BACKGROUND: Acute herpes zoster is a prevalent condition. One of its major symptoms is pain, which can highly influence patient's quality of life. Pain therapy is limited. Acupuncture is supposed to soften neuropathic pain conditions and might therefore act as a therapeutic alternative. Objective of the present study is to investigate whether a 4 week semi-standardised acupuncture is non-inferior to sham laser acupuncture and the anticonvulsive drug gabapentine in the treatment of pain associated with herpes zoster. METHODS/DESIGN: Three-armed, randomised, placebo-controlled trial with a total follow-up time of 6 months. Up to estimated 336 patients (interim analyses) with acute herpes zoster pain (VAS>30 mm) will be randomised to one of three groups (a) semi-standardised acupuncture (168 patients); (b) gabapentine with individualised dosage between 900-3600 mg/d (84 patients); (c) sham laser acupuncture. Intervention takes place over 4 weeks, all patients will receive analgesic therapy (non-opioid analgesics: metamizol or paracetamol and opioids: tramadol or morphine). Therapy phase includes 4 weeks in which group (a) and (c) consist of 12 sessions per patient, (b) visits depend on patients needs. Main outcome measure is to assess the alteration of pain intensity before and 1 week after treatment sessions (visual analogue scale VAS 0-100 mm). Secondary outcome measure are: alteration of pain intensity and frequency of pain attacks; alteration of different aspects of pain evaluated by standardised pain questionnaires (NPI, PDI, SES); effects on quality of life (SF 36); analgesic demand; alteration of sensoric perception by systematic quantitative sensory testing (QST); incidence of postherpetic neuralgia; side effects and cost effectiveness. Credibility of treatments will be assessed. DISCUSSION: This study is the first large-scale randomised placebo controlled trial to evaluate the efficacy of acupuncture compared to gabapentine and sham treatment and will provide valuable new information about the clinical and physiological effects of acupuncture and gabapentine in the treatment of acute herpes zoster pain. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if acupuncture can be shown to be an effective treatment strategy in acute herpes zoster pain. TRIAL REGISTRATION: NCT00885586.

BACKGROUND: Acute herpes zoster is a prevalent condition. One of its major symptoms is pain, which can highly influence patient's quality of life. Pain therapy is limited. Acupuncture is supposed to soften neuropathic pain conditions and might therefore act as a therapeutic alternative. Objective of the present study is to investigate whether a 4 week semi-standardised acupuncture is non-inferior to sham laser acupuncture and the anticonvulsive drug gabapentine in the treatment of pain associated with herpes zoster. METHODS/DESIGN: Three-armed, randomised, placebo-controlled trial with a total follow-up time of 6 months. Up to estimated 336 patients (interim analyses) with acute herpes zoster pain (VAS>30 mm) will be randomised to one of three groups (a) semi-standardised acupuncture (168 patients); (b) gabapentine with individualised dosage between 900-3600 mg/d (84 patients); (c) sham laser acupuncture. Intervention takes place over 4 weeks, all patients will receive analgesic therapy (non-opioid analgesics: metamizol or paracetamol and opioids: tramadol or morphine). Therapy phase includes 4 weeks in which group (a) and (c) consist of 12 sessions per patient, (b) visits depend on patients needs. Main outcome measure is to assess the alteration of pain intensity before and 1 week after treatment sessions (visual analogue scale VAS 0-100 mm). Secondary outcome measure are: alteration of pain intensity and frequency of pain attacks; alteration of different aspects of pain evaluated by standardised pain questionnaires (NPI, PDI, SES); effects on quality of life (SF 36); analgesic demand; alteration of sensoric perception by systematic quantitative sensory testing (QST); incidence of postherpetic neuralgia; side effects and cost effectiveness. Credibility of treatments will be assessed. DISCUSSION: This study is the first large-scale randomised placebo controlled trial to evaluate the efficacy of acupuncture compared to gabapentine and sham treatment and will provide valuable new information about the clinical and physiological effects of acupuncture and gabapentine in the treatment of acute herpes zoster pain. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if acupuncture can be shown to be an effective treatment strategy in acute herpes zoster pain. TRIAL REGISTRATION: NCT00885586.

