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Infantile Spasms—Have We Made Progress?

  • Sarah Aminoff Kelley
  • Kelly G. KnuppEmail author
Epilepsy (CW Bazil, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Epilepsy

Abstract

Purpose of the Review

The care of children with infantile spasms is full of areas of ambiguity, despite practice parameters and randomized trials. This review is to update the current care of children with infantile spasms.

Recent Findings

Several recent studies have generated new data to guide management including a randomized trial supporting combination therapy of hormone treatment and vigabatrin as an initial treatment for infantile spasms. Studies have suggested that we are not consistent in our recognition of hypsarrhythmia, while additional studies suggest that the presence or absence of this pattern may not have any predictive value. Additionally, the use of appropriate medications as well as an early diagnosis has the most impact on short-term outcomes.

Summary

Children with infantile spasms benefit most from early diagnosis and early treatment with appropriate standard medications such as hormonal therapy (ACTH or prednisolone) or vigabatrin.

Keywords

Infantile spasms Hypsarrhythmia ACTH Vigabatrin Epileptic spasms West syndrome 

Notes

Compliance with Ethical Standards

Conflict of Interest

Sarah Aminoff Kelley declares no conflict of interest.

Kelly G. Knupp has received grants from the Colorado Department of Health, PERF, and West Pharmaceuticals, as well as research funding from Zogenix and Greenwich Pharmaceuticals (DSMB).

