Overview
Definition:
Infantile spasms (IS), also known as West syndrome, is a severe epilepsy syndrome characterized by a triad of: 1
Infantile spasms (sudden, brief flexion or extension of the body and limbs)
2
Hypsarrhythmia on electroencephalogram (EEG)
3
Developmental delay or regression
It typically presents in infancy between 3 and 12 months of age.
Epidemiology:
Incidence is estimated at 1 in 2,000 to 1 in 4,000 live births
It accounts for approximately 5% of all childhood epilepsies
There is a slight male predominance
The etiology can be idiopathic or secondary to various brain abnormalities, including genetic disorders, congenital malformations, hypoxic-ischemic encephalopathy, metabolic disorders, and infections.
Clinical Significance:
Infantile spasms are a medical emergency due to the high risk of developmental delay, intellectual disability, and progression to other severe epilepsy syndromes like Lennox-Gastaut syndrome if left untreated
Early diagnosis and prompt initiation of appropriate treatment are crucial for improving neurodevelopmental outcomes and seizure control.
Clinical Presentation
Symptoms:
Characteristic spasms: sudden, brief (1-2 second) tonic contractions, often in clusters, typically occurring on waking or falling asleep
Flexor spasms (most common): head drops forward, arms jerk up or forward
Extensor spasms: limbs extend
Asymmetrical spasms: occur on one side
Developmental regression: loss of previously acquired milestones such as smiling, sitting, or babbling
Irritability and poor feeding are also common.
Signs:
Physical examination may reveal normal findings between spasms
In symptomatic cases, signs of underlying neurological deficits may be present, such as hypotonia, hypertonia, or cranial nerve palsies
Neurological assessment may show developmental delay or regression.
Diagnostic Criteria:
Diagnosis is confirmed by a characteristic EEG pattern of hypsarrhythmia (chaotic, high-amplitude, multiform spike and slow-wave discharges across all scalp leads with no or minimal background activity) and the presence of infantile spasms
The triad of spasms, hypsarrhythmia, and developmental delay/regression defines West syndrome.
Diagnostic Approach
History Taking:
Detailed history of seizure semiology: precise description of the movements, timing (e.g., upon waking, during sleep), frequency, duration, and triggers
Developmental history: age of onset, regression of milestones, and past developmental trajectory
Family history of epilepsy or neurological disorders
History of prenatal insults, birth complications, or postnatal infections
Any known metabolic or genetic conditions.
Physical Examination:
Complete neurological examination: assess tone, reflexes, cranial nerves, motor function, and sensory function
Assess for dysmorphic features suggestive of genetic syndromes
Developmental assessment to quantify delay or regression.
Investigations:
Electroencephalogram (EEG): mandatory for diagnosis, showing hypsarrhythmia
If hypsarrhythmia is not seen on routine EEG, prolonged EEG monitoring (e.g., 24-hour or sleep-deprived EEG) is indicated
Magnetic Resonance Imaging (MRI) of the brain: essential to identify underlying structural causes, such as cortical malformations, hippocampal sclerosis, or tumors
Metabolic screening: urine and serum tests for amino acids, organic acids, ammonia, lactate, and glucose to rule out metabolic disorders
Genetic testing: chromosomal microarray, gene panels for specific epilepsy syndromes (e.g., SCN1A, CDKL5, ARX) may be considered, especially in cryptogenic or syndromic cases
Lumbar puncture: to rule out central nervous system infections if suspected.
Differential Diagnosis:
Other epileptic spasms: myoclonic seizures, tonic seizures, and generalized tonic-clonic seizures
Brief myoclonic jerks: can be mistaken for spasms
Sandifer syndrome: characterized by paroxysmal abnormal posturing secondary to gastroesophageal reflux
Benign sleep myoclonus: non-epileptic, occurring only during sleep
Sandifer syndrome: characterized by paroxysmal abnormal posturing secondary to gastroesophageal reflux.
Management
Initial Management:
Immediate initiation of anti-epileptic drug (AED) therapy is paramount once diagnosis is confirmed
The choice of initial therapy depends on guidelines, availability, and underlying etiology
Hormonal therapy (ACTH) and vigabatrin are the first-line options.
