CC BY-NC-ND 4.0 · International Journal of Epilepsy 2020; 06(01): 04-14
DOI: 10.1055/s-0040-1708562
Review Article

Management of Infantile Spasms: An Updated Review

Mary Iype
1   Department of Pediatric Neurology, Government Medical College, Kerala, India
,
Kiren George Koshy
2   Department of General Medicine, Government Medical College Trivandrum, Trivandrum, India
› Author Affiliations

Abstract

Infantile spasms remain the most challenging of the epileptic encephalopathies of childhood. Infantile spasms are classified as an epileptic encephalopathy, as the adverse cognitive and behavioral burden of the condition is out of proportion to the burden one would expect from the underlying etiology or the accompanying magnetic resonance imaging. The ictal and interictal electroencephalographic (EEG) activity is presumed to contribute to the progressive cerebral dysfunction. In many of these children, the underlying etiology also contributes to the severe mental subnormality and autistic behavior. Though it is the syndromic approach that guides the pediatric epileptologist, it is best to keep in mind that one syndrome may evolve into another in infancy and early childhood. A baby with Ohtahara syndrome may, after 2 to 7 months, begin to have spasms. Lennox-Gastaut syndrome with its typical seizure types and EEG may evolve in a child with infantile spasms.

The unique modalities used in the treatment of infantile spasms make early recognition important. It is, however, also of paramount importance to make an etiological diagnosis as the underlying etiology may be eminently treatable. The treating physician cannot abandon them as wholly “intractable” epilepsy. The excellent response to treatment in the few who just cannot be defined or accurately predicted drives the physician to exercise his brain. Use of the two well-accepted modalities of treatment; vigabatrin and adrenocorticotrophic hormone singly or in combination, oral steroids in high dose, ketogenic diet, the conventional antiepileptic medications, and strategies to target the basic cause have been tried out by various clinicians. Here, we have made an attempt to collate evidence and describe the progress in the management of infantile spasms.



