Biomedical subjects

Eric H Kossoff

Publications and source records attributed to Eric H Kossoff.

28 records · Page 2Linked to original sources

PubMed2004

Effect of an external responsive neurostimulator on seizures and electrographic discharges during subdural electrode monitoring.

PURPOSE: Approved neural-stimulation therapies for epilepsy use prolonged intermittent stimulation paradigms with no ability to respond automatically to seizures. METHODS: A responsive neurostimulator that can automatically analyze electrocortical potentials, detect electrographic seizures, and rapidly deliver targeted electrical stimuli to suppress them was evaluated in an open multicenter trial in 50 patients, 40 of whom received responsive cortical stimulation via subdural electrodes implanted for epilepsy surgery evaluations. RESULTS: Four patients, ages 15 to 28 years, monitored at three institutions, with clinical and electrographic response to neurostimulation, are described. Electrographic seizures were altered and suppressed in these patients during trials of neurostimulation lasting < or =68 h, with no major side effects. In one patient, stimulation appeared also to improve the baseline EEG. CONCLUSIONS: Responsive cortical neurostimulation may be a safe and effective treatment for partial epilepsy. This information was derived from a small group of patients in an observation study. A double-blind, controlled Food and Drug Administration (FDA)-approved study of a permanently implanted responsive neurostimulation system to treat medically refractory partial seizures is under way.

Adolescent↗

PubMed2003

Efficacy of the Atkins diet as therapy for intractable epilepsy.

The ketogenic diet is effective for treating seizures in children with epilepsy. The Atkins diet can also induce a ketotic state, but has fewer protein and caloric restrictions, and has been used safely by millions of people worldwide for weight reduction. Six patients, aged 7 to 52 years, were started on the Atkins diet for the treatment of intractable focal and multifocal epilepsy. Five patients maintained moderate to large ketosis for periods of 6 weeks to 24 months; three patients had seizure reduction and were able to reduce antiepileptic medications. This provides preliminary evidence that the Atkins diet may have a role as therapy for patients with medically resistant epilepsy.

Adolescent↗

PubMed2003

Landau-Kleffner syndrome responsive to levetiracetam.

A 5-year-old girl with Landau-Kleffner syndrome is discussed. The child began having seizures at age 4 associated with language deterioration despite anticonvulsant therapy. With levetiracetam monotherapy to a dose of 60 mg/kg/day and discontinuation of carbamazepine and valproic acid, her language has improved and seizures are controlled. Levetiracetam should be considered as therapy for Landau-Kleffner syndrome.

Anticonvulsants↗

PubMed2003

The ketogenic diet: adolescents can do it, too.

PURPOSE: To determine both the efficacy of and compliance with the ketogenic diet in the adolescent population. METHODS: A retrospective study of 45 patients, aged 12-19 years, consecutively enrolled in a ketogenic diet program from 1994 to 2002, was performed. Thirty-seven patients were from The Johns Hopkins Medical Institutions; eight were from The University of Texas at Houston. Charts were reviewed, and patients were contacted by telephone. RESULTS: Six months after diet initiation, 28 (62%) of 45 remained on the ketogenic diet, with six (21%) of 28 having 50-90% seizure reduction, and eight (29%) of 28 having >90%. At 12 months, 20 (44%) of 45 remained on the diet, with seven (35%) of 20 having 50-90% seizure reduction and six (30%) of 20 achieving >90% efficacy. Only 22% discontinued the diet for perceived restrictiveness. The mean diet duration was 1.2 years. Patients with multiple seizure types did best, whereas gender, prior seizure frequency, diet ratio, and age did not influence outcome. Patients dependent on parents for daily care were more likely to remain on the diet at 6 months, but had less efficacy. Weight loss (60%) and menstrual dysfunction (45% of female subjects) were the most commonly reported side effects. CONCLUSIONS: The ketogenic diet is as well tolerated and efficacious for adolescents with epilepsy as for the general childhood population.

Adolescent↗

PubMed2003

Encephalofacial angiomatosis sparing the occipital lobe and without facial nevus: on the spectrum of Sturge-Weber syndrome variants?

