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Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update

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Abstract

Infantile spasms are the typical seizures of West syndrome, an infantile epileptic encephalopathy with poor outcomes. There is an increasing need to identify more effective and better tolerated treatments for infantile spasms. We have optimized the rat model of infantile spasms due to structural etiology, the multiple-hit rat model, for therapy discovery. Here, we test three compounds administered after spasms induction in the multiple hit model for efficacy and tolerability. Specifically, postnatal day 3 (PN3) male Sprague-Dawley rats were induced by right intracerebral injections of doxorubicin and lipopolysaccharide. On PN5 p-chlorophenylalanine was given intraperitoneally (i.p.). Daily monitoring of weights and developmental milestones was done and rats were intermittently video monitored. A blinded, randomized, vehicle-controlled study design was followed. The caspase 1 inhibitor VX-765 (50–200 mg/kg i.p.) and the GABAB receptor inhibitor CGP35348 (12.5–100 mg/kg i.p.) each was administered in different cohorts as single intraperitoneal injections on PN4, using a dose- and time-response design with intermittent monitoring till PN5. 17β-estradiol (40 ng/g/day subcutaneously) was given daily between PN3-10 and intermittent monitoring was done till PN12. None of the treatments demonstrated acute or delayed effects on spasms, yet all were well tolerated. We discuss the implications for therapy discovery and challenges of replication trials.

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References

  1. Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, O’Dell C, Shields WD, Trevathan E, Wheless JW (2010) Infantile spasms: a US consensus report. Epilepsia 51(10):2175–2189. doi:10.1111/j.1528-1167.2010.02657.x

    Article  PubMed  Google Scholar 

  2. Riikonen R (2014) Recent advances in the pharmacotherapy of infantile spasms. CNS Drugs 28(4):279–290. doi:10.1007/s40263-014-0139-5

    Article  CAS  PubMed  Google Scholar 

  3. Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, Grinspan Z, Hartman AL, Kossoff EH, Gaillard WD, Mytinger JR, Joshi S, Shellhaas RA, Sullivan J, Dlugos D, Hamikawa L, Berg AT, Millichap J, Nordli DR Jr, Wirrell E, Pediatric Epilepsy Research C (2016) Response to treatment in a prospective national infantile spasms cohort. Ann Neurol 79(3):475–484. doi:10.1002/ana.24594

    Article  PubMed  Google Scholar 

  4. Knupp KG, Leister E, Coryell J, Nickels KC, Ryan N, Juarez-Colunga E, Gaillard WD, Mytinger JR, Berg AT, Millichap J, Nordli DR Jr, Joshi S, Shellhaas RA, Loddenkemper T, Dlugos D, Wirrell E, Sullivan J, Hartman AL, Kossoff EH, Grinspan ZM, Hamikawa L, Pediatric Epilepsy Research Consortium (2016) Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia 57(11):1834–1842. doi:10.1111/epi.13557

    Article  CAS  PubMed  Google Scholar 

  5. Riikonen R (2017) Combination therapy for treatment of infantile spasms. Lancet Neurol 16(1):19–20. doi:10.1016/S1474-4422(16)30276-9

    Article  PubMed  Google Scholar 

  6. Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, Snead OC 3rd, Child Neurology S, American Academy of Neurology (2012) Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 78(24):1974–1980. doi:10.1212/WNL.0b013e318259e2cf

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lado FA, Moshe SL (2002) Role of subcortical structures in the pathogenesis of infantile spasms: what are possible subcortical mediators? Int Rev Neurobiol 49:115–140

    Article  CAS  PubMed  Google Scholar 

  8. Galanopoulou AS, Moshe SL (2015) Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: a view from preclinical studies. Neurobiol Dis 79:135–149. doi:10.1016/j.nbd.2015.04.015

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dulac O, Bast T, Dalla Bernardina B, Gaily E, Neville B (2010) Infantile spasms: toward a selective diagnostic and therapeutic approach. Epilepsia 51(10):2218–2219 (author reply 2221). doi:10.1111/j.1528-1167.2010.02736.x