Publication History

Article published online:
27 April 2020

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  • References

  • 1 Fisher RS, Cross JH, D’Souza C. et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia 2017; 58 (04) 531-542
  • 2 Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol 1991; 6 (04) 355-364
  • 3 Osborne JP, Lux AL, Edwards SW. 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 (10) 2168-2174
  • 4 Michaud JL, Lachance M, Hamdan FF. et al. The genetic landscape of infantile spasms. Hum Mol Genet 2014; 23 (18) 4846-4858
  • 5 Weaving LS, Christodoulou J, Williamson SL. et al. Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation. Am J Hum Genet 2004; 75 (06) 1079-1093
  • 6 Kalscheuer VM, Tao J, Donnelly A. et al. Disruption of the serine/threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation. Am J Hum Genet 2003; 72 (06) 1401-1411
  • 7 Lee HH, Hur YJ. Glucose transport 1 deficiency presenting as infantile spasms with a mutation identified in exon 9 of SLC2A1. Korean J Pediatr 2016; 59 (Suppl. 01) S29-S31
  • 8 Iype M, Saradakutty G, Kunju PA. et al. Infantile spasms: a prognostic evaluation. Ann Indian Acad Neurol 2016; 19 (02) 228-235
  • 9 O’Callaghan FJ, Lux AL, Darke K. 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 (07) 1359-1364
  • 10 Wirrell EC, Shellhaas RA, Joshi C, Keator C, Kumar S, Mitchell WG. Pediatric Epilepsy Research Consortium. How should children with West syndrome be efficiently and accurately investigated? Results from the National Infantile Spasms Consortium. Epilepsia 2015; 56 (04) 617-625
  • 11 Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2013; (06) CD001770
  • 12 Riikonen R. Recent advances in the pharmacotherapy of infantile spasms. CNS Drugs 2014; 28 (04) 279-290
  • 13 Hamano S, Yamashita S, Tanaka M, Yoshinari S, Minamitani M, Eto Y. Therapeutic efficacy and adverse effects of adrenocorticotropic hormone therapy in west syndrome: differences in dosage of adrenocorticotropic hormone, onset of age, and cause. J Pediatr 2006; 148 (04) 485-488
  • 14 Hrachovy RA, Frost Jr JD, Glaze DG. High-dose, long-duration versus low-dose, short-duration corticotropin therapy for infantile spasms. J Pediatr 1994; 124 (5 Pt 1) 803-806
  • 15 Yanagaki S, Oguni H, Hayashi K. et al. A comparative study of high-dose and low-dose ACTH therapy for West syndrome. Brain Dev 1999; 21 (07) 461-467
  • 16 Go CY, Mackay MT, Weiss SK. et al. Child Neurology Society, American Academy of Neurology. 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 (24) 1974-1980
  • 17 Walker SD, Kälviäinen R. Non-vision adverse events with vigabatrin therapy. Acta Neurol Scand Suppl 2011; 124 (192) 72-82
  • 18 Krauss GL, Johnson MA, Miller NR. Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings. Neurology 1998; 50 (03) 614-618
  • 19 Butler WH, Ford GP, Newberne JW. A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-Hooded rats. Toxicol Pathol 1987; 15 (02) 143-148
  • 20 Lux AL, Edwards SW, Hancock E. et al. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet 2004; 364 (9447): 1773-1778
  • 21 Lux AL, Edwards SW, Hancock E. et al. United Kingdom Infantile Spasms Study. 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 (11) 712-717
  • 22 Darke K, Edwards SW, Hancock E. et al. trial steering committee on behalf of participating investigators. 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 (05) 382-386
  • 23 Chiron C, Dumas C, Jambaqué I, Mumford J, Dulac O. Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 1997; 26 (02) 389-395
  • 24 Ahmed R. Comparative study of corticotrophin vs. vigabatrin therapy in infantile spasm. Pak J Med Sci 2007; 23 (01) 141-144
  • 25 Elterman RD, Shields WD, Mansfield KA, Nakagawa J. US Infantile Spasms Vigabatrin Study Group. Randomized trial of vigabatrin in patients with infantile spasms. Neurology 2001; 57 (08) 1416-1421
  • 26 Elterman RD, Collins SD, Shields D, Mansfield KA, Nakagawa J. Efficacy of vigabatrin in subjects with infantile spasms. Epilepsia 2005; 46 (S8) 142
  • 27 Elterman RD, Shields WD, Bittman RM, Torri SA, Sagar SM, Collins SD. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol 2010; 25 (11) 1340-1347
  • 28 Sergott RC, Wheless JW, Smith MC. et al. Evidence-based review of recommendations for visual function testing in patients treated with vigabatrin. Neuroophthalmology 2010; 34 (01) 20-35
  • 29 O’Callaghan FJ, Edwards SW, Alber FD. et al. participating investigators. 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 (01) 33-42
  • 30 Wanigasinghe J, Arambepola C, Ranganathan SS, Sumanasena S. Randomized, single-blind, parallel clinical efficacy trial of oral prednisolone versus intramuscular corticotrophin: a 12 month assessment of spasm control in West Syndrome. Pediatr Neurol 2017; 76: 14-19
