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Comparative Study of Dietary and Immunological Management of Refractory Epilepsy in Children

Primary Purpose

Refractory Epilepsy

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
RiTUXimab Injection [Rituxan]
Sponsored by
Assiut University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Epilepsy

Eligibility Criteria

1 Month - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1-Age 1 month up to 17 years 2-Both male and female 3-Epileptic patient on two tolerated and appropriately chosen and used antiepilptic drugs with no response

Exclusion Criteria:

  • 1-Neonate 2-Epieptic patient on monotherapy 3-Conditions mimic epilepsy 4-Pseudo refractioness 5-Absolute contraindications for the use of diet therapy include carnitine deficiency (primary), carnitine palmitoyltransferase (CPT) I OR II deficiency, carnitine translocase deficiency, β-oxidation defects, pyruvate carboxylase deficiency, and porphyria 6-Contraindication for Rituximab:

    1. Hypersensitivity to any component, murine proteins. b. Heart failure c. Active infection

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Active Comparator

    Active Comparator

    Active Comparator

    Arm Label

    RITUXIMAB

    KETOGENIC DIET

    TRACE ELEMENTS

    CORTICOSTEROID

    Arm Description

    rituximab INTRAVENOUS 750MG/m2 every 2 weeks for 2 doses

    The common element of these different approaches is variable reduction in the amount of carbohydrate with appropriate increase in fat. Diets that produce a state of ketosis are referred to as ''ketogenic"

    . Essential trace elements that include zinc, copper, magnesium, and selenium

    corticosteroid pulse therapy 30 mg /kg /day for 5 days monthly for 6 month

    Outcomes

    Primary Outcome Measures

    a-seizure frequency b-antiepileptic drugs c-compliance to treatment d-number of hospital admission
    number of attacks of fits during monitoring

