RESUMEN
OBJECTIVE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as adjunctive therapy in children (4 to 16 years) with treatment-resistant partial-onset seizures. METHODS: This multicenter, randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 14-week double-blind treatment period. During the treatment period, patients received either placebo or LEV add-on therapy and were up-titrated to a target dose of 60 mg/kg/day. RESULTS: One hundred ninety-eight patients (intent-to-treat population) provided evaluable data. The reduction in partial-onset seizure frequency per week for LEV adjunctive therapy over placebo adjunctive therapy was significant (26.8%; p = 0.0002; 95% CI 14.0% to 37.6%). A 50% or greater reduction of partial seizure frequency per week was attained in 44.6% of the LEV group (45/101 patients), compared with 19.6% (19/97 patients) receiving placebo (p = 0.0002). Seven (6.9%) LEV-treated patients were seizure-free during the entire double-blind treatment period, compared with one (1.0%) placebo-treated patient. One or more adverse events were reported by 88.1% of LEV-treated patients and 91.8% of placebo patients. The most common treatment-emergent adverse events were somnolence, accidental injury, vomiting, anorexia, hostility, nervousness, rhinitis, cough, and pharyngitis. A similar number of patients in each group required a dose reduction or withdrew from the study as a result of an adverse event. CONCLUSION: Levetiracetam adjunctive therapy administered at 60 mg/kg/day is efficacious and well tolerated in children with treatment-resistant partial seizures.
Asunto(s)
Epilepsias Parciales/diagnóstico , Epilepsias Parciales/tratamiento farmacológico , Piracetam/análogos & derivados , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Levetiracetam , Masculino , Pediatría/métodos , Piracetam/administración & dosificación , Piracetam/efectos adversos , Efecto Placebo , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Infantile spasms are a rare but devastating pediatric epilepsy that, outside the United States, is often treated with vigabatrin. The authors evaluated the efficacy and safety of vigabatrin in children with recent-onset infantile spasms. METHODS: This 2-week, randomized, single-masked, multicenter study with a 3- year, open-label, dose-ranging follow-up study included patients who were younger than 2 years of age, had a diagnosed duration of infantile spasms of no more than 3 months, and had not previously been treated with adrenocorticotropic hormone, prednisone, or valproic acid. Patients were randomly assigned to receive low-dose (18-36 mg/kg/day) or high-dose (100-148 mg/kg/day) vigabatrin. Treatment responders were those who were free of infantile spasm for 7 consecutive days beginning within the first 14 days of vigabatrin therapy. Time to response to therapy was evaluated during the first 3 months, and safety was evaluated for the entire study period. RESULTS: Overall, 32 of 142 patients who were able to be evaluated for efficacy were treatment responders (8/75 receiving low-dose vigabatrin vs 24/67 receiving high doses, p < 0.001). Response increased dramatically after approximately 2 weeks of vigabatrin therapy and continued to increase over the 3-month follow-up period. Time to response was shorter in those receiving high-dose versus low-dose vigabatrin (p = 0.04) and in those with tuberous sclerosis versus other etiologies (p < 0.001). Vigabatrin was well tolerated and safe; only nine patients discontinued therapy because of adverse events. CONCLUSIONS: These results confirm previous reports of the efficacy and safety of vigabatrin in patients with infantile spasms, particularly among those with spasms secondary to tuberous sclerosis.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Espasmos Infantiles/tratamiento farmacológico , Vigabatrin/administración & dosificación , Anticonvulsivantes/efectos adversos , Preescolar , Femenino , Humanos , Lactante , Masculino , Método Simple Ciego , Resultado del Tratamiento , Vigabatrin/efectos adversosRESUMEN
OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology develops practice parameters as strategies for patient management based on analysis of evidence. For this practice parameter, the authors reviewed available evidence on evaluation of the first nonfebrile seizure in children in order to make practice recommendations based on this available evidence. METHODS: Multiple searches revealed relevant literature and each article was reviewed, abstracted, and classified. Recommendations were based on a three-tiered scheme of classification of the evidence. RESULTS: Routine EEG as part of the diagnostic evaluation was recommended; other studies such as laboratory evaluations and neuroimaging studies were recommended as based on specific clinical circumstances. CONCLUSIONS: Further studies are needed using large, well-characterized samples and standardized data collection instruments. Collection of data regarding appropriate timing of evaluations would be important.