  • 31 Hussain SA, Shinnar S, Kwong G. et al. Treatment of infantile spasms with very high dose prednisolone before high dose ACTH. Epilepsia 2014; 55 (01) 103-107
  • 32 Chellamuthu P, Sharma S, Jain P, Kaushik JS, Seth A, Aneja S. High dose (4 mg/kg/day) versus usual dose (2 mg/kg/day) oral prednisolone for treatment of infantile spasms: an open-label, randomized controlled trial. Epilepsy Res 2014; 108 (08) 1378-1384
  • 33 Kossoff EH, Hartman AL, Rubenstein JE, Vining EP. High-dose oral prednisolone for infantile spasms: an effective and less expensive alternative to ACTH. Epilepsy Behav 2009; 14 (04) 674-676
  • 34 Knupp KG, Coryell J, Nickels KC. et al. Pediatric Epilepsy Research Consortium. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol 2016; 79 (03) 475-484
  • 35 Ware TL, Mackay MT, Harvey AS, Freeman JL. Epileptic spasms: experience with a high-dose oral corticosteroid protocol. J Paediatr Child Health 2012; 48 (11) 985-989
  • 36 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 (08) 1403-1407
  • 37 Kayyali HR, Gustafson M, Myers T, Thompson L, Williams M, Abdelmoity A. Ketogenic diet efficacy in the treatment of intractable epileptic spasms. Pediatr Neurol 2014; 50 (03) 224-227
  • 38 Kang HC, Lee YJ, Lee JS. et al. Comparison of short- versus long-term ketogenic diet for intractable infantile spasms. Epilepsia 2011; 52 (04) 781-787
  • 39 Wang D, Pascual JM, Yang H. et al. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol 2005; 57 (01) 111-118
  • 40 Kossoff EH, Thiele EA, Pfeifer HH, McGrogan JR, Freeman JM. Tuberous sclerosis complex and the ketogenic diet. Epilepsia 2005; 46 (10) 1684-1686
  • 41 Kossoff EH, Zupec-Kania BA, Auvin S. et al. Charlie Foundation, Matthew’s Friends, Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 2018; 3 (02) 175-192
  • 42 Dressler A, Trimmel-Schwahofer P, Reithofer E. et al. The ketogenic diet in infants–advantages of early use. Epilepsy Res 2015; 116: 53-58
  • 43 Dressler A, Benninger F, Trimmel-Schwahofer P. et al. Efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone for infantile spasms: a single-center parallel-cohort randomized controlled trial. Epilepsia 2019; 60 (03) 441-451
  • 44 Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet in infantile spasms refractory to first-line treatment. Seizure 2012; 21 (01) 45-48
  • 45 Sharma S, Goel S, Jain P, Agarwala A, Aneja S. Evaluation of a simplified modified Atkins diet for use by parents with low levels of literacy in children with refractory epilepsy: a randomized controlled trial. Epilepsy Res 2016; 127: 152-159
  • 46 Hussain SA, Shin JH, Shih EJ. et al. Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms. Seizure 2016; 35: 59-64
  • 47 Pietz J, Benninger C, Schäfer H, Sontheimer D, Mittermaier G, Rating D. Treatment of infantile spasms with high-dosage vitamin B6. Epilepsia 1993; 34 (04) 757-763
  • 48 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 (02) 322-329
  • 49 Galanopoulou AS, Gorter JA, Cepeda C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target. Epilepsia 2012; 53 (07) 1119-1130
  • 50 Li M, Zhou Y, Chen C. et al. Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis. Orphanet J Rare Dis 2019; 14 (01) 39
  • 51 Curatolo P, Bjørnvold M, Dill PE. et al. The role of mTOR inhibitors in the treatment of patients with tuberous sclerosis complex: evidence- based and expert opinions. Drugs 2016; 76 (05) 551-565
  • 52 Alrifai MT, AlShaya MA, Abulaban A, Alfadhel M. Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center. Pediatr Neurol 2014; 51 (03) 390-397
  • 53 Salar S, Moshé SL, Galanopoulou AS. Metabolic etiologies in West syndrome. Epilepsia Open 2018; 3 (02) 134-166
  • 54 Fukuoka M, Kuki I, Kawawaki H. et al. Quinidine therapy for West syndrome with KCNTI mutation: a case report. Brain Dev 2017; 39 (01) 80-83
  • 55 Korman SH, Wexler ID, Gutman A, Rolland MO, Kanno J, Kure S. Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation. Ann Neurol 2006; 59 (02) 411-415
  • 56 Sfaello I, Castelnau P, Blanc N, Ogier H, Evrard P, Arzimanoglou A. Infantile spasms and Menkes disease. Epileptic Disord 2000; 2 (04) 227-230
  • 57 Dunin-Wasowicz D, Kasprzyk-Obara J, Jurkiewicz E, Kapusta M, Milewska-Bobula B. Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatment. Dev Med Child Neurol 2007; 49 (09) 684-692
  • 58 Riikonen R, Donner M. ACTH therapy in infantile spasms: side effects. Arch Dis Child 1980; 55 (09) 664-672
  • 59 Kwon YS, Jun YH, Hong YJ, Son BK. Topiramate monotherapy in infantile spasm. Yonsei Med J 2006; 47 (04) 498-504
