Ketogenic parenteral nutrition in three paediatric patients with epilepsy with migrating focal seizures.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare epilepsy syndrome, characterized by an onset of multifocal seizures before the age of six months and a rather typical ictal EEG pattern. The ketogenic diet (KD) has been shown to be a treatment option in these patients with variable results. The KD is generally given by enteral formula or solid food, however, patients on the KD often have coexisting medical disorders that may impair the gastrointestinal tract and, in these cases, parenteral nutrition support may be needed. We present our experience with three patients who had been on the KD because of EIMFS, who were acutely unable to absorb nutrients through the intestinal tract. For these patients, we were unable to reach ketogenic ratios higher than 1.5:1 because of the limited fat intake via the parenteral route. This ratio, nevertheless, was adequate for maintenance of seizure control while allowing short-term bowel rest. Even though our report is limited as it provides no controlled evidence, ketogenic parenteral nutrition should be considered in children on the KD when enteral nutrition is not feasible. Special care should be taken to maintain ketosis and avoid undesired carbohydrates. Patients may respond well to ketogenic parenteral nutrition in spite of a lower ketogenic ratio.

The glucose transporter type 1 (Glut1) syndromes.

The glucose transporter type 1 (Glut1) is the most important energy carrier of the brain across the blood-brain barrier. In the early nineties, the first genetic defect of Glut1 was described and known as the Glut1 deficiency syndrome (Glut1-DS). It is characterized by early infantile seizures, developmental delay, microcephaly, and ataxia. Recently, milder variants have also been described. The clinical picture of Glut1 defects and the understanding of the pathophysiology of this disease have significantly grown. A special form of transient movement disorders, the paroxysmal exertion-induced dyskinesia (PED), absence epilepsies particularly with an early onset absence epilepsy (EOAE) and childhood absence epilepsy (CAE), myoclonic astatic epilepsy (MAE), episodic choreoathetosis and spasticity (CSE), and focal epilepsy can be based on a Glut1 defect. Despite the rarity of these diseases, the Glut1 syndromes are of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms especially if it is started as early as possible. The present article summarizes the clinical features of Glut1 syndromes and discusses the underlying genetic mutations, including the available data on functional tests as well as the genotype-phenotype correlations. This article is part of the Special Issue "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Effect of modified Atkins diet in adults with drug-resistant focal epilepsy: A randomized clinical trial.

OBJECTIVE: Ketogenic diets reduce seizures in children with drug-resistant epilepsy. Whether adults benefit from similar treatment has not been clarified. We therefore examined the efficacy of the modified Atkins diet in adults with drug-resistant focal epilepsy. METHODS: We performed a randomized clinical trial (RCT) with patients >16 years who had at least 3 seizures per month despite having tried at least 3 antiepileptic drugs. They were randomized to either 12 weeks on the modified Atkins diet (diet group) or habitual diet (control group). Primary endpoint was a change in seizure frequency from baseline to the intervention period, comparing those on diet with controls. RESULTS: We assigned 37 patients to the diet group and 38 to the control group. Nine of the patients in the diet group and 4 controls were excluded. Of those who completed the dietary intervention (n = 24), median seizure change was -1.0 (interquartile range [IQR] -13.7-8.8), while in the control group (n = 32) the median change was 4.5 (IQR -4.8-33.5). The median difference between the groups was -7.0 (95% confidence interval [CI] -37.0-3.0; P = .21). In the intention-to-treat analysis, the relative risk (RR) for achieving >50% seizure reduction was 1.8 (95% CI 0.3-10.2; P = .65), while for achieving >25% seizure reduction RR was 2.43 (95% CI 0.94-6.28; P = .06). We observed no serious adverse events. SIGNIFICANCE: In this RCT investigating the effect of an adjunctive modified Atkins diet on seizure frequency in adults with difficult-to-treat focal epilepsy, we found a significant reduction in seizure frequency in the diet group compared to the controls, but only for moderate benefit (>25% seizure reduction) among those who completed the intervention. However, seizure response varied considerably between individuals, perhaps negatively influenced by a drop in serum concentrations of antiepileptic drugs.

Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI.

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study.

AIM: Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. METHODS: We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste-Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow-up visit. RESULTS: We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2-20.7 years) at the initiation of treatment. The average length of follow-up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow-up visit, respectively. One became seizure-free. Adverse effects were reported in 11 patients and none were severe. Responders and non-responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). CONCLUSION: Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.

Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

OBJECTIVE: The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. METHODS: We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. RESULTS: Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. SIGNIFICANCE: The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not.

Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

Ketogenic diet in adolescents and adults with epilepsy.

PURPOSE: The ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. METHOD: Twenty-nine adult and adolescent patients (mean age 32 years, range 11-51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. RESULTS: Fifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13-35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. CONCLUSION: The ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment.

Historic, clinical, and prognostic features of epileptic encephalopathies caused by CDKL5 mutations.

Mutations within the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene are important causes of early-onset epileptic encephalopathies. We sought to determine the historic, clinical, and prognostic features of epilepsy secondary to CDKL5 mutations. We performed retrospective chart reviews of children at our institution with epilepsy and CDKL5 mutations. Six children were identified. One manifested a deletion in exons 10-15 of the CDKL5 gene, another manifested a single base-pair duplication in exon 3, and the rest manifested base-pair exchanges. The mean age of seizure onset was 1.8 months (range, 1-3 months). Although the majority (4/6, 67%) presented with partial-onset seizures, all children developed infantile spasms. All children demonstrated developmental delay and visual impairment. Although such mutations are X-linked, two children were boys. They did not present with more severe phenotypes than their female counterparts. Despite trials of antiepileptic drugs (mean, 5; range, 3-7), steroids/adrenocorticotropic hormone (4/6; 67%), and the ketogenic diet (6/6; 100%), all children manifested refractory seizures at last follow-up. Although no treatment eliminated seizures, topiramate, vigabatrin, and the ketogenic diet were most helpful at reducing seizure frequency.

[Remarkable effect of a modified ketogenic diet in a boy with focal seizures followed by epileptic spasms in a cluster].

A modified ketogenic diet was demonstrated to be remarkably effective in a child with intractable symptomatic focal epilepsy with combined seizures of focal seizures and epileptic spasms (ES) in a cluster (ESC). ES started at 8 months of age and disappeared with ACTH therapy. At the age of 13 months, the child began to have intractable focal seizures that, later, were followed by ESC 10 times a day. Brain MRI showed only a non-specific diffuse cerebral atrophy. Interictal EEG showed high amplitude diffuse disorganized slow waves with prominent sharp waves predominant over the bilateral occipital region. We started a modified ketogenic diet (mKD) treatment without fasting or a water/calorie limitation. Since the 20th day of mKD, the patient has been seizure free (6 months) without adverse effects. EEG showed remarkable improvement and he has some improvement in the developmental milestones. A modified ketogenic diet is easier to start and continue compared to the classic ketogenic diet, and should be tried in intractable epilepsies that are not treatable surgically early in life from the developmental prognosis point of view.

Traditional and non-traditional treatments for autism spectrum disorder with seizures: an on-line survey.

BACKGROUND: Despite the high prevalence of seizure, epilepsy and abnormal electroencephalograms in individuals with autism spectrum disorder (ASD), there is little information regarding the relative effectiveness of treatments for seizures in the ASD population. In order to determine the effectiveness of traditional and non-traditional treatments for improving seizures and influencing other clinical factor relevant to ASD, we developed a comprehensive on-line seizure survey. METHODS: Announcements (by email and websites) by ASD support groups asked parents of children with ASD to complete the on-line surveys. Survey responders choose one of two surveys to complete: a survey about treatments for individuals with ASD and clinical or subclinical seizures or abnormal electroencephalograms, or a control survey for individuals with ASD without clinical or subclinical seizures or abnormal electroencephalograms. Survey responders rated the perceived effect of traditional antiepileptic drug (AED), non-AED seizure treatments and non-traditional ASD treatments on seizures and other clinical factors (sleep, communication, behavior, attention and mood), and listed up to three treatment side effects. RESULTS: Responses were obtained concerning 733 children with seizures and 290 controls. In general, AEDs were perceived to improve seizures but worsened other clinical factors for children with clinical seizure. Valproic acid, lamotrigine, levetiracetam and ethosuximide were perceived to improve seizures the most and worsen other clinical factors the least out of all AEDs in children with clinical seizures. Traditional non-AED seizure and non-traditional treatments, as a group, were perceived to improve other clinical factors and seizures but the perceived improvement in seizures was significantly less than that reported for AEDs. Certain traditional non-AED treatments, particularly the ketogenic diet, were perceived to improve both seizures and other clinical factors.For ASD individuals with reported subclinical seizures, other clinical factors were reported to be worsened by AEDs and improved by non-AED traditional seizure and non-traditional treatments. The rate of side effects was reportedly higher for AEDs compared to traditional non-AED treatments. CONCLUSION: Although this survey-based method only provides information regarding parental perceptions of effectiveness, this information may be helpful for selecting seizure treatments in individuals with ASD.