    Secondary Outcome Measures

    Full Information

    First Posted
    September 2, 2020
    Last Updated
    September 2, 2020
    Sponsor
    Assiut University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04542629
    Brief Title
    Comparative Study of Dietary and Immunological Management of Refractory Epilepsy in Children
    Official Title
    Comparative Study of Dietary and Immunological Management of Refractory Epilepsy in Children Attending Assiut Pediatric University Hospital
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    October 1, 2020 (Anticipated)
    Primary Completion Date
    August 20, 2021 (Anticipated)
    Study Completion Date
    August 20, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Assiut University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Comparison of the efficacy of Rituximab and ketogenic diet in controlling refractory seizures versus the traditional lines as corticosteroid and trace elements. Improving the management of children with refractory seizures
    Detailed Description
    Definition of refractory epilepsy A task force of the International League Against Epilepsy proposed that drug-resistant epilepsy be defined as failure of adequate trials of two tolerated and appropriately chosen and used antiseizure drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom (1) . This requires application of the intervention at adequate strength/dosage for a sufficient length of time (2)..Terms refractory" intractable", drug-resistant" pharmaco-resistant" have been used interchangeably in several documented literature in different time periods (3). The first antiseizure drug fails in 20 to 40 percent of children with epilepsy; lack of efficacy and side effects contribute to treatment failure (4) Epidemiology About 10-20 % children with epilepsy develop drug refractory epilepsy (5).In a systematic review of 35 observational studies that included over 13,000 patients with epilepsy and 3900 patients with drug resistant epilepsy( DRE), the pooled prevalence of (DRE) was 30 percent, and the pooled incidence proportion was 15 percent (6). Risk factors - A high number of seizures prior to diagnosis and treatment - Genetic or inherited syndromes, for both generalized and localization-related epilepsy, have a better prognosis than symptomatic/cryptogenic epilepsy in both pediatric and adult populations (7). Localization-related epilepsy underlies more than half of the cases of DRE in children (8,9). Other findings more variably associated with the risk of DRE include a presentation with status epilepticus , a longer duration of epilepsy , a family history of epilepsy , a history of febrile convulsions , abnormal ( ELECTROENCEPHALOGRAM ) EEG findings . An abnormal neurologic examination and/or developmental delays (10,11). Some pediatric studies have found that seizure onset in later childhood or adolescence appears to be more likely to be associated with DRE than seizures with onset between the ages of 5 and 10 years (12). Causes (13,14 ) Epilepsy syndromes Infancy • Epilepsy of infancy with migrating focal seizures West syndrome Dravet syndrome Doose syndrome Childhood Lennox-Gastaut syndrome Epileptic encephalopathy with continuous spike and wave during sleep Metabolic • Pyridoxine dependent epilepsy • Biotinidase biosynthesis deficiency • Organic acidemia • Urea cycle disorders • Non-ketotic hyperglycinemia Aminoacidopathies Mitochondrial disorders including Alpers syndrome Hashimoto encephalopathy Structural Abnormality • Malformations: Neuronal migration defects and neural tube defects • Neurocutaneous syndromes , Infectious/Inflammatory: , • Hypoxic ischemic encephalopathy, • Rasmussen encephalitis Stroke Tumors Mesial temporal sclerosis Autoimmune epilepsies : N-methyl-D-aspartate receptor(NMDAR), Connective tissue disorders • Systemic lupus erythematosus, • Wegener's granulomatosis , sarcoidsosis, celiac disease, Crohn's disease, Behcet's Sjorgren's syndrome, EVALUATION A- History and presentation : The approach depends upon age of onset, accurate description: pre-ictal, ictal, postictal events, precipitating events, seizure types, evolution relation to fever, previous history of febrile seizures (simple/complex), associated non-epileptic events, intake of (ANTI EPILPTIC DRUGS )AEDs with dose, developmental history, sleep history, detailed birth and peri-/antenatal history etc. B-Clinical examination depends upon anthropometry, syndromic facial dysmorphism, neurocutaneous features and detailed neurological and systemic assessment C- Pseudo-refractoriness indicates a condition in which seizures persist because the condition has not been adequately treated. The most common causes of pseudo refractory epilepsy include Inappropriate diagnosis -Cardiogenic (arrhythmias) and vasovagal events (syncope) Parasomnias Movement