levetiracetam and Developmental-Disabilities

Dyskinesia of the ADCY5 mutation is a rare movement-onset disorder in childhood. It is characterized by isolated chorea movements or associated with myoclonus and dystonia affecting the limbs, neck and face. The low number of patients and families still does not allow an adequate genotype-phenotype relationship.. The case of a child with movement disorders of early onset is presented in a family with three generations of affected members. An updated review of the casuistry and management of this rare disease is made.. A 6-year-old boy referred for language delay and hyperactivity. After six months of follow-up he begins to show chorea movements of predominantly facial and limb roots, especially when waking up. At one year of follow-up, generalized chorea at rest with orofacial involvement and awkward gait begins to show. His family history includes his mother, grandfather, maternal uncle and cousin, who were diagnosed with Meige's syndrome (oromandibular dystonia and periorbital muscles) with choreiform-like movement disorders without affiliation since childhood. The brain study by MRI showed no alterations. A clinical exome targeting movement disorders was performed that discovered the pathogenic mutation in the ADCY5 gene causing autosomal familial dyskinesia.. The c.1126G>A p.A376T mutation shows a natural history with a non-progressive clinical phenotype in three generations of affected members, with childhood debut and response to guanfacine treatment.. Discinesia asociada a ADCY5 en la infancia: a propósito de una familia y revisión actualizada.. Introducción. La discinesia de la mutación ADCY5 es un raro trastorno del movimiento de inicio en la infancia. Se caracteriza por movimientos coreicos aislados o asociados a mioclonías y distonías que afectan a las extremidades, el cuello y la cara. El escaso número de pacientes y familias no permite aún una adecuada relación genotipo-fenotipo. Objetivos. Presentar el caso de un niño con trastornos del movimiento de inicio precoz en el seno de una familia con tres generaciones de afectados, y realizar una revisión actualizada de la casuística y el tratamiento de esta rara enfermedad. Caso clínico. Varón de 6 años, remitido por retraso del lenguaje e hiperactividad. Tras seis meses de seguimiento, comenzó a presentar movimientos coreicos de predominio facial y de la raíz de los miembros, especialmente al despertar. Al año de seguimiento, se evidenció corea generalizado en reposo con afectación orofacial y torpeza en la marcha. Como antecedentes familiares destacaban su madre, abuelo, tío y prima maternos, que fueron diagnosticados de síndrome de Meige (distonía oromandibular y músculos periorbitarios) con trastornos del movimiento de tipo coreiforme sin filiar desde la infancia. El estudio cerebral por resonancia magnética no presentó alteraciones. Se realizó un exoma clínico dirigido a trastornos del movimiento que descubrió la mutación patógena en el gen ADCY5 causante de la discinesia familiar autosómica. Conclusión. La mutación c.1126G>A p.A376T muestra una historia natural con un fenotipo clínico no progresivo en tres generaciones de afectados, con inicio en la infancia y respuesta al tratamiento con guanfacina.

Topics: Adenylyl Cyclases; Amino Acid Substitution; Attention Deficit Disorder with Hyperactivity; Child; Developmental Disabilities; Drug Resistance; Female; Guanfacine; Humans; Language Development Disorders; Levetiracetam; Male; Meige Syndrome; Movement Disorders; Mutation, Missense; Pedigree; Point Mutation

Epilepsy with myoclonic-atonic seizures (EMAS) is a rare childhood onset epileptic encephalopathy. There is no clear consensus for recommended treatments, and pharmacoresistance is common. To better assess the clinical phenotype, most effective treatment, and determinants of cognitive and seizure outcomes, three major pediatric epilepsy centers combined data, creating the largest cohort of patients with EMAS ever studied to date.. Authors performed a retrospective chart review of patients with EMAS who received care at the authors' institutions.. A total of 166 children were identified. Global developmental delay (>1 domain) was present in 2% of children at onset and 49% during the course of the disease. Afebrile seizures occurred after the age of 2 years in 88%, generalized tonic-clonic seizures in 60%, and drop attack or myoclonic seizures in 30%. At onset, electroencephalography (EEG) found 28% normal, background slowing in 20%, and epileptiform discharges or seizures in 69%. Subsequent EEG found slowing in 62% and discharges or seizures in 90%. Response (>50% seizure reduction) to the first three antiseizure drugs (ASDs) was 26% (levetiracetam, 17%; valproic acid, 31%; other ASDs combined, 26%). Diet therapy was used as a second or third therapy in 19% and ultimately used in 57%; response was 79%, significantly greater than the first three ASDs (P = .005, χ. This large cohort of children with EMAS clarifies areas of variability in practice. Diet therapy is by far the most effective treatment; failure to respond was associated with failure to attain seizure freedom. This therapy should be used early in the treatment in EMAS. This study also identified a bidirectional link between cognitive and seizure outcomes.

Topics: Anticonvulsants; Child; Child, Preschool; Cohort Studies; Developmental Disabilities; Diet, Ketogenic; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Infant; Levetiracetam; Male; Retrospective Studies; Treatment Outcome; Valproic Acid

Infants with brain injury are susceptible to developmental delays. Survivors of neonatal seizures are at risk for developmental delay, epilepsy, and further neurological comorbidities. Despite advances in neonatal critical care, the prevalence of adverse long-term outcomes and seizure recurrence remains unchanged. Our goal is to determine if early treatment of neonatal seizures with phenobarbital or levetiracetam is associated with worse neurodevelopmental outcomes in brain-injured infants.. We conducted a retrospective cohort study of 119 infants admitted between 2013 and 2017 who were at risk for developmental delay and assessed in our clinic. We compared brain injury infants with neonatal seizures to brain injury infants without neonatal seizures using Bayley scores (BSID III) at 9-14 months gestational age. A comparison of Bayley scores between those exposed to phenobarbital and levetiracetam was conducted.. Twenty-two children with neonatal seizures scored lower than 53 children without seizures in all domains with significant values in composite scores for cognitive function (p = 0.003) and language (p = 0.031). We found no difference in scores at 9-14 months between infants exposed to phenobarbital versus levetiracetam.. Our results suggest that in infants with brain injury, the occurrence of neonatal seizures has an adverse effect on neurodevelopmental outcomes. The choice of antiseizure medication may not play a significant role in their outcomes.

