Diagnostic pathway and management of first seizures in infants with Sturge-Weber syndrome.

AIM: Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment. METHOD: A single-centre case series of 49 infants explored early SWS care. Ninety-two per cent of children developed seizures aged 0 to 3 years; 55% of cases were before diagnostic magnetic resonance imaging (MRI) or tertiary referral. Delay in SWS diagnosis affected 31% of infants because of a lack of gadolinium enhancement for initial MRI. First seizures were frequently prolonged, with phenytoin administration necessary in 46%. Presymptomatic antiseizure medication prophylaxis (n = 8/49) decreased seizure burden. No patients on antiseizure medication prophylaxis suffered status epilepticus for longer than 30 minutes, and half of them (n = 4) had not developed seizures at last follow-up (aged 2-10 years). RESULTS: A parental survey enabled further service evaluation. Eighty-three per cent of parents considered local clinicians' understanding of SWS inadequate: 61% felt insufficiently informed about SWS and 81% received no epilepsy education before seizures. INTERPRETATION: To overcome the identified shortfalls, guidelines towards improving and standardizing SWS management are proposed.

Diagnostic algorithm for children presenting with epilepsia partialis continua.

OBJECTIVE: To characterize a cohort of children with epilepsia partialis continua (EPC) and develop a diagnostic algorithm incorporating key differential diagnoses. METHODS: Children presenting with EPC to a tertiary pediatric neurology center between 2002 and 2019 were characterized. RESULTS: Fifty-four children fulfilled EPC criteria. Median age at onset was 7 years (range 0.6-15), with median follow-up of 4.3 years (range 0.2-16). The diagnosis was Rasmussen encephalitis (RE) in 30 of 54 (56%), a mitochondrial disorder in 12 of 54 (22.2%), and magnetic resonance imaging (MRI) lesion-positive focal epilepsy in 6 of 54 (11.1%). No diagnosis was made in 5 of 54 (9%). Children with mitochondrial disorders developed EPC earlier; each additional year at presentation reduced the odds of a mitochondrial diagnosis by 26% (P = .02). Preceding developmental concerns (odds ratio [OR] 22, P < .001), no seizures prior to EPC (OR 22, P < .001), bilateral slowing on electroencephalogram (EEG) (OR 26, P < .001), and increased cerebrospinal fluid (CSF) protein level (OR 16) predicted a mitochondrial disorder. Asymmetry or hemiatrophy was evident on MRI at presentation with EPC in 18 of 30 (60%) children with RE, and in the remainder at a median of 6 months (range 3-15) after EPC onset. The first diagnostic test is brain MRI. Hemiatrophy may permit a diagnosis of RE with unilateral clinical and EEG findings. For children in whom a diagnosis of RE cannot be made on first scan but the clinical and radiological presentation resembles RE, repeat imaging every 6 months is recommended to detect progressive unicortical hemiatrophy, and brain biopsy should be considered. Evidence of intrathecal inflammation (oligoclonal bands and raised neopterin) can be supportive. In children with bihemispheric EPC, rapid polymerase gamma testing is recommended and if negative, sequencing mtDNA and whole-exome sequencing on blood-derived DNA should be performed. SIGNIFICANCE: Children presenting with EPC due to a mitochondrial disorder show clinical features distinguishing them from RE and structural epilepsies. A diagnostic algorithm for children with EPC will allow targeted investigation and timely diagnosis.

Autism spectrum disorder, social communication difficulties, and developmental comorbidities in Sturge-Weber syndrome.

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by the combination of a facial naevus flammeus and pial angioma, often associated with learning difficulties and/or epilepsy. Here, we report on the neuropsychological characteristics of a cohort of 92 children with SWS seen at a national referral center between 2002 and 2015. Almost a quarter (24%) had a diagnosis of autism spectrum disorder (ASD), with 45% overall having evidence of social communication difficulties (SCD). Autism spectrum disorder was more commonly seen in those individuals with bilateral angioma (p = 0.021). Significant behavioral difficulties were reported in 50% while 26% had difficulties with sleep. Difficulties with social communication, behavior, and sleep were closely associated with one another. They were not, however, significantly associated with markers of epilepsy severity and were noted to occur even in children without epilepsy. The prevalence of ASD/SCD, sleep difficulties, and behavioral disorders seen in SWS is high and reflects the complex needs of this group.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable.

Symptoms of anxiety and depression in school-aged children with active epilepsy: A population-based study.

