topiramate and Spasms--Infantile

Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.. We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.. Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.. Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.. This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Topics: Anticonvulsants; Child; Diet, Ketogenic; Epilepsy; Humans; Infant; Infant, Newborn; Lamotrigine; Levetiracetam; Quality of Life; Spasms, Infantile; Topiramate

The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented e

Topics: Autism Spectrum Disorder; Bromides; Cannabidiol; Clobazam; Cognition; Ethosuximide; Everolimus; Felbamate; Fenfluramine; Humans; Lacosamide; Lamotrigine; Levetiracetam; Pregabalin; Spasms, Infantile; Sulfides; Topiramate; Valproic Acid; Vigabatrin; Zinc Compounds; Zonisamide

Treatment of the catastrophic epilepsies [infantile spasms (IS), Lennox-Gastaut syndrome (LGS), and progressive myoclonic epilepsy (PME)] remains a challenge to clinicians. For IS, adrenocorticotropic hormone has traditionally been the drug of choice in the United States but may be associated with serious side effects in some patients. Vigabatrin has shown promise in treating IS patients, particularly those with tuberous sclerosis. However, the drug is associated with visual field loss and is not commercially available in the United States. Newer antiepilepsy drugs (AEDs), such as zonisamide, topiramate (TPM), and lamotrigine (LTG), may be useful in patients with IS. Although LTG, TPM, and felbamate are approved in the United States for the treatment of LGS, the overall effectiveness of therapy in patients with LGS is poor. For PME, valproate is a first-line treatment. Zonisamide and levetiracetam also show promise. Supplementation with certain cofactors to correct deficiencies and increase mitochondrial function may be useful in some patients with PME, but response to such therapy is not well documented. Advances in our understanding of the etiologies, mechanisms, and genetics underlying the catastrophic epilepsies may facilitate more effective pharmacologic interventions.

Topics: Anticonvulsants; Child, Preschool; Epilepsies, Myoclonic; Epilepsy; Fructose; Humans; Infant; Isoxazoles; Lamotrigine; Spasms, Infantile; Topiramate; Treatment Outcome; Triazines; Vigabatrin; Zonisamide

Topiramate is an antiepileptic drug (AED) which appears to have a broad range of antiseizure activity in humans. A previous overview focused primarily on results of trials of topiramate in adults with epilepsy, and this review highlights the use of topiramate in children. Clinical trials have shown that topiramate is effective when used adjunctively in children with refractory partial-onset seizures and generalised tonic-clonic seizures. The drug significantly reduced seizure frequency compared with placebo in children with partial-onset epilepsy after 16 weeks of double-blind adjunctive treatment (33.1 vs 10.5%); the frequency of secondarily generalised seizures was also markedly reduced. During a nonblind extension of this trial, the mean dosage was titrated from 4.8 to 9 mg/kg/day and further reductions in the frequency of seizures were observed (71% compared with prestudy levels). In 2 mixed adult/paediatric populations with primary generalised tonic-clonic seizures, topiramate (target dosage 5.2 to 9.3 mg/kg/day) reduced the seizure rate compared with those receiving placebo. This difference was significant in one trial (56.7 vs 9%) but not in another (57.1 vs 33.2%). A subanalysis of the paediatric patients found that the favourable effect of topiramate on seizure rates was not age-related. Topiramate (median average dosage 5.1 mg/kg/day) was also found to be useful as adjunctive therapy in the management of Lennox-Gastaut syndrome and significantly reduced the mean frequency of drop attacks by 14.8% compared with an increase of 5.1% with placebo. Further gains in seizure control were made in a nonblind extension of this trial where the mean topiramate dosage was 10 mg/kg/day. Nine of 11 patients in 1 pilot trial of children with otherwise intractable West syndrome, and 5 of 10 in another, achieved a > or =50% reduction in seizure rate with topiramate (target dosage up to 24 mg/kg/day). In an 18-month extension of the former trial (mean dosage 29 mg/kg/day) a > or =50% reduction in seizures was maintained in 7 of 11 children. Adverse events associated with adjunctive topiramate therapy in children were predominantly neuropsychiatric and generally mild to moderate in severity. Behavioural and cognitive problems do occur and are a limiting factor in some children. Also, weight loss can be problematical in some individuals. Withdrawal rates were low in the controlled trials (4.8%), but appear to be more frequent in noncomparative and post-marketing stu. Well controlled studies have demonstrated that topiramate is an effective agent for the adjunctive therapy of partial and generalised tonic-clonic seizures in children. Treatment-limiting adverse events do occur, but these may be managed by slow titration. Although comparative studies with the other newer AEDs used in adjuntive therapy are required, topiramate is an important extension to the range of drugs that may be used to treat refractory epilepsy in children.

Topics: Animals; Anticonvulsants; Child; Clinical Trials as Topic; Disease Models, Animal; Drug Administration Schedule; Drug Interactions; Drug Tolerance; Epilepsy; Fructose; Humans; Infant; Randomized Controlled Trials as Topic; Seizures; Spasms, Infantile; Tissue Distribution; Topiramate

The management of epilepsy in children requires careful evaluation, classification, and pharmacologic treatment. With classic antiepileptic drugs (AEDs), at least 25% of children remain refractory to appropriate therapy. The past decade has allowed the introduction of a number of newer AEDs for treatment of both adults and children with epilepsy. These include felbamate, gabapentin, lamotrigine, topiramate, tiagabine, and vigabatrin. Emerging information regarding the efficacy of these AEDs in treating childhood epilepsy syndromes suggests advantages for many patients. Limited data are available that define the optimal use of new AEDs in pediatric patients. Further research must be completed to validate the positive effects described in existing clinical trials of the new AEDs in the treatment of childhood epilepsy.

