A review of traditional and novel treatments for seizures in autism spectrum disorder: Findings from a systematic review and expert panel

Frontiers in Public Health

Volumn 1, Issue SEP, 2013, Pages

  Frye, Richard E ^a   Rossignol, Daniel ^b   Casanova, Manuel F ^c   Martin, Victoria ^d   Brown, Gregory L ^d   Edelson, Stephen ^e   Coben, Robert ^f   Lewine, Jeffrey ^g   Slattery, John C ^a   Lau, Chrystal ^a   Hardy, Paul ^h   Fatemi, S Hossein ⁱ   Folsom, Timothy D ⁱ   MacFabe, Derrick ^j   Adams, James B ^k  

^a ARKANSAS CHILDREN S HOSPITAL RESEARCH INSTITUTE   (United States)

^b Rossignol Medical Center   (United States)

^c UNIVERSITY OF LOUISVILLE   (United States)

^d Autism Recovery and Comprehensive Health Medical Center   (United States)

^e Autism Research Institute   (United States)

^f NEW YORK UNIVERSITY   (United States)

^g UNIVERSITY OF NEW MEXICO   (United States)

^h Hardy Healthcare Associates   (United States)

ⁱ UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^j UNIVERSITY OF WESTERN ONTARIO   (Canada)

^k ARIZONA STATE UNIVERSITY   (United States)

more..

Author keywords

Anti epileptic drugs; Autism spectrum disorder; Epilepsy; Gluten free casein free diet; Ketogenic diet; Seizures; Treatment

Indexed keywords

EID: 85013620221     PISSN: None     EISSN: 22962565     Source Type: Journal    
DOI: 10.3389/fpubh.2013.00031     Document Type: Review

References (302)

