In 1841, Dr. William J. West penned a letter to Lancet in which he described an unusual condition in his 4-month-old son, James, that was characterized by “… slight bobbings of the head forward”…which “… increased in frequency, and at length became so powerful, as to cause a compete heaving of the head forward toward his knees, and then immediately relaxing in an upright position. … these bowings and relaxings would be repeated alternately at intervals of a few seconds, and repeated from ten to twenty or more times at each attack, which attack would not continue more than two or three minutes; he sometimes has two, three, or more attacks in the day ….” Dr. West went on to describe a reduction in a developmental trajectory in his child that was normal prior to the onset of these events: he states that since the onset of the spells his son “… neither possesses the intellectual vivacity, or the power of moving his limbs, of a child of his age.” This remarkable letter, now over 160 years old, remains the most eloquent clinical description of what we now know as infantile spasms. It describes the relentless nature of the condition, the early age of onset, the classical clinical presentation, and the developmental regression associated with infantile spasms.1
In 1952, Gibbs and Gibbs2 described the classical interictal electroencephalographic (EEG) pattern associated with infantile spasms, called hypsarrhythmia. This EEG is characterized by a chaotic and disorganized background of high-voltage, asynchronous spike and slow-wave activity. Although hypsarrhythmia is certainly characteristic of infantile spasms, it should be remembered that the EEG findings in infantile spasms are dynamic and hypsarrhythmia is but a point on a continuum of epileptiform changes observed on the EEG in this disorder. Therefore, the absence of hypsarrhythmia in the presence of clinical evidence of infantile spasms and other types of epileptiform abnormalities on the EEG does not in any way exclude the diagnosis of infantile spasms.
The term West Syndrome refers to an age-related triad of epileptic spasms, developmental regression, and hypsarrhythmia on EEG. Although this triad may be used synonymously with infantile spasms, the latter should refer strictly to the massive myoclonus because infantile spasms may occur in the absence of either hypsarrhythmia or mental retardation. The incidence of infantile spasm is 1 per 2000–4000 live births3,4 and the prevalence rate is 0.15–0.2 per 1000 children of age 10 years or younger.5 It is slightly more common in males, accounting for about 60% of cases, and a family history exists in 3%–6%.
The epileptic syndrome of infantile spasms begins in infancy, with initial onset mostly between 3 and 7 months of life in more than 50% of cases. Over 90% of cases begin before 12 months of life.6
The clinical spasms are brief and sudden contractions of the axial musculature, which may occur in clusters several times a day. Although there is no predilection for day or night, they appear to be temporally related to sleep. They tend to occur upon awakening or as the infant falls asleep. Spasms are occasionally triggered by loud noises usually associated with arousal from sleep but are not exacerbated by photic stimulation. They are clinically distinct from myoclonic and tonic seizures with an initial contraction phase followed by a more sustained tonic phase.7 The spasms can be divided into flexor, extensor, or mixed depending on the muscle groups involved. Most infants have more than one type, and the type observed may be influenced by the body position at the time the spasm occurs. They can be symmetric or asymmetric. Mixed spasms are most common, followed by flexor spasms, with extensor type being the least common.6
Flexor spasm is the most characteristic of West syndrome. The infant appears to be in a self-hugging posture with sudden adduction or abduction of the arms. When abdominal muscles are involved, the infant may bend at the waist, giving rise to the term, “jackknife” seizure. The combination of jackknife seizure plus adduction of the arms with or without neck flexor muscle involvement is called “salaam” seizures.
Extensor spasms are characterized by abrupt extension of the neck, trunk, and legs with extension and abduction of the arms, simulating a Moro reflex. The mixed flexor-extensor spasms are a combination of leg extension with flexion of neck, trunk, and arms. The spasms may manifest as head nods when only the neck flexor muscles are involved. In children who are walking, drop attacks may be the initial manifestation. The type of spasms does not seem to be affected by etiology nor the prognosis; however, the symmetry of spasms is important because the presence of asymmetry may indicate focal cortical brain pathology.7
Developmental regression is an important, but not invariable component of infantile spasms. However, the long-term prognosis for unselected cases of infantile spasms is generally poor with well over 50% of children having significant cognitive impairment after infantile spasms. In one-third of cases, development is normal before onset.8 Previously normal infants may have developmental regression with the onset of infantile spasm. Axial hypotonia and loss of hand grasp are the frequently lost skill. Guzzetta et al noted that the development of visual inattention expressed as loss of eye contact has a negative prognostic significance.9
Infantile spasms may be classified into three main groups—symptomatic, idiopathic, and cryptogenic. Symptomatic cases are those where there is structural brain abnormality or metabolic cause in a child with preexisting neurologic abnormality. The term cryptogenic infantile spasms is used when there are no apparent causes identified although a cause is suspected, usually because the child is developmentally delayed or has some other neurological impairment before the onset of the spasms. Idiopathic is used to describe children with no identifiable cause and who have a normal neurological examination and normal development prior to the onset of infantile spasms.
