Outcome at age 7 of epilepsy presenting in the first 2 years of life. A population-based study.

OBJECTIVE: Existing data suggest that epilepsy presenting in the first few years of life carries a worse prognosis than later onset. However, studies are few and methods differ, making interpretations of data uncertain. This study analyzes outcome at age 7 and potential prognostic factors in a well-characterized population-based cohort with epilepsy onset during the first 2 years of life. METHODS: An incidence cohort of 116 prospectively identified cases of epilepsy with seizure onset before age 2 years was described in Stödberg et al. (2020). Cases were originally retrieved from the Stockholm Incidence Registry of Epilepsy (SIRE), which registered all cases with a first unprovoked epileptic seizure from September 1, 2001, in Northern Stockholm. Data on treatment and outcome at age 7 years were collected from electronic medical records and through interviews with parents. Outcome and potential prognostic factors were analyzed with descriptive statistics and multivariable log binomial regression analysis. RESULTS: Eleven children (9.5%) died before age 7. Polytherapy was common. Epilepsy surgery was performed in two children. At age 7 years, 61 of 116 children (53%) had been seizure-free for the last 2 years or longer. Intellectual disability was diagnosed in 57 of 116 children (49%), autism spectrum disorder in 13 (11%), and cerebral palsy in 28 (24%). West syndrome had a similar seizure remission rate but a worse cognitive outcome. There was no difference in outcome between first and second year onset. Six predictors, including etiology, remained associated with two or more outcome variables after regression analysis. SIGNIFICANCE: About half of children with infantile-onset epilepsy will become seizure-free and half of them will have intellectual disability. Etiology was confirmed as a major independent predictor of outcome. Our study contributes to a more firm knowledge base when counseling parents of infants diagnosed with epilepsy.

Childhood-onset seizures: A long-term cohort study of use of antiepileptic drugs, and drugs for neuropsychiatric conditions.

OBJECTIVE: We conducted a long-term follow-up of a cohort of children with newly diagnosed unprovoked seizures to assess treatment with antiepileptic drugs (AEDs), neuroleptics, antidepressants and medication for attention deficit hyperactivity disorder (ADHD) with special attention to the impact of comorbidities on the use of such medication. METHODS: Our study cohort comprised 769 children (28 days-18 years), living in Stockholm Sweden, with a first unprovoked seizure identified between 2001 and 2006. Information on neurodevelopmental comorbidities and Cerebral Palsy (CP) at seizure onset was collected from medical records. Information on treatment with AEDs, neuroleptics, antidepressants and ADHD medication was retrieved by linkage to the Swedish National Prescription Registry between 2005 and 2014. The association between comorbidities and drug treatments was assessed by odds ratios (OR) with 95 % confidence intervals (CI), adjusted for age and sex. RESULTS: Eight years after the index seizure, 31 % of the children were on AEDs, and this was more common among children with any of the comorbidities studied (OR; 4.0 95 % CI 2.9-5.6) compared to those without such comorbidities, and within this group of comorbidities particularly for those with CP (OR; 5.2 95 % CI: 2.9-9.3). Children with neurodevelopmental comorbidity or CP at baseline were more likely to receive neuroleptics (ORs 8 years after the index seizure; 6.9, 95 % CI: 2.4-19.8), antidepressants (OR; 2.3, 95 % CI: 1.0-5.5) and ADHD medication (OR; 3.6, 95 % CI: 1.8-7.2) than children without the studied comorbidities. CONCLUSION: Children with seizures in combination with neurodevelopmental comorbidities or CP, especially CP, have a more frequent use of AEDs, neuroleptics, antidepressants, and ADHD medication up to 13 years following the initial seizure than children without comorbidity. Our data highlight the treatment burden in children with epilepsy and comorbidities.

Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study.