METHODS: Children (5-15 years) with active epilepsy were screened using the parent-report (n=69) and self-report (n=48) versions of the Spence Children's Anxiety Scale (SCAS) and the self-report version of the Children's Depression Inventory (CDI) (n=48) in a population-based sample. RESULTS: A total of 32.2% of children (self-report) and 15.2% of children (parent-report) scored ≥1 SD above the mean on the SCAS total score. The subscales where most difficulty were reported on parent-report were Physical Injury and Separation Anxiety. There was less variation on self-report. On the CDI, 20.9% of young people scored ≥1 SD above the mean. Children reported significantly more symptoms of anxiety on the SCAS total score and three of the subscales (p<.05). There was a significant effect on the SCAS total score of respondents by seizure type interaction, suggesting higher scores on SCAS for children with generalized seizures on self- but not parent-report. Higher CDI scores were significantly associated with generalized seizures (p>.05). SUMMARY: Symptoms of anxiety were more common based on self-report compared with parent-report. Children with generalized seizures reported more symptoms of depression and anxiety.

Features of autism spectrum disorder (ASD) in childhood epilepsy: a population-based study.

In a defined geographical area in the south of the UK, 115 children with active epilepsy (i.e., children who had seizures in the last year and/or children who were taking antiepileptic drugs (AEDs)) were identified via a computerized database and liaison with local pediatricians. Eighty-five (74%) of the children (5-15years of age) underwent a comprehensive psychological assessment. Twenty-one percent of the children met the DSM-IV-TR criteria for ASD, and 61% of those with ASD had another DSM-IV-TR behavioral or motor disorder. The Autism Spectrum Screening Questionnaire (ASSQ) was completed by parents (n=69) and by teachers (n=67) of children with an IQ>34. Only 9% of children on parent ratings and 15% of children on teacher ratings had no features of ASD. Parents reported significantly (p<.05) more features of ASD on the ASSQ compared with teachers. Factors significantly associated with responses on the ASSQ included respondent (parents reported more features), school placement (more features in specialized settings), and respondent by school placement interaction. Effective screening for ASD in children with epilepsy will need a consideration of the impact of informant and school placement on ratings. In conclusion, features of ASD were common in children with epilepsy regardless of cognitive ability. The ASSQ was a useful screening instrument in this population, and combining parent and teacher forms was optimal in terms of screening properties.

Features of developmental coordination disorder in active childhood epilepsy: a population-based study.

AIMS: To provide data on parent-reported features of developmental coordination disorder (DCD) and describe neurobehavioural comorbidity in children with epilepsy and DCD. METHOD: Eighty-five (74% of those eligible) children (44 males, 41 females; age range 5-15y) with active childhood epilepsy (an epileptic seizure in the last year and/or currently taking antiepileptic drugs) in a population-based cohort underwent comprehensive multidisciplinary assessment. The DCD Questionnaire (DCD-Q) was completed by parents (n=69) of children with an IQ>34, of whom 56 did not have cerebral palsy (CP), and were considered for a diagnosis of DCD. RESULTS: Of those considered for a DCD diagnosis, 16 (29%) met DSM-IV-TR criteria whereas 34 (61%) scored in the at-risk range on the DCD-Q. The sensitivity of the DCD-Q was 100% (95% CI 76-100) and specificity was 55% (95% CI 39-70). Significant predictors of higher scores on the DCD-Q included the presence of autism spectrum disorder, CP, and early seizure onset. Increasing age and IQ were independently associated with higher DCD-Q scores. Intellectual disability, attention-deficit-hyperactivity disorder, academic underachievement, and specific memory problems were the most common neurobehavioural difficulties in those with both DCD and epilepsy. INTERPRETATION: Parent-reported symptoms of DCD are very common in childhood epilepsy. The DCD-Q has good sensitivity but lower specificity in this population.

Academic achievement in school-aged children with active epilepsy: a population-based study.