  • 60 Lee GM, Lee KS, Lee EH, Chung S. Short term outcomes of topiramate monotherapy as a first-line treatment in newly diagnosed West syndrome. Korean J Pediatr 2011; 54 (09) 380-384
  • 61 Knupp KG, Leister E, Coryell J. et al. Pediatric Epilepsy Research Consortium. Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort. Epilepsia 2016; 57 (11) 1834-1842
  • 62 Jones K, Snead OC II, Boyd J, Go C. Adrenocorticotropic hormone versus prednisolone in the treatment of infantile spasms post vigabatrin failure. J Child Neurol 2015; 30 (05) 595-600
  • 63 Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics 1996; 97 (03) 375-379
  • 64 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 (03) 255-262
  • 65 Inui T, Kobayashi T, Kobayashi S. et al. Efficacy of long term weekly ACTH therapy for intractable epilepsy. Brain Dev 2015; 37 (04) 449-454
  • 66 O’Callaghan FJK, Edwards SW, Alber FD. et al. International Collaborative Infantile Spasms Study (ICISS) investigators. Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial. Lancet Child Adolesc Health 2018; 2 (10) 715-725
  • 67 Hussain SA. Treatment of infantile spasms. Epilepsia Open 2018; 3 (Suppl, Suppl 2) 143-154
  • 68 Mytinger JR, Quigg M, Taft WC, Buck ML, Rust RS. Outcomes in treatment of infantile spasms with pulse methylprednisolone. J Child Neurol 2010; 25 (08) 948-953
  • 69 Hassanzadeh A Rad, Aminzadeh V. Infantile spasms treated with intravenous methylprednisolone pulse. Iran J Child Neurol 2017; 11 (02) 8-12
  • 70 Millichap JG, Millichap JJ. Prediction of infantile spasms recurrence after ACTH therapy. Pediatr Neurol Briefs 2015; 29 (12) 93
  • 71 Yamada K, Toribe Y, Kimizu T. et al. Predictive value of EEG findings at control of epileptic spasms for seizure relapse in patients with West syndrome. Seizure 2014; 23 (09) 703-707
  • 72 Khatami A, Sell E, Aggag M, Miller E. Brain MRI findings in infantile spasm: outcome correlations in a patient cohort. Open J Med Imag 2016; 6 (03) 80-92
  • 73 Thomas B, Al Dossary N, Widjaja E. MRI of childhood epilepsy due to inborn errors of metabolism. Am J Roentgenol 2010; 194 (05) W367-74
  • 74 Sakaguchi Y, Kidokoro H, Ogawa C. et al. Longitudinal findings of MRI and PET in West Syndrome with subtle focal cortical dysplasia. Am J Neuroradiol 2018; 39 (10) 1932-1937
  • 75 Chugani HT, Ilyas M, Kumar A. et al. Surgical treatment for refractory epileptic spasms: The Detroit series. Epilepsia 2015; 56 (12) 1941-1949
  • 76 Chugani HT, Luat AF, Kumar A, Govindan R, Pawlik K, Asano E. α-[11C]-Methyl-L-tryptophan–PET in 191 patients with tuberous sclerosis complex. Neurology 2013; 81 (07) 674-680
  • 77 Eltze CM, Chong WK, Bhate S, Harding B, Neville BG, Cross JH. Taylor-type focal cortical dysplasia in infants: some MRI lesions almost disappear with maturation of myelination. Epilepsia 2005; 46 (12) 1988-1992
  • 78 Chipaux M, Dorfmüller G, Fohlen M. et al. Refractory spasms of focal onset—a potentially curable disease that should lead to rapid surgical evaluation. Seizure 2017; 51: 163-170
  • 79 Nabbout R, Belousova E, Benedik MP. et al. TOSCA Consortium and TOSCA Investigators. Epilepsy in tuberous sclerosis complex: findings from the TOSCA study. Epilepsia Open 2018; 4 (01) 73-84
  • 80 Cobourn K, Fayed I, Keating RF, Oluigbo CO. Early outcomes of stereoelectroencephalography followed by MR-guided laser interstitial thermal therapy: a paradigm for minimally invasive epilepsy surgery. Neurosurg Focus 2018; 45 (03) E8 DOI: 10.3171/2018.6.
  • 81 Peacock WJ, Wehby-Grant MC, Shields WD. et al. Hemispherectomy for intractable seizures in children: a report of 58 cases. Childs Nerv Syst 1996; 12 (07) 376-384
  • 82 Loddenkemper T, Holland KD, Stanford LD, Kotagal P, Bingaman W, Wyllie E. Developmental outcome after epilepsy surgery in infancy. Pediatrics 2007; 119 (05) 930-935
  • 83 Jonas R, Asarnow RF, LoPresti C. et al. Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms. Neurology 2005; 64 (04) 746-750
  • 84 Gulati S, Jain P, Kannan L, Sehgal R, Chakrabarty B. The clinical characteristics and treatment response in children with West syndrome in a developing country: a retrospective case record analysis. J Child Neurol 2015; 30 (11) 1440-1447
  • 85 Khreisat WH. Clinical profile of infants with hypsarrhythmia. Acta Inform Med 2011; 19 (03) 149-152
  • 86 Kulsoom S, Ibrahim SH, Jafri SK, Moorani KN, Anjum M. Infantile Spasms: Clinical profile and treatment outcomes. Pak J Med Sci 2018; 34 (06) 1424-1428
  • 87 Keshave A, Yende-Zuma N, Mubaiwa L, Adhikari M. The clinical profile and outcome of children with West syndrome in KwaZulu-Natal Province, South Africa: a 10-year retrospective review. S Afr J Child Health 2017; 11 (03) 135-140 DOI: 10.7196/SAJCH.2017.v11i3.1300.