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Latest American and European Updates on Infantile Spasms

  • Andrew L. Lux
Pediatric Neurology (D Nordli, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pediatric Neurology

Abstract

Infantile spasms remain a challenging condition to study and treat, and although they form the commonest epilepsy syndrome with onset in infancy, the challenge is broadened by the wide range of potential underlying causes. The field of study remains dynamic, with debates relating to case definitions and organising structures for classification of seizures and epilepsies in general, and a newly proposed genetic and biologic classification specifically for infantile spasms. There have been recent consensus statements, a Delphi process eliciting prioritised quality-of-care indicators, systematic reviews of treatment, and a survey of clinical practice in the USA. There is increasing evidence that longer duration of spasms is associated with poorer neurodevelopmental outcomes. It has taken many years to develop an animal model that reasonably represents infantile spasms, but there are now several animal models, and they are leading to innovative and valuable studies that suggest novel treatments.

Keywords

Infantile spasms West syndrome Infantile seizures Consensus statement Guidelines Epilepsy syndrome ACTH Vigabatrin Visual field loss Animal model Classification Aetiology Neurodevelopmental outcome 

Notes

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

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

  1. 1.
    •• Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51:676–85. This is a further initiative by the ILAE Commission on Classification and Terminology to develop concepts, definitions, clear terminology, and an overall classification and structure for the clinical management and design of studies for epilepsies.PubMedCrossRefGoogle Scholar
  2. 2.
    Caraballo RH, Ruggieri V, Gonzalez G, Cersósimo R, Gamboni B, Rey A, et al. Infantile spasms without hypsarrhythmia: a study of 16 cases. Seizure. 2011;20:197–202.PubMedCrossRefGoogle Scholar
  3. 3.
    •• Paciorkowski AR, Thio LL, Dobyns WB. Genetic and biologic classification of infantile spasms. Pediatr Neurol. 2011;45:355–67. This is a thorough and thoughtful review of genetic causes of infantile spasms, outlining how many of the newer genetic diagnoses are linked to key pathways of development in the central nervous system. This article also suggests models that might explain the pathogenesis of infantile spasms, with some emphasis on GABAergic gene regulation in the developing forebrain and abnormal expression of genes controlling synaptic molecules.PubMedCrossRefGoogle Scholar
  4. 4.
    Adachi M, Abe Y, Aoki Y, Matsubara Y. Epilepsy in RAS/MAPK syndrome: two cases of cardio-facio-cutaneous syndrome with epileptic encephalopathy and a literature review. Seizure. 2012;21:55–60.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Deprez L, Weckhuysen S, Holmgren P, Suls A, Van Dyck T, Goossens D, et al. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75:1159–65.PubMedCrossRefGoogle Scholar
  7. 7.
    Mirzaa GM, Paciorkowski AR, Smyser CD, Willing MC, Lind AC, Dobyns WB. The microcephaly-capillary malformation syndrome. Am J Med Genet A. 2011;155A:2080–7.PubMedGoogle Scholar
  8. 8.
    Striano P, Paravidino R, Sicca F, Chiurazzi P, Gimelli S, Coppola A, et al. West syndrome associated with 14q12 duplications harboring FOXG1. Neurology. 2011;76:1600–2.PubMedCrossRefGoogle Scholar
  9. 9.
    Tohyama J, Yamamoto T, Hosoki K, Nagasaki K, Akasaka N, Ohashi T, et al. West syndrome associated with mosaic duplication of FOXG1 in a patient with maternal uniparental disomy of chromosome 14. Am J Med Genet A. 2011;155:2584–8.CrossRefGoogle Scholar
  10. 10.
    Bahi-Buisson N, Eisermann M, Nivot S, Bellanné-Chantelot C, Dulac O, Bach N, et al. Infantile spasms as an epileptic feature of DEND syndrome associated with an activating mutation in the potassium adenosine triphosphate (ATP) channel, Kir6.2. J Child Neurol. 2007;22(9):1147–50.PubMedCrossRefGoogle Scholar
  11. 11.
    Coppola G, Grosso S, Verrotti A, D'Aniello A, Pascotto A. Simultaneous onset of infantile spasms in monozygotic twins. Pediatr Neurol. 2010;43:127–30.PubMedCrossRefGoogle Scholar