disorders (paroxysmal dyskinesias, cataplexy) Psychogenic nonepileptic seizure (PNES) can mimic epileptic seizures. , do not respond to antiseizure drug therapy. While not without limitations, video-EEG monitoring is the gold standard test for the diagnosis of PNES Bad compliance ; Missed dose Incorrect drug An incorrect diagnosis of seizure classification leading to incorrect drug choice It is not uncommon for diopathic generalized epilepsy syndromes to be unrecognized and inappropriately treated with antiseizure drugs that are more appropriate to localization-related epilepsy . Inadequate dosage Inadequate frequency Enzyme induction, especially if more than one antiepilptic drug AED or other medication is used Inadequate anticonvulsant therapy D-Investigation for the patients include; 1-EEG Routine EEG is a must for the clinical diagnosis of epilepsy and associated syndrome. For the majority of patients with epilepsy, routine EEG is sufficient to classify seizure type and to start treatment But for refractory epilepsy ( RE) and a doubtful seizure, video-EEG monitoring is the best diagnostic tool available. 2-Drug level monitor 3-Serum electrolyte, serum glucose 4-MRI brain ; High-resolution MRI helps in isolating the cause of focal epilepsies and to predict long-term outcome and spontaneous remission in patients. In some cases, follow-up MRI reveals an etiology for epilepsy (such as cerebral neoplasm, autoimmune encephalitis) that was not seen on the initial study and requires specific therapies in addition to antiseizure drugs . 5- Metabolic Work up Arterial blood gas (ABG ) Serum ammonia ,lactate Tandem mass screening 6-Genetic Testing as karyotyping , gene sequence ,-Fundus examination The presence of features like dysmorphism, growth retardation, intellectual disability and hypotonia may indicate an underlying genetic syndrome, 7-CSF culture, analysis • Lumbar puncture of infectious process 8-vascuilitis panel Complete blood cell count Erythrocyte sedimentation rate CRP ( C REACTIVE PROTEIN ) VWF Ag (VON WILLEBRAND FACTOR) C 3, 4 (COMPLEMENT 3, 4) Antinuclear AB (ANTIBODY) Antiphospholipid AB Antineutrophil cytoplasmic AB Anti-DNA AB 9-autoimmune encephalitis (Hashimotos ) antithyroid peroxidase AB, anti-TSH receptor AB Anti-NMDA-R AB Anti-MOG AB (if CNS demyelination) abdominal ultrasound and -MRI abdomen;To detect ovarian teratoma as in autoimmune encephalitis F-Practice recommendations for AED trial: Optimise the dose of each AED by increasing the dose incrementally. If the maximum dose is ineffective introduce a second AED while continuing on the first. If seizure control is achieved, consider tapering the first AED. The advice to "start low and go slow" is appropriate 2. If one or two AEDs are ineffective, rational polytherapy should be explored. 3. Consider using AEDs with different mechanisms of action 4. Avoid using an AED that may worsen or provoke seizures Carbamazepine (CBZ), Oxcarbazepine (OXC), Phenytoin (PHT), Vigabatrin (VGB) and Tiagabine (TGB) may worsen myoclonus and absence seizures Gabapentin (GBP) and Lamotrigine (LTG) may worsen myoclonus (Benzodiazepines given intravenously may worsen tonic seizures but may be very useful in treating Lennox-Gastaut and does not contraindicate their use Background A-Immunotherapy Evidence that the immune system is involved in the pathogenesis of epilepsy particularly, medically refractory epilepsy, has given rise to the use of adjunctive immunotherapy to slow or change the epileptogenic process. The presumed immune therapeutic mechanism (ACTH, corticosteroids, plasmapheresis human immunoglobulin G, rituximab, azathioprine, and cyclophosphamide) is the removal of various neuroimmunological mechanisms involved. However, new models suggest suppression of endogenous brain agent's proconvulsant (neuropeptides) There is limited data of these treatments outside of specific epileptic encephalopathies such as West syndrome, Rasmussen encephalitis, Landau Kleffner and specific antibody mediated encephalitis such as anti NMDA encephalitis a) Corticosteroids: Their immunological mechanisms are inhibition diapedesis and therefore infiltration of lymphocytes to the injured areas, attenuating production of inflammatory humoral mediators (IL-2) and inhibition of leukocyte function (helper T lymphocytes mainly) as well as endothelial cells. Dose: Methylprednisolone 30 mg /kg /day for 5 days up to 1 gm /day ,pulsed monthly for 6 months (15). b) Plasmapheresis: the activity of auto-Abs can be modulated by treatment with IVIGs and by plasma treatment, which consists of the mechanical removal of Abs (16) c) Human immunoglobulin G: . IgGIV inhibits activation of innate cells, suppression of the production of proinflammatory cytokines, and soluble factors as tumor necrosis factor and interleukins induced by this factor. In endothelial cells and