Topics: Acetates; Adult; Age Factors; Amines; Anticonvulsants; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Epilepsy; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Nipecotic Acids; Phenylcarbamates; Propylene Glycols; Spasms, Infantile; Tiagabine; Topiramate; Triazines; Vigabatrin

To compare the effectiveness of 2 novel antiepileptic drugs, topiramate and levetiracetam, as a second line treatment for infantile spasm when oral steroids fail.. Forty infants under 2 years with clinically- and EEG-proven infantile spasms that did not respond to prednisone (2mg/kg/day in 2 divided doses) were recruited and randomized into 2 groups. They were randomly assigned to either topiramate (group 1; 1mg/kg/day for 3 days then increased by 1mg/kg/day every third day up to 6mg/kg/day) or levetiracetam (group 2; 10mg/kg/day for 5 days and then increased by 10mg/kg/day every 5 days up to 60mg/kg/day). The study was conducted in the Pediatric Neurology Department at the National Neuroscience Institute of King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia between January 2008 and December 2010.. Of the 20 patients included in the final data analysis, 11 (55%) were administered topiramate and 9 (45%) levetiracetam. Eighteen patients did not respond to the first drug, and subsequently to the other drug when crossed-over. Two patients with infantile spasm responded to either one drug without crossover. Their EEGs improved with time.. The present study demonstrated the ineffectiveness of topiramate and levetiracetam suggesting current treatment modalities are grossly inadequate underscoring the urgent need for more research efforts to overcome current deficiencies. Two patients with cryptogenic infantile spasm responded to treatment suggesting the potential for treatment of such patients with these 2 drugs, and merits further multicenter investigation.

Topics: Anticonvulsants; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Female; Fructose; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Prednisone; Prospective Studies; Retreatment; Spasms, Infantile; Topiramate; Treatment Failure

A prospective study was conducted for the purpose of identifying the efficacy and safety of a protocol, first-line topiramate (TPM) followed by low-dose adrenocorticotropic hormone (ACTH) as the second drug, in the treatment of infantile spasms.. 40 children newly diagnosed with infantile spasms between 2007 and 2008 were enrolled in this study. They received an initial dose of 0.5-1mg/kg/day TPM, with 0.5-1mg/kg/day ascending every 3-7 days up to the target dose within the first 1 month. Partial/nonresponders for TPM were subsequently added low-dose and short-duration ACTH as the second treatment. Both efficiency and side effects were evaluated during the follow-up period.. Infants became spasms-free in 27 (67.5%) of all patients comprising 10 patients treated with TPM monotherapy and 17 with the combination of TPM and ACTH. Greater than 75% reduction in the frequency of spasms was found in 4 of all patients and at least 50% reduction in 4 patents as well. Side effects occurred in 29 (72.5%) patients; apart from 6 patients who needed moderately medical intervention, side effects throughout the trial were mild and well tolerated.. This prospective study demonstrated that, on the basis of primary TPM therapy, the combination treatment both TPM and low-dose ACTH was effective and available for the patients with infantile spasms.

Topics: Adrenocorticotropic Hormone; Age of Onset; Anticonvulsants; Drug Therapy, Combination; Electroencephalography; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Prospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

Topiramate is a new antiepileptic drug with a broad spectrum of efficacy. Reports on the use of topiramate for treatment of infantile spasms are limited. We prospectively followed 15 children with recently diagnosed infantile spasms treated with topiramate for efficacy and tolerability. Twelve patients had symptomatic infantile spasms, and two patients had cryptogenic infantile spasms. Topiramate was started at a dose of 3 mg/kg/day and titrated up to a dose of 27 mg/kg/day in 2 to 3 weeks. The primary efficacy measure was comparison of the seizure rate during the 2-week baseline with the median seizure rate during the first 2 months of treatment with topiramate. We also compared baseline electroencephalograms (EEGs) with post-treatment EEGs. The median seizure rate reduction during the first 2 months of treatment was 41% (P = .002). Three patients became spasm free (20%), five had > 50% reduction, and three had at least 25% reduction. Four patients did not respond. Three of 15 patients had clearing of hypsarrhythmia. Topiramate was generally well tolerated, with irritability being the most common side effect. Topiramate was efficacious and well tolerated; one patient discontinued the medication because of adverse effects. (J Child Neurol 2006;21:17-19).

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Electroencephalography; Female; Fructose; Humans; Infant; Male; Prospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

The clinical and electroencephalographic (EEG) response to combined therapy with vigabatrin and topiramate was evaluated in five patients ages 7 to 15 months affected by West syndrome in an open-label trial. Four patients had cryptogenic and one patient had symptomatic (tuberous sclerosis) West syndrome. In cryptogenic patients who failed to respond to pyridoxine, vigabatrin was titrated to 80 to 100 mg/kg. Because control of infantile spasms or an EEG improvement was not obtained with vigabatrin treatment, topiramate was added (3-3.8 mg/kg/day). In all patients, the combined therapy with topiramate and vigabatrin achieved a rapid and complete normalization of infantile spasms, and in three patients with cryptogenic West syndrome, the EEG also became normal. In only one patient, transient anorexia was observed. This drug combination led to rapid neurodevelopmental normalization in cryptogenic patients. The results are promising and justify more trials in larger numbers of children with West syndrome.

Topics: Anticonvulsants; Brain; Child Development; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Psychomotor Performance; Spasms, Infantile; Topiramate; Vigabatrin

Topiramate is an effective treatment for several types of seizures. The aim of this study is to assess the efficacy and tolerability of slow topiramate dose titration as add-on therapy in childhood epilepsy. This investigation is a prospective open-label, single-center, add-on study in 22 children with a diagnosis of refractory epilepsy. Topiramate (dose 0.5-2 mg/kg/day) was titrated at 2-week intervals up to the recommended dose of 6-12 mg/kg/day. Seizure frequency rate reduction was significant, declining from 23 +/- 5.1 seizures/week (mean +/- S.E.M.) at baseline phase to 3.5 +/- 1.2 seizures/week at the end of the 16-week stabilization phase (P < 0.001). After 16 weeks of stabilization, 19 patients (86%) had more than 50% seizure reduction. Seven patients (31%) were 100% seizure-free. Two patients (9%) manifested no improvement; only one patient (5%) did not tolerate the added drug and discontinued topiramate. One patient manifested severe side effects, whereas 21 patients experienced mild to moderate side effects mostly represented by somnolence, nervousness, and anorexia with or without weight loss. We conclude that slow dose titration improves efficacy and tolerability of topiramate as add-on therapy in the treatment in refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Epilepsy; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Infant; Male; Prospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

