitive deficit are reported in patients with PCDH-19 mutations and epilepsy. Autism spectrum disorder (ASD) and, often, cognitive profile are usually assessed clinically. We studied autism phenotype and cognitive outcome in a series of patients using standardized tools for development and ASD. We aimed to describe the phenotype of ASD in this series and to understand whether ASD is strictly linked to intellectual disability (ID) or is present as a comorbidity. METHODS: Eight females aged 5 to 17years old with PCDH-19 mutations and epilepsy were recruited. For ASD diagnosis, the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnosis Observation Schedule (ADOS) were administered. Patients underwent a neuropsychological examination with tests measuring global intellectual efficiency (WPPSI-III and WISC-IV), language, and executive and social cognition abilities. Parental adaptive behavioral questionnaires were also obtained (VABS, CBCL, and BRIEF). RESULTS: Six out of eight patients presented with ASD and ID. Two patients had neither ASD nor ID, and both had the latest age of onset for their epilepsy. All cognitive functions were deficient, but theory-of-mind abilities compared to other cognitive features were even impaired. Features of ASD lacked major repetitive and stereotyped behaviors and show some differences with the classical ASD features related to ID. CONCLUSION: Our results show a large spectrum of ID and a very high rate of ASD in patients with epilepsy and PCDH-19 mutations. Autism spectrum disorder seems to be a genuine comorbidity, more than a consequence of ID. It highlights the importance of standardized psychiatric and cognitive evaluation in order to establish a tailored rehabilitation program.

Language recovery after left hemispherotomy for Rasmussen encephalitis.

PURPOSE: Hemispherotomy (H) is the gold standard treatment to cure epilepsy in Rasmussen encephalitis (RE). Linguistic prognosis after surgery remains the main issue when the dominant hemisphere is involved. The topic of the present research is to specify the long-term linguistic profile of the right hemisphere after left dominant H for RE. METHODS: We followed 6 children 8.4 to 14.6 years of age who underwent left H for RE. Preoperatively, four children experienced aphasia, but for two, worsening occurred after surgery. Age at H ranged from 4.1 to 8.4 years. The mean duration of epilepsy was 1.2 years and 5.6 years for follow-up. Neuropsychological evaluation included longitudinal follow-up of intellectual efficiency measurement and a long-term outcome of language using various components of receptive and expressive oral speech with computerized tasks. KEY FINDINGS: Preoperatively, verbal comprehension index (VCI) was dramatically decreased in 4/6 patients, and performance reasoning index (PRI) was low in 5/6 participants, demonstrating a global impact of RE itself. Postoperatively, all children recovered sufficiently to attend a regular VCI (above 70) in a mean of 5 years after H, and 5/6 recovered normal or adapted school. There was a dissociation in favor of VCI, while PRI decreased in 5/6 patients. We found a specific linguistic profile for these children recovering language in the right hemisphere: normal verbal comprehension, and weakness of grammatical judgment, word repetition, statement production, semantic verbal fluency and metaphonological abilities. Language recovery scores were statistically correlated with those of Working Memory Index. SIGNIFICANCE: This study emphasizes for the first time the ability of the right hemisphere to functionally reorganize language over a long period of time following left H for RE. Syntactic abilities and phonology remain low and support the hypothesis of an early left hemispheric specialization. Nevertheless, lexico-semantic processes recover in the right hemisphere that could reflect a pre-existing potential of both hemispheres. Our results support a decision to proceed to H in classical left RE disease until the late childhood even if there is no complete aphasia before surgery. These data should be taken in account in the overall postoperative follow-up and rehabilitation strategy.

Reading impairment in an adolescent with temporo-occipital epilepsy. Pre- and post-surgical evaluation.

We present a 16 year-old right-handed case who underwent a left temporo-occipital resection to treat intractable epilepsy. Pre- and post-surgical evaluations showed an average intellectual quotient, preserved abilities in language and visuo-spatial functions and increased reading and spelling deficits (difficulties with irregular words, homophones and phonologically valid spelling errors of irregularly spelled words, associated with preserved performances in non-words). This pattern of characteristic lexical route deficits highlights the major role of the temporo-occipital areas in reading acquisition. We discussed the consequences of temporo-occipital dysfunction on reading.

