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Ketogenic Diet (ketogenic + diet)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Efficacy and Tolerability of the Ketogenic Diet According to Lipid:Nonlipid Ratios,Comparison of 3:1 with 4:1 Diet

EPILEPSIA, Issue 4 2007
Joo Hee Seo
Summary:,Purpose: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1. Methods: Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored. Results: (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p < 0.05). (3) For seizure-free patients who started on the 4:1 diet, antiepileptic efficacy was maintained after changing to the 3:1 diet, while 10 (83.3%) of 12 patients who were not seizure free with the 3:1 diet showed increased seizure reduction after changing to the 4:1 diet. (4) Complications from the KD and laboratory data were not significantly different between the two groups. Conclusions: The 4:1 KD showed greater antiepileptic efficacy than the 3:1 diet with higher seizure-free outcome. In most cases, seizure free outcome was maintained even after changing the ratio to 3:1. Dietary tolerability was better in the 3:1 diet than the 4:1 with less frequent gastrointestinal symptoms. [source]

Combined Ketogenic Diet and Vagus Nerve Stimulation: Rational Polytherapy?

EPILEPSIA, Issue 1 2007
Eric H. Kossoff
Summary:,Objective: The concept of "rational polypharmacy" has been associated with anticonvulsant management for decades, but the term has not been applied to nonpharmacologic therapies. Methods: We conducted a multicenter, retrospective study of children who received concurrent diet (ketogenic or modified Atkins) and vagus nerve stimulation (VNS) treatment for medically intractable epilepsy. Results: Thirty children in total from six epilepsy centers were treated over a 6-yr period. The median age at the initiation of combination therapy was 10 yr (range, 4,24 yr). Sixteen (53%) received dietary therapy followed by VNS; no differences were noted between centers. After 3 months, 21 (70%) had seizure reduced by >50% over the previous single nonpharmacologic treatment, of whom 13 (62%) had improvement within the first month. A 5-min VNS off-time correlated with >90% seizure reduction (p = 0.02). The median duration of nonpharmacologic polytherapy was 12 months (range, 0.5,96 months); 17 (57%) remain on dual therapy at this time. No side effects were noted. Most patients who discontinued combination therapy did so because of a lack of efficacy rather than restrictiveness. Conclusions: In this small group, the combined use of diet and VNS appeared synergistic and yielded rapid benefits. It may be more effective with longer VNS off-times. Further prospective studies of this combination in refractory pediatric epilepsy are needed to help guide optimal use. [source]

Selenium Deficiency Associated with Cardiomyopathy: A Complication of the Ketogenic Diet

EPILEPSIA, Issue 4 2003
A. G. Christina Bergqvist
Summary: ,Purpose: The ketogenic diet (KD) is an efficacious treatment for intractable epilepsy, associated with infrequent side effects. The KD is known to be deficient in most vitamins and minerals and may be deficient in trace minerals. We report biochemical selenium deficiency in nine patients on the KD, including one who developed cardiomyopathy. Methods: A whole-blood selenium level was obtained on the symptomatic patient after noting the patient's poor appearance on physical examination. Children already treated and children beginning the KD were then evaluated prospectively for selenium status by measuring whole-blood or serum selenium as part of routine laboratory evaluation every 3 months. Results: The index case had no detectable whole-blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy. Thirty-nine additional children had the selenium status evaluated. Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing). They were referred for cardiology evaluations, which were normal. Selenium supplementation improved levels in all children. Low levels were seen in some children after only a few months of treatment. Conclusions: The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated. Screening for selenium deficiency is suggested if the patient KD regimen does not meet ,75% of the RDA or if the child is symptomatic. Nutrient supplementation should provide adequate trace elements for children treated with the KD. The KD requires close monitoring of the overall nutritional status. [source]

On the Anticonvulsant Effect of Acetone and the Ketogenic Diet

EPILEPSIA, Issue 12 2002
Sergei S. Likhodii
First page of article [source]