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    West WJ. On a peculiar form of infantile convulsions. Lancet. 1841;35:724–5.CrossRefGoogle Scholar
  2. 2.
    Riikonen R, Donner M. Incidence and aetiology of infantile spasms from 1960 to 1976: a population study in Finland. Dev Med Child Neurol. 1979;21:333–43.CrossRefPubMedGoogle Scholar
  3. 3.
    Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol. 1991;6:355–64.CrossRefPubMedGoogle Scholar
  4. 4.
    Sidenvall R, Eeg-Olofsson O. Epidemiology of infantile spasms in Sweden. Epilepsia. 1995;36:572–4.CrossRefPubMedGoogle Scholar
  5. 5.
    Dura-Trave T, Yoldi-Petri ME, Gallinas-Victoriano F. Incidence of epilepsies and epileptic syndromes among children in Navarre, Spain: 2002 through 2005. J Child Neurol. 2008;23:878–82.CrossRefPubMedGoogle Scholar
  6. 6.
    Berg AT, Coryell J, Saneto RP, Grinspan ZM, Alexander JJ, Kekis M, et al. Early-life epilepsies and the emerging role of genetic testing. JAMA Pediatr. 2017;171:863–71.CrossRefPubMedGoogle Scholar
  7. 7.
    Verity CM, Ross EM, Golding J. Epilepsy in the first 10 years of life: findings of the child health and education study. BMJ. 1992;305:857–61.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gibbs FA, Gibbs EL. Atlas of electroencephalography. Cambridge: Mass.: Addison-Wesley Press; 1978.Google Scholar
  9. 9.
    SOREL L, DUSAUCY-BAULOYE A. Findings in 21 cases of Gibbs’ hypsarrhythmia; spectacular effectiveness of ACTH. Acta Neurol Psychiatr Belg. 1958;58:130–41.PubMedGoogle Scholar
  10. 10.
    LOW NL. Infantile spasms with mental retardation. II. Treatment with cortisone and adrenocorticotropin. Pediatrics. 1958;22:1165–9.PubMedGoogle Scholar
  11. 11.
    Jung MJ, Lippert B, Metcalf BW, Bohlen P, Schechter PJ. Gamma-vinyl GABA (4-amino-hex-5-enoic acid), a new selective irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice. J Neurochem. 1977;29:797–802.CrossRefPubMedGoogle Scholar
  12. 12.
    Chiron C, Dulac O, Beaumont D, Palacios L, Pajot N, Mumford J. Therapeutic trial of vigabatrin in refractory infantile spasms. J Child Neurol. 1991:Suppl 2:52.Google Scholar
  13. 13.
    Westall CA, Wright T, Cortese F, Kumarappah A, Snead OC, Buncic JR. Vigabatrin retinal toxicity in children with infantile spasms: an observational cohort study. Neurology. 2014;83:2262–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wheless JW, Carmant L, Bebin M, Conry JA, Chiron C, Elterman RD, et al. Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy. Epilepsia. 2009;50:195–205.CrossRefPubMedGoogle Scholar
  15. 15.
    Fong CY, Osborne JP, Edwards SW, Hemingway C, Hancock E, Johnson AL, et al. An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms. Dev Med Child Neurol. 2013;55:862–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Lux AL, Osborne JP. A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group. Epilepsia. 2004;45:1416–28.CrossRefPubMedGoogle Scholar
  17. 17.
    Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51:2175–89.CrossRefPubMedGoogle Scholar
  18. 18.
    Wirrell EC, Shellhaas RA, Joshi C, Keator C, Kumar S, Mitchell WG. How should children with west syndrome be efficiently and accurately investigated? Results from the national infantile spasms consortium. Epilepsia. 2015;56:617–25.CrossRefPubMedGoogle Scholar
  19. 19.
    Osborne JP, Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, et al. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. 2010;51:2168–74.CrossRefPubMedGoogle Scholar
  20. 20.
    Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015;56:1185–97.CrossRefPubMedGoogle Scholar
  21. 21.
    Hrachovy RA, Frost JD Jr, Kellaway P. Hypsarrhythmia: variations on the theme. Epilepsia. 1984;25:317–25.CrossRefPubMedGoogle Scholar
  22. 22.
    Watanabe K, Negoro T, Aso K, Matsumoto A. Reappraisal of interictal electroencephalograms in infantile spasms. Epilepsia. 1993;34:679–85.CrossRefPubMedGoogle Scholar
  23. 23.
    Hussain SA, Kwong G, Millichap JJ, Mytinger JR, Ryan N, Matsumoto JH, et al. Hypsarrhythmia assessment exhibits poor interrater reliability: a threat to clinical trial validity. Epilepsia. 2015;56:77–81.CrossRefPubMedGoogle Scholar
  24. 24.
    •• Mytinger JR, Hussain SA, Islam MP, Millichap JJ, Patel AD, Ryan NR, et al. Improving the inter-rater agreement of hypsarrhythmia using a simplified EEG grading scale for children with infantile spasms. Epilepsy Res. 2015;116:93–8. This study suggests a scale to be used in clinical practice to improve inter-rater reliability of hypsarrhythmia. CrossRefPubMedGoogle Scholar