Asunto(s)
Epilepsia/diagnóstico , Adolescente , Adulto , Preescolar , Humanos , Lactante , Recién Nacido , Convulsiones Febriles/diagnóstico , Factores de TiempoRESUMEN
PURPOSE: Children with partial-onset seizures, with or without secondary generalization, participating in a double-blind, placebo-controlled trial of topiramate (TPM) as adjunctive therapy were eligible to participate in an open-label, long-term extension study. METHODS: A total of 83 children (mean age, 9 years) continued long-term open-label TPM therapy in which the dosages of TPM and concomitant antiepileptic drugs (AEDs) were adjusted according to clinical response (mean TPM dosage, 9 mg/kg/day). RESULTS: Seizure frequency over the last 3 months of therapy was reduced > or =50% in 57% of children; 14% of children were seizure-free > or =6 months at the last visit. During treatment periods up to 2 1/2 years (mean, 15 months), 6% of children discontinued because of treatment-emergent adverse events; 13% discontinued because of inadequate seizure control. CONCLUSIONS: From these findings, TPM is well tolerated and provides long-term seizure control in children with partial-onset seizures.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Fructosa/análogos & derivados , Adolescente , Factores de Edad , Niño , Preescolar , Método Doble Ciego , Esquema de Medicación , Epilepsias Parciales/diagnóstico , Fructosa/uso terapéutico , Humanos , Placebos , Índice de Severidad de la Enfermedad , Topiramato , Resultado del TratamientoRESUMEN
PURPOSE: Children with recurrent or progressive central nervous system (CNS) tumors have an unfavorable prognosis. Based on Pediatric Oncology Group (POG) institutional pilot data, low-dose oral methotrexate (MTX) was studied. METHODS: Eight dosages of MTX 7.5 mg/m2 every 6 hours were administered on a weekly schedule for as long as 18 months. Patients in six different brain tumor strata were accrued. RESULTS: The response rates (complete or partial responses) were as follows: astrocytoma 2 of 10, malignant glioma 1 of 19, medulloblastoma 0 of 18, brainstem tumor 0 of 12, ependymoma 1 of 7, and miscellaneous histologic types 0 of 12. The main toxicities, mucositis, myelosuppression, and hepatic transaminase elevation were considered tolerable. CONCLUSION: Low-dose oral MTX showed no significant activity against malignant glioma, medulloblastoma, brainstem tumors, and miscellaneous histologic types. Indeterminate but low response rates were observed in children with astrocytoma and ependymoma. This regimen will not be recommended for front-line therapy.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Metotrexato/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Encefálicas/patología , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Metotrexato/efectos adversos , Recurrencia Local de Neoplasia/patologíaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of topiramate 6 mg/kg/day in children (age 2 to 16 years) as adjunctive therapy for uncontrolled partial-onset seizures with or without secondarily generalized seizures in a multicenter, randomized, double-blind, placebo-controlled trial. METHODS: Patients with at least six partial-onset seizures during the 8-week baseline phase were treated with either topiramate (n = 41) or placebo (n = 45) for 16 weeks. RESULTS: Topiramate-treated patients had a greater median percent reduction from baseline in average monthly partial-onset seizure rate than placebo-treated patients (33.1% versus 10.5%, p = 0.034), a greater proportion of treatment responders (i.e., patients with a > or = 50% seizure rate reduction; 16 of 41 [39%] versus 9 of 45 [20%], p = 0.080), and patients with a > or = 75% seizure rate reduction (7 of 41 [17%] versus 1 of 45 [2%], p = 0.019), and better parental global evaluations of improvement in seizure severity (p = 0.019). Emotional lability (12% versus 4%), fatigue (15% versus 7%), difficulty with concentration or attention (12% versus 2%), and forgetfulness/impaired memory (7% versus 0%) were more frequent among topiramate-treated than placebo-treated patients. Most treatment-emergent adverse events were mild or moderate in severity. No topiramate-treated patients discontinued the study due to adverse events. CONCLUSIONS: Topiramate was safe and effective in the treatment of partial-onset seizures in children.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Fructosa/análogos & derivados , Adolescente , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Método Doble Ciego , Femenino , Fructosa/administración & dosificación , Fructosa/efectos adversos , Fructosa/uso terapéutico , Humanos , Lactante , Masculino , TopiramatoRESUMEN
This report concerns 37 children and teenagers operated upon for intractable seizures between 1990 and 1994. Follow-up is at least 3 years. Fourteen children underwent pure temporal lobe resections; 71% are seizure free, and 93% have a better than 90% decrease in seizure frequency. The presence of a lesion on magnetic resonance imaging, the side of the lesion, or the presence of abnormal pathology had no influence on the result of resection. 28% of the children who had extratemporal resections are seizure free, and 83% have a greater than 90% decrease in seizure frequency. There was a trend to better results in those with a lesion on magnetic resonance imaging. In the small group with temporal plus extratemporal foci, the results were poor with only 60% showing a greater than 90% reduction in seizure frequency.