Topiramate (TPM) is a new anti-epileptic drug with proven efficacy against partial seizures in adults. Its use in children is less well documented. In a retrospective study, 41 patients with intractable childhood epilepsy were treated with TPM as add-on therapy for an average period of 15 months. They were classified according to seizure type and etiology. The dose was titrated for effect and ranged between 2 and 24 mg/kg/d. Of the 41 patients being treated, six became seizure free, ten had a seizure reduction of more than 75% and eight a seizure reduction of between 50 and 75%. The most remarkable effect was seen in seven patients with West syndrome. Of these, four patients became seizure free and one had more than 75% seizure reduction. Adverse effects including sedation, fatigue, difficulties with verbal expression and anorexia were noted in 15 patients. None of these effects were important enough to interrupt treatment. We conclude that TPM as adjunctive therapy is a promising drug in children with intractable epilepsy, especially in the patients with West syndrome.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Female; Fructose; Humans; Infant; Male; Retrospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

The long-term effectiveness of topiramate (TPM) was evaluated in children with West syndrome previously refractory to antiepileptic drug (AED) therapy.. Children with infantile spasms who completed a pilot study were eligible to enter a long-term extension phase in which the dosages of TPM and other AEDs could be adjusted to optimal response (maximum, 50 mg/kg/day TPM). The mean duration of long-term therapy was 18 months in the 11 children who were followed; the mean TPM dosage was 29 mg/kg/day.. Eight (73%) children were continuing TPM therapy at the time data were analyzed; four (50%) children were spasm free, seven (88%) had experienced a > or =50% reduction in spasms, and three (38%) were able to achieve TPM monotherapy.. TPM was well tolerated in that no patients discontinued because of adverse events. The response achieved with TPM during the pilot study was maintained in most children.

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Female; Fructose; Humans; Infant; Male; Pilot Projects; Spasms, Infantile; Topiramate; Treatment Outcome; Video Recording; Weight Gain

This study's goal was to provide preliminary data on the pharmacokinetics of topiramate (TPM) in a cohort of infants (younger than 4 years) participating in an open-label trial of TPM in refractory infantile spasms.. The pharmacokinetics of TPM were assessed in infants receiving a stable TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5. 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluorescence polarization immunoassay. The noncompartmental analysis module of WinNonlin was used to calculate individual patient pharmacokinetics profiles.. Five infants (ages, 23.5-29.5 months) formed the study cohort. These infants had been given TPM for a median of 9 months (range, 6-11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was receiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme-inducing agents; n = 2, non-enzyme-inducing drugs). TPM pharmacokinetics in infants appears to be linear. In this cohort, mean TPM plasma clearance (CL/F, 66.6+/-27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substantially higher than that reported for adults. TPM CL/F was higher and the calculated half-life shorter in the infants receiving concomitant enzyme-inducing AEDs.. Based on this small cohort of patients, it appears that infants may require significantly larger TPM doses, based on weight, than children, adolescents, or adults. Titration to effect and not absolute TPM dose should guide therapy in this age group.

Topics: Adolescent; Adult; Age Factors; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorescence Polarization Immunoassay; Fructose; Humans; Infant; Male; Spasms, Infantile; Topiramate

West syndrome is a rare epileptic syndrome associated with infantile spasms, a specific abnormal electroencephalographic pattern (termed hypsarrhythmia), and mental retardation. Management of this disorder is difficult because current treatment regimens, including many anticonvulsants and hormones, are often ineffective. Topiramate (TPM) is a new antiepileptic drug that may be effective in pediatric epilepsies. We conducted a pilot study to test the effects of rapid TPM dosing in patients with refractory infantile spasms.. Eleven children with refractory infantile spasms were given an initial dose of 25 mg TPM per day in addition to their current therapy. Dosage was increased by 25 mg every 2-3 days until spasms were controlled, the maximal tolerated dose was reached, or the maximal dose of 24 mg/kg/day was achieved. Efficacy was primarily assessed by video EEG and secondarily by parental count of spasm frequency.. Five (45%) subjects became spasm free during the study, with absence of infantile spasms and hypsarrhythmia (either classic or modified) proven by video EEG. Nine subjects, including the five spasm free, achieved a spasm reduction of > or =50%. Spasm frequency decreased from 25.6+/-19.3 to 6.9+/-5.9 spasms/day. Sixty-four percent of the subjects were able to achieve TPM monotherapy.. Results in this cohort of 11 patients with refractory disease show TPM to be a promising new agent for the treatment of infantile spasms.

Topics: Adult; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Female; Fructose; Humans; Infant; Male; Monitoring, Physiologic; Pilot Projects; Spasms, Infantile; Topiramate; Treatment Outcome; Videotape Recording