We report two cases of leptomeningeal angiomatosis in atypical frontoparietotemporal locations without an associated facial port-wine stain. Evidence of a leptomeningeal angioma was found in each when they were evaluated for headaches and seizures. The diagnosis of a leptomeningeal angioma was suggested by calcifications noted on computed tomographic scan of the head and confirmed with contrast-enhanced magnetic resonance images of the brain. We hypothesize that given the lack of occipital involvement with the angioma, and therefore the noncontiguous nature of this lesion with the developing upper facial ectoderm, the failure to develop a facial angioma would be expected. We found that the useof an anticonvulsant along with a migraine prophylactic medication appeared to have the greatest efficacy in these two cases, whereas anticonvulsants alone were less helpful. This diagnosis should be considered in any child presenting with seizures or complicated migraines and intracranial calcifications.

Adolescent↗

PubMed2002

Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide.

BACKGROUND: Epilepsy affects 80% of patients with Sturge-Weber syndrome; the majority of seizures begin before the age of 1. When seizures are intractable to medications and unihemispheric, hemispherectomy is often advised. OBJECTIVE: To examine the natural history of patients who underwent hemispherectomy and identify the outcomes in terms of seizure reduction, cognition, and motor deficits. METHODS: A questionnaire was mailed to the parents of patients identified by the Sturge-Weber Foundation as having had a hemispherectomy between 1979 and 2001. Forty-six percent (32/70) of the parents responded. RESULTS: The mean age at onset of seizures was 4 months, and the median age at surgery was 1.2 years. Children had failed to respond to 3.7 anticonvulsants prior to surgery and averaged 387 seizures/month. Forty-seven percent had complications (e.g., hemorrhage and hypertension) in the perioperative period; however, 81% are currently seizure-free, with 53% off anticonvulsants. Hemispherectomy type (anatomic versus functional versus hemidecortication) did not influence outcome. Age at onset of seizures did not predict seizure freedom; however, an older age at hemispherectomy was positively correlated. Postoperative hemiparesis was not more severe than before surgery. Cognitive outcome was not related to the age at operation, side of operation, or seizure freedom. CONCLUSIONS: Children undergoing hemispherectomy presented at a young age and had frequent seizures for approximately 1 year but are now mostly seizure-free. Age at surgery did not have an adverse effect on either seizure or cognitive outcomes.

Adolescent↗

PubMed2002

The intracerebral administration of phenytoin using controlled-release polymers reduces experimental seizures in rats.

PURPOSE: An alternative strategy for the treatment of intractable seizures may be to administer anticonvulsants directly into the brain near the site of a seizure focus using controlled-release polymers. We describe the pharmacokinetics of a phenytoin-ethylene-vinyl acetate (EVAc) controlled-release polymer and report the reduction of seizures in a cobalt-induced rat model of epilepsy with the intracerebral delivery of phenytoin using surgically implanted polymers. METHODS: In the pharmacokinetics study, the drug release rate of 50%-loaded phenytoin-EVAc polymers (n=3) was determined in vitro over 15 weeks initially and then several months later (over a 2-week period after 1 year of in vivo release). In the efficacy study, 85 rats underwent implantation of skull-mounted cortical electrodes for electrocorticography (ECoG) and then underwent application of cobalt chloride to the cerebral cortex for the induction of seizures. Rats in the treatment group (n=9) underwent surgical implantation of phenytoin-EVAc polymers and rats in the control group (n=10) underwent implantation of empty EVAc polymers. In the morbidity study, the potential histologic pathology of the intracerebral delivery of increasing doses of phenytoin from the polymer (10, 20, 30, and 50% loading) was assessed. RESULTS: Phenytoin was released in vitro from EVAc polymers in a controlled fashion with an initial release of 0.20% of the total loaded dose per week and a continued release of 0.70% of the total loaded dose per week after 365 days of implantation in the brain. The intracerebral controlled-release of phenytoin resulted in a statistically significant reduction in seizure activity in the treatment group as evidenced by lower Racine scores. The four groups of rats (n=5 per group) that underwent intracerebral implantation of 10, 20, 30, or 50%-loaded phenytoin-EVAc polymers displayed expected average weight gain and normal behavior over 365 days. One rat in the 50% group, however, died 354 days after polymer implantation for undetermined reasons. CONCLUSIONS: The intracerebral delivery of phenytoin using an EVAc polymer, which will release this drug for a calculated period of 3.5 years, resulted in a significant reduction in seizures in a rat model of cobalt-induced epilepsy by both behavioral and ECoG criteria. In rats, the long-term interstitial delivery of phenytoin in the brain was not associated with any deleterious effects.