  12. 12.
    •• Kamien BA, Cardamone M, Lawson JA, Sachdev R. A genetic diagnostic approach to infantile epileptic encephalopathies. J Clin Neurosci. 2012;19:934–41. This is a practical and user-friendly review of the causes of infantile seizures, many aspects of which are directly applicable to the management of infantile spasms. The framework, which it is suggested forms an effective and efficient triage for patients presenting with infantile spasms, is based on the organisation of concepts and terminology described in [1].PubMedCrossRefGoogle Scholar
  13. 13.
    Gkampeta A, Pavlou E. Infantile spasms (West syndrome) in children with inborn errors of metabolism: a review of the literature. J Child Neurol. 2012;27:1295–301.PubMedCrossRefGoogle Scholar
  14. 14.
    • 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. This study reports a representative sample of causes of infantile spasms, reminding us that many of the specific causes are sufficiently frequent to facilitate stratification or studies that might detect consistent interactions (effect-modification) between cause and treatment intervention.PubMedCrossRefGoogle Scholar
  15. 15.
    Suleiman J, Brenner T, Gill D, Troedson C, Sinclair AJ, Brilot F, et al. Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies. Dev Med Child Neurol. 2011;53:1058–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Stockler S, Plecko B, Gospe SM, Coulter-Mackie M, Connolly M, van Karnebeek C, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab. 2011;104:48–60.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    • Autry AR, Trevathan E, Van Naarden Braun K, Yeargin-Allsopp M. Increased risk of death among children with Lennox-Gastaut syndrome and infantile spasms. J Child Neurol. 2010;25:441–7. This is an important follow-up on epidemiological outcomes from a cohort study in Atlanta.PubMedCrossRefGoogle Scholar
  19. 19.
    Eisermann MM, DeLaRaillère A, Dellatolas G, Tozzi E, Nabbout R, Dulac O, et al. Infantile spasms in Down syndrome—effects of delayed anticonvulsive treatment. Epilepsy Res. 2003;55:21–7.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    O'Callaghan FJ, Lux AL, Darke K, Edwards SW, Hancock E, Johnson AL, et al. 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. 2011;52:1359–64.PubMedCrossRefGoogle Scholar
  22. 22.
    • Auvin S, Hartman AL, Desnous B, Moreau AC, Alberti C, Delanoe C, et al. Diagnosis delay in West syndrome: Misdiagnosis and consequences. Eur J Pediatr. 2012;171:1695–701. This is the most recent of a series of studies suggesting that diagnostic delay is likely to be associated with poorer neurodevelopmental outcomes, aggregately if not for all individuals. Unfortunately, diagnostic delay remains common, particularly where initial presentation is to a primary care physician rather than a paediatrician.PubMedCrossRefGoogle Scholar
  23. 23.
    Napuri S, Le Gall E, Dulac O, Chaperon J, Riou F. Factors associated with treatment lag in infantile spasms. Dev Med Child Neurol. 2010;52:1164–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Partikian A, Mitchell WG. Neurodevelopmental and epilepsy outcomes in a North American cohort of patients with infantile spasms. J Child Neurol. 2010;25:423–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Vendrame M, Guilhoto LM, Loddenkemper T, Gregas M, Bourgeois BF, Kothare SV. Outcomes of epileptic spasms in patients aged less than 3 years: single-center United States experience. Pediatr Neurol. 2012;46:276–80.PubMedCrossRefGoogle Scholar
  26. 26.
    • Mytinger JR, Joshi S. The current evaluation and treatment of infantile spasms among members of the Child Neurology Society. J Child Neurol. 2012;27:1289–94. Despite the relatively low response rate, this is a useful survey that indicates a broad range of approaches to the management of infantile spasms and demonstrates the need for clearer consensus.PubMedCrossRefGoogle Scholar
  27. 27.
    •• 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. This presents a highly experienced group’s consensus on the management of infantile spasms with a basic outline of approaches to aetiologic investigation that is supplemented by [3, 12].PubMedCrossRefGoogle Scholar