OBJECTIVE: Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis. METHODS: Children presenting with a first unprovoked epileptic seizure before age 2 years and registered in the Stockholm Incidence Registry of Epilepsy (SIRE) between September 1, 2001 and December 31, 2006, were retrieved and their medical records up to age 7 years reviewed. Children who met the epilepsy criteria were included in the study cohort. WES/WGS was offered in cases of suspected genetic etiology regardless of whether a structural or metabolic diagnosis had been established. RESULTS: One hundred sixteen children were included, of which 88 had seizure onset during the first year of life and 28 during the second, corresponding to incidences of 139 and 42/100 000 person-years, respectively. An epilepsy syndrome could be diagnosed in 54% of cases, corresponding to a birth prevalence of 1/1100. Structural etiology was revealed in 34% of cases, a genetic cause in 20%, and altogether etiology was known in 65% of children. The highest diagnostic yield was seen in magnetic resonance imaging (MRI) with 65% revealing an etiology. WES/WGS was performed in 26/116 cases (22%), with a diagnostic yield of 58%. SIGNIFICANCE: Epilepsy syndromes can be diagnosed and etiologies revealed in a majority of early onset cases. NGS can identify a molecular diagnosis in a substantial number of children, and should be included in the work-up, especially in cases of epileptic encephalopathy, cerebral malformation, or metabolic disease without molecular diagnosis. A genetic diagnosis is essential to genetic counselling, prenatal diagnostics, and precision therapy.

Neurodevelopmental comorbidities and seizure control 24 months after a first unprovoked seizure in children.

PURPOSE: To follow children with newly diagnosed unprovoked seizures to determine (1) whether the prevalence of neurodevelopmental comorbidities and cerebral palsy (CP) changed after the initial seizure, and (2) the association between studied comorbidities and seizures 13-24 months after seizure onset or initiation of treatment. METHODS: Analyses were based on 750 children (28 days-18 years) with a first unprovoked seizure (index) included in a population-based Incidence Registry in Stockholm between 2001 and 2006. The children were followed for two years and their medical records were examined for a priori defined neurodevelopmental/psychiatric comorbidities and CP and seizure frequency. Baseline information was collected from medical records from before, and up to six months after, the index seizure. Odds ratios (OR) of repeated seizures 13-24 months after the first seizure or after initiation of anti-epileptic drug treatment was calculated by logistic regression and adjusted for age and sex. RESULTS: At baseline, 32% of the children had neurodevelopmental/psychiatric comorbidities or CP compared to 35%, 24 months later. Children with such comorbidities more often experienced seizures 13-24 months after the index seizure (OR 2.87, CI 2.07-3.99) with the highest OR in those with CP or attention deficit hyperactivity disorder (ADHD). Children diagnosed at age <1 year exhibited the highest prevalence of comorbidities as well as OR for repeated seizures. A combination of young age and comorbidity was associated with an OR for repeated seizures of 5.12 (CI 3.03-8.65). Among the children without comorbidities 76% were seizure free 13-24 months after the index seizure or after initiation of AED treatment compared to 53% of children with comorbidities. CONCLUSIONS: This study indicates that neurodevelopmental comorbidities and CP in children with epilepsy tend to be present already at seizure onset and that such comorbidities are strong indicators of poor outcome regarding seizure control with or without treatment.

The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months.

PURPOSE: To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. METHODS: The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. RESULTS: The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. CONCLUSION: The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied.

Copy number variations in children with brain malformations and refractory epilepsy.

Brain malformations are a major cause of therapy-refractory epilepsy as well as neurological and developmental disabilities in children. This study examined the frequency and the nature of copy number variations among children with structural brain malformations and refractory epilepsy. The medical records of all children born between 1990 and 2009 in the epilepsy registry at the Astrid Lindgren's Children's Hospital were reviewed and 86 patients with refractory epilepsy and various brain malformations were identified. Array-CGH analysis was performed in 76 of the patients. Pathogenic copy number variations were detected in seven children (9.2%). In addition, rearrangements of unclear significance, but possibly pathogenic, were detected in 11 (14.5%) individuals. In 37 (48.7%) patients likely benign, but previously unreported, copy number variants were detected. Thus, a large proportion of our patients had at least one rare copy number variant. Our results suggest that array-CGH should be considered as a first line genetic test for children with cerebral malformations and refractory epilepsy unless there is a strong evidence for a specific monogenic syndrome.