1. Deykin EY, MacMahon B. The incidence of seizures among children with autistic symp-toms. Am J Psychiatry (1979) 136:1310-2.
2. Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry (1990) 29:127-9. doi:10.1097/00004583-199001000-00020
3. Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol (2002) 1:352-8. doi:10.1016/S1474-4422(02)00160-6
4. Danielsson S, Gillberg IC, Bill-stedt E, Gillberg C, Olsson I. Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 indi-viduals diagnosed in childhood. Epilepsia (2005) 46:918-23. doi:10. 1111/j.1528-1167.2005.57504.x
5. Hara H. Autism and epilepsy: a retrospective follow-up study. Brain Dev (2007) 29:486-90. doi: 10.1016/j.braindev.2006.12.012
6. Viscidi EW,Triche EW,Pescosolido MF, McLean RL, Joseph RM, Spence SJ, et al. Clinical char-acteristics of children with autism spectrum disorder and co-occurring epilepsy. PLoS One (2013) 8:e67797. doi:10.1371/ journal.pone.0067797
7. Sansa G, Carlson C, Doyle W, Weiner HL, Bluvstein J, Barr W, et al. Medically refractory epilepsy in autism. Epilepsia (2011) 52:1071-5. doi:10.1111/j. 1528-1167.2011.03069.x
8. Gilby KL, O'Brien TJ. Epilepsy, autism, and neurodevelopment: kindling a shared vulnerability? Epilepsy Behav (2013) 26:370-4. doi:10.1016/j.yebeh.2012.11.002
9. Tuchman R. Autism and social cognition in epilepsy: implica-tions for comprehensive epilepsy care. Curr Opin Neurol (2013) 26:214-8. doi:10.1097/WCO. 0b013e32835ee64f
10. Frye RE, Sreenivasula S, Adams JB. Traditional and non-traditional treatments for autism spec-trum disorder with seizures: an on-line survey. BMC Pediatr (2011) 11:37. doi:10.1186/1471-2431-11-37
11. RossignolDA.Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann Clin Psychiatry (2009) 21:213-36.
12. Richardson WS, Wilson MC, Nishikawa J, Hayward RS. The well-built clinical question: a key to evidence-based decisions. ACP J Club (1995) 123:A12-3.
13. Frye RE, Casanova M, Brown GL, Martin V, Edelson S, Lewine J, et al. A consensus statement from the Elias Tembenis Seizure Think Tanks. AutismScience Digest (2012) 1:5-10.
14. Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, etal. The Oxford 2011 Levels of Evidence. Oxford Centre for Evidence-Based Med-icine (2011). Available from: http://www.cebm.net/index.aspx? o=5653 [accessed September 3 2011].
15. Aman MG, van Bourgondien ME, Wolford PL, Sarphare G. Psychotropic and anticonvulsant drugs in subjects with autism: prevalence and patterns of use. J Am Acad Child Adolesc Psychiatry (1995) 34:1672-81. doi:10.1097/ 00004583-199512000-00018
16. Gillberg C. The treatment of epilepsy in autism. J Autism Dev Disord (1991) 21:61-77. doi:10. 1007/BF02206998
17. Uvebrant P, Bauziene R. Intractable epilepsy in chil-dren. The efficacy of lamot-rigine treatment, including non-seizure-related benefits. Neuropediatrics (1994) 25:284-9. doi:10.1055/s-2008-1073041
18. Komoto J, Usui S, Hirata J. Infan-tile autism and affective disor-der. J Autism Dev Disord (1984) 14:81-4. doi:10.1007/BF02408557
19. Deonna T, Ziegler AL, Moura-Serra J, Innocenti G. Autistic regression in relation to limbic pathology and epilepsy: report of two cases. Dev Med Child Neu-rol (1993) 35:166-76. doi:10.1111/ j.1469-8749.1993.tb11619.x
20. Rittey CD. Case summary: Ben-jamin. Seizure (1994) 3(Suppl A):25-7.
21. Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monother-apy for epileptic seizures and syndromes. Epilepsia (2013) 54:551-63. doi:10.1111/epi.12074
22. Hollander E, Soorya L, Wasser-man S, Esposito K, Chaplin W, Anagnostou E. Divalproex sodium vs. placebo in the treat-ment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol (2006) 9:209-13. doi:10.1017/ S1461145705005791
23. Anagnostou E, Esposito K, Soorya L, Chaplin W, Wasserman S, Hollander E. Divalproex versus placebo for the prevention of irritability associated with fiuoxe-tine treatment in autism spectrum disorder. J Clin Psychopharmacol (2006) 26:444-6. doi:10.1097/01. jcp.0000227703.72117.bc
24. Hollander E, ChaplinW, Soorya L, Wasserman S, Novotny S, Rusoff J, et al. Divalproex sodium vs placebo for the treatment of irri-tability in children and adoles-cents with autism spectrum dis-orders. Neuropsychopharmacology (2010) 35:990-8. doi:10.1038/npp. 2009.202
25. Hellings JA,Weckbaugh M, Nickel EJ, Cain SE, Zarcone JR, Reese RM, et al.A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. J Child Adolesc Psychopharmacol (2005) 15:682-92. doi:10.1089/cap.2005. 15.682
26. Hollander E, Dolgoff-Kaspar R, CartwrightC,Rawitt R,Novotny S. An open trial of divalproex sodium in autism spectrum disorders. J Clin Psychiatry (2001) 62:530-4. doi:10.4088/JCP.v62n07a05
27. Gillberg C, Schaumann H. Epilepsy presenting as infantile autism? Two case studies. Neu-ropediatrics (1983) 14:206-12. doi:10.1055/s-2008-1059580
28. Sovner R. The use of valproate in the treatment of mentally retarded persons with typical and atypical bipolar disorders. J Clin Psychiatry (1989) 50(Suppl):40-3.
29. Nass R, Petrucha D. Acquired aphasia with convulsive disorder: a pervasive developmental dis-order variant. J Child Neu-rol (1990) 5:327-8. doi:10.1177/ 088307389000500411
30. Plioplys AV. Autism: electroen-cephalogram abnormalities and clinical improvement with valproic acid. Arch Pediatr Ado-lesc Med (1994) 148:220-2. doi:10.1001/archpedi.1994. 02170020106021
31. Childs JA, Blair JL. Valproic acid treatment of epilepsy in autis-tic twins. J Neurosci Nurs (1997) 29:244-8. doi:10.1097/01376517-199708000-00005
32. Damore J, Stine J, Brody L. Medication-induced hypomania in Asperger's disorder. J Am Acad Child Adolesc Psychiatry (1998) 37:248-9. doi:10.1097/00004583-199803000-00006
33. Rugino TA, Samsock TC. Leve-tiracetam in autistic children: an open-label study. JDev Behav Pedi-atr (2002) 23:225-30. doi:10.1097/ 00004703-200208000-00006
34. Wasserman S, Iyengar R, Chap-lin WF, Watner D, Waldoks SE, Anagnostou E, et al. Levetirac-etam versus placebo in child-hood and adolescent autism: a double-blind placebo-controlled study. Int Clin Psychopharmacol (2006) 21:363-7. doi:10.1097/01. yic.0000224787.13782.0f
35. Belsito KM, Law PA, Kirk KS, Landa RJ, Zimmerman AW. Lam-otrigine therapy for autistic disor-der: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord (2001) 31:175-81. doi: 10.1023/A:1010799115457
36. Placidi F, Marciani MG, Diomedi M, Scalise A, Pauri F, Giacomini P, et al. Effects of lamotrigine on nocturnal sleep, daytime somno-lence and cognitive functions in focal epilepsy. Acta Neurol Scand (2000) 102:81-6. doi:10.1034/j. 1600-0404.2000.102002081.x
37. Vajda FJ, Dodd S, Horgan D. Lam-otrigine in epilepsy, pregnancy and psychiatry -a drug for all seasons? J Clin Neurosci (2013) 20:13-6. doi:10.1016/j.jocn.2012. 05.024
38. Rezaei V, Mohammadi MR, Gha-nizadeh A, Sahraian A, Tabrizi M Rezazadeh SA, et al. Double-blind placebo-controlled trial of risperi-done plus topiramate in children with autistic disorder. Prog Neu-ropsychopharmacol Biol Psychiatry (2010) 34:1269-72. doi:10.1016/j. pnpbp.2010.07.005
39. Canitano R. Clinical experience with topiramate to counteract neu-roleptic induced weight gain in 10 individuals with autistic spec-trum disorders. Brain Dev (2005) 27:228-32. doi:10.1016/j.braindev 2004.06.006
40. Bootsma HP, Aldenkamp AP Diepman L, Hulsman J, Lam-brechts D, Leenen L, et al. The effect of antiepileptic drugs on cognition: patient perceived cog-nitive problems of topiramate ver-sus levetiracetam in clinical prac-tice. Epilepsia (2006) 47(Suppl 2):24-7. doi:10.1111/j.1528-1167. 2006.00683.x
41. Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy Cochrane Database Syst Rev (2012) 3:CD001903.
42. Miranda MJ, Mortensen M Povlsen JH, Nielsen H, Beniczky S. Danish study of a modi-fied Atkins diet for medically intractable epilepsy in children: can we achieve the same results as with the classical ketogenic diet? Seizure (2011) 20:151-5. doi:10.1016/j.seizure.2010.11.010
43. Evangeliou A, Vlachonikolis I, Mihailidou H, Spilioti M Skarpalezou A, Makaronas N et al. Application of a ketogenic diet in children with autistic behavior: pilot study. J Child Neurol (2003) 18:113-8. doi:10. 1177/08830738030180020501
44. Herbert MR, Buckley JA. Autism and dietary therapy: case report and review of the literature. J Child Neurol (2013) 28:975-82. doi:10. 1177/0883073813488668
45. Fisher RS, Handforth A. Reassess-ment: vagus nerve stimulation for epilepsy: a report of the Therapeu-tics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurol-ogy (1999) 53:666-9. doi:10.1212/ WNL.53.4.666
