Tolerance, adherence, and acceptability of a ketogenic 2.5:1 ratio, nutritionally complete, medium chain triglyceride-containing liquid feed in children and adults with drug-resistant epilepsy following a ketogenic diet.

OBJECTIVE: To investigate incorporating a ready-to-use 2.5:1 ratio liquid feed into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. METHODS: Following a three-day baseline, patients (n = 19; age: 19 years [SD 13], range: 8-46 years) followed a KD for 28 days (control period), then incorporated ≥200 mL/day of a ready-to-use liquid feed, made with a ratio of 2.5 g of fat to 1 g of protein plus carbohydrate and including medium chain triglycerides ([MCTs]; 25.6% of total fat/100 mL) for 28 days as part of their KD (intervention period). Outcome measures (control vs intervention period) included gastrointestinal (GI) tolerance, adherence to KD and intervention feed, dietary intake, blood ß-hydroxybutyrate (BHB) concentration, seizure outcomes, health-related quality of life (HRQoL), acceptability and safety. RESULTS: Compared to the control period, during the intervention period, the percentage of patients reporting no GI symptoms increased (+5% [SD 5], p = 0.02); adherence to the KD prescription was similar (p = 0.92) but higher in patients (n = 5) with poor adherence (<50%) to KD during the control period (+33% [SD 26], p = 0.049); total MCT intake increased (+12.1 g/day [SD 14.0], p = 0.002), driven by increases in octanoic (C8; +8.3 g/day [SD 6.4], p < 0.001) and decanoic acid (C10; +5.4 g/day [SD 5.4], p < 0.001); KD ratio decreased (p = 0.047), driven by a nonsignificant increase in protein intake (+11 g/day [SD 44], p = 0.29); seizure outcomes were similar (p ≥ 0.63) but improved in patients (n = 6) with the worst seizure outcomes during the control period (p = 0.04); and HRQoL outcomes were similar. The intervention feed was well adhered to (96% [SD 8]) and accepted (≥88% of patients confirmed). SIGNIFICANCE: These findings provide an evidence-base to support the effective management of children and adults with drug-resistant epilepsy following a KD with the use of a ready-to-use, nutritionally complete, 2.5:1 ratio feed including MCTs. PLAIN LANGUAGE SUMMARY: This study examined the use of a ready-to-use, nutritionally complete, 2.5:1 ratio (2.5 g of fat to 1 g of protein plus carbohydrate) liquid feed, including medium chain triglycerides (MCTs), into a ketogenic diet (KD) in children and adults with drug-resistant epilepsy. The results show that the 2.5:1 ratio feed was well tolerated, adhered to, and accepted in these patients. Increases in MCT intake (particularly C8 and C10) and improvements in seizure outcomes (reduced seizure burden and intensity) and KD adherence also occurred with the 2.5:1 ratio feed in patients with the worst seizures and adherence, respectively.

Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial.

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research.

Impact of ketogenic diet therapy on growth in children with epilepsy.

RATIONALE: Ketogenic diet therapy (KDT) is an effective treatment for drug-resistant epilepsy in children. There is conflicting evidence regarding the impact of KDT on growth. We aimed to determine whether linear growth and weight were affected in children who followed KDT in the UK, and to explore potential associations with clinical or demographic factors with impacted growth. METHODS: A retrospective review of medical records of children with epilepsy following KDT at 3 UK centres was conducted. Height and weight measurements taken as part of routine clinical management were recorded at baseline, 1-8 years on diet, and 1-year post-diet. Measurements were converted into z-scores, and the differences from baseline analysed using Wilcoxon Signed Rank tests. Potential associations of impacted growth with feeding method, ambulatory status, diet type, age at diet onset and average daily protein intake were investigated using Mann-Whitney, Kruskal-Wallis tests or Spearman's Rank correlation. RESULTS: 265 individuals were included, of which 84 had post-diet data available. Median height z-score significantly decreased at 1- (n = 139, p = .018), 2- (n = 86, p < .0005) and 3 years (n = 27, p = .001) on diet. There was no significant change to height or weight z-score 1-year post-diet discontinuation. Median weight z-score significantly decreased from baseline at 4 years (n = 15, p = .020), and 6 years (n = 8, p = .025) on diet, but not at other time points. There was greater height z-score decrease in non-ambulatory children at 2 years (p = .009), in those following a classical diet compared with the modified ketogenic diet at 2 years (p = .006) and amongst younger children at 2 years (n = 86, p < .005) and 3 years (n = 27, p = .008) on diet. No significant differences were found in weight z-score change across any subgroup, following Bonferroni correction for multiple testing. CONCLUSIONS: Median linear growth was significantly adversely affected for the first 3 years on KDT but catch-up growth post diet discontinuation was observed. Non-ambulatory children, younger children, and individuals following a classical diet may be more vulnerable to impacted growth when on KDT, although this was not consistent across all time points. The potential short-term impact on linear growth should be discussed with individuals considering KDT, and monitored closely.