Ketogenic diet has been used in treating epilepsy for more than 80 years. It is based on a drastic change of proportions in the consumption of carbohydrates, proteins and fats. In everyday diet we consume approximately 34 per cent of fats, 50 per cent of carbohydrates and 14 per cent of proteins. While ketogenic diet consists in 80-90 per cent of fats and in 10-20 per cents of carbohydrates and proteins together. Despite its indisputable effectiveness, the functioning of the ketogenic diet has not been explained. It seems that its functioning mechanism is unique and results from a number of chronic metabolic changes as well as the adaptation in the cenral nervous system that occurs during its long-term application. The most recent clinical and experimental data suggest that the ketogenic diet also has neuroprotective properties, which makes it a useful alternative therapeutic method in the modification of the natural history of the diseases related with neurodegeneration processes.

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

BACKGROUND:Approximately one-third of patients with epilepsy continue to experience seizures despite adequate therapy with antiepileptic drugs. Drug-resistant epilepsy is even more frequent in subjects with intellectual disability. As a result, several non-pharmacological interventions have been proposed to improve quality of life in patients with intellectual disability and drug-resistant epilepsy. A number of studies have demonstrated that music can be effective at reducing seizures and epileptiform discharges. In particular, Mozart's sonata for two pianos in D major, K448, has been shown to decrease interictal EEG discharges and recurrence of clinical seizures in patients with intellectual disability and drug-resistant epilepsy as well. The aim of this study is to investigate the influence of Mozart's music on seizure frequency in institutionalized epileptic subjects with profound/severe intellectual disability.

SUBJECTS AND METHODS:Twelve patients (10 males and 2 females) with a mean age of 21.6 years were randomly assigned to two groups in a cross-over design; they listened to Mozart K448 once a day for six months.

RESULTS:A statistically significant difference was observed between the listening period and both baseline and control periods. During the music period, none of the patients worsened in seizure frequency; one patient was seizure-free, five had a greater than 50% reduction in seizure frequency and the remaining showed minimal (N=2) or no difference (N=4). The average seizure reduction compared to the baseline was 20.5%. Our results are discussed in relation to data in the literature considering differences in protocol investigation.

CONCLUSIONS:Music may be considered a useful approach as add-on therapy in some subjects with profound intellectual disability and drug-resistant epilepsy and can provide a new option for clinicians to consider, but further large sample, multicenter studies are needed to better understand the characteristics of responders and non-responders to this type of non-pharmacological intervention.

There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of∆-tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.

The ketogenic diet was developed in the 1920s as a treatment for intractable childhood seizures when few antiepileptic drugs (AEDs) were available. There are still children whose seizures are refractory even to modern therapy, but use of the ketogenic diet appears to be waning. At Johns Hopkins, we continue to believe that the diet is very effective and well accepted by patients and families. To reevaluate our opinion of the efficacy and acceptability of this form of therapy in patients cared for in the 1980s with the newer AEDs, we analyzed the records of 58 consecutive patients who had been started on the diet. Before using the diet, 80% of the patients had multiple seizure types and 88% were treated with multiple AEDs; these children were among our most intractable patients. Despite this, seizure control improved in 67% of patients with the ketogenic diet, and actuarial analysis indicated that 75% of these improved patients continued the diet for at least 18 months. Sixty-four percent had AEDs reduced, 36% became more alert, and 23% had improved behavior. The improvement in these patients with intractable seizures and the length of time that families maintained the regimen indicate that the ketogenic diet continues to have a very useful therapeutic role in selected patients and their families.

OBJECTIVE:The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet.

METHODS:We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown.

RESULTS:Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed.

SIGNIFICANCE:The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not.

Background:Even with the extensive use of ketogenic dietary therapies (KD), there still exist many areas of the world that do not provide these treatments. Implementing the ketogenic diet in different countries forms a real challenge in order to match the cultural and economic differences.

Aim:To assess the feasibility of implementing a ketogenic diet plan in a limited resource setting with identification of the compliance, tolerability and side effects in the target population and to assess the efficacy of the ketogenic diet in children with intractable epilepsy.

Method of the study:The medical records of 28 patients with intractable epilepsy, treated at The Children's Hospital - Cairo University from December 2012 to March 2014 with ketogenic dietary therapy were reviewed. The non-fasting protocol was followed without hospital admission. All children were started on a standardized classic ketogenic diet with a ratio ranging from 2.5-4:1 (grams of fat to combined carbohydrate and protein). Patients were followed at 1, 3 and 6 months after diet initiation.