STXBP1-related disorders are among the most common genetic epilepsies and neurodevelopmental disorders. However, the longitudinal epilepsy course and developmental end points, have not yet been described in detail, which is a critical prerequisite for clinical trial readiness. Here, we assessed 1281 cumulative patient-years of seizure and developmental histories in 162 individuals with STXBP1-related disorders and established a natural history framework. STXBP1-related disorders are characterized by a dynamic pattern of seizures in the first year of life and high variability in neurodevelopmental trajectories in early childhood. Epilepsy onset differed across seizure types, with 90% cumulative onset for infantile spasms by 6 months and focal-onset seizures by 27 months of life. Epilepsy histories diverged between variant subgroups in the first 2 years of life, when individuals with protein-truncating variants and deletions in STXBP1 (n = 39) were more likely to have infantile spasms between 5 and 6 months followed by seizure remission, while individuals with missense variants (n = 30) had an increased risk for focal seizures and ongoing seizures after the first year. Developmental outcomes were mapped using milestone acquisition data in addition to standardized assessments including the Gross Motor Function Measure-66 Item Set and the Grasping and Visual-Motor Integration subsets of the Peabody Developmental Motor Scales. Quantification of end points revealed high variability during the first 5 years of life, with emerging stratification between clinical subgroups. An earlier epilepsy onset was associated with lower developmental abilities, most prominently when assessing gross motor development and expressive communication. We found that individuals with neonatal seizures or early infantile seizures followed by seizure offset by 12 months of life had more predictable seizure trajectories in early to late childhood compared to individuals with more severe seizure presentations, including individuals with refractory epilepsy throughout the first year. Characterization of anti-seizure medication response revealed age-dependent response over time, with phenobarbital, levetiracetam, topiramate and adrenocorticotropic hormone effective in reducing seizures in the first year of life, while clobazam and the ketogenic diet were effective in long-term seizure management. Virtual clinical trials using seizure frequency as the primary outcome resulted in wide range

Topics: Anticonvulsants; Child; Child, Preschool; Epilepsy; Humans; Infant; Infant, Newborn; Munc18 Proteins; Seizures; Spasms, Infantile; Topiramate

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy.. The patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy.. To our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.

Topics: Anticonvulsants; Facies; Humans; Hyperventilation; Infant; Intellectual Disability; Male; Mutation, Missense; Spasms, Infantile; Topiramate; Transcription Factor 4

Dravet syndrome is a severe developmental and epileptic encephalopathy characterised by refractory seizures and cognitive dysfunction. The treatment is challenging, not least because the seizures are highly drug resistant, requiring multiple anti-seizure medications (ASMs), while some ASMs can exacerbate seizures. Initial treatments include the broad-spectrum ASMs valproate (VPA), and clobazam (CLB) in some regions; however, they are generally insufficient to control seizures. With this in mind, three adjunct ASMs have been approved specifically for the treatment of seizures in patients with Dravet syndrome: stiripentol (STP) in 2007 in the European Union and 2018 in the USA, cannabidiol (CBD) in 2018/2019 (in combination with CLB in the European Union) and fenfluramine (FFA) in 2020. These "add-on" therapies (mostly to VPA/CLB) are used as escalation therapies, with the choice dependent on availability in different countries, patient characteristics and caregiver preferences. Topiramate is also frequently used, with evidence of efficacy in Dravet syndrome, and there is anecdotal evidence of efficacy with bromide, which is frequently used in Germany and Japan. With a growing treatment landscape for Dravet syndrome, there can be practical challenges for clinicians, particularly with issues associated with polypharmacy. This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated. Standard laboratory and clinical parameters include blood counts, liver function tests, serum concentrations of ASMs, monitoring the growth of children, as well as weight loss and acceleration of behavioural problems. Regular cardiac monitoring is also important with FFA as it has previously been associated with cases of cardiac valve disease when used in adults at high doses (up to 120 mg/day) in combination with phentermine as a therapy for obesity. Importantly, no signs of heart valve disease have been documented to date at the low doses used in patients with developmental and epileptic encephalopathies. In addition, potential drug-drug interactions and their consequences are a key consideration in everyday practice. Interactions that potentially require dosage adjustments to alleviate adverse events include the following: STP + CLB resulting in increased plasma concentrations of CLB and its ac

Topics: Adult; Anticonvulsants; Cannabidiol; Child; Clobazam; Drug Therapy, Combination; Epilepsies, Myoclonic; Epileptic Syndromes; Fenfluramine; Humans; Sleepiness; Spasms, Infantile; Topiramate

To evaluate the safety, tolerability, and effectiveness of oral topiramate therapy in children with West syndrome.. The present study was designed as a prospective, observational study and was performed from July 2016 through June 2018 at a tertiary care pediatrics centre in North India. The study was approved by Institute Ethics Committee.. Data on 39 children with West syndrome were analyzed. Topiramate was used as an adjunct in 38 children who failed to hormonal therapy and/or vigabatrin and as initial monotherapy in one case. The study participants had a long treatment lag to hormonal therapy (median 2 mo, IQR 1-8), a preponderance of male sex (67%) and structural etiology (87%). Nine (23%) children had a cessation of epileptic spasms at a median dose of 3.8 mg/kg/d. However, seven children with initial response had relapses. There were no significant group differences between responders and non-responders. Overall, topiramate was well tolerated. Somnolence and lethargy with decreased oral intake were commonly observed adverse effects.. The study observed poor effectiveness of topiramate therapy, which is partially due to a long treatment lag and a high proportion of structural etiology.

Topics: Anticonvulsants; Drug Tolerance; Female; Humans; India; Infant; Male; Prospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome; Vigabatrin

Topics: Humans; Spasms, Infantile; Topiramate

Hormonal therapy is the first-line treatment for infantile spasms and is sometimes used in combination with topiramate for better seizure control and potentially improved developmental outcomes. Retrospective review of pediatric patients with infantile spasms, with data compiled on patient sex, age at onset, etiology, electroencephalographic and imaging findings, topiramate use, spasm resolution (at one, six, and 12 months), and developmental outcome (at 12 months). Of 105 patients screened, 55 (28 female) met inclusion criteria (28 [51%] had spasms with known etiology and 27 [49%] had spasms with unknown etiology). Forty-six patients were followed for 12 months or longer to determine seizure outcome; a 12-month developmental assessment was documented for 49 patients. Thirty-seven patients (67%) received combination therapy; 18 (33%) received hormonal therapy alone. Resolution of spasms was comparable among treatment groups, with no difference relative to spasm etiology (p>0.18 for all). No difference was found in developmental outcomes with and without adjunct topiramate (p=0.38). Combination therapy was the most common treatment at our institution. However, combination therapy was not found to be beneficial for the treatment of spasms or developmental outcomes when compared to hormonal therapy alone.