K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy.

This prospective open-label feasibility study aimed to evaluate acceptability, tolerability and compliance with dietary intervention with K.Vita, a medical food containing a unique ratio of decanoic acid to octanoic acid, in individuals with drug-resistant epilepsy. Adults and children aged 3-18 years with drug-resistant epilepsy took K.Vita daily whilst limiting high-refined sugar food and beverages. K.Vita was introduced incrementally with the aim of achieving ≤35% energy requirements for children or 240 ml for adults. Primary outcome measures were assessed by study completion, participant diary, acceptability questionnaire and K.Vita intake. Reduction in seizures or paroxysmal events was a secondary outcome. 23/35 (66%) children and 18/26 (69%) adults completed the study; completion rates were higher when K.Vita was introduced more gradually. Gastrointestinal disturbances were the primary reason for discontinuation, but symptoms were similar to those reported from ketogenic diets and incidence decreased over time. At least three-quarters of participants/caregivers reported favourably on sensory attributes of K.Vita, such as taste, texture and appearance, and ease of use. Adults achieved a median intake of 240 ml K.Vita, and children 120 ml (19% daily energy). Three children and one adult had ß-hydroxybutyrate >1 mmol/l. There was 50% (95% CI 39-61%) reduction in mean frequency of seizures/events. Reduction in seizures or paroxysmal events correlated significantly with blood concentrations of medium chain fatty acids (C10 and C8) but not ß-hydroxybutyrate. K.Vita was well accepted and tolerated. Side effects were mild and resolved with dietetic support. Individuals who completed the study complied with K.Vita and additional dietary modifications. Dietary intervention had a beneficial effect on frequency of seizures or paroxysmal events, despite absent or very low levels of ketosis. We suggest that K.Vita may be valuable to those with drug-resistant epilepsy, particularly those who cannot tolerate or do not have access to ketogenic diets, and may allow for more liberal dietary intake compared to ketogenic diets, with mechanisms of action perhaps unrelated to ketosis. Further studies of effectiveness of K.Vita are warranted.

Keto-on-the-Clock: A Survey of Dietetic Care Contact Time Taken to Provide Ketogenic Diets for Drug-Resistant Epilepsy in the UK.

Medical ketogenic diets (KDs) are effective yet resource-intensive treatment options for drug-resistant epilepsy (DRE). We investigated dietetic care contact time, as no recent data exist. An online survey was circulated to ketogenic dietitians in the UK and Ireland. Data were collected considering feeding route, KD variant and type of ketogenic enteral feed (KEF), and the estimated number of hours spent on patient-related activities during the patient journey. Fifteen dietitians representing nine KD centres responded. Of 335 patients, 267 (80%) were 18 years old or under. Dietitians spent a median of 162 h (IQR 54) of care contact time per patient of which a median of 48% (IQR 6) was direct contact. Most time was required for the classical KD taken orally (median 193 h; IQR 213) as a combined tube and oral intake (median 211 h; IQR 172) or a blended food KEF (median 189 h; IQR 148). Care contact time per month was higher for all KDs during the three-month initial trial compared to the two-year follow-up stage. Patients and caregivers with characteristics such as learning or language difficulties were identified as taking longer. Twelve out of fifteen (80%) respondents managed patients following the KD for more than two years, requiring an estimated median contact care time of 2 h (IQR 2) per patient per month. Ten out of fifteen (67%) reported insufficient official hours for dietetic activities. Our small survey gives insight into estimated dietetic care contact time, with potential application for KD provision and service delivery.

Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre.

Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the efficacy of KDT for super-refractory status epilepticus (SRSE). We systematically review evidence for use of KDT in children with SRSE and present a single UK tertiary centre's experience. Thirty one articles were included, of which 24 were "medium" or "low" quality. One hundred and forty seven children with SRSE started KDT, of which 141 (96%) achieved ketosis. KDT was started mean 5.3 days (range 1-420) after status epilepticus (SE) started. SRSE resolved in 85/141 (60%) children after mean 6.3 days (range 0-19) post SE onset, but it is unclear whether further treatments were initiated post-KDT. 13/141 (9%) children died. Response to KDT was more likely when initiated earlier (p = 0.03) and in females (p = 0.01). Adverse side effects were reported in 48/141 (34%), mostly gastrointestinal; potentially serious adverse effects occurred in ≤4%. Eight children with SRSE, all diagnosed with febrile infection-related epilepsy syndrome, were treated with KDT at Great Ormond Street Hospital for Children. KDT was initiated enterally at mean day 13.6+/- 5.1 of admission. Seven of 8 (88%) children reported adverse side effects, which were potentially serious in 4/8 (50%), including metabolic acidosis, hypoglycaemia and raised amylase. SE ceased in 6/8 (75%) children after mean 25+/- 9.4 days post onset, but other treatments were often started concomitantly and all children started other treatments post-KDT. Two of 8 (25%) children died during admission and another died post-admission. Four of the remaining 5 children continue to have drug-resistant seizures, one of whom remains on KDT; seizure burden was unknown for one child. Our findings indicate that KDT is possible and safe in children with SRSE. Cessation of SRSE may occur in almost two-thirds of children initiated with KDT, but a causal effect is difficult to determine due to concomitant treatments, treatments started post-KDT and the variable length of time post-KDT onset when SRSE cessation occurs. Given that serious adverse side effects seem rare and response rates are (cautiously) favorable, KDT should be considered as an early treatment option in this group.

Use of ketogenic diet therapy in infants with epilepsy: A systematic review and meta-analysis.

OBJECTIVE: Ketogenic diet therapy (KDT) is a group of high-fat, low-carbohydrate diets used as an effective treatment option for children and adults with drug-resistant epilepsy. There is limited research on the efficacy of KDT in infants, where there is the highest incidence of onset of the epilepsy. We aimed to systematically review studies that have reported on response to KDT in infants with epilepsy. METHODS: An online comprehensive literature search was performed, including studies that provided seizure frequency data for at least one infant younger than 2 years of age who was treated with KDT for ≥1 month. The proportions of infants achieving ≥50% seizure reduction, seizure-freedom rates, retention rates, and reported side effects were extracted from studies. Meta-analyses were performed using a random-effects model, and subgroup analyses were performed to investigate possible between-study heterogeneity. RESULTS: Thirty-three studies met inclusion criteria and were included in the final analysis, with a total of 534 infants with efficacy data. Two studies were randomized-controlled trials, and the remainder were uncontrolled cohort studies. All studies were categorized as low quality. Meta-analyses of uncontrolled studies estimate 59% (95% confidence interval [CI] 53-65) of infants achieved ≥50% seizure reduction and 33% (95% CI 26-43) of infants achieved seizure freedom. Retention rates ranged from 84% at 3 months to 27% at 24 months. The most commonly reported side effects were dyslipidemia (20/171, 12%), vomiting (11/171, 6%), constipation (7/171, 4%), gastroesophageal reflux (6/171, 4%), and diarrhea (6/171, 4%). SIGNIFICANCE: This review indicates that KDT is safe and tolerable and that it can be an effective treatment option for infants with drug-resistant epilepsy. However, there are few studies focusing on infants treated with KDT, and high-quality evidence is lacking. High-quality randomized-controlled trials are needed to confirm the effectiveness, safety, and tolerability of dietary treatment in this vulnerable age group.

Biochemical assessment of patients following ketogenic diets for epilepsy: Current practice in the UK and Ireland.

OBJECTIVE: Biochemical assessment is recommended for patients prior to initiating and following a ketogenic diet (KD). There is no published literature regarding current practice in the UK and Ireland. We aimed to explore practice in comparison with international guidelines, determine approximate costs of biochemical testing in KD patients across the UK and Ireland, and promote greater consistency in KD services nationally. METHODS: A survey was designed to determine the biochemical tests requested for patients at baseline, 3, 6, 12, 18, and 24 months + on KD. The survey was circulated to 39 centers across the UK and Ireland. RESULTS: Sixteen centers completed the survey. Full blood count, electrolytes, calcium, liver function tests (LFTs), lipid profile, and vitamin D were requested at all centers at baseline, in keeping with international guidelines. Bicarbonate, total protein, and urinalysis were less consistently requested. Magnesium and zinc were requested by all centers, despite not being specifically recommended for pre-diet evaluation in guidelines. Urea and electrolyte profiles and some LFTs were consistently requested at follow-up, in accordance with guidelines. Other LFTs and renal tests, full blood count, lipid profile, acylcarnitine profile, selenium, vitamin D, and urinalysis were less consistently requested at follow-up. The mean costs of the lowest and highest number of tests requested at baseline in our participating centers were £167.54 and £501.93; the mean costs of the lowest and highest number of tests requested at 3-month follow-up were £19.17 and £450.06. SIGNIFICANCE: Biochemical monitoring of KD patients varies widely across the UK and Ireland and does not fully correspond to international best practice guidelines. With an ongoing drive for cost-effectiveness within health care, further work is needed to streamline practice while ensuring patient safety.

