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ABSTRACT: We report the case of an 18-month-old child with infantile spasms and a hypsarrhythmic electroencephalogram (EEG) pattern associated with a porencephalic cyst. Surgical removal of the cyst and its surrounding tissue was performed following failure of medical therapy. Postoperatively, the patient has béen frée of infantile spasms for 12 months and the EEG has normalized. He has béen maintained on the same preoperative antiepileptic medications. This case suggests that surgical treatment is helpful in selected patients with infantile spasms and focal CNS lesions.
Epilepsia 11/2007; 32(5):668 - 671. · 3.96 Impact Factor
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ABSTRACT: A retrospective review of the safety, tolerability, and efficacy of vagus nerve stimulation (VNS) in 48 patients with intractable partial epilepsy was performed. Side effects were few and mild to moderate. Mean seizure frequency decreased by 26% after 1 year, 30% after 5 years, and 52% after 12 years with VNS treatment.
Neurology 10/2004; 63(6):1124-6. · 8.31 Impact Factor
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ABSTRACT: Fosphenytoin (Cerebyx), is a water soluble prodrug that is rapidly and completely converted to phenytoin. This study reports the injection-site tolerance and safety of intramuscular fosphenytoin (> 10 mg/kg doses) in 60 patients requiring a phenytoin loading dose. Patients received injections at single or multiple sites with volumes ranging from 4 to 30 ml per injection site. The majority of patients had no irritation (erythema, swelling, tenderness, bruising) or complaints of discomfort related to fosphenytoin injection either after injection (95%) or at follow-up (88%). Irritation, when reported, was mild in all cases. Forty of 60 patients (67%) reported transient side effects, primarily involving the central nervous system, such as nystagmus, dizziness or ataxia, which are commonly associated with phenytoin therapy. All patients received prescribed doses; no patient had an injection(s) stopped due to intolerance or side effects. No serious adverse events occurred with intramuscular fosphenytoin. In this study, intramuscular fosphenytoin was demonstrated to be a safe and well tolerated, and in many instances, a preferable alternative to other means of phenytoin loading.
Epilepsy Research 10/1997; 28(3):181-7. · 2.29 Impact Factor
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ABSTRACT: The finding of increased activity of the enzyme extracellular superoxide dismutase in four siblings with progressive myoclonus epilepsy of the Unverricht-Lundborg type (PME-UL) prompted the addition of antioxidants to these patients' treatment regimen. After 6 months treatment with vitamin E, selenium, riboflavin, and zinc, there was some improvement in patient awareness and speech. N-acetylcysteine (NAC) is a sulfhydryl antioxidant that increases cellular glutathione and the activity levels of several antioxidant enzymes and has additional actions that contribute to its demonstrated efficacy in preventing or decreasing damage in models of neuronal toxicity. We treated the affected siblings with 4 to 6 grams a day of NAC in addition to the other antioxidants and magnesium. There has been a marked decrease in myoclonus and some normalization of somatosensory evoked potentials with NAC treatment. The patients were treated with NAC for up to 30 months with continued beneficial effects. NAC may prevent further deterioration in the clinical course of patients with PME-UL and may be indicated in other neurodegenerative conditions where excess free radical activity may contribute to disease progression.
Neurology 12/1996; 47(5):1264-8. · 8.31 Impact Factor
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ABSTRACT: Safety, tolerability, and pharmacokinetics of fosphenytoin sodium, a water-soluble phenytoin prodrug, were investigated after a temporary substitution of intramuscular fosphenytoin for oral phenytoin sodium in 240 epileptic or neurosurgical patients taking oral phenytoin sodium (100-500 mg/d).
Patients were randomly assigned to 1 of 2 parallel groups. During screening and follow-up, patients were maintained on a regimen of oral phenytoin at an individualized dose. During treatment, the phenytoin-treated patients received intramuscular placebo and their prescribed dose of oral phenytoin; the fosphenytoin-treated patients received oral placebo and intramuscular fosphenytoin equimolar to their phenytoin dose.
Both groups had similar types and frequencies of mild to moderate adverse events. Fosphenytoin was as well tolerated as intramuscular placebo at the injection site. Intramuscular fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or greater plasma phenytoin concentrations.
Dosing adjustments are not required when intramuscular fosphenytoin is temporarily substituted or oral phenytoin therapy is resumed. Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible.