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Male; Outcome Assessment, Health Care; Retrospective Studies; Spasms, Infantile; Topiramate

To compare the clinical efficacy of high-dose prednisone monotherapy and the combination of hormone and moderate-dose topiramate (TPM) therapy in children with infantile spasms (IS) and late-onset epileptic spasms (ES), and to evaluate whether the addition of TPM would provide more benefits for patients.. All patients were assigned to receive either high-dose prednisone alone (the maximum doses was 60 mg a day) or high-dose prednisone with TPM (the moderate doses was 5 mg/kg/day). The primary outcome was the proportion of children who achieved cessation of spasms at day-49 or day-56 after initial treatment (the minimum duration of treatment were 49 days).. 77 patients were randomly divided into two groups. The control rate of spasms on day-14 in hormone monotherapy was similar to combination therapy (71.8% vs 76.3%, p = 0.796). The cessation of spasms rate of patients on day-49 or day-56 was also similar between the two groups (71.8% vs 65.8%, p = 0.569). After 4 months, the cessation of spasms rate of patients in the group of hormone monotherapy was higher than the group of combination therapy, but there was no significant difference (61.5% vs 50.0%, p = 0.308).. The efficacy of the combination therapy was not better than that of the monotherapy in achieving spasm freedom at 14-days, 49-days or 56-days and day-120 in the patients. Adding-on moderate-dose TPM did not help more children achieve spasm freedom and provided no benefit for prevention of IS and late-onset ES in short term. Higher-dose regimens of TPM might be more effective.

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Infant; Male; Outcome Assessment, Health Care; Prednisone; Spasms, Infantile; Topiramate

Infantile spasms (IS) was an epileptic disease with varied treatment widely among clinicians. Here, we aimed to compare and analyze the clinical characteristics of IS response to pyridoxine or topiramate monotherapy (TPM control IS).. The clinical manifestations, treatment processes and outcomes were analyzed in 11 pyridoxine responsive IS and 17 TPM-control IS.. Of the 11 patients with pyridoxine responsive IS, nine were cryptogenic/idiopathic. Age of seizure onset was 5.36 ± 1.48 months. Spasms were controlled within a week in most of the patients. At the last follow-up, EEG returned to normal in 8. Psychomotor development was normal in 6, mild delay in 3, severe delay in 2. Of the 17 patients with TPM-control IS, 10 were cryptogenic/idiopathic. The age of seizure onset was 5.58 ± 2.09 months. All patients were controlled within a month. At the last follow-up, EEG was normal in 10. Psychomotor development was normal in 8, mild delay in 5, severe delay in 4. Genetic analysis did not show any meaningful results.. The clinical characteristics and disease courses of pyridoxine responsive IS and TPM-control IS were similar, which possibly clued for a same pathogenic mechanism. Pyridoxine should be tried first in all IS patients, even in symptomatic cases. If patients were not responsive to pyridoxine, TPM could be tried.

Topics: Anticonvulsants; Chi-Square Distribution; Child, Preschool; China; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Female; Follow-Up Studies; Fructose; Humans; Infant; Male; Pyridoxine; Retrospective Studies; Risk Assessment; Severity of Illness Index; Spasms, Infantile; Statistics, Nonparametric; Time Factors; Topiramate; Treatment Outcome

Encephalopathy with continuous spike-wave during sleep (CSWS) is a particularly difficult-to-treat childhood epileptic syndrome. This study sought to present the EEG improvement and clinical efficacy of topiramate (TPM), a broad spectrum antiepileptic drug (AED), in a series of 21 children with CSWS encephalopathy.. We retrospectively reviewed the EEG results and clinical data of children with CSWS followed-up in our institution and treated with TPM. Sleep EEGs were performed 0-3 months prior to TPM introduction and then at 3 and 12 months. The exclusion criteria were (1) introduction of another AED and (2) withdrawal of a potentially aggravating AED during the first 3 months of treatment. In addition to spike index (SI), the severity of EEG abnormalities was rated using an original scale that also considered the spatial extent of interictal epileptiform discharges.. 21 patients were included (18 males, 4-14y, three symptomatic cases). At 3 months, sleep EEG was improved in 14 and normalized in four (TPM doses: 2-5.5 mg/kg/day). Among these 18 patients, 16 manifested cognitive or behavioural improvement. In a subgroup of seven patients with frequent seizures, five became seizure-free and one had over 75% decrease in seizure frequency. At the one-year follow-up, 20 children were still on TPM and 10 exhibited persistent EEG improvement without any other AED being introduced, most of them with clinical benefits.. TPM can decrease EEG abnormalities in epileptic encephalopathy with CSWS, achieving clinical improvement in the majority of patients. However, relapse may occur in the long-term in nearly half of cases. Otherwise, TPM has proven particularly useful in reducing seizure frequency in refractory cases.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Fructose; Humans; Male; Recurrence; Retrospective Studies; Sleep; Spasms, Infantile; Topiramate

Topics: Anticonvulsants; Clonazepam; Diagnosis, Differential; Electroencephalography; Female; Fructose; Humans; Infant, Newborn; Levetiracetam; Mutation; NAV1.2 Voltage-Gated Sodium Channel; Phenobarbital; Phonation; Piracetam; Receptors, N-Methyl-D-Aspartate; Spasms, Infantile; Topiramate

There is scant evidence to guide the management of infantile spasms after successful response to initial therapies. There is significant risk of relapse, largely because effective pharmacologic treatments cannot be continued long term because of concern for significant adverse events. Zonisamide (ZNS) and topiramate (TPM) are commonly used to prevent relapse, and the purpose of this study was to specifically evaluate the efficacy of ZNS and TPM as agents for secondary prevention of infantile spasms.. Patients with video-electroencephalography (EEG) confirmed resolution of infantile spasms were retrospectively identified. Relevant clinical data were systematically collected, including lead time from onset of spasms to successful treatment response, etiology of infantile spasms, number of treatment failures prior to response, timing of relapse, and detailed exposure data for ZNS and TPM.. We identified 106 patients with response to hormonal therapy (n = 58), vigabatrin (n = 25), or surgery (n = 23). To prevent relapse of infantile spasms, 37 patients received ZNS, 34 received TPM, 3 received both ZNS and TPM, and 38 patients received neither ZNS nor TPM. There were 44 relapses, occurring a median of 6.9 (3.2-10.8) months after initial response. Time to relapse was not affected by treatment with ZNS or TPM. Relapse was less likely among patients who were older (hazard ratio 0.97 [per month], p = 0.036) and those who responded to surgical resection (hazard ratio = 0.28, p = 0.017). Of note, we identified a relatively refractory cohort with multiple treatment failures and long lead time to initial response.. In this refractory cohort, neither ZNS nor TPM was successful in preventing relapse of infantile spasms, despite relatively high dosages. At this time, aside from surgical resection in eligible candidates, there is no known treatment that is efficacious in the prevention of relapse of infantile spasms.

