Infantile spasms (IS) are seizures seen in epilepsy of infancy and early childhood. The typical pattern of an infantile spasm occurs soon after arousal from sleep, and involves a sudden bending forward and stiffening of the body, arms, and legs. Additionally, arching of the torso can also be seen during an infantile spasm. Infantile spasms typically last for one to five seconds and occur in clusters, ranging from two to 100 spasms at a time.
Infantile spasms were first described by the English physician W.J. West (1794–1848) in 1841. West's paper, published in the first volume of the medical journal Lancet, was a landmark in the development of pediatric neurology, and the seizure syndrome also became known as West syndrome. West observed the condition in his own infant son, giving a precise and complete description of the symptoms, along with the gradual mental deterioration, and intractability of the syndrome. Other neurological disorders, such as cerebral palsy , may be seen in almost half of infants with infantile spasms.
Infantile spasms may have variable features, but have been categorized primarily into three subtypes based on manifestations of posture and patterns of muscle involvement during the seizure. Flexor spasms involve flexion of the neck, trunk, and extremities. Extensor spasms consist of extension of the neck, trunk, and extremities. Mixed flexor-extensor spasms involve combinations of the above.
In many patients, spasms exhibit characteristic patterns involving time. Fifty to eighty percent of the epileptic spasms occur in clusters of two to more than 100 seizures. Patients may have dozens of clusters and several hundred spasms per day, but individual variability in seizure frequency is often large. Although spasms rarely occur during sleep, clusters of spasms are frequently activated after awakening from sleep. Spasms are occasionally triggered by loud noises with associated arousal from drowsiness and sleep, but are generally not sensitive to stimulation by human voices.
In the United States, infantile spasms constitute 2% of childhood epilepsies, and 25% of epilepsies with onset in the first year of life. The rate of IS is 1.6–5.0 cases per 10,000 live births. As many as 5% of infants with this condition eventually die from complications of the seizures. Although males are affected slightly more often than females, no significant gender difference is noted.
Causes and Symptoms
The number of neurological diseases that can result in infantile spasms is very large, but some of the major categories include intrauterine injury and infection, disorders caused by lack of blood flow to the fetal brain, developmental malformations of the cerebral cortex, metabolic disorders, other genetic or chromosomal defects, meningitis, and tumors. These seizures are assumed to reflect abnormal interactions between the cortex and brainstem structures. The frequent onset of the spasms in infancy suggests that an immature central nervous system may be important in the formation of infantile spasm syndrome. One theory states that the effect of different stressors in the immature brain produces an abnormal excessive secretion of corticotropin-releasing hormone, which causes spasms.
In 90% of children with the condition, infantile spasms occur in the first year of life, typically between three to six months of age. Often, in the beginning, the attacks are brief, infrequent and not typical, so it is quite common for the diagnosis to be delayed. Frequently, because of the pattern of attacks and the cry that a child gives during or after an attack, they are initially thought to be due to colic, or gastric distress.
The typical pattern is of a sudden flexion (bending forward) in a tonic (stiffening) fashion of the body, arms, and legs. Sometimes, however, the episodes are of the extensor type (arching). Usually, they are symmetrical, but sometimes one side is affected more than the other.
Typically, each episode lasts a few seconds, followed by a pause of a few seconds, and a further spasm. While single spasms may occur, infantile spasms usually occur in sets of several spasms in a row. It is common for babies with infantile spasms to become irritable and for their development to slow down or even regress until the spasms are controlled.
Information about the child's seizures and about the pregnancy, birth, and progress since birth, will help the physician in making the diagnosis. The diagnosis of infantile spasms is made by a combination of the typical features, along with a characteristic electroencephalogram (EEG), which shows a very disorganized pattern termed hypsarrhythmia.
Most children with infantile spasms will need a number of tests, such as blood, urine, and cerebrospinal fluid (fluid which circulates around the brain and spinal cord) sampling, in an attempt to screen for any infection or metabolic abnormality. X-ray studies such as CT scans, ultrasound, or MRI will be performed to evaluate the structure of the brain.