46. ParkYD. The effects of vagus nerve stimulation therapy on patients with intractable seizures and either Landau-Kleffner syndrome or autism. Epilepsy Behav (2003) 4:286-90. doi:10.1016/S1525-5050(03)00080-5
47. Warwick TC, Griffith J, Reyes B, Legesse B, Evans M. Effects of vagus nerve stimulation in a patient with temporal lobe epilepsy and Asperger syndrome: case report and review of the literature. Epilepsy Behav (2007) 10:344-7. doi:10.1016/j.yebeh.2007.01.001
48. Danielsson S, Viggedal G, Gillberg C, Olsson I. Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: a prospective 2-year follow-up study. Epilepsy Behav (2008) 12:298-304. doi:10.1016/j. yebeh.2007.10.007
49. Milgrom L. Is homeopathy pos-sible? J R Soc Promot Health (2006) 126:211-8. doi:10.1177/ 1466424006068237
50. Hoon AH Jr, Reiss AL. The mesial-temporal lobe and autism: case report and review. Dev Med Child Neurol (1992) 34:252-9. doi:10. 1111/j.1469-8749.1992.tb14999.x
51. Taylor DC, Neville BG, Cross JH. Autistic spectrum disorders in childhood epilepsy surgery candi-dates. Eur Child Adolesc Psychia-try (1999) 8:189-92. doi:10.1007/ s007870050128
52. Connolly MB, Hendson G, Stein-bok P. Tuberous sclerosis com-plex: a review of the manage-ment of epilepsy with emphasis on surgical aspects. Childs Nerv Syst (2006) 22:896-908. doi:10.1007/ s00381-006-0130-7
53. Tellez-Zenteno JF, Hernandez Ronquillo L, Moien-Afshari F, Wiebe S. Surgical outcomes in lesional and non-lesional epilepsy: a systematic review and meta-analysis. Epilepsy Res (2010) 89:310-8. doi:10.1016/j. eplepsyres.2010.02.007
54. Szabo CA, Wyllie E, Dolske M, Stanford LD, Kotagal P, Comair YG. Epilepsy surgery in chil-dren with pervasive develop-mental disorder. Pediatr Neurol (1999) 20:349-53. doi:10.1016/ S0887-8994(99)00003-X
55. Gillberg C, Uvebrant P, Carls-son G, Hedstrom A, Silfvenius H. Autism and epilepsy (and tuberous sclerosis?) in two pre-adolescent boys: neuropsychiatric aspects before and after epilepsy surgery. J Intellect Disabil Res (1996) 40(Pt 1):75-81. doi:10. 1111/j.1365-2788.1996.tb00606.x
56. Danielsson S, Viggedal G, Stef-fenburg S, Rydenhag B, Gill-berg C, Olsson I. Psychopathol-ogy, psychosocial functioning, and IQ before and after epilepsy surgery in children with drug-resistant epilepsy. Epilepsy Behav (2009) 14:330-7. doi:10.1016/j. yebeh.2008.10.023
57. McLellan A, Davies S, Heyman I, Harding B, Harkness W, Tay-lor D, et al. Psychopathology in children with epilepsy before and after temporal lobe resec-tion. Dev Med Child Neurol (2005) 47:666-72. doi:10.1111/j. 1469-8749.2005.tb01051.x
58. Danielsson S, Rydenhag B, Uve-brant P, Nordborg C, Olsson I. Temporal lobe resections in children with epilepsy: neuropsy-chiatric status in relation to neu-ropathology and seizure outcome. Epilepsy Behav (2002) 3:76-81. doi:10.1006/ebeh.2001.0297
59. Neville BG, Harkness WF, Cross JH, Cass HC, Burch VC, Lees JA, et al. Surgical treatment of severe autistic regression in childhood epilepsy. Pediatr Neu-rol (1997) 16:137-40. doi:10.1016/ S0887-8994(96)00297-4
60. Lewine JD, Andrews R, Chez M, Patil AA, Devinsky O, Smith M, et al. Magnetoencephalographic patterns of epileptiform activ-ity in children with regressive autism spectrum disorders. Pedi-atrics (1999) 104:405-18. doi:10. 1542/peds.104.3.405
61. Nass R,GrossA,Wisoff J,Devinsky O. Outcome of multiple subpial transections for autistic epilep-tiform regression. Pediatr Neu-rol (1999) 21:464-70. doi:10.1016/ S0887-8994(99)00029-6
62. Schramm J, Aliashkevich AF, GrunwaldT.Multiple subpial tran-sections: outcome and compli-cations in 20 patients who did not undergo resection. J Neurosurg (2002) 97:39-47. doi:10.3171/jns. 2002.97.1.0039
63. Blount JP, Langburt W, Otsubo H, Chitoku S, Ochi A, Weiss S, et al.Multiple subpial transections in the treatment of pediatric epilepsy. J Neurosurg (2004) 100:118-24.
64. Ntsambi-Eba G, Vaz G, Doc-quier MA, van Rijckevorsel K, Raftopoulos C. Patients with refractory epilepsy treated using a modi?ed multiple subpial tran-section technique. Neurosurgery (2013) 72:890-7; discussion 897-898. doi:10.1227/NEU. 0b013e31828ba750
65. Stefanatos GA, Grover W, Geller E. Case study: corticosteroid treat-ment of language regression in per-vasive developmental disorder. J Am Acad Child Adolesc Psychiatry (1995) 34:1107-11. doi:10.1097/ 00004583-199508000-00022
66. Shenoy S, Arnold S, Chatila T. Response to steroid therapy in autism secondary to autoimmune lymphoproliferative syndrome. J Pediatr (2000) 136:682-7. doi:10. 1067/mpd.2000.105355
67. Chez MG, Loeffel M, Buchanan C. Pulse high dose steroids as combi-nation therapy with valproic acid in epileptic aphasia patients with pervasive developmental delay or autism. Ann Neurol (1998) 44:539.
68. Grosso S, Farnetani M, Mostar-dini R, Cordelli D, Berardi R, Balestri P. A comparative study of hydrocortisone versus defiaza-cort in drug-resistant epilepsy of childhood. Epilepsy Res (2008) 81:80-5. doi:10.1016/j.eplepsyres. 2008.04.016
69. You SJ, Jung DE, Kim HD, Lee HS, Kang HC. Efficacy and prognosis of a short course of prednisolone therapy for pediatric epilepsy. Eur J Paediatr Neurol (2008) 12:314-20. doi:10.1016/j.ejpn.2007.09.003
70. Boris M, Goldblatt A, Edelson SM. Improvement in children with autism treated with intravenous gamma globulin. J Nutr Envi-ronMed (2005) 15:169-76. doi:10. 1080/13590840600681827
71. Gupta S. Treatment of children with autism with intravenous immunoglobulin. J Child Neurol (1999) 14:203-5.
72. DelGiudice-Asch G, Simon L, Schmeidler J, Cunningham-Rundles C, Hollander E. Brief report: a pilot open clinical trial of intravenous immunoglobulin in childhood autism. J Autism Dev Disord (1999) 29:157-60. doi:10.1023/A:1023096728131
73. Plioplys AV. Intravenous immunoglobulin treatment of children with autism. J Child Neurol (1998) 13:79-82. doi:10.1177/088307389801300207
74. van Engelen BG, Renier WO, Weemaes CM. Immunoglobu-lin treatment in human and experimental epilepsy. J Neu-rol Neurosurg Psychiatry (1994) 57(Suppl):72-5. doi:10.1136/jnnp. 57.Suppl.72
75. van Engelen BG, Renier WO, Weemaes CM, Gabreels FJ, Meinardi H. Immunoglobulin treatment in epilepsy, a review of the literature. Epilepsy Res (1994) 19:181-90. doi:10.1016/0920-1211(94)90061-2
76. Billiau AD, Witters P, Ceulemans B, Kasran A, Wouters C, Lagae L. Intravenous immunoglobulins in refractory childhood-onset epilepsy: effects on seizure frequency, EEG activity, and cere-brospinal fiuid cytokine profile. Epilepsia (2007) 48:1739-49. doi:10.1111/j.1528-1167.2007. 01134.x
77. Mikati MA, Kurdi R, El-Khoury Z, Rahi A, Raad W. Intra-venous immunoglobulin ther-apy in intractable childhood epilepsy: open-label study and review of the literature. Epilepsy Behav (2010) 17:90-4. doi:10.1016/j.yebeh.2009.10.020
78. Coben R, Linden M, Myers TE. Neurofeedback for autistic spectrum disorder: a review of the literature. Appl Psychophysiol Biofeedback (2010) 35:83-105. doi: 10.1007/s10484-009-9117-y
79. Sterman MB. Basic concepts and clinical findings in the treatment of seizure disorders with EEG oper-ant conditioning. Clin Electroen-cephalogr (2000) 31:45-55.
80. Tan G, Thornby J, Hammond DC, Strehl U, Canady B, Arne-mann K, et al. Meta-analysis of EEG biofeedback in treat-ing epilepsy. Clin EEG Neu-rosci (2009) 40:173-9. doi:10. 1177/155005940904000310
81. Coben R.Neurofeedback for autis-tic disorders: emerging empirical evidence. In: Casanova MF, editor. Imaging the Brain in Autism. New York: Springer Science+Business Media (2013). p. 107-34.
82. Coben R, Padolsky I. Assessment-guided neurofeedback for autis-tic spectrum disorder. J Neu-rother (2007) 11:5-23. doi:10. 1300/J184v11n01_02
83. Kouijzer MEJ, de Moor JMH, Ger-rits BJL,CongedoM, van SchieHT. Neurofeedback improves exec-utive functioning in children with autism spectrum disorders. Res Autism Spectr Disord (2009) 3:145-62. doi:10.1016/j.rasd.2008. 05.001
84. Kouijzer MEJ, van Schie HT, de Moor JMH, Gerrits BJL, Con-gedo M, Buitelaar JK. Neurofeed-back improves executive function-ing in children with autism spec-trum disorders. Res Autism Spectr Disord (2010) 4:386-99. doi:10. 1016/j.rasd.2009.10.007
85. Coben R, McKeon K. EEG assess-ment and treatment for autism spectrum disorders. Autism File (2009) 32:40-7.
86. Coben R, McKeon K. EEG assess-ment and treatment of seizures in children with autism spectrum disorder: a case example. Neuro-connections (2009): p. 17-2.
87. Legarda SB, McMahon D, Othmer S, Othmer S. Clinical neurofeed-back: case studies, proposedmech-anism, and implications for pedi-atric neurology practice. J Child Neurol (2011) 26:1045-51. doi:10. 1177/0883073811405052
