Infantile Spasm (West Syndrome)
- Author: Tracy A Glauser, MD; Chief Editor: Amy Kao, MD more...
West syndrome is a severe epilepsy syndrome composed of the triad of infantile spasms, an interictal electroencephalogram (EEG) pattern termed hypsarrhythmia, and mental retardation, although the diagnosis can be made even if 1 of the 3 elements is missing (according to the international classification). (See Presentation and Workup.)
West syndrome is an age-dependent expression of a damaged brain, and most patients with infantile spasms have some degree of developmental delay. The term infantile spasm has been used to describe the seizure type, the epilepsy syndrome, or both. In this article, the term infantile spasm is synonymous with West syndrome. (See Prognosis and Presentation.)
The syndrome's namesake, Dr W J West, gave the first detailed description of infantile spasms, which occurred in his own child. In a letter to the editor of The Lancet in 1841, West described the events as "bobbings" that "cause a complete heaving of the head forward towards his knees, and then immediately relaxing into the upright position … [T]hese bowings and relaxings would be repeated alternately at intervals of a few seconds, and repeated from 10 to 20 or more times at each attack, which would not continue more than 2 or 3 minutes; he sometimes has 2, 3 or more attacks in the day."
This detailed clinical description was followed approximately 100 years later by the report of the typical interictal EEG pattern termed hypsarrhythmia. (See Workup.)
The eponym West syndrome was created in the early 1960s by Drs. Gastaut, Poirier, and Pampiglione.
Conditions to consider in the differential diagnosis of West syndrome include the following:
Epilepsy in children with mental retardation
Benign myoclonus of early infancy
Infantile spasms are believed to reflect abnormal interactions between the cortex and brainstem structures. Focal lesions early in life may secondarily affect other sites in the brain, and hypsarrhythmia may represent this abnormal activity arising from multiple brain sites. The frequent onset of infantile spasms in infancy suggests that an immature central nervous system (CNS) may be important in the syndrome’s pathogenesis.
The brain-adrenal axis also may be involved. One theory states that the effect of different stressors in the immature brain produces an abnormal, excessive secretion of corticotropin-releasing hormone (CRH), causing spasms. The clinical response to adrenocorticotropic hormone (ACTH) and glucocorticoids can be explained by the suppression of CRH production.
An existing animal model of infantile spasm may provide better insight into the pathogenesis of this disorder. The model uses a sodium channel blocker, tetrodotoxin (TTX), that is infused into the hippocampus of rodents. This infusion has produced clinical spasms in rats with electrographic findings similar to those seen in human infantile spasms.
Infantile spasms can be classified according to their suspected etiology as symptomatic, cryptogenic, or idiopathic.
Patients are diagnosed with symptomatic infantile spasms if an identifiable factor is responsible for the syndrome. Virtually any disorder that can produce brain damage can be associated with infantile spasms. The list of etiologies can be subdivided into prenatal disorders, perinatal disorders, and postnatal disorders.
Prenatal disorders associated with infantile spasms include the following:
Perinatal disorders giving rise to infantile spasms include the following:
Postnatal disorders associated with infantile spasms include the following:
Maple syrup urine disease
Evaluating children with infantile spasms for possible tuberous sclerosis is critical, as this is the single most common disorder, accounting for 10-30% of prenatal cases of infantile spasm. Tuberosis sclerosis is an autosomally dominant inherited disease with variable manifestations, including cardiac tumors, kidney tumors, cutaneous malformations such as ash-leaf hypopigmented lesions, and seizures.
Of patients with infantile spasms, 70-75% have symptomatic epilepsy; this percentage depends on the degree of sophistication of diagnostic studies. (The development of more exquisite neurodiagnostic techniques is expected to alter the relative proportion of symptomatic, cryptogenic, and idiopathic cases that has been reported.)
Patients have cryptogenic infantile spasms if no cause is identified but a cause is suspected and the epilepsy is presumed to be symptomatic.
The proportion of cryptogenic cases varies from 8-42%. This wide range may be related to variations in the definition of the term cryptogenic and the age of patients at diagnosis, since assessment of developmental level in early infancy is difficult.
Patients may be considered to have idiopathic infantile spasms if normal psychomotor development occurs prior to the onset of symptoms, no underlying disorders or definite presumptive causes are present, and no neurologic or neuroradiologic abnormalities exist. Some investigators use the terms idiopathic and cryptogenic interchangeably. The percentage of idiopathic cases reportedly is 9-14%.
There has been an increased understanding of the role of genetic defects in the etiology of infantile spasms. Two specific genetic defects have a phenotypic presentation similar to that of the early onset of infantile spasms. The first is an abnormality in the short arm of chromosome X. The gene ARX is associated with a wide variety of structural abnormalities and early onset infantile spasms. The second abnormality is in the cyclin-dependent kinase-like protein 5 (CDKL5) and has similar phenotypic presentations to those of ARX mutations.
Occurrence in the United States
Infantile spasm constitutes 2% of childhood epilepsies but 25% of epilepsy with onset in the first year of life. The rate of infantile spasm is estimated to be 2.5-6.0 cases per 10,000 live births. Its prevalence rate is 1.5-2.0 cases per 10,000 children aged 10 years or younger.
