Ketogenic Diet Initiation Research Articles

Ketogenic Diet as a Therapeutic Intervention for Doose Syndrome: A Case Report and Review of Current Evidence

Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome or myoclonic–astatic epilepsy (MAE), represents a challenging pediatric epilepsy syndrome, initially described by Doose et al. in 1970. MAE accounts for 1%–2.2% of juvenile-onset epilepsy cases, characterized by normal early development, followed by seizure onset between 7 months and 6 years. Seizure types include myoclonic, myoclonic-atonic, generalized tonic–clonic, and atypical absences, often accompanied by nonconvulsive status epilepticus. Electroencephalogram typically shows parietal-dominant rhythmic theta activity or a posterior 4 Hz pattern. While conventional antiseizure medications (ASMs) offer some efficacy, outcomes vary widely, and up to 50% of patients may experience refractory seizures and poor intellectual outcomes. The ketogenic diet (KD), a high-fat, low-carbohydrate diet inducing ketosis, has shown promise in reducing seizure frequency and severity in refractory epilepsy, including MAE. This case report describes a successful outcome with a South Indian style KD in a 3-year-old boy with Doose syndrome presenting with 20–25 daily head drop seizures despite multiple ASMs and steroid therapy. Initiation of a home-based KD utilizing traditional household ingredients significantly reduced seizure frequency by 60% within 1 month and 80% within 2 months and was 100% seizure-free in 3rd month following KD, alongside developmental improvements. The KD was well-tolerated, with improved nutritional status. This case underscores KD’s potential as a viable complementary therapy for MAE, emphasizing the need for ongoing parental support and supervision to ensure dietary adherence and optimize outcomes. It is commonly believed that the KD is challenging for the South Indian population to follow due to the high carbohydrate content in South Indian cuisine. However, this case demonstrates that a KD can indeed be tailored around South Indian dishes, highlighting the uniqueness of this approach. When the diet is customized to consider a child’s dietary habits, culture, and cuisine, it becomes easier to follow over the long term, leading to effective seizure control. Further research is necessary to refine dietary protocols and evaluate long-term efficacy in MAE management.

Optimizing ketogenic diet therapy for childhood epilepsy: Identifying key factors for seizure control and psychomotor enhancement.

To identify key factors influencing the therapeutic efficacy of the ketogenic diet (KD) for children with drug-resistant epilepsy and elucidate their interconnected relationships to optimize clinical practice. Participants were selected from children receiving KD treatment at West Second University Hospital of Sichuan University from September 2015 to October 2023. Clinical factors pre-KD and post-KD (at the third month) were analyzed systematically using an analytical framework. Descriptive analyses, univariate analyses, and multivariate regression analyses were performed for the entire cohort and subgroups of genetic and non-genetic (i.e., structural and unknown) etiologies. Thereby, the most significant predictors were identified for each relevant dependent variable. Path analysis diagrams were used for visual representation. Of 156 patients, genetic etiology was prevalent (38.5%). In the genetic subgroup, channelopathies predicted lower baseline seizure frequency and increased chance of seizure freedom with KD. Frequent seizures and complex history of anti-seizure medications (ASMs) predicted severe baseline psychomotor abnormalities. Younger age at KD initiation benefited psychomotor improvement. In the non-genetic subgroup, lower baseline seizure frequency increased the likelihood of seizure freedom post-KD. Concurrent use of multiple ASMs helped achieve ≥50% seizure reduction. Boys were more likely to experience psychomotor improvement. A significant correlation was found between ≥50% seizure reduction and psychomotor improvement in both subgroups. Delayed KD initiation (longer epilepsy duration at KD start) was related to a greater number of ASMs used, infrequent seizures, and older age at epilepsy onset. In addition, patients with channelopathies had delayed initiation of KD. Children with genetic epilepsy display more pronounced characteristics of epileptic encephalopathy. Early KD intervention is crucial for channelopathies, notably SCN1A variants. For other drug-resistant epilepsy cases, KD alongside diverse ASMs may improve seizure control and developmental outcomes. However, the patient population benefiting most from early KD tends to start the treatment later, urging a re-evaluation of KD decision-making paradigms.