88. Jambaque I, Chiron C, Dumas C, Mumford J, Dulac O. Mental and behavioural outcome of infan-tile epilepsy treated by vigaba-trin in tuberous sclerosis patients. Epilepsy Res (2000) 38:151-60. doi: 10.1016/S0920-1211(99)00082-0
89. Bombardieri R, Pinci M, Moavero R, Cerminara C, Curatolo P. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol (2010) 14:146-9. doi:10.1016/j.ejpn.2009. 03.003
90. Cusmai R, Moavero R, Bom-bardieri R, Vigevano F, Cura-tolo P. Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. Epilepsy Behav (2011) 22:735-9. doi:10.1016/j. yebeh.2011.08.037
91. Humphrey A, Neville BG, Clarke A, Bolton PF. Autistic regres-sion associated with seizure onset in an infant with tuberous scle-rosis. Dev Med Child Neurol (2006) 48:609-11. doi:10.1111/j. 1469-8749.2006.tb01324.x
92. Chiron C, Dumas C, Jambaque I, Mumford J, Dulac O. Random-ized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res (1997) 26:389-95. doi: 10.1016/S0920-1211(96)01006-6
93. Schaefer GB, Mendelsohn NJ, Professional P, Guidelines C. Clinical genetics evaluation in identifying the etiology of autism spectrum disor-ders: 2013 guideline revisions. Genet Med (2013) 15:399-407. doi:10.1038/gim.2013.32
94. Berry-Kravis E. Epilepsy in fragile X syndrome. Dev Med Child Neu-rol (2002) 44:724-8. doi:10.1111/j. 1469-8749.2002.tb00277.x
95. Incorpora G, Sorge G, Sorge A, Pavone L. Epilepsy in fragile X syndrome. Brain Dev (2002) 24:766-9. doi:10.1016/S0387-7604(02)00102-X
96. Alanay Y, Unal F, Turanli G, Alikasifoglu M, Alehan D, Akyol U, et al. A multidisciplinary approach to the management of individuals with fragile X syndrome. J Intellect Disabil Res (2007) 51:151-61. doi:10.1111/j. 1365-2788.2006.00942.x
97. Berry-Kravis E, Raspa M, Loggin-Hester L, Bishop E,Holiday D, Bai-ley DB. Seizures in fragile X syn-drome: characteristics and comor-bid diagnoses. Am J Intellect Dev Disabil (2010) 115:461-72. doi:10. 1352/1944-7558-115.6.461
98. Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, et al. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allo-pregnanolone. Hum Mol Genet (2012) 21:2923-35. doi:10.1093/ hmg/dds118
99. Heulens I, D'Hulst C, Van Dam D, De Deyn PP, Kooy RF. Pharmacological treat-ment of fragile X syndrome with GABAergic drugs in a knockout mouse model. Behav Brain Res (2012) 229:244-9. doi:10.1016/j.bbr.2012.01.031
100. Wijetunge LS, Chattarji S, Wyllie DJ, Kind PC. Fragile X syndrome: from targets to treatments. Neu-ropharmacology (2013) 68:83-96. doi:10.1016/j.neuropharm.2012. 11.028
101. Osterweil EK, Chuang SC, Chubykin AA, Sidorov M, Bianchi R, Wong RK, et al. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syn-drome. Neuron (2013) 77:243-50. doi:10.1016/j.neuron.2012.01.034
102. Mines MA, Jope RS. Glycogen synthase kinase-3: a promising therapeutic target for fragile x syndrome. Front Mol Neurosci (2011) 4:35. doi:10.3389/fnmol. 2011.00035
103. Frye RE, Rossignol D. Metabolic disorders and abnormalities asso-ciated with autism spectrum dis-order. J Pediatr Biochem (2012) 2:181-91.
104. Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J. Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol (2002) 17:435-9. doi:10.1177/088307380201700607
105. Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R, et al. A modern approach to the treatment of mitochondrial dis-ease. Curr Treat Options Neu-rol (2009) 11:414-30. doi:10.1007/ s11940-009-0046-0
106. Frye RE, Rossignol D. Treatments for mitochondrial dysfunction associated with autism spectrum disorders. J Pediatr Biochem(2012) 2:241-9.
107. Rossignol DA, Frye RE.Mitochon-drial dysfunction in autism spec-trumdisorders: a systematic review and meta-analysis. Mol Psychiatry (2012) 17:290-314. doi:10.1038/ mp.2010.136
108. Geier DA, Kern JK, Davis G, King PG, Adams JB, Young JL, et al. A prospective double-blind, randomized clinical trial of lev-ocarnitine to treat autism spec-trum disorders. Med Sci Monit (2011) 17:I15-23. doi:10.12659/ MSM.881792
109. Fahmy SF, El-Hamamsy MH, Zaki OK, Badary OA. L-carnitine supplementation improves the behavioral symptoms in autistic children. Res Autism Spectr Dis-ord (2013) 7:159-66. doi:10.1016/ j.rasd.2012.07.006
110. Adams JB,Holloway C. Pilot study of a moderate dose multivita-min/mineral supplement for chil-dren with autistic spectrum dis-order. J Altern Complement Med (2004) 10:1033-9. doi:10.1089/ acm.2004.10.1033
111. Adams JB,AudhyaT,McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Effect of a vita-min/mineral supplement on chil-dren and adults with autism. BMC Pediatr (2011) 11:111. doi: 10.1186/1471-2431-11-111
112. Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, et al. A ran-domized controlled pilot trial of oral N-acetylcysteine in chil-dren with autism. Biol Psychia-try (2012) 71:956-61. doi:10.1016/ j.biopsych.2012.01.014
113. Ghanizadeh A, Moghimi-Sarani E. A randomized double blind placebo controlled clinical trial of N-acetylcysteine added to risperi-done for treating autistic disorders. BMC Psychiatry (2013) 13:196. doi:10.1186/1471-244X-13-196
114. Ghanizadeh A, Derakhshan N. N-acetylcysteine for treatment of autism, a case report. J ResMed Sci (2012) 17:985-7.
115. Obeid R,McCaddon A,Herrmann W. The role of hyperhomocys-teinemia and B-vitamin deficiency in neurological and psychiatric dis-eases. Clin Chem Lab Med (2007) 45:1590-606. doi:10.1515/CCLM. 2007.356
116. Boris M, Goldblatt A, Galanko J, James SJ. Association of MTHFR gene variants with autism. J Ind Hyg Toxicol (2004) 9:106-8.
117. James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, et al. Metabolic endophe-notype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet (2006) 141B:947-56. doi:10.1002/ ajmg.b.30366
118. Goin-Kochel RP, Porter AE, Peters SU, Shinawi M, Sahoo T, Beaude-tal. The MTHFR 677C->T poly-morphism and behaviors in chil-dren with autism: exploratory genotype-phenotype correlations. Autism Res (2009) 2:98-108. doi: 10.1002/aur.70
119. Mohammad NS, Jain JM, Chin-takindi KP, Singh RP, Naik U, Akella RR. Aberrations in folate metabolic pathway and altered susceptibility to autism. Psychi-atr Genet (2009) 19:171-6. doi:10. 1097/YPG.0b013e32832cebd2
120. Pasca SP, Dronca E, Kaucsar T, Craciun EC, Endreffy E, Fer-encz BK, et al. One carbon metabolism disturbances and the C677T MTHFR gene polymor-phism in children with autism spectrumdisorders. J CellMolMed (2009) 13:4229-38. doi:10.1111/j. 1582-4934.2008.00463.x
121. Liu X, Solehdin F, Cohen IL, Gon-zalez MG, Jenkins EC, Lewis ME, et al. Population-and family-based studies associate the MTHFR gene with idiopathic autism in sim-plex families. J Autism Dev Disord (2011) 41:938-44. doi:10.1007/ s10803-010-1120-x
122. Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Dalla Bernardina B, et al. Oxida-tive stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic BiolMed (2012) 52:2128-41. doi:10.1016/j. freeradbiomed.2012.03.011
123. Guo T, Chen H, Liu B, Ji W, Yang C. Methylenetetrahydro-folate reductase polymorphisms C677T and risk of autism in the Chinese Han population. Genet Test Mol Biomarkers (2012) 16:968-73. doi:10.1089/gtmb. 2012.0091
124. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, et al.Maternal periconceptional folic acid intake and risk of autism spectrum disorders and develop-mental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr (2012) 96:80-9. doi:10.3945/ajcn. 110.004416
125. Pu D, Shen Y, Wu J. Association between MTHFR gene polymor-phisms and the risk of autism spectrum disorders: a meta-analysis. Autism Res (2013). doi: 10.1002/aur.1300. [Epub ahead of print].
126. Adams M, Lucock M, Stuart J, Fardell S, Baker K, Ng X. Pre-liminary evidence for involve-ment of the folate gene poly-morphism 19bp deletion-DHFR in occurrence of autism. Neurosci Lett (2007) 422:24-9. doi:10.1016/ j.neulet.2007.05.025
127. Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cere-bral folate receptor autoantibod-ies in autism spectrum disorder. Mol Psychiatry (2013) 18:369-81. doi:10.1038/mp.2011.175
128. Ramaekers VT, Quadros EV, Sequeira JM. Role of folate recep-tor autoantibodies in infantile autism. Mol Psychiatry (2013) 18:270-1. doi:10.1038/mp.2012.22
129. Frye RE, Naviaux RK. Autis-tic disorder with complex IV overactivity: a new mitochondr-ial syndrome. J Ped Neurol (2011) 9:427-34.
130. Ramaekers VT, Sequeira JM, Blau N, Quadros EV. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol (2008) 50:346-52. doi:10.1111/j.1469-8749.2008. 02053.x