Topics: Cohort Studies; Electroencephalography; Female; Fructose; Humans; Infant; Isoxazoles; Male; Recurrence; Spasms, Infantile; Statistics, Nonparametric; Survival Analysis; Topiramate; Video Recording; Vigabatrin; Zonisamide

Several immune mechanisms are suspected in the unknown etiology of West syndrome (WS). We report a male infant who suffered from WS and X-linked T-B+NK- severe combined immunodeficiency (X-SCID) with a missense mutation of the IL2RG gene (c.202G>A, p.Glu68Lys). He promptly began vitamin B6 and valproic acid treatment, but infantile spasms (IS) and hypsarrhythmia persisted. Administration of intravenous immunoglobulin and the change to topiramate (TPM) at 7 months of age resulted in the rapid resolution of IS. The CD4/8 ratio in his peripheral blood increased from 0.04-0.09 to 0.20-1.95 following unrelated cord blood transplantation (UCBT). In vitro lymphocyte proliferation in response to phytohemagglutinin or concanavalin A and the ability of B lymphocytes to produce antibodies improved as well. Electroencephalogram findings became normal 1 month after UCBT. Thus, we consider that T-cell dysfunction and/or impairments in T-B cell interactions due to X-SCID may have played important roles in the onset of WS. Immune-modulating therapies along with the administration of TPM effectively treated this severe epileptic syndrome in our patient.

Topics: Anticonvulsants; B-Lymphocytes; Child, Preschool; Fructose; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Infant; Infant, Newborn; Interleukin Receptor Common gamma Subunit; Male; Mutation, Missense; Severe Combined Immunodeficiency; Spasms, Infantile; T-Lymphocytes; Topiramate

Infantile spasms are seizures typical of an age-related epileptic encephalopathy. Although evidence supporting topiramate for infantile spasms is lacking, many clinicians use it for this indication. The aim of this study was to determine the rate of infantile spasm remission with topiramate at our institution. A low rate of infantile spasm remission was hypothesized.. This was a single-center retrospective medical record review of patients treated with topiramate for infantile spasms between January 2009 and September 2013. Records were reviewed for accuracy of diagnosis and outcome. Clinical remission of infantile spasms was defined as resolution for at least 28 days at any time during treatment with topiramate. For patients with clinical remission, posttreatment electroencephalographs were reviewed to assess for electrographic remission. To assess for confounding variables affecting remission rate, demographics and outcomes were compared with patients treated with adrenocorticotropic hormone within the same period using the same criteria for remission.. Three of 31 (9.7%) patients achieved clinical remission with topiramate, two of whom also experienced electrographic remission. The third patient had electrographic remission with previous adrenocorticotropic hormone treatment but infantile spasm remission only after receiving topiramate. All three of these patients experienced subsequent electroclinical relapse during topiramate therapy. Although there were no significant demographic differences between the topiramate and adrenocorticotropic hormone cohorts, more adrenocorticotropic hormone patients achieved clinical remission (9.7% versus 56%; P < 0.001).. Remission of infantile spasms with topiramate was uncommon and no patient experienced persistent electroclinical remission. These findings suggest that infantile spasms respond poorly to topiramate.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Anticonvulsants; Child; Child, Preschool; Female; Fructose; Humans; Infant; Male; Recurrence; Retrospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

We investigated the efficacy, safety, and tolerability of high-dose topiramate with rapid dose titration in 12 children with symptomatic West syndrome who suffered from severe motor and intellectual disabilities.. Topiramate was introduced as add-on therapy at the daily dose of 1 mg/kg/day, followed by increments of 2 mg/kg at 3- or 4-day intervals, up to a maximum of 19 or 20 mg/kg/day. The ages at the start of topiramate therapy ranged from 5 to 22 months. Prior to the topiramate therapy, the patients had received 2 to 6 antiepileptic agents with (8 patients) or without ACTH (4 patients).. Topiramate appeared to be effective in 8 of the 12 patients (67%); four became seizure-free;three showed greater than 90% seizure reduction; one showed greater than 50% seizure reduction. The maintenance dose was 7 to 20 mg/kg/day (mean:17.9 +/- 3.9 mg/kg/day). In 4 of these 8 patients (50%), the spasms relapsed several months after complete cessation or diminution in the frequency of the spasms following treatment with topiramate. All of the 8 topiramate-responsive patients could continue the topiramate therapy throughout this study. The duration of topiramate therapy was 7 to 42 months (median: 12.5 months). There were no severe side effects that necessitated discontinuation of topiramate, including kidney stones.. High-dose topiramate with rapid dose titration was revealed to be effective, safe, and well-tolerated in children with symptomatic West syndrome.