Dynamics of glucose concentration changes during ketogenic diet initiation in pediatric patients with drug-resistant epilepsy – analysis of glucose values in individual patients

Dynamics of glucose concentration changes during ketogenic diet initiation in pediatric patients with drug-resistant epilepsy – analysis of glucose values in individual patients

Efficacy and safety of a smartphone application-based treatment of ketogenic diet in pediatric refractory epilepsy.

We aimed to find predictors for smartphone application-based ketogenic diet (KD) treatment effectiveness and safety. The efficacy was evaluated according to the reduction in seizure frequency after the intervention of KD; safety was evaluated based on adverse effects. The ordinal logistic regression analysis was used to explore the influencing factors of efficacy. The study sample included 116 males and 65 females with a median age of 2.27 years. The baseline frequency of seizure was more than five times/day in 123 children, 50.83% of them received three or more antiepileptic drugs (AEDs). Seventy-two patients' KD initiation mode was outpatient, and 73 completed the 12-month follow-up. A total of 88 (48.62%) patients had reported a reduction in seizure ≥50%. Compared with 12 months, those who had received KD therapy for only 3 (P = 0.009) and 6 months (P = 0.005) were more likely to show negative outcomes. Outpatient initiation had better outcomes (P = 0.029) than inpatient initiation. For the number of AEDs applied, patients on two AEDs were more likely to achieve better outcomes (P = 0.001). Adverse events had been noted among 77 patients; BMI Z-score at KD initiation was associated with adverse effects (P = 0.003). Our study suggested that outpatient initiation and long-term treatment of KD should be encouraged. Our research shows that the KD is a helpful treatment for children with refractory epilepsy, reducing seizures by more than 50% in nearly half of the cases, with some experiencing complete seizure freedom. We used a smartphone app to improve communication between patients and their healthcare teams, resulting in a high retention, and app usage was linked to reduced adverse effects. We recommend early consideration of KD treatment for patients failing two AED, encourage outpatient initiation, and advocate for longer-term KD use.

A case-control evaluation of Spasm control and Tolerability of the Modified Atkins diet versus classic ketogenic diet in Chinese Children with infantile epileptic spasms syndrome

ObjectiveThis study was conducted to compare the efficacy, tolerability and safety of the modified Atkins diet (MAD) and the classic ketogenic diet (KD) in Chinese children with infantile epileptic spasms syndrome. MethodsWe retrospectively recruited and analyzed 56 children with infantile epileptic spasms syndrome started on the MAD (n = 21) and classic KD (n = 35) at our institution from June 2016 to July 2022. ResultsThe MAD group had exhibited comparable rates of spasm reduction (>50%) as the classic KD group at the time point of 3 months (66.7% for MAD, 75% for KD; p = 0.510), 6 months (75% for MAD, 82.6% for KD; p = 0.694), and 12 months (84.6% for MAD, 90.9% for KD; p = 1.000). The probability of patients remaining on the MAD was higher (p = 0.048) than those consuming the classic KD. By analyzing discontinuation reasons, we found that the MAD patients had a lower rate of poor compliance than the classic KD patients (p = 0.014). Response to the diet at 1 month and fewer anti-seizure medicines (ASMs) had tried before KD initiation were possible factors in regard to likelihood of spasm-free response to the diet therapy at 3 months (p = 0.001 and p = 0.014, respectively). ConclusionsThe efficacy of spasm control was similar in the MAD, with better tolerability and higher compliance compared to the classic KD. Therefore, MAD could be the primary treatment for children in China with- infantile epileptic spasms syndrome. Additionally, an earlier beginning of the diet treatment may have significant advantages.

Dynamics of glucose concentration during the initiation of ketogenic diet treatment in children with refractory epilepsy: Results of continuous glucose monitoring.