General Anesthesia and the Ketogenic Diet: Clinical Experience in Nine Patients

EPILEPSIA, Issue 5 2002
Ignacio Valencia
Summary: ,Purpose: To determine if children actively on the ketogenic diet (KD) can safely undergo general anesthesia (GA) for surgical procedures. Methods: The records of children treated with the KD at Children's Hospital (Boston, Massachusetts) from 1995 to the present were reviewed. The charts of children who had received GA while on the diet were evaluated with regard to demographics, procedure information, anesthesia records, blood chemistries, and perioperative course. Of 71 children on the KD during the period of the study, nine (12.7%) had procedures requiring GA while on the diet. Results: Nine children received GA for surgical procedures ranging from central line placement to hemispherectomy while on the KD. At the time of GA, the children ranged from age 1 to 6 years, and had been on the KD for 2,60 months. The patients received carbohydrate-free intravenous solutions perioperatively. Anesthesia duration ranged from 20 min to 11.5 h; for longer procedures, serum pH, glucose, and electrolyte levels were monitored. Serum glucose levels remained stable in all patients, but serum pH typically decreased; the largest reduction was to 7.16. In three procedures, patients received intravenous bicarbonate because of level of acidosis. There were no perioperative complications. Conclusions: Children on the KD can safely undergo GA for surgical procedures. Although serum glucose levels appear to remain stable, serum pH or bicarbonate levels should be monitored because of the risk of metabolic acidosis. [source]

Effectiveness of the ketogenic diet in a broad range of seizure types and EEG features for severe childhood epilepsies

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2010
S. Beniczky
Background,,, Ketogenic diet (KD) is an effective treatment for pharmacoresistant epilepsy: more than half of the patients show a greater than 50% reduction in seizures. Objective,,, To identify clinical or electroencephalogram (EEG) variables predicting the response to KD. Methods,,, Clinical and EEG data were retrospectively analysed from 50 consecutive patients treated by KD for severe, pharmacoresistant epilepsy. Most of the patients (70%) had retarded mental and motor development. Results,,, Three months after the start of the KD two-thirds (33) of the patients were responders (had a more than 50% reduction in seizure frequency). The presence of epileptiform EEG discharges in the temporal region correlated with an unfavourable response (P = 0.03). The presence of bilateral synchronous epileptiform discharges, and the presence of complex partial seizures approached significance but all other variables did not. Conclusions,,, Our results further support that KD is efficient in a wide variety of epileptic patients with a broad range of EEG features. However, patients with epileptiform discharges in the temporal region are less likely to achieve therapeutic response. [source]

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

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2006
Darcy K Groesbeck BS
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. [source]

Growth of children on the ketogenic diet

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2002
Eileen P G Vining MD
This is a prospective cohort study of 237 children (130 males, 107 females) placed on the ketogenic diet for control of intractable epilepsy (mean age at starting diet 3 years 8 months; age range 2 months to 9 years 10 months); average length of follow-up was 308 days. There were 133 children on the diet at 1 year and 76 at 2 years. Height and weight measurements were converted into age- and sex-appropriate z scores. There was a rapid drop in weight z scores in the first 3 months. After this initial period, the weight z score remained constant in children who started the diet below the median weight for their age and sex, although z scores continued to decrease in children starting above the median. There was a small decrease in height z scores in the first 6 months (<0.5); however, there were larger changes by 2 years. There was no difference based on sex for either height or weight. The ketogenic diet generally provides sufficient nutrition to maintain growth within normal parameters over a defined period. Very young children grow poorly on the diet and should be followed-up carefully over long periods of use. [source]

Energy requirements of spasticity

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2001
Cheryl Hemingway MBCh B
Direct measurement of energy expended by spasticity in children with severe spastic quadriparesis is difficult. Insertion of an intrathecal baclofen pump in a 13-year-old boy with severe spasticity and profound mental retardation* resulted in an estimated 30 to 40% decrease in his spasticity. As he had been on a carefully calculated ketogenic diet and fed by gastrostomy, his precise caloric intake was known. Decrease in spasticity, on the same caloric intake, led to marked weight gain. Reduction of 100 calories intake resulted in new weight stability. It was possible therefore, to estimate indirectly energy used by his spasticity. This 100 calories, representing 34% of calories above his resting energy requirement, corresponded to an independently estimated 30 to 40% of caloric expenditure of his spasticity. It was concluded that when calculation of calories is critical, energy utilization by spasticity must be taken into consideration. [source]