macrophages, suggesting a mechanism antiepileptic Dose:400 mg.kg /day for 5 days D--Rituximab: Rituximab, a chimeric monoclonal antibody that binds to CD20, was the first monoclonal antibody to be approved for clinical use in the therapy of cancer. It is approved for use against indolent B-cell non-Hodgkin's lymphoma (NHL), although its use has expanded significantly beyond that indication to virtually any CD20-positive NHL, and more recently into other areas such as autoimmune disorders ) Rituximab targets CD20, a transmembrane protein present on virtually all B cells from the stage at which they become committed to B-cell development until it is downregulated when they differentiate into antibody-secreting plasma cells (17) Numerous review articles whose primary focus is the action of rituximab in the treatment of RA, systemic lupus erythematosus (SLE) and other autoimmune diseases were published in 2006. Although there is a clear consensus that substantial clinical benefits are associated with rituximab therapy, the exact mechanism(s) by which the B-cell depletion promoted by rituximab ameliorates autoimmune disease activity remains an area of active discussion.(18, 19) The most likely mechanisms have naturally centered on the pathogenic role of B cells in autoimmune disease: these include the potential of B cells to give rise to plasma cells that secrete autoantibodies as well as the ability of autoantigen-specific B cells to present antigens to autoreactive T cells, which leads to T-cell activation, cytokine release and inflammation. In certain cases the results of clinical trials have demonstrated moderate correlations between reduction of autoantibody levels and lessening of disease symptoms, which has emphasized the role of autoantibodies in disease pathology. In other studies such correlations have not been observed, which has led investigators to favor B cell-T cell interactions as the most important in the etiology of tissue injury in autoimmune diseases. (20 ,21) B-Dietary Therapy ketogenic diet rationale; The common element of these different approaches is variable reduction in the amount of carbohydrate with appropriate increase in fat. Diets that produce a state of ketosis are referred to as ''ketogenic" When deprived of glucose through restriction of carbohydrate intake, the human body begins metabolizing fat.In doing so, ketone bodies (acetoacetate, acetone, and hydroxybutyrate) are produced . (22). KDT is associated with increased mitochondrial biogenesis, oxidative phosphorylation, enhanced gamma-aminobutyric acid (GABA) levels, reduced neuronal excitability and firing, and stabilized synaptic function (23) Indicated Dietary therapy has been reported as effective in the treatment of seizures associated with glucose transporter 1 deficiency, pyruvate dehydrogenase deficiency, infantile spasms, absence epilepsy, myoclonic atonic epilepsy (Doose syndrome), Dravet syndrome, tuberous sclerosis complex, mitochondrial disorders, Lennox-Gastaut syndrome, Sturge-Weber syndrome, and Rett syndrome (24) Results from the randomized control trial indicated that 38% of children had more than 50% reduction in seizure frequency, and 7% had more than 90% reduction in seizure frequency three months after starting classic ketogenic diet. Retrospective studies reported a higher rate of seizure control (25). Contraindications Absolute contraindications for the use of diet therapy include carnitine deficiency (primary), carnitine palmitoyltransferase (CPT) I OR II deficiency, carnitine translocase deficiency, β-oxidation defects, pyruvate carboxylase deficiency, and porphyria. trace elements and antioxidants; The equilibrium of trace elements is essential for a healthy nervous system due to their key roles in activation of specific enzyme in many pathways of the central nervous system function metabolism Essential trace elements that include zinc, copper, magnesium, and selenium might play a role in the pathogenesis of seizures because of their possible influence on synaptogenesis, their actions on ligand- and voltage-gated ion channels, their effects on membrane lipid peroxidation and turnover of some neurotransmitters, and their roles in immunity (26) Antioxidative defense mechanisms are important pathways involving trace elements. The accumulation of free radicals may lead to seizures and increases the risk o f their recurrence, because oxidative stress produces peroxidated membrane lipids and damages the cells . Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are two major enzymes that are involved in antioxidative defense mechanisms. Selenium (Se), zinc (Zn), and copper (Cu) are important trace elements that participate in the structure of these enzymes patients with intractable epilepsy had significantly decreased levels of serum Se and Zn in comparison to the controlled group(27)

