Definition
Infantile spasms are an early childhood epileptic seizure disorder that usually occurs between 3 and 12 months of age. They are characterized by sudden, brief tonic spasms in clusters, often accompanied by developmental regression and a distinctive hypsarrhythmia pattern on EEG. This condition is a neurologic emergency that requires prompt evaluation and treatment.
Description
- Infantile spasms, now officially called Infantile Epileptic Spasms Syndrome (IESS), is an epilepsy syndrome that begins early and is characterized by:
- Groups of short spasms, which can be flexor, extensor, or mixed.
- Developmental regression or stagnation.
- Hypsarrhythmia or modified hypsarrhythmia observed on EEG.
- It is regarded as a neurologic emergency that demands swift diagnosis and intervention (AAN/CNS practice guidelines).
Epidemiology
Incidence/Prevalence
- Infantile spasms occur at an incidence of approximately 1.6 to 4.5 per 10,000 live births in the United States.
- Population-based studies estimate the prevalence at approximately 0.14–0.19 per 1,000 children under age 10.
Age
- The average age of onset ranges from 3 to 7 months, peaking around 4 to 6 months.
- Although most cases begin in infancy, onset has been observed as early as the first week of life and as late as several years.
Gender
- There is a slight predominance of males, with an estimated male-to-female ratio of about 60:40.
- Studies indicate there isn't a significant gender disparity, implying that both sexes are substantially impacted.
Race
- Infantile spasms happen in all ethnic groups, with no clear evidence of a strong racial preference in the literature.
- There is minimal U.S.-specific data on race or ethnicity concerning infantile spasms, and detailed epidemiologic studies broken down by race are rare.
Risk factors
- General
- Perinatal asphyxia
- Prematurity
- Low birthweight
- Maternal infection
- Maternal substance use
- Family history
- Physiological
- Tuberous sclerosis
- Brain malformations
- Genetic mutations
- Metabolic disorders
- CNS infections
Etiology
- In America, most infantile spasms are caused by underlying neurological conditions rather than environmental or parenting influences. The main causes are grouped into several major etiologic categories:
- Structural brain abnormalities include hypoxic-ischemic encephalopathy, perinatal stroke, intracranial hemorrhage, cortical dysplasia, and lissencephaly.
- Genetic and chromosomal disorders include tuberous sclerosis complex (TSC), Down syndrome, ARX, CDKL5, STXBP1, and SCN2A mutations.
- Metabolic disorders, including mitochondrial disease and inborn errors of metabolism.
- Idiopathic/Cryptogenic — approximately 10–30% of cases have no identifiable cause.
- Pathophysiology:
- Disrupted cortical–subcortical brain networks during early development cause abnormal neuronal synchronization and produce the characteristic hypsarrhythmia pattern seen on EEG.
- Increased levels of corticotropin-releasing hormone (CRH) and reduced GABAergic inhibition raise neuronal excitability, leading to spasmodic seizures.
History
- Seizure Description: Brief spasms lasting 1–2 seconds, involving flexor, extensor, or mixed movements, typically occurring upon waking or when drowsy.
- Symptom Pattern: Repeated spasms every few seconds that last several minutes; parental video recordings are often helpful.
- Family History: Epilepsy and neurodevelopmental disorders.
- Tuberous Sclerosis Screening: Inquire about skin lesions, family history, or prior TSC diagnosis (a common cause in the U.S.).
- Perinatal and medical risk factors include prematurity, perinatal asphyxia, neonatal seizures, CNS malformations, previous CNS infections, and metabolic or genetic disorders.
Physical findings on examination
- Observation of Spasms: Sudden, symmetric flexion and extension episodes that occur in clusters; the infant may cry afterwards.
- General Neurologic Exam: Presence of abnormal tone (hypotonia or hypertonia), delayed developmental milestones, limited visual engagement, and weak social responsiveness.
- Reflexes: Rapid reflex responses, continued primitive reflexes, or uneven findings.
- Skin Examination (TSC Focus):
- Hypomelanotic macules, also known as “ash leaf spots,”
- Shagreen patch
- Facial angiofibromas
- Head & Growth Parameters: Microcephaly or macrocephaly, depending on the underlying cause.
- Developmental Assessment: Noted global developmental delay or regression during interaction.
General treatment items
- Adrenocorticotropic Hormone (ACTH)
- Regarded as the gold standard first-line treatment.
- Typically administered as a high-dose intramuscular ACTH injection.
- High-Dose Oral Corticosteroids
- Prednisolone is the most frequently used alternative when ACTH is unavailable or too costly.
- Vigabatrin
- First-line treatment is crucial when infantile spasms are caused by Tuberous Sclerosis Complex (TSC).
- Needs to be monitored for visual field toxicity.
- Pharmacologic Therapies:
- Other Antiseizure Medications
- Used when first-line agents fail:
- Topiramate
- Valproic acid
- Zonisamide
- Levetiracetam
- Benzodiazepines (clonazepam, clobazam)
- Ketogenic Diet (KD)
- Typically utilized for refractory spasms.
- Can greatly decrease spasms and enhance hypsarrhythmia.
Surgical Interventions
- Focal Cortical Resection
- Used when a single, resectable lesion is identified, such as cortical dysplasia or encephalomalacia.
- Hemispherotomy / Hemispherectomy
- For unilateral structural brain abnormalities causing spasms (e.g., hemimegalencephaly).
- Corpus Callosotomy
- Used for persistent epileptic spasms when other surgical options are not suitable.
- Laser Ablation (MR-guided LITT)
- A newer, minimally invasive option available for certain focal epileptogenic lesions.
Adjunctive Therapies
- Ketogenic Diet (KD)
- Also listed as a second-line therapy; functions as both a treatment and an adjunct.
- Vagus Nerve Stimulation (VNS)
- It is not a first-line treatment but can be useful in cases where medication resistance occurs.
- Developmental and Supportive Therapies
- Early intervention through physical, occupational, and speech therapy.
- Necessary because of the risk of developmental delay.
- Nutritional Support
- Important to note if corticosteroids lead to weight gain or metabolic issues.
- Vision Monitoring
- Necessary for vigabatrin because of the risk of retinal toxicity.
Medications indicated with specific doses
Toxoids
Immunoglobulins
Vasodilators
Thrombolytic agents
Dietary or Activity restrictions
- Reduce salt and sugar consumption while on steroid therapy to lower the risk of hypertension, weight gain, and fluid retention.
- Avoid activities that could cause sudden spasms, which might lead to injury, such as being on elevated surfaces or sitting without support.
Disposition
Admission Criteria
- Any infant suspected of having spasms and requiring video-EEG confirmation should be admitted immediately.
- Infants who require urgent MRI or begin hormonal therapy (such as ACTH or high-dose steroids) must be monitored inpatient.
Discharge criteria
- Spasms are being controlled or are improving since starting treatment.
- Diagnostic evaluation has been completed, including EEG, MRI, and laboratory tests.
- Caregivers receive training on medication management and how to monitor side effects.
- A clear follow-up plan with pediatric neurology has been arranged.