Tove Hallböök

Increased childhood incidence of narcolepsy in western Sweden after H1N1 influenza vaccination

Objectives: To assess the incidence of narcolepsy between January 2000 and December 2010 in children in western Sweden and its relationship to the Pandemrix vaccination, and to compare the clinical and laboratory features of these children. Methods: The children were identified from all local and regional pediatric hospitals, child rehabilitation centers, outpatient pediatric clinics, and regional departments of neurophysiology. Data collection was performed with the aid of a standardized data collection form, from medical records and telephone interviews with patients and parents. The laboratory and investigational data were carefully scrutinized. Results: We identified 37 children with narcolepsy. Nine of them had onset of symptoms before the H1N1 vaccination and 28 had onset of symptoms in relationship to the vaccination. The median age at onset was 10 years. All patients in the postvaccination group were positive for human leukocyte antigen (HLA)–DQB1*0602. Nineteen patients in the postvaccination group, compared with one in the prevaccination group, had a clinical onset that could be dated within 12 weeks. Conclusion: Pandemrix vaccination is a precipitating factor for narcolepsy, especially in combination with HLA-DQB1*0602. The incidence of narcolepsy was 25 times higher after the vaccination compared with the time period before. The children in the postvaccination group had a lower age at onset and a more sudden onset than that generally seen.

Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood

PURPOSE Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with refractory epilepsy. There is growing evidence of additional quality of life (QOL) benefits of VNS. We report the effects of VNS on seizure frequency and severity and how these changes are related to cognitive abilities, QOL, behaviour and mood in 15 children with medically refractory and for surgery not eligible epilepsy. METHODS Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with Bayley Scales of Infant Development (BSID), Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R), Wechlser Intelligence Scales for Children (WISC-III) depending on the childs level of functioning, a Visual Analogue Scale for validating QOL, Child Behaviour Checklist (CBCL) for quantifying behaviour problems, Dodrill Mood Analogue Scale and Birleson Depression Self-Rating Scale, and the National Hospital Seizure Severity Scale (NHS3). A diary of seizure frequency was collected. RESULTS Six of 15 children showed a 50% or more reduction in seizure frequency; one of these became seizure-free. Two children had a 25-50% seizure reduction. Two children showed increased seizure frequency. In 13 of 15 children there was an improvement in NHS3. The parents reported shorter duration of seizure and recovery phase. There were no changes in cognitive functioning. Twelve children showed an improvement in QOL. Eleven of these also improved in seizure severity and mood and five also in depressive parameters. CONCLUSION This study has shown a good anti-seizure effect of VNS, an improvement in seizure severity and in QOL and a tendency to improvement over time regarding behaviour, mood and depressive parameters. The improvement in seizure severity, QOL, behaviour, mood and depressive parameters was not related to the anti-seizure effect.

Ketogenic Diet Improves Sleep Quality in Children with Therapy-resistant Epilepsy.

Summary:  Purpose: The study purpose was to evaluate sleep structure during ketogenic diet (KD) treatment in children with therapy‐resistant epilepsy and to correlate possible alterations with changes in clinical effects on seizure reduction, seizure severity, quality of life (QOL), and behavior.

Effects of ketogenic diet on epileptiform activity in children with therapy resistant epilepsy