131. Moretti P, Sahoo T,Hyland K, Bot-tiglieri T, Peters S,Del Gaudio D, et al. Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology (2005) 64:1088-90. doi:10.1212/ 01.WNL.0000154641.08211.B7
132. Ramaekers VT, Rothenberg SP, Sequeira JM, Opladen T, Blau N, Quadros EV, et al. Autoantibod-ies to folate receptors in the cere-bral folate deficiency syndrome. N Engl J Med (2005) 352:1985-91. doi:10.1056/NEJMoa043160
133. Moretti P, Peters SU, Del Gau-dio D, Sahoo T, Hyland K, Bot-tiglieri T, et al. Brief report: autistic symptoms, developmen-tal regression, mental retardation, epilepsy, and dyskinesias in CNS folate deficiency. J Autism Dev Disord (2008) 38:1170-7. doi:10. 1007/s10803-007-0492-z
134. Ramaekers VT, Blau N, Sequeira JM, Nassogne MC, Quadros EV. Folate receptor autoimmunity and cerebral folate deficiency in low-functioning autism with neu-rological deficits. Neuropediatrics (2007) 38:276-81. doi:10.1055/s-2008-1065354
135. Frye RE, Donner E, Golja A, Rooney CM. Folinic acid-responsive seizures presenting as breakthrough seizures in a 3-month-old boy. J Child Neurol (2003) 18:562-9. doi:10.1177/ 08830738030180081001
136. Djukic A. Folate-responsive neu-rologic diseases. Pediatr Neurol (2007) 37:387-97. doi:10.1016/j. pediatrneurol.2007.09.001
137. Gallagher RC, Van Hove JL, Scharer G, Hyland K, Plecko B, Waters PJ, et al. Folinic acid-responsive seizures are identical to pyridoxine-dependent epilepsy. Ann Neurol (2009) 65:550-6. doi: 10.1002/ana.21568
138. Gorker I, Tuzun U. Autistic-like findings associated with a urea cycle disorder in a 4-year-old girl. J Psychiatry Neurosci (2005) 30:133-5.
139. Serrano M, Martins C, Perez-Duenas B, Gomez-Lopez L, Mur-gui E, Fons C, et al. Neuropsychi-atric manifestations in late-onset urea cycle disorder patients. J Child Neurol (2010) 25:352-8. doi:10. 1177/0883073809340696
140. Braissant O. Current concepts in the pathogenesis of urea cycle dis-orders. Mol Genet Metab (2010) 100(Suppl 1):S3-12. doi:10.1016/j. ymgme.2010.02.010
141. van Karnebeek CD, Stockler S. Treatable inborn errors ofmetabo-lism causing intellectual disability: a systematic literature review. Mol Genet Metab (2012) 105:368-81. doi:10.1016/j.ymgme.2011.11.191
142. Pearl PL, Gibson KM, Cortez MA, Wu Y, Carter Snead O III, Knerr I, et al. Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. J Inherit Metab Dis (2009) 32:343-52. doi: 10.1007/s10545-009-1034-y
143. Schulze A. Creatine deficiency syndromes. Mol Cell Biochem (2003) 244:143-50. doi:10.1023/A: 1022443503883
144. ZaffanelloM,ZamboniG, Fontana E,Zoccante L,Tato L.Acase of par-tial biotinidase deficiency associ-ated with autism. Child Neuropsy-chol (2003) 9:184-8. doi:10.1076/ chin.9.3.184.16457
145. SikoraDM,Pettit-KekelK,Penfield J,Merkens LS,SteinerRD.The near universal presence of autism spec-trum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A (2006) 140:1511-8.
146. Bukelis I, Porter FD, Zimmerman AW, Tierney E. Smith-Lemli-Opitz syndrome and autism spectrum disorder. Am J Psychiatry (2007) 164:1655-61. doi:10.1176/appi. ajp.2007.07020315
147. MartinA,Koenig K, Scahill L,Tier-ney E, Porter FD, Nwokoro NA. Smith-Lemli-Opitz syndrome. J Am Acad Child Adolesc Psychia-try (2001) 40:506-7. doi:10.1097/ 00004583-200105000-00008
148. Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplemen-tation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet (1997) 68:305-10. doi:10.1002/(SICI) 1096-8628(19970131)68:3<305: :AID-AJMG11>3.0.CO;2-X
149. Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, et al. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet (1997) 68:311-4. doi:10.1002/(SICI) 1096-8628(19970131)68:3<311: :AID-AJMG12>3.3.CO;2-8
150. Nwokoro NA, Mulvihill JJ. Cho-lesterol and bile acid replacement therapy in children and adultswith Smith-Lemli-Opitz (SLO/RSH) syndrome. Am JMed Genet (1997) 68:315-21. doi:10.1002/(SICI) 1096-8628(19970131)68:3<315: :AID-AJMG13>3.0.CO;2-W
151. Aneja A, Tierney E. Autism: the role of cholesterol in treatment. Int Rev Psychiatry (2008) 20:165-70. doi:10.1080/09540260801889062
152. Tierney E,Conley SK,Goodwin H, Porter FD. Analysis of short-term behavioral effects of dietary cho-lesterol supplementation in Smith-Lemli-Opitz syndrome. Am J Med Genet A (2010) 152A:91-5. doi:10. 1002/ajmg.a.33148
153. Novarino G, El-Fishawy P, Kay-serili H, Meguid NA, Scott EM, Schroth J, et al. Mutations in BCKD-kinase lead to a poten-tially treatable formof autismwith epilepsy. Science (2012) 338:394-7. doi:10.1126/science.1224631
154. Dufour F, Nalecz KA, Nalecz MJ, Nehlig A. Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations. Neu-rosci Res (2001) 40:255-63. doi:10. 1016/S0168-0102(01)00232-2
155. Fox JT, Tullidge GM. Pyridoxine (vitamin B6) in epilepsy; a clinical trial. Lancet (1946) 2:345. doi:10. 1016/S0140-6736(46)90842-2
156. Ernsting W, Ferwerda T. Vit-amin B6 in treatment of epilepsy. J Am Med Assoc (1952) 148:1540.
157. MartinA,Koenig K, Scahill L,Tier-ney E, Porter FD, Nwokoro NA. Smith-Lemli-Opitz syndrome. J Am Acad Child Adolesc Psychia-try (2001) 40:506-7. doi:10.1097/ 00004583-200105000-00008
158. Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplemen-tation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet (1997) 68:305-10. doi:10.1002/(SICI) 1096-8628(19970131)68:3<305: :AID-AJMG11>3.0.CO;2-X
159. Irons M, Elias ER, Abuelo D, Bull MJ, Greene CL, Johnson VP, et al. Treatment of Smith-Lemli-Opitz syndrome: results of a multicenter trial. Am J Med Genet (1997) 68:311-4. doi:10.1002/(SICI) 1096-8628(19970131)68:3<311: :AID-AJMG12>3.3.CO;2-8
160. Nwokoro NA, Mulvihill JJ. Cho-lesterol and bile acid replacement therapy in children and adultswith Smith-Lemli-Opitz (SLO/RSH) syndrome. Am JMed Genet (1997) 68:315-21. doi:10.1002/(SICI) 1096-8628(19970131)68:3<315: :AID-AJMG13>3.0.CO;2-W
161. Aneja A, Tierney E. Autism: the role of cholesterol in treatment. Int Rev Psychiatry (2008) 20:165-70. doi:10.1080/09540260801889062
162. Tierney E,Conley SK,Goodwin H, Porter FD. Analysis of short-term behavioral effects of dietary cho-lesterol supplementation in Smith-Lemli-Opitz syndrome. Am J Med Genet A (2010) 152A:91-5. doi:10. 1002/ajmg.a.33148
163. Novarino G, El-Fishawy P, Kay-serili H, Meguid NA, Scott EM, Schroth J, et al. Mutations in BCKD-kinase lead to a poten-tially treatable formof autismwith epilepsy. Science (2012) 338:394-7. doi:10.1126/science.1224631
164. Dufour F, Nalecz KA, Nalecz MJ, Nehlig A. Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations. Neu-rosci Res (2001) 40:255-63. doi:10. 1016/S0168-0102(01)00232-2
165. Fox JT, Tullidge GM. Pyridoxine (vitamin B6) in epilepsy; a clinical trial. Lancet (1946) 2:345. doi:10. 1016/S0140-6736(46)90842-2
166. Ernsting W, Ferwerda T. Vit-amin B6 in treatment of epilepsy. J Am Med Assoc (1952) 148:1540.
167. Erol I, Alehan F, Gumus A. West syndrome in an infant with vita-min B12 deficiency in the absence of macrocytic anaemia. Dev Med Child Neurol (2007) 49:774-6. doi:10.1111/j.1469-8749.2007. 00774.x
168. James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, et al. Efficacy of methylcobalamin and folinic acid treatment on glu-tathione redox status in children with autism.AmJClinNutr (2009) 89:425-30. doi:10.3945/ajcn.2008. 26615
169. Kazutosh N, Naoko N, Emiko T, Man U, Mituki T, Tomohiro N, et al. A preliminary study of methylcobalamin therapy in autism. J TokyoWomen'sMed Univ (2005) 75, 64-69.
170. Topcu M, Saatci I, Haliloglu G, Kesimer M, Coskun T. D-glyceric aciduria in a six-month-old boy presenting with West syndrome and autistic behaviour. Neurope-diatrics (2002) 33:47-50. doi:10. 1055/s-2002-23600
171. Al-OwainM,KayaN,Al-Shamrani H,Al-BakheetA,QariA,Al-Muaigl S, et al. Autism spectrum disorder in a child with propionic acidemia. JIMD Rep (2013) 7:63-6. doi:10. 1007/8904_2012_143
172. Zafeiriou DI, Ververi A, Salomons GS, Vargiami E, Haas D, Papadopoulou V, et al. L-2-hydroxyglutaric aciduria present-ing with severe autistic features. Brain Dev (2008) 30:305-7. doi: 10.1016/j.braindev.2007.09.005
173. Lofthouse N, Hendren R, Hurt E, Arnold LE, Butter E. A review of complementary and alterna-tive treatments for autism spec-trum disorders. Autism Res Treat (2012) 2012:870391. doi:10.1155/ 2012/870391
174. Ault B, Evans RH, Francis AA, Oakes DJ, Watkins JC. Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. J Physiol (1980) 307:413-28.
175. Hallak M. Effect of parenteral magnesium sulfate administration on excitatory amino acid receptors in the rat brain.Magnes Res (1998) 11:117-31.