OBJECTIVE: To provide population-based data on the performance of school-aged children with epilepsy on measures of academic achievement and factors associated with this performance after controlling for IQ. METHODS: Eighty-five (74%) of 115 children with "active" epilepsy (experienced a seizure in the past year and/or on antiepileptic drugs [AEDs]) underwent psychological assessment including measures of IQ, aspects of working memory and processing speed. Sixty-five of the 85 were able to complete subtests on the Wide Range Achievement Test-Fourth Edition (WRAT-4). Paired sample t-tests were conducted to compare subtest scores. Factors associated with academic performance after controlling for IQ were examined using linear regression. RESULTS: Seventy-two percent of the children, who could complete subtests on the WRAT-4, displayed "low achievement" (1 standard deviation [SD] below test mean) and 42% displayed "underachievement" (1 SD below assessed IQ) on at least one of the four WRAT-4 subtests. The mean scores on the Math Computation subtest and Sentence Comprehension subtest were significantly lower than scores on the Word Reading (p < 0.05) and Spelling (p < 0.001) subtests. Younger age at seizure onset was associated (p < 0.05) with decreased scores on three of the four WRAT-4 subtests after controlling for IQ. Difficulties with auditory working memory were associated with difficulties on reading comprehension (p < 0.05), and parent-reported difficulties with school attendance were associated with decreased scores on the Spelling and Word Reading subtests after controlling for IQ (p < 0.05). SIGNIFICANCE: Difficulties with academic achievement are common in school-aged children with "active" epilepsy. Much of the difficulties can be attributed to lowered global cognition. However, specific cognitive deficits, younger onset of first seizure, and school attendance difficulties may contribute to difficulties independent of global cognition. There is a need to screen all children with "active" epilepsy for difficulties in school achievement, to identify contributory factors and to identify efficacious interventions for ameliorating such difficulties.

GNAQ/GNA11 Mosaicism Is Associated with Abnormal Serum Calcium Indices and Microvascular Neurocalcification.

Mosaic mutations in genes GNAQ or GNA11 lead to a spectrum of diseases including Sturge-Weber syndrome and phakomatosis pigmentovascularis with dermal melanocytosis. The pathognomonic finding of localized "tramlining" on plain skull radiography, representing medium-sized neurovascular calcification and associated with postnatal neurological deterioration, led us to study calcium metabolism in a cohort of 42 children. In this study, we find that 74% of patients had at least one abnormal measurement of calcium metabolism, the commonest being moderately low serum ionized calcium (41%) or high parathyroid hormone (17%). Lower levels of ionized calcium even within the normal range were significantly associated with seizures, and with specific antiepileptics despite normal vitamin D levels. Successive measurements documented substantial intrapersonal fluctuation in indices over time, and DEXA scans were normal in patients with hypocalcemia. Neurohistology from epilepsy surgery in five patients revealed not only intravascular, but perivascular and intraparenchymal mineral deposition and intraparenchymal microvascular disease in addition to previously reported findings. Neuroradiology review clearly demonstrated progressive calcium deposition in individuals over time. These findings and those of the adjoining paper suggest that calcium deposition in the brain of patients with GNAQ/GNA11 mosaicism may not be a nonspecific sign of damage as was previously thought, but may instead reflect the central postnatal pathological process in this disease spectrum.

Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: evidence of clinical benefit.

PURPOSE: To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. METHODS: This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. KEY FINDINGS: Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6­18 years). With use of a combination of a behavioral management program and MPH 0.3­1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69­0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. SIGNIFICANCE: Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed.

North Thames multi-centre service evaluation: Ethical considerations during COVID-19.

Objectives: During the COVID-19 pandemic, healthcare resources including staff were diverted from paediatric services to support COVID-positive adult patients. Hospital visiting restrictions and reductions in face-to-face paediatric care were also enforced. We investigated the impact of service changes during the first wave of the pandemic on children and young people (CYP), to inform recommendations for maintaining their care during future pandemics. Design: A multi-centre service evaluation was performed through a survey of consultant paediatricians working within the North Thames Paediatric Network, a group of paediatric services in London. We investigated six areas: redeployment, visiting restrictions, patient safety, vulnerable children, virtual care and ethical issues. Results: Survey responses were received from 47 paediatricians across six National Health Service Trusts. Children's right to health was largely believed to be compromised by the prioritisation of adults during the pandemic (81%; n = 33). Sub-optimal paediatric care due to redeployment (61%; n = 28) and the impact of visiting restrictions on CYP's mental health (79%; n = 37) were reported. Decreased hospital attendances of CYP were associated with parental fear of COVID-19 infection-risks (96%; n = 45) and government 'stay at home' advice (89%; n = 42). Reductions in face-to-face care were noted to have disadvantaged those with complex needs, disabilities and safeguarding concerns. Conclusion: Consultant paediatricians perceived that paediatric care was compromised during the first wave of the pandemic, resulting in harm to children. This harm must be minimised in subsequent pandemics. Recommendations for future practice which were developed from our findings are provided, including maintaining face-to-face care for vulnerable children.