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Refractory Epilepsy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    140 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    RITUXIMAB
    Arm Type
    Experimental
    Arm Description
    rituximab INTRAVENOUS 750MG/m2 every 2 weeks for 2 doses
    Arm Title
    KETOGENIC DIET
    Arm Type
    Active Comparator
    Arm Description
    The common element of these different approaches is variable reduction in the amount of carbohydrate with appropriate increase in fat. Diets that produce a state of ketosis are referred to as ''ketogenic"
    Arm Title
    TRACE ELEMENTS
    Arm Type
    Active Comparator
    Arm Description
    . Essential trace elements that include zinc, copper, magnesium, and selenium
    Arm Title
    CORTICOSTEROID
    Arm Type
    Active Comparator
    Arm Description
    corticosteroid pulse therapy 30 mg /kg /day for 5 days monthly for 6 month
    Intervention Type
    Drug
    Intervention Name(s)
    RiTUXimab Injection [Rituxan]
    Other Intervention Name(s)
    KETOGENIC DIET, TRACE ELEMENTS, CORTICOSTEROID INJECTION
    Intervention Description
    375 MG/M2 /WEEK INFUSION
    Primary Outcome Measure Information:
    Title
    a-seizure frequency b-antiepileptic drugs c-compliance to treatment d-number of hospital admission
    Description
    number of attacks of fits during monitoring
    Time Frame
    1 YEAR