Presurgical language lateralization assessment by fMRI and dichotic listening of pediatric patients with intractable epilepsy.

OBJECTIVE: The aim of this study was to evaluate the clinical use of a method to assess hemispheric language dominance in pediatric candidates for epilepsy surgery. The method is designed for patients but has previously been evaluated with healthy children. METHODS: Nineteen patients, 8-18 years old, with intractable epilepsy and candidates for epilepsy surgery were assessed. The assessment consisted of two functional MRI protocols (fMRI) intended to target frontal and posterior language networks respectively, and a behavioral dichotic listening task (DL). Regional left/right indices for each fMRI task from the frontal, temporal and parietal lobe were calculated, and left/right indices of the DL task were calculated from responses of consonants and vowels, separately. A quantitative analysis of each patient's data set was done in two steps based on clearly specified criteria. First, fMRI data and DL data were analyzed separately to determine whether the result from each of these assessments were conclusive or not. Thereafter, the results from the individual assessments were combined to reach a final conclusion regarding hemispheric language dominance. RESULTS: For 14 of the 19 subjects (74%) a conclusion was reached about their hemispheric language dominance. Nine subjects had a left-sided and five subjects had a right-sided hemispheric dominance. In three cases (16%) DL provided critical data to reach a conclusive result. CONCLUSIONS: The success rate of conclusive language lateralization assessments in this study is comparable to reported rates on similar challenged pediatric populations. The results are promising but data from more patients than in the present study will be required to conclude on the clinical applicability of the method.

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.

Growth charts and long-term sequelae in extreme preterm infants--from full-term age to 10 years.

AIM: To describe growth pattern from full-term age to 10 years in infants born before 26 weeks of gestation. METHOD: This retrospective longitudinal cohort contained 123 children from Karolinska Hospital, Stockholm, during 1990-2002. Length/height (Ht), weight (Wt) and head circumference (HC) were recorded monthly during the first year, every 3 months until 2 years and yearly thereafter, but HC at 15 months and at median age of 8.1/9.7 years (range 2-14) in boys/girls. RESULTS: For boys/girls at birth, the mean Z-score for Ht was -0.2/-0.2, for Wt 0.0/-0.2 and for HC 0.0/-0.3. At term, the mean Z-score for Ht was -3.8/-3.1, for Wt -3.0/-2.5 and for HC -1.7/-1.2. At 1 year, the mean Z-score for Ht was-1.3/-1.3, for Wt -1.9/-1.7 and for HC -1.2/-1.0. At 2 years, the mean Z-score for Ht was -1.3/-1.1, for Wt -1.6/-1.2 and at 10 years for Ht -0.7/-0.4; that was on average -0.3 below mid-parental height; for Wt -0.2/-0.2. Long-term sequelae were found in 48% of the boys and 34% of the girls. CONCLUSION: By 10 years of age, the attained mean Ht was in accordance with their genetic potential and almost half of these children had significant long-term sequelae.

Medical conditions affect the outcome of early intervention in preschool children with autism spectrum disorders.

The aim was to explore the frequency of genetic and other medical conditions, including epilepsy, in a population-based group of 208 preschool children with early diagnosis of Autism spectrum disorders (ASD) and to relate outcome at a 2-year follow-up to the co-existing medical findings. They had all received early intervention. The Vineland Adaptive Behaviour Scales (VABS-II) composite score served as the primary outcome measure. In the total group, 38/208 children (18 %) had a significant medical or genetic condition. Epilepsy was present in 6.3 % at the first assessment and in 8.6 % at follow-up and was associated with more severe intellectual impairment. A history of regression was reported in 22 %. Children with any medical/genetic condition, including epilepsy, as well as children with a history of regression had significantly lower VABS-II scores at the 2-year follow-up. Children with a medical/genetic condition, including epilepsy, had been diagnosed with ASD at an earlier age than those without such conditions, and early age at diagnosis also correlated negatively with adaptive functioning outcome. The results underscore the importance of considering medical/genetic aspects in all young children with ASD and the requirement to individualize and tailor interventions according to their specific needs.