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Epilepsias Parciales/cirugía , Adolescente , Niño , Preescolar , Electroencefalografía , Epilepsias Parciales/diagnóstico , Epilepsias Parciales/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
An uncommon but well-recognized occurrence in patients with Dandy-Walker malformation is sudden unexpected death. The mechanism of demise has not been established. We report three patients with Dandy-Walker malformation that experienced sudden unexpected death without uncal or tonsillar herniation, the mechanism usually proposed for demise in such situations. Our findings suggest the possibility of vascular compromise as the cause of the sudden unexpected death in these patients. Early and effective relief of the pressure in the posterior fossa may prevent the occurrence of this catastrophic complication.
Asunto(s)
Encéfalo/patología , Síndrome de Dandy-Walker/patología , Muerte Súbita/patología , Tronco Encefálico/patología , Cerebelo/patología , Ventrículos Cerebrales/patología , Niño , Preescolar , Femenino , Humanos , Presión Intracraneal/fisiología , MasculinoRESUMEN
It has previously been reported in a single-institution trial that progression-free survival of children with medulloblastoma treated with radiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cisplatin, and vincristine chemotherapy during and after radiotherapy was better than the outcome in children treated with radiotherapy alone. To better characterize long-term outcome and duration of disease control, this treatment approach was used for 10 years and expanded to three institutions. Sixty-three children with posterior fossa medulloblastomas were treated with craniospinal local-boost radiotherapy and adjuvant chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligible for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic disease, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factors who received reduced-dose craniospinal radiotherapy (2400 cGy) were also eligible for entry into the study. Sixty-three of 66 eligible patients (95%) were entered and placed on this treatment regimen. Forty-two patients had brainstem involvement, 15 had metastatic disease at the time of diagnosis, and 19 had received a subtotal resection. Progression-free survival for the entire group at 5 years is 85% +/- 6%. Three children have succumbed to a second malignancy, and overall 5-year event-free survival is 83% +/- 6%. Progression-free survival was not adversely affected by younger age at diagnosis, brainstem involvement, or subtotal resection. Five-year actuarial progression-free survival for patients who received reduced-dose radiotherapy was similar to that for patients receiving conventional-dose radiotherapy. Patients with metastatic disease at the time of diagnosis had a 5-year progression-free survival rate of 67% +/- 15%, as compared to 90% +/- 6% for those patients with localized disease at the time of diagnosis (p = 0.037). The authors conclude that overall progression-free survival remains excellent for children with posterior fossa medulloblastomas treated with this drug regimen. Chemotherapy has a definite role in the management of children with medulloblastoma. Further studies are indicated to define which subpopulations of children with medulloblastoma benefit from chemotherapy and what regimens are optimum in increasing disease control and, possibly, in reducing the amount of radiotherapy required.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/radioterapia , Cisplatino/administración & dosificación , Lomustina/administración & dosificación , Meduloblastoma/tratamiento farmacológico , Meduloblastoma/radioterapia , Vincristina/administración & dosificación , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Cerebelosas/cirugía , Quimioterapia Adyuvante , Niño , Preescolar , Estudios de Cohortes , Terapia Combinada , Irradiación Craneana , Supervivencia sin Enfermedad , Humanos , Lactante , Meduloblastoma/cirugía , Invasividad Neoplásica , Siembra Neoplásica , Neoplasia Residual/patología , Dosificación Radioterapéutica , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Neoplasias Encefálicas/cirugía , Ganglioglioma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Encéfalo/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Terapia Combinada , Craneotomía , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/patología , Fibrosarcoma/cirugía , Estudios de Seguimiento , Ganglioglioma/tratamiento farmacológico , Ganglioglioma/patología , Proteína Ácida Fibrilar de la Glía/análisis , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/cirugía , Gliosarcoma/tratamiento farmacológico , Gliosarcoma/patología , Gliosarcoma/cirugía , Humanos , Lactante , Masculino , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/cirugía , Meningioma/tratamiento farmacológico , Meningioma/patología , Meningioma/cirugía , Mitosis/efectos de los fármacos , Mitosis/fisiología , Estadificación de NeoplasiasRESUMEN
A 2-year-old boy with microcephaly, developmental delay, and minimal anomalies was found to have an extra submetacentric chromosome equivalent to 18pter----q12. Review of the phenotypes produced by various triplicated 18 regions supports the hypothesis that no one chromosome 18 region is sufficient to produce the phenotype of trisomy 18. The mild phenotype of trisomy 18p, the variable phenotype of trisomy 18pter----q12, and the discontinuous phenotype of triplication for band 18q12 alone emphasizes that the contribution of triplicated loci to the phenotype is neither additive nor invariant.