PURPOSE The purpose was to quantify changes of epileptiform activity during ketogenic diet (KD) treatment in children with therapy resistant epilepsy, and evaluate how these changes are related to activity stage and to clinical effects on seizure frequency, seizure severity, attentional behaviour, quality of life (QOL), and beta-hydroxybutyrate (betaOHb). METHODS Eighteen children were investigated with 24h ambulatory EEG monitoring 1 week prior to KD initiation and, after 3 months of KD treatment. Epileptiform activity was evaluated by automated spike detection. This data was compared with data presented in a previous study published in Epilepsia 2006, on sleep structure and different activity stages, clinical data on seizure frequency, seizure severity, QOL and attentional behaviour on the same children [Hallbook, T., Lundgren, J., Rosén, I., 2007. Ketogenic diet improves sleep quality in children with therapy resistant epilepsy. Epilepsia 48, 59-65]. RESULTS After 3 months of KD treatment the number of interictal epileptiform discharges (IEDs) was significantly reduced (p<0.001). When considering the four activity stages separately, the reduction was significant during non-rapid eye movement sleep stage 2, slow wave sleep (SWS) and rapid eye movement (REM) sleep (p=0.001, 0.001, 0.002), and not significantly so during awake (p=0.07). Beta-hydroxybutyrate was significantly increased (p<0.001). There was a significant correlation between the reduction in IEDs and clinical seizures (Spearman r=0.6, p=0.005) and between improvement in attentional behaviour and the increase in betaOHb (Spearman r=0.5, p=0.03). There was no significant correlation between changes in attentional behaviour and IEDs or clinical seizures. CONCLUSION This study shows that KD reduces the number of IEDs, especially during sleep. It shows a correlation between reduction in epileptiform activity and clinical seizures. There were no correlations between reduction in epileptiform activity and clinical seizures and improvement in QOL or attention. The increase in betaOHb correlated with improvement in attention.

Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy

Purpose:  To assess the impact of contralateral magnetic resonance imaging (MRI) findings on seizure outcome after hemispherectomy for refractory epilepsy.

Effects of ketogenic diet on vascular function.

BACKGROUND Ketogenic diet is a well-established treatment in children with difficult to treat epilepsy. Very little is known about the long-term effects on vascular atherogenic and biochemical processes of this high-fat and low carbohydrate and protein diet. METHODS We evaluated 26 children after one year and 13 children after two years of ketogenic diet. High resolution ultrasound-based assessment was used for carotid artery intima-media thickness (cIMT), carotid artery distensibility and carotid artery compliance. Blood lipids including high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, (LDL-C), total cholesterol (TC), apolipoprotein A (apoA), apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hsCRP) were analysed. RESULTS A gradual decrease in carotid distensibility and an increase in LDL-C, apoB and the TC:LDL-C and LDL-C:HDL-C ratios were seen at three and 12 months of KD-treatment. These differences were not significant at 24 months. cIMT, BMI and hsCRP did not show any significant changes. CONCLUSIONS The initial alterations in lipids, apoB and arterial function observed within the first year of KD-treatment appear to be reversible and not significant after 24 months of treatment.

Long term effects on epileptiform activity with vagus nerve stimulation in children.

PURPOSE We report long-term effects of vagus nerve stimulation (VNS) on epileptiform activity in 15 children, and how these changes are related to activity stage and to clinical effects on seizure reduction, seizure severity (NHS3) and quality of life (QOL). METHODS Initially, and after 3 and 9 months of VNS-treatment, 15 children were investigated with 24 h ambulatory EEG monitoring for spike detection. The number of interictal epileptiform discharges (IEDs) and the inter spike intervals (ISIs) were analysed during 2 h in the awake state, and 1h of rapid eye movement (REM)-, spindle- and delta-sleep, respectively. Total number and duration of electrographic seizure episodes were also analysed. RESULTS At 9 months the total number of IEDs was significantly reduced (p=0.04). There was a tendency of reduction in all activity stages, and significantly so in delta-sleep (p=0.008). Total electrographic seizure number was significantly reduced in the 24 h EEG at 3 and 9 months (p=0.03, 0.05). There was a significant concordance in direction of changes in epileptiform activity and electrographic seizures at 9 months (p=0.04). Concordance in direction of changes was seen in 9 of 15 children between clinical seizures and IED (p>0.3), in 10 of 15 children between QOL and IED (p=0.3) and in 8 of 15 children between NHS3 and IED (p>0.3). There was no direct correlation between the extent of improvement in these clinical data and the degree of spike reduction. CONCLUSION This study shows that VNS reduces IEDs especially in REM and delta sleep, as well as the number of electrographic seizures. It also shows a concordance between reduction in IEDs and electrographic seizures.

Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia

BACKGROUND This Scandinavian collaborative retrospective study of children treated with ketogenic diet (KD) highlights indications and effectiveness over two years follow-up. METHODS Five centres specialised in KD collected data retrospectively on 315 patients started on KD from 1999 to 2009. Twenty-five patients who stopped the diet within four weeks because of compliance-problems and minor side-effects were excluded. Seizure-type(s), seizure-frequency, anti-epileptic drugs and other treatments, mental retardation, autism-spectrum disorder and motor-dysfunction were identified and treatment-response was evaluated. RESULTS An intention-to-treat analysis was used. Responders (>50% seizure-frequency reduction) at 6, 12 and 24 months were 50%, 46% and 28% respectively, seizure-free were 16%, 13% and 10%. Still on the diet were 80%, 64% and 41% after 6, 12 and 24 months. No child had an increased seizure-frequency. The best seizure outcome was seen in the group with not-daily seizures at baseline (n = 22), where 45%, 41% and 32% became seizure-free at 6, 12 and 24 months A significant improvement in seizure-frequency was seen in atonic seizures at three months and secondary generalised seizures at three and six months. Side-effects were noted in 29 subjects; most could be treated and only two stopped due to hyperlipidaemia and two due to kidney-stones. In 167 patients treated with potassium-citrate, one developed kidney-stones, compared with six of 123 without potassium-citrate treatment (relative risk = 8.1). CONCLUSIONS As the first study of implementing KD in children in the Scandinavian countries, our survey of 290 children showed that KD is effective and well tolerated, even in such severe patients with therapy-resistant epilepsy, more than daily seizures and intellectual disability in the majority of patients. Long-term efficacy of KD was comparable or even better than reported in newer AEDs. Addition of potassium citrate reduced risk of kidney-stones. Our data indicate that the response might be predicted by seizure-frequency before initiation of the diet but not by age, seizure-type or aetiology.

Psychiatric comorbidity and cognitive profile in children with narcolepsy with or without association to the H1N1 influenza vaccination.

OBJECTIVES To evaluate psychiatric comorbidity and the cognitive profile in children and adolescents with narcolepsy in western Sweden and the relationship of these problems to H1N1 vaccination. PATIENTS Thirty-eight patients were included in the study. DESIGN We performed a population-based, cross-sectional study to investigate psychiatric comorbidity using a test battery of semistructured interviews generating Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnoses, including the Development and Well-Being Assessment and the attention deficit hyperactivity disorder rating scale. The Autism Spectrum Screening Questionnaire and the Positive and Negative Syndrome Scale were used to screen for autistic traits and psychotic symptoms, respectively. The cognitive assessments were made by a clinical psychologist using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, the Wechsler Intelligence Scale for Children, Fourth Edition, or the Wechsler Adult Intelligence Scale, Fourth Edition. MEASUREMENTS AND RESULTS In the post-H1N1 vaccination (PHV) narcolepsy group (n = 31), 43% of patients had psychiatric comorbidity, 29% had attention deficit hyperactivity disorder (ADHD) inattentive type, 20% had major depression, 10% had general anxiety disorder, 7% had oppositional defiant disorder (ODD), 3% had pervasive developmental disorder not otherwise specified (i.e., atypical autism), and 3% had eating disorder not otherwise specified (anorectic type). In the non-post-H1N1 vaccination (nPHV) narcolepsy group, one of seven patients had ADHD, inattentive type and ODD. The most frequent psychiatric symptom was temper tantrums, which occurred in 94% of the patients in the PHV group and 71% of the patients in the nPHV narcolepsy group. The cognitive assessment profile was similar in both groups and showed normal results for mean full-scale IQ and perceptual speed but decreased verbal comprehension and working memory. Patients with psychiatric comorbidity had a significantly lower full-scale IQ compared to those without. CONCLUSION Our study indicates increased psychiatric comorbidity in children and adolescents with narcolepsy. The identified cognitive profile with significantly lower verbal comprehension and working memory compared with the normal mean index could have important implications for social relations and schooling. The small numbers of patients with nPHV narcolepsy make it difficult to draw firm conclusions about the possible differences between the two groups of patients.

Dravet syndrome in Sweden: a population-based study

To assess the prevalence and incidence of Dravet syndrome in children diagnosed in Sweden between 2007 and 2011, and to describe neurological comorbidity, disease course, phenotypes, and treatment effects.