The ketogenic diet (KD) is a diet low in carbohydrates and rich in fats which has long been used to treat refractory epilepsy. The metabolic changes related to the KD may increase the risk of hypoglycemia, especially during the first days. The study focused on the impact of KD initiation on glycemia in non-diabetic patients with refractory epilepsy. The subjects were 10 pediatric patients (6 boys, mean age 6.1 ± 2.4 years), treated for intractable epilepsy. Blinded continuous glucose monitoring system (CGM) Dexcom G4 was used. Patients started on their regular diet in the first 36 hours of monitoring, followed by an increase in lipids intake and a gradual reduction of carbohydrates (relations 1:1; 2:1; 3:1; 3.5:1). We analyzed changes in glycemia during fat: nonfat ratio changes using a generalized linear model. The mean monitored time per person was 6 days, 10 hours and 44 minutes. The mean ± SD glycemia for the regular diet was 4.84 ± 0.20 mmol/L, for the carbohydrates/fat ratio of 1:1 it was 4.03 ± 0.16, for the ratio of 2:1 it was 3.57 ± 0.10, for the ratio 3:1 it was 3.39 ± 0.13 and for the final ratio of 3.5:1 it was 2.79 ± 0.06 mmol/L (P < 0.001). The portions of time spent in glycemia ≤3.5 mmol/L (≤2.5 mmol/L respectively) were: on the normal diet 0.88% (0.31%) of the monitored period, during 1:1 KD ratio 1.92% (0.95%), during 2:1 ratio 3.18% (1.02%), and during 3:1 and 3.5:1 ratios 13.64% (2.36%) of the monitored time (P < 0.05). Continuous glucose monitoring system shows the dynamic of glucose concentration in ketogenic diet treatment initiation. It may be a useful tool to control the effects of this diet on glucose metabolism, especially in hypoglycemia detection.

Factors Associated With Growth in Patients Treated With the Classic Ketogenic Diet for Drug-Resistant Epilepsy

BackgroundSuboptimal growth and malnutrition are often cited as complications of ketogenic diet therapy in patients with drug-resistant epilepsy; however, there is conflicting evidence on the factors that contribute to growth. MethodsThis is an observational, case-based study to evaluate growth in patients with drug-resistant epilepsy treated with the classic ketogenic diet for at least 12 months. Age, gender, height, weight, and body mass index (BMI) were collected at baseline and epilepsy clinic standard-of-care visits (one month, six months, and 12 months after diet initiation). Dietary intake and laboratory measures including glucose, bicarbonate, and beta-hydroxybutyrate were also collected. Results119 patients were included. After ketogenic diet initiation, there was a significant fall in height z score from baseline to 12 months (−0.15, P = 0.001) but no other significant changes in weight, weight-for-length/BMI, or height z scores were noted between any time points within the 12 months after diet initiation. When separated by age, height z score changes were limited to those aged zero to three years. This was accompanied by a significant decrease in energy intake 12 months after treatment in this age group. When separated by diet route, weight z scores at each time point were significantly lower in the group eating by mouth than tube. ConclusionsOur study provides further evidence that the classic ketogenic diet impacts growth. Our population demonstrated restriction in linear growth in those aged zero to three years, which correlated with declines in energy intake, and weight declines limited to patients fed by mouth.

The ketogenic diet plus standard of care for adults with recently diagnosed glioblastoma: Results from a phase 1 trial.