Archives of Neurology 09/1996; 53(8):764-8. · 7.58 Impact Factor
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ABSTRACT: Phenobarbital, diazepam, lorazepam, and phenytoin are all currently used for the treatment of acute seizures, including status epilepticus. None of these drugs is considered ideal. Fosphenytoin is a new phenytoin prodrug that fulfills many of the properties of an ideal anticonvulsant drug. The safety, tolerance, and pharmacokinetics of intramuscularly administered fosphenytoin have been evaluated in three clinical trials involving patients requiring loading or maintenance doses of phenytoin. These investigations demonstrated that fosphenytoin is rapidly and completely absorbed after injection into muscle and is quickly converted to produce therapeutic phenytoin plasma concentrations within 30 min of administration. Plasma concentrations of phenytoin achieved with i.m. fosphenytoin exceeded those associated with an equimolar dose of oral phenytoin. i.m. fosphenytoin was well tolerated both locally and systemically. Only mild and transient reactions occurred at the injection site. The most common systemic adverse events reported--somnolence, nystagmus, dizziness, and ataxia--are side effects commonly seen with phenytoin and tended to be mild. Preexisting seizure disorders remained stable. Combination treatment with i.v. diazepam or lorazepam to attain rapid seizure control and i.m. fosphenytoin to maintain the anticonvulsant effect theoretically offers many advantages for control of acute seizures and should be studied.
Neurology 07/1996; 46(6 Suppl 1):S24-8. · 8.31 Impact Factor
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ABSTRACT: We report a patient with Friedreich's disease (FD) who exhibited abnormalities of antioxidant metabolism, including decreased levels of glutathione peroxidase, glutathione reductase, and selenium, and an increased lipid peroxide index. These abnormalities became normal after treatment with N-acetylcysteine, selenium, and low-dose vitamin E therapy. Treatment was associated with a decreased rate of clinical decline. FD is a neurodegenerative disorder that may be related to disturbed antioxidant metabolism; the disorder may be treatable with antioxidant compounds.
Clinical Neuropharmacology 07/1996; 19(3):271-5. · 2.17 Impact Factor
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ABSTRACT: We conducted a randomized double-blind comparison of three doses of the novel antiepileptic drug (AED) topiramate (200, 400, and 600 mg/day) and placebo as adjunctive therapy in patients with refractory partial onset epilepsy receiving one or two other AEDs at therapeutic concentrations. A total of 181 patients completed the 12-week baseline phase and were randomized to double-blind therapy. Median percent reductions from baseline in average monthly seizure rate, the principal efficacy evaluation, were 13% for placebo, 30% for topiramate 200 mg/day, 48% for topiramate 400 mg/day, and 45% for topiramate 600 mg/day. For the seizure rate comparison of active drug to placebo p values were: topiramate 200 mg/day, p = 0.051; topiramate 400 mg/day, p = 0.007; topiramate 600 mg/day, p < 0.001. Percent responders ( > or = 50% reduction in seizure rates) were 18% for placebo, 27% for topiramate 200 mg/day, 47% for topiramate 400 mg/day (p = 0.013), and 46% for topiramate 600 mg/day (p = 0.027). A significant (p = 0.003) reduction in secondarily generalized seizures compared with placebo treatment was also documented with topiramate. Topiramate plasma concentrations were closely related to dosage, and there were no significant interactions between topiramate and other AEDs. The minimal effective dose of topiramate in this study population was approximately 200 mg/day. Mild or moderate CNS symptoms were the primary treatment-emergent adverse events, but treatment-limiting adverse events occurred in only 9% of patients given topiramate compared with 7% given placebo. Results of this initial well-controlled study in patients indicate that topiramate is a very promising new AED.
