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Biomedical subjects

Eric H Kossoff

Publications and source records attributed to Eric H Kossoff.

At least 19 recordsLinked to original sources
PubMed2006

The importance of parental expectations of cognitive improvement for their children with epilepsy prior to starting the ketogenic diet.

Although the success rates and complications of various treatment options for children with intractable epilepsy have been described, the actual expectations of parents for these treatments are less clear. Since 1998, parents at our institution have written their goals in a letter before starting their children on the ketogenic diet. One hundred consecutive letters were evaluated. The most common first goal was seizure improvement, second was anticonvulsant reduction, and third was cognitive improvement. Ninety percent requested improvement in cognition or alertness. These expectations were either met or exceeded at 6 months in 52-60% of children. Achieving or surpassing parental expectations for cognitive improvement correlated with longer diet duration (P=0.04), but meeting goals for seizure or anticonvulsant reduction did not. Cognitive improvement (P<0.001) and >90% seizure reduction (P=0.04) at 6 months positively correlated with longer eventual diet duration. Expectations for cognitive improvement need to be discussed prior to beginning the ketogenic diet.

Anticonvulsants↗
PubMed2006

State of the ketogenic diet(s) in epilepsy.

Fasting has been recognized as a treatment for seizures since ancient times. The ketogenic diet is a low-carbohydrate, adequate-protein, high-fat diet that biochemically mimics the fasting state and has been used to successfully treat seizures for 85 years. The diet has enjoyed a resurgence in popularity over the past decade and is gaining acceptance and use worldwide. Many studies over the past several years have explored possible mechanisms of action for the ketogenic diet. This review addresses these studies, as well as recent research regarding possible indications for the diet, variations in its initiation, side effect profiles, and the recent use of modified formulations to improve tolerability.

Diet, Carbohydrate-Restricted↗
PubMed2006

Treatment of infantile spasms.

Infantile spasms are associated with a diverse range of conditions, and treatment options are available. However, outcomes remain generally poor, particularly for those with symptomatic etiologies. First-line therapy is considered to be hormonal (adrenocorticotropic hormone; ACTH), which some evidence suggests is more effective when started early. However, side effects may place limits on its use acutely and long-term. There is additional evidence for vigabatrin, specifically for infantile spasms secondary to tuberous sclerosis complex. In refractory cases, candidacy for surgical management should be explored, along with new-generation anticonvulsants (eg, topiramate, zonisamide) and the ketogenic diet. There is urgent need for further treatment trials comparing anticonvulsants with ACTH and a satisfactory animal model for the study of spasms.

Journal Article↗
PubMed2006

Epilepsy surgery for the neurocutaneous disorders.

Patients with neurophakomatoses were not always considered to be candidates for surgical resection of epileptogenic foci, given the multifocal nature of their disease. Advances in imaging, monitoring, and surgical technique have allowed the identification of particularly active areas of cortex that may provide these patients with better seizure control than medications alone. Options for surgical resection range from focal resections (in those with localized disease) to hemispherectomies (in those with hemispheric involvement).

Epilepsy↗
PubMed2006

Long-term use of the ketogenic diet in the treatment of epilepsy.

Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1-1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely.

Adolescent↗
PubMed2006

A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy.

PURPOSE: The Atkins diet may induce ketosis as does the ketogenic diet, without restrictions on calories, fluids, protein, or need for an inpatient fast and admission. Our objective was to evaluate the efficacy and tolerability of a modified Atkins diet for intractable childhood epilepsy. METHODS: Twenty children were treated prospectively in a hospital-based ambulatory clinic from September 2003 to May 2005. Children aged 3-18 years, with at least three seizures per week, who had been treated with at least two anticonvulsants, were enrolled and received the diet over a 6-month period. Carbohydrates were initially limited to 10 g/day, and fats were encouraged. Parents measured urinary ketones semiweekly and recorded seizures daily. All children received vitamin and calcium supplementation. RESULTS: In all children, at least moderate urinary ketosis developed within 4 days (mean, 1.9). Sixteen (80%) completed the 6-month study; 14 chose to remain on the diet afterward. At 6 months, 13 (65%) had >50% improvement, and seven (35%) had >90% improvement (four were seizure free). Mean seizure frequency after 6 months was 40 per week (p = 0.005). Over a 6-month period, mean serum blood urea nitrogen increased from 12 to 17 mg/dl (p = 0.01); creatinine was unchanged. Cholesterol increased from 192 to 221 mg/dl, (p = 0.06). Weight did not change significantly (34.0-33.7 kg); only six children lost weight. A stable body mass index over time correlated with >90% improvement (p = 0.004). CONCLUSIONS: A modified Atkins diet is an effective and well-tolerated therapy for intractable pediatric epilepsy.