Topics: Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fructose; Humans; Infant; Male; Spasms, Infantile; Topiramate; Treatment Outcome

To determine Topiramate efficacy on treatment of infantile spasms and ancillary seizures, and whether there were any improvements on EEG.. A retrospective study of 18 patients with infantile spasms recruited from the Pediatric Unit at King Fahd Hospital of the University, Dammam University, Saudi Arabia was carried out between January 2004 and December 2008. Topiramate was used as treatment in 7 males and 11 females aged 2-14 months. The maximum dose was 12 mg/kg/day.. The etiology in 9 (50%) patients was cryptogenic, 6 (33%) symptomatic, and 3 (17%) idiopathic. After Topiramate treatment 6 (33%) were spasm free, 8 (44%) had ≥50% reduction, 2 (11%) had no change, and one (6%) had worsening of their spasms. Eight patients had ancillary seizures, 2 (25%) were seizure free, 2 (25%) had ≥50% seizure reduction, and 4 (50%) had no change in the ancillary seizure. The EEG showed hypsarrhythmia in 14 (78%). Post Topiramate, the EEG was normal in one (5%), improved in 3 (17%), showed persistent hypsarrhythmia in 8 (44%), and evolved to other features in 3 (17%). Three patients developed side effects such as weight loss and irritability, for which 2 patients stopped the medication.. Topiramate has a good effect on the clinical features of West syndrome, but not on the EEG. It was tolerated with minimal side effects.

Topics: Anticonvulsants; Electroencephalography; Female; Fructose; Humans; Infant; Male; Retrospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome

Lennox-Gastaut syndrome (LGS) is a well-defined epileptic encephalopathy highly drug resistant. The first-line treatment option is valproate (VPA), usually in combination with lamotrigine. VPA has been linked to serious hepatotoxicity. We report a 22-year-old liver transplanted patient with LGS successfully treated with VPA in combination with phenobarbital (100 mg/d; blood level: 36 mg/l), lamotrigine (125 mg/d; blood level: 4.81 mg/l) and topiramtate (175 mg/d), as well as immunosuppressive, antiviral, anti-anemic, hypo-phosphoric and alkaline medication. On VPA 1000 mg/d, the seizure frequency decreased significantly. Taking into consideration the patient's good tolerance and the normal liver function, VPA was increased to 1500 mg/d. At this dose the daily drop attacks and generalized tonic-clonic seizures totally ceased. The patient presented only some tonic seizures around awakening. During many years, VPA was avoided in this patient because of its potential hepatotoxicity. However the good functioning of the transplanted liver permitted its introduction. VPA can be used safely in liver transplanted patients under the strict control of the hepatic function.

Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Electroencephalography; Female; Fructose; Humans; Immunosuppressive Agents; Intellectual Disability; Lamotrigine; Lennox Gastaut Syndrome; Liver Function Tests; Liver Transplantation; Phenobarbital; Seizures; Spasms, Infantile; Topiramate; Triazines; Valproic Acid; Young Adult

Topiramate is an antiepileptic medicine that has been used adjunctively in the treatment of refractory seizures in Japan since 2007. Topiramate has been shown to inhibit specific carbonic anhydrase activity in the kidney and may induce a distal type of renal tubular acidosis. Case 1 : A 22-year-old male was referred to our hospital after complaining of left flank pain. He developed a seizure disorder and had been using topiramate for 4 months. Drip infusion pyelography showed a left ureteral stone. Case 2 : A 7-year-old boy presented with gross hematuria. He developed West syndrome and had been using topiramate for 6 months. A computed tomographic scan showed a right kidney stone.

Topics: Anticonvulsants; Child; Epilepsy; Fructose; Humans; Infant; Kidney Calculi; Male; Spasms, Infantile; Topiramate; Urolithiasis; Young Adult

Topics: Anticonvulsants; Child; Child, Preschool; Female; Fructose; Humans; Infant; Longitudinal Studies; Male; Spasms, Infantile; Topiramate

The authors report on the case of a 6-week-old boy who presented with infantile spasms. At 2.5 months of age, the patient underwent a right hemispherectomy. Approximately 3 months postoperatively, the patient presented with left coronal craniosynostosis. Subsequent cranial vault remodeling resulted in satisfactory cosmesis. Four years after surgery, the patient remains seizure free without the need for anticonvulsant medications. The authors believe this to be the first reported case of iatrogenic craniosynostosis due to hemispherectomy, and they describe 2 potential mechanisms for its development. This case suggests that, in the surgical treatment of infants with intractable epilepsy, minimization of brain volume loss through disconnection techniques should be considered, among other factors, when determining the best course of action.

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Clonazepam; Craniosynostoses; Craniotomy; Electroencephalography; Epilepsy; Fructose; Hemispherectomy; Humans; Infant; Male; Postoperative Complications; Spasms, Infantile; Tomography, X-Ray Computed; Topiramate

We systematically reviewed the files of 51 infants presenting with infantile spasms and hypsarrhythmia in order to study the initial treatment strategies and the long term outcome. 80% of the infants were classified as symptomatic. In the nine participating centres, different treatment protocols were used, but the large majority of the children received vigabatrin as first line treatment. Second line options included hormonal treatment, topiramate and valproate. The time to reach cessation of infantile spasms was significantly shorter in the cryptogenic group than in the symptomatic group (50% at 13 days versus 66 days respectively) and was irrespective of the treatment used. The late follow up data (>2 years) showed that 60% of the children had epilepsy and that 75% of the children had a delay in their psychomotor development. Again, outcome in the cryptogenic group was better than in the symptomatic group, but also in the cryptogenic group, 50% of the children had a clear developmental delay, even if spasms were controlled early in the course of the disease. Our retrospective study illustrates that not only the underlying brain dysfunction is the major determinant for later outcome in infantile spasms (symptomatic group) but also even a short period of infantile spasms can be responsible for later developmental delay (cryptogenic group).

