Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures.

PURPOSE: To evaluate the efficacy and tolerability of adjunctive levetiracetam in very young children (aged 1 month to <4 years) with partial-onset seizures inadequately controlled with one or two antiepileptic drugs. METHODS: This multicenter, double-blind, randomized, placebo-controlled study consisted of a 48-h inpatient baseline video-EEG (electroencephalography) and a 5-day inpatient treatment period (1-day up-titration; 48-h evaluation video-EEG in the last 2 days). Children who experienced at least two partial-onset seizures during the 48-h baseline video-EEG were randomized to either levetiracetam [40 mg/kg/day (age 1 to <6 months); 50 mg/kg/day (age >or=6 months to <4 years] or placebo. RESULTS: Of 175 patients screened, 116 patients were randomized [60 levetiracetam; 56 placebo; intent-to-treat (ITT) population], and 111 completed the study. The responder rate in average daily partial-onset seizures frequency (48-h video-EEG monitoring; primary efficacy variable) was 43.1% for levetiracetam [modified ITT (mITT) = 58] versus 19.6% for placebo (mITT = 51; p=0.013), with odds ratio for response 3.11 [95% confidence interval (CI), 1.22-8.26]. The median percent reduction from baseline in average daily partial-onset seizure frequency was 43.6% for levetiracetam and 7.1% for placebo with a median difference between treatment groups of 39.2% (95% CI, 17.5-62.2; p < 0.001). In general, levetiracetam was well tolerated. Treatment-emergent adverse events were reported by 55.0% levetiracetam- and 44.6% placebo-treated patients (ITT population). The most frequently reported adverse events were somnolence (13.3% levetiracetam, 1.8% placebo) and irritability (11.7% levetiracetam, 0% placebo). DISCUSSION: Adjunctive levetiracetam is an efficacious and well-tolerated treatment for partial-onset seizures in infants and young children.

Prospective Open-Label, Single-Arm, Multicenter, Safety, Tolerability, and Pharmacokinetic Studies of Intravenous Levetiracetam in Children With Epilepsy.

Levetiracetam given via intravenous administration has been shown to be an effective alternative in adults with epilepsy when oral administration is not feasible. This study was a prospective single-arm, multicenter study to assess tolerability, safety, and pharmacokinetics of intravenous levetiracetam in children with epilepsy. Children with epilepsy ages 1 month to 16 years requiring intravenous levetiracetam were enrolled. Assessments included vital signs, electrocardiogram, hematology, chemistry, plasma concentrations of antiepileptic medications, weight, physical/neurological examinations, and pharmacokinetics. A total of 52 patients were enrolled. Mild to moderate treatment-emergent adverse events occurred in 63%, the most frequent being pyrexia and dry mouth. Most other treatment-emergent adverse events were considered unrelated to intravenous levetiracetam administration. Therefore, intravenous levetiracetam in the acute setting was overall well tolerated in children 1 month to 16 years.

A long-term open-label extension study assessing cognition and behavior, tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4 to 16 years with partial-onset seizures.

The objective of this study was to assess cognition and behavior in children (4-16 years; n = 103) with partial-onset seizures using the Leiter-R International Performance Scale and Achenbach Child Behavior Checklist. The study was a multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD] change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome scores improved from baseline at weeks 24 and 48 (total problems mean [SD] change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well tolerated (most frequently reported central nervous system-related treatment-emergent adverse events: headache [24.3%], aggression [7.8%], irritability [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse events. Levetiracetam provided good and sustained seizure control (median percentage reduction from baseline in partial-onset seizure frequency/wk during maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all seizure types for ≥40 weeks. In children, adjunctive levetiracetam was associated with long-term stability in cognitive functioning and improvement in emotional/behavioral functioning over time.

Adjunctive levetiracetam in patients aged 1 month to <4 years with partial-onset seizures: subpopulation analysis of a prospective, open-label extension study of up to 48 weeks.