Adolescent↗
PubMed2006

The outcome of children with intractable seizures: a 3- to 6-year follow-up of 67 children who remained on the ketogenic diet less than one year.

PURPOSE: To determine the long-term outcome of children with difficult-to-control seizures who remained on the ketogenic diet for <1 year. METHODS: Between 1994 and 1996, 150 children with epilepsy, refractory to at least two medications, initiated the ketogenic diet according to the Hopkins protocol. Three to six years after diet initiation, all the families were contacted by telephone or questionnaire to assess their child's current seizure status, medications, and therapies. RESULTS: Sixty-seven children discontinued the diet within 1 year of initiation. Follow-up data were available for 54 of these children. Ten subsequently had surgery, and three underwent VNS implantation. These operated-on children were significantly more likely to be >50% controlled at follow-up than were those managed with medications alone (p < 0.05). A statistically significant difference in long-term outcome was noted between those who responded while on the diet, even if they discontinued it before 1 year, and those who did not (p < 0.05), but no statistical correlation was found between length of time that they had remained on the diet and long-term prognosis. CONCLUSIONS: Almost half of the children who discontinued the diet during the first year had a decrease in seizures when assessed 3-6 years later. Twenty-two percent of these had become seizure free without surgery. We were unable to ascertain whether this may have been due to new medications. Those who saw some improvement while on the diet were more likely to have a favorable long-term outcome. Resective surgery, in children who were candidates, or vagal nerve stimulation (VNS) implantation, was more likely to result in significant seizure improvement than was management with medications alone. Whether or not the diet was effective, most families did not regret trying it and would recommend it to others.

Adolescent↗
PubMed2006

Medication-overuse headache in children: is initial preventive therapy necessary?

Chronic daily headaches can be a difficult problem in children as well as adults. Over half of the cases of chronic daily headaches in adults are thought to be due to medication-overuse headache, and treatment consists of discontinuation of these analgesics. Since many patients are also treated with preventive agents at the time of analgesic withdrawal, it is difficult to determine whether discontinuation alone is the most effective treatment. A retrospective study was performed to evaluate the outcomes of 43 children (ages 6-17 years) with medication-overuse headache 1 month after withdrawal of analgesics: 20 children received daily doses of a preventive medication, and 23 received no preventive medication. Headache reduction was assessed 1 month later. There was no difference in the percentage, with 90% or greater headache reduction at 1 month between children treated by withdrawal of analgesic drugs only and those receiving preventive medications (57% vs 50%, respectively). There was no influence of age, gender, use of triptans as rescue agents, or caffeine use on outcomes. A previous duration of headaches over 2 years was negatively correlated with overall outcome. We advise discontinuation of analgesics in all children with medication-overuse headache, without the necessity for starting daily preventive agents concurrently. Should headaches persist after 1 month, such agents can be added. (J Child Neurol 2006;21:45-48).

Adolescent↗
PubMed2005

The ketogenic diet.

BACKGROUND: The ketogenic diet is a low-carbohydrate, adequate-protein, and high-fat diet with a long history of use for the treatment of intractable seizures in children. This dietary therapy has been enjoying increasing popularity in recent years, despite the availability of increasing numbers of new antiepileptic drugs and surgical treatments. REVIEW SUMMARY: The authors review the history of the ketogenic diet, the traditional protocol in initiating it, possible mechanisms of its action, evidence for efficacy, and side effects. In addition, they highlight some of the areas of active research in this field as well as future directions and unanswered questions. CONCLUSION: The ketogenic diet is an efficacious and relatively safe treatment of intractable seizures. Despite its long history, however, much remains unknown about the diet, including its mechanisms of action, the optimal protocol, and the full range of its applicability. Investigations of the diet are providing new insight into the mechanisms behind seizures and epilepsy itself, as well as possible new therapies.

