levetiracetam 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

To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).. Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.. We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.. This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Ethosuximide; Hormones; Humans; Infant; Lamotrigine; Levetiracetam; Network Meta-Analysis; Nitriles; Odds Ratio; Piracetam; Pyridones; Spasms, Infantile; Treatment Outcome; Triazines; Valproic Acid

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

Topics: Anticonvulsants; Body Weight; Brain; Deglutition Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Electroencephalography; Female; Humans; Infant; Levetiracetam; Male; Muscle Hypotonia; Piracetam; Spasms, Infantile; Treatment Outcome

The combination of axial spasms in clusters, hypsarrhythmia, and psychomotor delay beginning in the first year of life defines West syndrome. Adrenocorticotrophic hormone remains the choice of treatment for many neurologists. Recent controlled studies support vigabatrin as first-line therapy, and open-label studies suggest that topiramate, lamotrigine, and zonisamide may be useful in treating spasms. Studies regarding the efficacy and safety of such treatments often come from small, uncontrolled trials and are often inconclusive. Levetiracetam is effective for treating localization-related epilepsy, but it is uncertain whether it is effective for treating West syndrome. To evaluate the efficacy of levetiracetam monotherapy in newly diagnosed cryptogenic West syndrome, levetiracetam was used initially in the treatment of five patients with cryptogenic West syndrome. On admission, levetiracetam (30 mg/kg) tablets were crushed and administered via nasogastric tube. Two patients were seizure free, two patients experienced a 50% reduction in seizure frequency, and one patient had no improvement in seizure frequency. There were no relapses in the two patients at 6 months after the cessation of seizures. It appears that levetiracetam may be effective in the initial treatment of selected patients with cryptogenic West syndrome.

Topics: Anticonvulsants; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Spasms, Infantile; Treatment Outcome

We determined the yield, genetic spectrum, and actual origin of de novo mutations (DNMs) for infantile spasms (ISs) in a Chinese cohort. The efficacy of levetiracetam (LEV) for STXBP1-related ISs was explored also.. Targeted sequencing of 153 epilepsy-related candidate genes was applied to 289 Chinese patients with undiagnosed ISs. Trio-based amplicon deep sequencing was used for all DNMs to distinguish somatic/mosaic mutations from germline ones.. Total of 26 DNMs were identified from 289 recruited Chinese patients with undiagnosed ISs. Among them, 24 DNMs were interpreted as pathogenic mutations based on American College of Medical Genetics and Genomics guidelines, contributing to 8.3% (24/289) of diagnosis yield in the Chinese IS cohort. CDKL5 and STXBP1 are the top genes with recurrent DNMs, accounting for 3.1% (9/289) of yield. Further deep resequencing for the trio members showed that 22.7% (5/22) of DNMs are actually somatic in the proband or a parent. These somatic carriers presented milder seizure attacks than those with true germline DNMs. After treatment with LEV for half a year, three patients with DNM in STXBP1 showed improved clinical symptoms, including seizure-free and normal electroencephalogram, except for a patient with a second DNM in DIAPH3.. Our study confirmed the contribution and genetic spectrum of DNMs in Chinese IS patients. Somatic mutation account for a quarter of DNMs in IS cases. Treatment with LEV improved the prognosis of STXBP1-related ISs.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Female; Formins; Gene Frequency; Germ-Line Mutation; Humans; Infant; Levetiracetam; Male; Mosaicism; Munc18 Proteins; Protein Serine-Threonine Kinases; Spasms, Infantile

PCDH19 Girls clustering epilepsy (GCE) has a phenotypic spectrum that includes developmental and epileptic encephalopathy. PCDH19-GCE presents with clusters of seizures in the first years of life. Although patients typically outgrow their seizures, many are left with intellectual disability. Here we retrospectively assess the effect of levetiracetam in two independent cohorts of females with PCDH19-GCE.. Cohort A was identified by searching our epilepsy genetics research database for girls with PCDH19-GCE who had trialled levetiracetam. Cohort B consisted of girls aged 2 years or older, including women, participating in an international online questionnaire. Information regarding seizure frequency and levetiracetam use was obtained by in-person patient interview and review of clinical records for cohort A, and by patient report for cohort B.. Cohort A consisted of 17 females, aged 3-37 years, who had a trial of levetiracetam at an average age of 10.7 years. 13/17 females became seizure free for >12 months; while 10/17 remained seizure free for >24 months. Cohort B comprised 62 females, aged 1.5-41 years. 26/62 became seizure free for >12 months, and 19/62 for >24 months on levetiracetam therapy.. Levetiracetam was effective in two cohorts of females with PCDH19-GCE where 42% and 76% of females became seizure free for >12 months, respectively. Levetiracetam is an effective therapy for females with PCDH19-GCE and should be considered early in the management of the highly refractory clusters of seizures that characterise this genetic disease.