Cryptogenic cases account for 9%–15% of infantile spasms cases.10 The number of symptomatic cases has increased over the years due to advancement in neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) that facilitate better detection of subtle brain abnormalities causing infantile spasms.
The symptomatic cases can be further classified into three etiologic subgroups depending on the timing of presumed causes: prenatal, perinatal, and postnatal.11
Tuberous sclerosis (TS) is a major cause of infantile spasms, with up to 50% of all patients with TS presenting with infantile spasms which peak between 4 and 6 months of age.12 The number of diseases that can cause infantile spasms is enormous but the major categories include cortical dysgenesis, chromosomal aberrations and genetic syndromes, infections, certain metabolic conditions and vitamin deficiency, vascular insult, and tumors and trauma (Table 28–1).
| Etiology | Examples |
|---|---|
| Cortical dysgenesis | Cortical dysplasia Laminar heterotropia Lissencephaly Hemimegalencephaly Septal dysplasia Schizencephaly Pachygyria Porencephaly Microgyria Agenesis of corpus callosum |
| Chromosomal aberrations and genetic syndromes | Tuberous sclerosis Incontinentia pigmenti Neurofibromatosis Sturge Weber syndrome Aicardi’s syndrome Down’s syndrome |
| Infections | CMV Toxoplasma Herpes encephalitis Bacterial meningitis Brain abscess |
| Metabolic | Inborn errors of metabolism: phenylketonuria, amino acid and organic acidopathies, nonketotic hyperglycinemia Pyridoxine deficiency/dependency Mitochondrial disorders Neonatal hypoglycemia |
| Vascular | Hypoxic-ischemic insult Hemorrhagic insult |
| Tumors | Ependymomas Gliomas Gangliogliomas Choroids plexus papillomas |
| Trauma |
A comprehensive evaluation of children with infantile spasms includes a complete history and physical examination including Wood’s lamp evaluation as well as an initial EEG. Once a diagnosis of infantile spasms is made, an extensive search for the etiology such as structural brain abnormalities with neuroimaging studies, metabolic and chromosomal abnormalities should be performed.
The characteristic interictal EEG finding of infantile spasms is the hypsarrhythmia pattern described by Gibbs and Gibbs,2 which consists of a disorganized and asynchronous background pattern of high-amplitude spikes and slow waves (Fig. 28–1). It may be present during wakefulness and sleep. However, this pattern is seen most often during early infancy in approximately 66% of cases. The chaotic pattern becomes more organized by early childhood, and may evolve into the generalized sharp and slow-wave pattern seen in Lennox–Gastaut syndrome.
Kellaway et al6 described several ictal EEG patterns associated with infantile spasms. The electrodecremental response, described as high-voltage sharp- or slow-wave discharges followed by generalized voltage attenuation lasting more than 1 second, is the most common, occurring in more than 70% of recorded spasms. Other types include various combinations of generalized sharp- and slow-wave discharges and electrodecremental fast activity (Fig. 28–1).
Focal EEG abnormalities can be seen in a subset of patients with infantile spasms.13,14 The combination of asymmetric spasms and focal or asymmetric hypsarrhythmia pattern with focal ictal discharges strongly suggest the presence of focal brain lesion.
Although computerized tomography (CT) scans are readily available and can detect some underlying focal or diffuse brain pathology, MRI is much more sensitive in picking up smaller lesions including neuronal migrational anomalies, abnormal myelination, and demarcation of the gray and white mater.15 However, it should be remembered that MRI in a child less than 2 years of age, which includes the vast majority of patients with new onset spasms, could still miss cortical migrational abnormalities because of immaturity of white matter.
The value of interictal PET scans in revealing focal areas of hypometabolism, which may correlate with cortical dysplasia in some cases where MRI is normal, was first reported by Chugani et al16 and subsequently validated by others.17
Blood and urine tests can be done to search for metabolic, genetic, and infectious etiologies that cause symptomatic infantile spasms. They also serve as baseline studies before initiation of treatment.
Blood tests should include but not be limited to: complete blood count (CBC) and differential count, electrolytes (sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate), pH, lactate, blood urea nitrogen (BUN), creatinine, glucose, creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin, alkaline phosphatase, thyroid function, serum amino acid screen, cytomegalovirus (CMV) and toxoplasma IgG and IgM, and/or polymerase chain reaction (PCR) studies. Chromosomal studies can also be done especially if there is a family history.
Urine tests should include urinalysis, amino acid screen, organic acid screen, CMV culture, or PCR. Electrocardiogram and chest X-ray should be performed especially if cardiac examination is abnormal. Ophthalmology, cardiology, and genetics consultations can also be requested as needed.