Neurology 06/1996; 46(6):1684-90. · 8.31 Impact Factor
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Movement Disorders 02/1996; 11(1):106-7. · 4.51 Impact Factor
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ABSTRACT: Vagus nerve stimulation (VNS) was shown to reduce seizure frequency in refractory epilepsy patients in two pilot studies. Based on these results, a multicenter, prospectively randomized, parallel, double-blind study of patients with refractory partial seizures was initiated. After a 12–week baseline period, identical vagus nerve stimulators were implanted and patients randomized to either a high or low 14–week VNS treatment paradigm. The primary objective was to demonstrate that high VNS (therapeutic parameters) was more effective in reducing partial seizure frequency than was low VNS (less or noneffective parameters). Patients continued receiving antiepileptic drugs (AEDs) with plasma concentrations held constant throughout the study. We report results of the first 67 patients to exit the 14-week acute phase. After 14 weeks of VNS, 31 patients receiving high VNS experienced a mean seizure frequency percentage reduction of 30.9%, which was statistically significant as compared with the mean seizure frequency percentage reduction of 11.3% in 36 patients receiving low VNS (p = 0.029, t test; p = 0.036, Wilcoxon rank-sum test). In addition to the significant intra group p-values, mean seizure frequency percentage change reached statistical significance for high VNS (p < 0.001) but not low VNS (p = 0.072) as compared with baseline. Twelve of 31 (38.7%) patients receiving high VNS achieved at least 50% reduction in seizure frequency whereas 7 of 36 (19.4%) patients receiving low VNS experienced at least 50% reduction after 14 weeks. The implant procedure and VNS therapy were well tolerated. Our study confirmed the effectiveness of VNS as treatment for epilepsy patients with refractorypartial seizures.RéSUMé: La stimulation du nerf vague (SNV) reduit la frequence des crises chez les patients presentant une epilepsie refractaire, ceci été montre dans deux études pilotes. A partir de ces résultats, une étude multicentrique, randomisée de fason prospective, parallele, en double-aveugle de patients présentant des crises partielles refractaires, a été mise en place. Après une périodes de base de 12 semaines, des stimulateurs du nerf vague identique ont été implantes et les patients ont été distribues de façon randomisée entre deux paradigmes de 14 semaines de traitement par SNV, haut ou bas. L'objectif primaire etait de demontrer qu'une SNV haute (parametres therapeutiques) était plus efficace dans rédution des crises partielles qu'une stimulation basse (parametres inferieurs ou non efficaces). Les patients ont continue a recevoir un traitement antiepileptique, les taux plasmatiques des medicaments etant maintenus constants tout au long de l'étude. Les auteurs rapportent les resultats obtenus chez les 77 premiers patients qui ont termine la phase aigue de 14 semaines. Après 14 semaines de SNV, 31 patients sous SNV haute, ont perp une réduction de la fréquence moyenne des crises de 30.9%, qui était statistiquement significative en comparaison la réduction moyenne de fréquence des crises de 11.3% chez les 36 patients recevant la SNV basse (p = 0.029 t test: p = 0.036, test Wilcoxon). En plus des valeurs p significatives entre les groupes, pourcentage de modifications de la frequence des crises atteint une signification statistique pour les SNV hautes (p < 0.001) mais pas pour les SNV basses (p = 0.072) par comparaison avec la période de base. Douze des 31 patients sous SNV haute (38.7%) ont obtenu une réduction supérieure ou égale a 50% dans la fréquence des crises, alors que celle des 36 patients recevant la SNV basse (19.4%) ont observi une réduction superieure ou égale a 50% aprts 14 semaines. La procedure d'implantation et le traitement par SNV ont été bien tolerés. Cette étude confirme l'efficacite de la SNV comme traitement chez les patients presentant des crises partielles rebelles.RESUMEN: En dos estudios piloto la estimulación del nervio vago (VNS) ha mostrado la posibilidad de reducir la frecuencia de los ataques parciales en pacientes con epilepsia refractaria a1 tratamiento. Basfindose en estos resultados, los autores iniciaron un estudio multictntrico, prospectivo, randomizado, paralelo y doble ciego en pacientes con ataques parciales refractarios. Tras 12 semanas de period0 basal, se implantaron idhticos estimuladores del nervio vago en pacientes randornizados, para ser sometidos a un paradigma terapCutico con VNS ALTA o BAJA durante 14 semanas. El objetivo fundamental consistió en demostrar que la VNS ALTA (parfimetros terapeuticos) fue más eficaz en la reducción de ataques parciales que la VNS BAJA (parkmetros de menor o ausencia