The prevalence and profile of autism in Sturge-Weber syndrome.

A systematic retrospective case note review was undertaken to investigate autism diagnostic factors in 124 individuals with Sturge-Weber syndrome (SWS). Social Responsiveness Scale questionnaires were then analysed to explore the severity and profile of autism characteristics in 70 participants. Thirty-two to forty percent of participants had a clinical diagnosis of autism and half of those without a diagnosis showed significant social communication difficulties. Children had a relative strength in social awareness and social motivation, which are typically much reduced in people with autism. This finding may explain why, to date, the diagnosis has often been overlooked in this population. The research therefore suggests that children with Sturge-Weber should be screened to identify social communications difficulties and provided with timely support.

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency).

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-alpha-aminoadipic semialdehyde/L-Delta1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-alpha-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-alpha-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios.

Work of a paediatric bioethics centre during the COVID-19 pandemic first phase.

OBJECTIVES: Decisions with an ethical component have been controversial during the COVID-19 pandemic, whether leaked intensive care unit (ICU)-rationing documents, transfer of people to care-homes to 'protect the National Health Service' or the duty to treat patients despite inadequate personal protective equipment. To counter criticism of ethics per se, and to help those planning ethics support we describe the practical work of a children's hospital bioethics team in supporting children, families and clinicians during this unprecedented period. DESIGN/SETTING: Three phases of activity: (i) preparation: we composed several documents to support/guide hospital teams and, together with colleagues, provided them to regional inpatient, community and hospice settings. We adapted existing mechanisms to combat workforce moral injury; (ii) activity (March-June 2020): was highest in our rapid response service where children/families consider difficult treatment decisions with medical teams. Education provided 'pandemic webcasts' on decision-making and broader child-health concerns. Staff support was essential, especially for those deployed to overwhelmed local adult ICUs. Research ascertained young people's views on the pandemic; (iii) reflection: focussed on (a) research about future re-deployment to adult services and minimisation of moral distress/injury, (b) remote video-conferencing-parents'/participants' experience/ability to consider complex ethical issues and (c) role of faith/non-faith in society's recovery and children's views. MAIN OUTCOME/CONCLUSIONS: Our bioethics team's role during the pandemic included: case reviews via video-conferencing, many involving innovative therapy for severely unwell children with COVID-19/Paediatric-Inflammatory-Multisystem Syndrome-Temporally associated with SARS-CoV-2 together with their parents; processes to protect healthcare staff from moral harm and research/educational activity focused on paediatric-specific ethical arising during the pandemic.

Neurological presentations and cognitive outcome in Sturge-Weber syndrome.

INTRODUCTION: This study of children with Sturge-Weber syndrome (SWS) profiled neurological presentations; compared patients with (+) and without (-) port-wine stain (PWS); and determined risk factors for intellectual and language impairments. METHODS: A retrospective case note review was conducted at a national centre. RESULTS: This cohort (n = 140, male 72, median follow up 114 months) showed sex parity. Intellectual disability ("ID": IQ ≤ 70) affected half (66), being severe (IQ ≤ 40) in two-fifths (27) with ID. Language disorder (core score≤70) affected half (57). Neurological presentations were: status epilepticus 57% (80), hemiplegia 58% (81), headaches 36% (50) and acutely acquired neurological deficits lasting over 24 h 40% (56). One-seventh (20) were PWS(-). This group had: fewer lobes with angioma (p < 0.0001); and less frequent ID (p = 0.002) or language disorder (p = 0.013). Seizure frequency and status epilepticus prevalence did not differ from PWS(+). ID and language disorder were associated with: more lobes with angioma; earlier seizure onset; more frequent status epilepticus and seizure clusters. On multivariable analysis recurrent status epilepticus (p = 0.037) and multi-lobe involvement (p = 0.002) increased the risk of severe intellectual disability. Active epilepsy was associated with language disorder (p = 0.030). CONCLUSIONS: This is the largest reported series documenting detailed developmental profiles of children with SWS, including ID and ASD. PWS(+) shows high rates of ID and language disorder. PWS(-) SWS has a more favourable outcome. Cognitive outcome is contingent on number of affected lobes and bilateral involvement. Epilepsy exerts an additional deleterious effect on language and cognition. A high percentage of children have a history of status epilepticus, with evidence that this impacts language and cognitive outcomes. Acutely acquired neurological deficits did not penalise either. Regular structured clinical and developmental assessment permit greater identification of neurological and neurodevelopmental impairments in SWS, and appropriate support.

