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1.
AJNR Am J Neuroradiol ; 42(9): 1695-1701, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244128

RESUMO

BACKGROUND AND PURPOSE: There is a paucity of data regarding the incidence of structural brain lesions in children with new-onset unprovoked seizures. Our aim was to determine the frequencies and types of epileptogenic lesions detected on a dedicated epilepsy protocol MR imaging according to age group, the presence of developmental delay, and the number and types of seizures. MATERIALS AND METHODS: Consecutive children between 6 months and 18 years of age with new-onset unprovoked seizures were included. The frequencies and types of epileptogenic lesions were determined and then stratified according to sex, age groups, the presence of developmental delay, and the number and types of seizures at presentation. Multivariate analysis was used to identify variables significantly associated with the presence of epileptogenic lesions. RESULTS: One thousand children were included. An epileptogenic lesion was identified in 26%, with malformations of cortical development being the most common lesion (32%), followed by hypoxic-ischemic injury (20%) and vascular etiologies (16%). Univariate analysis showed a significant increase in the frequency of epileptogenic lesions with decreasing age, the presence of developmental delay, and the number and types of seizures at presentation. The presence of developmental delay and seizure type at presentation remained significant in a multivariate analysis. CONCLUSIONS: We documented a relatively high rate of epileptogenic lesions in children with new-onset seizures, with the presence of developmental delay and specific seizure types being associated with a higher likelihood of detecting an epileptogenic lesion on neuroimaging. This study fulfills the requirements of the study design recommended by the Practice Committee of the American Academy of Neurology, and we hope that our results will assist the relevant societies and committees in formulating neuroimaging guidelines for children with new-onset seizures.


Assuntos
Imageamento por Ressonância Magnética , Neuroimagem , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Convulsões/diagnóstico por imagem , Convulsões/epidemiologia
2.
J Chem Phys ; 153(23): 234303, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33353333

RESUMO

Metal-ligand cluster ions are structurally characterized by means of gas-phase infrared multiple photon dissociation spectroscopy. The mass-selected complexes consist of one or two metal cations M3+ (M = Al, Fe, or Ru) and two to five anionic bidentate acetylacetonate ligands. Experimental IR spectra are compared with different density functional theory calculations, namely, PBE/TZVP, B3LYP/6-31G*, and M06/6-31+G**. Frequency analysis was also performed at different levels, namely, scaled static harmonic and unscaled static anharmonic, or with ab initio molecular dynamics simulations at the PBE/TZVP level. All methods lead to simulated spectra that fit rather well with experimental data, and the spectral red shifts of several main bands, in the 1200 cm-1-1800 cm-1 range, are sensitive to the strength of the metal-ligand interaction and to the spin state of the ion. Due to the rigidity of those complexes, first principles molecular dynamics calculations provide spectra similar to that produced by static calculations that are already able to catch the main spectral signatures using harmonic calculations at the B3LYP/6-31G* level.

3.
J Thromb Haemost ; 8(1): 54-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19817994

RESUMO

BACKGROUND: A high incidence of thrombotic events in thalassemia intermedia (TI) patients led to the identification of a hypercoagulable state. Brain involvement has not been widely studied in TI, although limited reports confirm a low incidence of overt stroke and high incidence of silent brain infarcts. PATIENTS/METHODS: This was a prospective study conducted on 30 adult, splenectomized TI patients. Patients were screened for absence of neurological signs or symptoms, and stroke-related risk factors. Patient charts were reviewed for demographics, duration since splenectomy, and any history of transfusion therapy. Blood samples were obtained for complete blood counts and serum ferritin. Direct determination of liver iron concentration (LIC) was performed by R2 magnetic resonance imaging (MRI). Brain MRI was performed on all patients, looking for ischemic lesions and/or atrophy. RESULTS: The mean age of patients was 32.1 +/- 11 years (range, 18-54 years), with a male to female ratio of 13:17. Eighteen patients (60%) had evidence of one or more white matter lesions (WMLs) on brain MRI, all involving the subcortical white matter. Fourteen patients had evidence of multiple WMLs, with a mean of 5 +/- 10 lesions (range, 2 to > 40 lesions). The vast majority of patients (94%) had small (< 0.5 cm) to medium (0.5-1.5 cm) WMLs, with only one patient showing evidence of a large (> 1.5 cm) WML. Eleven patients (37%) had mild cerebral atrophy. On multivariate analysis only age and transfusion history were independently and significantly associated with the occurrence of zero, single or multiple WMLs. CONCLUSION: WMLs and brain atrophy are a common finding in adult, splenectomized, TI patients. Increasing age and transfusion naivety are associated with a higher incidence and multiplicity of lesions.