BACKGROUND: In a recent double-blind, placebo-controlled study, adjunctive levetiracetam (LEV) was reported to be effective and well tolerated during 5-day treatment in patients aged 1 month to <4 years with partial-onset seizures. A study was planned to fulfill the regulatory requirement to evaluate the long-term safety of LEV as adjunctive therapy for partial-onset seizures in pediatric patients. OBJECTIVE: This study evaluated the long-term effectiveness and tolerability of adjunctive LEV in infants and young children with partial-onset seizures. METHODS: This was a prospective, open-label, outpatient, multicenter study (N01148; ClinicalTrials.gov identifier NCT00152516) conducted as an extension of a previously published study (N01009; NCT00175890). Patients were enrolled from 3 sources, as follows: (1) patients who had completed study N01009; (2) patients who had failed screening for entry into study N01009 but fulfilled the eligibility criteria for entry into this study; and (3) patients who were directly enrolled. The study consisted of a 2- to 4-week retrospective baseline period (and a 3- to 10-day prospective baseline period for directly enrolled patients), a 2- to 8-week uptitration/conversion period, and a maintenance period. Eligible patients were required to have epilepsy with partial-onset seizures, treated with a stable regimen of 1 or 2 antiepileptic drugs. Patients received adjunctive LEV, 20 to 80 mg/kg/d, for up to 48 weeks (total study duration). The primary variable for effectiveness was the percentage reduction from baseline in the weekly frequency of partial-onset seizures, as recorded in patients' diaries. Data for effectiveness were also analyzed by age strata (1 month to <1 year, 1 to <2 years, and 2 to <4 years). Neuropsychological assessment was conducted with the Bayley Scales of Infant Development, Second Edition (BSID-II). All analyses were performed on observed data, and the last-observation-carried-forward approach was not used. The intent-to-treat (ITT) population was defined as all patients who took at least one dose of LEV during the study. Treatment-emergent adverse events (TEAEs) were assessed by observation, spontaneous reporting, standard questions, review of diary cards, and neuropsychologists' clinical reports. Additional measures included physical and neurologic examinations, vital signs, ECGs, routine blood chemistry, and routine hematology assessments. RESULTS: The study included 152 patients in the ITT population. In total, 51.3% (78/152) of the patients were male, and mean (SD) age was 23.5 (12.4) months. The mean LEV maintenance dose was 56.1 (16.2) mg/kg/d, and the median (Q1-Q3) treatment duration was 287.8 (209.0-295.5) days. Ninety-seven patients (63.8%) completed the study. The BSID-II subpopulation included 51 patients. During maintenance, the overall median (Q1-Q3) percentage reduction from baseline in the weekly frequency of partial-onset seizures was 56.0% (-10.9% to 92.8%), which was sustained over time and appeared comparable across the age strata (1 month to <1 year, n = 25, 50.9%; 1 to <2 years, n = 48, 58.0%; and 2 to <4 years, n = 59, 55.0%). The overall responder rate (ie, ≥50% reduction from baseline in weekly partial-onset seizures) was 53.8% (71/132), was maintained over time, and was consistent across the age strata (1 month to <1 year, 52.0%; 1 to <2 years, 56.3%; and 2 to <4 years, 52.5%). Mean BSID-II raw scores for psychomotor development and behavioral functioning remained static, whereas mental development appeared to improve over time, although this was not tested statistically. At least one TEAE was reported in 143 patients (94.1%). The most frequently reported TEAEs were pyrexia (60/152; 39.5%), upper respiratory tract infection (42/152; 27.6%), and vomiting (28/152; 18.4%). The most common TEAEs affecting the central nervous system were convulsion (25/152; 16.4%), irritability (19/152; 12.5%), and somnolence (16/152; 10.5%). Most TEAEs (77.0%) were mild or moderate in intensity. CONCLUSION: Adjunctive LEV treatment for up to 48 weeks was associated with effective and sustained seizure control and had an acceptable tolerability profile in this small, selected population of infants and young children aged 1 month to <4 years with partial-onset seizures.

Sindrome de Guillain-Barre / Guillain-Barre syndrome

Teniendo en cuenta que el Sindrome de Guillain-Barre no es infrecuente en nuestro medio, analizamos el cuadro clinico haciendo un analisis del LCR, la presencia de antecedentes o no y su tratamiento. Estudiamos 50 pacientes con diagnostico de Sindrome de Guillain-Barre en un total de 5601 hospitalizaciones en el FINC entre el 1o de Noviembre de 1973 y 31 de Diciembre de 1979. La frecuencia en pacientes hospitalizados fue de 0.89%. Hubo predominio en el sexo masculino 3,1:1 con una mayor incidencia en la tercera decada. 48 pacientes presentaron el cuadro clinico caracteristico y 2 un sindrome de Miller Fisher. En una tercera parte de los pacientes se encontro el antecedente infeccioso previo. El electromiograma es concluyente a partir de la segunda semana de iniciada la enfermedad. Despues de 15 dias el LCR mostro siempre un aumento significativo de las proteinas sin el correspondiente aumento de las celulas. Sin embargo, no existe relacion entre el nivel de las proteinas y la severidad, forma de iniciacion o de progresion de la enfermedad y el descenlace del sindrome.

Sifilis del sistema nervioso / Nervous system syphilis

La sifilis y sus consecuencias en el sistema nervioso central, han vuelto a ser un reto para el neurologo clinico, como consecuencia del resurgimiento de esta entidad en la ultima decada. Se presentan 15 pacientes con diagnostico de neurosifilis, manejadas por el Servicio de Neurologia del Hospital de San Jose, de Bogota, estudiadas en los ultimos tres anos. Se evidencio predominio masculino, siendo las manifestaciones neuro-oftalmologicas las mas frecuentes. El VDRL fue positivo en 85.7% y el FTA-ABS, en el 100%, en el LCR. El 60% de los pacientes presento examen citoquimico del LCR anormal. 14 pacientes fueron tratados con penicilina G cristalina, 24 millones de u. por via endovenosa por 15 a 21 dias. Se hace una revision historica y bibliografica de la entidad.