Genome-wide association study: Exploring the genetic basis for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy.

OBJECTIVE: With the exception of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDTs) are unknown. We aimed to determine whether common variation across the genome influences the response to KDT for epilepsy. METHODS: We genotyped individuals who were negative for glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Genotyping was performed with the Infinium HumanOmniExpressExome Beadchip. Hospital records were used to obtain demographic and clinical data. KDT response (≥50% seizure reduction) at 3-month follow-up was used to dissect out nonresponders and responders. We then performed a genome-wide association study (GWAS) in nonresponders vs responders, using a linear mixed model and correcting for population stratification. Variants with minor allele frequency <0.05 and those that did not pass quality control filtering were excluded. RESULTS: After quality control filtering, the GWAS of 112 nonresponders vs 123 responders revealed an association locus at 6p25.1, 61 kb upstream of CDYL (rs12204701, P = 3.83 × 10-8 , odds ratio [A] = 13.5, 95% confidence interval [CI] 4.07-44.8). Although analysis of regional linkage disequilibrium around rs12204701 did not strengthen the likelihood of CDYL being the candidate gene, additional bioinformatic analyses suggest it is the most likely candidate. SIGNIFICANCE: CDYL deficiency has been shown to disrupt neuronal migration and to influence susceptibility to epilepsy in mice. Further exploration with a larger replication cohort is warranted to clarify whether CDYL is the causal gene underlying the association signal.

An examination of biochemical parameters and their association with response to ketogenic dietary therapies.

OBJECTIVE: In the absence of specific metabolic disorders, accurate predictors of response to ketogenic dietary therapies (KDTs) for treating epilepsy are largely unknown. We hypothesized that specific biochemical parameters would be associated with the effectiveness of KDT in humans with epilepsy. The parameters tested were ß-hydroxybutyrate, acetoacetate, nonesterified fatty acids, free and acylcarnitine profile, glucose, and glucose-ketone index (GKI). METHODS: Biochemical results from routine blood tests conducted at baseline prior to initiation of KDT and at 3-month follow-up were obtained from 13 adults and 215 children with KDT response data from participating centers. One hundred thirty-two (57%) of 228 participants had some data at both baseline and 3 months; 52 (23%) of 228 had data only at baseline; 22 (10%) of 228 had data only at 3 months; and 22 (10%) of 228 had no data. KDT response was defined as ≥50% seizure reduction at 3-month follow-up. RESULTS: Acetyl carnitine at baseline was significantly higher in responders (p < 0.007). It was not associated with response at 3-month follow-up. There was a trend for higher levels of free carnitine and other acylcarnitine esters at baseline and at 3-month follow-up in KDT responders. There was also a trend for greater differences in levels of propionyl carnitine and in ß-hydroxybutyrate measured at baseline and 3-month follow-up in KDT responders. No other biochemical parameters were associated with response at any time point. SIGNIFICANCE: Our finding that certain carnitine fractions, in particular baseline acetyl carnitine, are positively associated with greater efficacy of KDT is consistent with the theory that alterations in energy metabolism may play a role in the mechanisms of action of KDT.

Ketogenic dietary therapies in adults with epilepsy: a practical guide.

Ketogenic dietary therapies are an effective treatment option for children with drug-resistant epilepsy. There is an increasing worldwide interest in using these diets to manage adult epilepsy; uncontrolled studies show similar response rates to those in children. Despite this, there are only a few centres with dedicated services for adults. We clearly need controlled studies of this treatment in adults. Here, we aim to familiarise adult neurologists with the evidence base for these diets and give practical advice on starting and maintaining them in adults.

Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAF<0.01 was evaluated. 303 Individuals had KCNJ11 and 246 individuals had BAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAF<0.01. No significant results were obtained from association analyses, with either KDT response phenotype. P-values were similar when accounting for ethnicity using a stratified Cochran-Mantel-Haenszel test. There did not seem to be a consistent effect of rare variants on response to KDT, although the cohort size was too small to assess significance. Common variants in KCNJ11 and BAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes.