Assuntos
Isquemia Encefálica/etiologia , Encéfalo/patologia , Imagem de Difusão por Ressonância Magnética , Esplenectomia , Talassemia/complicações , Talassemia/cirurgia , Adolescente , Adulto , Fatores Etários , Atrofia , Transfusão de Sangue , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/patologia , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Líbano/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Talassemia/epidemiologia , Talassemia/patologia , Adulto Jovem
4.
Lupus ; 18(9): 845-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19578111

RESUMO

Familial Mediterranean fever (FMF) was recently associated with a hypercoagulable state. However, clinically overt thrombosis remains a rare event limited to patients with other predisposing factors. We herein present a child with FMF who experienced a stroke. An extensive thrombophilia work-up revealed multiple inherited and acquired risk factors. In areas with high prevalence of prothrombotic mutations and in children who are products of consanguineous marriages, early screening for concurrent thrombotic risk factors is warranted; as this may help design an optimal management plan and prevent unfavourable outcomes.


Assuntos
Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/genética , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Adolescente , Consanguinidade , Fator V/genética , Feminino , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação/genética , Fatores de Risco
5.
Acta Neurol Scand ; 113(6): 395-404, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16674606

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of oxcarbazepine in patients with diabetic neuropathy in a multicenter, double-blind, placebo-controlled, dose-ranging 16-week study. METHODS: A total of 347 patients were randomized to oxcarbazepine 600 mg/day (n = 83), 1,200 mg/day (n = 87), 1,800 mg/day (n = 88), or placebo (n = 89). The primary efficacy variable was change in mean visual analog scale (VAS) score from baseline to the last week of the study. RESULTS: No difference between any oxcarbazepine group and the placebo group was noted for the primary efficacy variable. Both the 1,200- and 1,800-mg/day groups showed a trend toward statistical significance (P = 0.101, P = 0.096, respectively). Statistically significant differences were found between the oxcarbazepine 1,200-mg/day (P = 0.038) and 1,800-mg/day (P = 0.005) groups and placebo in the overall mean weekly VAS scores for the entire double-blind treatment phase. CONCLUSIONS: Although the primary efficacy variable did not reach statistical significance, patients taking oxcarbazepine 1,200 and 1,800 mg/day showed improvements in VAS scores compared with placebo. Oxcarbazepine may provide clinically meaningful pain relief in patients with painful diabetic neuropathy.


Assuntos
Carbamazepina/análogos & derivados , Neuropatias Diabéticas/tratamento farmacológico , Dor/tratamento farmacológico , Adulto , Idoso , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Carbamazepina/administração & dosagem , Carbamazepina/efeitos adversos , Tontura/induzido quimicamente , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Oxcarbazepina , Dor/etiologia , Medição da Dor/efeitos dos fármacos , Cooperação do Paciente , Efeito Placebo , Resultado do Tratamento
6.
Neurology ; 64(3): 475-80, 2005 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-15699378