de eficacia). Los pacientes continuaron con sus medicaciones antiepilepticas y niveles plasmiticos rnantenidos constantes durante el estudio. De 67 pacientes, después de 14 semanas de VNS, 31 recibieron VNS ALTA y experimentaron un 30.9% de réduction de la frecuencia de los ataques que fue estadisticamente significativa cuando se compard con el promedio de reducción de ataques (I 1.3%) en 36 enferrnos que recibieron VNS BAJA (p = 0.029, t test; p = 0.036, Wilcoxon test). Ademas de los valores p significativos intra-grupo, el promedio del procentaje de cambios en la frecuencia de ataques alcanzo significado estadistico en las VNS ALTAS (p < 0.001) pero no en las VNS BAJAS (p = 0.072) cuando se compararon con los valores basales. Doce de 31 pacientes (38.7%) que recibieron VNS ALTAS alcanzaron al menos un 50% de reducción de los ataques mientras que 7 de 36 (19.4%) que recibieron VNS BAJAS experimentaron a1 menos un 50% de reduccidn despuCs de 14 semanas. La terapia con VNS fue bien tolerada. Los resultados de este estudio confirman la eficacia de la VNS como tratamiento para los casos de ataques epilCpticos parciales refractarios.ZUSAMMENFASSUNG: In zwei Pilotstudien war gezeigt worden, daβ die Vagusstimulation (VNS) die Frequenz von Partialanfallen bei therapierefraktaren Epilepsiepatienten reduziert. Auf der Basis dieser Ergebnisse wurde eine multizentrische, prospektiv randomisierte, parallele Doppelblindstudie bei Patienten mit therapierefraktaren Partialanfallen begonnen. Nach einer zwolfwochigen Kontrollphase wurden identische Vagusstimulatoren implantiert und die Patienten entweder nach einem “starken” oder nach einem “schwachen” vierzehnwochigen VNS-Behandlungsparadigma randomisiert. Hauptziel wares zu zeigen, daβ eine starke VNS (therapeutische Parameter) effektiver bei der Reduktion von Partialanfallen als eine schwache VNS (geringer oder nicht effektive Parameter) ist. Die Patienten erhielten weiter Antiepileptika, wobei die Plasmakonzentrationen über den Untersuchungsraum hin konstant gehalten wurden. Wir berichten über Ergebnisse der ersten 67 Patienten aus der vierzehnwochigen akuten Phase. Nach 14 Wochen VNS zeigten 31 Patienten mit einer starken VNS eine mittlere Anfällsfrequenzabnahme von 30.9%, das ist statistisch signifikant im Vergleich zur mittleren Anfdlsfrequenzreduktion von 11.3% bie 36 Patienten mit schwacher VNS (p = 0.029, t test; p = 0.036, WilcoxonRangsummentest). Zusatzlich zu diesen signifikanten p-Werten erreichte die mittlere Anderung der Anfällsfrequenz im Vergleich zum Ausgangsbefund für die starke VNS-Stimulation Signifikanzniveau (p < 0.001), jedoch nicht bei der schwachen VNS (p = 0.072). 12 von 31 (38.7%) Patienten mit starker VNS erzielten eine mindestens 50-prozentige Abnahme der Anfällsfrequenz, wahrend 7 von 36 (19.4%) Patienten mit schwacher VNS eine mindestens 50-prozentige Reduktion nach 14 Wochen erzielten. Implantation und VNS-Therapie wurden gut vertragen. Unsere Untersuchung bestatigt, dalj VNS eine wirkungsvolle Behandlung für Epilepsiepatienten mit thrapierefraktaren Partialanfallen ist.
Epilepsia 04/1994; 35(3):616 - 626. · 3.96 Impact Factor
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ABSTRACT: We treated 14 patients with medically refractory partial seizures by stimulation of the vagus nerve in two single-blind pilot studies. Patients received stimulation through an implantable, programmable NeuroCybernetic Prosthesis, consisting of a pulse generator and a lead-electrode assembly. The mean reduction in seizure frequency after 14 to 35 months of vagal stimulation was 46.6%. Of the 14 patients, five (35.7%) had a 50% or greater reduction in seizure frequency. Two patients, one of whom had had 10 to 100 seizures per day before stimulation, have been seizure-free for over 1 year. Adverse events were primarily limited to initial hoarseness and a tingling sensation at the electrode site in the neck when the device was activated. Most patients tolerated the device and stimulation well. There were no permanent adverse events. Some cases of medically refractory partial seizures are improved by vagal stimulation.
Neurology 08/1993; 43(7):1338-45. · 8.31 Impact Factor
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ABSTRACT: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters EEGs under certain stimulus parameters. We report EEG effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and we believed that analysis of electrophysiologic effects of vagal nerve stimulation would help elucidate the brain areas affected. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Stimulation at various stimulus frequencies and amplitudes had no noticeable effect on EEG activity whether the patient was under general anesthesia, awake, or asleep, but vagus nerve stimulation may interrupt ongoing ictal EEG activity.