    Article  PubMed  Google Scholar 

  10. Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Lux AL, Newton RW, O’Callaghan FJ, Verity CM, Osborne JP, trial steering committee on behalf of participating investigators (2010) Developmental and epilepsy outcomes at age 4 years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: a multi-centre randomised trial. Arch Dis Child 95(5):382–386. doi:10.1136/adc.2009.160606

    Article  PubMed  Google Scholar 

  11. O’Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, Likeman M, Lux AL, Mackay M, Mallick AA, Newton RW, Nolan M, Pressler R, Rating D, Schmitt B, Verity CM, Osborne JP, participating i (2017) Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol 16(1):33–42. doi:10.1016/S1474-4422(16)30294-0

    Article  PubMed  Google Scholar 

  12. Hancock EC, Osborne JP, Edwards SW (2013) Treatment of infantile spasms. Cochrane Database Syst Rev. doi:10.1002/14651858.CD001770.pub3

    Google Scholar 

  13. Riikonen R (1982) A long-term follow-up study of 214 children with the syndrome of infantile spasms. Neuropediatrics 13(1):14–23. doi:10.1055/s-2008-1059590

    Article  CAS  PubMed  Google Scholar 

  14. Lombroso CT (1983) A prospective study of infantile spasms: clinical and therapeutic correlations. Epilepsia 24(2):135–158

    Article  CAS  PubMed  Google Scholar 

  15. Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O’Callaghan FJ, Verity CM, Osborne JP, United Kingdom Infantile Spasms Study (2005) The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol 4(11):712–717. doi:10.1016/S1474-4422(05)70199-X

    Article  CAS  PubMed  Google Scholar 

  16. O’Callaghan FJ, Lux AL, Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM, Osborne JP (2011) The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia 52(7):1359–1364. doi:10.1111/j.1528-1167.2011.03127.x

    Article  PubMed  Google Scholar 

  17. Kivity S, Lerman P, Ariel R, Danziger Y, Mimouni M, Shinnar S (2004) Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia 45(3):255–262

    Article  CAS  PubMed  Google Scholar 

  18. Auvin S, Hartman AL, Desnous B, Moreau AC, Alberti C, Delanoe C, Romano A, Terrone G, Kossoff EH, Del Giudice E, Titomanlio L (2012) Diagnosis delay in West syndrome: misdiagnosis and consequences. Eur J Pediatr 171(11):1695–1701. doi:10.1007/s00431-012-1813-6

    Article  PubMed  Google Scholar 

  19. Cohen-Sadan S, Kramer U, Ben-Zeev B, Lahat E, Sahar E, Nevo Y, Eidlitz T, Zeharia A, Kivity S, Goldberg-Stern H (2009) Multicenter long-term follow-up of children with idiopathic West syndrome: ACTH versus vigabatrin. Eur J Neurol 16(4):482–487. doi:10.1111/j.1468-1331.2008.02498.x

    Article  CAS  PubMed  Google Scholar 

  20. Mohamed BP, Scott RC, Desai N, Gutta P, Patil S (2011) Seizure outcome in infantile spasms–a retrospective study. Epilepsia 52(4):746–752. doi:10.1111/j.1528-1167.2010.02963.x

    Article  PubMed  Google Scholar 

  21. Hussain K, Walsh TJ, Chazen JL (2016) Brain MRI findings with vigabatrin therapy: case report and literature review. Clin Imaging 40(1):180–182. doi:10.1016/j.clinimag.2015.07.016

    Article  PubMed  Google Scholar 

  22. Willmore LJ, Abelson MB, Ben-Menachem E, Pellock JM, Shields WD (2009) Vigabatrin: 2008 update. Epilepsia 50(2):163–173

    Article  CAS  PubMed  Google Scholar 

  23. Riikonen R (2015) Long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia 56(5):807–809. doi:10.1111/epi.12953

    Article  PubMed  Google Scholar 

  24. Riikonen R, Donner M (1980) ACTH therapy in infantile spasms: side effects. Arch Dis Child 55(9):664–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Konishi Y, Hayakawa K, Kuriyama M, Saito M, Fujii Y, Sudo M (1995) Effects of ACTH on brain midline structures in infants with infantile spasms. Pediatr Neurol 13(2):134–136

    Article  CAS  PubMed  Google Scholar 

  26. Wray CD, Benke TA (2010) Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms. Pediatr Neurol 43(3):163–166. doi:10.1016/j.pediatrneurol.2010.04.005