  25. 25.
    Bajammal R, Nariai H, Numis A, Rajaraman R, Sankar R, Hussain S. Ideal duration of video-EEG to confirm response to therapy in the treatment of infantile spasms. American Epilepsy Society Meeting 2017 Abstract.Google Scholar
  26. 26.
    •• Demarest ST, Shellhaas RA, Gaillard WD, Keator C, Nickels KC, Hussain SA, et al. The impact of hypsarrhythmia on infantile spasms treatment response: observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017;58:2098–103. This study demonstrates that EEG findings at onset (absence or presence of hypsarrythmia or presence of modified hypsarrhythmia) do not predict short-term outcomes, and use of standard medications predicts short-term outcomes. CrossRefPubMedGoogle Scholar
  27. 27.
    Whitney R, Jan S, Zak M, McCoy B. The utility of surveillance electroencephalography to guide early antiepileptic drug therapy in infants with tuberous sclerosis complex. Pediatr Neurol. 2017;72:76–80.CrossRefPubMedGoogle Scholar
  28. 28.
    Kato M, Das S, Petras K, Sawaishi Y, Dobyns WB. Polyalanine expansion of ARX associated with cryptogenic West syndrome. Neurology. 2003;61:267–76.CrossRefPubMedGoogle Scholar
  29. 29.
    Weaving LS, Christodoulou J, Williamson SL, Friend KL, McKenzie OL, Archer H, et al. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet. 2004;75:1079–93.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mignot C, Moutard ML, Trouillard O, Gourfinkel-An I, Jacquette A, Arveiler B, et al. STXBP1-related encephalopathy presenting as infantile spasms and generalized tremor in three patients. Epilepsia. 2011;52:1820–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Sundaram SK, Chugani HT, Tiwari VN, Huq AH. SCN2A mutation is associated with infantile spasms and bitemporal glucose hypometabolism. Pediatr Neurol. 2013;49:46–9.Google Scholar
  32. 32.
    Boutry-Kryza N, Labalme A, Ville D, de Bellescize J, Touraine R, Prieur F, et al. Molecular characterization of a cohort of 73 patients with infantile spasms syndrome. Eur J Med Genet. 2015;58:51–8.Google Scholar
  33. 33.
    Hussain SA, Lay J, Cheng E, Weng J, Sankar R, Baca CB. Recognition of infantile spasms is often delayed: the ASSIST study. J Pediatr 2017;190. 221:e1.Google Scholar
  34. 34.
    Kivity S, Lerman P, Ariel R, Danziger Y, Mimouni M, Shinnar S. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia. 2004;45:255–62.CrossRefPubMedGoogle Scholar
  35. 35.
    Tibussek D, Klepper J, Korinthenberg R, Kurlemann G, Rating D, Wohlrab G, et al. Treatment of infantile spasms: report of the Interdisciplinary Guideline Committee Coordinated by the German-Speaking Society for Neuropediatrics. Neuropediatrics. 2016;47:139–50.CrossRefPubMedGoogle Scholar
  36. 36.
    Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2019;364:1773–8.CrossRefGoogle Scholar
  37. 37.
    Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, et al. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol. 2016;79:475–84.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    •• O'Callaghan FJ, Edwards SW, Alber FD, Hancock E, Johnson AL, Kennedy CR, et al. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol. 2017;16:33–42. Randomized trial demonstrating superior efficacy of combination therapy (hormonal therapy and vigabatrin) compared to monotherapy. CrossRefPubMedGoogle Scholar
  39. 39.
    Curatolo P, Jozwiak S, Nabbout R, TSC Consensus Meeting for SEGA and Epilepsy Management. Management of epilepsy associated with tuberous sclerosis complex (TSC): clinical recommendations. Eur J Paediatr Neurol. 2012;16:582–6.CrossRefPubMedGoogle Scholar
  40. 40.
    Bebin M Preventing epilepsy using vigabatrin in INfants with tuberous sclerosis complex (PREVeNT trial) [online]. Available at: https://clinicaltrials.gov/ct2/show/NCT02849457?cond=Tuberous+Sclerosis&rank=8.
  41. 41.
    Knupp KG, Leister E, Coryell J, Nickels KC, Ryan N, Juarez-Colunga E, et al. Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia. 2016;57:1834–42.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Zou LP, Lin Q, Qin J, Cai FC, Liu ZS, Mix E, et al. Evaluation of open-label topiramate as primary or adjunctive therapy in infantile spasms. Clin Neuropharmacol. 2008;31:86–92.CrossRefPubMedGoogle Scholar
  43. 43.
    Mahmoud AA, Rizk TM, Mansy AA, Ali JA, Al-Tannir MA. Ineffectiveness of topiramate and levetiracetam in infantile spasms non-responsive to steroids. Open labeled randomized prospective study. Neurosciences (Riyadh). 2013;18:143–6.Google Scholar