Anticonvulsants↗
PubMed2005

Worldwide use of the ketogenic diet.

PURPOSE: Over the past decade, the use of the ketogenic diet internationally has increased dramatically. The purpose of this survey was to evaluate the use of the diet worldwide. METHODS: With the use of the Internet, e-mail requests for information about international ketogenic diet centers (outside the United States) were made over a 9-month period. Assistance also was obtained from the Child Neurology Society and International League Against Epilepsy. Questions included patient enrollment (total and annually), year the diet was first offered, unique cultural and religious issues in the country, community opinion, and research interests. RESULTS: Successful communication was made with 73 academic centers in 41 countries outside the United States. Sixteen (39%) countries provided information from multiple centers. The median duration offering the diet was 8 years (range, 1-45 years). The average number of patients enrolled to date was 71.6 per country, with 5.4 new patients annually. Common difficulties included avoiding rice intake, tolerating higher fat-to-protein and carbohydrate ratios (e.g., 4:1), finding specific nutritional labels on foods, and handling the growing interest from large populations with limited resources. Nevertheless, cultural and religious issues were generally not limiting; physician and patient acceptance of the diet as an option is high; and most meals were similar among countries. Centers often had great pride in their programs, and international collaborative groups are forming rapidly. A website is now available with updated center information at http://www.neuro.jhmi.edu/Epilepsy/Peds/ketoworldwide.htm CONCLUSIONS: Despite occasional difficulties, the ketogenic diet is being used worldwide.

Academic Medical Centers↗
PubMed2005

Can you predict an immediate, complete, and sustained response to the ketogenic diet?

PURPOSE: Although the ketogenic diet has been in use for >80 years, little agreement exists as to which patients are most likely to have dramatic, sudden, and complete seizure control. METHODS: A case-control study was performed of children with intractable epilepsy started on the ketogenic diet at our institution since June 2001. Patients with a dramatic response were defined as those becoming seizure free within 2 weeks of diet onset. These children were compared with all other patients treated with the diet over the same time period in terms of patient demographics, epilepsy characteristics, and diet parameters. RESULTS: Eighteen early, dramatic responders over a 3-year period were identified and compared with 89 patients who were not similarly improved. The absence of complex partial seizures as the predominant seizure type (0 vs. 23%; p = 0.02) correlated with this dramatic success. The presence of infantile spasms (39% vs. 20%; p = 0.09) approached significance, but all other variables did not. CONCLUSIONS: An early, dramatic response to the ketogenic diet is more likely in patients with predominant seizure types other than complex partial. It may also be more likely to occur in children who have infantile spasms. In all other patient demographics and diet parameters, an equal likelihood of similar success was found.

Body Mass Index↗
PubMed2005

Tuberous sclerosis complex and the ketogenic diet.

PURPOSE: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early-onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described. METHODS: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5-year period at Johns Hopkins Hospital and Massachusetts General Hospital. RESULTS: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a >50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a >90% response. Five children had at least a 5-month seizure-free response. Diet duration ranged from 2 months to 5 years (mean, 2 years). CONCLUSIONS: In this limited-duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC.

Adolescent↗
PubMed2005

Experience in the use of the ketogenic diet as early therapy.

The ketogenic diet has traditionally been considered an anticonvulsant therapy of last resort, despite excellent efficacy and limited side effects. We hypothesized that the ketogenic diet would have similar results in patients with new-onset epilepsy. A retrospective study was conducted of patients started on the ketogenic diet since 1994. Thirteen of 460 (2.8%) patients were started on the ketogenic diet as early (zero or one prior anticonvulsant) therapy for seizures. Of those remaining on the diet, 60% (6 of 10) had a > 90% seizure reduction at 6 months and 100% (6 of 6) had a > 90% reduction at 12 months. Patients with infantile spasms were as likely to achieve > 50% seizure reduction at 6 months as patients with other seizure types (75% vs 60%; P = .6). The ketogenic diet can be a valuable therapy before epilepsy becomes intractable. In the 13 patients reported, efficacy without side effects was achieved similarly to that with patients with intractable epilepsy.

