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, symmetric or asymmetric flexion of the head, trunk, and/or limbs)
2
Hypsarrhythmia on electroencephalogram (EEG)
3
Developmental delay or regression.
Epidemiology:
IS affects approximately 1 in 2,000 to 1 in 4,000 live births
It typically presents between 3 and 12 months of age, with a peak onset at 6 months
It is more common in males
Etiologies are diverse, including genetic, chromosomal, metabolic, and structural brain abnormalities, with cryptogenic (idiopathic) forms also recognized.
Clinical Significance:
Early diagnosis and aggressive treatment of infantile spasms are crucial due to their association with significant developmental impairment, cognitive deficits, and a higher risk of developing other epilepsy syndromes later in life
Prompt recognition of hypsarrhythmia is key to initiating timely intervention and improving neurodevelopmental outcomes.
Clinical Presentation
Symptoms:
Classic epileptic spasms: sudden, rapid, synchronous or asynchronous jerks of the body
Typically occur in clusters, especially upon waking or falling asleep
Spasms can be flexor (most common, involving neck, trunk, and limbs), extensor, or mixed
Developmental regression may be noted, with loss of achieved milestones (e.g., loss of social smile, head control, sitting ability).
Signs:
Physical examination may reveal hypotonia, hypertonia, or a lack of purposeful motor activity
There may be subtle neurological deficits
In cryptogenic IS, the physical exam may be normal initially
Associated features depend on the underlying etiology, such as dysmorphic features in chromosomal abnormalities or focal neurological signs in structural brain lesions.
Diagnostic Criteria:
The diagnostic triad for West syndrome is: 1
Infantile spasms (clinical description)
2
Hypsarrhythmia (EEG pattern: chaotic, asynchronous, high-voltage slow waves and spikes diffusely distributed)
3
Developmental arrest or regression
The diagnosis is primarily based on clinical presentation and characteristic EEG findings.
Diagnostic Approach
History Taking:
Detailed history of the paroxysmal events is paramount
Inquire about the nature, frequency, timing (especially related to sleep/wake cycles), and symmetry of jerks
Assess developmental milestones achieved and any subsequent loss
Family history of epilepsy or neurological disorders is important
Ask about antenatal and perinatal history, infections, and exposure to toxins.
Physical Examination:
A thorough neurological examination is essential, looking for signs of hypotonia, hypertonia, focal neurological deficits, dysmorphic features, or evidence of trauma
Assess for primitive reflexes and their persistence or absence
Funduscopic examination to rule out retinal abnormalities may be considered.
Investigations:
Electroencephalogram (EEG) is the gold standard for diagnosing hypsarrhythmia
A prolonged EEG (e.g., 24-hour ambulatory EEG) may be necessary to capture the characteristic pattern
MRI brain is crucial for identifying structural causes
perform this early
Metabolic screening (e.g., urine organic acids, plasma amino acids, ammonia, lactate) and genetic testing (e.g., chromosomal microarray, epilepsy gene panels) are indicated to identify treatable etiologies.
Differential Diagnosis:
Other paroxysmal events in infancy that can mimic IS include: benign myoclonus of infancy (Sandifer syndrome), shuddering attacks, Sandifer syndrome, gastroesophageal reflux with opisthotonos, postprandial apnea, and spasmus nutans
These can usually be differentiated by clinical observation and EEG findings.
Management
Initial Management:
Immediate initiation of treatment is critical
The primary goal is to abolish spasms and normalize the EEG pattern, which improves neurodevelopmental outcomes
Patients should be managed in a center with expertise in pediatric epilepsy.
Medical Management:
First-line treatment is typically high-dose oral corticosteroids (prednisolone or ACTH)
For ACTH, initial dose is 2.5-4.0 IU/kg/day IM, tapered over 2-6 weeks
Prednisolone is often preferred for ease of administration, starting at 2 mg/kg/day, tapered over 4-6 weeks
Vigabatrin is another highly effective first-line option, particularly for tuberous sclerosis complex, with typical dose of 50-150 mg/kg/day
Other antiepileptic drugs (AEDs) like topiramate, valproate, or zonisamide may be used as add-on therapy if first-line treatments fail.
Surgical Management:
Surgery is considered in intractable cases with a clearly identifiable focal lesion (e.g., cortical dysplasia, hippocampal sclerosis, tumor) that is believed to be the generator of the spasms
Resective surgery can be highly effective in achieving seizure freedom and improving development in selected patients.
Supportive Care:
Comprehensive care involves multidisciplinary management
Physical, occupational, and speech therapy are vital for addressing developmental delays and functional impairments
Behavioral interventions and parental support are also crucial
Regular follow-up with neurology, developmental pediatrics, and other specialists is necessary.
Complications
Early Complications:
Treatment side effects: Steroid-induced complications include irritability, insomnia, increased appetite, weight gain, immunosuppression, hypertension, hyperglycemia, and electrolyte imbalances
Vigabatrin can cause visual field constriction
ophthalmologic monitoring is essential
Development of other seizure types, such as Lennox-Gastaut syndrome.
Late Complications:
Long-term sequelae often include intellectual disability, autistic spectrum disorder, behavioral problems, and a significantly increased risk of developing refractory epilepsy
Persistent developmental delay or regression can occur despite treatment.
Prevention Strategies:
Prompt diagnosis and initiation of effective treatment are the primary strategies to prevent severe long-term sequelae
Identifying and treating underlying etiologies when possible can also improve outcomes
Close monitoring for treatment-related side effects and prompt management of these is also important.
Prognosis
Factors Affecting Prognosis:
The prognosis is variable and depends heavily on the etiology, age of onset, and response to treatment
Favorable prognostic factors include early diagnosis and treatment, cryptogenic (idiopathic) etiology, and a rapid cessation of spasms and EEG normalization
Unfavorable factors include a symptomatic etiology (especially severe brain malformations), later onset, poor response to initial treatment, and persistence of hypsarrhythmia.
Outcomes:
Approximately 50-70% of infants achieve seizure freedom with appropriate treatment
However, a significant proportion will develop other epilepsy syndromes and persistent neurodevelopmental impairments
Long-term cognitive outcomes range from normal intelligence to severe intellectual disability.
Follow Up:
Long-term follow-up is essential
This includes regular neurological and developmental assessments, ongoing EEG monitoring to detect recurrence or evolution of seizure patterns, and management of associated comorbidities
Vision screening is mandatory for vigabatrin users
Transition to adult epilepsy services is required.
Key Points
Exam Focus:
Recognize the triad of IS: spasms, hypsarrhythmia, developmental regression
Know the EEG pattern of hypsarrhythmia (chaotic, high-voltage, diffuse spikes and slow waves)
First-line treatments: ACTH, high-dose corticosteroids, vigabatrin
Differentiate IS from other infantile paroxysmal events
Prognosis is linked to etiology and treatment response.
Clinical Pearls:
Always ask parents to show a video of the spells if possible
this is invaluable
Remember that spasms can be subtle and mistaken for colic or startle responses
EEG is diagnostic
don't delay referral
Early, aggressive treatment is the key to better outcomes
Tuberous sclerosis complex is a common cause where vigabatrin is often preferred.
Common Mistakes:
Delaying EEG if IS is suspected
Mistaking spasms for other benign neonatal/infantile phenomena
Inadequate dosage or duration of first-line treatment
Not investigating for underlying etiology
Failing to monitor for treatment side effects, especially visual field defects with vigabatrin and metabolic effects with steroids.