Changes in pediatric referrals after the 2009 ketogenic diet consensus recommendations.

BACKGROUND: In 2009, the International Ketogenic Diet Study Group published recommendations for children receiving ketogenic diet (KD) therapy for epilepsy. The document included a table listing epilepsy syndromes and conditions in which the KD has been particularly beneficial, hoping that physicians would refer children for the KD sooner. PURPOSE: To measure the impact of these 2009 recommendations on referral practice, we compared children initiated on the KD at Johns Hopkins Hospital (JHH) 10 years before and after the recommendations. RESULTS: Overall, children referred to the KD who met indications increased from the pre- to post-recommendation group, 44 % (112/256) to 69 % (175/255) (p < 0.001), with JHH neurologists specifically referring more frequently (10/112, 9 % to 58/175, 33 %) (p < 0.01). Referrals increased for Glut-1 deficiency (0 % to 2.4 %, p = 0.015), Dravet syndrome (0 % to 6.7 %, p < 0.01), Rett syndrome (0.4 % to 3 %, p = 0.018), and formula-fed only status (16 % to 31 %, p < 0.01). The chances of > 50 % seizure reduction for all children referred improved slightly between decades (56 % to 61 %, p = 0.30). CONCLUSIONS: Following the 2009 recommendations, our study shows there was an increase in referrals for children with indications at our center. Referrals from neurologists at our own institution increased the most. Ketogenic diet efficacy improved slightly over time but did not reach significance.

Does the ketogenic ratio matter when using ketogenic diet therapy in pediatric epilepsy?

The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less-restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the KD in children with epilepsy.

Treatment Guideline Nonadherence Pretransport Associated With Need for Higher Level of Care in Children Transferred to a Pediatric Tertiary Care Center for Status Epilepticus.

OBJECTIVES: We sought to investigate the association between adherence to the American Epilepsy Society (AES) 2016 guidelines for management of convulsive status epilepticus (SE) and clinical outcomes among children requiring interhospital transport for SE. We hypothesized that pretransport guideline nonadherence would be associated with needing higher level of care posttransfer. METHODS: This was a retrospective cohort study of children aged 30 days to 18 years transferred to our pediatric tertiary center from 2017 to 2019 for management of SE. Their care episodes were classified as 2016 American Epilepsy Society guideline adherent or nonadherent. There were 40 referring hospitals represented in this cohort. RESULTS: Of 260 care episodes, 55 (21%) were guideline adherent, 184 (71%) were guideline nonadherent, and 21 (8%) had insufficient data to determine guideline adherence. Compared with the adherent group, patients in the nonadherent care group had longer hospitalizations (32 hours [17-68] vs 21 hours [7-48], P = 0.006), were more likely to require intensive care unit admission (47% vs 31%), and less likely to be discharged home from the emergency department (16% vs 35%; χ 2 test, P = 0.01). Intubation rates did not differ significantly between groups (25% vs 18%, P = 0.37). When we fit a multivariable model to adjust for confounding variables, guideline nonadherence was associated with need for higher level of care (odds ratio, 2.04; 95% confidence interval, 1.04-3.99). Treatment guideline adherence did not improve over the 3-year study period (2017: 22%, 2018: 19%, 2019: 29% [χ 2 test for differences between any 2 years, P = 0.295]). CONCLUSIONS: Guideline nonadherence pretransport was associated with longer hospitalizations and need for higher level of care among children transferred for SE at our institution. These findings suggest a need to improve SE guideline adherence through multifaceted quality improvement efforts targeting both the prehospital and community hospital settings.

Six-month effects of modified Atkins diet implementation on indices of cardiovascular disease risk in adults with epilepsy.