2076 Background: Facing limited treatment options, brain tumor patients are often highly motivated to use complementary therapies, including diet, to help themselves. There is now an abundance of preclinical evidence suggesting possible benefit with a ketogenic diet (KD) for brain tumor patients, but clinical evidence is still limited. Thus, we conducted a single-arm, phase 1 safety and feasibility trial of a KD among patients with recently diagnosed glioblastoma (GBM) during standard- of-care (SOC) treatment. Methods: Adults with GBM within 3 months of diagnosis followed a supervised 16-week diet intervention of a standard 3:1 KD (Fat(g):Carbohydrate+Protein(g)) plus SOC chemoradiation. Primary outcome was safety, evaluated by weekly assessments of weight and body mass index (BMI). Secondary outcomes included feasibility (pre-specified as &gt; 50% of patients maintaining blood ketone levels &gt; 0.3 mM over 50% of study days), progression-free survival (PFS), overall survival (OS), health-related quality-of-life (QOL), and cognitive function. Twice daily blood glucose and ketone levels, weight/BMI, physical activity, and sleep were assessed by remote monitoring. Results: Seventeen patients were evaluable: 53% women, median age 55, median Karnofsky Performance Status 85. All participants met the primary safety objective with no instances of excessive weight loss or related serious adverse events. Adherence to KD was high: all 17 patients maintained nutritional ketosis (≥0.3 mM/dL) &gt;50% of study days, where 14 patients maintained nutritional ketosis &gt;85% of study days. Median time to ketosis from diet initiation was 3 days. Diet-related AEs were mild and manageable; no patients came off study due to inability to tolerate KD. Median progression-free survival (PFS) and overall survival (OS) were 12.5 months and 28.6 months from KD initiation respectively. QOL, symptom control, and cognitive function remained stable or improved, although these did not reach statistical significance. Conclusions: This phase 1 trial demonstrates that KD is safe and feasible for GBM patients receiving SOC, may improve outcomes, and provides a foundation for future randomized trials to assess efficacy. Clinical trial information: NCT03451799 .

Analysis of the efficacy and safety of inpatient and outpatient initiation of KD for the treatment of pediatric refractory epilepsy using generalized estimating equations.

To compare the efficacy and safety of inpatient and outpatient initiation ketogenic diet (KD) protocol of pediatric refractory epilepsy. Eligible children with refractory epilepsy were randomly assigned to receive KD with inpatient and outpatient initiation. The generalized estimation equation (GEE) model was used to analyze the longitudinal variables of seizure reduction, ketone body, weight, height, body mass index (BMI), and BMI Z-score at different follow-up times between the two groups. Between January 2013 and December 2021, 78 and 112 patients were assigned to outpatient and inpatient KD initiation groups, respectively. There were no statistical differences between the two groups based on baseline demographics and clinical characteristics (all Ps > 0.05). The GEE model indicated that the rate of reduction of seizures≥50% in the outpatient initiation group was higher than that of the inpatient initiation group (p = 0.049). A negative correlation was observed between the seizure reduction and blood ketone body at 1, 6, and 12 months (all Ps < 0.05). There were no significant differences in height, weight, BMI, and BMI Z-score between the two groups over the 12-month period by the GEE models (all Ps > 0.05). Adverse events were reported by 31 patients (43.05%) in the outpatient KD initiation group and 46 patients (42.20%) in the inpatient KD initiation group, but these differences were not statistically significant (p = 0.909). Our study shows that outpatient KD initiation is a safe and effective treatment for children with refractory epilepsy.

Застосування кетогенної дієти в педіатрії: спектр можливостей

Purpose - to describe the possibilities of using a ketogenic diet (KD) in the pediatric population for therapeutic purposes in refractory seizure syndrome and congenital metabolic disorders. The historical aspects of the development of special medical nutrition to achieve stable ketosis in children for the treatment of seizures of various genesis are briefly highlighted; the development of the evidence base for the effectiveness of the KD in children is presented. A review of current data on the multifactorial mechanisms of neuroprotective effects of KD is carried out. In particular, individual ways of modulating fundamental biochemical pathways, presynaptic and postsynaptic changes in vesicular transport and release of excitotoxic and inhibitory substrates at synapses are considered. Four types of diets are described according to the distribution of proteins, fats, and carbohydrates: the classic, modified Atkins diet, medium-chain triglyceride diet, and low glycemic index diet. The indications and contraindications for the appointment of medical ketogenic dietary therapy are considered. The most appropriate age periods of childhood for the type of KD are outlined to achieve maximum effectiveness. The authors describe in detail the main objectives of the stages of preparation of the child and family for the start of dietary treatment, the principles of initiation of KD, laboratory and instrumental monitoring and discontinuation of ketogenic dietary therapy. Particular attention is paid to the issue of counseling a child before starting a KD, the main steps in calculating the proportion of macronutrients and the principles of daily nutrition. The possibilities of prescribing medical ketogenic dietary therapy outside of refractory seizures, in particular, in glucose transaminase 1 deficiency syndrome, pyruvate dehydrogenase deficiency, mitochondrial disorders, heart failure, and brain injury, are analyzed. Available special products for medical purposes (clinical nutrition) for the organization of medical ketogenic therapy in pediatric patients, especially in the first years of life, are presented. No conflict of interests was declared by the authors.