  28. 28.
    Dulac O, Bast T, Dalla Bernardina B, Gaily E, Neville B. Infantile spasms: toward a selective diagnostic and therapeutic approach. Epilepsia. 2010;51(10):2218–9. author reply 2221.PubMedCrossRefGoogle Scholar
  29. 29.
    Statement of endorsement: Infantile spasms. Pediatrics 2012, 130:e1050.Google Scholar
  30. 30.
    •• Go CY, Mackay MT, Weiss SK, Stephens D, Adams-Webber T, Ashwal S, et al. 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. 2012;78:1974–80. This is an updated evidence-based guideline that is endorsed by influential professional bodies.PubMedCrossRefGoogle Scholar
  31. 31.
    Mackay MT, Weiss SK, Adams-Webber T, Ashwal S, Stephens D, Ballaban-Gill K, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004;62:1668–81.PubMedCrossRefGoogle Scholar
  32. 32.
    • Wang CJ, Jonas R, Fu CM, Ng CY, Douglass L. Quality-of-care indicators for infantile spasms. J Child Neurol. 2013;28(1):13–20. Given the paucity of high-class evidence for the optimal treatment of infantile spasms, this is an attempt to define pragmatic standards of care for infants with epileptic spasms.PubMedCrossRefGoogle Scholar
  33. 33.
    • Appleton RE, Freeman A, Cross JH. Diagnosis and management of the epilepsies in children: A summary of the partial update of the 2012 NICE epilepsy guideline. Arch Dis Child 2012.Google Scholar
  34. 34.
    • Arya R, Shinnar S, Glauser TA. Corticosteroids for the treatment of infantile spasms: a systematic review. J Child Neurol. 2012;27:1284–8. A systematic approach to reviewing the evidence on the relative efficacy of corticotropins and corticosteroids, and the relative efficacy of higher-dose and lower-dose regimens is presented.PubMedCrossRefGoogle Scholar
  35. 35.
    Mytinger JR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in treatment of infantile spasms with pulse methylprednisolone. J Child Neurol. 2010;25:948–53.PubMedCrossRefGoogle Scholar
  36. 36.
    Ben-Menachem E. Mechanism of action of vigabatrin: correcting misperceptions. Acta Neurol Scand. 2011;124(Suppl192):5–15.CrossRefGoogle Scholar
  37. 37.
    Lerner JT, Salamon N, Sankar R. Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms. Neuropsychiatr Dis Treat. 2010;6:731–40.PubMedGoogle Scholar
  38. 38.
    Heim MK, Gidal BE. Vigabatrin-associated retinal damage: potential biochemical mechanisms. Acta Neurol Scand. 2012;126:219–28.PubMedCrossRefGoogle Scholar
  39. 39.
    Good WV. Measuring field loss in children administered vigabatrin: a problem in search of a solution. J AAPOS. 2011;15:411–2.PubMedCrossRefGoogle Scholar
  40. 40.
    •• Sergott RC, Wheless JW, Smith MC, Westall CA, Kardon RH, Arnold A, et al. Evidence-based review of recommendations for visual function testing in patients treated with vigabatrin. Neuroophthalmology. 2010;34:20–35.CrossRefGoogle Scholar
  41. 41.
    McCoy B, Wright T, Weiss S, Go C, Westall CA. Electroretinogram changes in a pediatric population with epilepsy: is vigabatrin acting alone? J Child Neurol. 2011;26:729–33.PubMedCrossRefGoogle Scholar
  42. 42.
    • Jammoul F, Dégardin J, Pain D, Gondouin P, Simonutti M, Dubus E, et al. Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats. Mol Cell Neurosci. 2010;43:414–21. Evidence from animal studies is presented that suggests a potential role of taurine in potentiating or ameliorating risks of visual field losses in association with vigabatrin.PubMedCrossRefGoogle Scholar
  43. 43.
    Froger N, Cadetti L, Lorach H, Martins J, Bemelmans AP, Dubus E, et al. Taurine provides neuroprotection against retinal ganglion cell degeneration. PLoS One. 2012;7:e42017.PubMedCrossRefGoogle Scholar
  44. 44.
    • Plant GT, Sergott RC. Understanding and interpreting vision safety issues with vigabatrin therapy. Acta Neurol Scand. 2011;124(Suppl192):57–71.CrossRefGoogle Scholar
  45. 45.
    Pearl PL, Vezina LG, Saneto RP, McCarter R, Molloy-Wells E, Heffron A, et al. Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia. 2009;50(2):184–94.PubMedCrossRefGoogle Scholar
  46. 46.
    •• Pellock JM, Faught E, Sergott RC, Shields WD, Burkhart GA, Krauss GL, et al. Registry initiated to characterize vision loss associated with vigabatrin therapy. Epilepsy Behav. 2011;22:710–7. This describes an important initiative designed to provide reliable data to inform benefit–risk analyses for treatment with vigabatrin.PubMedCrossRefGoogle Scholar