BACKGROUND/AIMS: Ketogenic diet therapies (KDTs) offer a needed therapeutic option for patients with drug-resistant epilepsy. The current study investigated biochemical and anthropometric indices of cardiovascular disease (CVD) risk in adults with epilepsy treated with KDT over 6 months. METHOD: 65 adults with epilepsy naïve to diet therapy were enrolled in a prospective longitudinal study and instructed on modified Atkins diet (MAD) use. Seizure frequency, anthropometric measures, blood levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 and B, and lipoprotein sub-fractions were assessed at baseline, 3 months, and 6 months. RESULTS: Subsequent to study enrollment, 34 participants were lost to follow-up, elected not to start, or stopped MAD prior to study completion, leaving a total of 31 participants in the study at 6 months. Compared to baseline, participants on MAD showed significant reductions in median seizure frequency/week, weight, body mass index, waist and hip circumference, and percent body fat at 3 and 6 months. Compared to baseline, participants on MAD for 3 months showed significantly increased levels of total, small and medium LDL particles, ApoB and ApoB/A1 ratio. At 6 months, only small LDL particles and ApoB levels remained elevated and levels of ApoA1 had risen, suggesting possible compensatory adaptation over time. CONCLUSIONS: This study provides evidence demonstrating the efficacy and cardiovascular safety of 6 months of MAD use by adults with epilepsy. It also highlights an index of CVD risk - small LDL particles - that should be closely monitored.Trial registration: ClinicalTrials.gov identifier: NCT02694094..

Epilepsy with myoclonic-atonic seizures (Doose syndrome): Clarification of diagnosis and treatment options through a large retrospective multicenter cohort.

OBJECTIVE: Epilepsy with myoclonic-atonic seizures (EMAS) is a rare childhood onset epileptic encephalopathy. There is no clear consensus for recommended treatments, and pharmacoresistance is common. To better assess the clinical phenotype, most effective treatment, and determinants of cognitive and seizure outcomes, three major pediatric epilepsy centers combined data, creating the largest cohort of patients with EMAS ever studied to date. METHODS: Authors performed a retrospective chart review of patients with EMAS who received care at the authors' institutions. RESULTS: A total of 166 children were identified. Global developmental delay (>1 domain) was present in 2% of children at onset and 49% during the course of the disease. Afebrile seizures occurred after the age of 2 years in 88%, generalized tonic-clonic seizures in 60%, and drop attack or myoclonic seizures in 30%. At onset, electroencephalography (EEG) found 28% normal, background slowing in 20%, and epileptiform discharges or seizures in 69%. Subsequent EEG found slowing in 62% and discharges or seizures in 90%. Response (>50% seizure reduction) to the first three antiseizure drugs (ASDs) was 26% (levetiracetam, 17%; valproic acid, 31%; other ASDs combined, 26%). Diet therapy was used as a second or third therapy in 19% and ultimately used in 57%; response was 79%, significantly greater than the first three ASDs (P = .005, χ2 ). Seizure freedom occurred in 57% and was less likely in the case of persistent global developmental delays (P < .001), seizure recorded on subsequent EEGs (P = .027), and failure to respond to diet therapy (P = .005). Development was normal in 47%, and 12% had delays in one domain, which was less likely in the case of global developmental delay after epilepsy onset (P < .001) and failure to achieve seizure freedom (P < .001). SIGNIFICANCE: This large cohort of children with EMAS clarifies areas of variability in practice. Diet therapy is by far the most effective treatment; failure to respond was associated with failure to attain seizure freedom. This therapy should be used early in the treatment in EMAS. This study also identified a bidirectional link between cognitive and seizure outcomes.

Does the size of a ketogenic diet admission group influence outcomes?

INTRODUCTION: Most pediatric centers admit children with epilepsy for several days when initiating the ketogenic diet (KD). At some institutions, children are admitted in groups in order to save staff time and allow families to bond together for support. It is unknown if admitting children in larger groups for the KD affects outcomes. METHODS: We performed a retrospective study of all children with intractable epilepsy admitted for KD initiation at Johns Hopkins Hospital from 2010 to 2020. Charts were reviewed for size of admission groups, 3-month seizure reduction, and total KD duration. A linear mixed effects model was used to analyze KD duration between different size admission groups. RESULTS: 245 children were started on the KD, mean age 5.2 years. Thirty-three (13%) children were admitted in one-child admission groups, 52 (21%) in 2-children groups, 78 (32%) in 3-children groups, 72 (29%) in 4-children groups, and 10 (4%) in 5-children groups. At our center, fewer large admission groups and shorter KD durations have occurred over time. After adjusting for time, the 3-children admission group had higher KD duration than 1-child (1.9 times duration, p = 0.035). Additionally, after grouping cohort sizes into small (1-2 patients) versus large (3-5 patients), KD durations in the large groups were 1.6 times those in the small groups, p = 0.036. There was no statistically significant correlation between the size of the admission groups and 3-month seizure reduction. CONCLUSIONS: Admitting children in larger groups, specifically 3 children at a time, was associated with longer KD durations. This may be due to parent support from groups, listening and learning from other parents' questions, or other factors.