Topics: Anticonvulsants; Brain Injuries; Case-Control Studies; Developmental Disabilities; Female; Gestational Age; Humans; Infant; Levetiracetam; Male; Phenobarbital; Retrospective Studies; Seizures

Synaptic vesicle protein 2A (SV2a) is the binding site of the antiepileptic drug levetiracetam and the only known synaptic vesicle target of an epilepsy medication. To date, no pathogenic mutation in SV2A, which is the gene encoding synaptic vesicle glycoprotein 2A, has been identified in humans. We report a homozygous mutation in the SV2A gene in a patient with intractable epilepsy.. We investigated a patient with intractable epilepsy, involuntary movements, microcephaly, and developmental and growth retardation. Both parents were multiply consanguineous and an earlier-born brother of the proband had a similar course and died at 7 months of age. Detailed clinical history, imaging, electroencephalograph and metabolic testing were obtained. Full exome sequencing was performed using genomic DNA isolated from the patient and both parents.. Exome sequencing identified a homozygous arginine to glutamine mutation in amino acid position 383 (R383Q) in exon 5 of the SV2A gene. Both parents were carriers for the R383Q variant, suggesting that R383Q is a recessive mutation. There were no other candidate alterations in the exome that could explain the phenotype in the proband. The amino acid arginine at position 383 of SV2a gene is evolutionally conserved throughout vertebrates. R383Q change is not observed in known healthy cohorts, exome databases, or the Database of Single Nucleotide Polymorphisms. The R383Q mutation is located in the second adenine binding domain in SV2a protein and may alter adenine nucleotides binding to SV2a.. Our report provides the elusive evidence that an SV2A mutation can be a cause of epilepsy in humans. Levetiracetam, which binds to SV2A, was not effective as an antiepileptic medication. The location of the mutation in our patient supports an important role of adenine nucleotides binding in SV2A function.

Topics: Anticonvulsants; Child, Preschool; Developmental Disabilities; Dyskinesias; Epilepsy; Female; Growth Disorders; Humans; Levetiracetam; Membrane Glycoproteins; Microcephaly; Mutation; Nerve Tissue Proteins; Piracetam

We investigated the relationship between behavioral problems, location of electroencephalogram (EEG) paroxysmal abnormalities (PA), and treatment with levetiracetam in children with pervasive developmental disorder (PDD) and epilepsy.. Twelve PDD children with epilepsy were included in the study. All patients had EEG PA (frontal spikes, 8; rolandic, 3; generalized, 1). After a 3-month baseline period, patients were given levetiracetam with an initial dose of 10 mg/kg/day for the first week, followed by increments of 5 mg/kg/day every week. Levetiracetam dosage was then adjusted up to a maximum of 60 mg/kg/day. EEG recordings were performed every 3 months, focusing on PA frequency. We counted the frequency of seizures and EEG PA, and scored instances of panic/aggressive behaviors.. Eight (66.7%) of the 12 patients were considered to be responders to clinical seizures and EEG findings (≥50% reduction in both seizures and PA frequency). Six (75%) of these eight patients were considered to be responders for behavioral problems (≥50% reduction in panic/aggressive behavior). These six patients had frontal EEG paroxysms, whereas the remaining two patients without behavioral responses had rolandic EEG paroxysms. Patients with frontal PA showed a significantly higher correlation between EEG/clinical seizures and behavioral improvements (p < 0.05).. The present data indicated the usefulness of LEV in reducing behavioral problems related to the reduction of seizures and frontal spikes in PDD for some but not all of the patients. Thus, levetiracetam represents an important addition to treatment for PDD children with epilepsy presenting with frontal EEG paroxysms.

Topics: Adolescent; Anticonvulsants; Behavioral Symptoms; Brain Waves; Child; Developmental Disabilities; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Severity of Illness Index

For patients with epilepsy, anti-epileptic medication is generally the first line of treatment, but treating pregnant women with epilepsy can be a challenge. Standard anti-epileptic medications have caused developmental abnormalities, so much effort has been put into developing antiepileptic medications with minimal teratogenic effects. In this experimental study, the new-generation anti-epileptic medication levetiracetam and the standard anti-epileptic medication valproic acid were compared in terms of teratogenicity by studying embryonic development in 360 fertile White-Leghorn chicken eggs (conception day 0). We found that levetiracetam may cause severe developmental abnormalities, and is likely not safe for use in pregnant women. As expected, valproic acid caused more frequent developmental abnormalities than levetiracetam, and the risk increased still further when both drugs were administered in combination. Levetiracetam should be used cautiously in pregnant women with epilepsy.

Topics: Animals; Anticonvulsants; Chick Embryo; Developmental Disabilities; Dose-Response Relationship, Drug; Levetiracetam; Piracetam; Time Factors; Valproic Acid

Topics: Anticonvulsants; Brain; Child; Cognition; Cognition Disorders; Developmental Disabilities; Electroencephalography; Epilepsy; Evoked Potentials; Humans; Levetiracetam; Neuropsychological Tests; Nootropic Agents; Piracetam; Recovery of Function