RESUMO

OBJECTIVE: To evaluate the efficacy, tolerability, and safety of two pregabalin regimens administered as adjunctive therapy to that of placebo in patients with medically refractory partial epilepsy. METHODS: A multicenter, double-blind, randomized, parallel-group, placebo-controlled trial was performed. Following a prospective 8-week baseline phase, patients were randomized to 12 weeks of double-blind treatment with placebo or pregabalin 600 mg/day administered twice daily (BID) or three times daily (TID). Primary efficacy was measured as change in seizure frequency from baseline of either pregabalin regimen compared with placebo. Secondary efficacy comparisons included the proportion of patients experiencing > or =50% reduction in seizure frequency (responder rate) and median percentage change from baseline in seizure frequency. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluation. Efficacy and safety analyses were performed on the intent-to-treat (ITT) population. RESULTS: Pregabalin treatment resulted in seizure frequency reductions: 53% for pregabalin TID (p < or = 0.0001) and 44% for pregabalin BID (p < or = 0.0001) compared with a 1% increase for placebo. Responder rates were 49% for pregabalin TID and 43% for pregabalin BID compared with 9% for placebo (p < or = 0.001). Both pregabalin regimens were similar in efficacy and tolerability. The most common AEs were dizziness, somnolence, and ataxia. CONCLUSIONS: Pregabalin administered at 600 mg/day is safe, generally well tolerated, and efficacious as adjunctive therapy for the treatment of patients with partial seizures, with or without secondary generalizations. This dose can be administered on a twice daily or three times daily schedule with similar efficacy and tolerability results.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Ácido gama-Aminobutírico/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Ataxia/induzido quimicamente , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacocinética , Bloqueadores dos Canais de Cálcio/uso terapêutico , Tontura/induzido quimicamente , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pregabalina , Estudos Prospectivos , Resultado do Tratamento , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/efeitos adversos , Ácido gama-Aminobutírico/farmacocinética , Ácido gama-Aminobutírico/uso terapêutico
7.
Neurology ; 62(8): 1252-60, 2004 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-15111659

RESUMO

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.


Assuntos
Aminas , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos , Epilepsia/tratamento farmacológico , Frutose/análogos & derivados , Ácido gama-Aminobutírico , Acetatos/efeitos adversos , Acetatos/farmacocinética , Acetatos/uso terapêutico , Doença Aguda , Adolescente , Adulto , Anticonvulsivantes/farmacocinética , Carbamazepina/efeitos adversos , Carbamazepina/análogos & derivados , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Criança , Ensaios Clínicos Controlados como Assunto/estatística & dados numéricos , Interações Medicamentosas , Medicina Baseada em Evidências/estatística & dados numéricos , Frutose/efeitos adversos , Frutose/farmacocinética , Frutose/uso terapêutico , Gabapentina , Humanos , Lamotrigina , Oxcarbazepina , Topiramato , Resultado do Tratamento , Triazinas/efeitos adversos , Triazinas/farmacocinética , Triazinas/uso terapêutico
8.
Neurology ; 62(8): 1261-73, 2004 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-15111660

RESUMO

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.


Assuntos
Aminas , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Frutose/análogos & derivados , Ácido gama-Aminobutírico , Acetatos/efeitos adversos , Acetatos/uso terapêutico , Adulto , Carbamazepina/efeitos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Criança , Ensaios Clínicos como Assunto/estatística & dados numéricos , Resistência a Medicamentos , Medicina Baseada em Evidências/estatística & dados numéricos , Frutose/efeitos adversos , Frutose/uso terapêutico , Gabapentina , Humanos , Isoxazóis/efeitos adversos , Isoxazóis/uso terapêutico , Lamotrigina , Levetiracetam , Ácidos Nipecóticos/efeitos adversos , Ácidos Nipecóticos/uso terapêutico , Oxcarbazepina , Piracetam/efeitos adversos , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Tiagabina , Topiramato , Resultado do Tratamento , Triazinas/efeitos adversos , Triazinas/uso terapêutico , Zonisamida
9.
Neurology ; 57(5): 864-71, 2001 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-11552018

