Infantile spasms are seizures characterized by sudden flexion of the arms, forward flexion of the trunk, extension of the legs, and most often exhibition of hypsarrhythmia (disorganized wave patterns) on electroencephalography. Treatment is adrenocorticotropic hormone, oral corticosteroids, or vigabatrin.Infantile spasms are seizures characterized by sudden flexion of the arms, forward flexion of the trunk, extension of the legs, and most often exhibition of hypsarrhythmia (disorganized wave patterns) on electroencephalography. Treatment is adrenocorticotropic hormone, oral corticosteroids, or vigabatrin.
Infantile spasms last a few seconds and can recur many times a day. They usually manifest in children < 1 year of age and peak between 4 months and 6 months of age (1). Seizures may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures; in particular, infantile spasms may progress to other forms of epilepsy, such as Lennox-Gastaut syndrome (2).
Infantile spasms are rare and occur in approximately 1.5/100,000 children per year worldwide (3).
West syndrome is a type of infantile spasm and a subset of a broader group of epileptic spasms called infantile epileptic spasms syndrome. It is used to describe children with infantile spasms who exhibit hypsarrhythmia on electroencephalography (4). Some children who have infantile spasms but who do not meet all criteria for West syndrome may still be diagnosed with infantile epileptic spasms syndrome. If the clinical manifestations of infantile spasms develop or continue to otherwise manifest outside of infancy, they are termed epileptic spasms.
General references
1. Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol. 1991;6(4):355-364. doi:10.1177/088307389100600412
2. Riikonen R. Infantile Spasms: Outcome in Clinical Studies. Pediatr Neurol. 2020;108:54-64. doi:10.1016/j.pediatrneurol.2020.01.015
3. Jia JL, Chen S, Sivarajah V, Stephens D, Cortez MA. Latitudinal differences on the global epidemiology of infantile spasms: systematic review and meta-analysis. Orphanet J Rare Dis. 2018;13(1):216. Published 2018 Nov 29. doi:10.1186/s13023-018-0952-x
4. Pavone P, Polizzi A, Marino SD, et al. West syndrome: a comprehensive review. Neurol Sci. 2020;41(12):3547-3562. doi:10.1007/s10072-020-04600-5
Etiology of Infantile Spasms
Infantile spasms usually occur in infants with serious brain disorders and developmental abnormalities that often have already been recognized. These disorders may include the following:
Tuberous sclerosis complex is a common cause of infantile spasms that can lead to drug-resistant epilepsy. Sturge-Weber syndrome and neurofibromatosis are other neurocutaneous causes.
Rarely, chromosomal abnormalities (eg, Down syndrome), structural malformations of the central nervous system (eg, Aicardi syndrome), and congenital neurotropic infections (eg, syphilis, Zika virus infection, cytomegalovirus infection) can lead to infantile spasms.
Sometimes the cause of infantile spasms cannot be identified.
Pathophysiology of Infantile Spasms
The pathophysiology of neurologic injury that leads to infantile spasms is believed to be influenced by several factors. Inborn errors of metabolism and genetic predispositions can lead to neurologic damage similar to the effects of structural defects (organic pathologies). Additionally, acquired factors such as hypoxia-ischemia and infections also may cause neurologic injury after birth. Consequently, abnormal interactions between the cortex and brain stem may manifest as infantile spasms.
Symptoms and Signs of Infantile Spasms
Spasms begin with a sudden, rapid, tonic contraction of the trunk and limbs, sometimes for several seconds. Spasms range from subtle head nodding to contraction of the whole body.
There are 3 types of spasms: flexor, extensor, or, more often, both (mixed). Flexor spasms cause sudden flexion of the neck, trunk, arms, and legs. Extensor spasms usually cause central (neck and trunk) spasms. Mixed spasms commonly cause flexion of the upper body with extension of the legs. In all 3 types, spasms usually occur in clusters, often several dozen, in close succession and occur typically after children wake up and occasionally when falling asleep. Sometimes, at first, they are mistaken for the startle reflex. The postictal state can be characterized by motor unresponsiveness.
Developmental delays (see Childhood Development) may be present before the onset of infantile spasm. In infants with normal development, developmental regression (eg, children may stop smiling or lose the ability to sit up or roll over) can occur after onset of infantile spasms.
Diagnosis of Infantile Spasms
Electroencephalography (EEG) with awake and asleep stages
Neuroimaging, preferably MRI
Evaluation for underlying etiology, if not already diagnosed
Previous history (eg, neonatal hypoxic-ischemic encephalopathy) and/or symptoms and signs suggest the diagnosis of infantile spasms in some children. Physical and neurologic examinations are done, but often no pathognomonic findings are identified except in children with tuberous sclerosis complex or other neurocutaneous syndromes.