Long-term outcomes of children treated with the ketogenic diet in the past

EPILEPSIA, Issue 7 2010
Amisha Patel
Summary Purpose:, The ketogenic diet has well-established short- and long-term outcomes for children with intractable epilepsy, but only for those actively receiving it. However, no information exists about its long-term effects years after it has been discontinued. Methods:, Living subjects were identified who were treated at the Johns Hopkins Hospital with the ketogenic diet from November 1993 to December 2008 for ,1 month, and had discontinued it ,6 months prior to this study. Of 530 patients who were eligible, 254 were successfully contacted by phone or e-mail with a survey and request for laboratory studies. Results:, Questionnaires were completed by 101 patients, with a median current age of 13 years (range 2,26 years). Median time since discontinuing the ketogenic diet was 6 years (range 0.8,14 years). Few (8%) still preferred to eat high fat foods. In comparison to the 52% responder rate (>50% seizure reduction) at ketogenic diet discontinuation, 79% were now similarly improved (p = 0.0001). Ninety-six percent would recommend the ketogenic diet to others, yet only 54% would have started it before trying anticonvulsants. Lipids were normal (mean total cholesterol 158 mg/dl), despite most being abnormal while on the ketogenic diet. The mean Z scores for those younger than age 18 years were ,1.28 for height and ,0.79 for weight. In those 18 years of age or older, the mean body mass index (BMI) was 22.2. Discussion:, This is the first study to report on the long-term effects of the ketogenic diet after discontinuation. The majority of subjects are currently doing well with regard to health and seizure control. [source]

Type 1 diabetes and epilepsy: Efficacy and safety of the ketogenic diet

EPILEPSIA, Issue 6 2010
Anastasia Dressler
Summary Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD. [source]

The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet

EPILEPSIA, Issue 8 2009
Peter F. Morrison
Summary It is unknown if any particular anticonvulsants modify the likelihood of seizure reduction when used in combination with the ketogenic diet (KD). A retrospective study was performed of 217 consecutive children who started the KD from 2000,2007. Patients included did not have any changes to their anticonvulsant dose. Efficacy data at 3 months on the KD were analyzed with respect to the six most frequently used anticonvulsants in this cohort. A total of 115 patients were included. Children receiving phenobarbital in combination with the KD were significantly less likely to have a >50% seizure reduction (p = 0.003). Conversely, those receiving zonisamide in combination with the KD at onset were more likely to have a >50% reduction (p = 0.04). These results provide practical information to clinicians who are treating children receiving both the KD and anticonvulsants. [source]

A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy

EPILEPSIA, Issue 5 2009
Elizabeth G. Neal
Summary Purpose:, To conduct the first randomized trial on classical and medium-chain triglyceride (MCT) versions of the ketogenic diet, examining efficacy and tolerability after 3, 6, and 12 months. Methods:, One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet. Seizure frequency was assessed after 3, 6, and 12 months. Treatment withdrawals were documented. Tolerability was assessed by questionnaire, and blood ketone levels were measured. Results:, Of the 61 children who started a classical diet and the 64 who started an MCT diet, data from 94 were available for analysis: 45 classical and 49 MCT. After 3, 6, and 12 months there were no statistically significant differences in mean percentage of baseline seizures between the two groups (3 months: classical 66.5%, MCT 68.9%; 6 months: classical 48.5%, MCT 67.6%; 12 months: classical 40.8%, MCT 53.2%; all p > 0.05). There were no significant differences between groups in numbers achieving greater than 50% or 90% seizure reduction. Serum acetoacetate and ,-hydroxybutyrate levels at 3 and 6 months were significantly higher in children on the classical diet (p < 0.01); this was the case at 12 months for acetoacetate. There were no significant differences in tolerability except increased reports in the classical group of lack of energy after 3 months and vomiting after 12 months. Discussion:, This study has shown classical and MCT ketogenic diet protocols to be comparable in efficacy and tolerability; both ways of implementing the diet have their place in the treatment of childhood epilepsy. [source]

A blinded, crossover study of the efficacy of the ketogenic diet

EPILEPSIA, Issue 2 2009
John M. Freeman
Summary Despite over 80 years of use, the ketogenic diet (KD) has never been tested in a blinded manner. Twenty children with intractable Lennox-Gastaut syndrome (LGS) were fasted 36 h and then randomized to receive the classic KD in conjunction with a solution containing either 60 g/day of glucose or saccharin. Parents and physicians were blinded to both the solution composition and level of ketosis. A crossover to the KD with the alternate solution occurred following the sixth day and a repeat fast. A 24-h electroencephalography (EEG) was obtained at baseline and after each arm. After administration of the solution, there was moderate evidence of a reduction in parent-reported seizures between the glucose and saccharin arms, with a median difference of 1.5 seizures per day (p = 0.07). There was no reduction in the number of EEG-identified events, with a median reduction of 7 events per day (p = 0.33). Ketosis was not completely eliminated in the glucose-added arm. [source]