Infantile spasm occurs in 0.05 (Estonia) to 0.41 (Oulu, Finland) of 1000 live births and in 1.4% (Estonia), 4.2% (Odense, Denmark), and 7.6% (Tampere, Finland) of children with epilepsy.
Sex- and age-related demographics
Although males are affected by infantile spasm slightly more often than females, no significant gender difference is noted in infantile spasm. Ninety percent of infantile spasms begin in infants younger than 12 months. Peak onset is at age 4-6 months.
The long-term overall prognosis for patients with infantile spasm is poor and is related directly to the condition’s etiology.[7, 8] Infants with idiopathic West syndrome have a better prognosis than do infants with symptomatic West syndrome. Only 14% of infants with symptomatic West syndrome have normal or borderline-normal cognitive development, compared with 28-50% of infants with idiopathic West syndrome. Mental retardation is severe in 70% of patients, often with psychiatric problems such as autistic features or hyperactivity.
Infrequently, spasms may persist in adulthood. It has been found that 50-70% of patients develop other seizure types and that 18-50% of patients will develop Lennox-Gastaut syndrome or some other form of symptomatic generalized epilepsy.[6, 9]
Subsets of patients among the symptomatic West syndrome group seem to have a better prognosis. A retrospective study of 17 children with trisomy 21 and infantile spasms found that 13 of 16 survivors were seizure free for more than 1 year and that 10 patients were no longer taking anticonvulsants.
A study of 15 children with neurofibromatosis type 1 and infantile spasms also reported a relatively benign seizure and cognitive outcome.
Favorable prognostic factors also include the following:
Cryptogenic or idiopathic etiology
Age of onset of over 4 months
Absence of atypical spasms and partial seizures
Absence of asymmetrical EEG abnormalities
Short time from onset to treatment
Early, sustained response to treatment
Infants with symptomatic infantile spasms have been shown to be at higher risk for the development of autism spectrum disorders, compared with those infants with cryptogenic or idiopathic spasms.[10, 11]
The premature death rate for infantile spasm ranges from 5-31%. The upper limit comes from a study of 214 Finnish children with a history of infantile spasms who were followed for a mean period of 25 years (range, 20-30 y). Most of the deaths (61%) occurred at or before age 10 years, while only 10% occurred after age 20 years.
Pies NJ, Beardsmore CW. West & West syndrome--a historical sketch about the eponymous doctor, his work and his family. Brain Dev. 2003 Mar. 25(2):84-101. [Medline].
West WJ. Infantile spasm. Lancet. 1841. 1:724.
Wang J, Wang J, Zhang Y, Yang G, Shang AJ, Zou LP. Proteomic analysis on infantile spasm and prenatal stress. Epilepsy Res. 2014 Sep. 108(7):1174-83. [Medline].
Stafstrom CE. Animal models of infantile spasms: is the holy grail finally in sight?. Epilepsy Curr. 2008 Sep-Oct. 8(5):131-3. [Medline].
Zupanc ML. Infantile spasms. Expert Opin Pharmacother. 2003 Nov. 4(11):2039-48. [Medline].
Karvelas G, Lortie A, Scantlebury MH, Duy PT, Cossette P, Carmant L. A retrospective study on aetiology based outcome of infantile spasms. Seizure. 2009 Apr. 18(3):197-201. [Medline].
Lux AL, Osborne JP. The influence of etiology upon ictal semiology, treatment decisions and long-term outcomes in infantile spasms and West syndrome. Epilepsy Res. 2006 Aug. 70 Suppl 1:S77-86. [Medline].
Goh S, Kwiatkowski DJ, Dorer DJ. Infantile spasms and intellectual outcomes in children with tuberous sclerosis complex. Neurology. 2005 Jul 26. 65(2):235-8. [Medline].
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 Sep. 22(9):1102-7. [Medline].
Saemundsen E, Ludvigsson P, Rafnsson V. Risk of autism spectrum disorders after infantile spasms: a population-based study nested in a cohort with seizures in the first year of life. Epilepsia. 2008 Nov. 49(11):1865-70. [Medline].
Endoh F, Yoshinaga H, Ishizaki Y, Oka M, Kobayashi K, Ohtsuka Y. Abnormal fast activity before the onset of West syndrome. Neuropediatrics. 2011 Feb. 42(2):51-4. [Medline].
Parisi P, Bombardieri R, Curatolo P. Current role of vigabatrin in infantile spasms. Eur J Paediatr Neurol. 2007 Nov. 11(6):331-6. [Medline].
Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007 Dec. 9(4):353-412. [Medline].
Peltzer B, Alonso WD, Porter BE. Topiramate and adrenocorticotropic hormone (ACTH) as initial treatment for infantile spasms. J Child Neurol. 2009 Apr. 24(4):400-5. [Medline].