The treatment team usually includes pediatric neurologists, neurosurgeons, nurses specializing in epilepsy care, and dietitians. In addition to conventional therapies, the team provides the latest in diagnostic and therapeutic approaches, including such innovations as the ketogenic diet, diagnostic video telemetry, and epilepsy surgery for intractable seizures. New epilepsy studies focus in investigating promising new drugs and other novel therapies.
Due to the poor prognosis of infantile spasms, treatment is usually initiated quickly and aggressively after diagnosis, often at the risk of serious side effects, with the hope of changing the natural history of the disease. Antiepileptic medications are the mainstay of therapy for infants with infantile spasms. Unfortunately, no one medical treatment gives satisfactory relief for all patients. In most open-label or retrospective studies, adrenocorticotrophic hormone ACTH or prednisone induces a reduction or complete cessation of spasms, as well as an improvement in the EEG, in approximately 50–75% of patients. This effect is usually achieved within a couple weeks. Patients unresponsive to ACTH may respond to prednisone and vice-versa. A large variety of ACTH doses have been used, but there is no evidence that larger doses (150 units/day) are more effective than lower doses (20–30 units/day). While relapses occur in about one-third to one-half of patients, a second course of ACTH is often effective.
Among conventional anti-seizure drugs, valproate and nitrazepam have been shown to be effective as first-line therapy. In addition to medication, there are some potential surgical options for infantile spasms, although they may only be applicable to a small percentage of patients. Although in most patients the precise source of the spasms in the brain cannot be localized, there is a small minority of patients who have secondarily generalized spasms from lesions in the brain that can be surgically removed.
Newer anti-seizure medicines such as Vigabatrin, although not yet approved in the United States, have shown promise in reducing the frequency of infantile spasms by increasing the brain's available amount of GABA, a neurotransmitter that helps transmit information as it bridges the gaps between nerve cells.
Recovery and rehabilitation
Infantile spasms usually cease spontaneously by age five, but are often replaced by seizures of other types. Therefore, emphasis is placed on lifelong seizure prevention rather than recovery. Maintaining control of seizures in infancy can sometimes reduce developmental delays and mental retardation , although most infants will already have significant neurological impairment before the onset of symptoms.
Although as of early 2004, there were no ongoing clinical trials for infantile spasms, the National Institutes of Health (NIH) sponsors research related to many seizure disorders. Information on the numerous current clinical trials for the study and treatment of seizure disorders can be found at the NIH website: <http://clinicaltrials.gov/search/term=Seizure+Disorder>.
Infantile spasms usually resolve with or without treatment in the majority of patients, generally by mid-childhood. However, other seizure types arise in 50–70% of patients. Similarly, on long-term follow-up, chronic intractable (unable to respond to treatment) epilepsy is present in approximately 50% of patients with a history of infantile spasms.
Mental retardation occurs in 70–90% of persons with infantile spasms, usually involving severe to profound retardation. Other neurological deficits, such as cerebral palsy, may be seen in about 30–50% of patients. By far, the most important factor in predicting neurological prognosis, including developmental outcome and long-term epilepsy, is the underlying cause of the seizures.
Factors that have been associated with a good prognosis include normal neurological exam and development at onset, absence of other seizure types at onset, older age of onset, short duration of spasms, and early effective treatment of spasms (reported with ACTH).
Once infants begin to have infantile spasms, they often fail to meet new milestones and may even regress, losing mental or physical skills previously learned. When the seizures begin, parents may notice a loss of interest in people and objects in the child's environment. Social interaction may diminish, smiling may cease, sleep may become disrupted, and the child may seem irritable or indifferent to surroundings. A child who had learned to sit may stop sitting or even lose the ability to roll over; a child who had been babbling happily may become silent or fussy.
Frost, James D., Jr., and Richard A. Hrachovy. Infantile Spasms: Diagnosis, Management and Prognosis. New York: Kluwer Academic Publishers, 2003.
Shields, W. D. "West's syndrome." J. Child Neurol 17 (2002): S76–79.
West, W. J. "On a peculiar form of infantile convulsions." Lancet (1840–1841) I: 724–725.
National Institute of Neurological Disorders and Stroke. NINDS Infantile Spasms Information Page. (April 5, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/infantilespasms.htm>.
Francisco de Paula Careta
Iuri Drumond Louro