176. Hallak M, Berman RF, Irtenkauf SM, EvansMI, Cotton DB. Periph-eral magnesium sulfate enters the brain and increases the thresh-old for hippocampal seizures in rats. Am J Obstet Gynecol (1992) 167:1605-10. doi:10.1016/ 0002-9378(92)91749-Z
177. Mathern GW, Pretorius JK, Men-doza D, Lozada A, Leite JP, Chimelli L, et al. Increased hip-pocampal AMPA and NMDA receptor subunit immunoreactiv-ity in temporal lobe epilepsy patients. J Neuropathol Exp Neu-rol (1998) 57:615-34. doi:10.1097/ 00005072-199806000-00008
178. Mikuni N, Babb TL, Ying Z, Najm I, Nishiyama K, Wylie C, et al. NMDA-receptors 1 and 2A/B coassembly increased in human epileptic focal cortical dysplasia. Epilepsia (1999) 40:1683-7. doi:10. 1111/j.1528-1157.1999.tb01584.x
179. Chaistitwanich R, Mahoney AW, Hendricks DG, Sisson DV. Dietary calcium and phosphorus and seizure susceptibility of magne-sium deficient rats. Pharmacol Biochem Behav (1987) 27:443-9. doi:10.1016/0091-3057(87) 90347-9
180. Sinert R, Zehtabchi S, Desai S, Peacock P, Altura BT, Altura BM. Serum ionized magnesium and calcium levels in adult patients with seizures. Scand J Clin Lab Invest (2007) 67:317-26. doi:10. 1080/00365510601051441
181. Gupta SK, Manhas AS, Gupta VK, Bhatt R. Serum magnesium lev-els in idiopathic epilepsy. J Assoc Physicians India (1994) 42:456-7.
182. Hunter LA, Gibbins KJ. Magne-sium sulfate: past, present, and future. JMidwiferyWomens Health (2011) 56:566-74. doi:10.1111/j. 1542-2011.2011.00121.x
183. Zou LP, Wang X, Dong CH, Chen CH, Zhao W, Zhao RY. Three-week combination treat-ment with ACTH + magnesium sulfate versus ACTHmonotherapy for infantile spasms: a 24-week, randomized, open-label, follow-up study in China. Clin Ther (2010) 32:692-700. doi:10.1016/j. clinthera.2010.04.008
184. Abdelmalik PA, Politzer N, Carlen PL. Magnesium as an effective adjunct therapy for drug resistant seizures. Can J Neurol Sci (2012) 39:323-7.
185. Shorvon S, Ferlisi M. The out-come of therapies in refrac-tory and super-refractory convul-sive status epilepticus and rec-ommendations for therapy. Brain (2012) 135:2314-28. doi:10.1093/ brain/aws091
186. Visser NA, Braun KP, Leijten FS, van Nieuwenhuizen O, Wokke JH, van den Bergh WM. Magne-sium treatment for patients with refractory status epilepticus due to POLG1-mutations. J Neurol (2011) 258:218-22. doi:10.1007/ s00415-010-5721-2
187. Lelord G, Muh JP, Barthelemy C, Martineau J, Garreau B, Callaway E. Effects of pyridoxine and mag-nesium on autistic symptoms -initial observations. J Autism Dev Disord (1981) 11:219-30. doi:10. 1007/BF01531686
188. LelordG,Callaway E,Muh JP.Clin-ical and biological effects of high doses of vitamin B6 and magne-siumon autistic children. Acta Vit-aminol Enzymol (1982) 4:27-44.
189. Findling RL, Maxwell K, Scotese-Wojtila L, Huang J, Yamashita T, Wiznitzer M. High-dose pyri-doxine and magnesium adminis-tration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. J Autism Dev Disord (1997) 27:467-78. doi:10. 1023/A:1025861522935
190. Tolbert L, Haigler T, Waits MM, Dennis T. Brief report: lack of response in an autistic population to a low dose clinical trial of pyri-doxine plus magnesium. J Autism Dev Disord (1993) 23:193-9. doi: 10.1007/BF01066428
191. Kaluzna-Czaplinska J, Socha E, Rynkowski J. B vitamin supple-mentation reduces excretion of urinary dicarboxylic acids in autis-tic children. Nutr Res (2011) 31:497-502. doi:10.1016/j.nutres. 2011.06.002
192. Faber S, Zinn GM, Kern JC II, Kingston HM. The plasma zinc/serum copper ratio as a bio-marker in children with autism spectrum disorders. Biomarkers (2009) 14:171-80. doi:10.1080/ 13547500902783747
193. Yasuda H, Yoshida K, Yasuda Y, Tsutsui T. Infantile zinc deficiency: association with autism spectrum disorders. Sci Rep (2011) 1:129. doi:10.1038/srep00129
194. Jackson MJ, Garrod PJ. Plasma zinc, copper, and amino acid levels in the blood of autistic children. J Autism Child Schizophr (1978) 8:203-8. doi:10.1007/BF01537869
195. Adams JB,AudhyaT,McDonough-Means S, Rubin RA, Quig D, Geis E, et al. Nutritional and meta-bolic status of childrenwith autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) (2011) 8:34. doi:10.1186/1743-7075-8-34
196. Ganesh R, Janakiraman L. Serum zinc levels in children with sim-ple febrile seizure. Clin Pediatr (Phila) (2008) 47:164-6. doi:10. 1177/0009922807306165
197. Mollah MA, Rakshit SC, Anwar KS, Arslan MI, Saha N, Ahmed S, et al. Zinc concentration in serum and cerebrospinal fiuid simultaneously decrease in chil-dren with febrile seizure: findings from a prospective study in Bangladesh. Acta Paediatr (2008) 97:1707-11. doi:10.1111/j.1651-2227.2008.01001.x
198. Farahani HN, Ashthiani AR, Masihi MS. Study on serum zinc and selenium levels in epileptic patients. Neurosciences (2013) 18:138-42.
199. Seven M, Basaran SY, Cengiz M, Unal S, Yuksel A. Deficiency of selenium and zinc as a causative factor for idiopathic intractable epilepsy. Epilepsy Res (2013) 104:35-9. doi:10.1016/j. eplepsyres.2012.09.013
200. Williamson A, Spencer D. Zinc reduces dentate granule cell hyperexcitability in epileptic humans. Neuroreport (1995) 6:1562-4. doi:10.1097/00001756-199507310-00024
201. Fukahori M, Itoh M. Effects of dietary zinc status on seizure sus-ceptibility and hippocampal zinc content in the El (epilepsy)mouse. Brain Res (1990) 529:16-22. doi: 10.1016/0006-8993(90)90806-M
202. Roach ES, Carlin L. N,N-dimethylglycine for epilepsy. N Engl JMed (1982) 307:1081-2. doi: 10.1056/NEJM198210213071717
203. Roach ES, Gibson P. Failure of N,N-dimethylglycine in epilepsy. Ann Neurol (1983) 14:347. doi:10. 1002/ana.410140314
204. Gascon G, Patterson B, Year-wood K, Slotnick H. N,N-dimethylglycine and epilepsy. Epilepsia (1989) 30:90-3. doi:10. 1111/j.1528-1157.1989.tb05288.x
205. Bolman WM, Richmond JA. A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. J AutismDev Dis-ord (1999) 29:191-4. doi:10.1023/ A:1023023820671
206. Kern JK, Miller VS, Cauller PL, Kendall PR, Mehta PJ, Dodd M. Effectiveness of N,N-dimethylglycine in autism and pervasive developmental disorder. J Child Neurol (2001) 16:169-73. doi:10.2310/7010.2001.17515
207. Barbeau A, Donaldson J. Zinc, taurine, and epilepsy. Arch Neu-rol (1974) 30:52-8. doi:10.1001/ archneur.1974.00490310054009
208. Bergamini L,Mutani R,Delsedime M, Durelli L. First clinical expe-rience on the antiepileptic action of taurine. Eur Neurol (1974) 11:261-9. doi:10.1159/000114324
209. Barbeau A, Inoue N, Tsukada Y, Butterworth RF. The neu-ropharmacology of taurine. Life Sci (1975) 17:669-77. doi:10.1016/ 0024-3205(75)90520-2
210. El Idrissi A, Messing J, Scalia J, Trenkner E. Prevention of epilep-tic seizures by taurine. Adv Exp Med Biol (2003) 526:515-25. doi: 10.1007/978-1-4615-0077-3_62
211. El Idrissi A, L'Amoreaux WJ. Selective resistance of taurine-fed mice to isoniazide-potentiated seizures: in vivo functional test for the activity of glutamic acid decarboxylase. Neuroscience (2008) 156:693-9. doi:10.1016/j. neuroscience.2008.07.055
212. Davison AN, Kaczmarek LK. Tau-rine -a possible neurotransmitter? Nature (1971) 234:107-8. doi:10. 1038/234107a0
213. Knerr I, Pearl PL, Bottiglieri T, Snead OC, Jakobs C, Gibson KM. Therapeutic concepts in succinate semialdehyde dehydro-genase (SSADH; ALDH5a1) defi-ciency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient eval-uation, studies in Aldh5a1-/-mice and characterization of gamma-hydroxybutyric acid pharmacology. J Inherit Metab Dis (2007) 30:279-94. doi:10.1007/s10545-007-0574-2
214. Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Geier MR. A prospective study of transsulfuration biomarkers in autistic disorders. Neurochem Res (2009) 34:386-93. doi:10.1007/ s11064-008-9782-x
215. El Idrissi A, Boukarrou L,Dokin C, BrownWT. Taurine improves con-gestive functions in amousemodel of fragile X syndrome. Adv Exp Med Biol (2009) 643:191-8. doi:10. 1007/978-0-387-75681-3_19
216. Marchesi GF, Quattrini A, Scarpino O, Dellantonio R. Therapeutic effects of taurine in epilepsy: a clinical and polyphys-iographic study (author's transl). Riv Patol Nerv Ment (1975) 96:166-84.
217. Fukuyama Y, Ochiai Y. Therapeu-tic trial by taurine for intractable childhood epilepsies. Brain Dev (1982) 4:63-9. doi:10.1016/S0387-7604(82)80103-4
218. Koivisto K, Sivenius J, Keranen T, Partanen J, Riekkinen P, Gothoni G, et al. Clinical trial with an experimental taurine derivative, taltrimide, in epileptic patients. Epilepsia (1986) 27:87-90. doi:10 1111/j.1528-1157.1986.tb03506.x