Diagnosing and managing childhood absence epilepsy by telemedicine.

The diagnosis of childhood absence epilepsy (CAE) is typically based on history and description of spells, supported by an office-based positive hyperventilation test and confirmed by routine electroencephalography (EEG). In the current coronavirus disease 2019 (COVID-19) pandemic, many pediatric neurologists have switched to telemedicine visits for nonemergent outpatient evaluations. We present a series of children diagnosed as having CAE on the basis of a positive hyperventilation test performed during remote televisits. Several of these children were begun on treatment for CAE prior to obtaining an EEG, with significant seizure reduction. Our series documents the feasibility of CAE diagnosis and management by telemedicine.

Autism and developmental disability caused by KCNQ3 gain-of-function variants.

OBJECTIVE: Recent reports have described single individuals with neurodevelopmental disability (NDD) harboring heterozygous KCNQ3 de novo variants (DNVs). We sought to assess whether pathogenic variants in KCNQ3 cause NDD and to elucidate the associated phenotype and molecular mechanisms. METHODS: Patients with NDD and KCNQ3 DNVs were identified through an international collaboration. Phenotypes were characterized by clinical assessment, review of charts, electroencephalographic (EEG) recordings, and parental interview. Functional consequences of variants were analyzed in vitro by patch-clamp recording. RESULTS: Eleven patients were assessed. They had recurrent heterozygous DNVs in KCNQ3 affecting residues R230 (R230C, R230H, R230S) and R227 (R227Q). All patients exhibited global developmental delay within the first 2 years of life. Most (8/11, 73%) were nonverbal or had a few words only. All patients had autistic features, and autism spectrum disorder (ASD) was diagnosed in 5 of 11 (45%). EEGs performed before 10 years of age revealed frequent sleep-activated multifocal epileptiform discharges in 8 of 11 (73%). For 6 of 9 (67%) recorded between 1.5 and 6 years of age, spikes became near-continuous during sleep. Interestingly, most patients (9/11, 82%) did not have seizures, and no patient had seizures in the neonatal period. Voltage-clamp recordings of the mutant KCNQ3 channels revealed gain-of-function (GoF) effects. INTERPRETATION: Specific GoF variants in KCNQ3 cause NDD, ASD, and abundant sleep-activated spikes. This new phenotype contrasts both with self-limited neonatal epilepsy due to KCNQ3 partial loss of function, and with the neonatal or infantile onset epileptic encephalopathies due to KCNQ2 GoF. ANN NEUROL 2019;86:181-192.

Ketogenic diet therapy provision in the COVID-19 pandemic: Dual-center experience and recommendations.

The current coronavirus-19 pandemic has changed dramatically how neurologists care for children and adults with epilepsy. Stay-at-home orders and resistance to hospitalizations by patients have led epileptologists to engage in telemedicine and reevaluate how to provide elective services. Ketogenic diet therapy is often started in the hospital, with families educated in hospital-based classes, but this is difficult to do in this current pandemic. At our two academic centers, both our pediatric and adult epilepsy diet centers have had to quickly consider alternative methods to both start and maintain ketogenic diet therapy. This paper provides several examples of how ketogenic diet therapy can be provided to patients in unique ways, along with recommendations from other experts and patients, learned over the past few months.

Ketogenic dietary therapies for epilepsy and beyond.

PURPOSE OF REVIEW: The ketogenic diet, a high-fat, low-carbohydrate therapy, has become an established treatment for pediatric epilepsy since 1921. There has recently been an increase in important studies on the ketogenic diet, and this review will highlight the most recent in order to provide a synthesis of where this field stands today. RECENT FINDINGS: Clinical studies continue to support the use of ketogenic diets in epilepsy, with more recent trials supporting its use in adults. Clinical recommendations published in 2018 based on a decade of practice and research, guide implementation and management of the ketogenic diet in epilepsy. One of the most rapidly growing 'indications' includes the role of ketogenic diets in status epilepticus. An exciting new potential mechanism for how the ketogenic diet exerts its antiseizure effects is through changing the composition of the gut microbiome. Lastly, ketogenic diets are being applied to a range of neurological conditions from autism to Alzheimer's disease. SUMMARY: The ketogenic diet is a versatile therapy, with growing clinical evidence and guidelines, widely used for the treatment of epilepsy. New indications include status epilepticus and neurological conditions other than epilepsy.