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of oxcarbazepine (OXC) as monotherapy for patients with uncontrolled partial seizures. METHODS: A multicenter, double-blind, randomized, parallel-group, dose-controlled monotherapy trial compared OXC at 2400 mg/day with OXC at 300 mg/day in patients with uncontrolled partial-onset seizures previously receiving carbamazepine (CBZ) monotherapy. During a 28-day open-label conversion phase, patients were tapered off CBZ and titrated to OXC 2400 mg/day. After a 56-day open-label baseline phase on OXC 2400 mg/day, patients entered a 126-day double-blind treatment phase in which they were randomized to continue OXC at 2400 mg/day or were down titrated over 6 weeks to OXC at 300 mg/day. Patients met the efficacy endpoint by completing the double-blind treatment phase or by meeting one of four predefined exit criteria. The primary efficacy variable was time to meeting one of the exit criteria. The secondary efficacy variable was the percentage of patients meeting one of the exit criteria in each of the two treatment groups. RESULTS: Of the 143 patients enrolled, 96 were randomized in the double-blind treatment phase. Time to meeting an exit criterion was significantly in favor of the OXC 2400 mg/day group (p = 0.0001). The median time to meeting an exit criterion was 68 days for the OXC 2400 mg/day Group and 28 days for the OXC 300 mg/day Group. In addition, the percentage of patients meeting one of the exit criteria was significantly lower for the OXC 2400 mg/day Group (p = 0.0001). Overall, OXC was well tolerated with the most common adverse events consisting of fatigue, nausea, ataxia, and headache. CONCLUSION: This trial demonstrated that OXC at 2400 mg/day is well tolerated and efficacious when administered as monotherapy in patients with uncontrolled partial onset seizures.


Assuntos
Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticonvulsivantes/sangue , Carbamazepina/análogos & derivados , Carbamazepina/sangue , Criança , Método Duplo-Cego , Epilepsias Parciais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxcarbazepina , Resultado do Tratamento
10.
Epilepsia ; 42(12): 1563-8, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11879367

RESUMO

PURPOSE: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes. METHODS: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification. RESULTS: Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases. CONCLUSIONS: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.


Assuntos
Epilepsia/diagnóstico , Adolescente , Adulto , Fatores Etários , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Pré-Escolar , Eletroencefalografia/estatística & dados numéricos , Epilepsias Parciais/classificação , Epilepsias Parciais/diagnóstico , Epilepsia/classificação , Epilepsia do Lobo Frontal/classificação , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia Generalizada/classificação , Epilepsia Generalizada/diagnóstico , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Tomografia Computadorizada por Raios X/estatística & dados numéricos
12.
Epilepsy Behav ; 2(6): 616-617, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12609409
13.
Pharmacotherapy ; 20(8 Pt 2): 152S-158S, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10937814

RESUMO

Oxcarbazepine is approved as monotherapy and adjunctive therapy for partial seizures with and without secondarily generalized seizures in adults and as adjunctive therapy for partial-onset seizures in children aged 4-16 years. The clinical development of oxcarbazepine is different from the newer antiepileptic drugs (AEDs) in the extent and concordance of results across clinical trials. The safety and efficacy of oxcarbazepine was evaluated in adjunctive therapy trials, in comparative monotherapy trials with classic AEDs in adults and children with newly diagnosed epilepsy, in monotherapy therapeutic failure design trials in patients with refractory partial seizures, and in trigeminal neuralgia and affective disorder. The results of oxcarbazepine in treating epilepsy are discussed.


Assuntos
Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Carbamazepina/análogos & derivados , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Método Duplo-Cego , Humanos , Oxcarbazepina , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Neurology ; 54(12): 2245-51, 2000 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-10881247

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Criança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Epilepsias Parciais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxcarbazepina , Modelos de Riscos Proporcionais , Sódio/sangue , Resultado do Tratamento
15.
Clin Neurophysiol ; 110(10): 1717-25, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10574287

RESUMO

OBJECTIVE: Previous coherence studies of human intracranial electroencephalograms (EEGs) can be faulted on two methodological issues: (1) coherence estimates in a majority were formed from a very small number of independent sample spectra, and (2) the statistical significance of coherence estimates was either not reported or was poorly evaluated. Coherence estimator performance may be poor when a small number of independent sample spectra are employed, and the coupling of poor estimation and statistical testing can result in inaccuracy in the measurement of coherence. The performance characteristics of the coherence estimator and statistical testing of coherence estimates are described in this manuscript. METHODS: The bias, variance, probability density functions, and confidence intervals of the estimate of magnitude squared coherence (MSC); and power analysis for the test of zero MSC were developed from the exact analytic form of the probability density function of the estimate of MSC for Gaussian random processes. The coherence of a single epoch of background EEG, recorded from a patient with intractable seizures, was evaluated with different parameter values to aid in the exposition of the concepts developed here. RESULTS: The statistical characteristics of WOSA coherence estimates are a function of a single estimator parameter, the number of independent sample spectra employed in the estimation. Bias and variance are high, confidence intervals may be large, and the probability of Type II errors is high if a small number of independent sample spectra are employed. A considerable improvement in measurement accuracy is possible with careful selection of estimator parameter values. CONCLUSIONS: Coherence measurement accuracy can be improved over previous applications by attention to estimator performance and accurate statistical testing of coherence estimates.