Low-Carbohydrate High-Fat Diet: A SWOC Analysis.

Insulin resistance (IR) plays a role in the pathogenesis of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, obesity, and neurodegenerative diseases, including Alzheimer's disease. The ketogenic diet (KD) is a low-carbohydrate/high-fat diet that arose in the 1920s as an effective treatment for seizure control. Since then, the KD has been studied as a therapeutic approach for various IR-related disorders with successful results. To date, the use of the KD is still debatable regarding its safety. Some studies have acknowledged its usefulness, while others do not recommend its long-term implementation. In this review, we applied a SWOC (Strengths, Weaknesses, Opportunities, and Challenges) analysis that revealed the positive, constructive strengths of the KD, its potential complications, different conditions that can make used for it, and the challenges faced by both physicians and subjects throughout a KD. This SWOC analysis showed that the KD works on the pathophysiological mechanism of IR-related disorders such as chronic inflammation, oxidative stress and mitochondrial stress. Furthermore, the implementation of the KD as a potential adjuvant therapy for many diseases, including cancer, neurodegenerative disorders, polycystic ovary syndrome, and pain management was proven. On the other hand, the short and long-term possible undesirable KD-related effects, including nutritional deficiencies, growth retardation and nephrolithiasis, should be considered and strictly monitored. Conclusively, this review provides a context for decision-makers, physicians, researchers, and the general population to focus on this dietary intervention in preventing and treating diseases. Moreover, it draws the attention of scientists and physicians towards the opportunities and challenges associated with the KD that requires attention before KD initiation.

Effects of the ketogenic diet therapy in patients with STXBP1-related encephalopathy

ObjectiveWe aimed to investigate the effects of ketogenic diet (KD) and modified Atkins diet (MAD) in patients with epileptic encephalopathy, caused by the STXBP1 (syntaxin-binding protein 1) gene mutation. MethodsWe retrospectively evaluated the data of patients with STXBP1-related epileptic encephalopathy who were started on either KD or MAD between January 1, 2005, and June 30, 2021, in Severance Children’s Hospital. ResultsTwelve patients were examined. The median age of seizure onset was 1.5 months [interquartile range (IQR): 0–3] with a median age of dietary therapy initiation at 4.5 months (IQR: 3.0–9.3) and a median diet duration of 6.5 months (IQR: 2.8–13.3). The patients had various epilepsy syndromes: nine (75 %) patients had early infantile developmental and epileptic encephalopathy, two (16.7 %) had infantile epileptic spasms syndrome, and one (8.3 %) had developmental and epileptic encephalopathy. Three patients (25 %) were definite KD responders who achieved seizure freedom within the median of 2 months from KD initiation and remained seizure-free for a median of 36 months (IQR: 29.5–60.0). One patient (8.3 %) was a possible KD responder, seizure-free with KD initiation and steroid therapy while 8 were non-responders (66.7 %). The definite KD responders shared similar clinical characteristics as the rest, except that there were significantly more patients that had seizure onset at ≥ 6 months (p = 0.045) in the definite KD responder group. ConclusionWe demonstrated dietary therapy was highly effective for some patients with STXBP1-related epileptic encephalopathy, especially those with later onset.

