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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Unraveling the nutritional challenges in epilepsy: Risks, deficiencies, and management strategies: A systematic review. World J Exp Med 2025; 15:104328. [DOI: 10.5493/wjem.v15.i2.104328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/24/2025] [Accepted: 03/18/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Malnutrition and epilepsy share a complex bidirectional relationship, with malnutrition serving as a potential risk factor for epilepsy development, while epilepsy, in turn, often exerts profound effects on nutritional status. Nutritional interventions have emerged as a critical adjunctive approach in epilepsy management.
AIM To explore the multifaceted associations between malnutrition and epilepsy, structured into three primary sections: (1) Elucidating the impact of malnutrition as a risk factor for epilepsy onset; (2) Examining the reciprocal influence of epilepsy on nutritional status, and (3) Evaluating diverse nutritional interventions in the management of epilepsy.
METHODS A systematic search was conducted across PubMed, Scopus, and Web of Science databases utilizing defined keywords related to malnutrition, epilepsy, and nutritional interventions. Inclusion criteria encompassed various study types, including clinical trials, animal models, cohort studies, case reports, meta-analyses, systematic reviews, guidelines, editorials, and review articles. Four hundred sixteen pertinent references were identified, with 198 review articles, 153 research studies, 21 case reports, 24 meta-analyses, 14 systematic reviews, 4 guidelines, and 2 editorials meeting the predefined criteria.
RESULTS The review revealed the intricate interplay between malnutrition and epilepsy, highlighting malnutrition as a potential risk factor in epilepsy development and elucidating how epilepsy often leads to nutritional deficiencies. Findings underscored the importance of nutritional interventions in managing epilepsy, showing their impact on seizure frequency, neuronal function, and overall brain health.
CONCLUSION This systematic review emphasizes the bidirectional relationship between malnutrition and epilepsy while emphasizing the critical role of nutritional management in epilepsy treatment. The multifaceted insights underscore the need for a holistic approach to addressing nutritional aspects alongside conventional epilepsy management strategies.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Governmental Hospitals, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, The Royal College of Surgeons in Ireland, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 15503, Muharraq, Bahrain
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Rezazadeh K, Barzegar M, Nezamdoost E, Shoaran M, Abbasi MM, Ghasemi B, Madadi S, Raeisi S. Hepatic toll of keto: unveiling the inflammatory and structural consequences of ketogenic diet in rats. BMC Nutr 2025; 11:72. [PMID: 40200308 PMCID: PMC11980344 DOI: 10.1186/s40795-025-01057-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 03/28/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND The ketogenic diet (KD) has been used as a therapeutic diet for a range of diseases such as epilepsy, obesity, and cancer. However, it may cause some adverse effects that are not well known. This study aimed to assess the possible impact of the KD on liver structure and function, as well as hepatic inflammatory markers. METHODS Ninety male rats were randomly divided into two groups: the normal diet group consumed a standard rat chow, and the KD group consumed a diet composed of 90% fat, 8% protein, and 2% carbohydrates for 30 days. The serum levels of lipid profile (cholesterol and triglyceride), liver enzymes, hepatic levels of inflammatory markers, and steatosis grading were evaluated and compared between the two groups. RESULTS The serum cholesterol and alanine transaminase (ALT) levels in the KD group were significantly higher than in the normal diet group. However, there were no significant differences between groups in serum triglyceride and aspartate transaminase (AST) levels. Hepatic inflammatory markers, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), both were higher in the KD group compared to the normal diet group. In the liver biopsy, the degree of steatosis was significantly higher in the KD group compared to the normal diet group. CONCLUSION The KD may cause hepatic adverse effects by inducing steatosis and inflammation.
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Affiliation(s)
- Khatereh Rezazadeh
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Barzegar
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Erfan Nezamdoost
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Shoaran
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Babollah Ghasemi
- Division of Clinical Laboratory, , Zahra Mardani Azari Children Training, Research, and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Solmaz Madadi
- Division of Clinical Laboratory, , Zahra Mardani Azari Children Training, Research, and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Raeisi
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Kang JS, Kim H, Baek JH, Song M, Park H, Jeong W, Chung HJ, Yoo DY, Lee DK, Park SW, Kim HJ. Activation of glutamine synthetase (GS) as a new strategy for the treatment of major depressive disorder and other GS-related diseases. Acta Pharmacol Sin 2025; 46:880-891. [PMID: 39775502 PMCID: PMC11950325 DOI: 10.1038/s41401-024-01441-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025]
Abstract
Glutamine synthetase (GS) plays a crucial role in the homeostasis of the glutamate-glutamine cycle in the brain. Hypoactive GS causes depressive behaviors. Under chronic stress, GS has no change in expression, but its activity is decreased due to nitration of tyrosine (Tyr). Thus, we speculate that agents that prevent nitration or facilitate denitration of GS would be candidates for new antidepressants. Using human recombinant GS and mouse lysate from the medial prefrontal cortex, we demonstrated that Tyr (0.0313-0.5 µM) dose-dependently protected GS activity against peroxynitrite-induced Tyr-nitration of GS. Diet supplementation with Tyr exerted significant antidepressant effects in a chronic immobilization stress depression mouse model. We further found that dipeptides, such as tyrosyl-glutamine (YQ), that had appropriate chemical properties for medication also increased GS activity both in vitro and in vivo and exerted antidepressant effects. Because reduced GS activity also occurs in epilepsy and hyperammonemia, we evaluated whether Tyr and YQ had therapeutic effects. Interestingly, Tyr or YQ administration significantly attenuated kainic acid-induced seizures in mice and reduced blood ammonia levels in azoxymethane- or bile duct ligation-induced hyperammonemia mouse models, which was accompanied by an increment in GS activity. The activation of GS was accomplished by a decrement in Tyr-nitration, so-called Tyr-denitration. Therefore, this study demonstrates that the activation of GS could be a new strategy to treat depression and other GS-related diseases.
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Affiliation(s)
- Jae Soon Kang
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Hwajin Kim
- Department of Pharmacology and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Ji Hyeong Baek
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Miyoung Song
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Hyeongchan Park
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Wonjune Jeong
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Hye Jin Chung
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Dae Young Yoo
- Department of Anatomy and Cell Biology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea
| | - Dong Kun Lee
- Department of Physiology and Convergence Medical Sciences, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea
| | - Sang Won Park
- Department of Pharmacology and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
| | - Hyun Joon Kim
- Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Medical Science, Tyrosine Peptide Multiuse Research Group, Anti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National University, Jinju, Gyeongnam, Republic of Korea.
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Ray S, Nathan J, Godhia M. Efficacy and tolerability of classical and polyunsaturated fatty acids ketogenic diet in controlling paediatric refractory epilepsy - A randomized study. Epilepsy Res 2024; 204:107395. [PMID: 38908324 DOI: 10.1016/j.eplepsyres.2024.107395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 04/15/2024] [Accepted: 06/10/2024] [Indexed: 06/24/2024]
Abstract
OBJECTIVES To measure and compare the efficacy and tolerability of a classical ketogenic diet (CKD) and a polyunsaturated fatty acids ketogenic diet (PUFAKD) in managing childhood refractory epilepsy. Efficacy was assessed by measuring the change in seizure frequency at 3, 6, 9, and 12 months within and between groups. The percentage reduction in seizures at <50 %, 50-90 %, >90 %, and 100 % was also measured. Tolerability was assessed and compared by recording adverse events - vomiting, nausea, lethargy, and constipation. METHODS 52 children, aged 2-10 years, were randomized, 25 in the CKD group and 27 in the PUFAKD group. Fat: carbohydrate + protein ratio of 2.2:1-4:1 was maintained in both diets; the PUFAKD group only used unsaturated fats with an omega 3: omega 6 ratio of 1:2.8. Ketone levels were measured using keto-dipsticks, with 4+ and 4++ (80-160 mg/dL) being the most optimal values. RESULTS A significant decrease (p=0.001) in seizures was observed (n=52), with no significant difference (p=0.537) between the two groups. The mean seizure reduction was 71.1 %, with no significant difference (p=0.488) in both groups. The mean compliance rate was 78.3 % (n=52). A statistically significant linear trend existed between a higher compliance rate and a greater reduction in seizures (p = 0.042, Z=4.039) among all children (n=52). Nausea (p=0.033) and vomiting (p=0.014) occurred more in PUFAKD than in CKD. CONCLUSION No significant difference was seen in seizure reduction between the two groups. Compliance correlates with a greater seizure reduction. Despite similar seizure reduction rates, the novel PUFAKD exhibited poorer compliance and more pronounced adverse effects compared to CKD. CKD remained a superior choice over the novel PUFAKD in the management of paediatric refractory epilepsy. More controlled trials with varying PUFA compositions are recommended for long-term evaluations.
