Vigabatrin for Infantile Spasms
Vigabatrin for Infantile Spasms
Infantile spasms describe a pediatric epilepsy syndrome characterized by frequent clusters of brief symmetric muscle contractions; the condition is often associated with developmental delay. When infantile spasms are accompanied by hypsarrhythmia on electroencephalogram, the condition is labeled West syndrome. The mainstay of treatment for infantile spasms is adrenocorticotropic hormone; however, vigabatrin, a vinyl derivative of γ-aminobutyric acid, has been used for the treatment of infantile spasms in Europe since 1989. In 2009, vigabatrin was approved by the United States Food and Drug Adminstration (FDA) for use as monotherapy in the treatment of infantile spasms in patients aged 1 month–2 years when the benefits of treatment outweigh the risks. Results from numerous trials examining the role of vigabatrin in infantile spasms have been published; many of these trials were small, open-label, or noncontrolled. Although clinical trials have provided some insight into the utility of vigabatrin for the treatment of infantile spasms, these studies have notable limitations. In addition, vigabatrin is associated with a black-box warning that describes the potential for permanent bilateral concentric visual field defects. Currently, vigabatrin is available through a manufacturer-sponsored program in accordance with its FDA-approved Risk Evaluation and Mitigation Strategy. Although several guidelines recommend vigabatrin as a first-line therapy for infantile spasms, specifically infantile spasms related to tuberous sclerosis, it is still unclear whether vigabatrin should supersede hormone therapy as first-line therapy. Further research comparing the two therapies is needed.
Infantile spasms is a term that describes a pediatric epilepsy syndrome characterized by brief, symmetric muscle contractions typically involving flexor and/or extensor muscles. The incidence of infantile spasms is approximately 1 in every 2000–4000 infants; the peak onset is within the first year of life. The spasms associated with this disorder often occur in clusters several times each day and can be classified as symptomatic, cryptogenic, or idiopathic. Symptomatic cases are those with identifiable causes. These are further differentiated according to the etiologic timing as being prenatal (malformations, chromosomal abnormalities, neurocutaneous syndromes, and metabolic disorders), perinatal (traumatic delivery, asphyxia, kernicterus), or postnatal (head trauma, intracranial tumors or hemorrhage, anoxia, central nervous system infections). Cryptogenic cases are those whose underlying etiology cannot be identified despite a strong suspicion of such an etiology; idiopathic cases have an absence of an identifiable underlying cause or other neurologic signs or symptoms. When accompanied by a characteristic electroencephalographic pattern called hypsarrhythmia, the manifestation is referred to asWest syndrome. Many patients with infantile spasms and West syndrome also have developmental delay and poor developmental outcomes associated with the underlying etiology.
The mainstay of therapy for infantile spasms has traditionally been adrenocorticotropic hormone (ACTH) or corticosteroids. Although neither the pathology of infantile spasms nor the pharmacologic basis for this treatment modality is yet well defined, it is theorized that increased corticotropin-releasing hormone in infancy may trigger increased neuronal firing. This may be suppressed by ACTH or corticosteroid treatment, but the use of ACTH or high-dose corticosteroids may be limited because of their associated adverse effects. The availability of vigabatrin provides clinicians with a treatment option for infantile spasms that is not based on corticosteroids. Also, some sources have suggested that vigabatrin could be prescribed for patients based on the infantile spasm classification and underlying etiology, including those whose syndrome is associated with tuberous sclerosis.
Vigabatrin has been used in some European countries, specifically in the United Kingdom, since 1989. However, as it only recently acquired approval for use in the United States in 2009, caregivers sought to obtain vigabatrin from other countries before U.S. Food and Drug Administration (FDA) approval. Hence, although there exists a substantial amount of scientific literature dedicated to vigabatrin, it is likely that U.S. clinicians will have limited knowledge of this drug. We therefore conducted a literature search of MEDLINE and cross-referenced in Embase (1980–August 2010). The key search term vigabatrin was used. Results were limited to English-language articles, human studies, and all infants and children up to age 18 years. In addition, bibliographies of selected review articles were used to identify relevant literature. Federally maintained clinical trial Web sites and Internet sources were used to identify ongoing clinical trials.
