Exploring the relationship between preferences for high fat foods and efficacy of the ketogenic and modified Atkins diets among children with seizure disorders.

PURPOSE: Previous research has indicated that children with seizures may prefer high fat foods - a preference compatible with ketogenic and modified Atkins dietary therapies. The purpose of this prospective study was to examine the relationship between fat preference and efficacy of therapeutic diets in treating intractable seizures among a pediatric population. METHODS: Preference for high fat foods was directly assessed in a sample of 30 children prior to commencing either the ketogenic or modified Atkins diet. Seizure control was assessed at 1, 3, 6, and 12 months following diet initiation. Using an intent-to-treat analysis, correlations between fat preference and diet efficacy were examined at each follow-up and across the follow-up period. RESULTS: At individual follow-ups, correlations between fat preference and diet efficacy varied in terms of both strength and significance; however, modest, positive correlations with fat preference were significant when examining high levels of efficacy (100% seizure reduction, ≥90% seizure reduction) across a 1-year follow-up period. CONCLUSION: These findings provide preliminary evidence that fat preference, when directly assessed, may be a useful predictor of treatment efficacy for the ketogenic and modified Atkins diets; however, further research is necessary.

Intermittent fasting: a "new" historical strategy for controlling seizures?

In antiquity, fasting was a treatment for epilepsy and a rationale for the ketogenic diet (KD). Preclinical data indicate the KD and intermittent fasting do not share identical anticonvulsant mechanisms. We implemented an intermittent fasting regimen in six children with an incomplete response to a KD. Three patients adhered to the combined intermittent fasting/KD regimen for 2 months and four had transient improvement in seizure control, albeit with some hunger-related adverse reactions.

Efficacy of the ketogenic diet in Lennox-Gastaut syndrome: a retrospective review of one institution's experience and summary of the literature.

AIM: To determine the efficacy of the ketogenic diet for children with Lennox-Gastaut syndrome (LGS) at our institution and in the literature. METHOD: The records of children with LGS initiated on the ketogenic diet at our institution from 1994 to 2010 were reviewed. Inclusion criteria included the presence of ≤2.5Hz spike-and-wave complexes on electroencephalogram, multiple seizure types including tonic, atonic, or atypical absence, developmental delay, and age under 1 year. We additionally reviewed the literature for cases of LGS treated with the ketogenic diet and their outcomes. RESULTS: Seventy-one children (41 males, 30 females, median age 3y 6mo, range 18mo-18y), with LGS were initiated on the ketogenic diet. Using an intent-to-treat analysis, after 6 months, 36 (51%) achieved more than 50% seizure reduction, 16 (23%) experienced more than 90% seizure reduction, and 1 (1%) achieved seizure freedom. Results were similar after 12 months. Age, sex, side effects, valproate use, and history of infantile spasms were not predictive of more than 90% seizure reduction. In the literature, 88 of 189 (47%) children with LGS had more than 50% seizure reduction after 3 to 36 months of ketogenic diet treatment. INTERPRETATION: The ketogenic diet is efficacious in the treatment of LGS, with approximately one-half of children responding at 12 months.

Is there an ideal way to discontinue the ketogenic diet?

It is unclear what the ideal weaning speed of the ketogenic diet should be and the resultant risk of seizure worsening. A retrospective chart review was performed of children who discontinued the ketogenic diet at Johns Hopkins Hospital from January 2000 to June 2010. Speed of discontinuation was categorized into immediate (<1 week), quick (1-6 weeks), or slow (>6 weeks) rates. One hundred and eighty-three children were identified. Children with both a longer diet duration (p=0.004) and lower seizure frequency (p<0.001) were weaned more slowly by our group. There was no significant difference in the incidence of seizures worsening between discontinuation rates. However, there was an increased risk of seizures worsening in those specifically with a 50-99% seizure reduction (30% vs. 8%, p<0.0001) and for that level of seizure improvement, in those who were receiving more anticonvulsants (1.4 vs. 0.8, p=0.01). In summary, there does not appear to be an increased risk of seizure exacerbation with rapid ketogenic diet discontinuations. Those who improved 50-99% and were receiving more anticonvulsants were at the highest risk overall. Discontinuing the ketogenic diet over weeks rather than months appears safe.

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

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 >or=1 month, and had discontinued it >or=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.

Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet.