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Affiliation(s)
- Subhasree Ray
- Corporate Medical Services, Reliance Industries Limited, Mumbai, India.
| | | | - Meena Godhia
- Food Sc. & Nutrition, S.N.D.T. Women's University, Mumbai, India
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Van Roessel IMAA, Van Den Brink M, Dekker J, Ruitenburg-van Essen BG, Tissing WJE, van Santen HM. Feasibility, safety, and efficacy of dietary or lifestyle interventions for hypothalamic obesity: A systematic review. Clin Nutr 2024; 43:1798-1811. [PMID: 38955055 DOI: 10.1016/j.clnu.2024.05.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 04/11/2024] [Accepted: 05/16/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND & AIMS A dysfunctional hypothalamus may result in decreased feelings of satiety (hyperphagia), decreased energy expenditure, and increased fat storage as a consequence of hyperinsulinemia. Hypothalamic dysfunction may thus lead to morbid obesity and can be encountered in childhood as a consequence of congenital, genetic, or acquired disorders. There is currently no effective treatment for hypothalamic obesity (HO). However, comparable to alimentary obesity, dietary and lifestyle interventions may be considered the cornerstones of obesity treatment. We questioned the effect of dietary or lifestyle interventions for HO and systematically searched the literature for evidence on feasibility, safety, or efficacy of dietary or lifestyle interventions for childhood hypothalamic overweight or obesity. METHODS A systematic search was conducted in MEDLINE (including Cochrane Library), EMBASE, and CINAHL (May 2023). Studies assessing feasibility, safety, or efficacy of any dietary or lifestyle intervention in children with hypothalamic overweight or obesity, were included. Animal studies, studies on non-diet interventions, and studies with no full text available were excluded. Because the number of studies to be included was low, the search was repeated for adults with hypothalamic overweight or obesity. Risk of bias was assessed with an adapted Cochrane Risk of Bias Tool. Level of evidence was assessed using the GRADE system. Descriptive data were described, as pooled-data analysis was not possible due to heterogeneity of included studies. RESULTS In total, twelve studies were included, with a total number of 118 patients (age 1-19 years) of whom one with craniopharyngioma, one with ROHHAD-NET syndrome, 50 with monogenic obesity, and 66 with Prader-Willi syndrome (PWS). Four studies reported a dietary intervention as feasible. However, parents did experience difficulties with children still stealing food, and especially lowering carbohydrates was considered to be challenging. Seven studies reported on efficacy of a dietary intervention: a well-balanced restrictive caloric diet (30% fat, 45% carbohydrates, and 25% protein) and various hypocaloric diets (8-10 kcal/cm/day) were considered effective in terms of weight stabilization or decrease. No negative effect on linear growth was reported. Four studies reported on specific lifestyle interventions, of which three also included a dietary intervention. Combined dietary and lifestyle intervention resulted in decreased BMI, although BMI returned to baseline values on long-term. One additional study was identified in adults after brain trauma and showed a significant reduction in BMI in one out of eight patients after a combined dietary and lifestyle intervention. CONCLUSIONS Hypocaloric diet or restrictive macronutrient diet with lower percentage of carbohydrates seems feasible and effective for childhood HO, although most of the studies had a high risk of bias, small cohorts without control groups, and were conducted in children with PWS only, compromising the generalizability. Lifestyle interventions only resulted in BMI decrease in short-term, indicating that additional guidance is needed to sustain its effect in the long-term. Literature on feasibility and efficacy of a dietary or lifestyle intervention for hypothalamic overweight or obesity is scarce, especially in children with acquired HO (following treatment for a suprasellar tumor). There is need for prospective (controlled) studies to determine which dietary and lifestyle intervention are most helpful for this specific patient group.
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Affiliation(s)
- I M A A Van Roessel
- Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
| | - M Van Den Brink
- Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Laboratory of Behavioral Gastronomy, Centre for Healthy Eating and Food Innovation, Nassaustraat 36, 5911 BV, Venlo, the Netherlands
| | - J Dekker
- Department of Dietetics, Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands
| | - B G Ruitenburg-van Essen
- Department of Dietetics, Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands
| | - W J E Tissing
- Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pediatric Oncology and Hematology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands
| | - H M van Santen
- Princess Máxima Center, Heidelberglaan 25, 3584 CS Utrecht, the Netherlands; Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center, Lundlaan 6, 3584 EA Utrecht, the Netherlands
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Acuña-Catalán D, Shah S, Wehrfritz C, Nomura M, Acevedo A, Olmos C, Quiroz G, Huerta H, Bons J, Ampuero E, Wyneken U, Sanhueza M, Arancibia F, Contreras D, Cárdenas JC, Morales B, Schilling B, Newman JC, González-Billault C. Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice. Cell Rep Med 2024; 5:101593. [PMID: 38843842 PMCID: PMC11228662 DOI: 10.1016/j.xcrm.2024.101593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 02/26/2024] [Accepted: 05/14/2024] [Indexed: 06/21/2024]
Abstract
Aging compromises brain function leading to cognitive decline. A cyclic ketogenic diet (KD) improves memory in aged mice after long-term administration; however, short-term effects later in life and the molecular mechanisms that govern such changes remain unclear. Here, we explore the impact of a short-term KD treatment starting at elderly stage on brain function of aged mice. Behavioral testing and long-term potentiation (LTP) recordings reveal that KD improves working memory and hippocampal LTP. Furthermore, the synaptosome proteome of aged mice fed a KD long-term evidence changes predominantly at the presynaptic compartment associated to the protein kinase A (PKA) signaling pathway. These findings were corroborated in vivo by western blot analysis, with high BDNF abundance and PKA substrate phosphorylation. Overall, we show that a KD modifies brain function even when it is administered later in life and recapitulates molecular features of long-term administration, including the PKA signaling pathway, thus promoting synaptic plasticity at advanced age.