P.077 Response to the ketogenic diet in refractory epileptic spasms at BC Children’s Hospital

Background: Epileptic spasms (ES) are a devastating seizure type with poor neurodevelopmental outcome; 1/3 are resistant to treatment with first line therapies. Recently attention has been drawn to the ketogenic diet (KD) as a potentially effective therapy, though data regarding optimal time of initiation, and its sustained effectiveness, are lacking. Methods: Retrospective chart review of all patients with ES treated with KD at BC Children’s Hospital between 2002 and 2020 (n=28) with comparison of spasm response based on age of initiation of KD in two groups: &lt; 12 months (n=11) and ≥ 12 months (n=17). Results: Comparing the &lt;12 months and ≥ 12 months groups showed: unknown etiology in 9% vs 25%; spasm freedom for 3 months on KD in 18% vs 41%; median time to spasm freedom was 2 vs 6 weeks; relapse after a period of spasm freedom occurred in 66% vs 70%. Conclusions: Although more effective in children ≥ 12 months of age in the first 3 months, spasm freedom in either group was not sustained with KD. KD is recommended as early therapy for refractory ES, but this study suggests clinicians be aware the KD has limited efficacy in long-term control of ES and must be used with other therapies.

Efficacy and tolerability of ketogenic diet therapy in 55 Chinese children with drug-resistant epilepsy in Northwest China

BackgroundDue to the tradition of carbohydrate-rich diet, challenges exist for ketogenic diet (KD) implementation in Northwest China. This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.MethodsIn this single-center study, 55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019. The efficacy of KD, reasons for discontinuation, duration of retention and rate of adverse events were evaluated.ResultsFifty-five children aged from 2.2 months to 169.7 months were included, with a median age at KD initiation of 14.1 months, and 32 cases (58.2%) responded to the diet therapy at the last contact. The responder rates were 16.4% (9/55), 36.4% (20/55), 30.9% (17/55), 27.3% (15/55) at 1, 3, 6 and 12 months, respectively. Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness. Poor compliance and lack of response were main reasons for discontinuation of KD. There are a few side effects of KD, most of which were minor.ConclusionsThe KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resistant epilepsy in Northwest China. Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.

The efficacy of non-fasting ketogenic diet protocol in the management of intractable epilepsy in pediatric patients: a single center study from Saudi Arabia.

ObjectiveTo review the characteristics and outcomes of pediatric patients on a ketogenic diet (KD), an established treatment option for individuals with intractable epilepsy, in a tertiary epilepsy center.MethodsThis retrospective study included pediatric patients diagnosed with intractable epilepsy who had experienced no benefits from at least two appropriately chosen antiseizure medications. All patients were hospitalized, started a KD without fasting, and were observed for complications and tolerance. The etiology of epilepsy, side effects, and KD efficacy on seizure outcomes were also examined.ResultsOf 16 children included in the study, nine (56%) experienced significant seizure improvement, with three becoming seizure-free during the KD. Ten patients were fed orally, and six were fed through gastrostomy feeding tubes. Most were on a 3:1 ratio, and nine reached ketosis within the first three days of KD initiation. Initial recurrent hypoglycemia was documented in four patients, and four experienced vomiting and acidosis. Most families complied with the diet, and all of the children gained weight during the study period.ConclusionKetogenic diets are an established and effective treatment for childhood epilepsy, with reversible mild adverse effects. A non-fasting KD protocol is a safe and effective option for children with intractable epilepsy.

Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus

BackgroundSuper-refractory status epilepticus (SRSE) is extremely difficult to control and associated with poor outcomes. Ketogenic diet (KD) has been increasingly used for SRSE treatment. Enteral ketosis induction in SRSE is sometimes unfeasible, leading to the use of parenteral KD which has limited data among children. ObjectivesTo assess the effectiveness of KD and compare parenteral and enteral ketosis induction as treatment options in pediatric SRSE patients. MethodsThis study is a retrospective medical record review of children < 15 years old diagnosed with SRSE who received KD as one of the treatment modalities during 2007–2021 at King Chulalongkorn Memorial Hospital, Thailand. ResultsKD was used in 14 (77.8%) of the 18 pediatric SRSE cases whose age ranged from 2 months to 13.5 years. The leading etiologies of SRSE were immune-mediated encephalitis, infectious encephalitis, and epilepsy. Ketosis was induced via enteral route (kEN) in 8/14 and parenteral route (kPN) in 6/14 cases. The median time from the onset of SRSE to KD initiation was 6 days (IQR 4.8–9.3) with no demonstrable difference between groups. The median time to achieve significant ketosis was significantly shorter in the kPN (2 days; IQR 1.8–4) compared to the kEN group (5 days (3.3–7.8)). Nonetheless, the median time after ketosis induction to SRSE termination when anesthetic infusion was stopped was not statistically difference between the kPN (14 days; IQR 8.5–18) and the kEN group (10.5 days (5.5–15.3)). Hypertriglyceridemia was found more in the kPN (6/6, 100%) compared to the kEN group (3/8, 37.5%). All survivors (12/14) were seizure free at discharge. ConclusionParenteral ketosis induction achieved the target ketosis quicker than enteral induction but showed no difference in efficacy and duration for SRSE termination in our study. The adverse effects were minimal and controllable. Both parenteral and enteral KD could be considered early during SRSE treatment.

Novel imaging findings in pyruvate dehydrogenase complex (PDHc) deficiency-Results from a nationwide population-based study.

The vast clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency continues to pose challenges both in diagnostics and disease monitoring. Prompt diagnosis is important to enable early initiation of ketogenic diet. The patients were recruited from an ongoing population-based study in Sweden. All patients with a genetically confirmed diagnosis who had been investigated with an MRI of the brain were included. Repeated investigations were assessed to study the evolution of the MRI changes. Sixty-two MRI investigations had been performed in 34 patients (23 females). The genetic cause was mutations in PDHA1 in 29, PDHX and DLAT in 2 each, and PDHB in 1. The lesions were prenatal developmental in 16, prenatal clastic in 18, and postnatal clastic in 15 individuals. Leigh-like lesions with predominant involvement of globus pallidus were present in 12, while leukoencephalopathy was present in 6 and stroke-like lesions in 3 individuals. A combination of prenatal developmental and clastic lesions was present in 15 individuals. In addition, one male with PDHA1 also had postnatal clastic lesions. The most common lesions found in our study were agenesis or hypoplasia of corpus callosum, ventriculomegaly, or Leigh-like lesions. Furthermore, we describe a broad spectrum of other MRI changes that include leukoencephalopathy and stroke-like lesions. We argue that a novel important clue, suggesting the possibility of PDHc deficiency on MRI scans, is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development.

Novel UBE3A pathogenic variant in a large Georgian family produces non-convulsive status epilepticus responsive to ketogenic diet

PurposeTo report the effect of the ketogenic diet (KD) on non-convulsive status epilepticus (NCSE) due to Angelman syndrome (AS) in two members of a large Georgian family affected by a novel frameshift variant in the UBE3A gene (NM_000462.3). MethodsWe evaluated two members of this family who were affected with clinical and EEG features of AS. Clinical history with special emphasis on development, seizure type, frequency, and treatment was reviewed. Routine and long-term video EEG monitoring were conducted, particularly during NCSE. A non-fasting inpatient KD protocol was implemented using blended food orally with full administration of 4:1 (fat to non-fat) ratio. Urine ketone bodies (KBs), measured with urine ketone acetone strips readings, reached 150 mg/dL in both patients. ResultsPatients had characteristic signs of AS and presented with epilepsy between the age of 2–4 years. As methylation tests were negative, next generation sequencing disclosed a c.2365del variant. For both, NCSE was revealed by cognitive deterioration and did not respond to anti-seizure medication. As recommended, IV pyridoxine, benzodiazepines, and valproic acid were administered, but without success. For both patients, NCSE resolved on the second-third day of KD initiation, before the appearance of ketonuria and resulting in improved communication, mood and sleep. ConclusionKD is safe and effective for the treatment of NCSE due to AS. Resolution before the appearance of ketone bodies points to a possible mechanism of action of KD.