Caraballo R, Vaccarezza M, Cersósimo R, Rios V, Soraru A, Arroyo H, et al. Long-term follow-up of the ketogenic diet for refractory epilepsy: multicenter Argentinean experience in 216 pediatric patients. Seizure. 2011 Oct. 20(8):640-5. [Medline].
Eun SH, Kang HC, Kim DW, Kim HD. Ketogenic diet for treatment of infantile spasms. Brain Dev. 2006 Oct. 28(9):566-71. [Medline].
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 Sep. 49(9):1504-9. [Medline].
Baram TZ, Mitchell WG, Tournay A, et al. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996 Mar. 97(3):375-9. [Medline].
Mackay M, Weiss S, Snead OC. Treatment of infantile spasms: an evidence-based approach. Int Rev Neurobiol. 2002. 49:157-84. [Medline].
Kondo Y, Okumura A, Watanabe K. Comparison of two low dose ACTH therapies for West syndrome: their efficacy and side effect. Brain Dev. 2005 Aug. 27(5):326-30. [Medline].
Hrachovy RA, Frost JD Jr, Kellaway P, et al. Double-blind study of ACTH vs prednisone therapy in infantile spasms. J Pediatr. 1983 Oct. 103(4):641-5. [Medline].
Kivity S, Lerman P, Ariel R. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia. 2004 Mar. 45(3):255-62. [Medline].
Aicardi J, Mumford JP, Dumas C, et al. Vigabatrin as initial therapy for infantile spasms: a European retrospective survey. Sabril IS Investigator and Peer Review Groups. Epilepsia. 1996 Jul. 37(7):638-42. [Medline].
Riikonen RS. Favourable prognostic factors with infantile spasms. Eur J Paediatr Neurol. 2009 Apr 10. [Medline].
Appleton RE, Peters AC, Mumford JP, et al. Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia. 1999 Nov. 40(11):1627-33. [Medline].
Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol. 1999 Feb. 14(2):71-4. [Medline].
Fejerman N, Cersosimo R, Caraballo R, et al. Vigabatrin as a first-choice drug in the treatment of West syndrome. J Child Neurol. 2000 Mar. 15(3):161-5. [Medline].
Nielsen JC, Kowalski KG, Karim A, Patel M, Wesche DL, Tolbert D. Population Pharmacokinetics Analysis of Vigabatrin in Adults and Children with Epilepsy and Children with Infantile Spasms. Clin Pharmacokinet. 2014 Aug 30. [Medline].
Blennow G, Starck L. High dose B6 treatment in infantile spasms. Neuropediatrics. 1986 Feb. 17(1):7-10. [Medline].
Pietz J, Benninger C, Schafer H, et al. Treatment of infantile spasms with high-dosage vitamin B6. Epilepsia. 1993 Jul-Aug. 34(4):757-63. [Medline].
Ito M, Seki T, Takuma Y. Current therapy for West syndrome in Japan. J Child Neurol. 2000 Jun. 15(6):424-8. [Medline].
Debus OM, Kurlemann G. Sulthiame in the primary therapy of West syndrome: a randomized double-blind placebo-controlled add-on trial on baseline pyridoxine medication. Epilepsia. 2004 Feb. 45(2):103-8. [Medline].
Veggiotti P, Cieuta C, Rex E, et al. Lamotrigine in infantile spasms [letter]. Lancet. 1994 Nov 12. 344(8933):1375-6. [Medline].
Cianchetti C, Pruna D, Coppola G. Low-dose lamotrigine in West syndrome. Epilepsy Res. 2002 Sep. 51(1-2):199-200. [Medline].
Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms. Epilepsia. 1998 Dec. 39(12):1324-8. [Medline].
Hosain SA, Merchant S, Solomon GE, Chutorian A. Topiramate for the treatment of infantile spasms. J Child Neurol. 2006 Jan. 21(1):17-9. [Medline].
Yanagaki S, Oguni H, Yoshii K. Zonisamide for West syndrome: a comparison of clinical responses among different titration rate. Brain Dev. 2005 Jun. 27(4):286-90. [Medline].
Yamauchi T, Aikawa H. Efficacy of zonisamide: our experience. Seizure. 2004 Dec. 13 Suppl 1:S41-8; discussion S49. [Medline].
Gümüs H, Kumandas S, Per H. Levetiracetam monotherapy in newly diagnosed cryptogenic West syndrome. Pediatr Neurol. 2007 Nov. 37(5):350-3. [Medline].
Partikian A, Mitchell WG. Major adverse events associated with treatment of infantile spasms. J Child Neurol. 2007 Dec. 22(12):1360-6. [Medline].
Lux AL, Edwards SW, Hancock E. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2004 Nov 13-19. 364(9447):1773-8. [Medline].
Lux AL, Edwards SW, Hancock E. 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 Nov. 4(11):712-7. [Medline].
Hammoudi DS, Lee SS, Madison A. Reduced visual function associated with infantile spasms in children on vigabatrin therapy. Invest Ophthalmol Vis Sci. 2005 Feb. 46(2):514-20. [Medline].
Mackay MT, Weiss SK, Adams-Webber T. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004 May 25. 62(10):1668-81. [Medline].