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Affiliation(s)
- Diego Acuña-Catalán
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile
| | - Samah Shah
- The Buck Institute for Research on Aging, Novato, CA, USA
| | | | | | - Alejandro Acevedo
- Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile
| | - Cristina Olmos
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile
| | - Gabriel Quiroz
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile
| | - Hernán Huerta
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile
| | - Joanna Bons
- The Buck Institute for Research on Aging, Novato, CA, USA
| | - Estibaliz Ampuero
- Neurobiology of Behavior Laboratory, Department of Biology, Universidad de Santiago de Chile, Santiago, Chile
| | - Ursula Wyneken
- IMPACT, Center for Interventional Medicine for Precision and Advanced Cellular Therapy, and Faculty of Medicine, Universidad de Los Andes, Santiago, Chile
| | - Magdalena Sanhueza
- Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile
| | - Felipe Arancibia
- Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile
| | - Darwin Contreras
- Laboratory of Neuroscience, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago, Chile
| | - Julio César Cárdenas
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; The Buck Institute for Research on Aging, Novato, CA, USA; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile; Department of Chemistry and Biochemistry and Center for Aging and Longevity Studies University of California, Santa Barbara, CA, USA
| | - Bernardo Morales
- Laboratory of Neuroscience, Faculty of Chemistry and Biology, Universidad de Santiago de Chile, Santiago, Chile
| | | | - John C Newman
- The Buck Institute for Research on Aging, Novato, CA, USA
| | - Christian González-Billault
- Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences, Universidad de Chile, Santiago, Chile; The Buck Institute for Research on Aging, Novato, CA, USA; Institute of Nutrition and Food Technology (INTA), Universidad de Chile, Santiago, Chile; Department of Neurosciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
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Urio OH, Kija E, Weckhuysen S, Makungu H, Naburi H. Drug resistant epilepsy and associated factors among children with epilepsies in tanzania: a cross-sectional study. BMC Neurol 2024; 24:8. [PMID: 38166885 PMCID: PMC10759687 DOI: 10.1186/s12883-023-03508-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 12/12/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND Epilepsy contributes to high morbidity among children and adolescents in developing countries. A quarter of all children with epilepsy will be resistant to anti-seizure medications (ASMs), with associated neurocognitive impairments and risk of higher mortality. This study aimed to estimate and characterize drug-resistant epilepsy (DRE) (defined as failure to achieve sustained remission after adequate trials of two tolerated and appropriately chosen ASMs) and its associated factors among children and adolescents with epilepsies attending the pediatric neurology clinic at Muhimbili National Hospital (MNH), Dar es Salaam Tanzania. METHODS This cross-sectional study was conducted from June 2020 to June 2021. Children with epilepsies and who had been treated with ASMs for at least 3 months were eligible for inclusion. Exclusion criteria included children whose caregivers denied consent and those who exhibited acute medical conditions necessitating admission on the scheduled visit day. Data on demographic characteristics, perinatal history, detailed history of the seizures semiology, drug history, magnetic resonance imaging (MRI), and electroencephalography (EEG) results were obtained from caregivers and medical records available during recruitment. Seizures and epilepsies were classified using the 2017 International League Against Epilepsy (ILAE) classification. Logistic regression was used to determine factors associated with DRE. RESULTS A total of 236 children and adolescents aged between 4 months and 15 years (Median age 72 months (IQR = 42-78)) were enrolled in this study. We found the proportion of DRE to be 14.8% in this cohort. Of the thirty-five patients with DRE, 60% had generalized epilepsy and almost 25% had a diagnosis of an epilepsy syndrome, the most common being Lennox-Gastaut syndrome (LGS). Structural abnormalities on brain MRI were seen in almost 80% of all patients with DRE, the most prevalent being cystic encephalomalacia, which was observed in 34% of patients. Patients using both ASMs and alternative therapies accounted for 9% of this cohort. The onset of seizures during the first month of life (aOR = 1.99; 95%CI 1.7-4.6; p = 0.031) and high initial seizure frequency (aOR = 3.6; 95%CI 1.6-8;p = 0.002) were found to be independently associated with DRE. CONCLUSION The proportion of DRE in Tanzania is high. Patients with neonatal onset seizures and high initial seizure frequency should be followed up closely to ensure early diagnosis of DRE.
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Affiliation(s)
- Obrey H Urio
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
| | - Edward Kija
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | | | - Hilda Makungu
- Department of radiology, Muhimbili National Hospital, Dar es Salaam, Tanzania
| | - Helga Naburi
- Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
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Rafli A, Handryastuti S, Karyanti MR, Devaera Y, Hafifah CN, Mangunatmadja I, Kadim M, Herini ES, Nofi LS, Ratnawati A, Fitrianti S. The Effectiveness of Modified Atkins Ketogenic Diet on Children with Intractable Epilepsy: A Pilot Study from Indonesia. J Nutr Metab 2023; 2023:9222632. [PMID: 39263373 PMCID: PMC11390222 DOI: 10.1155/2023/9222632] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 10/22/2023] [Accepted: 12/15/2023] [Indexed: 09/13/2024] Open
Abstract
Background The ketogenic diet has recently been explored as a potential treatment approach for intractable epilepsy in children and has been applied in various parts of the world. The ketogenic diet is also effective for the treatment of mood disorders, especially for adolescent and young adults with epilepsy. The Modified Atkins Diet (MAD) is the less restrictive type of ketogenic diet with similar principles as the classic type. However, no study has been conducted to evaluate the use of MAD in children with severe epilepsy in Indonesia. This study aims to assess the effectiveness, tolerance, compliance, and the adverse effects of MAD in children with intractable epilepsy during a 6-month monitoring period. Methods This is a pilot experimental study involving children aged 2-18 years old with intractable epilepsy at the Pediatric Neurology and the Pediatric Nutrition & Metabolic Diseases Clinics at the Dr. Cipto Mangunkusumo Hospital Jakarta between November 2021 and June 2022. Results A total of 31 subjects met the inclusion criteria and received the MAD in the first month, followed by 13 (41.9%) subjects in the third month, and 9 (29%) subjects in the sixth month. The MAD reduced the seizure frequency by 50% (p = 0.144), 62% (p = 0.221), and 83.3% (p = 0.028) in the first, third, and sixth months, respectively. The most frequent adverse effects are vomiting and diarrhea. Noncompliance was observed in 18 (58.1%) subjects. A sample of the MAD food menu guidebook was developed to make it easier for parents to adhere to the diet. Conclusions The MAD reduces the mean seizure frequency in children with intractable epilepsy in the first, third, and sixth months, with a statistical significance in the sixth month. A further randomized, controlled, and multicenter clinical trial with a larger sample size and longer observation period is required. This trial is registered with Protocol ID 20-10-1323.
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Affiliation(s)
- Achmad Rafli
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Setyo Handryastuti
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Mulya Rahma Karyanti
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Yoga Devaera
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Cut Nurul Hafifah
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Irawan Mangunatmadja
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Muzal Kadim
- Department of Child Health Dr. Cipto Mangunkusumo Hospital-Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Elisabeth Siti Herini
- Department of Child Health Dr. Sardjito Hospital-Faculty of Medicine Public Health and Nursing Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Lora Sri Nofi
- Nutrition and Food Service Unit, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Ariek Ratnawati
- Nutrition and Food Service Unit, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
| | - Suci Fitrianti
- Nutrition and Food Service Unit, Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia
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Carmody LC, Gargano MA, Toro S, Vasilevsky NA, Adam MP, Blau H, Chan LE, Gomez-Andres D, Horvath R, Kraus ML, Ladewig MS, Lewis-Smith D, Lochmüller H, Matentzoglu NA, Munoz-Torres MC, Schuetz C, Seitz B, Similuk MN, Sparks TN, Strauss T, Swietlik EM, Thompson R, Zhang XA, Mungall CJ, Haendel MA, Robinson PN. The Medical Action Ontology: A tool for annotating and analyzing treatments and clinical management of human disease. MED 2023; 4:913-927.e3. [PMID: 37963467 PMCID: PMC10842845 DOI: 10.1016/j.medj.2023.10.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/31/2023] [Accepted: 10/14/2023] [Indexed: 11/16/2023]
Abstract
BACKGROUND Navigating the clinical literature to determine the optimal clinical management for rare diseases presents significant challenges. We introduce the Medical Action Ontology (MAxO), an ontology specifically designed to organize medical procedures, therapies, and interventions. METHODS MAxO incorporates logical structures that link MAxO terms to numerous other ontologies within the OBO Foundry. Term development involves a blend of manual and semi-automated processes. Additionally, we have generated annotations detailing diagnostic modalities for specific phenotypic abnormalities defined by the Human Phenotype Ontology (HPO). We introduce a web application, POET, that facilitates MAxO annotations for specific medical actions for diseases using the Mondo Disease Ontology. FINDINGS MAxO encompasses 1,757 terms spanning a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. These terms annotate phenotypic features associated with specific disease (using HPO and Mondo). Presently, there are over 16,000 MAxO diagnostic annotations that target HPO terms. Through POET, we have created 413 MAxO annotations specifying treatments for 189 rare diseases. CONCLUSIONS MAxO offers a computational representation of treatments and other actions taken for the clinical management of patients. Its development is closely coupled to Mondo and HPO, broadening the scope of our computational modeling of diseases and phenotypic features. We invite the community to contribute disease annotations using POET (https://poet.jax.org/). MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO). FUNDING NHGRI 1U24HG011449-01A1 and NHGRI 5RM1HG010860-04.