QOLP-04. THE KETOGENIC DIET PLUS STANDARD CARE FOR RECENTLY DIAGNOSED GLIOBLASTOMA: A PHASE 1 SAFETY AND FEASIBILITY TRIAL

Abstract INTRODUCTION There is abundant interest in the potential therapeutic and supportive role of a ketogenic diet (KD) for glioblastoma patients. We conducted a single-arm phase 1 trial to assess the safety and feasibility of KD plus standard-of-care (SOC) in glioblastoma patients (NCT03451799). METHODS Adults within 3 months of diagnosis participated in a 16-week intervention of a classic 3:1 KD (grams fat : grams carbohydrate + protein) with dietitian support. Blood glucose and ketone levels were assessed twice daily (Keto-Mojo), with remote monitoring of daily weight and activity (Fitbit). The primary objective was to assess safety (weight stability, CTCAE) and feasibility (maintaining ketosis &amp;gt; 0.3mM for &amp;gt; 50% of study period). Secondary objectives included assessments of progression-free survival (PFS), overall survival (OS), health-related quality of life (HRQOL), and cognition (MoCA). RESULTS From 04/2018-02/2021, 14 patients were evaluable: female:male, 8:6, median age 55 years, KPS 80, BMI 24.5. MGMT promoter methylation: 6 present, 7 absent, 1 indeterminate. Adherence to KD was high, with all patients maintaining ketosis ( &amp;gt; 0.3mM) &amp;gt; 50% and 11 patients maintaining ketosis &amp;gt; 85% of study days. Adverse events (&amp;gt; Grade 2) potentially attributable to KD: appetite loss (Grade 2: 2); fatigue (Grade 2: 5); flu-like symptoms (Grade 2: 1); constipation (Grade 2: 5, Grade 3: 1). No patients were removed from study for safety reasons. HRQOL was stable, with improvements in role function (not statistically significant). MoCA score improved in 10/14 patients. Median PFS and OS from KD initiation were 11.7 and 29.1 months, respectively. CONCLUSION Our findings suggest that a supervised KD plus SOC is safe and feasible in glioblastoma patients. KD was well-tolerated with encouraging trends in HRQOL and cognition. PFS and OS in this small trial compare favorably to historical control. A multicenter phase 2 trial powered to assess efficacy is planned.

P.107 Response to the Ketogenic Diet in refractory epileptic spasms at BC Children’s Hospital

Background: Epileptic spasms (ES) are a devastating seizure type with poor neurodevelopmental outcome; 1/3 are resistant to treatment with first line therapies. Recently attention has been drawn to the ketogenic diet (KD) as a potentially effective therapy, though data regarding optimal time of initiation, and its sustained effectiveness, are lacking. Methods: Retrospective chart review of all patients with ES treated with KD at BC Children’s Hospital between 2002 and 2020 (n=28) with comparison of spasm response based on age of initiation of KD in two groups: &lt; 12 months (n=11) and ≥ 12 months (n=17). Results: Comparing the &lt;12 months and ≥ 12 months groups showed: unknown etiology in 9% vs 25%; spasm freedom for 3 months on KD in 18% vs 41%; median time to spasm freedom was 2 vs 6 weeks; relapse after a period of spasm freedom occurred in 66% vs 70%. Conclusions: Although more effective in children ≥ 12 months of age in the first 3 months, spasm freedom in either group was not sustained with KD. KD is recommended as early therapy for refractory ES, but this study suggests clinicians be aware the KD has limited efficacy in long-term control of ES and must be used with other therapies.