History of the ketogenic diet

EPILEPSIA, Issue 2008
James W. Wheless
Summary Fasting and other dietary regimens have been used to treat epilepsy since at least 500 BC. To mimic the metabolism of fasting, the ketogenic diet (KD) was introduced by modern physicians as a treatment for epilepsy in the 1920s. For two decades this therapy was widely used, but with the modern era of antiepileptic drug treatment its use declined dramatically. By the end of the twentieth century this therapy was available in only a small number of children's hospitals. Over the past 15 years, there has been an explosion in the use, and scientific interest in the KD. This review traces the history of one of the most effective treatments for childhood epilepsy. [source]

Medium-chain triglyceride (MCT) ketogenic therapy

EPILEPSIA, Issue 2008
Yeou-mei Christiana Liu
Summary The medium-chain triglyceride diet (MCTD) is a variant of the classic 4:1 ketogenic diet (KD) introduced in 1971 by Huttenlocher as an attempt to improve the palatability of the KD by allowing more carbohydrates yet preserving ketosis. Although initially found to be equally effective as the classic KD, use of the MCTD declined because of frequent gastrointestinal side effects such as cramps, diarrhea, and vomiting. Recently, we have used the MCTD in more than 50 patients. We have found excellent seizure control, similar to the classic KD, and with careful monitoring, we have encountered minimal side effects. The MCTD should remain a viable dietary option for children with refractory epilepsy who have large appetites, can tolerate more calories, or cannot accept the restrictions of the classic KD. [source]

The Modified Atkins Diet

EPILEPSIA, Issue 2008
Eric H. Kossoff
Summary In 2003, a case series was published describing the benefits of a less restrictive ketogenic diet (KD) started as an outpatient without a fast and without any restrictions on calories, fluids, or protein. This "Modified Atkins Diet" (MAD) restricts carbohydrates to 10 g/day (15 g/day in adults) while encouraging high fat foods. Now 5 years later, there have been eight prospective and retrospective studies published on this alternative dietary therapy, both in children as well as adults. In these reports, 45 (45%) have had 50,90% seizure reduction, and 28 (28%) >90% seizure reduction, which is remarkably similar to the traditional KD. This review will discuss basics and tips to best provide the MAD, evidence for its efficacy, suggestions about the role of ketosis in dietary treatment efficacy, and its side effect profile. Lastly, the possible future benefits of this treatment for new-onset seizures, adults, neurologic conditions other than epilepsy, and developing countries of the world will be discussed. [source]

Peroxisome proliferator-activated receptor alpha and the ketogenic diet

EPILEPSIA, Issue 2008
Tim Cullingford
Summary Peroxisome proliferator-activated receptor alpha (PPAR,) is a drug/fatty acid-activated trans cription factor involved in the starvation response, and is thus relevant to the ketogenic diet (KD). This article summarizes research indicating the role of PPAR, in central and peripheral nervous system function with particular reference to downstream targets relevant to anticonvulsant action. [source]

Ketosis and brain handling of glutamate, glutamine, and GABA

EPILEPSIA, Issue 2008
Marc Yudkoff
Summary We hypothesize that one mechanism of the anti-epileptic effect of the ketogenic diet is to alter brain handling of glutamate. According to this formulation, in ketotic brain astrocyte metabolism is more active, resulting in enhanced conversion of glutamate to glutamine. This allows for: (a) more efficient removal of glutamate, the most important excitatory neurotransmitter; and (b) more efficient conversion of glutamine to GABA, the major inhibitory neurotransmitter. [source]

The contribution of norepinephrine and orexigenic neuropeptides to the anticonvulsant effect of the ketogenic diet

EPILEPSIA, Issue 2008
David Weinshenker
Summary The ketogenic diet (KD) is a high-fat, low-carbohydrate, low-protein diet used to treat refractory epilepsy. Despite its efficacy and many years of investigation, the mechanism by which the KD exerts its anticonvulsant effect remains controversial and poorly understood. The purpose of this article is to review the available data considering two classes of molecules that may contribute to the anticonvulsant effect of the KD: norepinephrine and the orexigenic neuropeptides galanin and neuropeptide Y. [source]