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Affiliation(s)
- Leigh C Carmody
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
| | | | - Sabrina Toro
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | | | - Margaret P Adam
- University of Washington School of Medicine, Seattle, WA, USA
| | - Hannah Blau
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
| | | | - David Gomez-Andres
- Pediatric Neurology, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain
| | - Rita Horvath
- Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge CB2 0PY, UK
| | - Megan L Kraus
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Markus S Ladewig
- Department of Ophthalmology, Klinikum Saarbrücken, Saarbrücken, Germany
| | - David Lewis-Smith
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Hanns Lochmüller
- Children's Hospital of Eastern Ontario Research Institute, Ottowa, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada; Department of Neuropediatrics and Muscle Disorders, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany; Centro Nacional de Análisis Genómico, Barcelona, Spain
| | | | | | - Catharina Schuetz
- Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Berthold Seitz
- Department of Ophthalmology, Saarland University Medical Center UKS, Homburg, Saar, Germany
| | - Morgan N Similuk
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Teresa N Sparks
- Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Timmy Strauss
- Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Emilia M Swietlik
- Department of Medicine, University of Cambridge, Heart and Lung Research Institute, Cambridge CB2 0BB, UK
| | - Rachel Thompson
- Children's Hospital of Eastern Ontario Research Institute, Ottowa, Canada
| | | | | | | | - Peter N Robinson
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
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10
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Güleryüz C, Eker E, Karacan Küçükali G, Şakar M, Genç FN, Muratoğlu Şahin N, Elmaoğulları S, Çetinkaya S, Savaş Erdeve Ş. Unfavorable Effects of Low-carbonhydrate Diet in a Pediatric Patient with Type 1 Diabetes Mellitus. J Clin Res Pediatr Endocrinol 2023; 15:444-448. [PMID: 35014244 PMCID: PMC10683544 DOI: 10.4274/jcrpe.galenos.2021.2021-10-18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 12/14/2021] [Indexed: 12/01/2022] Open
Abstract
A balanced and healthy diet is very important in type 1 diabetes mellitus (T1DM) in childhood. In addition to regulating blood glucose with diet, diet should also support optimal growth. Low-carbohydrate diet aims to provide daily energy from fats and was originally used for childhood epilepsy. We present a patient with T1DM who experienced unfavorable effects when on a low-carbohydrate diet.
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Affiliation(s)
- Ceren Güleryüz
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatrics, Ankara, Turkey
| | - Ece Eker
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatrics, Ankara, Turkey
| | - Gülin Karacan Küçükali
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Merve Şakar
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Fatma Nur Genç
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Nursel Muratoğlu Şahin
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Selin Elmaoğulları
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Semra Çetinkaya
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
| | - Şenay Savaş Erdeve
- University of Health Sciences Turkey, Ankara Dr. Sami Ulus Children Health and Diseases Training and Research Hospital, Department of Pediatric Endocrinology, Ankara, Turkey
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11
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Baghdadi LR, Alhomaidi RA, Alhelal FS, Alqahtani AA, Aldosary SA, Almohammedi SM, Almutairi RA, Jad LA, AlShammari HH. Effect of a ketogenic diet on decrease of seizures in refractory epilepsy among children (infancy to 14 years old) in Saudi Arabia: a cross-sectional study. Transl Pediatr 2023; 12:1676-1689. [PMID: 37814716 PMCID: PMC10560352 DOI: 10.21037/tp-23-211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 08/02/2023] [Indexed: 10/11/2023] Open
Abstract
Background Refractory (intractable/pharmaco-resistant) epilepsy in children is considered if disabling seizures continue despite appropriate trials of two anti-seizure drugs, either alone or in combination. Ketogenic diets are used as a treatment option in many countries for children with refractory seizures; however, few patients have tried it in Saudi Arabia. Therefore, we examined the relationship between the exposure to a ketogenic diet and its effect in decreasing seizure frequency in infants and children up to 14 years who had refractory epilepsy and assessed factors that could improve the outcome of seizures. Methods This cross-sectional study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected by reviewing medical records of eligible children (infants and children up to 14 years old) with refractory epilepsy who were on ketogenic diets. Socioeconomic data of the parents (guardians) were collected via phone interviews after verbal consent from the parents (guardians). Results We recruited 95 children (aged 10 months to 14 years) with refractory epilepsy and on Ketogenic diets. Up to 44% of patients on 3:1 and 4.5:1 ratio ketogenic diets had decreased seizure frequency while patients on 1:1 and 2:1 ratio ketogenic diets showed no decrease in seizures. Patients with generalized epilepsy who were on ketogenic diets had the most improvement in seizure outcomes (56.1%) and patients on ketogenic diets who were ambulatory indoors and outdoors (66.7%) showed a high level of improvement in seizure outcomes compared to patients with who were non-ambulatory (21.9%). Lower improvements in seizure frequency in epileptic patients on ketogenic diets were associated with low education levels of parents (33.3% high school vs. 50% undergraduate school), low incomes [<11,400±7,560.864 Saudi riyal (SR)], and diagnosis of seizures in patients >8 years old. Conclusions Ketogenic diets are a promising approach for treatment of refractory epilepsy among children. The improvement in seizure outcomes was associated with higher ratios of ketogenic diets (3:1 and 4.5:1), and higher physical activity. Sociodemographic factors, including parents' (guardians') education levels and income influenced the improvement of seizures.
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Affiliation(s)
- Leena R. Baghdadi
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | | | | | | | | | | | | | - Lamyaa A. Jad
- Pediatric Neurology Department, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Hasna H. AlShammari
- Pediatric Neurology Department, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia
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12
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Carmody LC, Gargano MA, Toro S, Vasilevsky NA, Adam MP, Blau H, Chan LE, Gomez-Andres D, Horvath R, Kraus ML, Ladewig MS, Lewis-Smith D, Lochmüller H, Matentzoglu NA, Munoz-Torres MC, Schuetz C, Seitz B, Similuk MN, Sparks TN, Strauss T, Swietlik EM, Thompson R, Zhang XA, Mungall CJ, Haendel MA, Robinson PN. The Medical Action Ontology: A Tool for Annotating and Analyzing Treatments and Clinical Management of Human Disease. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.07.13.23292612. [PMID: 37503136 PMCID: PMC10370244 DOI: 10.1101/2023.07.13.23292612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]
Abstract
Navigating the vast landscape of clinical literature to find optimal treatments and management strategies can be a challenging task, especially for rare diseases. To address this task, we introduce the Medical Action Ontology (MAxO), the first ontology specifically designed to organize medical procedures, therapies, and interventions in a structured way. Currently, MAxO contains 1757 medical action terms added through a combination of manual and semi-automated processes. MAxO was developed with logical structures that make it compatible with several other ontologies within the Open Biological and Biomedical Ontologies (OBO) Foundry. These cover a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. We have created a database of over 16000 annotations that describe diagnostic modalities for specific phenotypic abnormalities as defined by the Human Phenotype Ontology (HPO). Additionally, 413 annotations are provided for medical actions for 189 rare diseases. We have developed a web application called POET (https://poet.jax.org/) for the community to use to contribute MAxO annotations. MAxO provides a computational representation of treatments and other actions taken for the clinical management of patients. The development of MAxO is closely coupled to the Mondo Disease Ontology (Mondo) and the Human Phenotype Ontology (HPO) and expands the scope of our computational modeling of diseases and phenotypic features to include diagnostics and therapeutic actions. MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO).