    Article  PubMed  PubMed Central  Google Scholar 

  27. Committee for Medicinal Products for Human Use (2010) Guideline on clinical investigation of medicinal products in the treatment of epileptic disorders. European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070043.pdf. Accessed 4 March 2017

  28. Pellock JM, Carman WJ, Thyagarajan V, Daniels T, Morris DL, D’Cruz O (2012) Efficacy of antiepileptic drugs in adults predicts efficacy in children: a systematic review. Neurology 79(14):1482–1489. doi:10.1212/WNL.0b013e31826d5ec0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dunne J, Rodriguez WJ, Murphy MD, Beasley BN, Burckart GJ, Filie JD, Lewis LL, Sachs HC, Sheridan PH, Starke P, Yao LP (2011) Extrapolation of adult data and other data in pediatric drug-development programs. Pediatrics 128(5):e1242–e1249. doi:10.1542/peds.2010-3487

    Article  PubMed  Google Scholar 

  30. Galanopoulou AS, Mowrey WB (2016) Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy. Epilepsia Open 1(3–4):86–101

    Article  PubMed  Google Scholar 

  31. Haines ST, Casto DT (1994) Treatment of infantile spasms. Ann Pharmacother 28(6):779–791. doi:10.1177/106002809402800616

    Article  CAS  PubMed  Google Scholar 

  32. Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D, Ballaban-Gill K, Baram TZ, Duchowny M, Hirtz D, Pellock JM, Shields WD, Shinnar S, Wyllie E, Snead OC 3rd, American Academy of Neurology, Child Neurology Society (2004) Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology 62(10):1668–1681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Stafstrom CE, Moshe SL, Swann JW, Nehlig A, Jacobs MP, Schwartzkroin PA (2006) Models of pediatric epilepsies: strategies and opportunities. Epilepsia 47(8):1407–1414. doi:10.1111/j.1528-1167.2006.00674_1.x

    Article  PubMed  Google Scholar 

  34. Scantlebury MH, Galanopoulou AS, Chudomelova L, Raffo E, Betancourth D, Moshe SL (2010) A model of symptomatic infantile spasms syndrome. Neurobiol Dis 37(3):604–612. doi:10.1016/j.nbd.2009.11.011

    Article  PubMed  Google Scholar 

  35. Briggs SW, Mowrey W, Hall CB, Galanopoulou AS (2014) CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms. Epilepsia 55(1):94–102. doi:10.1111/epi.12424

    Article  CAS  PubMed  Google Scholar 

  36. Raffo E, Coppola A, Ono T, Briggs SW, Galanopoulou AS (2011) A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis 43(2):322–329. doi:10.1016/j.nbd.2011.03.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Akman O, Briggs SW, Galanopoulou AS (2012) Long-term follow up of the multiple-hit model of symptomatic infantile spasms. Epilepsy Curr 13:147

    Google Scholar 

  38. Jequier Gygax M, Klein BD, White HS, Kim M, Galanopoulou AS (2014) Efficacy and tolerability of the galanin analog NAX 5055 in the multiple-hit rat model of symptomatic infantile spasms. Epilepsy Res 108(1):98–108. doi:10.1016/j.eplepsyres.2013.10.015

    Article  CAS  PubMed  Google Scholar 

  39. Noe FM, Polascheck N, Frigerio F, Bankstahl M, Ravizza T, Marchini S, Beltrame L, Bandero CR, Loscher W, Vezzani A (2013) Pharmacological blockade of IL-1beta/IL-1 receptor type 1 axis during epileptogenesis provides neuroprotection in two rat models of temporal lobe epilepsy. Neurobiol Dis 59:183–193. doi:10.1016/j.nbd.2013.07.015

    Article  CAS  PubMed  Google Scholar 

  40. Ravizza T, Lucas SM, Balosso S, Bernardino L, Ku G, Noe F, Malva J, Randle JC, Allan S, Vezzani A (2006) Inactivation of caspase-1 in rodent brain: a novel anticonvulsive strategy. Epilepsia 47(7):1160–1168. doi:10.1111/j.1528-1167.2006.00590.x