CSF levels of dopamine and serotonin, but not norepinephrine, metabolites are influenced by the ketogenic diet in children with epilepsy.

The ketogenic diet (KD) is a non-pharmacological treatment of medically refractory epilepsy in children. Its mechanisms of action are still unclear but monoamine neurotransmitters have been proposed to be involved. Norepinephrine, dopamine, and serotonin are known to modulate seizure susceptibility in many animal models. We examined whether the concentrations of norepinephrine, dopamine, and serotonin metabolites were affected by the KD in children with pharmacoresistant epilepsy. The metabolites of norepinephrine, HMPG, of dopamine, HVA, and of serotonin, 5-HIAA, were analyzed in cerebrospinal fluid (CSF) before and 3 months after starting the KD. Twenty-six children (mean age 5.9 years) participated. Twenty-one children had generalized epilepsy and five partial. CSF was sampled by lumbar puncture. Seizure frequency before and during the diet was determined. Highly significant changes were found for HVA (p=0.0002) and 5-HIAA (p=0.004), which were both decreased during the KD compared to before diet. The levels of HMPG were unchanged. However, no differences were found between response groups. Valproate medication affected the levels of HMPG during diet with decreased levels in children on valproate and increased in those not on valproate (p=0.04). Our study indicates that the KD significantly alters the levels of metabolites of dopamine and serotonin but with a stable ratio HVA/5-HIAA in the CSF of children with refractory epilepsy, which finding may be of importance for the mechanism of action.

Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans.

OBJECTIVE: To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. METHODS AND RESULTS: We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid-binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. CONCLUSIONS: Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9.

Growth dependence on insulin-like growth factor-1 during the ketogenic diet.

PURPOSE: To examine the influence of the ketogenic diet (KD) on linear growth and insulin-like growth factor I (IGF-I) levels in children with pharmacotherapy-resistant epilepsy. METHODS: A prospective study was designed to evaluate growth, serum IGF-I levels, blood beta-hydroxybutyric acid (beta-OHB), and seizure frequency before and during KD in 22 children (median age 5.5 years). Growth was assessed by measurements of weight, height, body mass index (BMI), and height velocity. Standard deviation scores (SDS) were calculated for all measured parameters as well as for serum IGF-I to eliminate the influence of age- and sex-related differences among patients. RESULTS: Fourteen of the 22 patients responded to the KD. Weight, height, BMI, and height velocity decreased significantly during the KD. We found that the KD had profound influence on growth and IGF-I levels. No correlation was found between seizure response and growth alterations. Height velocity correlated negatively with beta-OHB during the KD. The slope of the regression of height velocity against IGF-I decreased significantly during the KD. CONCLUSIONS: Height velocity was most affected in those with pronounced ketosis, which implies that, in clinical practice, the level of ketosis should be related to outcomes in seizure response and growth. Our data indicate that growth disturbances and the decreased sensitivity of growth to similar IGF-I levels during KD are independent of seizure reduction. The metabolic status induced by KD may be the mechanism underlying both alterations of linear growth and seizure reduction.

Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group.

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden: First report from the Stockholm Incidence Registry of Epilepsy (SIRE).

PURPOSE: To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE). METHODS: From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records. RESULTS: After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%. CONCLUSIONS: We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.

The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man.