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Affiliation(s)
- Leigh C Carmody
- The Jackson Laboratory for Genomic Medicine,Farmington,CT,United States
| | - Michael A Gargano
- The Jackson Laboratory for Genomic Medicine,Farmington,CT,United States
| | - Sabrina Toro
- University of Colorado Anschutz Medical Campus,Aurora,CO,United States
| | | | - Margaret P Adam
- University of Washington School of Medicine, Seattle, WA, United States
| | - Hannah Blau
- The Jackson Laboratory for Genomic Medicine,Farmington,CT,United States
| | | | - David Gomez-Andres
- Pediatric Neurology, Vall d'Hebron Institut de Recerca (VHIR), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus., Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain
| | - Rita Horvath
- Department of Clinical Neurosciences, University of Cambridge, Robinson Way CB2 0PY, Cambridge UK
| | - Megan L Kraus
- University of Colorado Anschutz Medical Campus,Aurora,CO,United States
| | - Markus S Ladewig
- Department of Ophthalmology,Klinikum Saarbrücken,Saarbrücken,Germany
| | - David Lewis-Smith
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom
| | | | | | | | - Catharina Schuetz
- Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Berthold Seitz
- Department of Ophthalmology,Saarland University Hospital UKS,Homburg/Saar Germany
| | - Morgan N Similuk
- National Institute of Allergy and Infectious Diseases,National Institutes of Health,Bethesda,MD,United States
| | - Teresa N Sparks
- Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143
| | - Timmy Strauss
- Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Emilia M Swietlik
- Department of Medicine, University of Cambridge, Heart and Lung Research Institute, CB2 0BB, Cambridge, UK
| | | | | | | | - Melissa A Haendel
- University of Colorado Anschutz Medical Campus,Aurora,CO,United States
| | - Peter N Robinson
- The Jackson Laboratory for Genomic Medicine,Farmington,CT,United States
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13
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Poorshiri B, Barzegar M, Afghan M, Shiva S, Shahabi P, Golchinfar Z, Yousefi Nodeh HR, Raeisi S. The effects of ketogenic diet on beta-hydroxybutyrate, arachidonic acid, and oxidative stress in pediatric epilepsy. Epilepsy Behav 2023; 140:109106. [PMID: 36745963 DOI: 10.1016/j.yebeh.2023.109106] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 01/02/2023] [Accepted: 01/19/2023] [Indexed: 02/06/2023]
Abstract
The exact mechanism of a ketogenic diet (KD) as a suitable alternative therapeutic approach for drug-resistant epilepsy (DRE) in alleviating seizures is not yet fully understood. The present study aimed to evaluate the role of the KD in reducing oxidative stress (OS) by increasing the ketone body beta-hydroxybutyrate (BHB) and Arachidonic acid (ARA), an essential polyunsaturated fatty acid, as a possible mechanism in relieving seizure attacks in children with DRE. Forty children with refractory epilepsy were included in the present study. The serum levels of BHB, ARA, and OS markers, malondialdehyde (MDA), and 8-hydroxyl-deoxyguanosine (8-OHdG), were evaluated in children with DRE and compared before and after the three months of KD therapy. Thirty-four of 40 included children could complete the three-month KD therapy. Twenty-one (61.76%) patients had more than a 50% reduction in seizure frequency after the KD (responders). The remaining 13 children were considered non-responders to the diet. The serum levels of ARA and BHB significantly (p < 0.05) increased after the KD therapy. The serum levels of OS parameters MDA and 8-OHdG before the diet therapy were significantly (p < 0.05) higher than those after the administration. The serum levels of BHB and MDA after the KD therapy in the responders were respectively higher and lower than those in the non-responders (p < 0.001). Ketogenic diet might reduce brain OS by increasing BHB and ARA. The role of BHB in diminishing OS and seizure might be more remarkable than ARA.
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Affiliation(s)
- Bita Poorshiri
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Barzegar
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammadreza Afghan
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Siamak Shiva
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parviz Shahabi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zahra Golchinfar
- Department of Food Science and Technology, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sina Raeisi
- Pediatric Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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14
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Verdoodt F, Watanangura A, Bhatti SFM, Schmidt T, Suchodolski JS, Van Ham L, Meller S, Volk HA, Hesta M. The role of nutrition in canine idiopathic epilepsy management: Fact or fiction? Vet J 2022; 290:105917. [PMID: 36341888 DOI: 10.1016/j.tvjl.2022.105917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 10/25/2022] [Accepted: 10/25/2022] [Indexed: 11/05/2022]
Abstract
In the last decade, nutrition has gained interest in the management of canine idiopathic epilepsy (IE) based on growing scientific evidence. Diets can serve their functions through many pathways. One potential pathway includes the microbiota-gut-brain axis, which highlights the relationship between the brain and the intestines. Changing the brain's energy source and a number of dietary sourced anti-inflammatory and neuroprotective factors appears to be the basis for improved outcomes in IE. Selecting a diet with anti-seizure effects and avoiding risks of proconvulsant mediators as well as interference with anti-seizure drugs should all be considered in canine IE. This literature review provides information about preclinical and clinical evidence, including a systematic evaluation of the level of evidence, suggested mechanism of action and interaction with anti-seizure drugs as well as pros and cons of each potential dietary adaptation in canine IE.
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Affiliation(s)
- Fien Verdoodt
- Equine and Companion Animal Nutrition, Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium; Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Antja Watanangura
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany; Veterinary Research and Academic Service, Faculty of Veterinary Medicine, Kasetsart University, Kamphaeng Saen, Nakhon Pathom, Thailand
| | - Sofie F M Bhatti
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Teresa Schmidt
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Luc Van Ham
- Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Sebastian Meller
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Holger A Volk
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany; Center for Systems Neuroscience (ZSN), Hannover, Germany
| | - Myriam Hesta
- Equine and Companion Animal Nutrition, Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
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15
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Habashy KJ, Ahmad F, Ibeh S, Mantash S, Kobeissy F, Issa H, Habis R, Tfaily A, Nabha S, Harati H, Reslan MA, Yehya Y, Barsa C, Shaito A, Zibara K, El-Yazbi AF, Kobeissy FH. Western and ketogenic diets in neurological disorders: can you tell the difference? Nutr Rev 2022; 80:1927-1941. [PMID: 35172003 DOI: 10.1093/nutrit/nuac008] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025] Open
Abstract
The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials.