Favourable response to ketogenic dietary therapies: undiagnosed glucose 1 transporter deficiency syndrome is only one factor.

AIM: We aimed to determine whether response to ketogenic dietary therapies (KDT) was due to undiagnosed glucose transporter type 1 deficiency syndrome (GLUT1-DS). METHOD: Targeted resequencing of the SLC2A1 gene was completed in individuals without previously known GLUT1-DS who received KDT for their epilepsy. Hospital records were used to obtain demographic and clinical data. Response to KDT at various follow-up points was defined as seizure reduction of at least 50%. Seizure freedom achieved at any follow-up point was also documented. Fisher's exact and gene-burden association tests were conducted using the PLINK/SEQ open-source genetics library. RESULTS: Of the 246 participants, one was shown to have a novel variant in SLC2A1 that was predicted to be deleterious. This individual was seizure-free on KDT. Rates of seizure freedom in cases without GLUT1-DS were below 8% at each follow-up point. Two cases without SLC2A1 mutations were seizure-free at every follow-up point recorded. No significant results were obtained from Fisher's exact or gene-burden association tests. INTERPRETATION: A favourable response to KDT is not solely explained by mutations in SLC2A1. Other genetic factors should be sought to identify those who are most likely to benefit from dietary treatment for epilepsy, particularly those who may achieve seizure freedom.

Assessing parents' attitudes towards ketogenic dietary therapies.

We aimed to assess and quantify parental beliefs regarding ketogenic dietary therapies (KDTs). We also aimed to determine whether beliefs were related to response to KDTs. Adapted versions of the Beliefs about Medicine Questionnaire were completed by parents of children following KDTs for epilepsy. Demographic and clinical data were collected from hospital records. Ketogenic dietary therapy response was defined as ≥50% seizure reduction compared to baseline. Many parents had a positive perception of KDTs and were convinced of the necessity of KDTs for their children, although beliefs were wide-ranging. Over half of parents reported concerns about the potential long-term effects of KDTs. Parental beliefs about KDTs were significantly correlated with patient response. This was an attempt to quantify parents' beliefs regarding the use of KDTs for their child's epilepsy. The questionnaire may be used to identify individuals with a less positive attitude towards KDTs and who may be less likely to report a favorable response to KDTs. It is unknown whether people who have positive beliefs about KDTs engage in less nonadherent behavior or whether beliefs regarding KDTs simply reflect outcomes. The evidence behind the long-term side effects of KDTs should be emphasized when counseling patients and their families.

Ketogenic dietary therapies for adults with epilepsy: feasibility and classification of response.

Ketogenic dietary therapies are an effective treatment for children with drug-resistant epilepsy. There is currently no high-quality evidence regarding ketogenic dietary therapies in adults, and further research has been recommended. This audit aimed to provide further evidence for the feasibility of dietary treatment for adults and to consider factors that may aid response classification in this population. We evaluated the effectiveness and tolerability of ketogenic dietary therapies in 23 adults with epilepsy attending specialist clinics. Medical notes were used to obtain seizure frequency information and other effects associated with dietary treatment. Individuals who achieved ≥50% seizure reduction at all follow-up points were classified as responders. Response rates, in terms of seizure frequency, were similar to those commonly reported in pediatric cohorts: 9/23 (39%) adults were classified as responders. These responders remained on the diet for at least one year (follow-up: 1-10 years). Other benefits reported by patients, but not quantified, included a reduction in seizure severity and increased alertness and concentration. Such factors often favor continuation of ketogenic dietary therapies despite a <50% seizure reduction. One individual experienced psychosis while following dietary treatment; most commonly reported adverse events were gastrointestinal. Adverse events did not lead to discontinuation of treatment in any cases. Our findings suggest that adults with epilepsy are able to follow ketogenic dietary therapies long-term, and such treatment can lead to seizure reduction. Other aspects besides seizure frequency may be relevant when classifying response in adults, and appropriate ways to quantify these factors should be considered for use in future studies.

Can we predict a favourable response to Ketogenic Diet Therapies for drug-resistant epilepsy?

Ketogenic Dietary Therapies (KDT) are an effective treatment option for some people with drug-resistant epilepsy. They are, however, resource-intensive and can cause adverse side effects. Predictors of response would improve the selection process and perhaps further our understanding of the mechanisms behind dietary treatments for epilepsy. We conducted a literature review to identify factors that may influence response to KDT. We found no strong evidence that there are any specific factors that affect response. Gender and intellectual status do not seem to affect response; evidence is inconsistent for all other factors. Experimental studies may point us in the right direction for future work.