219. Airaksinen EM, Koivisto K, Kera-nen T, Pitkanen A, Riekkinen PJ Oja SS, et al. Biochemical and clin-ical studies on epileptic patients during two phase I trials with the novel anticonvulsant taltrimide Epilepsy Res (1987) 1:308-11. doi 10.1016/0920-1211(87)90008-8
220. Kasziba E, Flancbaum L, Fitz-patrick JC, Schneiderman J, Fisher H. Simultaneous determination of histidine-containing dipeptides histamine, methylhistamine and histidine by high-performance liq-uid chromatography. J Chromatogr (1988) 432:315-20.
221. Flancbaum L, Fitzpatrick JC, Brot-man DN, Marcoux AM, Kasz-iba E, Fisher H. The presence and significance of carnosine in histamine-containing tissues of several mammalian species. Agents Actions (1990) 31:190-6. doi:10 1007/BF01997607
222. Chez MG, Buchanan CP Aimonovitch MC, Becker M Schaefer K, Black C, et al. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spec-trum disorders. J Child Neuro (2002) 17:833-7. doi:10.1177/ 08830738020170111501
223. Scherkl R, Hashem A, Frey HH Histamine in brain -its role in regulation of seizure susceptibility Epilepsy Res (1991) 10:111-8. doi 10.1016/0920-1211(91)90003-X
224. Kamei C, Ishizawa K, Kakinok H, Fukunaga M. Histaminer-gic mechanisms in amygdaloid-kindled seizures in rats. Epilepsy Res (1998) 30:187-94. doi:10 1016/S0920-1211(98)00005-9
225. Zhang LS, Chen Z, Huang YW Hu WW, Wei EQ, Yanai K Effects of endogenous hista-mine on seizure development of pentylenetetrazole-induced kin-dling in rats. Pharmacology (2003) 69:27-32. doi:10.1159/000071263
226. Kamei C, Okuma C. Role of cen-tral histamine in amygdaloid kin-dled seizures. Nihon Yakurigaku Zasshi (2001) 117:329-34. doi:10 1254/fpj.117.329
227. OkumaC,Hirai T,KameiC.Mech-anism of the inhibitory effect of histamine on amygdaloid-kindled seizures in rats. Epilepsia (2001) 42:1494-500. doi:10.1046/j.1528-1157.2001.05601.x
228. Jin CL, Yang LX, Wu XH, Li Q Ding MP, Fan YY, et al. Effects of carnosine on amygdaloid-kindled seizures in Sprague-Dawley rats Neuroscience (2005) 135:939-47. doi:10.1016/j.neuroscience.2005. 06.066
229. Wu XH,DingMP,Zhu-Ge ZB,Zhu YY, Jin CL, Chen Z. Carnosine, a precursor of histidine, amelio-rates pentylenetetrazole-induced kindled seizures in rat. Neurosci Lett (2006) 400:146-9. doi:10. 1016/j.neulet.2006.02.031
230. ZhuYY,Zhu-Ge ZB,WuDC,Wang S, Liu LY, Ohtsu H, et al. Carno-sine inhibits pentylenetetrazol-induced seizures by histaminer-gicmechanisms in histidine decar-boxylase knock-out mice. Neu-rosci Lett (2007) 416:211-6. doi: 10.1016/j.neulet.2007.01.075
231. Kozan R, Sefil F, Bagirici F. Anticonvulsant effect of carno-sine on penicillin-induced epilep-tiform activity in rats. Brain Res (2008) 1239:249-55. doi:10.1016/ j.brainres.2008.08.019
232. Taha AY, Burnham WM, Auvin S. Polyunsaturated fatty acids and epilepsy. Epilepsia (2010) 51:1348-58. doi:10.1111/j.1528-1167.2010.02654.x
233. Terra VC, Arida RM, Rabello GM, Cavalheiro EA, Scorza FA. The utility of omega-3 fatty acids in epilepsy: more than just a farmed tilapia! Arq Neuropsiquiatr (2011) 69:118-21.
234. Yuen AW, Sander JW, Fluegel D, Patsalos PN, Bell GS, Johnson T, et al. Omega-3 fatty acid supplemen-tation in patients with chronic epilepsy: a randomized trial. Epilepsy Behav (2005) 7:253-8. doi:10.1016/j.yebeh.2005.04.014
235. Yuen AW, Flugel D, Poepel A, Bell GS, Peacock JL, Sander JW. Non-randomized open trial of eicosapentaenoic acid (EPA), an omega-3 fatty acid, in ten peo-ple with chronic epilepsy. Epilepsy Behav (2012) 23:370-2. doi:10. 1016/j.yebeh.2011.11.030
236. DeGiorgio CM, Miller P, Mey-mandi S, Gornbein JA. n-3 Fatty acids (fish oil) for epilepsy, car-diac risk factors, and risk of SUDEP: clues froma pilot, double-blind, exploratory study. Epilepsy Behav (2008) 13:681-4. doi:10. 1016/j.yebeh.2008.08.001
237. Bromfield E, Dworetzky B, Hur-witz S, Eluri Z, Lane L, Replan-sky S, et al. A randomized trial of polyunsaturated fatty acids for refractory epilepsy. Epilepsy Behav (2008) 12:187-90. doi:10.1016/j. yebeh.2007.09.011
238. Puri BK, Koepp MJ, Holmes J, Hamilton G, Yuen AW. A 31-phosphorus neurospectroscopy study of omega-3 long-chain polyunsaturated fatty acid inter-vention with eicosapentaenoic acid and docosahexaenoic acid in patients with chronic refractory epilepsy. Prostaglandins Leukot Essent FattyAcids (2007) 77:105-7. doi:10.1016/j.plefa.2007.07.004
239. Vancassel S,DurandG,Barthelemy C, Lejeune B, Martineau J, Guil-loteau D, et al. Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids (2001) 65:1-7. doi:10.1054/ plef.2001.0281
240. Bell JG, MacKinlay EE, Dick JR, MacDonald DJ, Boyle RM, Glen AC. Essential fatty acids and phos-pholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent FattyAcids (2004) 71:201-4. doi:10.1016/j.plefa.2004.03.008
241. Wiest MM, German JB, Har-vey DJ, Watkins SM, Hertz-Picciotto I. Plasma fatty acid pro-files in autism: a case-control study. Prostaglandins Leukot Essent Fatty Acids (2009) 80:221-7. doi: 10.1016/j.plefa.2009.01.007
242. Bell JG, Miller D, MacDonald DJ, MacKinlay EE, Dick JR, Chesel-dine S, et al. The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr (2010) 103:1160-7. doi:10. 1017/S0007114509992881
243. Meguid NA, Atta HM, Gouda AS, Khalil RO. Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem (2008) 41:1044-8. doi:10.1016/j.clinbiochem.2008. 05.013
244. Meiri G, Bichovsky Y, Belmaker RH. Omega 3 fatty acid treatment in autism. J Child Adolesc Psy-chopharmacol (2009) 19:449-51. doi:10.1089/cap.2008.0123
245. Politi P, Cena H, Comelli M, Mar-rone G, Allegri C, Emanuele E, et al. Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study. Arch Med Res (2008) 39:682-5. doi:10.1016/ j.arcmed.2008.06.005
246. Johnson CR, Handen BL, Zimmer M, Sacco K. Polyunsaturated fatty acid supplementation in young children with autism. J Dev Phys Disabil (2010) 22:1-10. doi:10. 1007/s10882-009-9152-x
247. Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry (2007) 61:551-3. doi:10.1016/j.biopsych. 2006.05.007
248. Bent S, Bertoglio K, Ashwood P, Bostrom A, Hendren RL. A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder. J Autism Dev Disord (2011) 41:545-54. doi:10. 1007/s10803-010-1078-8
249. Rao ML, Roy R, Bell IR, Hoover R. The defining role of structure (including epitaxy) in the plausi-bility of homeopathy. Homeopathy (2007) 96:175-82. doi:10.1016/j. homp.2007.03.009
250. Wolf U,Wolf M, Heusser P, Thur-neysen A, Baumgartner S.Homeo-pathic preparations of quartz, sul-fur and copper sulfate assessed by UV spectroscopy. Evid Based Complement Alternat Med (2009) 2011:692798. doi:10.1093/ecam/ nep036
251. Ernst E. Winnowing the chaff of charlatanism from the wheat of science. Evid Based Complement Alternat Med (2010) 7:425-6. doi: 10.1093/ecam/nen089
252. Reilly D, Taylor M, Beattie N, Campbell J, McSharry C, Aitchi-son T, et al. Is evidence for homeopathy reproducible? Lancet (1994) 344(8937):1601-6. doi:10. 1016/S0140-6736(94)90407-3
253. Linde K, Clausius N, Ramirez G, Melchart D, Eitel F, Hedges LV, et al. Are the clinical effects of home-opathy placebo effects? A meta-analysis of placebo-controlled tri-als. Lancet (1997) 350:834-43. doi: 10.1016/S0140-6736(97)02293-9
254. Shang A, Huwiler-Muntener K, Nartey L, Juni P, Dorig P, Sterne J, et al. Are the clini-cal effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of home-opathy and allopathy. Lancet (2005) 366:726-32. doi:10.1016/ S0140-6736(05)67177-2
255. Frei H, Everts R, Ammon K, Kauf-mann F, Walther D, Hsu-Schmitz S, et al. Homeopathic treatment of children with attention deficit hyperactivity disorder: a random-ized, double blind, placebo con-trolled crossover trial. Eur J Pediatr (2005) 164:758-67. doi:10.1007/ s00431-005-1735-7
256. Barvalie P. Epilepsy -Acute Emergency. Hpathy Ezine (2006). Available from: http: //www.hpathy.com/casesnew/ barvalia-cuprum-met.asp
257. Bently G. A Case of Epilepsy. Hpathy Ezine (2007). Available from: http://www.hpathy.com/ casesnew/bentley-china.asp
258. Robinson TW. Homeopathic secretin in autism: a clin-ical pilot study. Br Home-opath J (2001) 90:86-91. doi:10.1054/homp.1999.0468
259. Whiteley P, Haracopos D, Knivs-berg AM, Reichelt KL, Parlar S, Jacobsen J, et al. The ScanBrit randomised, controlled, single-blind study of a gluten-and casein-free dietary intervention for children with autism spec-trum disorders. Nutr Neurosci (2010) 13:87-100. doi:10.1179/ 147683010X12611460763922
260. Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord (2006) 36:413-20. doi: 10.1007/s10803-006-0079-0