Verbal and spatial learning after temporal lobe excisions in children: an adaptation of the Grober and Buschke procedure.

Using an adaptation of Grober and Buschke's procedure, we assessed verbal and visuospatial learning abilities in 16 children after left or right anteromesial temporal resection and 16 healthy controls to evaluate material-specific memory deficits. All children had relatively well-preserved verbal and spatial learning capacities after unilateral temporal resection. Children who had left temporal resection showed impaired verbal memory performance despite semantic control by cued recall. No memory deficits with visual material were detected in children who underwent right anteromesial temporal resection. Grober and Buschke's procedure appears relevant for the detection of verbal memory disorders in children with left-sided temporal resection.

Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype.

OBJECTIVE: We aimed to assess a cohort of young patients with Dravet syndrome (DS) for intellectual disability (ID) and autism spectrum disorder (ASD) using standardized tools and parental questionnaires to delineate their specific profiles. METHODS: We included 35 patients with DS aged 24 months to 7 years, excluding patients with a developmental age (DA) <18 months (n = 5). We performed specific tests adapted for ID (Psychoeducational Profile, Third Edition [PEP-3]), in addition to the Child Development Inventory (CDI) and Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaires. We used 2 standardized tools for ASD: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). We compared the with parental questionnaires and the VABS-II, and with ASD characteristics. RESULTS: PEP-3 subscales showed pathologic development in all but one patient (97%): ID in 23 of 30 (77%), and borderline cognitive functioning in 6 of 30 (22%). Eleven patients (39%) had ASD and 2 (7%) had a Social Communication Disorder (SCD) diagnosis. We found no difference between PEP-3 and CDI categorization except for fine motor skills. We found significant negative correlations between ADOS-2 and PEP-3 for the majority of scores. For patients aged older than 50 months, 2 groups emerged (ASD/no ASD) with significant difference in DA. The logistic regression for ASD diagnosis explained by VABS-II showed a significant effect for Socialization, Motor Skills, and Adaptive Behavior. SIGNIFICANCE: We found a high prevalence of ID in patients with DS. ID is characterized by expressive and comprehensive communication deficits in addition to visuospatial difficulties. ASD showed a specific profile with a relative preservation of social skills, emphasizing a possible underdiagnosis. Parental questionnaires can provide a good assessment of cognitive profile and might allow the difficulty of addressing cognitive scales in DS to be overcome. The profile of ID and ASD should help to establish early adapted rehabilitation programs and emphasizes the global need for care beyond seizures in DS and other developmental epileptic encephalopathies.

Patients with dravet syndrome in the era of stiripentol: A French cohort cross-sectional study.

OBJECTIVE: The aim of this study was to assess outcome and seizure response to treatment with stiripentol (STP) associated to valproate (VPA) and clobazam (CLB), which we have used in our center since the 1990s, in patients with Dravet syndrome (DS). METHODS: We performed a cross-sectional study of all DS patients with SCN1A mutations who had at least one visit to our center in 2013. A total of 54 patients were included (32 males, 22 females), whose ages ranged from 2.5 to 22 years. RESULTS: Seizure onset ranged from 2 to 9 months (mean 5 months). Treatment started at a mean age of 7 months with valproate (VPA) as first therapy in 83% of patients. STP was prescribed in 96% at an average age of 20 months. At last follow-up (up to 22 years, median 8 years), 96% were still receiving STP, with VPA and clobazam (CLB) in 91%. Additional therapies were prescribed in 72% of patients. Most patients (96%) continued to have clonic or tonic-clonic seizures but they were brief (<5min, with last status epilepticus (SE) episode being before 4 years of age). Seizures occurred weekly (>3/month) in 38% of patients, monthly (1-3/month) in 40%, and yearly in the remaining patients. None presented with daily seizures. Seizure frequency at last visit was related to the age of treatment initiation, the age of last SE, and SCN1A mutation type. CONCLUSIONS: Triple therapy with STP, VPA, and CLB was maintained long-term by 96% of this large DS cohort because the reduced frequency and severity of seizures STP provided when added to CLB and VPA was durable. Nevertheless, only a few patients achieved seizure freedom and persisting seizures remains a concern in the majority of patients.