FGF21 is a critical metabolic regulator, pivotal for fasting adaptation and directly regulated by PPARalpha in rodents. However, the physiological role of FGF21 in man is not yet defined and was investigated in our study. Serum FGF21 varied 250-fold among 76 healthy individuals and did not relate to age, gender, body mass index (BMI), serum lipids, or plasma glucose. FGF21 levels had no diurnal variation and were unrelated to bile acid or cholesterol synthesis. Ketosis induced by a 2 day fast or feeding a ketogenic diet (KD) did not influence FGF21 levels, whereas a 74% increase occurred after 7 days of fasting. Hypertriglyceridemic nondiabetic patients had 2-fold elevated FGF21 levels, which were further increased by 28% during fenofibrate treatment. FGF21 circulates in human plasma and increases by extreme fasting and PPARalpha activation. The wide interindividual variation and the induction of ketogenesis independent of FGF21 levels indicate that the physiological role of FGF21 in humans may differ from that in mice.

Polyunsaturated fatty acids and cerebrospinal fluid from children on the ketogenic diet open a voltage-gated K channel: a putative mechanism of antiseizure action.

PURPOSE: Many children with epilepsy do not satisfactorily respond to conventional pharmacological therapy, but to the ketogenic diet, a high-fat, low-carbohydrate diet. This diet increases the concentrations of ketone bodies and polyunsaturated fatty acids (PUFAs) in cerebrospinal fluid (CSF) and plasma. However, its anticonvulsant mechanism is not known. METHODS: To investigate the mechanism by which the diet protects against seizures, we studied the effects of several PUFAs (docosahexaenoic acid, eicosapentaenoic acid, and linoleic acid), ketone bodies (beta-hydroxybuturic acid and acetoacetic acid), and CSF from patients on the ketogenic diet on the voltage-gated Shaker K channel expressed in Xenopus oocytes. RESULTS: We found that PUFAs at concentrations down to 21microM clearly increased the K current by shifting the conductance versus voltage curve in negative direction along the voltage axis. CSF from patients on the ketogenic diet has similar but smaller effects. In contrast, high concentrations (1-5mM) of ketone bodies did not affect the K current. Computer simulations showed that the observed shifts for clinically relevant concentrations of PUFAs, and CSF from patients could effectively impair repetitive firing. CONCLUSIONS: These data suggest that the ketogenic diet could prevent epileptic seizures by PUFA-induced openings of voltage-gated K channels.

Influence of the ketogenic diet on 24-hour electroencephalogram in children with epilepsy.

The ketogenic diet is a therapeutic diet used to treat medically refractory epilepsy in children. It was found to be effective and safe. Apart from a reduced number of seizures, positive cognitive effects were described. The mechanisms of action are not fully understood, but both antiseizure and antiepileptogenic effects were proposed. Among other changes ascribed to the introduction of the diet, changes in electroencephalogram patterns might contribute to an understanding of the effects of the ketogenic diet. In this study, 23 children (mean age, 6.5 years) with pharmacoresistant epilepsy were started on the diet. They were examined via 24-hour ambulatory electroencephalogram directly before starting the diet, and after 3 months of treatment. The changing electroencephalogram pattern was evaluated qualitatively and semiquantitatively. Background activity, interictal epileptiform activity, ictal activity, and seizure reduction were evaluated. Quality of life was estimated on a visual analog scale. In 15 of 23 patients, the electroencephalogram indicated improvement in terms of more normal background activity or decreased interictal epileptiform activity. This improvement was seen in both seizure-reduction responders and nonresponders, and was not predictive of response to treatment.

Late onset bradyarrhythmia during vagus nerve stimulation.

Vagus nerve stimulation (VNS) is widely used to treat refractory epilepsy. It is usually safe and has few side effects. Cardiac arrhythmia has been reported during lead tests performed during implantation of the device, but never during regular treatment. We report here a case where vagally induced bradyarrhythmia, perfectly correlated with the stimulation periods, suddenly occurred two years and four months after the VNS implantation. The diagnosis was based on the appearance of syncope-like episodes. No specific cause could be found to explain the appearance of the episodes. To our knowledge, this is the first report on this severe and life-threatening side effect of VNS and should alert clinicians to its possibility. However, considering the large number of VNS implantations performed worldwide, it must be regarded as an extremely rare complication.