How often is antiseizure drug-free ketogenic diet therapy achieved?

The ketogenic diet (KD) is often started not only for seizure reduction but also to potentially wean antiseizure drugs (ASDs) in children with epilepsy. Although there have been several publications regarding ASD reduction on the KD, it is unknown how often complete medication withdrawal occurs. We reviewed the charts of all children started on the KD at Johns Hopkins Hospital and Johns Hopkins All Children's Hospital from 1/11 to 4/18. Children were defined as achieving drug-free diet (DFD) status if they started the KD on at least 1 ASD and achieved a period of time where they were on the KD alone. Over the time period, 232 children were evaluated; DFD status occurred in 43 (18.5%), of which 32 (13.8% of the full cohort) remained off ASDs for the remainder of their KD treatment course. Eleven children restarted ASD after a mean of 7 months. Children achieving DFD therapy were more likely to be younger, have fewer ASDs at KD onset, have Glut1 deficiency or epilepsy with myoclonic-atonic seizures, but were less likely to have Lennox-Gastaut syndrome or a gastrostomy tube.

Immediate outcomes in early life epilepsy: A contemporary account.

RATIONALE: Early-life epilepsies (ELEs) include some of the most challenging forms of epilepsy to manage. Given recent diagnostic and therapeutic advances, a contemporary assessment of the immediate short-term outcomes can provide a valuable framework for identifying priorities and benchmarks for evaluating quality improvement efforts. METHODS: Children with newly diagnosed epilepsy and onset <3 years were prospectively recruited through 17 US hospitals, from 2012 to 2015 and followed for 1 year after diagnosis. Short-term outcome included mortality, drug resistance, evolution of nonsyndromic epilepsy to infantile spasms (IS) and from IS to other epilepsies, and developmental decline. Multivariable analyses assessed the risk of each outcome. RESULTS: Seven hundred seventy-five children were recruited, including 408 (53%) boys. Median age at onset was 7.5 months (interquartile range (IQR): 4.2-16.5), and 509 (66%) had onset in the first year of life. Of 22 deaths that occurred within one year of epilepsy diagnosis, 21 were children with epilepsy onset in infancy (<12 months). Of 680 children followed ≥6 months, 239 (35%) developed drug-resistant seizures; 34/227 (15%) infants with nonsyndromic epilepsy developed IS, and 48/210 (23%) initially presenting with IS developed additional seizure types. One hundred of 435 (23%) with initially typical development or only mild/equivocal delays at seizure onset, had clear developmental impairment within one year after initial diagnosis. Each outcome had a different set of predictors; however, younger age and impaired development at seizure onset were broadly indicative of poorer outcomes. Type of epilepsy and early identification of underlying cause were not reliable predictors of these outcomes. CONCLUSION: Early-life epilepsies carry a high risk of poor outcome which is evident shortly after epilepsy diagnosis. Onset in infancy and developmental delay is associated with an especially high risk, regardless of epilepsy type. The likelihood of poor outcomes is worrisome regardless of specific clinical profiles.

Impact of the modified Atkins diet on cardiovascular health in adults with epilepsy.

AIM: The current study investigated biochemical and vascular markers of cardiovascular health in adult patients with epilepsy treated with long-term (greater than 1year) ketogenic diet therapy compared with controls. METHOD: Anthropometric measures, serum fasting lipid panel, apolipoproteins A-1 and B, lipoprotein sub-fractions as well as common carotid intima-media thickness (cIMT), and plaque presence were assessed in 20 adult patients with epilepsy on a modified Atkins diet (MAD) for >1year started as an adult compared with 21 adult patients with epilepsy naïve to diet therapy. RESULTS: Patients treated with MAD had significantly lower weight, body mass index, waist and hip circumference, percent body fat, and serum triglyceride levels when compared with control patients. In contrast, they had significantly higher serum levels of small low-density-lipoprotein (LDL) particles and were significantly more likely to have LDL pattern B in which small LDL particles predominate when compared with controls. However, there was no significant difference in cIMT or plaque presence between groups. CONCLUSION: Our results provide clinical evidence demonstrating the cardiovascular safety of a high-fat, low-carbohydrate diet used in adults with epilepsy for at least 12months. It also highlights potential markers of cardiovascular risk - small dense LDL particles - that should be closely monitored in adults treated with diet therapy long-term.

