TIMELY TREATMENT
IS CRUCIAL

Treat urgently—Time to treatment impacts outcomes

First-line treatment with standard therapy is by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.1

Aim of treatment2

  • Obtain complete clinical cessation of all spasms
  • Obtain clearance of the hypsarrhythmia on follow-up EEG

Lead time to treatment (LTTT) <4 weeks is associated with a 51.9% improvement in neurodevelopmental outcomes compared to LTTT >4 weeks.3

Standard first-line treatments

Standard first-line treatments

Use of standard first-line medications has by far the largest impact on the odds of response to first-line treatment.1 Other treatment options include epilepsy surgery, ketogenic diet, other antiepileptic medications, and other strategies.2

Standard first-line treatments

Visit the American Academy of Neurology Guidelines on treatment for infantile spasms.
See guidelines

Know your institution’s treatment protocol.

Consensus guidance is lacking

Currently there are no agreements on standardized treatment protocols in IS for good developmental outcomes, including agents used, dosage regimen, and treatment duration.2,4,5

Assess treatment efficacy with EEG at 2 weeks4

If epileptic spasms or hypsarrhythmia have not resolved, consider other treatment options by or before day 14 of treatment.4

Lennox-Gastaut syndrome

Longer time to first treatment is a risk factor for Lennox-Gastaut syndrome (LGS)

A retrospective chart review to determine the prevalence of LGS in a high-risk cohort IS found 36% (35/97) of children met the criteria for LGS.5

Time between spasm onset to initiation of treatment was less than 1 month in 66.3% of patients and did not correlate with the development of LGS.5

Potential risk factors to develop LGS were children with IS who5:

  • Did not respond or had poor response to first treatment for IS
  • Had developmental delay at onset
  • Had seizures prior to the onset of infantile spasms

There was no difference in development of LGS between medications used as the first treatment for IS, and no difference based on response to subsequent treatments.5

Therapeutic lag (time between spasm onset to initiation of treatment) was less than 1 month in 66.3% of patients and did not correlate with the development of LGS.5

There is support that children with IS who had reduced therapeutic lag time were less likely to have developmental delay at 4 years of age.3,6

Reduced lag time to treatment may reduce risk of developmental delay and progression.3,6

Etiology

Etiology is the most important predictor of outcome7

Etiology of infantile spasms is still evolving. More than 200 causes have been identified, but knowledge is still evolving.2

In high-risk infants, maintaining a strong suspicion and proactively inquiring about symptoms can aid in early diagnosis, even if detailed information isn't voluntarily provided.8

Investigate etiology—
Perform a brain MRI within 4 weeks of diagnosis + genetic/metabolic testing.4

Etiology of infantile spasms2

Opportunity Goal
≈50-60% structural causes
  • Perinatal insults (including prenatal asphyxia)
  • Malformation of brain and cortical development, including:
    • Lissencephaly (LIS1, DCX, TUBA1A, ARX)
    • Focal cortical dysplasia, usually posterior
    • Polymicrogyria and malformations associated with Tuberous Sclerosis
    • Hemispheric malformations (TSC1/2, DEPDC5, NPRL2, NPRL3, MTOR)
    • Posterior malformations (Pontocerebellar-CASK, RARS2)
  • Neurocutaneous– NF1
  • Hypomelanosis of Ito
≈8% chromosomal
  • Down’s Syndrome
  • Williams Syndrome (del 7q11.23)
  • Miller-Dieker Syndrome (del 17p13.3)
  • Pallister-Killian Syndrome (tetrasomy 12p)
<8% metabolic
  • Phenylketonuria, Non-ketotic hyperglycinemia, Methyl-malonic acidemia, cobalamin disorders, Maple syrup urine disease, Menkes disease
  • Pyridoxine-related epilepsies, Mitochondrial, pyruvate dehydrogenase deficiency, Congenital disorders of glycosylation, Biotinidase deficiency, Glucose transporter deficiency (GLUT-1)

Single gene disorders

  • Common genes– CDKL5, STXBP1, ARX (more than 30 further less common genes have been described to be associated with infantile spasms and West syndrome)
20%-30% idiopathic No identified etiology
DON’T MISS IS TIP

Diagnose and treat first!
Etiology and outcomes still depend on early diagnosis and reduced therapeutic lag time.7

References
  1. Demarest ST, Shellhaas RA, Gaillard WD, et al. The impact of hypsarrhythmia on infantile spasms treatment response: observational cohort study from the National Infantile Spasms Consortium. Epilepsia. 2017;58(12):2098-2103. doi:10.1111/epi.13937
  2. Chopra SS. Infantile spasms and West syndrome — a clinician’s perspective. Indian J Pediatr. 2020;87(12):1040-1046. doi:10.1007/s12098-020-03279-y
  3. Widjaja E, Go C, McCoy B, Snead OC. Neurodevelopmental outcome of infantile spasms: a systematic review and meta-analysis. Epilepsy Res. 2015;109:155-162. doi:10.1016/j.eplepsyres.2014.11.012
  4. Messer R, Knupp KG. Infantile spasms: opportunities to improve care. Semin Neurol. 2020;40(2):236-245. doi:10.1055/s-0040-1705121
  5. Nelson JA, Demarest S, Thomas J, Juarez-Colunga E, Knupp KG. Evolution of infantile spasms to Lennox-Gastaut syndrome: what is there to know? J Child Neurol. 2021;36(9):752-759. doi:10.1177/08830738211000514
  6. 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(7):1359-1364. doi:10.1111/j.1528-1167.2011.03127.x
  7. Riikonen R. Infantile spasms: outcome in clinical studies. Pediatr Neurol. 2020;108:54-64. doi:10.1016/j.pediatrneurol.2020.01.015
  8. Jauhari P. Current knowledge, attitude and practice (KAP) of pediatricians on infantile spasms and the way forward. Indian J Pediatr. 2018;85(10):823-824. doi:10.1007/s12098-018-2760-7