261. Pennesi CM, Klein LC. Effective-ness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report. Nutr Neurosci (2012) 15:85-91.
262. Peltola M, Kaukinen K, Dastidar P, Haimila K, Partanen J, Haapala AM, et al.Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitiv-ity. J Neurol Neurosurg Psychia-try (2009) 80:626-30. doi:10.1136/ jnnp.2008.148221
263. Haavik S, Altman K, Woelk C. Effects of the Feingold diet on seizures and hyperactivity: a single-subject analysis. J Behav Med (1979) 2:365-74. doi:10. 1007/BF00844740
264. Sonuga-Barke EJ, Brandeis D, Cortese S,DaleyD, FerrinM,Holt-mann M, et al. Nonpharmacolog-ical interventions for ADHD: sys-tematic review and meta-analyses of randomized controlled trials of dietary and psychological treat-ments. Am J Psychiatry (2013) 170:275-89. doi:10.1176/appi.ajp. 2012.12070991
265. Frye RE, Rotenberg A, Ous-ley M, Pascual-Leone A. Tran-scranial magnetic stimulation in child neurology: current and future directions. J Child Neu-rol (2008) 23:79-96. doi:10.1177/ 0883073807307972
266. Hoffman RE, Cavus I. Slow transcranial magnetic stimula-tion, long-term depotentiation, and brain hyperexcitability dis-orders. Am J Psychiatry (2002) 159:1093-102. doi:10.1176/appi. ajp.159.7.1093
267. Sokhadze EM, El-Baz A, Baruth J, Mathai G, Sears L, Casanova MF. Effects of low frequency repet-itive transcranial magnetic stim-ulation (rTMS) on gamma fre-quency oscillations and event-related potentials during pro-cessing of illusory figures in autism. J Autism Dev Disord (2009) 39:619-34. doi:10.1007/ s10803-008-0662-7
268. Sokhadze E, Baruth J, Tasman A, Mansoor M, Ramaswamy R, Sears L, et al. Low-frequency repeti-tive transcranial magnetic stimu-lation (rTMS) affects event-related potential measures of novelty pro-cessing in autism.Appl Psychophys-iol Biofeedback (2010) 35:147-61. doi:10.1007/s10484-009-9121-2
269. Casanova MF, Buxhoeveden DP, Switala AE, Roy E. Minicolum-nar pathology in autism. Neu-rology (2002) 58:428-32. doi:10. 1212/WNL.58.3.428
270. Casanova MF, van Kooten IA, Switala AE, van Engeland H,Hein-sen H, Steinbusch HW, et al. Minicolumnar abnormalities in autism. Acta Neuropathol (2006) 112:287-303. doi:10.1007/s00401-006-0085-5
271. Sokhadze EM, Baruth JM, Sears L, SokhadzeGE, El-BazAS,Casanova MF. Prefrontal neuromodulation using rTMS improves error mon-itoring and correction function in autism.Appl Psychophysiol Biofeed-back (2012) 37:91-102. doi:10. 1007/s10484-012-9182-5
272. Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, et al. A randomized clinical trial of repetitive transcranialmag-netic stimulation in patients with refractory epilepsy. Ann Neurol (2006) 60:447-55. doi:10.1002/ ana.20950
273. Theodore WH, Hunter K, Chen R, Vega-Bermudez F, Boroojerdi B, Reeves-Tyer P, et al. Tran-scranial magnetic stimulation for the treatment of seizures: a con-trolled study. Neurology (2002) 59:560-2. doi:10.1212/WNL.59.4. 560
274. Cantello R, Rossi S, Varrasi C, Ulivelli M, Civardi C, Bartalini S, et al. Slow repetitive TMS for drug-resistant epilepsy: clin-ical and EEG findings of a placebo-controlled trial. Epilepsia (2007) 48:366-74. doi:10.1111/j. 1528-1167.2006.00938.x
275. Kimiskidis VK, Kugiumtzis D, Papagiannopoulos S, Vlaikidis N. Transcranial magnetic stimula-tion (TMS) modulates epilepti-form discharges in patients with frontal lobe epilepsy: a preliminary EEG-TMS study. Int J Neural Syst (2013) 23:1250035. doi:10.1142/ S0129065712500359
276. Rossignol DA, Frye RE. A review of research trends in physio-logical abnormalities in autism spectrum disorders: immune dys-regulation, infiammation, oxida-tive stress,mitochondrial dysfunc-tion and environmental toxicant exposures. Mol Psychiatry (2012) 17:389-401. doi:10.1038/mp.2011. 165
277. Stafstrom CE, Hagerman PJ, Pessah IN. Pathophysiology of epilepsy in autism spectrum disorders. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 4th ed. Bethesda, MD: National Center for Biotechnology Information, US (2012). Available from: http://www.ncbi.nlm.nih. gov/books/NBK98169/
278. Kagan-Kushnir T, Roberts SW, SneadOC III. Screening electroen-cephalograms in autism spec-trum disorders: evidence-based guideline. J Child Neurol (2005) 20:197-206.
279. Depositario-Cabacar DF, Zelleke TG. Treatment of epilepsy in chil-dren with developmental disabil-ities. Dev Disabil Res Rev (2010) 16:239-47. doi:10.1002/ddrr.116
280. Kwan P, Brodie MJ. Neuropsy-chological effects of epilepsy and antiepileptic drugs. Lancet (2001) 357:216-22. doi:10.1016/S0140-6736(00)03600-X
281. Chadman KK, Guariglia SR, Yoo JH. New directions in the treat-ment of autism spectrum disor-ders from animal model research. Expert Opin Drug Discov (2012) 7:407-16. doi:10.1517/17460441. 2012.678828
282. Coghlan S, Horder J, Inkster B, Mendez MA, Murphy DG, Nutt DJ. GABA system dysfunction in autism and related disorders: from synapse to symptoms. Neurosci Biobehav Rev (2012) 36:2044-55. doi:10.1016/j.neubiorev.2012.07. 005
283. Calandre EP, Dominguez-Granados R, Gomez-Rubio M, Molina-Font JA. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand (1990) 81:504-6. doi:10.1111/j. 1600-0404.1990.tb01008.x
284. De Vivo DC, Bohan TP, Coulter DL, Dreifuss FE, Greenwood RS, Nordli DR Jr, et al. L-carnitine supplementation in childhood epilepsy: current perspectives. Epilepsia (1998) 39:1216-25. doi:10.1111/j.1528-1157.1998. tb01315.x
285. Lheureux PE, Hantson P. Carni-tine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila) (2009) 47:101-11. doi:10. 1080/15563650902752376
286. Frye RE, Rossignol DA.Mitochon-drial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res (2011) 69:41R-7. doi:10.1203/PDR. 0b013e318212f16b
287. Coulter DL. Carnitine deficiency: a possible mechanism for val-proate hepatotoxicity. Lancet (1984) 1:689. doi:10.1016/S0140-6736(84)92209-8
288. Coulter DL. Carnitine, valproate, and toxicity. J Child Neurol (1991) 6:7-14. doi:10.1177/088307389100600102
289. Major P, Greenberg E, Khan A, Thiele EA. Pyridoxine sup-plementation for the treatment of levetiracetam-induced behav-ior side effects in children: pre-liminary results. Epilepsy Behav (2008) 13:557-9. doi:10.1016/j. yebeh.2008.07.004
290. Davis GP,McCarthy JT,Magill DB, Coffey B. Behavioral effects of lev-etiracetam mitigated by pyridox-ine. J Child Adolesc Psychopharma-col (2009) 19:209-11. doi:10.1089/ cap.2009.19202
291. Finsterer J, Zarrouk Mahjoub S. Mitochondrial toxicity of antiepileptic drugs and their tolerability in mitochondrial dis-orders. Expert Opin Drug Metab Toxicol (2012) 8:71-9. doi:10. 1517/17425255.2012.644535
292. Berger I, Segal I, Shmueli D, Saada A. The effect of antiepilep-tic drugs on mitochondrial activ-ity: a pilot study. J Child Neu-rol (2010) 25:541-5. doi:10.1177/ 0883073809352888
293. Kim YJ, Ko HH, Han ES, Lee CS. Lamotrigine inhibition of rotenone-or 1-methyl-4-phenylpyridinium-induced mito-chondrial damage and cell death. Brain Res Bull (2007) 71:633-40. doi:10.1016/j.brainresbull.2006. 12.006
294. Kossoff EH, Zupec-Kania BA, Rho JM. Ketogenic diets: an update for child neurologists. J Child Neu-rol (2009) 24:979-88. doi:10.1177/ 0883073809337162
295. Mantis JG, Fritz CL,Marsh J,Hein-richs SC, Seyfried TN. Improve-ment in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets. Epilepsy Behav (2009) 15:133-41. doi:10.1016/j. yebeh.2009.02.038
296. Masino SA, Kawamura M, Wasser CD, Pomeroy LT, Ruskin DN. Adenosine, ketogenic diet and epilepsy: the emerging therapeu-tic relationship between metabo-lism and brain activity. Curr Neu-ropharmacol (2009) 7:257-68. doi: 10.2174/157015909789152164
297. Jozwiak S, Kossoff EH, Kotulska-Jozwiak K. Dietary treatment of epilepsy: rebirth of an ancient treatment. Neurol Neurochir Pol (2011) 45:370-8.
298. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, et al.Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neu-rol (2006) 60:223-35. doi:10.1002/ ana.20899
299. Bough K. Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia (2008) 49(Suppl 8):91-3. doi:10.1111/j.1528-1167.2008. 01846.x
300. Horvath R, Gorman G, Chin-nery PF. How can we treat mito-chondrial encephalomyopathies? Approaches to therapy. Neurother-apeutics (2008) 5:558-68. doi:10. 1016/j.nurt.2008.07.002
301. Finsterer J. Treatment of mito-chondrial disorders. Eur J Paedi-atrNeurol (2010) 14:29-44. doi:10. 1016/j.ejpn.2009.07.005
302. Pickett J, Xiu E, Tuchman R, Daw-son G, Lajonchere C. Mortality in individuals with autism, with and without epilepsy. J Child Neu-rol (2011) 26:932-9. doi:10.1177/ 0883073811402203