Assuntos
Eletroencefalografia/métodos , Eletroencefalografia/normas , Teoria de Sistemas , Adulto , Intervalos de Confiança , Epilepsia Parcial Complexa/diagnóstico , Epilepsia Parcial Complexa/fisiopatologia , Lateralidade Funcional , Humanos , Masculino , Distribuição Normal , Probabilidade , Desempenho Psicomotor/fisiologia , Reprodutibilidade dos Testes
16.
Epilepsia ; 40 Suppl 6: S13-6; discussion S73-4, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10530677

RESUMO

The efficacy and safety of gabapentin as monotherapy for treatment of partial onset seizures were evaluated in three large multicenter, double-blind, parallel-group, dose-controlled trials. In the first trial, 275 outpatients with refractory partial epilepsy maintained on stable doses of one or two antiepileptic drugs (AEDs) were switched to gabapentin (GBP) monotherapy at 600 mg, 1200 mg, or 2400 mg daily. Patients were required to exit the 26-week double-blind phase of the study if they experienced worsening of seizure frequency. With respect to time to exit, there was no statistically significant difference among the three groups; only 3% of patients withdrew from the trial because of adverse events. In the second study, 82 hospitalized patients with medically refractory epilepsy were tapered off baseline AEDs and randomly assigned to GBP monotherapy at 300 mg/day or 3600 mg/day. Patients remained in the trial for a maximum of 8 days but had to exit the trial if they experienced one or more exit events. Time to exit was significantly longer in patients in the 3600-mg group (151 h) compared with those in the 300-mg group (85 h) (p = 0.0001). None of the patients withdrew from the trial because of side effects. In the third study, 292 patients with newly diagnosed partial seizures were randomized to GBP 300, 900, or 1800 mg/day or to carbamazepine (CBZ) 600 mg/day. Patients remained in the trial for up to 6 months or until they experienced an exit event. Mean time to exit was significantly longer for patients who received GBP 900 mg/day (p = 0.02) or 1800 mg/day (p = 0.04) compared with those who received 300 mg/day. The completion rate for the CBZ group (37%) was similar to that of the GBP 900-mg (39%) and 1800-mg (38%) groups. Patients receiving CBZ had a higher withdrawal rate because of adverse events compared with the GBP 900-mg and 1800-mg groups. The results of these trials provide good evidence of the efficacy and safety of GBP as monotherapy for the treatment of partial-onset seizures.


Assuntos
Acetatos/uso terapêutico , Aminas , Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos , Epilepsias Parciais/tratamento farmacológico , Ácido gama-Aminobutírico , Acetatos/efeitos adversos , Assistência Ambulatorial , Anticonvulsivantes/efeitos adversos , Carbamazepina/uso terapêutico , Ensaios Clínicos Controlados como Assunto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Gabapentina , Hospitalização , Humanos , Estudos Multicêntricos como Assunto , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Epilepsia ; 40 Suppl 6: S51-6; discussion S73-4, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10530683

RESUMO

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural gamma-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.