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Affiliation(s)
| | - Fatima Ahmad
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Stanley Ibeh
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Sarah Mantash
- PRASE and Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Fatima Kobeissy
- Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Hawraa Issa
- PRASE and Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Ralph Habis
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Ali Tfaily
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Comprehensive Epilepsy Program, Department of Neurology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Sanaa Nabha
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Hayat Harati
- Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Mohammad Amine Reslan
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Yara Yehya
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Chloe Barsa
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Abdullah Shaito
- Biomedical Research Center, Department of Biomedical Sciences at College of Health Sciences, and College of Medicine, Qatar University, Doha, Qatar
| | - Kazem Zibara
- PRASE and Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon
| | - Ahmed F El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt
| | - Firas H Kobeissy
- Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
- Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience, and Chemistry, University of Florida, Gainesville, Florida, USA
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16
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Cicek E, Sanlier N. The place of a ketogenic diet in the treatment of resistant epilepsy: a comprehensive review. Nutr Neurosci 2022:1-14. [PMID: 35791085 DOI: 10.1080/1028415x.2022.2095819] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Objective: The ketogenic diet (KD) is a high-fat, adequate-protein, and low-carb diet. Ketone bodies increase in the blood due to low carbohydrate content and high-fat content in the diet. The most important feature of the ketogenic diet is that it causes the production of ketone bodies in the liver. Ketone bodies are an alternative fuel to glucose for the brain and form the structure necessary for the cell membrane and biosynthesis of triglycerides. The ketogenic diet provides evidence on seizure control with anticonvulsant effects. In this review, the positive/negative effects of KD on seizure control, place, importance, quality of life, cognition, and behavior in the treatment of resistant epilepsy were examined.Methods: Scientific information on the subject was obtained from the literature accessed through databases such as MEDLINE, Embase, Web of Science, Cochrane Central, www.ClinicalTrials.gov, PubMed, Science Direct, and Google Scholar.Results: Although it has started to be used as a treatment method in many diseases today, the main area of effect of KD is drug-resistant epilepsy. In order for the ketogenic diet to be successful in these patients, it is necessary to choose the appropriate patient, medical treatment and diet plan, inform the patient sufficiently, and perform frequent monitoring in accordance with the follow-up criteria. It is argued that KD is one of the most effective treatments for epilepsy.Conclusion: The fact that KDs generally have a restricted diet pattern, the need for supplementation, biochemical findings and possible side effects raise the issue of diet sustainability. More clinical studies are needed to generalize.
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Affiliation(s)
- Ebru Cicek
- Ankara Medipol University, School of Health Sciences, Department of Nutrition and Dietetics, Ankara, Turkey
| | - Nevin Sanlier
- Ankara Medipol University, School of Health Sciences, Department of Nutrition and Dietetics, Ankara, Turkey
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17
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Carneiro L, Pellerin L. Nutritional Impact on Metabolic Homeostasis and Brain Health. Front Neurosci 2022; 15:767405. [PMID: 35153657 PMCID: PMC8829049 DOI: 10.3389/fnins.2021.767405] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 12/13/2021] [Indexed: 12/18/2022] Open
Abstract
Aging in modern societies is often associated with various diseases including metabolic and neurodegenerative disorders. In recent years, researchers have shown that both dysfunctions are related to each other. Although the relationship is not fully understood, recent evidence indicate that metabolic control plays a determinant role in neural defects onset. Indeed, energy balance dysregulation affects neuroenergetics by altering energy supply and thus neuronal activity. Consistently, different diets to help control body weight, blood glucose or insulin sensitivity are also effective in improving neurodegenerative disorders, dampening symptoms, or decreasing the risk of disease onset. Moreover, adapted nutritional recommendations improve learning, memory, and mood in healthy subjects as well. Interestingly, adjusted carbohydrate content of meals is the most efficient for both brain function and metabolic regulation improvement. Notably, documented neurological disorders impacted by specific diets suggest that the processes involved are inflammation, mitochondrial function and redox balance as well as ATP production. Interestingly, processes involving inflammation, mitochondrial function and redox balance as well as ATP production are also described in brain regulation of energy homeostasis. Therefore, it is likely that changes in brain function induced by diets can affect brain control of energy homeostasis and other brain functions such as memory, anxiety, social behavior, or motor skills. Moreover, a defect in energy supply could participate to the development of neurodegenerative disorders. Among the possible processes involved, the role of ketone bodies metabolism, neurogenesis and synaptic plasticity, oxidative stress and inflammation or epigenetic regulations as well as gut-brain axis and SCFA have been proposed in the literature. Therefore, the goal of this review is to provide hints about how nutritional studies could help to better understand the tight relationship between metabolic balance, brain activity and aging. Altogether, diets that help maintaining a metabolic balance could be key to both maintain energy homeostasis and prevent neurological disorders, thus contributing to promote healthy aging.
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Affiliation(s)
- Lionel Carneiro
- Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, United States
| | - Luc Pellerin
- Inserm U1082, Université de Poitiers and CHU de Poitiers, Poitiers, France
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18
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Sivathanu D, Kewalramani D, Kumar Manokaran R. Favorable response to classic ketogenic diet in a child with anti-GAD 65 antibody mediated super refractory status epilepticus. Epilepsy Behav Rep 2022; 19:100557. [PMID: 35789965 PMCID: PMC9250004 DOI: 10.1016/j.ebr.2022.100557] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 05/30/2022] [Accepted: 06/05/2022] [Indexed: 11/10/2022] Open
Abstract
Autoimmune encephalitis is a disease condition which presents with refractory seizures in children requiring immunotherapy. KD is a non-pharmacological treatment modality used worldwide in people with drug-resistant epilepsy. It acts through many anti-inflammatory mechanisms leading to seizure control. This article highlights the use of adjuvant effect of ketogenic diet in anti GAD-65 antibody positive autoimmune encephalitis. It is the need of the hour to formulate treatment protocols incorporating newer treatment strategies including KD. Autoimmune encephalitis refers to a spectrum of inflammatory brain diseases which can present as drug-resistant seizures in children. Hereby, we report a case of anti-GAD-65 antibody encephalitis in a 7-year-old child who presented with superrefractory status epilepticus (SRSE). The traditional management with multiple anti-seizure medications at appropriate dosage and immunotherapy was tried despite which the child continued to have seizures. Hence the child was initiated on a classic ketogenic diet. He achieved ketosis within 48 h of diet initiation and there was a drastic reduction in the seizure frequency followed by a completed remission. Hence, this non-pharmacological intervention was an effective adjunct in achieving seizure control in our patient. A ketogenic diet has been sparingly used for the management of post-encephalitic epilepsy and autoimmune epilepsy. However, the data onthe effectiveness of the ketogenic diet in the management of autoimmune encephalitis is scarce. Starting KD early in the disease course helped not only in seizure control but also preserved the cognitive and neurological well-being of the child.
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19
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Modified Atkins Diet vs Low Glycemic Index Treatment for Drug-Resistant Epilepsy in Children: An Open Label, Randomized Controlled Trial. Indian Pediatr 2021. [DOI: 10.1007/s13312-021-2299-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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20
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Ketogenic diet: a pharmaceutical guide for the management of drug therapy in the pediatric population. Int J Clin Pharm 2020; 42:326-330. [PMID: 32185606 DOI: 10.1007/s11096-020-01013-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 03/10/2020] [Indexed: 10/24/2022]
Abstract
For a ketogenic diet to be effective, strict control of carbohydrate intake is paramount. Factors such as medications may upset this delicate balance. The aim of this commentary is to provide physicians who are treating patients with a ketogenic diet, with a step-by-step guide. A list of unsuitable excipients was established. A flowchart with the title "Can this drug be prescribed to a patient following a ketogenic diet?" was then drafted. The first step is to determine the international nonproprietary name, dosage, form and composition. The amount of unsuitable excipients is calculated. Suitable alternatives may be discussed with the pharmacist. As a last resort, the ketogenic diet itself may need to be adapted. The answers provided are included in a database. Determining the amount of unsuitable excipients is a complex task requiring pharmaceutical expertise. Our flowchart can be used in order to provide a clear pathway for answering such questions.