Animals↗

PubMed2002

Kidney stones, carbonic anhydrase inhibitors, and the ketogenic diet.

PURPOSE: Because carbonic anhydrase inhibitors and the ketogenic diet are each known risk factors for kidney stones, simultaneous use of these therapies has been discouraged. The objective of this study was to establish the prevalence of nephrolithiasis in children in this combination-therapy population. METHODS: Since 1996, 301 children have been started on the ketogenic diet at our institution. A retrospective cohort study of renal calculi in ketogenic diet patients was performed to evaluate the increased risk with combined use of a carbonic anhydrase inhibitor. RESULTS: In 15 (6.7%) of 221 children on the ketogenic diet without the use of carbonic anhydrase inhibitors, stones developed. In five (6.3%) of the 80 children on the diet in combination with topiramate or zonisamide, stones developed. There was no difference between these two groups (p = 0.82). No child was treated with either acetazolamide or more than one carbonic anhydrase inhibitor simultaneously. Prior ketogenic diet duration was shorter (10.4 vs. 22.4 months; p = 0.03), and more children had either a family history of renal stones or significant urologic abnormalities (80 vs. 27%; p = 0.04) in the combination-therapy group. CONCLUSIONS: The combined use of carbonic anhydrase inhibitors and the ketogenic diet does not increase the risk of kidney stones. We recommend that all patients treated with combination therapy should be treated with increased hydration. Urine alkalinization should be considered for children with previous renal abnormalities, family histories of kidney stones, hematuria, or elevated urine calcium-to-creatinine ratios. If renal stones are found, we advocate discontinuation of the carbonic anhydrase inhibitor.

Carbonic Anhydrase Inhibitors↗

PubMed2002

Neonatal hypocalcemic seizures: case report and literature review.

Seizures during the neonatal period have a broad differential diagnosis, many with a specific treatment and prognosis. In the case reported, a combination of dietary and endocrinologic abnormalities resulted in hypocalcemic seizures, which continued despite aggressive correction of serum ionized calcium levels. Serial electroencephalograms (EEG) performed during the hospitalization were markedly abnormal, and treatment with anticonvulsant drugs was considered given the persistence of seizures despite normalization of serum calcium levels. After 4 days of intravenous calcium administration, the seizure activity resolved, and the patient returned to his normal baseline level of functioning. This case highlights the clinical course of neonatal hypocalcemic seizures, EEG findings in several cases, and possible mechanisms for both hypocalcemic precipitation of seizures and anticonvulsant ineffectiveness.

Calcium Gluconate↗

PubMed2002

Efficacy of the ketogenic diet for infantile spasms.

OBJECTIVE: The objective of this study was to determine whether the ketogenic diet is safe, well-tolerated, and efficacious in the treatment of infantile spasms. METHODS: During a 4-year period, 23 children with infantile spasms, aged 5 months to 2 years, were started on the ketogenic diet; 9 (39%) had symptomatic infantile spasms, and 16 (70%) had hypsarrhythmia. Children had an average prediet exposure to 3.3 anticonvulsants. Two children were enrolled before any medication had been tried. Seizure reduction was analyzed retrospectively, using parent reports and electroencephalograms (EEGs) when available. RESULTS: At 3, 6, 9, and 12 months, 38%, 39%, 53%, and 46%, respectively, of all patients currently on the diet were >90% improved (3 were seizure-free at 12 months); 67%, 72%, 93%, and 100% were >50% improved. Fifty-six percent remained on the diet at 12 months, 46% of whom were >90% improved and 100% were >50%. Fifty percent of those with hypsarrhythmia and follow-up EEGs had EEG improvement. Fifty-seven percent had their medications reduced or discontinued by 12 months. Fifty-seven percent had improvement in development, which was correlated with seizure control. Independent factors that predicted improvement included age younger than 1 year and previous exposure to 3 or fewer anticonvulsants. No child has died, and 7 children had diet-related adverse reactions (nephrolithiasis, gastroesophageal reflux). DISCUSSION: The ketogenic diet is a safe, well-tolerated, and possibly effective potential alternative to other therapies for infantile spasms.

Child, Preschool↗