Response to treatment in a prospective national infantile spasms cohort.

OBJECTIVE: Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi-square tests and multivariate logistic regression models. RESULTS: Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p < 0.001). Fifty-five percent of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p < 0.001). Neither etiology nor development significantly modified the response pattern by treatment group. INTERPRETATION: Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies.

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort.

OBJECTIVE: Infantile spasms (IS) represent a severe epileptic encephalopathy presenting in the first 2 years of life. Recommended first-line therapies (hormonal therapy or vigabatrin) often fail. We evaluated response to second treatment for IS in children in whom the initial therapy failed to produce both clinical remission and electrographic resolution of hypsarhythmia and whether time to treatment was related to outcome. METHODS: The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of IS. Children were considered nonresponders to first treatment if there was no clinical remission or persistence of hypsarhythmia. Treatment was evaluated as hormonal therapy (adrenocorticotropic hormone [ACTH] or oral corticosteroids), vigabatrin, or "other." Standard treatments (hormonal and vigabatrin) were compared to all other nonstandard treatments. We compared response rates using chi-square tests and multivariable logistic regression models. RESULTS: One hundred eighteen infants were included from 19 centers. Overall response rate to a second treatment was 37% (n = 44). Children who received standard medications with differing mechanisms for first and second treatment had higher response rates than other sequences (27/49 [55%] vs. 17/69 [25%], p < 0.001). Children receiving first treatment within 4 weeks of IS onset had a higher response rate to second treatment than those initially treated later (36/82 [44%] vs. 8/34 [24%], p = 0.040). SIGNIFICANCE: Greater than one third of children with IS will respond to a second medication. Choosing a standard medication (ACTH, oral corticosteroids, or vigabatrin) that has a different mechanism of action appears to be more effective. Rapid initial treatment increases the likelihood of response to the second treatment.

The molecular and phenotypic spectrum of IQSEC2-related epilepsy.

OBJECTIVE: IQSEC2 is an X-linked gene associated with intellectual disability (ID) and epilepsy. Herein we characterize the epilepsy/epileptic encephalopathy of patients with IQSEC2 pathogenic variants. METHODS: Forty-eight patients with IQSEC2 variants were identified worldwide through Medline search. Two patients were recruited from our early onset epileptic encephalopathy cohort and one patient from personal communication. The 18 patients who have epilepsy in addition to ID are the subject of this study. Information regarding the 18 patients was ascertained by questionnaire provided to the treating clinicians. RESULTS: Six affected individuals had an inherited IQSEC2 variant and 12 had a de novo one (male-to-female ratio, 12:6). The pathogenic variant types were as follows: missense (8), nonsense (5), frameshift (1), intragenic duplications (2), translocation (1), and insertion (1). An epileptic encephalopathy was diagnosed in 9 (50%) of 18 patients. Seizure onset ranged from 8 months to 4 years; seizure types included spasms, atonic, myoclonic, tonic, absence, focal seizures, and generalized tonic-clonic (GTC) seizures. The electroclinical syndromes could be defined in five patients: late-onset epileptic spasms (three) and Lennox-Gastaut or Lennox-Gastaut-like syndrome (two). Seizures were pharmacoresistant in all affected individuals with epileptic encephalopathy. The epilepsy in the other nine patients had a variable age at onset from infancy to 18 years; seizure types included GTC and absence seizures in the hereditary cases and GTC and focal seizures in de novo cases. Seizures were responsive to medical treatment in most cases. All 18 patients had moderate to profound intellectual disability. Developmental regression, autistic features, hypotonia, strabismus, and white matter changes on brain magnetic resonance imaging (MRI) were prominent features. SIGNIFICANCE: The phenotypic spectrum of IQSEC2 disorders includes epilepsy and epileptic encephalopathy. Epileptic encephalopathy is a main clinical feature in sporadic cases. IQSEC2 should be evaluated in both male and female patients with an epileptic encephalopathy.

Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges.

OBJECTIVES: Over 250 medical centers worldwide offer ketogenic diets to children with epilepsy; however, access to these therapies has been extremely limited for adults until recent years. We examine our 5-year experience creating and implementing a dedicated Adult Epilepsy Diet Center designed to provide adults with epilepsy access to ketogenic diets. MATERIAL AND METHODS: Outpatients seen at the Johns Hopkins Adult Epilepsy Diet Center from August 2010 thru September 2015 age 18years and older were enrolled in a prospective open-label observational study. Patients that also enrolled in ongoing clinical diet trials were excluded from this study. Participant demographics, diet type, urine and/or serum ketones, laboratory studies, seizure frequency, diet duration, reason for discontinuing diet therapy, and side effects were recorded. A subgroup analysis of participants that met International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE) and were treated de novo with a Modified Atkins Diet (MAD) was performed to compare outcomes with the current literature regarding efficacy of other antiseizure treatments for DRE. RESULTS: Two hundred and twenty-nine adults attended the Adult Epilepsy Diet Center, and 168 met inclusion criteria. Two-thirds (n=113, 67%) were women with an age range of 18-86years at the initial visit. Thirty-five participants (21%, n=133) were already on a therapeutic diet while 79% (n=133) were naïve to diet therapy at the time of the initial visit. Diet-naïve participants were typically prescribed MAD (n=130, 98%), unless unable to intake adequate oral nutrition, in which case they were prescribed KD (n=1) or a combination of oral MAD and ketogenic formula (n=2). Twenty-nine of 130 (22%) participants prescribed MAD elected not to start or were lost to follow-up, and 101 (78%) began MAD. A subgroup analysis was performed on one hundred and six participants naïve to diet therapy that met International League Against Epilepsy criteria for DRE, were able to tolerate oral nutrition, and were prescribed a MAD. Relative to the number of enrolled participants who had reliable follow-up results for a given duration (including those that ultimately elected not to start or were later lost to follow-up), at 3months, 36% of these participants responded (≥50% seizure reduction) to diet therapy, and 16% were seizure-free. At 1year, 30% responded, and 13% were seizure-free. At 4years, 21% responded, and 7% were seizure-free. Hyperlipidemia was the most common side effect (occurring in 39% of screened participants, including those on a therapeutic diet prior to the initial visit). Weight loss was also common (occurring in 19% of all participants treated with a ketogenic diet therapy) yet was often an intended effect. SIGNIFICANCE: This study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults, although long-term adherence was limited and further adequately controlled studies are necessary to determine the efficacy of ketogenic diets in the treatment of adults with epilepsy.

The impact of the modified Atkins diet on lipid profiles in adults with epilepsy.

OBJECTIVES: The modified Atkins diet (MAD) is a high fat, low carbohydrate ketogenic diet used to treat intractable seizures in children and adults. The long-term impact on fasting lipid profiles (FLPs) remains unknown. This study was designed to detect significant lipid changes in adults on MAD. METHODS: Patients were observed prospectively. A FLP was obtained in all patients at the first visit then serially. Patients were started on a 20 g per day net carbohydrate limit MAD. They were screened for risk for coronary heart disease and counseled to reduce saturated fats by a registered dietitian if deemed at risk. Patients that remained on MAD for 3 or more months with one or more follow-up FLP were included. RESULTS: Thirty-seven patients (14 male), mean age 33 years (SD 13, range 18-59) met study criteria. Median diet duration was 16 months (range 3-41). Total cholesterol and low-density lipoprotein (LDL) increased significantly over the first 3 months of MAD (P = 0.01 and 0.008, respectively), but were not significantly different from baseline after 1 year of treatment (P = 0.2 and P = 0.5, respectively). High-density lipoprotein levels trended upward in the first 3 months (P = 0.05) and triglycerides remained unchanged (P = 0.5). In 12 patients followed for 3 or more years, no cardiovascular or cerebrovascular events were reported. DISCUSSION: Although total cholesterol and LDL increased over the first 3 months of the MAD, these values normalized within a year of treatment, including in patients treated with MAD for more than 3 years.

What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world.