Age of Onset↗
PubMed2005

Comorbidity of epilepsy and headache in patients with Sturge-Weber syndrome.

Sturge-Weber syndrome is associated with leptomeningeal angioma, trigeminal port-wine stain, epilepsy, and glaucoma. Clinically, many patients with Sturge-Weber syndrome are observed to have both seizures and headaches, but this has never been described in the literature. A questionnaire was mailed to 190 patients with reported comorbid epilepsy and headache as identified by the Sturge-Weber Foundation. Sixty-eight surveys were returned anonymously; 55 reported both seizures and headaches. The median age at headache onset was 8 years, with a median of three headaches per month. Fifty-eight percent felt that headaches were an equal or greater problem. Ibuprofen and acetaminophen were the most frequently tried abortive medications; 22% had tried sumatriptan. Only 22% reported a neurologist suggesting the use of an anticonvulsant as a preventive agent. Subjects with a family history of headaches had an earlier age at headache onset (7.5 vs 11 years; P = .02), and those with a family history of seizures were more likely to report behavior problems (69% vs 33%; P = .02). Subjects reporting learning problems or hemiparesis had an earlier age at seizure onset. Migraine-like headaches can be as significant a problem as epilepsy for patients with Sturge-Weber syndrome. Despite this, triptans and prophylactic medications (including anticonvulsants) were used in less than half of the patients. Correlations of family history with both age at symptom onset and behavior problems suggest that genetic substrate could be one factor determining the variable neurologic manifestations seen in Sturge-Weber syndrome.

Age of Onset↗
PubMed2004

Improvement in alertness and behavior in children treated with combination topiramate and vagus nerve stimulation.

It has been reported that vagus nerve stimulation (VNS) improves behavior in children, whereas topiramate has a less clear effect. Three boys, aged 5-12 years, with generalized slow spike-wave discharges and refractory epilepsy, were treated with combination therapy of topiramate and VNS. All three had a significant reduction in seizures, but even more dramatic improvement in aggression, social interaction, and ambulation. The Cyberonics Patient Outcome Registry was subsequently queried and a beneficial effect of this combination therapy on behavior (specifically alertness) beyond that of VNS and other anticonvulsants was noted. This did not appear to be due solely to seizure reduction, which was observed only differentially at 12 months.

Anticonvulsants↗
PubMed2004

The impact of early versus late anticonvulsant reduction after ketogenic diet initiation.

The ideal timing of anticonvulsant reduction for a child started on the ketogenic diet is unclear. The records of 81 children started on the ketogenic diet consecutively over a 2-year period were reviewed for a 6-month period after diet initiation. During their first 6 months on the ketogenic diet, medications were tapered in 53 of 81 (65%) patients, with 30 of 53 (57%) considered "early" (tapered during diet initiation or within the first month afterward). No differences were seen between the early and late groups with respect to percentage with > 90% seizure reduction at 3 months (47% vs 48%), diet duration (1.1 vs 0.9 years), percentage remaining on the ketogenic diet to date (73% vs 65%), or improved alertness (63% vs 57%). Nine of fifty-three (17%) had transient seizure increases during medication tapering, with no correlation to the timing in which this occurred; however, five were taking benzodiazepines or barbiturates. All had > 50% seizure reduction at 3 months despite the transient worsening. Early reduction of anticonvulsants in children initiated on the ketogenic diet appears to be safe and well tolerated. However, it offers no specific advantage compared with a later taper.

Adolescent↗
PubMed2004

More fat and fewer seizures: dietary therapies for epilepsy.

The ketogenic diet is a high-fat, adequate protein, low carbohydrate diet that has been used for the treatment of intractable childhood epilepsy since the 1920s. The diet mimics the biochemical changes associated with starvation, which create ketosis. Although less commonly used in later decades because of the increased availability of anticonvulsants, the ketogenic diet has re-emerged as a therapeutic option. Only a decade ago the ketogenic diet was seen as a last resort; however, it has become more commonly used in academic centres throughout the world even early in the course of epilepsy. The Atkins diet is a recently used, less restrictive, therapy that also creates ketosis and can lower the number of seizures. Dietary therapies may become even more valuable in the therapy of epilepsy when the mechanisms underlying their success are understood.

Dietary Fats↗