Encephalopathy in children with Dravet syndrome is not a pure consequence of epilepsy.

BACKGROUND: Dravet syndrome (DS) is currently considered as an epileptic encephalopathy, a condition in which epilepsy causes deterioration or developmental delay but preliminary data suggested that cognitive course may worsen independently from epilepsy. Our objective was to prospectively analyze the neuropsychological features in a large cohort of DS patients and its relationships with epilepsy and SCN1A mutation. METHODS: 81 examinations were performed in 67 patients with typical DS (9m-24y, 15 longitudinally studied) using Brunet-Lezine (developmental/intelligence quotient [DQ/IQ] and DQ sub-scores), Achenbach, Conners, and a semi-quantitative psychomotor score (SQPS). We studied the correlation between DQ/IQ/SQPS and age, epilepsy characteristics, and whether patients presented SCN1A mutation. RESULTS: DQ/IQ significantly decreased with age (r = -.53, p < .001), from normal before 2y (mean 80, range 64-105) to low after 3y (mean 48, range 30-69), with hyperactivity and attention disorders hampering learning abilities especially up to 6y. However, raw (not age-adjusted) DQ sub-scores increased with age during the first decade, showing that there is no regression. We did not find any significant correlation between DQ/IQ at last evaluation and epilepsy data, i.e. first seizure (age, type, duration, fever), seizures during the course (type, fever sensitivity), status epilepticus (age of onset, number, fever), photosensitivity, and treatment, except for myoclonus and focal seizures which were associated with a lower QD/IQ after 3y. SCN1A mutated patients (n = 58) seemed to exhibit worse psychomotor course than non-mutated ones (n = 9) (severe SQPS in 26% vs 0%), although their epilepsy tended to be less severe (tonic seizures in 12% vs 44% [p = 0.04], first status epilepticus before 6 m in 26% vs 67% [p = .02], mean number of SE 2.5 vs 4.5 [p = .09]). DQ sub-scores were dissociated throughout the whole course: from onset hand-eye coordination was significantly lower than language, posture and sociability (p < .01). Dissociation seemed to be more frequent in mutated than in non-mutated patients (motor SQPS was normal for in 77% vs 44% [p = 0.017] whereas language SQPS was normal for 47% vs 100%). CONCLUSIONS: Although psychomotor/cognitive delay declines with age, there is no regression. In addition, encephalopathy is not a pure consequence of epilepsy but SCN1A mutation seems to play an additional, direct role.

Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children.

OBJECTIVE: To describe initial and follow-up electroencephalographic (EEG) characteristics in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. METHODS: Consecutive polygraphic video-EEG recordings were analyzed in nine pediatric patients with anti-NMDAR encephalitis at the initial stage of the disease and during the intermediate period until motor recovery. EEG characteristics in waking and sleep stages as well as EEG correlates of abnormal movements are described. RESULTS: In six patients, [corrected] the waking EEG showed preserved background activity and either focal or unilateral hemispheric slowing. These children had more favorable outcome than the three children with diffuse slowing. Unilateral [corrected] abnormal movements contra-lateral to hemispheric or focal slowing were also indicative of milder severity when compared to generalized abnormal movements and diffuse slowing. During non-rapid eye movement (NREM) sleep, a decrease in the expected slow waves and unilateral or diffuse theta-alpha band rhythms were observed in six children, not correlated with the outcome, representing a suggestive EEG pattern of anti-NMDAR encephalitis. [corrected]. CONCLUSIONS: In pediatric patients presenting behavioral disorders and abnormal movements, early EEG patterns may be suggestive of anti-NMDAR encephalitis. Moreover early electro-clinical presentation contributes to outcome prediction. SIGNIFICANCE: This case series demonstrates that early EEG patterns may be suggestive of anti-NMDAR encephalitis in pediatric patients with behavioral disorders and abnormal movements.