Assuntos
Acetatos/uso terapêutico , Aminas , Analgésicos/uso terapêutico , Ácidos Cicloexanocarboxílicos , Herpes Zoster/complicações , Neuralgia/tratamento farmacológico , Ácido gama-Aminobutírico , Administração Tópica , Fatores Etários , Idoso , Assistência Ambulatorial , Anticonvulsivantes/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Capsaicina/uso terapêutico , Carbamazepina/uso terapêutico , Ensaios Clínicos como Assunto , Estudos Cross-Over , Método Duplo-Cego , Esquema de Medicação , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Neuralgia/epidemiologia , Neuralgia/etiologia , Dor/tratamento farmacológico , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Epilepsia ; 40(8): 1100-2, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10448822

RESUMO

PURPOSE: To examine the outcome of inpatient diagnostic closed circuit TV-EEG (CCTV-EEG) monitoring in a consecutive series of elderly patients admitted to an adult epilepsy-monitoring unit (EMU) over a continuous 6-year period. METHODS: Retrospective review of all admissions to a university hospital adult EMU. Those older than 60 years were identified. Patients who were monitored for status epilepticus were excluded. Data on duration of events, frequency of events, physical examination, medications, preadmission EEG, brain imaging, length of stay, and interictal and ictal EEG were obtained. RESULTS: Of the 18 patients admitted for monitoring only, mean age was 69.5 years (range, 60-90 years). Mean length of stay was 4.3 days (range, 2-9 days). Five patients had complex partial seizures recorded. Three patients, all treated with anti-epileptic drugs (AEDs), had no spells recorded, and no additional diagnostic information was gained from the admission. The other 10 patients, eight of whom had been treated with AEDs, were symptomatic during their admission, leading to a variety of neurologic but not epileptic, psychiatric, or other medical disorders, and allowing tapering of AEDs. CONCLUSIONS: In elderly patients with suspected epilepsy, CCTV-EEG is a very useful diagnostic tool. In this series of 18, 10 patients were diagnosed with potentially treatable medical illnesses not responsive to AEDs.


Assuntos
Eletroencefalografia/métodos , Epilepsia/diagnóstico , Hospitalização , Monitorização Fisiológica , Televisão , Adulto , Fatores Etários , Idoso , Anticonvulsivantes/uso terapêutico , Diagnóstico Diferencial , Epilepsia/tratamento farmacológico , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
JAMA ; 280(21): 1831-6, 1998 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-9846777

RESUMO

CONTEXT: Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. DESIGN: Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. SETTING: Outpatient clinics at 20 sites. PATIENTS: The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale. INTERVENTION: Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. MAIN OUTCOME MEASURES: The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results. RESULTS: Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06). CONCLUSION: Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.


Assuntos
Acetatos/uso terapêutico , Aminas , Analgésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos , Neuropatias Diabéticas/complicações , Dor/tratamento farmacológico , Dor/etiologia , Ácido gama-Aminobutírico , Neuropatias Diabéticas/tratamento farmacológico , Método Duplo-Cego , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida
20.
Electroencephalogr Clin Neurophysiol ; 106(4): 369-73, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9741765

RESUMO

OBJECTIVE: To examine the frequency of interictal epileptiform activity (IEA) in elderly patients with epilepsy. DESIGN AND METHODS: From a consecutive 13,905 EEGs recorded over 5 years at a university hospital EEG laboratory, 558 studies were performed on outpatients aged 60 years or more. Medical record review identified 125 patients in whom a confident clinical diagnosis of epilepsy was made by a board-certified neurologist. The EEG findings in these patients were reviewed. The effects of various variables on the likelihood of detecting IEA were calculated using Fisher's test and chi-square analysis. RESULTS: IEA were present on the first EEG in 35% of 55 patients (mean age 65 years) with pre-existing epilepsy, and 26% of 70 patients (mean age 70 years) with seizure onset after 60 years. There were no significant differences in the frequency of IEA in patients with late onset epilepsy in the 7th or in the 8th decades of life. Most IEA were focal. Activation procedures added little additional information. Patients with more than one seizure per month were significantly more likely to have IEA (P = 0.016). There were no major differences in likelihood of IEA detection depending on the underlying cause of the seizures. CONCLUSIONS: The frequency of IEA in elderly patients with epilepsy is substantially lower than that reported in epileptic populations as a whole. This low rate of IEA in routine EEG studies must be recognized when considering the diagnosis of an epileptic syndrome for episodic events happening in the elderly.


Assuntos
Eletroencefalografia , Epilepsia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Epilepsias Parciais/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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