Current Treatment of Myoclonic Astatic Epilepsy: Clinical Experience at the Children's Hospital of Philadelphia

EPILEPSIA, Issue 9 2007
Sudha Kilaru
Summary:,Purpose: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET. Methods: Charts of subjects with MAE treated between 1998 and 2005 were reviewed. Results: Twenty-three subjects (19 boys), with a median (range) follow-up of 38 (2, 86) months were identified. Thirty-nine percent had a family history of epilepsy, and 39% had family history of febrile seizures. Age at seizure onset was a median of 36 (12,24) months. Initial EEG was normal in 30%. When seizures ceased, EEG background and epileptiform abnormalities persisted in 17 and 58%, respectively. On average, each subject was exposed to five AET. The most frequently used AET was valproate (83%). Seizure freedom occurred spontaneously in three subjects, with ethosuximide and levetiracetam in one each, valproate and lamotrigine in two each, topiramate in three and the ketogenic diet (KD) in five subjects. By 36 months after seizure onset, 67% achieved seizure freedom. At the last visit, 43% were developmentally normal, 52% had mild, and 5% had moderate cognitive disabilities. Time to seizure freedom did not correlate with cognitive outcome. Conclusions: The new generation of AET may offer significant benefit to children with MAE. The KD was the most effective AET in this series, and perhaps should be considered earlier in treatment. [source]

Temozolomide Treatment of Refractory Epilepsy in a Patient with an Oligodendroglioma

EPILEPSIA, Issue 7 2006
Ly Ngo
Summary:, A 40-year-old man with a left frontotemporal grade II oligodendroglioma developed seizures that were refractory to 14 antiepileptic medications, the ketogenic diet, and epilepsy surgery. With temozolomide therapy, his seizure frequency gradually changed from 30 partial seizures per day to a single simple partial seizure in 6 months. No additional therapeutic measures were introduced during this time. This reduction in seizure frequency appears attributable solely to temozolomide therapy. [source]

A Modified Atkins Diet Is Effective for the Treatment of Intractable Pediatric Epilepsy

EPILEPSIA, Issue 2 2006
Eric H. Kossoff
Summary:,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. [source]

General Anesthesia and the Ketogenic Diet: Clinical Experience in Nine Patients

Caloric Restriction Inhibits Seizure Susceptibility in Epileptic EL Mice by Reducing Blood Glucose

EPILEPSIA, Issue 11 2001
Amanda E. Greene
Summary: ,Purpose: Caloric restriction (CR) involves underfeeding and has long been recognized as a dietary therapy that improves health and increases longevity. In contrast to severe fasting or starvation, CR reduces total food intake without causing nutritional deficiencies. Although fasting has been recognized as an effective antiseizure therapy since the time of the ancient Greeks, the mechanism by which fasting inhibits seizures remains obscure. The influence of CR on seizure susceptibility was investigated at both juvenile (30 days) and adult (70 days) ages in the EL mouse, a genetic model of multifactorial idiopathic epilepsy. Methods: The juvenile EL mice were separated into two groups and fed standard lab chow either ad libitum (control, n = 18) or with a 15% CR diet (treated, n = 17). The adult EL mice were separated into three groups; control (n = 15), 15% CR (n = 6), and 30% CR (n = 3). Body weights, seizure susceptibility, and the levels of blood glucose and ketones (,-hydroxybutyrate) were measured over a 10-week treatment period. Simple linear regression and multiple logistic regression were used to analyze the relations among seizures, glucose, and ketones. Results: CR delayed the onset and reduced the incidence of seizures at both juvenile and adult ages and was devoid of adverse side effects. Furthermore, mild CR (15%) had a greater antiepileptogenic effect than the well-established high-fat ketogenic diet in the juvenile mice. The CR-induced changes in blood glucose levels were predictive of both blood ketone levels and seizure susceptibility. Conclusions: We propose that CR may reduce seizure susceptibility in EL mice by reducing brain glycolytic energy. Our preclinical findings suggest that CR may be an effective antiseizure dietary therapy for human seizure disorders. [source]

Seizures, ataxia, developmental delay and the general paediatrician: Glucose transporter 1 deficiency syndrome

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2006
David J Coman
Aim Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). Methods This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. Results The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. Conclusion Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort. [source]