    Article  CAS  PubMed  Google Scholar 

  41. Ravizza T, Noe F, Zardoni D, Vaghi V, Sifringer M, Vezzani A (2008) Interleukin converting enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1beta production. Neurobiol Dis 31(3):327–333. doi:10.1016/j.nbd.2008.05.007

    Article  CAS  PubMed  Google Scholar 

  42. Cortez MA, Shen L, Wu Y, Aleem IS, Trepanier CH, Sadeghnia HR, Ashraf A, Kanawaty A, Liu CC, Stewart L, Snead OC 3rd (2009) Infantile spasms and Down syndrome: a new animal model. Pediatr Res 65(5):499–503. doi:10.1203/PDR.0b013e31819d9076

    Article  PubMed  Google Scholar 

  43. Olivetti PR, Maheshwari A, Noebels JL (2014) Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome. Sci Transl Med 6(220):220ra212. doi:10.1126/scitranslmed.3007231

    Article  Google Scholar 

  44. Galanopoulou AS, Buckmaster PS, Staley KJ, Moshe SL, Perucca E, Engel J, Jr., Loscher W, Noebels JL, Pitkanen A, Stables J, White HS, O’Brien TJ, Simonato M, American Epilepsy Society Basic Science Committee, The International League Against Epilepsy Working Group On Recommendations For Preclinical Epilepsy Drug Discovery (2012) Identification of new epilepsy treatments: issues in preclinical methodology. Epilepsia 53(3):571–582. doi:10.1111/j.1528-1167.2011.03391.x

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ono T, Moshe SL, Galanopoulou AS (2011) Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms. Epilepsia 52(9):1678–1684. doi:10.1111/j.1528-1167.2011.03173.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pardo CA, Nabbout R, Galanopoulou AS (2014) Mechanisms of epileptogenesis in pediatric epileptic syndromes: Rasmussen encephalitis, infantile spasms, and febrile infection-related epilepsy syndrome (FIRES). Neurother 11(2):297–310. doi:10.1007/s13311-014-0265-2

    Article  CAS  Google Scholar 

  47. Maroso M, Balosso S, Ravizza T, Iori V, Wright CI, French J, Vezzani A (2011) Interleukin-1beta biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurother 8(2):304–315. doi:10.1007/s13311-011-0039-z

    Article  CAS  Google Scholar 

  48. Price MG, Yoo JW, Burgess DL, Deng F, Hrachovy RA, Frost JD Jr, Noebels JL (2009) A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. J Neurosci 29(27):8752–8763. doi:10.1523/JNEUROSCI.0915-09.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Katsarou A, Moshé SL, Galanopoulou AS (2016) Interneuronopathy as a non-genetic etiology of infantile spasms. In: American Epilepsy Society Basic Science Committee (ed) American Epilepsy Society annual meeting, Houston, American Epilepsy Society, p 3.002

    Google Scholar 

  50. Tao Y, Sun H, Sun H, Qiu X, Xu C, Shi C, Du J (2015) 17beta-estradiol activates mTOR in chondrocytes by AKT-dependent and AKT-independent signaling pathways. Int J Clin Exp Pathol 8(12):15911–15918

    PubMed  PubMed Central  Google Scholar 

  51. Yang WR, Wang Y, Wang Y, Zhang JJ, Zhang JH, Lu C, Wang XZ (2015) mTOR is involved in 17beta-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1. Mol Reprod Dev 82(4):305–314. doi:10.1002/mrd.22473

    Article  CAS  PubMed  Google Scholar 

  52. Kazi AA, Molitoris KH, Koos RD (2009) Estrogen rapidly activates the PI3K/AKT pathway and hypoxia-inducible factor 1 and induces vascular endothelial growth factor A expression in luminal epithelial cells of the rat uterus. Biol Reprod 81(2):378–387. doi:10.1095/biolreprod.109.076117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yu J, Henske EP (2006) Estrogen-induced activation of mammalian target of rapamycin is mediated via tuberin and the small GTPase Ras homologue enriched in brain. Cancer Res 66(19):9461–9466. doi:10.1158/0008-5472.CAN-06-1895