OBJECTIVE: Kidney stones are an adverse event with the ketogenic diet (KD), occurring in approximately 6% of children who are started on this therapy for intractable epilepsy. Potassium citrate (Polycitra K) is a daily oral supplement that alkalinizes the urine and solubilizes urine calcium, theoretically reducing the risk for kidney stones. METHODS: Children who started the KD from 2000 to 2008 at Johns Hopkins Hospital, with at least 1 month of follow-up, were evaluated (N = 313). From 2000 to 2005, children were treated with daily Polycitra K at 2 mEq/kg per day only in the setting of identified hypercalciuria, whereas, since 2006, it has been started for all children empirically at KD onset. RESULTS: Polycitra K was administered to 198 children preventatively overall, 4 (2.0%) of whom developed kidney stones, compared with 11 (10.5%) of 105 who did not receive Polycitra K (P = .003). Two children since 2006 refused Polycitra K, 1 of whom developed a kidney stone. Successful empiric administration of Polycitra K at KD onset resulted in a kidney-stone incidence of 0.9% (1 of 106) compared with administration only because of hypercalciuria, 6.7% (13 of 195; P = .02). Polycitra K resulted in less acidic urine (mean pH: 6.8 vs 6.2; P = .002) but not reduced serum acidosis. No adverse effects of oral citrates were reported. CONCLUSIONS: Oral potassium citrate is an effective preventive supplement against kidney stones in children who receive the KD, achieving its goal of urine alkalinization. Universal supplementation is warranted.

High-dose oral prednisolone for infantile spasms: an effective and less expensive alternative to ACTH.

The ideal treatment of infantile spasms is unclear, but many studies advocate hormonal treatment. In the United States, intramuscular ACTH is most widely used, despite the problematic financial cost and side effect profile. Since September 2007, we have replaced ACTH with high-dose oral prednisolone (40-60 mg/day) according to the 2004 United Kingdom Infantile Spasms Study (UKISS). Ten of 15 (67%) infants with new-onset and previously treated infantile spasms became spasm free within 2 weeks; 4 later recurred. More children with an idiopathic etiology for infantile spasms were spasm free than were symptomatic cases (88% vs 43%, P=0.10). Spasm freedom was equivalent to our most recent 15 infants receiving ACTH, with 13 (87%) responding, P=0.16. Oral prednisolone had fewer adverse effects (53% vs 80%, P=0.10) and was less expensive ($200 vs approximately $70,000) than ACTH. We now routinely recommend oral prednisolone to all families of children with infantile spasms.

Use of the ketogenic diet in neonates and infants.

The ketogenic diet (KD) is still viewed as virtually last-line therapy in childhood epilepsies, and specifically as unsafe and difficult to initiate and maintain in neonates and infants. Information is presented to show that the KD is safe and efficacious in this population, and should be carefully studied to determine its real usefulness as first-line or early therapy (one or fewer anticonvulsants) in the catastrophic epilepsies of infancy.

Management and risk factors for dyslipidemia with the ketogenic diet.

A prospective study was performed of all children started on the ketogenic diet at our institution for intractable epilepsy from January 2003 to March 2007 (n = 137), examining for baseline and follow-up total cholesterol and triglyceride levels. Interventions for dyslipidemia were analyzed for their effectiveness. At baseline, 25% of children had hypercholesterolemia (>200 mg/dL), which increased to 60% for those receiving the ketogenic diet. Children receiving a solely formula-based ketogenic diet were less likely to have hypercholesterolemia than those eating solid food after adjusting for age and initial ketogenic ratio (P < .001). Only a slightly higher likelihood of a 20% decrease in cholesterol occurred for those children in whom a dietary intervention was made compared with observation alone (60% vs 41%; P = .11). Hypercholesterolemia occurs in most children receiving a solid food based ketogenic diet but improved in approximately half, even without interventions.

Decreased relative efficacy of the ketogenic diet for children with surgically approachable epilepsy.

PURPOSE: In children with intractable, surgically approachable epilepsy, the ketogenic diet is often perceived as less efficacious than surgery. METHODS: A retrospective chart review was performed of 554 children started on the ketogenic diet since 1994. Forty-five children were identified as surgical candidates, with at least 2 focal routine EEGs, ictal video-EEG, and corresponding focal neuroimaging findings, of whom 24 eventually had resective surgery and were followed subsequently. A comparison cohort group was also created of 45 children matched for age and seizure frequency that received the diet but were not surgical candidates (multifocal or generalized seizures). RESULTS: Of the 24 children who received both dietary and surgical therapies, there was a higher likelihood after 6 months of both >90% seizure reduction (71% versus 17%) and seizure freedom (63% versus 0%) following surgery, both p < 0.0001. Similarly, the 45 cohort children who were not surgical candidates were more likely to be seizure-free (29% versus 13%, p = 0.041) and remained on the diet for shorter duration (10 months versus 18 months, p = 0.035) compared to the surgical group. CONCLUSION: Children with surgically approachable epilepsy do respond to the diet, but are more likely to be seizure-free following surgery.

Combined ketogenic diet and vagus nerve stimulation: rational polytherapy?

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.

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.

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.

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.

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.

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.

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.