Abstract and Introduction
Abstract
Infantile spasms describe a pediatric epilepsy syndrome characterized by frequent clusters of brief symmetric muscle contractions; the condition is often associated with developmental delay. When infantile spasms are accompanied by hypsarrhythmia on electroencephalogram, the condition is labeled West syndrome. The mainstay of treatment for infantile spasms is adrenocorticotropic hormone; however, vigabatrin, a vinyl derivative of γ-aminobutyric acid, has been used for the treatment of infantile spasms in Europe since 1989. In 2009, vigabatrin was approved by the United States Food and Drug Adminstration (FDA) for use as monotherapy in the treatment of infantile spasms in patients aged 1 month–2 years when the benefits of treatment outweigh the risks. Results from numerous trials examining the role of vigabatrin in infantile spasms have been published; many of these trials were small, open-label, or noncontrolled. Although clinical trials have provided some insight into the utility of vigabatrin for the treatment of infantile spasms, these studies have notable limitations. In addition, vigabatrin is associated with a black-box warning that describes the potential for permanent bilateral concentric visual field defects. Currently, vigabatrin is available through a manufacturer-sponsored program in accordance with its FDA-approved Risk Evaluation and Mitigation Strategy. Although several guidelines recommend vigabatrin as a first-line therapy for infantile spasms, specifically infantile spasms related to tuberous sclerosis, it is still unclear whether vigabatrin should supersede hormone therapy as first-line therapy. Further research comparing the two therapies is needed.
Introduction
Infantile spasms is a term that describes a pediatric epilepsy syndrome characterized by brief, symmetric muscle contractions typically involving flexor and/or extensor muscles. The incidence of infantile spasms is approximately 1 in every 2000–4000 infants; the peak onset is within the first year of life. The spasms associated with this disorder often occur in clusters several times each day and can be classified as symptomatic, cryptogenic, or idiopathic. Symptomatic cases are those with identifiable causes. These are further differentiated according to the etiologic timing as being prenatal (malformations, chromosomal abnormalities, neurocutaneous syndromes, and metabolic disorders), perinatal (traumatic delivery, asphyxia, kernicterus), or postnatal (head trauma, intracranial tumors or hemorrhage, anoxia, central nervous system infections). Cryptogenic cases are those whose underlying etiology cannot be identified despite a strong suspicion of such an etiology; idiopathic cases have an absence of an identifiable underlying cause or other neurologic signs or symptoms. When accompanied by a characteristic electroencephalographic pattern called hypsarrhythmia, the manifestation is referred to asWest syndrome. Many patients with infantile spasms and West syndrome also have developmental delay and poor developmental outcomes associated with the underlying etiology.
The mainstay of therapy for infantile spasms has traditionally been adrenocorticotropic hormone (ACTH) or corticosteroids. Although neither the pathology of infantile spasms nor the pharmacologic basis for this treatment modality is yet well defined, it is theorized that increased corticotropin-releasing hormone in infancy may trigger increased neuronal firing. This may be suppressed by ACTH or corticosteroid treatment, but the use of ACTH or high-dose corticosteroids may be limited because of their associated adverse effects. The availability of vigabatrin provides clinicians with a treatment option for infantile spasms that is not based on corticosteroids. Also, some sources have suggested that vigabatrin could be prescribed for patients based on the infantile spasm classification and underlying etiology, including those whose syndrome is associated with tuberous sclerosis.
Vigabatrin has been used in some European countries, specifically in the United Kingdom, since 1989. However, as it only recently acquired approval for use in the United States in 2009, caregivers sought to obtain vigabatrin from other countries before U.S. Food and Drug Administration (FDA) approval. Hence, although there exists a substantial amount of scientific literature dedicated to vigabatrin, it is likely that U.S. clinicians will have limited knowledge of this drug. We therefore conducted a literature search of MEDLINE and cross-referenced in Embase (1980–August 2010). The key search term vigabatrin was used. Results were limited to English-language articles, human studies, and all infants and children up to age 18 years. In addition, bibliographies of selected review articles were used to identify relevant literature. Federally maintained clinical trial Web sites and Internet sources were used to identify ongoing clinical trials.
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