OBJECTIVE: To summarize and evaluate the literature regarding the clinical features, epidemiology, etiology, pathophysiology, and treatment of infantile spasms. DATA SOURCES: A literature search of articles from January 1966 to July 1993 using MEDLINE, EM-Base, and Current Concepts/Life Sciences, as well as bibliographies of relevant articles. STUDY SELECTION: All identified original and review publications regarding the clinical features, epidemiology, etiology, pathophysiology, and treatment of infantile spasms were reviewed. Emphasis was placed on original studies published since 1975. DATA EXTRACTION: Data from published research were extracted and evaluated according to study design, sample size, dosing regimen, outcome measures, and treatment efficacy and safety. DATA SYNTHESIS: Infantile spasms constitute a rare epileptic syndrome with a poor long-term prognosis for normal intellectual development. The spasms are characterized by a brief symmetric contraction of the muscles of the neck, trunk, and/or extremities, often occurring in a series of 2 to more than 100 spasms during a single episode. The disorder is age-specific, with the peak onset of symptoms occurring between 2 and 8 months of age. Spasms of no identifiable cause in infants with normal development prior to the onset of infantile spasms are classified as cryptogenic or idiopathic, whereas those with an identifiable cause are classified as symptomatic. Long-term prognosis is best in cryptogenic cases, with 30–70 percent attaining normal intellect compared with 5–19 percent in symptomatic cases. The etiology and pathophysiology are not well understood. Recent theory postulates that infantile spasms may be caused by an excess of corticotropin-releasing hormone activity during infancy. The suspected association between the whole-cell pertussis vaccine and infantile spasms is coincidental. Few well-designed, prospective, controlled clinical trials for the treatment of infantile spasms have been conducted. CONCLUSIONS: Standard anticonvulsants such as phenytoin, the barbiturates, carbamazepine, and the succinimides have been ineffective. Of the anticonvulsants, only the benzodiazepines, valproic acid, and vigabatrin have shown efficacy in reducing spasm frequency and severity. Hormonal therapy with adrenocorticotropic hormone (ACTH) and/or prednisone has been the most frequently studied treatment modality and appears to be the most effective. Hormonal therapy achieves complete spasm control in 50?75 percent of infants within four weeks of initiation. Opinions differ regarding the relative efficacy between ACTH and prednisone, the need for early initiation of hormonal treatment, and the benefits of high dosages of ACTH (>40 units/d). No treatment has been shown conclusively to improve the long-term intellectual development of these infants. Neurosurgery may be the treatment of choice in select cases when a localized central nervous system abnormality can be demonstrated. Well-designed, blind, prospective clinical trials are needed to answer definitively many lingering questions regarding the treatment of infantile spasms.
Novel insights into the polycythemia–paraganglioma–somatostatinoma syndrome