Results:The median age was 60 months (range, 30-110). After 1 month from diet initiation, 16 patients (57%) remained on the diet. One of them (6.3%) had more than 90% reduction in seizure frequency, an additional 6 patients (37.5%) had a 50-90% reduction in seizure frequency. In total, seven out of the 16 patients continuing the diet for 1 month (43.8%) had more than 50% improvement in seizure control from the base line. Despite having 50-90% seizure control, three children discontinued the diet after one month.Three months after diet initiation, 6 patients (22%) remained on diet, 4 of them (66.7%) had more than 50%reduction in seizure frequency.At 6 months, only 3 patients remained on diet, 2 of them (66.6%) had 50-90% reduction in seizure frequency, while one patient (33.3%) showed better than 90% decrease in seizure.

Conclusion:The current study shows that the ketogenic diet could be implemented in medium resources countries and should be included in the management of children with intractable epilepsy.

The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s) (MCT) ketogenic diet, modified Atkins diet, and low glycemic index treatment.

INTRODUCTION:Ketogenic diet is a low carbohydrate diet, which can be used as a treatment for refractory childhood epilepsy. The first aim of this study was to evaluate its efficacy, in patients receiving ketogenic diet for at least three months, on epilepsy control, behaviour and awareness. The secondary aims were to evaluate the variation in the number of antiepileptic drugs, reasons for discontinuing the diet and adverse effects.

MATERIAL AND METHODS:Retrospective analysis of clinical records of patients who underwent ketogenic diet for refractory epilepsy, from October 2007 to January 2018, in a tertiary pediatric hospital.

RESULTS:In the twenty-nine eligible patients, the mean age of initiation was 7.9 years-old (+/- 5.6). Of those, 18 had a≥ 50% reduction of seizure activity, 19 a marked behaviour improvement and 18 improved awareness. The median number of antiepileptic drugs remained equal for the 15 patients who completed 18 months of treatment (three drugs). The main reason for discontinuing ketogenic diet was a familiar decision. The main adverse effects were hypercholesterolemia (n = 23) and hypertriglyceridemia (n = 21).

DISCUSSION:Results were comparable to those of other cohorts, namely age of initiation, proportion of patients completing ketogenic diet, most frequent reasons for stopping and significant improvement of alertness and behavior.

CONCLUSION:Beyond seizure control, patients experienced a marked improvement in behavior and awareness. It is necessary to develop strategies to increase the adherence of families to the diet.

BACKGROUND AND PURPOSE:In the present study, we reviewed the outcome of ketogenic diet (KD) use for the management of epilepsy in children with tuberous sclerosis complex (TSC).

METHODS:A total of 12 children with intractable epilepsy associated with TSC who were treated with KD at our hospital between March 1, 2008 and February 28, 2015 were retrospectively enrolled.

RESULTS:The mean age at the time of KD initiation was 73.1± 38.0 months. Patients were medically refractory to a mean of 4.8 ± 1.7 antiepileptic drugs. Nine patients (75.0%) had a history of infantile spasms. At 3 months after KD initiation, 10 patients (83.3%) had>50% seizure reduction. Moreover, 7 patients (58.3%) exhibited qualitative improvements in cognition and behavior after KD initiation, as reported by caregivers/parents. The mean duration of dietary therapy was 14.8± 12.8 months. Half of the patients in this study eventually underwent epilepsy surgery due to persistent seizures or seizure relapse.

CONCLUSION:KD is an important non-pharmacological treatment option for patients with intractable epilepsy associated with TSC. KD may improve cognition and behavior in addition to reducing seizure frequency.

PURPOSE:The ketogenic diet (KD) has been used as a therapeutic alternative to antiepileptic drugs (AEDs) for refractory epilepsy. Severe myoclonic epilepsy in infants or Dravet syndrome (DS) is one of the most malignant epileptic syndromes. In this retrospective study, we evaluated the efficacy and tolerability of the KD in patients with diagnostic criteria of DS.

METHODS:Between March 1, 1990, and August 31, 2004, 52 patients who met diagnostic criteria for DS were enrolled in a study at our department. Twenty of them were placed on the KD with the Hopkins protocol and followed up for a minimum of 1 year.

RESULTS:Three of the 20 original children stayed on the diet for 12 months, four children for 2 years, four children for 3 years, and two children for 4 years. One year after initiating the diet, 13 (65%) of the initial patients remained on the diet. Two (15%) patients were seizure free, eight (61.7%) children had a 75-99% decrease in seizures, and the remaining three (23%) children had a 50-74% decrease in seizures. Thus 1 year after starting the diet, 10 (77%) children had achieved a>75% decrease in their seizures. Four patients have been off the diet for>2 years; one of them is seizure free, two have sporadic seizures, and one, who abandoned the diet after 2 years of adhering to it, relapsed. No differences in seizure control when compared with age, sex, or seizure type were found.