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21
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Association of Child Neurology-Indian Epilepsy Society Consensus Document on Parental Counseling of Children with Epilepsy. Indian J Pediatr 2019; 86:608-616. [PMID: 31177510 DOI: 10.1007/s12098-019-02946-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Accepted: 03/29/2019] [Indexed: 10/26/2022]
Abstract
When a child is diagnosed with epilepsy, counseling regarding the same is done by the treating doctor. Most parents are frightened and have poor knowledge about epilepsy. Therapeutic advice including drug dosage, administration and side effects takes up the major part of physician's time, thereby neglecting important issues like home seizure management, follow up and others. These lacunae in knowledge require systematic patient and family education. To address these issues, an expert group meeting of pediatric neurologists and epileptologists in India along with social workers/epilepsy educators, legal experts, parents, and teachers was held. The various aspects regarding parental counseling in children with epilepsy were discussed and a consensus document was formulated. Here authors present the group consensus statement on counseling parents and caregivers of children with epilepsy. This document is intended to help physicians and pediatricians counsel the families when a child is diagnosed with epilepsy.
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22
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A Journey of Dietary Therapies for Epilepsy in Iran: Diet Restriction in the Ancient Era to the Ketogenic Diet in the Modern Period. IRANIAN JOURNAL OF CHILD NEUROLOGY 2019; 13:7-24. [PMID: 31327965 PMCID: PMC6586451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Revised: 05/19/2019] [Accepted: 05/23/2019] [Indexed: 12/04/2022]
Abstract
Epilepsy, in children, is a common neurological problem for referral to child neurology clinics. The prevalence of nonfebrile seizure in children (under 10 years old), is estimated from 5.2 to 8.1 per 1000. Also, the prevalence of epilepsy in Iran estimated about 5 %; it means 4 million people of Iranian population live with epilepsy in Iran. Although antiseizure drugs (ASDs) are the essential treatment modalities in most children, more than 30% of epileptic children have intractable seizures or they suffer from drug adverse effects secondary to these medications. Because only a limited number of epileptic patients benefit from surgical therapy using the additional therapeutic options is inevitable. There are many available nonpharmacologic proven therapies for refractory seizures that Dietary therapy ( Ketogenic Diet) is one of the important therapeutic options in this group. In this review, we will discuss the different features of pediatric epilepsy dietary therapies (Especially the Ketogenic Diet) in Iran and also the history of epilepsy in ancient Iran, utilization, effectiveness, side effects, tolerability, and acceptability as well as ongoing and future programs.
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Goswami JN, Sharma S. Current Perspectives On The Role Of The Ketogenic Diet In Epilepsy Management. Neuropsychiatr Dis Treat 2019; 15:3273-3285. [PMID: 31819454 PMCID: PMC6883945 DOI: 10.2147/ndt.s201862] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 10/18/2019] [Indexed: 12/31/2022] Open
Abstract
Drug-refractory epilepsy is a commonly prevalent pediatric neurological illness of global significance. Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has reemerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy. In addition, this modality has been recognized to reduce anti-epileptic exposure, improve cognition and behavioral profile of patients as well as improve the quality-of-life of care-givers. Current indications of KD include refractory epilepsy syndromes, selected metabolic disorders (such as pyruvate dehydrogenase deficiency) and a host of varied neurological entities. KD research has broadened the knowledge-base about its mechanisms of action. Four types of KD are in vogue currently with varying nutritional constitution, palatability, administration protocols and comparable efficacy. KD initiation and maintenance are the result of concerted effort of a team of pediatric neurologist/epileptologist, nutritionist and patient's primary care-giver. Consensus is being formulated about various practical aspects of KD such as patient-selection, parental counseling, baseline work-up, dietary prescription, nutritional supplementation, concurrent anti-epileptic drug administration, follow-up and treatment-duration. Novel applications of KD include its use in neonatal epilepsy and super-refractory status epilepticus and tailor-made formulations such as cooking oil-based KD in predominantly rice-fed populations. Increasing body of clinical experience, improved nutritional designs and translational research are promoting KD as a major therapeutic modality. Currently, KD forms a core essence in the armamentarium against refractory epilepsy. In this review, we summarize the recent advances and current perspectives in the use of KD in refractory epilepsy.
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Affiliation(s)
| | - Suvasini Sharma
- Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi 110001, India
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24
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25
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A pragmatic study on efficacy, tolerability and long term acceptance of ketogenic diet therapy in 74 South Indian children with pharmacoresistant epilepsy. Seizure 2018; 58:41-46. [DOI: 10.1016/j.seizure.2018.03.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2017] [Revised: 03/18/2018] [Accepted: 03/20/2018] [Indexed: 01/01/2023] Open
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Liu H, Yang Y, Wang Y, Tang H, Zhang F, Zhang Y, Zhao Y. Ketogenic diet for treatment of intractable epilepsy in adults: A meta-analysis of observational studies. Epilepsia Open 2018; 3:9-17. [PMID: 29588983 PMCID: PMC5839310 DOI: 10.1002/epi4.12098] [Citation(s) in RCA: 117] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2017] [Indexed: 12/13/2022] Open
Abstract
The ketogenic diet (KD) is an effective treatment for children with drug-resistant epilepsy and has been widely used in young children. Adult patients with intractable epilepsy would also benefit from this dietary treatment. However, only a few studies have been published, and the use of the KD in intractable epilepsy in adults has been limited. This meta-analysis summarized the findings of the relevant published studies to identify the efficacy of the KD for the treatment of intractable epilepsy in adults. In this meta-analysis, PubMed, Embase, and Cochrane Library were used for searching studies concerning the effects of the KD and its major subtypes with intractable epilepsy in adults published up to January 10, 2017. The primary outcomes were seizure freedom, seizure reduction by 50% or more, and seizure reduction by <50%. The quality of the methodology of the observational studies was reviewed by using the Newcastle-Ottawa Scale. We identified 402 articles, of which, 16 studies including 338 patients met the inclusion criteria. The results of the meta-analysis showed that the combined efficacy rates of all the symptoms of seizure freedom, seizure reduction by 50% or more, and seizure reduction below 50% in adults with intractable epilepsy were 13%, 53%, and 27%, respectively. The adverse reactions of the KD were mild, whereas low glycemic index diet (LGID) and low-dose fish oil diet (LFOD) may have fewer side effects. Weight loss, high level of low-density lipoprotein, and elevated total cholesterol were most frequent. The meta-analysis indicates that the KD for refractory epilepsy in adults is a well-tolerated treatment and that its side effects are acceptable, which show that the KD is a promising treatment in adult intractable epilepsy. Further research is needed to assess which type of diet or ratio is more effective in the KD treatment.