In vivo measurement of brain metabolites using two-dimensional double-quantum MR spectroscopy,exploration of GABA levels in a ketogenic diet

MAGNETIC RESONANCE IN MEDICINE, Issue 4 2003
Zhiyue J. Wang
Abstract A localized proton 2D double-quantum (DQ) spin-echo spectroscopy technique was implemented on 1.5 T clinical MRI scanners for the detection of ,-aminobutyrate (GABA) in the brain. The 2D approach facilitates separation of peaks overlapping with GABA in 1D DQ-filtered (DQF) spectra. This technique was applied to four normal adult volunteers and four children with intractable epilepsy. The coefficient of variation of the level of GABA and overlapping macromolecules at F2 = 3.0 ppm and F1 = 4.8 ppm was 0.08 in normal subjects. Three patients received 2D MRS scans before and after initiation of the ketogenic diet (KD): one patient showed a trend of decreasing GABA throughout the study, and two patients showed low initial GABA levels that increased over time. In addition to major metabolites and GABA, low-level metabolites (valine, leucine, and glutathione) were also identified in the 2D spectra. Magn Reson Med 49:615,619, 2003. © 2003 Wiley-Liss, Inc. [source]

Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis,

THE PROSTATE, Issue 1 2008
Stephen J. Freedland
Abstract BACKGROUND Recent evidence suggests carbohydrate intake may influence prostate cancer biology. We tested whether a no-carbohydrate ketogenic diet (NCKD) would delay prostate cancer growth relative to Western and low-fat diets in a xenograft model. METHODS Seventy-five male SCID mice were fed a NCKD (84% fat,0% carbohydrate,16% protein kcal), low-fat (12% fat,72% carbohydrate,16% protein kcal), or Western diet (40% fat,44% carbohydrate,16% protein kcal). Low-fat mice were fed ad libitum and the other arms fed via a modified-paired feeding protocol. After 24 days, all mice were injected with LAPC-4 cells and sacrificed when tumors approached 1,000 mm3. RESULTS Despite consuming equal calories, NCKD-fed mice lost weight (up to 15% body weight) relative to low-fat and Western diet-fed mice and required additional kcal to equalize body weight. Fifty-one days after injection, NCKD mice tumor volumes were 33% smaller than Western mice (rank-sum, P,=,0.009). There were no differences in tumor volume between low-fat and NCKD mice. Dietary treatment was significantly associated with survival (log-rank, P,=,0.006), with the longest survival among the NCKD mice, followed by the low-fat mice. Serum IGFBP-3 was highest and IGF-1:IGFBP-3 ratio was lowest among NCKD mice while serum insulin and IGF-1 levels were highest in Western mice. NCKD mice had significantly decreased hepatic fatty infiltration relative to the other arms. CONCLUSIONS In this xenograft model, despite consuming more calories, NCKD-fed mice had significantly reduced tumor growth and prolonged survival relative to Western mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet. Prostate 68: 11,19, 2008. © 2007 Wiley-Liss, Inc. [source]

Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1,

ANNALS OF NEUROLOGY, Issue 3 2009
Arvid Suls MSc
Absence epilepsies of childhood are heterogeneous with most cases following complex inheritance. Those cases with onset before 4 years of age represent a poorly studied subset. We screened 34 patients with early-onset absence epilepsy for mutations in SLC2A1, the gene encoding the GLUT1 glucose transporter. Mutations leading to reduced protein function were found in 12% (4/34) of patients. Two mutations arose de novo, and two were familial. These findings suggest GLUT1 deficiency underlies a significant proportion of early-onset absence epilepsy, which has both genetic counseling and treatment implications because the ketogenic diet is effective in GLUT1 deficiency. Ann Neurol 2009;66:415,419 [source]

Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models,

ANNALS OF NEUROLOGY, Issue 4 2009
Carl E. Stafstrom MD
Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Because carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine, or bicuculline, and in vivo against seizures evoked by 6Hz stimulation in mice, audiogenic stimulation in Fring's mice, and maximal electroshock and subcutaneous pentylenetetrazol (Metrazol) in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by 7.5mM [K+]o, 4-aminopyridine, and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6Hz stimulation in mice (effective dose [ED]50 = 79.7mg/kg) and audiogenic stimulation in Fring's mice (ED50 = 206.4mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a twofold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions, and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. Ann Neurol 2009;65:435,448. [source]