Although the epileptogenic mechanisms of infantile spasms is not well understood, an etiologic diagnosis can be identified in more than 70% of cases (4, 5), which may lead to a specific therapy that can have a dramatic influence on the outcome of the patient. It is, therefore, essential that an appropriate diagnostic evaluation be performed in every patient. Because infantile spasms has such characteristic clinical and electrographic features, it is easy to make the diagnosis if the epileptic nature of the spells is recognized. However, sometimes the spasms are subtle enough that the syndrome is not even considered.
Three key factors lead to the diagnosis. The first factor is age. Infantile spasms is a disorder of the developing nervous system and the spasms typically begin in the first year of life, most commonly between 4 and 8 months of age (6). Occasionally, they may begin in the neonatal period (7) or, rarely, much later in childhood (8). An atypical age of onset may help with etiologic diagnosis. For example, neonatal onset is associated with cortical dysplasia (9), whereas late onset (after 1 year of age) often is associated with genetic anomalies, hypoxic ischemic encephalopathy, and cortical dysplasia.
The second factor is the semiology. Clusters of flexion jerks of the neck, trunk, and extremities lasting 1–2 seconds are typical. Variations occur, such as extension of upper and lower extremities or both. Or, the spells may be very subtle, such as just a brief head drop (so-called Blitz-Nick-Krämpfe or “lightening neck spasms"), and often are misdiagnosed as a Moro reflex or simple startle reflex. In such cases, the epileptic nature of the spells may remain unappreciated for weeks or months. Although the spasms may happen as single jerk event, clusters are more common and often occur on awakening in the morning or after a nap (6). Other seizure types may arise concurrently or sequentially with infantile spasms.
The third factor is a very distinct EEG pattern. It is interesting to note that infantile spasm syndrome was not recognized as an epileptic disorder until the 1950s when Gibbs et al. described the characteristic and pathognomonic EEG abnormality called hypsarrhythmia (13). Hypsarrhythmia is a very high-voltage, disorganized pattern of EEG abnormality. A less chaotic pattern, called modified hypsarrhythmia, actually may be more common than hypsarrhythmia (14). Hypsarrhythmia or modified hypsarrhythmia is seen in about two thirds of cases. Other patterns, such as multifocal independent spike discharges (MISD), are present in the remainder. Although infantile spasms may be associated with other EEG abnormalities, hypsarrhythmia virtually never occurs in other epilepsy syndromes.Because infantile spasm seizures are frequent, it is common to capture the spells on a routine EEG, revealing the characteristic feature of electrodecrement immediately after the individual clinical spasm. If the EEG is normal, the diagnosis of infantile spasms should be reconsidered, as there are benign disorders that may appear clinically similar to infantile spasms (e.g., benign infantile myoclonus (15) or benign familial infantile convulsions.
These three factors are so distinctive that the clinical diagnosis of infantile spasms can be made with certainty in the vast majority of cases. Whereas the diagnosis of infantile spasms syndrome is usually easy, determining an etiologic diagnosis may be difficult. However, the etiologic diagnosis has such a profound impact on treatment and prognosis that an appropriate evaluation is essential in all cases.