CONCLUSIONS:Considering the severity and intractability of seizures in patients with DS, the fact that 10 of the 13 children who remained on the diet had a significant reduction in number of seizures shows that the KD is at present an interesting therapeutic alternative. Even in patients in whom seizure reduction was not dramatic, quality of life improved, and in all of them, the number of AEDs was reduced to one or two. We consider that children with DS should be offered the KD immediately after three adequate trials of AEDs have failed.

Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects.

BACKGROUND:Although a larger number of antiepileptic drugs became available in the last decades, epilepsy remains drug-resistant in approximately a third of patients. Ketogenic diet (KD), first proposed at the beginning of the last century, is complex and has anticonvulsant effects, yet not completely understood. Over the last decades, different types of ketogenic diets (KDs) have been developed, namely classical KD and modified Atkins diet (MAD). They offer an effective alternative for children and adults with drug-resistant epilepsies.

METHODS:We review several papers on KDs as an adjunctive treatment of refractory epilepsy of children and adults, discussing its efficacy and adverse events. Because of the heterogenous, uncontrolled nature of the studies, we analyzed all studies individually, without a meta-analysis.

RESULTS:KDs may be considered first choice treatment in some specific metabolic conditions, such as glucose-transporter type 1 and pyruvate dehydrogenase deficiencies, and mitochondrial complex I defects. Preliminary findings indicate that KDs may be specifically effective in some epileptic syndromes, such as West syndrome, severe myoclonic epilepsy of infancy, myoclonic-astatic epilepsy, febrile infection related epileptic syndrome, and drug-resistant idiopathic generalized epilepsies or refractory status epilepticus. Short term adverse events are usually mild in both children and adults, including gastrointestinal symptoms, hyperlipidemia, and hypercalciuria; potential long term adverse effects include nephrolitiasis, decreased bone density, and liver steatosis. Possible atherosclerotic effects remain a concern. Patients on KDs should be carefully monitored in specialized centers during initiation, maintenance and withdrawal periods, in order to minimize such adverse events, and to improve compliance. Although the majority of KD trials on children and adults with drug-resistant epilepsies are open-label, uncontrolled studies based on small samples, an increasing number of randomized controlled trials have provided better quality evidence on its efficacy in recent years.

CONCLUSION:There is a need for future randomized clinical trials aimed to confirm the efficacy of KDs in specific epileptic syndromes, and to provide further information about some practical unsolved problems, i.e. for how long KD treatment should be continued.

OBJECTIVE:For epilepsy with tuberous sclerosis complex (TSC), ketogenic diet (KD) therapy has been consistently reported to be more beneficial than the average KD therapy response. Herein, we aimed to investigate the long-term outcomes of a KD on patients with TSC and intractable epilepsy.

METHODS:This study included 31 patients with intractable epilepsy and TSC who were treated with the KD, and an intention-to-treat analysis was performed.

RESULTS:Overall, 21 of the 31 patients (67.7%) had>50% reduction in seizures at 3 months after initiating the KD. Thirteen of the 31 patients (41.9%) were seizure-free for at least 3 months, but 10 of these 13 patients (76.9%) experienced seizure recurrence during the 24-month follow-up period. Finally, at 24 months of the KD observational period, there was>50% response in 10 of the 31 patients (32.3%), including seizure-free patients (6 of 31 patients, 19.4%). Most of the patients (12 of 13, 92.3%) who experienced seizure freedom had>50% reduction in seizures within 1 month after initiating the KD, and this result was the only factor associated with seizure freedom in the current study.

CONCLUSION:The KD appeared to be an effective therapeutic modality for intractable pediatric epilepsy in TSC, but it did not exhibit guaranteed efficacy over a long-term period.

Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement ofγ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, suchas adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures.

WHAT IS KNOWN AND OBJECTIVE:Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly. Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs. The present review summarizes studies on the anticonvulsant properties of phytocannabinoids.

METHODS:Literature search using the PubMed database to identify studies on phytocannabinoids and epilepsy.

RESULTS AND DISCUSSION:Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration.

WHAT IS NEW AND CONCLUSION:Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects. Cannabidiol and cannabidivarin should be tested in randomized, controlled clinical trials, especially in infantile epileptic syndromes.

BACKGROUND:Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far.

CASE:Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions.

RESULTS:We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet.

CONCLUSION:Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.