Topics: Adolescent; Adult; Anticonvulsants; Cadherins; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Levetiracetam; Protocadherins; Retrospective Studies; Spasms, Infantile; Young Adult

Topics: Animals; Anticonvulsants; Chromosomes, Human, Pair 9; Drug Substitution; Electroencephalography; Epilepsies, Partial; GABA Agonists; Humans; Infant; Levetiracetam; Male; Models, Animal; Motor Skills; Neurodevelopmental Disorders; Phenobarbital; Polymorphism, Single Nucleotide; Receptors, GABA-B; Spasms, Infantile; Vigabatrin

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

Norrie disease is an X-linked recessive disorder that is characterized by congenital blindness. Although epileptic seizures are observed in some patients with Norrie disease, little is known about this phenomenon. Here, we report the manifestation of epilepsy in siblings with Norrie disease to increase our knowledge of epilepsy in this condition. Three brothers with congenital blindness were diagnosed with Norrie disease after genetic analyses indicated the deletion of exon 2 of the NDP gene. The eldest brother had suffered from epileptic seizures since the age of 11years, and his seizures were resistant to antiepileptic drugs. Although the second brother had no epileptic seizures, the youngest sibling had experiences epileptic seizures since the age of 8years. His seizures were controlled using lamotrigine and levetiracetam. An electroencephalography (EEG) revealed epileptiform discharges in the occipital areas in all three brothers. A study of these patients will increase our knowledge of epilepsy in patients with Norrie disease.

Topics: Anticonvulsants; Blindness; Chromosomes, Human, X; Electroencephalography; Epilepsy; Eye Proteins; Genetic Diseases, X-Linked; Humans; Lamotrigine; Levetiracetam; Nerve Tissue Proteins; Nervous System Diseases; Pedigree; Phenotype; Piracetam; Retinal Degeneration; Siblings; Spasms, Infantile; Triazines

West syndrome is an age-dependent epilepsy with onset peak in the first year of life whose aetiology may be symptomatic or cryptogenic. Long-term cognitive and neurological prognosis is usually poor and seizure outcome is also variable. Over the past two decades a few patients with favourable cognitive outcome and with total recovery from seizures were identified among the cryptogenic group suggesting an idiopathic aetiology. Recent research has described two children with idiopathic WS who later developed a childhood absence epilepsy.. We reviewed the medical records of patients with West syndrome admitted to the our Child Neuropsychiatry Unit in the last 15 years in order to know the clinical evolution of infantile spasms.We report a child with West syndrome with onset at 8 months of age followed by some clusters of bilateral, arrhythmic myoclonic jerks of the upper limbs, mainly on awakening, synchronous with the generalized discharges of 4 Hz spike-wave occurring at 12 years of age and by co-occurrence of a later generalized tonic-clonic seizure at 14 years and four months, both sensitive to Levetiracetam suggesting a juvenile myoclonic epilepsy.. This unusual evolution, never previously reported, suggests that both electroclinical features mentioned above may share some pathophysiological processes genetically determined which produce a susceptibility to seizure and emphasizes that the transition between different age-related epileptic phenotypes may involve also the West syndrome.

Topics: Adolescent; Brain; Disease Progression; Humans; Infant; Levetiracetam; Magnetic Resonance Imaging; Male; Myoclonic Epilepsy, Juvenile; Piracetam; Spasms, Infantile

Topics: Anticonvulsants; Child; Humans; Intellectual Disability; Lennox Gastaut Syndrome; Levetiracetam; Male; Piracetam; Spasms, Infantile; Status Epilepticus

The Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood, characterized by electro-clinical triad of generalized spike-wave activity, slow (POL) in the electroencephalogram (EEG), multiple types of seizures and development delay. This paper intends to describe the syndrome in a patient with a history of hypoxic-ischaemic encephalopathy and Lennox-Gastaut syndrome, and a good response to treatment with levetiracetam (LEV).. Descriptive study on the development of a 3 year old child with intrauterine asphyxia, multiorgan failure, metabolic acidosis, hypovolemic shock, and seizures with cerebral oedema, who developed a West syndrome, resistant to drug treatment. The semiology of seizures progressively changed to generalized episodes of hypertonia and myoclonus, with slow spike-wave electroencephalographic activity.. With the diagnosis of Lennox-Gastaut syndrome the patient was treated with levetiracetam, showing a substantial improvement in the cognitive sphere, in the control of seizures, and electroencephalographic findings.. Lennox-Gastaut syndrome is one of the most severe epileptic syndromes in paediatric patients. Levetiracetam can help cognitive improvement, and contribute to seizure control in these patients.

Topics: Anticonvulsants; Child, Preschool; Humans; Intellectual Disability; Lennox Gastaut Syndrome; Levetiracetam; Male; Piracetam; Spasms, Infantile

In contrast to drugs established to treat neonatal seizures, levetiracetam shows little neurotoxicity in experimental animal models and has good safety records in adults and children. Here, we present results from a survey on the off-label use of levetiracetam in newborn infants among neonatologists and pediatric neurologists in German university hospitals.

Topics: Anticonvulsants; Drug Utilization; Germany; Health Surveys; Hospitals, University; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Off-Label Use; Piracetam; Spasms, Infantile

An 11-month-old infant with a 5-month history of seizures and a 3-month history of infantile spasms is described. EEG showed epileptic encephalopathy. The infantile spasms were resistant to treatment with clobazam. Following the introduction of levetiracetam, there was clinical cessation of seizures with resolution of seizure activity on the EEG. This is the second report in the literature of effective treatment of infantile spasms with levetiracetam.

Topics: Anticonvulsants; Electroencephalography; Humans; Infant; Levetiracetam; Male; Piracetam; Spasms, Infantile