Comparison of short- versus long-term ketogenic diet for intractable infantile spasms.

PURPOSE: To compare the prognoses between short-term (8 months) and conventional long-term (> 2 years) trials involving patients with refractory infantile spasms who successfully completed the ketogenic diet (KD). METHODS: Of 40 patients who achieved seizure-free outcomes and showed improvement in hypsarrhythmic patterns within 6 months of the KD, with a 3:1 fat to nonfat ratio as an add-on treatment, 16 patients were randomized into the short-term trial group and the diet was tapered throughout two additional months. Twenty-four patients were randomized into a long-term trial group, and 19 patients could successfully discontinue the diet after 2 years. Primary outcome measures included seizure relapse and frequency of 35 patients for > 12 months after successful completion of the KD. KEY FINDINGS: Of 16 patients in the short-term trial group, two patients relapsed with clusters of spasms, and one patient had recurrence of occasional focal seizures. Of 19 patients in the long-term trial group, two patients progressed to Lennox-Gastaut syndrome and one patient experienced recurrence of occasional focal seizures with secondary generalization. An early response to the KD, evidenced by short latency before seizure freedom and disappearance of hypsarrythmia and cryptogenic etiology, may indicate a successful early discontinuation of the KD. Significant growth failure was complicated only in conventional long-term trial group. SIGNIFICANCE: Use of the KD for only 8 months in children who become spasm-free appears to be justified, with similar outcomes, recurrence rate, and less growth disturbance than a longer-term, traditional use.

RMSSD, a measure of vagus-mediated heart rate variability, is associated with risk factors for SUDEP: the SUDEP-7 Inventory.

OBJECTIVE: The goal of this study was to determine if specific measures of heart rate variability (HRV) are associated with the total score on a new seven-item inventory for sudden unexplained death in epilepsy (SUDEP). METHODS: Nineteen subjects with intractable partial seizures, at least three per month, were enrolled in a randomized clinical trial of omega-3 fatty acids in epilepsy. At study entry, subjects underwent a 1-hour ECG recording for the determination of HRV. To estimate the risk of SUDEP, we assembled a seven-item inventory (the SUDEP-7 Inventory) from risk factors prospectively validated by T.S. Walczak, I.E. Leppik, M. D'Amelio M, et al. (Neurology 2001;56:519-25). The SUDEP-7 score was then correlated with measures of HRV using the Pearson correlation and other parametric and nonparametric methods. RESULTS: Subjects had highly drug-resistant seizures, with a mean seizure frequency of 22.8 seizures per month. Scores on the SUDEP-7 inventory ranged from 1 to 7 of a maximum possible score of 12. RMSSD, a measure of high-frequency HRV, was inversely correlated with the SUDEP-7 score, r=-0.64, P=0.004. Subjects with higher SUDEP-7 scores had reduced levels of HRV (RMSSD). Other time-dependent measures of HRV (SDNN, SDANN) were not significantly correlated with SUDEP risk scores. CONCLUSIONS: RMSSD, a measure of HRV, which reflects the integrity of vagus nerve-mediated autonomic control of the heart, is highly associated with the total score on a new seven-item SUDEP risk inventory. Lower RMSSD values were associated with higher risk scores on the new SUDEP risk inventory. This provides new evidence that HRV (specifically RMSSD) is a marker of SUDEP risk.

Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?

It has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less-restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information was obtained from 27 patients who made this dietary change from four different institutions. Ten (37%) patients had ≥10% additional seizure reduction with the KD over the MAD, of which five became seizure-free. The five children who did not improve on the MAD failed to improve when transitioned to the KD. A higher incidence of improvement with the KD occurred for those with myoclonic-astatic epilepsy (70% vs. 12% for all other etiologies, p = 0.004), including all who became seizure-free. These results suggest that the KD probably represents a "higher dose" of dietary therapy than the MAD, which may particularly benefit those with myoclonic-astatic epilepsy.

Rational treatment options with AEDs and ketogenic diet in Landau-Kleffner syndrome: still waiting after all these years.

Antiepileptic drugs (AEDs) remain a first treatment approach in Landau-Kleffner syndrome (LKS) and related syndromes. In the current literature, only class IV evidence is available. Inclusion criteria and outcome parameters are ill-defined. Most commonly, valproate, ethosuximide, and/or benzodiazepines are used. More recent case series show that sulthiame and especially levetiracetam can be considered as effective drugs. Smaller studies also point to the ketogenic diet as a valuable treatment option in LKS.