    Article  CAS  PubMed  Google Scholar 

  54. Chachua T, Di Grazia P, Chern CR, Johnkutty M, Hellman B, Lau HA, Shakil F, Daniel M, Goletiani C, Veliskova J, Velisek L (2016) Estradiol does not affect spasms in the betamethasone-NMDA rat model of infantile spasms. Epilepsia 57(8):1326–1336. doi:10.1111/epi.13434

    Article  CAS  PubMed  Google Scholar 

  55. Pan Y, Gerasimov MR, Kvist T, Wellendorph P, Madsen KK, Pera E, Lee H, Schousboe A, Chebib M, Brauner-Osborne H, Craft CM, Brodie JD, Schiffer WK, Dewey SL, Miller SR, Silverman RB (2012) (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115), a potent gamma-aminobutyric acid aminotransferase inactivator for the treatment of cocaine addiction. J Med Chem 55(1):357–366. doi:10.1021/jm201231w

    Article  CAS  PubMed  Google Scholar 

  56. Doumlele K, Conway E, Hedlund J, Tolete P, Devinsky O (2016) A case report on the efficacy of vigabatrin analogue (1S, 3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115) in a patient with infantile spasms. Epilepsy Behav Case Rep 6:67–69. doi:10.1016/j.ebcr.2016.08.002

    Article  PubMed  PubMed Central  Google Scholar 

  57. Samueli S, Abraham K, Dressler A, Groppel G, Muhlebner-Fahrngruber A, Scholl T, Kasprian G, Laccone F, Feucht M (2016) Efficacy and safety of everolimus in children with TSC—associated epilepsy—Pilot data from an open single-center prospective study. Orphanet J Rare Dis 11(1):145. doi:10.1186/s13023-016-0530-z

    Article  PubMed  PubMed Central  Google Scholar 

  58. French JA, Lawson JA, Yapici Z, Ikeda H, Polster T, Nabbout R, Curatolo P, de Vries PJ, Dlugos DJ, Berkowitz N, Voi M, Peyrard S, Pelov D, Franz DN (2016) Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 388(10056):2153–2163. doi:10.1016/S0140-6736(16)31419-2

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

ASG reports grants from NINDS-R01NS91170, NINDS-1U54NS100064, Department of Defense (W81XWH-13-1-0180), and the Infantile Spasms Initiative from CURE (Citizens United for Research in Epilepsy), and acknowledges also research funding from the Heffer Family and the Segal Family Foundations and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families. WBM reports grant support from NINDS-1U54NS100064, Department of Defense (W81XWH-13-1-0180), the Infantile Spasms Initiative from CURE (Citizens United for Research in Epilepsy), and the Rett Syndrome Research Trust. SLM is the Charles Frost Chair in Neurosurgery and Neurology. He reports grants NINDS-NS020253, NINDS-NS43209, NINDS-NS45911, NINDS-1U54NS100064 and a grant from the US Department of Defense (W81XWH-13-1-0180), CURE Infantile Spasms Initiative grant and donations from the Heffer Family and the Segal Family Foundations and the Abbe Goldstein/Joshua Lurie and Laurie Marsh/Dan Levitz families. SLM holds a US patent for the multiple hit rat model (#7863499); no financial profits or conflicts have ensued as a result of this patent. We would like to thank Charles B. Hall, PhD (Division of Biostatistics, Albert Einstein College of Medicine) who performed the power analysis on the repeat administration treatment studies. We also wish to acknowledge the excellent technical assistance of Mrs Hong Wang.

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Authors and Affiliations

  1. Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, NY, USA

    Aristea S. Galanopoulou, Wei Liu, Qianyun Li, Oleksii Shandra & Solomon L. Moshé

  2. Dominick P. Purpura Department of Neuroscience, Montefiore/Einstein Epilepsy Center, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Kennedy Center Rm 306, Bronx, NY, 10461, USA

    Aristea S. Galanopoulou & Solomon L. Moshé

  3. Division of Biostatistics, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

    Wenzhu B. Mowrey

  4. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA

    Solomon L. Moshé

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  1. Aristea S. Galanopoulou
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Correspondence to Aristea S. Galanopoulou.

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Galanopoulou, A.S., Mowrey, W.B., Liu, W. et al. Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update. Neurochem Res 42, 1949–1961 (2017). https://doi.org/10.1007/s11064-017-2282-0

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