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Developmental Disabilities; Follow-Up Studies; Fructose; Humans; Infant; Retrospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome; Valproic Acid; Vigabatrin

Topics: Anticonvulsants; Child, Preschool; Clinical Trials as Topic; Electroencephalography; Female; Fructose; Humans; Infant; Neuroprotective Agents; Spasms, Infantile; Topiramate

Historically, adrenocorticotropic hormone was used as a first-line treatment for infantile spasms; however, there has been increasing use of topiramate as initial therapy. Here, we report a retrospective study of adrenocorticotropic hormone (ACTH) and topiramate as initial treatment for infantile spasms. The neurology patient database at the Children's Hospital of Philadelphia was searched using the International Classification of Diseases, Ninth Revision code for infantile spasms, and 50 patients were randomly chosen for chart review. We identified 31 patients receiving either adrenocorticotropic hormone or topiramate monotherapy (adrenocorticotropic hormone n = 12, topiramate n = 19) as a first-line treatment for infantile spasms. A total of 26 patients were symptomatic and 5 cryptogenic. Six patients treated with adrenocorticotropic hormone had resolution of clinical spasms and hypsarrhythmia within a month, but 3 relapsed. Of the 19 patients treated with topiramate, 4 patients eventually, though over a period of 0, 1, 8, or 69 months, had resolution of spasms and hypsarrhythmia.

Topics: Adrenocorticotropic Hormone; Age of Onset; Anorexia; Anticonvulsants; Brain; Dose-Response Relationship, Drug; Female; Fructose; Hormones; Humans; Infant; Lethargy; Male; Retrospective Studies; Selection Bias; Spasm; Spasms, Infantile; Topiramate; Treatment Outcome; Tremor

The aim of this study is to investigate the efficacy and tolerability of topiramate in a large number of children with West syndrome. The authors performed a retrospective, questionnaire-based data collection in specialized epilepsy units in Germany. Patients with West syndrome and hypsarrhythmia could be included if topiramate treatment had started at an age of < or =3 years. Data of 100 patients were evaluated. Nearly all patients were severely affected and had been treated with multiple antiepileptic drugs with insufficient effect. Topiramate was introduced at a median age of 11.9 months. The median starting dosage was 1.6 mg/kg body weight per day, increased to a median maximum dosage of 12.0 mg/kg. Sixty-one patients received between 1 and 3 antiepileptic drugs in addition to topiramate. The median daily dose considered by the attending physicians to be most effective regarding seizure reduction was 10 mg/kg. A significant reduction in the number of seizures per week was achieved. A total of 17.5% of patients became free of seizures, and in 47%, the seizure frequency decreased by at least 50%. Hypsarrhythmia or status-like electroencephalography patterns remitted in 18 of 83 cases. Side effects were reported in 25% of children and included mostly sedation, loss of appetite, weight loss, and metabolic acidosis. These side effects were statistically related to the number of additional antiepileptic drugs but not to the topiramate dosage. In 17% of patients, topiramate treatment was discontinued because of side effects and in a further 4% because of worsening of seizures. In 44% of patients, treatment was continued for more than 3 months. In conclusion, the data suggest that topiramate is a useful drug in treating West syndrome. However, because of the inherent limitations of the retrospective study design, future prospective controlled studies should be performed.

Topics: Anticonvulsants; Electroencephalography; Fructose; Humans; Infant; Infant, Newborn; Retrospective Studies; Severity of Illness Index; Spasms, Infantile; Topiramate; Treatment Outcome

Infantile spasm is an age-related refractory epilepsy. Topiramate is a new anticonvulsant with multiple mechanisms of action, and it may be effective for treating pediatric epilepsies. To evaluate the efficacy and tolerability of first-line topiramate treatment for infantile spasm, 20 patients received topiramate monotherapy during this study. They were treated with an initial dose of 1mg/kg/day, with a progressive titration of 1 mg/kg a week until their spasms were controlled and a maximum dose of 12 mg/kg/day was achieved. The evaluation of the treatment efficacy was based on the spasm frequency data that was obtained by the scalp and video-EEG, and by the parental count of spasm. Thirty percent of the subjects became spasm-free during the study. Six of 20 subjects (30%) had cessation of spasm and disappearance of hypsarrhythmia as seen via the video EEG; four (50%) of eight idiopathic patients had a response, whereas two (17%) of 12 patients with symptomatic infantile spasm responded. Seventy of the patients, including the spasm-free patients, had a reduction in their seizure frequency of more than 50%, and 10% of the patients had a reduction in their seizure frequency of less than 50%. The clusters of spasm frequency decreased from 10.6 +/- 8.5 to 3.5 +/- 1.4 clusters/day. Topiramate is effective and tolerated in those patients suffering from infantile spasm. Our results suggest that this drug should be considered as a new first-line drug for treating infantile spasm.

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Electroencephalography; Female; Fructose; Humans; Infant; Male; Spasms, Infantile; Topiramate; Treatment Outcome

Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d-fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported.. We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis.. Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression.. This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.

Topics: Adolescent; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Fever; Fructose; Humans; Hypohidrosis; Infant; Male; Spasms, Infantile; Sweating; Topiramate

Topiramate is a new anti-epileptic drug with proven efficacy against partial seizures in adults. A retrospective assessment of the use of topiramate in drug-resistant childhood epilepsy was undertaken. Thirty-four children (median age of 10 years; range 2-18 years) were treated for a median of 9 months (range 6-18 months). The starting dose was 0.25-2.0 mg/kg/day increasing to a maximum of 13 mg/kg/day. Generalized seizures occurred in 27 patients, partial seizures in 15 and infantile spasms in two. Epilepsies were localization-related in 15 patients and generalized in 18. One patient had severe myoclonic epilepsy in infancy. Two patients had Lennox-Gastaut syndrome, five (two currently and three previously) had West syndrome and one had epilepsy with myoclonic absences. Twenty patients had a substantial (> 50%) reduction in seizure frequency; two of whom became seizure-free. Two-patients had an increase in seizures. Efficacy was seen against simple and complex partial seizures, generalized tonic-clonic seizures (primarily generalized), atonic and tonic seizures, myoclonic seizures and infantile spasms. There was no response in the one patient with myoclonic absence seizures. Adverse effects were reported in nine patients; appetite suppression occurred in five patients, behaviour disturbances in three, somnolence in two and poor concentration in one patient. Topiramate is efficacious in a wide spectrum of childhood epilepsies and is well tolerated.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance, Multiple; Epilepsies, Partial; Female; Fructose; Humans; Male; Spasms, Infantile; Topiramate; Treatment Outcome