  44. 44.
    Auvichayapat N, Tassniyom S, Treerotphon S, Auvichayapat P. Treatment of infantile spasms with sodium valproate followed by benzodiazepines. J Med Assoc Thail. 2007;90:1809–14.Google Scholar
  45. 45.
    Gumus H, Kumandas S, Per H. Levetiracetam monotherapy in newly diagnosed cryptogenic West syndrome. Pediatr Neurol. 2007;37:350–3.CrossRefPubMedGoogle Scholar
  46. 46.
    Kang HC, Lee YJ, Lee JS, Lee EJ, Eom S, You SJ, et al. Comparison of short- versus long-term ketogenic diet for intractable infantile spasms. Epilepsia. 2011;52:781–7.CrossRefPubMedGoogle Scholar
  47. 47.
    Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia. 2008;49:1504–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Prezioso G, Carlone G, Zaccara G, Verrotti A. Efficacy of ketogenic diet for infantile spasms: a systematic review. Acta Neurol Scand. 2018;137:4–11.CrossRefPubMedGoogle Scholar
  49. 49.
    Wilmshurst JM, Gaillard WD, Vinayan KP, Tsuchida TN, Plouin P, Van Bogaert P, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015;56:1185–97.CrossRefPubMedGoogle Scholar
  50. 50.
    Wang YJ, Zhang Y, Liang XH, Yang G, Zou LP. Effects of adrenal dysfunction and high-dose adrenocorticotropic hormone on NMDA-induced spasm seizures in young Wistar rats. Epilepsy Res. 2012;100:125–31.CrossRefPubMedGoogle Scholar
  51. 51.
    Olivetti PR, Noebels JL. Interneuron, interrupted: molecular pathogenesis of ARX mutations and X-linked infantile spasms. Curr Opin Neurobiol. 2012;22:859–65.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Olivetti PR, Maheshwari A, Noebels JL. Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome. Sci Transl Med. 2014;6:220ra12.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Scantlebury MH, Gibbs SA, Foadjo B, Lema P, Psarropoulou C, Carmant L. Febrile seizures in the predisposed brain: a new model of temporal lobe epilepsy. Ann Neurol. 2005;58:41–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Ono T, Moshe SL, Galanopoulou AS. Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms. Epilepsia. 2011;52:1678–84.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Galanopoulou AS, Mowrey WB, Liu W, Li Q, Shandra O, Moshe SL. Preclinical screening for treatments for infantile spasms in the multiple hit rat model of infantile spasms: an update. Neurochem Res. 2017;42:1949–61.CrossRefPubMedGoogle Scholar
  56. 56.
    Swann J, Le J, Frost J. Infantile spasms: ACTH dose response relationships. American Epilepsy Society Meeting 2017Abstract.Google Scholar
  57. 57.
    Riikonen R. A long-term follow-up study of 214 children with the syndrome of infantile spasms. Neuropediatrics. 1982;13:14–23.CrossRefPubMedGoogle Scholar
  58. 58.
    Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, et al. 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. 2005;4:712–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Lux AL, et al. 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. 2010;95:382–6.CrossRefPubMedGoogle Scholar
  60. 60.
    Widjaja E, Go C, McCoy B, Snead OC. Neurodevelopmental outcome of infantile spasms: a systematic review and meta-analysis. Epilepsy Res. 2015;109:155–62.CrossRefPubMedGoogle Scholar
  61. 61.
    Dilber C, Caliskan M, Sonmezoglu K, Nisli S, Mukaddes NM, Tatli B, et al. Positron emission tomography findings in children with infantile spasms and autism. J Clin Neurosci. 2013;20:373–6.CrossRefPubMedGoogle Scholar
  62. 62.
    Saemundsen E, Ludvigsson P, Rafnsson V. Autism spectrum disorders in children with a history of infantile spasms: a population-based study. J Child Neurol. 2007;22:1102–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Lagae L, Verhelst H, Ceulemans B, De Meirleir L, Nassogne MC, De Borchgrave V, et al. Treatment and long term outcome in West syndrome: the clinical reality. A multicentre follow up study. Seizure. 2010;19:159–64.CrossRefPubMedGoogle Scholar
  64. 64.
    Bitton JY, Demos M, Elkouby K, Connolly M, Weiss SK, Donner EJ, et al. Does treatment have an impact on incidence and risk factors for autism spectrum disorders in children with infantile spasms? Epilepsia. 2015;56:856–63.CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Johns Hopkins HospitalBaltimoreUSA
  2. 2.University of Colorado Denver, Anschutz Medical CampusChildren’s Hospital ColoradoAuroraUSA

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