levetiracetam and Attention-Deficit-Disorder-with-Hyperactivity

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

Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.. To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.. This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.. Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.. The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.. Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).. Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.

Topics: Adolescent; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Incidence; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Topiramate; Valproic Acid

Juvenile myoclonic epilepsy (JME) constitutes about 10% of all epilepsies. Because of executive dysfunction, people with JME may be prone to impulsivity and risk-taking behavior. Our aim was to investigate whether psychosocial issues associated with impulsivity are more prominent in people with JME than in those with other types of genetic generalized epilepsy (GGE). Patients with GGE were recruited retrospectively through the Drammen Hospital records in Buskerud County, Norway, 1999-2013. They were invited to a semi-structured interview, either at the hospital or at home. Ninety-two patients with JME and 45 with other types of GGE were interviewed. Variables were evaluated in terms of their association with JME versus other GGE diagnosis using a logistic regression model. Juvenile myoclonic epilepsy was associated with use of illicit recreational drugs and police charges, although with borderline significance (odds ratio [OR] 3.4, p = 0.087 and OR 4.2, p = 0.095); JME was also associated with being examined for attention-deficit hyperactivity disorder (ADHD) in females (OR 15.5, p = 0.015), a biological parent with challenges like addiction or violent behavior (OR 3.5, p = 0.032), and use of levetiracetam (OR 5.1, p = 0.014). After controlling for group differences, we found psychosocial complications to be associated with JME, potentially influencing the lives of the individuals and their families to a greater extent than the seizures per se. Thus, JME should be considered a disorder of the brain in a broader sense than a condition with seizures only.

Topics: Adolescent; Adult; Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Cross-Sectional Studies; Electroencephalography; Female; Humans; Impulsive Behavior; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Retrospective Studies; Social Behavior; Young Adult

The comorbidity of Attention Deficit Hyperactivity Disorder (ADHD) with sleep disorders has been extensively studied. In particular, Restless Legs Syndrome (RLS) appears to be consistently more frequent in children with ADHD. Several papers also draw attention to the frequent occurrence of epileptic seizures and EEG abnormalities in ADHD children. We performed a preliminary open label study to evaluate the efficacy of Levetiracetam (LEV) to ameliorate the sleep pattern and reduce RLS symptoms in children with a complex comorbidity between Attention Deficit Hyperactivity Disorder (ADHD), RLS and focal interictal epileptic discharges (IEDs) on EEG. We recruited seven children (all males, aged between 5 and 12years) who fulfilled the following criteria: ADHD diagnosis combined subtype; presence of idiopathic RLS; and presence of focal IEDs on EEG. All children were given LEV at a starting dose of approximately 10-20mg/kg/day followed by 10mg/kg/day incrementing at 1-week intervals up to 50-60mg/kg/day given in two separate doses. At a 3 and 6month follow-up, all children showed significant improvement (p<0.05) in global International RLS Rating Scale (IRLS-RS). Parents' reports revealed improved sleep quality with fewer awakenings and restorative sleep in their children. LEV was well tolerated and no major side effects were reported. With an accessory report we observed the reduction of epileptiform EEG activity during sleep. In most patients (6 on 7) the discharges completely disappeared; in the last patient epileptiform EEG activity was significantly reduced. These children may represent a subgroup of ADHD patients in which the hyperactivity and attention difficulties might be aggravated by sleep disturbances and by IEDs. LEV could represent a therapeutic option for these comorbid conditions.

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Comorbidity; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Restless Legs Syndrome; Sleep; Surveys and Questionnaires

Symptoms of attention deficit hyperactivity disorder (ADHD) are more common in children with epilepsy than in the general paediatric population. Epileptiform discharges in EEG may be seen in children with ADHD also in those without seizure disorders. Sleep enhances these discharges which may be suppressed by levetiracetam.. To assess the effect of levetiracetam on focal epileptiform discharges during sleep in children with ADHD.. In this retrospective study a new semi-automatic quantitative method based on the calculation of spike index in 24-h ambulatory EEG recordings was applied. Thirty-five ADHD children, 17 with focal epilepsy, one with generalised epilepsy, and 17 with no seizure disorder were evaluated. Follow-up 24-h EEG recordings were performed after a median time of four months.. Mean spike index was 50 prior to levetiracetam treatment and 21 during treatment. Seventeen children had no focal interictal epileptiform discharges in EEG at follow-up. Five children had a more than 50% reduction in spike index. Thus, a more than 50% reduction in spike index was found in 22/35 children (63%). Out of these an improved behaviour was noticed in 13 children (59%).. This study shows that treatment with levetiracetam reduces interictal epileptiform discharges in children with ADHD. There is a complex relationship between epilepsy, ADHD and epileptiform activity, why it is a need for prospective studies in larger sample sizes, also to ascertain clinical benefits.

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Child; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Sleep Stages; Wakefulness