  47. 47.
    Hong AM, Turner Z, Hamdy RF, Kossoff EH. Infantile spasms treated with the ketogenic diet: prospective single-center experience in 104 consecutive infants. Epilepsia. 2010;51:1403–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Numis AL, Yellen MB, Chu-Shore CJ, Pfeifer HH, Thiele EA. The relationship of ketosis and growth to the efficacy of the ketogenic diet in infantile spasms. Epilepsy Res. 2011;96:172–5.PubMedCrossRefGoogle Scholar
  49. 49.
    • 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. A consensus is established on case definitions and preferred outcome measures for clinical studies of infantile spasms, on the basis of a Delphi process involving 30 participants from 15 countries.PubMedCrossRefGoogle Scholar
  50. 50.
    Olson HE, Loddenkemper T, Vendrame M, Poduri A, Takeoka M, Bergin AM, et al. Rufinamide for the treatment of epileptic spasms. Epilepsy Behav. 2011;20:344–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Chhun S, Troude P, Villeneuve N, Soufflet C, Napuri S, Motte J, et al. A prospective open-labeled trial with levetiracetam in pediatric epilepsy syndromes: continuous spikes and waves during sleep is definitely a target. Seizure. 2011;20:320–5.PubMedCrossRefGoogle Scholar
  52. 52.
    Veerapandiyan A, Singh P, Mikati MA. Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures. Epileptic Disord. 2012;14:99–103.PubMedGoogle Scholar
  53. 53.
    Chugani HT, Asano E, Sood S. Infantile spasms: who are the ideal surgical candidates? Epilepsia. 2010;51(Suppl1):94–6.PubMedCrossRefGoogle Scholar
  54. 54.
    • Stafstrom CE. Infantile spasms: a critical review of emerging animal models. Epilepsy Curr. 2009;9:75–81. This is a brief review of animal models with a critical appraisal of the attributes required for a valid and useful model.PubMedCrossRefGoogle Scholar
  55. 55.
    Velísek L, Chachua T, Yum MS, Poon KL, Velísková J. Model of cryptogenic infantile spasms after prenatal corticosteroid priming. Epilepsia. 2010;51(Suppl3):145–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Chachua T, Yum MS, Velíšková J, Velíšek L. Validation of the rat model of cryptogenic infantile spasms. Epilepsia. 2011;52:1666–77.PubMedCrossRefGoogle Scholar
  57. 57.
    Frost JD, Lee CL, Hrachovy RA, Swann JW. High frequency EEG activity associated with ictal events in an animal model of infantile spasms. Epilepsia. 2011;52:53–62.PubMedCrossRefGoogle Scholar
  58. 58.
    Cortez MA, Shen L, Wu Y, Aleem IS, Trepanier CH, Sadeghnia HR, et al. Infantile spasms and Down syndrome: a new animal model. Pediatr Res. 2009;65:499–503.PubMedCrossRefGoogle Scholar
  59. 59.
    Chudomelova L, Scantlebury MH, Raffo E, Coppola A, Betancourth D, Galanopoulou AS. Modeling new therapies for infantile spasms. Epilepsia. 2010;51(Suppl3):27–33.PubMedCrossRefGoogle Scholar
  60. 60.
    Scantlebury MH, Galanopoulou AS, Chudomelova L, Raffo E, Betancourth D, Moshé SL. A model of symptomatic infantile spasms syndrome. Neurobiol Dis. 2010;37:604–12.PubMedCrossRefGoogle Scholar
  61. 61.
    • Raffo E, Coppola A, Ono T, Briggs SW, Galanopoulou AS. A pulse rapamycin therapy for infantile spasms and associated cognitive decline. Neurobiol Dis. 2011;43:322–9. Using one of the new animal models to investigate whether a biologically plausible but innovative approach to treatment has sufficient empirical support to merit further investigation and potential application to treatment in humans.PubMedCrossRefGoogle Scholar
  62. 62.
    Fat MJ, Doja A, Barrowman N, Sell E. YouTube videos as a teaching tool and patient resource for infantile spasms. J Child Neurol. 2011;26:804–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Jobst BC. Infantile spasms: the devil is in the details, but do we see the forest for the trees? Epilepsy Curr. 2011;11:151–2.PubMedCrossRefGoogle Scholar
  64. 64.
    Mohamed BP, Scott RC, Desai N, Gutta P, Patil S. Seizure outcome in infantile spasms—a retrospective study. Epilepsia. 2011;52:746–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Paediatric NeurologyBristol Royal Hospital for ChildrenBristolUK

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