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Affiliation(s)
- Hongyan Liu
- School of Public Health and Management Chongqing Medical University Chongqing China.,Research Center for Medicine and Social Development Chongqing Medical University Chongqing China.,Collaborative Innovation Center of Social Risks Governance in Health Chongqing Medical University Chongqing China
| | - Yi Yang
- Department of Neurology The First Affiliated Hospital of Chongqing Medical University Chongqing China
| | - Yunbing Wang
- Department of Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical University Chongqing China
| | - Hong Tang
- Department of Critical Care Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China
| | - Fan Zhang
- School of Public Health and Management Chongqing Medical University Chongqing China.,Research Center for Medicine and Social Development Chongqing Medical University Chongqing China.,Collaborative Innovation Center of Social Risks Governance in Health Chongqing Medical University Chongqing China
| | - Yong Zhang
- School of Public Health and Management Chongqing Medical University Chongqing China.,Research Center for Medicine and Social Development Chongqing Medical University Chongqing China.,Collaborative Innovation Center of Social Risks Governance in Health Chongqing Medical University Chongqing China
| | - Yong Zhao
- School of Public Health and Management Chongqing Medical University Chongqing China.,Research Center for Medicine and Social Development Chongqing Medical University Chongqing China.,Collaborative Innovation Center of Social Risks Governance in Health Chongqing Medical University Chongqing China
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27
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Khodadadi S, Sobhani N, Mirshekar S, Ghiasvand R, Pourmasoumi M, Miraghajani M, Dehsoukhteh SS. Tumor Cells Growth and Survival Time with the Ketogenic Diet in Animal Models: A Systematic Review. Int J Prev Med 2017; 8:35. [PMID: 28584617 PMCID: PMC5450454 DOI: 10.4103/2008-7802.207035] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 12/19/2016] [Indexed: 12/22/2022] Open
Abstract
Recently, interest in targeted cancer therapies via metabolic pathways has been renewed with the discovery that many tumors become dependent on glucose uptake during anaerobic glycolysis. Also the inability of ketone bodies metabolization due to various deficiencies in mitochondrial enzymes is the major metabolic changes discovered in malignant cells. Therefore, administration of a ketogenic diet (KD) which is based on high in fat and low in carbohydrates might inhibit tumor growth and provide a rationale for therapeutic strategies. So, we conducted this systematic review to assess the effects of KD on the tumor cells growth and survival time in animal studies. All databases were searched from inception to November 2015. We systematically searched the PubMed, Scopus, Google Scholars, Science Direct and Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. To assess the quality of included studies we used SYRCLE's RoB tool. 268 articles were obtained from databases by primary search. Only 13 studies were eligible according to inclusion criteria. From included studies, 9 articles indicate that KD had a beneficial effect on tumor growth and survival time. Tumor types were included pancreatic, prostate, gastric, colon, brain, neuroblastoma and lung cancers. In conclusions, although studies in this field are rare and inconsistence, recent findings have demonstrated that KD can potentially inhibit the malignant cell growth and increase the survival time. Because of differences physiology between animals and humans, future studies in cancer patients treated with a KD are needed.
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Affiliation(s)
- Soheila Khodadadi
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nafiseh Sobhani
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somaye Mirshekar
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Ghiasvand
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Makan Pourmasoumi
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Miraghajani
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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28
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Mehta R, Goel S, Sharma S, Jain P, Mukherjee SB, Aneja S. Efficacy and tolerability of the modified Atkins diet in young children with refractory epilepsy: Indian experience. Ann Indian Acad Neurol 2016; 19:523-527. [PMID: 27994368 PMCID: PMC5144480 DOI: 10.4103/0972-2327.194463] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background: The modified Atkins diet (MAD) has been used predominantly in older children, adolescents, and adults. There is a paucity of data on the use of the MAD in refractory epilepsy in young children. Objectives: This study was planned to evaluate the efficacy and tolerability of the MAD in refractory epilepsy in young children. Methods: This study recruited children aged 9 months to 3 years with refractory seizures. Children received MAD for 6-month with the on-going anticonvulsant medications being continued unchanged. Reduction in seizure frequency was the primary outcome measure. Adverse effects were also studied. Results: Thirty-one children with daily seizures were studied with a median age of 18-month (range 9–30 months). West syndrome was the most common epilepsy syndrome (26, 86.6%). Twenty-one children remained on diet at 3 months and 13 at 6 months. The children who achieved >50% seizure reduction were 17 (54.8%) at 3 months and 9 (29%) at 6 months. Refusal to eat was a significant problem seen in eight children. Three children discontinued the diet due to adverse effects. Conclusion: The MAD was found to be feasible, effective, and well-tolerated.
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Affiliation(s)
- Ranju Mehta
- Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
| | - Shaiphali Goel
- Department of Pediatrics, Division of Pediatric Neurology, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
| | - Suvasini Sharma
- Department of Pediatrics, Division of Pediatric Neurology, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
| | - Puneet Jain
- Department of Neonatal, Pediatric and Adolescent Medicine, Division of Pediatric Neurology, BL Kapur Super Speciality Hospital, New Delhi, India
| | - Sharmila B Mukherjee
- Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
| | - Satinder Aneja
- Department of Pediatrics, Division of Pediatric Neurology, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
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SOLTANI D, GHAFFAR POUR M, TAFAKHORI A, SARRAF P, BITARAFAN S. Nutritional Aspects of Treatment in Epileptic Patients. IRANIAN JOURNAL OF CHILD NEUROLOGY 2016; 10:1-12. [PMID: 27375750 PMCID: PMC4928610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/30/2022]
Abstract
Epilepsy is a neurological disorder characterized by interruption of normal neuronal functions that is manifested by behavioral disorders, changing of awareness level, and presence of some sensory, autonomic and motor symptoms or signs. It is resulted from many different causes. Many antiepileptic drugs (AEDs) are considered to manage epileptic attacks. Some of them change metabolism and absorption of many nutrients. Therefore, epileptic patients may be in higher risk of nutrient deficiency and its unwelcome effects. In the present paper, we intend to review the relationship between nutrition and epilepsy in two aspects. In one aspect we discuss the nutritional status in epileptic patients, the causes of nutritional deficiencies and the way of compensation of the nutrient deficiencies. It will guide these patients to have a healthy life. In another aspect we explain the role of some nutrients and specific diets in management of epileptic attacks. It can help to better control of epileptic attacks in these patients.
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Affiliation(s)
- Danesh SOLTANI
- Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Majid GHAFFAR POUR
- Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas TAFAKHORI
- Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Payam SARRAF
- Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Sama BITARAFAN
- Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Souza-Monteiro JR, Hamoy M, Santana-Coelho D, Arrifano GP, Paraense RS, Costa-Malaquias A, Mendonça JR, da Silva RF, Monteiro WS, Rogez H, de Oliveira DL, do Nascimento JLM, Crespo-López ME. Anticonvulsant properties of Euterpe oleracea in mice. Neurochem Int 2015; 90:20-7. [DOI: 10.1016/j.neuint.2015.06.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2015] [Revised: 06/09/2015] [Accepted: 06/27/2015] [Indexed: 10/23/2022]
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Cao D, Badoe E, Zhu Y, Zhao X, Hu Y, Liao J. First Application of Ketogenic Diet on a Child With Intractable Epilepsy in Ghana. Child Neurol Open 2015; 2:2329048X15604593. [PMID: 28503594 PMCID: PMC5417030 DOI: 10.1177/2329048x15604593] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Accepted: 07/06/2015] [Indexed: 02/05/2023] Open
Abstract
The prevalence of epilepsy in sub-Saharan Africa is higher than in other parts of the world, but it is short of the effective measure on treating intractable epilepsy. Epilepsy surgery is not easy to be performed due to the high cost and demand of operational skills. The authors planned to perform ketogenic diet therapy for the children with intractable epilepsy in Ghana with regard to its low cost and simple procedure. The candidate is a 10-month-old girl with epilepsy with unknown etiology. Her seizures couldn't be controlled by more than 3 antiepileptic drugs. Her development delayed severely due to frequent seizures. The authors successfully applied ketogenic diet for her. Her seizures were completely controlled after 2 weeks' therapy. Her mental condition was improved after that. The authors get much experience from this case for further developing ketogenic diet in Africa. This is the first report that ketogenic diet was applied to control intractable epilepsy in West Africa.
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Affiliation(s)
- Dezhi Cao
- Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
| | - Eben Badoe
- Department of Child Health, College of Medicine and Child Health, University of Ghana
| | - Yanwei Zhu
- Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
| | - Xia Zhao
- Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
| | - Yan Hu
- Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
| | - Jianxiang Liao
- Shenzhen Children’s Hospital, Shenzhen, Guangdong, China
- Jianxiang Liao, Shenzhen Children’s Hospital, 7019 Yitian Road, Futian, Shenzhen, Guangdong 518038, China.
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