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Month
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1-Age 1 month up to 17 years 2-Both male and female 3-Epileptic patient on two tolerated and appropriately chosen and used antiepilptic drugs with no response Exclusion Criteria: 1-Neonate 2-Epieptic patient on monotherapy 3-Conditions mimic epilepsy 4-Pseudo refractioness 5-Absolute contraindications for the use of diet therapy include carnitine deficiency (primary), carnitine palmitoyltransferase (CPT) I OR II deficiency, carnitine translocase deficiency, β-oxidation defects, pyruvate carboxylase deficiency, and porphyria 6-Contraindication for Rituximab: Hypersensitivity to any component, murine proteins. b. Heart failure c. Active infection
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Duaa Mohammad Raafat Mahmoud, professor
    Phone
    01223112124
    Email
    duaa-raafat@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Ahlam Badawy Ali Badawy, assisstant professor
    Phone
    01006807866
    Email
    dr.ahlam_ali@yahoo.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Emad eldeen Mahmoud Hammad, professor
    Organizational Affiliation
    aAssiut University Children Hospital
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    19889013
    Citation
    Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshe SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3. Erratum In: Epilepsia. 2010 Sep;51(9):1922.
    Results Reference
    background
    PubMed Identifier
    19521080
    Citation
    Beleza P. Refractory epilepsy: a clinically oriented review. Eur Neurol. 2009;62(2):65-71. doi: 10.1159/000222775. Epub 2009 Jun 12.
    Results Reference
    background
    PubMed Identifier
    25106842
    Citation
    Aneja S, Jain P. Refractory epilepsy in children. Indian J Pediatr. 2014 Oct;81(10):1063-72. doi: 10.1007/s12098-014-1533-1. Epub 2014 Aug 9.
    Results Reference
    background
    PubMed Identifier
    19135617
    Citation
    Dudley RW, Penney SJ, Buckley DJ. First-drug treatment failures in children newly diagnosed with epilepsy. Pediatr Neurol. 2009 Feb;40(2):71-7. doi: 10.1016/j.pediatrneurol.2008.09.021.
    Results Reference
    background
    PubMed Identifier
    30426482
    Citation
    Kalilani L, Sun X, Pelgrims B, Noack-Rink M, Villanueva V. The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis. Epilepsia. 2018 Dec;59(12):2179-2193. doi: 10.1111/epi.14596. Epub 2018 Nov 13.
    Results Reference
    background
    PubMed Identifier
    16499772
    Citation
    Berg AT, Kelly MM. Defining intractability: comparisons among published definitions. Epilepsia. 2006 Feb;47(2):431-6. doi: 10.1111/j.1528-1167.2006.00440.x.
    Results Reference
    background
    PubMed Identifier
    10660394
    Citation
    Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9. doi: 10.1056/NEJM200002033420503.
    Results Reference
    background
    PubMed Identifier
    11756607
    Citation
    Dlugos DJ, Sammel MD, Strom BL, Farrar JT. Response to first drug trial predicts outcome in childhood temporal lobe epilepsy. Neurology. 2001 Dec 26;57(12):2259-64. doi: 10.1212/wnl.57.12.2259.
    Results Reference
    background
    PubMed Identifier
    11402099
    Citation
    Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. Early development of intractable epilepsy in children: a prospective study. Neurology. 2001 Jun 12;56(11):1445-52. doi: 10.1212/wnl.56.11.1445. Erratum In: Neurology 2001 Sep 11;57(5):939.
    Results Reference
    background
    PubMed Identifier
    11594910
    Citation
    Dlugos DJ. The early identification of candidates for epilepsy surgery. Arch Neurol. 2001 Oct;58(10):1543-6. doi: 10.1001/archneur.58.10.1543.
    Results Reference
    background
    PubMed Identifier
    22573629
    Citation
    Brodie MJ, Barry SJ, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012 May 15;78(20):1548-54. doi: 10.1212/WNL.0b013e3182563b19. Epub 2012 May 9.
    Results Reference
    background
    PubMed Identifier
    27275339
    Citation
    Nikodijevic D, Baneva-Dolnenec N, Petrovska-Cvetkovska D, Caparoska D. Refractory Epilepsy-MRI, EEG and CT scan, a Correlative Clinical Study. Open Access Maced J Med Sci. 2016 Mar 15;4(1):98-101. doi: 10.3889/oamjms.2016.029. Epub 2016 Feb 16.
    Results Reference
    background
    PubMed Identifier
    7506951
    Citation
    Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.
    Results Reference
    background
    PubMed Identifier
    16932648
    Citation
    Eisenberg R, Albert D. B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Jan;2(1):20-7. doi: 10.1038/ncprheum0042.
    Results Reference
    background
    PubMed Identifier
    16093832
    Citation
    Sfikakis PP, Boletis JN, Tsokos GC. Rituximab anti-B-cell therapy in systemic lupus erythematosus: pointing to the future. Curr Opin Rheumatol. 2005 Sep;17(5):550-7. doi: 10.1097/01.bor.0000172798.26249.fc.
    Results Reference
    background
    PubMed Identifier
    16622478
    Citation
    Edwards JC, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol. 2006 May;6(5):394-403. doi: 10.1038/nri1838.
    Results Reference
    background
    PubMed Identifier
    23739109
    Citation
    Cervenka MC, Kossoff EH. Dietary treatment of intractable epilepsy. Continuum (Minneap Minn). 2013 Jun;19(3 Epilepsy):756-66. doi: 10.1212/01.CON.0000431396.23852.56.
    Results Reference
    background
    PubMed Identifier
    17241207
    Citation
    Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007 Jan;48(1):43-58. doi: 10.1111/j.1528-1167.2007.00915.x.
    Results Reference
    background
    PubMed Identifier
    19535814
    Citation
    Kossoff EH, Zupec-Kania BA, Rho JM. Ketogenic diets: an update for child neurologists. J Child Neurol. 2009 Aug;24(8):979-88. doi: 10.1177/0883073809337162. Epub 2009 Jun 17.
    Results Reference
    background
    PubMed Identifier
    18456557
    Citation
    Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun;7(6):500-6. doi: 10.1016/S1474-4422(08)70092-9. Epub 2008 May 2.
    Results Reference
    background
    PubMed Identifier
    22406257
    Citation
    Yuen AW, Sander JW. Can magnesium supplementation reduce seizures in people with epilepsy? A hypothesis. Epilepsy Res. 2012 Jun;100(1-2):152-6. doi: 10.1016/j.eplepsyres.2012.02.004. Epub 2012 Mar 8.
    Results Reference
    background
    PubMed Identifier
    19154320
    Citation
    Hayashi M. Oxidative stress in developmental brain disorders. Neuropathology. 2009 Feb;29(1):1-8. doi: 10.1111/j.1440-1789.2008.00888.x.
    Results Reference
    background
    PubMed Identifier
    15007118
    Citation
    Kanner AM, Soto A, Gross-Kanner H. Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy. Neurology. 2004 Mar 9;62(5):708-13. doi: 10.1212/01.wnl.0000113763.11862.26.
    Results Reference
    background
    PubMed Identifier
    23647147
    Citation
    van Mierlo P, Carrette E, Hallez H, Raedt R, Meurs A, Vandenberghe S, Van Roost D, Boon P, Staelens S, Vonck K. Ictal-onset localization through connectivity analysis of intracranial EEG signals in patients with refractory epilepsy. Epilepsia. 2013 Aug;54(8):1409-18. doi: 10.1111/epi.12206. Epub 2013 May 3.
    Results Reference
    background
    PubMed Identifier
    17295615
    Citation
    Salmenpera TM, Symms MR, Rugg-Gunn FJ, Boulby PA, Free SL, Barker GJ, Yousry TA, Duncan JS. Evaluation of quantitative magnetic resonance imaging contrasts in MRI-negative refractory focal epilepsy. Epilepsia. 2007 Feb;48(2):229-37. doi: 10.1111/j.1528-1167.2007.00918.x.
    Results Reference
    background

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    Comparative Study of Dietary and Immunological Management of Refractory Epilepsy in Children

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