EEG is done to confirm the diagnosis and check for specific abnormalities. Typically, the interictal pattern is hypsarrhythmia (chaotic, high-voltage polymorphic delta and theta waves with superimposed multifocal spike discharges). Multiple variations (eg, focal or asymmetric hypsarrhythmia) are possible. The ictal pattern is usually a sudden, marked and diffuse attenuation of electrical activity.
Neuroimaging, preferably MRI, is done if it has not recently been done.
Tests to determine the cause
If it is not clear from neuroimaging or the previous history, tests to determine the cause may include
Laboratory tests (eg, complete blood count with differential; measurement of serum glucose, electrolytes, blood urea nitrogen, creatinine, sodium, calcium, magnesium, phosphorus, serum amino acids, and urine organic acids; liver tests) if a metabolic disorder is suspected but not diagnosed on newborn screeningLaboratory tests (eg, complete blood count with differential; measurement of serum glucose, electrolytes, blood urea nitrogen, creatinine, sodium, calcium, magnesium, phosphorus, serum amino acids, and urine organic acids; liver tests) if a metabolic disorder is suspected but not diagnosed on newborn screening
Genetic testing (epilepsy gene panels are available)
Cerebrospinal fluid (CSF) analysis to check for metabolic disorders
(See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.)
Treatment of Infantile Spasms
Intramuscular adrenocorticotropic hormone (ACTH)
Oral corticosteroids
Vigabatrin (especially for tuberous sclerosis complex)
Infantile spasms are not responsive to typical antiseizure medications.
The standard therapies for infantile spasms are usually ACTH and corticosteroids and, in some cases, vigabatrin (The standard therapies for infantile spasms are usually ACTH and corticosteroids and, in some cases, vigabatrin (1).
ACTH can be given daily IM as either high-dose or low-dose injections. The Pediatric Epilepsy Research Consortium (PERC) recommends the higher dose, given for 2 weeks and then tapered down every 3 days until 29 days of treatment are completed. If low-dose therapy is tried and has not stopped spasms within 2 weeks, the higher dose is used (2).
Corticosteroids (eg, oral prednisone) are given for 4 to 7 weeks.(eg, oral prednisone) are given for 4 to 7 weeks.
VigabatrinVigabatrin is the medication of choice when the spasms are caused by tuberous sclerosis complex. It is also often used in children with an established preexisting serious brain injury or malformation and in those who do not tolerate or respond to ACTH. Dosage of oral vigabatrin is increased gradually over about a week if needed. There is insufficient evidence that any other antiseizure medication or the ketogenic diet is effective.
In some patients with resistant spasms or with focal cortical malformation, epilepsy surgery can eliminate seizures.
There is evidence that the quicker effective therapy is initiated, the better the neurodevelopmental outcome, particularly when no cause is identified.
Treatment references
1. Go CY, Mackay MT, Weiss SK, 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(24):1974-1980. doi:10.1212/WNL.0b013e318259e2cf
2. Knupp KG, Coryell J, Nickels KC, et al. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol. 2016;79(3):475–484. doi:10.1002/ana.24594
Prognosis for Cerebral Palsy
The rate of premature death ranges from 5 to 31% (1) and is related to the etiology of the infantile spasms.
In a Finnish longitudinal study on 214 children with infantile spasms with a 100% follow-up rate, common long-term outcomes reported were autism and hyperkinetic behavior, and a significant proportion had intellectual disability. About one-third continued to have epileptic seizures. After the full follow-up period of 35 years, about one-third had died (2). Further longitudinal studies in other populations are needed for generalizability.
Prognosis references
1. Riikonen R. Long-term outcome of West syndrome: A study of adults with a history of infantile spasms. Epilepsia. 1996;37(4):367–372. doi:10.1111/j.1528-1157.1996.tb00573.x
2. Riikonen R. Infantile Spasms: Outcome in Clinical Studies. Pediatr Neurol. 2020;108:54-64. doi:10.1016/j.pediatrneurol.2020.01.015
Key Points
Infantile spasms last a few seconds and can recur many times a day; they may resolve spontaneously by about 5 years of age but are often replaced by other types of seizures.
Usually, infantile spasms occur in infants with underlying brain disorders and developmental abnormalities that have often already been recognized; tuberous sclerosis complex is a common cause.
Perform electroencephalography to confirm the diagnosis, and other tests (eg, brain MRI and metabolic and genetic testing) to evaluate the cause of infantile spasm.
Infantile spasms can be treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, or vigabatrin (the drug of choice for spasms caused by tuberous sclerosis complex). Infantile spasms can be treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, or vigabatrin (the drug of choice for spasms caused by tuberous sclerosis complex).