The ketogenic diet improves recently worsened focal epilepsy.

AIM: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. METHOD: From the 70 patients who received the ketogenic diet during a 3-year period at our institution, we retrospectively selected patients with focal epilepsy. There were 22 children, 13 females and nine males, aged from 5 months to 18 years 6 months (mean 6y 9mo, SD 5y 11mo). Fifteen had symptomatic and seven had cryptogenic focal epilepsy. Seizure frequency 1 week before initiating the ketogenic diet was compared with that at 1 month and at the last visit on the diet. RESULTS: Eleven patients were responders (defined as reduction of seizures by more than 50%) at 1 month. Responders were higher (p=0.046) in the group with a recent worsening of seizures than in those with stable seizure frequency. Seven patients were still seizure-free at 6 months on the diet. Tolerability was excellent in 10 patients. Five patients stopped the diet because of early side effects. INTERPRETATION: The ketogenic diet may be a valuable therapeutic option for children with pharmacoresistant focal epilepsy, particularly those with a recent deterioration of seizure control and neurological status. Because of its rapid effect, the ketogenic diet may be a useful support to intravenous emergency drugs in such a situation.

Growth dependence on insulin-like growth factor-1 during the ketogenic diet.

PURPOSE: To examine the influence of the ketogenic diet (KD) on linear growth and insulin-like growth factor I (IGF-I) levels in children with pharmacotherapy-resistant epilepsy. METHODS: A prospective study was designed to evaluate growth, serum IGF-I levels, blood beta-hydroxybutyric acid (beta-OHB), and seizure frequency before and during KD in 22 children (median age 5.5 years). Growth was assessed by measurements of weight, height, body mass index (BMI), and height velocity. Standard deviation scores (SDS) were calculated for all measured parameters as well as for serum IGF-I to eliminate the influence of age- and sex-related differences among patients. RESULTS: Fourteen of the 22 patients responded to the KD. Weight, height, BMI, and height velocity decreased significantly during the KD. We found that the KD had profound influence on growth and IGF-I levels. No correlation was found between seizure response and growth alterations. Height velocity correlated negatively with beta-OHB during the KD. The slope of the regression of height velocity against IGF-I decreased significantly during the KD. CONCLUSIONS: Height velocity was most affected in those with pronounced ketosis, which implies that, in clinical practice, the level of ketosis should be related to outcomes in seizure response and growth. Our data indicate that growth disturbances and the decreased sensitivity of growth to similar IGF-I levels during KD are independent of seizure reduction. The metabolic status induced by KD may be the mechanism underlying both alterations of linear growth and seizure reduction.

SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy.

SV2A, a synaptic vesicle protein, has been recently identified as a binding target for levetiracetam (Keppra). The specific mechanism by which SV2A binding leads to seizure protection has not yet been fully elucidated. However, a functional correlation between SV2A binding affinity and anticonvulsant potency has been observed in the mouse audiogenic seizure model. The present study was undertaken to test whether similar correlations exist in rodent models of partial and generalized epilepsies. As expected, there was a high degree of correlation between anticonvulsant potency and SV2A binding affinity in the mouse audiogenic seizure model (r(2)=0.77; p<0.001). A similar correlation was also observed in the mouse corneal kindling (r(2)=0.80; p<0.01) and in the rat model of generalized absence epilepsy (GAERS) (r(2)=0.72; p<0.01). Moreover, there were no significant differences between the slopes and intercepts of regression lines in these models. Interestingly, the protective potencies in these three epilepsy models were also well correlated with each other. As such, protective doses of a given SV2A ligand in one model could be easily predicted based on the data obtained in another model. Taken together, these results support the concept that SV2A protein is an important target for both partial and generalized epilepsies and thereby relevant for the generation of new antiepileptic drugs with potential broad-spectrum efficacy.

[The role of the ketogenic diet in the management of epilepsy]. / Zastosowanie diety ketogennej we wspomaganiu leczenia epilepsji.

Ketogenic Diet is effective in the treatment of epilepsy in both children and adults. KD increases the effectiveness of conventional therapies and can be applied for the treatment of other diseases. Simultaneously, KD is cheaper and does not possess as many adverse effects as conventional medicine.

The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.

PURPOSE: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures. METHODS: On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction. RESULTS: Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects. CONCLUSION: The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.