RESUMEN
OBJECTIVE: Seizures are common in individuals with duplications of chromosome 15q11.2-q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population. METHODS: A detailed electronic survey was conducted through the Dup15q Alliance containing comprehensive questions regarding seizures and their treatments in Dup15q. RESULTS: There were 95 responses from Dup15q families. For the 83 with idic(15), 63% were reported to have seizures, of which 81% had multiple seizure types and 42% had infantile spasms. Other common seizure types were tonic-clonic, atonic, myoclonic, and focal. Only 3 of 12 individuals with int dup(15) had seizures. Broad spectrum antiepileptic drugs (AEDs) were the most effective medications, but carbamazepine and oxcarbazepine were also effective, although typical benzodiazepines were relatively ineffective. There was a 24% response rate (>90% seizure reduction) to the first AED tried. For those with infantile spasms, adrenocorticotropic hormone (ACTH) was more effective than vigabatrin. SIGNIFICANCE: This is the largest study assessing seizures in Duplication 15q syndrome, but because this was a questionnaire-based study with a low return rate, it is susceptible to bias. Seizures are common in idic(15) and typically difficult to control, often presenting with infantile spasms and progressing to a Lennox-Gastaut-type syndrome. Seizures in those with int dup(15) are less common, with a frequency similar to the general autism population. In addition to broad spectrum AED, medications such as carbamazepine and oxcarbazepine are also relatively effective in controlling seizures in this population, suggesting a possible multifocal etiology, which may also explain the high rate of infantile spasms. Our small sample suggests a relative lack of efficacy of vigabatrin and other γ-aminobutyric acid (GABA)ergic medications, such as typical benzodiazepines, which may be attributable to abnormal GABAergic transmission resulting from the duplication of a cluster of GABAß3 receptor genes in the 15q11.2-13 region.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Recolección de Datos/métodos , Convulsiones/tratamiento farmacológico , Convulsiones/genética , Trisomía/genética , Adolescente , Niño , Preescolar , Cromosomas Humanos Par 15/genética , Femenino , Humanos , Masculino , Convulsiones/diagnóstico , Síndrome , Resultado del TratamientoRESUMEN
Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N=93) were classified into groups according to KD+/-CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD+ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD+TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population.
Asunto(s)
Anticonvulsivantes/efectos adversos , Dieta Cetogénica/efectos adversos , Fructosa/análogos & derivados , Isoxazoles/efectos adversos , Urolitiasis/inducido químicamente , Niño , Preescolar , Terapia Combinada/efectos adversos , Epilepsia/dietoterapia , Epilepsia/tratamiento farmacológico , Femenino , Fructosa/efectos adversos , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo , Topiramato , ZonisamidaRESUMEN
Sleep disturbances and epilepsy are common in Angelman syndrome (AS). This study examines seizure variables and sleep in a large AS cohort. Sleep disturbances and epilepsy were assessed in 290 individuals with AS using two questionnaires, including the Behavioral Evaluation of Disorders of Sleep (BEDS). Sensitivity to the sleeping environment, decreased nightly hours of sleep, and a difficulty initiating sleep were significantly correlated with the presence of epilepsy, particularly focal seizures. Use of multiple anticonvulsant drugs was shown to affect sleep. No significant associations were present between molecular subtypes of AS and individual sleep factors. Sleep problems appeared to be associated with epilepsy in individuals with AS, especially with focal and absence seizures and multiple seizure types. Results were consistent with those of prior studies assessing sleep in AS. Severity of epilepsy and use of anticonvulsant drugs may be related to a higher degree of sleep disturbance in this population.
Asunto(s)
Síndrome de Angelman/diagnóstico , Epilepsia/diagnóstico , Trastornos del Sueño-Vigilia/diagnóstico , Adulto , Síndrome de Angelman/epidemiología , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Niño , Comorbilidad , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/epidemiología , Epilepsia/epidemiología , Epilepsia Tipo Ausencia/diagnóstico , Epilepsia Tipo Ausencia/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Sistemas en Línea/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Trastornos del Inicio y del Mantenimiento del Sueño/diagnóstico , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Encuestas y CuestionariosRESUMEN
PURPOSE: Angelman syndrome (AS) commonly presents with epilepsy (>80%). The goal of this study was to examine the natural history and various treatments of epilepsy in AS in a large population. METHODS: A detailed electronic survey containing comprehensive questions regarding epilepsy in AS was conducted through the Angelman Syndrome Foundation. RESULTS: There were responses from 461 family members of individuals with AS, of whom 86% had epilepsy (60% with multiple seizure types), the most common being atonic, generalized tonic-clonic, absence, and complex partial. Partial-onset seizures only were reported in 11% of those with epilepsy. Epilepsy was most common among those with maternal deletions and unknown subtypes, with catastrophic epilepsies present in only these two subtypes. These epilepsies were refractory to medication, with only 15% responding to the first antiepileptic drug (AED). The most commonly prescribed AED were valproic acid and clonazepam, but lamotrigine and levetiracetam appeared to have similar efficacy and tolerability. DISCUSSION: This is the largest study to date assessing epilepsy in AS. Although epilepsy in AS is considered a generalized epilepsy, there was a high prevalence of partial seizures. There are few previous data regarding the use of newer AED in AS, and the results of this study suggest that these newer agents, specifically levetiracetam and lamotrigine, may have efficacy similar to that of valproic acid and clonazepam, and that they appear to have similar or better side-effect profiles. Nonpharmacologic therapies such as dietary therapy and vagus nerve stimulation (VNS) also suggest favorable efficacy and tolerability, although further studies are needed.