Transient episodes of hemiparesis in Sturge Weber Syndrome - Causes, incidence and recovery.

INTRODUCTION: Sturge Weber Syndrome (SWS) arises from a sporadic condition secondary to a post zygotic mutation in the GNAQ gene, manifested in the majority of cases by capillary malformation of the skin. Children present with seizures, acquired hemiparesis, transient hemiparesis and intellectual disabilities. This project aimed to establish incidence of transient episodes, their recovery time if full recovery was achieved, and events associated with the transient episode. METHODS: This was a retrospective cohort study, approved for clinical audit (Institution number 2182). Children with a diagnosis of SWS seen in a tertiary multidisciplinary clinic from September 2013 to September 2016 were included in the analysis. Data was collated from clinical notes. SPSS 21 was used for analysis. RESULTS: A total of 102 patients had a diagnosed of SWS, the mean age was 10.86 years (range 2-22years). 47/102 participants with SWS had permanent hemiparesis. 32/102 presented with transient episodes. All children with transient hemiparesis had epilepsy. Median recovery time to previous function, following a transient episode was 24 h (range 1 minute-4392 h). All participants fully recovered from the transient episode within a 6 months' time frame. The factors associated with transient episodes were seizures, or a blow to the head. CONCLUSIONS: To our knowledge this is the largest cohort of children with SWS analysed to describe occurrence, association and recovery time of transient hemiparesis. The findings informed service development including change in method to record details of transient episodes. Further information provided to other health professionals will be reviewed.

Flunarizine for Headache Prophylaxis in Children With Sturge-Weber Syndrome.

BACKGROUND: Children with Sturge-Weber syndrome can experience severe headache with or without transient hemiparesis. Flunarizine, a calcium antagonist, has been used for migraine. The experience with flunarizine for headache in a cohort of children at a national center for Sturge-Weber syndrome is reviewed, reporting its efficacy and adverse effect in this population. METHODS: We collected data from health care professionals' documentation on headache (severity, frequency, duration) before and on flunarizine in 20 children with Sturge-Weber syndrome. Adverse effects reported during flunarizine treatment were collated. The Wilcoxon signed rank test was used to determine the significance of pre- versus post-treatment effect. RESULTS: Flunarizine was used for headache alone (13) or mixed migrainous episodes and vascular events (7). The median duration of treatment was 145 days (range 43 to 1864 days). Flunarizine reduced headache severity (z = -3.354, P = 0.001), monthly frequency (z = -2.585, P = 0.01), and duration (z = -2.549, P = 0.01). Flunarizine was discontinued owing to intolerable adverse effects in a minority (2). Sedation and weight gain were the most common side effects. There were no reports of behavior change or extrapyramidal features. CONCLUSIONS: The most effective management for headaches in patients with Sturge-Weber syndrome has not been established. This retrospective observational study found benefit of flunarizine prophylaxis on headache severity, frequency, and duration in children with Sturge-Weber syndrome without severe side effects. Flunarizine is not licensed for use in the United Kingdom, but these data support its off-license specialist use for headache prophylaxis in Sturge-Weber syndrome.

Parent- and Teacher-Reported Symptoms of ADHD in School-Aged Children With Active Epilepsy: A Population-Based Study.

OBJECTIVE: Provide data on the distribution of parent- and teacher-reported symptoms of ADHD in childhood epilepsy and describe coexisting cognitive and behavioral disorders in children with both epilepsy and ADHD. METHOD: Eighty-five (74% of those eligible) children (5-15 years) in a population-based sample with active epilepsy underwent psychological assessment. The ADHD Rating Scale-IV (ADHD-RS-IV) scale was completed by parents ( n = 69) and teachers ( n = 67) of participating children with an IQ > 34. ADHD was diagnosed with respect to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). RESULTS: Parents reported significantly more symptoms of ADHD than teachers ( p < .001). Symptoms of inattention were more commonly reported than symptoms of hyperactivity-impulsivity ( p < .001). Neurobehavioral comorbidity was similar in those with ADHD and non-ADHD with the exception of oppositional defiant disorder (ODD) and developmental coordination disorder (DCD), which were more common in those with both epilepsy and ADHD. CONCLUSION: Symptoms of ADHD are very common in childhood epilepsy but prevalence is influenced by informant.