Medical Management:
First-line therapies: 1
Adrenocorticotropic Hormone (ACTH): Typically administered intramuscularly (IM)
Common regimens include high-dose depot ACTH (e.g., 20-40 units/day) or low-dose long-acting ACTH gel (e.g., 20-80 units 2-3 times weekly) for 4-6 weeks
Response rates are around 60-70%
2
Vigabatrin: An irreversible GABA transaminase inhibitor
Oral administration
Dosing is usually 50-100 mg/kg/day, divided into two doses
Response rates are also around 50-60%
It is often preferred in specific etiologies like Tuberous Sclerosis Complex (TSC)
Second-line therapies (if first-line fails): Pyridoxine (Vitamin B6) - high-dose regimens
Topiramate
Zonisamide
Sodium valproate (less preferred in infants due to potential liver toxicity)
Ketogenic diet or modified Atkin diet can be considered for refractory cases
Surgery: Considered for focal epilepsy with a clearly identifiable and resectable epileptogenic zone, particularly in tuberous sclerosis complex.
Surgical Management:
Surgical intervention is generally reserved for cases with a clearly identifiable focal lesion that is amenable to resection and has failed to respond to medical therapy
Resective surgery in focal epilepsy associated with infantile spasms, especially in Tuberous Sclerosis Complex, can lead to seizure freedom in some children
Corpus callosotomy may be considered for severe drop attacks and generalized tonic seizures but is less effective for infantile spasms themselves.
Supportive Care:
Nutritional support: ensure adequate caloric intake, especially if feeding difficulties are present
Developmental support: early intervention programs, physiotherapy, occupational therapy, and speech therapy are vital to address developmental delays
Genetic counseling: for families with identified genetic causes
Ongoing monitoring: regular clinical and EEG follow-up to assess treatment response, monitor for side effects, and detect relapse.
Complications
Early Complications:
Treatment-related side effects: Cushingoid features, hypertension, hyperglycemia, immunosuppression with ACTH
Visual field constriction (retinal abnormalities) with vigabatrin
Increased risk of infections with ACTH
Irritability and sedation with most AEDs.
Late Complications:
Neurodevelopmental impairment: intellectual disability, autism spectrum disorder, behavioral problems
Development of other epilepsy syndromes: Lennox-Gastaut syndrome, intractable focal epilepsy
Status epilepticus
Recurrence of spasms.
Prevention Strategies:
Early recognition and diagnosis of infantile spasms
Prompt initiation of effective treatment
Close monitoring for treatment efficacy and side effects
Regular follow-up with a pediatric neurologist
Proactive management of developmental delays with early intervention services.
Prognosis
Factors Affecting Prognosis:
Etiology: cryptogenic (idiopathic) infantile spasms generally have a better prognosis than symptomatic cases
Early age of onset (younger than 3 months) is associated with better outcomes
Early and complete cessation of spasms
Normal or near-normal development prior to onset
Response to initial therapy
Normal EEG after treatment.
Outcomes:
Approximately 50-60% of infants respond to ACTH or vigabatrin
Complete seizure remission is achieved in about 30-40%
However, a significant proportion will develop other severe epilepsy syndromes
Long-term prognosis is often guarded, with many children experiencing persistent intellectual disability and neurological deficits
Early diagnosis and treatment can significantly improve developmental outcomes and reduce the risk of developing other severe epilepsy types.
Follow Up:
Regular clinical evaluations and EEGs are crucial
Developmental assessments should be performed regularly
Visual field monitoring is recommended for all infants treated with vigabatrin, although routine ophthalmologic screening is not universally recommended for asymptomatic infants due to low incidence of clinically significant findings
Transition to long-term epilepsy management is necessary for infants who do not achieve sustained remission.
Key Points
Exam Focus:
ACTH and vigabatrin are first-line therapies
Vigabatrin is preferred in Tuberous Sclerosis Complex due to its efficacy and lower risk of precipitating other seizure types
ACTH is more effective in cryptogenic West syndrome
Hypsarrhythmia on EEG is the hallmark
Developmental regression is a key clinical feature
Early intervention is critical.
Clinical Pearls:
Always consider infantile spasms in infants with sudden, jerky movements, especially if occurring in clusters
The triad of spasms, hypsarrhythmia, and developmental regression is diagnostic
EEG is essential for diagnosis
consider prolonged monitoring if routine EEG is inconclusive
MRI brain helps identify treatable structural causes
Vigabatrin requires visual field monitoring awareness.
Common Mistakes:
Delaying diagnosis and treatment due to misinterpreting spasms as colic or reflux
Not obtaining an urgent EEG or MRI
Not considering vigabatrin in TSC
Inadequate follow-up for developmental and visual assessment
Treating with less effective first-line agents when ACTH or vigabatrin is indicated.