Asunto(s)
Síndrome de Angelman/terapia , Anticonvulsivantes/uso terapéutico , Epilepsia/terapia , Adolescente , Adulto , Síndrome de Angelman/tratamiento farmacológico , Síndrome de Angelman/epidemiología , Niño , Preescolar , Clonazepam/uso terapéutico , Comorbilidad , Esquema de Medicación , Resistencia a Medicamentos , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/terapia , Femenino , Humanos , Lactante , Lamotrigina , Levetiracetam , Masculino , Persona de Mediana Edad , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Encuestas y Cuestionarios , Síndrome , Resultado del Tratamiento , Triazinas/uso terapéutico , Estimulación del Nervio Vago/métodos , Ácido Valproico/uso terapéuticoRESUMEN
PURPOSE: To report the efficacy, safety, and tolerability of the low glycemic index treatment (LGIT) in pediatric epilepsy. METHODS: A retrospective chart review was performed on patients initiating the LGIT at the Massachusetts General Hospital between January 2002 and June 2008. Demographic and clinical information including seizure type, baseline seizure frequency, medications, blood chemistries, side effects, and anthropometrics were collected. Initiation of the LGIT was done in an outpatient setting. Patients were educated by a dietitian to restrict foods with high glycemic index and to limit total daily carbohydrates to 40-60 g. Change in seizure frequency was assessed at 1-, 3-, 6-, 9-, and 12-month follow-up intervals. RESULTS: Seventy-six children were included in the study. Eighty-nine percent had intractable epilepsy (>or=3 antiepileptic drugs). A greater than 50% reduction from baseline seizure frequency was observed in 42%, 50%, 54%, 64%, and 66% of the population with follow-up available at 1, 3, 6, 9, and 12 months, respectively. Increased efficacy was correlated with lower serum glucose levels at some time points, but not with beta-hydroxybutyrate (BOHB) changes or ketosis status at any time point. Only three patients reported side effects (transient lethargy). Blood urea nitrogen (BUN) was elevated in approximately one-third of follow-up laboratory studies. No significant changes were seen in body mass index (BMI) or BMI z-score at any follow-up interval. The most cited reason for treatment discontinuation was the restrictiveness of the diet, in 18 patients (24%). CONCLUSION: The LGIT was associated with reduced seizure frequency in a large fraction of patients, with limited side effects.
Asunto(s)
Glucemia/fisiología , Dieta Cetogénica/métodos , Epilepsia/dietoterapia , Índice Glucémico/fisiología , Pediatría , Resultado del Tratamiento , Adolescente , Antropometría/métodos , Niño , Preescolar , Epilepsia/clasificación , Epilepsia/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
The potential cognitive and psychosocial effects of childhood epilepsy have significant implications for a child's self-image and academic achievement. This study focuses on a 10-week karate program for children and adolescents with epilepsy aimed at increasing social confidence, self-concept, and quality of life, as well as reducing parental anxiety. Eleven children (8-16 years old) and their parents participated in this questionnaire study, and complete data were available for nine of these families. Measures consisted of the Piers-Harris Children's Self-Concept Scale, the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire, and the Parental Stress Index. By parental report, significant improvement in memory function and largely positive trends in quality of life on multiple subscales were observed. By child report, intellectual self-esteem and social confidence also improved. Parental stress decreased, although not significantly, suggesting a potential benefit and indicating a role for future interventions targeting family anxiety.
Asunto(s)
Epilepsia/psicología , Epilepsia/rehabilitación , Artes Marciales , Calidad de Vida , Autoimagen , Adolescente , Niño , Femenino , Humanos , Masculino , Relaciones Padres-Hijo , Pediatría , Proyectos Piloto , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
Clinical manifestations were retrospectively assessed in 5 families with tuberous sclerosis complex, including 1 pair of monozygotic twins. Interfamilial variation in tuber count was significantly larger than intrafamilial variation. Severity of epilepsy and cognitive profiles varied both between and within families, particularly between the monozygotic twins, and IQ was inversely related to tuber count. Cutaneous, renal, and cardiac findings did not appear to cluster within families. Although the monozygotic twins displayed similar physical manifestations of tuberous sclerosis complex (renal and cardiac hamartomas), they differed markedly in neurocognitive profiles. Phenotypic variation within these families may be explained largely as a function of the randomness of second-hit events that cause hamartomas in tuberous sclerosis complex or by as-yet-unidentified genetic modifiers. Familial variation in tuberous sclerosis complex phenotype has important implications for genetic counseling.