Epilepsia 10/1992; 33(6):1013 - 1020. · 3.96 Impact Factor
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ABSTRACT: Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve not only can alter the EEG but evokes activity in specific brain areas. We report effects of electrical stimulation of the vagus nerve in 9 patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The left vagus nerve in the neck was stimulated with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus nerve evoked potential showed some unusual properties: a scalp negative component occurred with a latency of 12 ms, very high amplitude (60 μV), and widespread scalp distribution. Field distribution studies indicated that this potential was myogenic in origin and generated in the region of the stimulating electrodes in the neck area. Chemically induced muscle paralysis confirmed this observation. Bipolar scalp recording showed several small-amplitude topographically distinct potentials occurring in 30 ms. No effect, either acute or chronic, could be detected on pattern-reversal evoked potentials, auditory brainstem evoked potentials, auditory 40-Hz potentials, or cognitive evoked potentials.
Epilepsia 10/1992; 33(6):1021 - 1028. · 3.96 Impact Factor
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ABSTRACT: Chronic administration of the experimental antiepileptic drug vigabatrin (gamma-vinyl GABA) to animals has been shown to cause dose-dependent neuropathological changes characterized by a microvacuolation in specific white matter tracts. This finding has led to some concern as to whether similar pathologic changes might occur in patients taking this medication. Here we report on analysis of tissue specimens taken during neurosurgery from three patients undergoing chronic vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For comparison, similar specimens were taken from three other patients not taking vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from each subject were prepared in an identical manner and examined with light and electron microscopy. All specimens were examined in a blinded fashion. There was some minor nonspecific myelinic splitting seen in both controls and vigabatrin-treated patients but there was no evidence for any drug-induced lesions similar to that seen in experimental animals.
Epilepsy Research 10/1992; 12(3):261-5. · 2.29 Impact Factor
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ABSTRACT: An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
Brain Research 07/1992; 583(1-2):300-3. · 2.73 Impact Factor
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ABSTRACT: We followed 66 patients with refractory complex partial seizures and a favorable initial response to vigabatrin for 5 to 72 (median, 43) months. Thirty-seven patients discontinued vigabatrin for the following reasons: benefit-to-risk evaluation, 8; seizure breakthrough, 6; adverse events, 6; seizure breakthrough and adverse events, 5; moved or lost, 4; no longer eligible for study, 2; non-drug-related death, 2; narcotic abuse, 1; and patient request, three. There were no clinically significant abnormalities in laboratory studies including SMA 12, complete blood count, ECG, EEG, and visual evoked response testing, and no toxicity other than reversible, dose-dependent side effects. Based on this and other long-term data, clinical trials of vigabatrin have resumed in the United States and Canada.
Neurology 04/1991; 41(3):363-4. · 8.31 Impact Factor
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ABSTRACT: Chronic intermittent stimulation of the vagus nerve is a new method currently being tested for the treatment of medically intractable complex partial seizures (CPS). We have studied the effects of vagal stimulation in nine patients with CPS for 4-16 months to determine its safety and efficacy. With the patients maintained on constant dosages of antiepileptic drugs, we recorded the electroencephalogram and electrocardiogram, and performed clinical laboratory tests and gastric analysis over a 6-week baseline period. The neurocybernetic prosthesis (NCP) was then implanted and connected to two spiral electrodes wound around the left vagus nerve. After a 4-week placebo period, vagal stimulation was started. Stimulation parameters were increased stepwise at monthly intervals until patients were being stimulated for 30-second periods at 20-50 Hz with 1-2 mA of current at 250-500 microseconds pulses. A second 4-week placebo period was added 3 months after the implantation. Thereafter, vagal stimulation was resumed and self-stimulation with magnetic activation was allowed for a 1-minute period at the onset of an aura. Six patients had a significant reduction in the frequency, intensity, or duration of seizures. All patients tolerated the implantation and stimulation well and none reported pain, discomfort, or important changes in their daily activities, sleep habits, eating, swallowing, or breathing. There were no remarkable changes in blood pressure or heart rate.
Pacing and Clinical Electrophysiology 02/1991; 14(1):108-15. · 1.35 Impact Factor
