NORD gratefully acknowledges Susan Koh, MD, Clinical Professor, Department of Pediatrics, University of Colorado School of Medicine; Director of the Pediatric Epilepsy Program, Children's Hospital of Colorado, for assistance in the preparation of this report.
Symptoms associated with West syndrome usually begin during the first year of life. The average age of onset for epileptic spasms is at 6 months. Epileptic spasms are characterized by involuntary muscle spasms that occur due to episodes of uncontrolled electrical disturbances in the brain (seizures). Each involuntary spasm typically begins suddenly and lasts for only a few seconds and occurs usually in clusters that can last entirely over 10-20 minutes. Such episodes, which may occur upon awakening or after feeding, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.
Infants with West syndrome also have severe electroencephalogram (EEG) high amplitude, chaotic spike wave patterns (hypsarrhythmia), and delays in acquiring skills that require coordination of muscles and voluntary movements (psychomotor retardation).
Approximately a third of children with West syndrome may develop recurrent epileptic seizures as they age. The syndrome often develops into the Lennox-Gastaut syndrome with mixed types of seizures that are difficult to control and is associated with intellectual disability. (For more information on Lennox-Gastaut syndrome, see the Related Disorders section below.). Approximately another third of children with West syndrome will continue to have epileptic spasms at an older age group. The last third to quarter of patients will have spasms that resolve with time, usually in patients who have no clear etiology.
A specific cause for West syndrome can be identified in approximately 70-75% of those affected (symptomatic). Any disorder that can lead to brain damage can be an underlying cause of West syndrome including trauma, brain malformations such as hemimegalencephaly or cortical dysplasia, infections, chromosomal abnormalities such as Down syndrome, neurocutaneous disorders such as tuberous sclerosis complex (TSC), Sturge Weber syndrome, incontinentia pigmenti, several different metabolic/genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup urine disorder, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency, Otahara’s syndrome, and an abnormality (mutation) in the ARX gene or CDKL5 gene located on the X chromosome.
The most common disorder responsible for West syndrome is tuberous sclerosis complex. (TSC). TSC is an autosomal dominant genetic condition associated with seizures, eye, heart and kidney tumors and skin findings.
X-linked West syndrome can be caused by a mutation in the CDKL5gene or the ARX gene in the X chromosome. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
West syndrome is a rare neurological syndrome that can affect males and females. The X-linked form of West syndrome affects males more often than females.
West syndrome has been estimated to affect .31 per 1000 live births in the United States. West syndrome accounts for approximately 30 percent of all cases of epilepsy affecting infants.
Clinical Testing and Work-up
The first step in the treatment of epileptic spasms is to characterize the patterns of brain activity through measurement with various devices. Among these are:
This is a painless and non-invasive means of recording the patterns of electrical activity of the brain. Electrodes placed on the scalp pick up and record the electrical waves during periods of activity and, with luck, during periods of sleep. If a pattern called hypsarrhythmia is noted, especially during sleep, this can help to suggest that a patient has infantile spasms. However, there are times when a patient may have infantile spasms and does not have the hypsarrhythmia pattern due to a lag time between clinical symptoms and EEG pattern. In addition, there are several illnesses that can mimic epileptic spasms and a long term videoEEG may confirm the diagnosis of epileptic spasms. Therefore, an overnight, long term video EEG monitoring is preferable compared to a routine 20 minute EEG study in some cases of infantile spasms.
Brain Scans, such as:
Computed Tomography (CT). Harnessing X-rays to a computer generates pictures of cross-sections of the brain from which the detail of development may be determined. CT is also very good at showing areas of calcification that in some cases, may be essential for the diagnosis. However, this does not provide as detailed a picture as a MRI.
Magnetic Resonance Imaging (MRI). This radiological technique produces detailed images of cross-sections or slices of the brain by using the magnetic properties of particular atoms found in the brain. The images are more detailed than a CT and can provide information concerning any malformation of the brain structures or other types of lesions commonly seen in epileptic spasms.
Infection as a cause of infantile spasms may be determined by blood tests, urine tests and lumbar puncture.
A Wood’s lamp is used to examine skin for lesions with lack of skin color in order to determine if tuberous sclerosis is a possible diagnosis.
Molecular genetic testing is available for mutations in the ARX and CDKL5 genes associated with X-linked West syndrome. It is also available for tuberous sclerosis complex. Some genetic disorders will require CSF fluid for genetic testing such as in nonketotic hyperglycemia which may require CSF samples to test for glycine as well as mitochondrial diseases which may require CSF to test for lactate. A genetic mutation of STXBP1 has recently been noted in patients with Otahara’s syndrome as well. There are several genetic panels available such as Gene Dx that can test children of a certain age for a variety of genetic conditions that are seen in epilepsies such as epileptic spasms.
Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.
In some cases, it is possible that treatment with anticonvulsant drugs may help reduce or control various types of seizure activity associated with West syndrome. The most common medications used to treat epileptic spasms include, adrenocorticotropic hormone (ACTH), prednisone, vigabatrin and pyridoxine. The benefits of the medication need to be weighed with the side effects of each treatment. For example, ACTH, prednisone and other steroids are known to cause issues with immunosuppression, hypertension, gastric issues, agitation and irritability, glucose in the urine, etc. Vigabatrin may cause an irreversible visual field defect, irritability, and transient hyperintensity of deep structures in the MRI. There is no standard protocol for using ACTH or other steroid treatment. It is unknown whether high dose ACTH or low dose ACTH is effective or whether the use of prednisone is more effective than ACTH. In a recent multicenter study looking at steroid treatment compared to vigabatrin, it was felt that steroids may have better seizure control compared to vigabatrin at 2 weeks of treatment, but that the effectiveness was the same after a year. In addition, vigabatrin was more effective in patients with tuberous sclerosis or cortical dysplasia compared to steroids.
It is felt that a shorter time between diagnosis and treatment will have less deleterious effect on the development compared to a longer lead time. If these treatments are not successful, other medications such as benzodiazepines (for example, clobazam), valproic acid, topiramate, rufinamide and zonisamide may be used. Ketogenic diet has also been successful at times in the treatment of infantile spasms. Finally, in cases where there is a malformation or tuberous sclerosis complex, epilepsy surgery may be helpful as a last ditch effort to control spasms.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Contact for additional information about West syndrome:
Susan Koh, MD
Director of the Epilepsy Program
Children’s Hospital of Colorado
Clinical Professor of Pediatrics
University of Colorado School of Medicine
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