By Aparna Polavarapu and Solomon L Moshé MD
Isabelle Rapin Division of Child Neurology
Saul R. Korey Department of Neurology and Department of Pediatrics
Albert Einstein College of Medicine and Montefiore Medical Center
Bronx, New York
Epilepsy in Down Syndrome
Epilepsy in Down Syndrome is an important disorder for families to be aware of. Though it is not very common, epilepsy occurs more frequently in those with Down Syndrome than in the general population, with a prevalence up to about 15%. Epilepsy can present at any age; however, it is more common to begin in infancy or in the 3rd decade of life. Various seizure types can occur, such as focal seizures where one side or both sides part of the body is affected, or quick jerking of the head, arms, or legs (these are called myoclonic seizures). Children with Down Syndrome also have an increased risk for infantile spasms, occurring in 5-30% of those with seizures.
What is infantile spasms?
Infantile spasms (IS) typically present between 4-9 months of age and are characterized by brief sudden flexion of the trunk with forward extension and stiffening of the arms and legs that last only a few seconds. Some children may have brief flexion of the head, or “head drops”, back arching and quick extension of the limbs. These seizures tend to cluster when the child awakens and are usually associated with developmental regression. EEG, a diagnostic study that superficially measures brain waves through the scalp, shows a characteristic pattern called hypsarrhythmia. Onset of IS is usually accompanied by developmental delay or regression and can result in further delays, cognitive impairment, development of different seizure types and hard to control epilepsy. The triad of infantile spasms, developmental regression and characteristic hypsarrhythmia on EEG is also referred to as West Syndrome. Identifying an infant quickly after symptoms become apparent is crucial to optimizing developmental and seizure outcomes. Physicians closely monitor developmental progress in infants, and any concerns of stagnation or regression are taken very seriously, frequently prompting a rapid referral to a child neurologist. In addition, concerns for new movements, sometimes described as “twitching”, “head drops” or “spasms” are also important symptoms triggering further evaluation for possible IS. Even when untreated, IS usually resolve on their own by 18 months, but can leave a child with worse developmental problems and will frequently have different seizure types. Early treatment often improves the outcome.
Infantile spasms in Down Syndrome
Children with Down Syndrome are prone to develop infantile spasms. We do not know yet why this happens. More research is needed to understand the connection between Down Syndrome and infantile spasms. In children with Down Syndrome, other factors can contribute to the risk for developing epilepsy, such as brain injury resulting from prematurity, hypoxic-ischemic encephalopathy or perinatal stroke.
Identifying subtle symptoms in infants with DS can be difficult, since preexisting developmental delays and atypical movements are common. Discussing any new symptoms or changes with the pediatrician can help with quicker evaluation and diagnosis. Referral to a child neurologist tends to happen quickly once suspicion is raised, as longer duration of IS negatively impacts outcomes. An EEG is done, frequently with in-hospital monitoring overnight, and if characteristic findings are present, therapy is discussed with families and quickly initiated.
Is the EEG different in kids with Down Syndrome and infantile spasms?
No. The EEG shows the characteristic hypsarrhythmia pattern indicative of infantile spasms, regardless of the cause or other underlying neurologic problems.
What are the available treatments?
Standard treatment for infantile spasms is one of two medications: hormonal treatment (steroids) or vigabatrin. In some cases, other antiseizure medications are used, if hormonal or vigabatrin treatment is not successful. A specialized diet, called the ketogenic diet can also be used for treatment.
Treatment with steroids
The most common hormonal treatments are high dose ACTH intramuscular injections, or high dose oral prednisolone. Steroids, especially at high doses, can result in many adverse reactions. Most children will have weight gain and mood changes, such as extreme irritability. Less commonly, sugar in the urine, high blood sugar, headaches, and mood changes can occur. More serious and rare side effects include gastrointestinal bleeding, high blood pressure, risk of serious infections due to lowered immunity, kidney and heart disease can also happen. Infants are closely monitored by parents and the neurology team, with periodic urine and blood tests. Treatment is typically over 4-6 weeks, with slow decrease in the steroid dose over that time. A repeat EEG and check in with the neurologist happen towards the end of therapy, to assess whether the spasms and hypsarrhythmia have resolved.
Treatment with vigabatrin
Vigabatrin is an antiseizure medication and is generally reserved for initial treatment in West syndrome due to a specific disorder called Tuberous Sclerosis. If steroids are not successful, vigabatrin can be used. A common short-term side effect is sleepiness, and with long term use there is the concern for peripheral visual field constriction. The treatment course for infantile spasms is generally short, up to about 6 months at most, and risk for peripheral visual loss is low. Repeat EEG and neurology follow up occurs about 4 weeks after treatment initiation and again at the end of therapy.
Treatment with other antiepileptic medications
Antiseizure medications that have been used as alternative therapy are topiramate, valproate and benzodiazepines. These options are usually used when hormonal or vigabatrin treatment doesn’t work. Side effects for all antiseizure medications can include sleepiness, irritability, unsteadiness and usually resolve once the body gets used to the medication. Specific side effects, such as kidney stones (topiramate), liver dysfunction (valproate), and excessive sleepiness and drooling (benzodiazepines) are some of the uncommon reactions. Side effects are discussed with the parents when treatment is initiated, so they are aware of what to look for.
Treatment with ketogenic diet
Ketogenic diet is a specific dietary therapy that is used for epilepsy that is not fully controlled by medications. The diet is a high fat and low carbohydrate/protein, along with fluid and calorie restriction. This diet has been effective in difficult to control epilepsy and has shown efficacy in infants with West syndrome. The diet is started in the hospital so blood and urine tests can be monitored. Children are carefully followed in the clinic to monitor for side effects, including low blood sugar, dehydration, lethargy, constipation, abdominal pain and increase in cholesterol. Food and drink are closely monitored and weighed to ensure strict proportions of fats and non-fats and can be a difficult diet for some children to follow. There are specialized nutritionists and recipes to help support the family as well.
How do we know the treatment is effective?
Symptoms resolve, and EEG (with sleep and preferably with video) shows the hypsarrhythmia has resolved. If these haven’t resolved, additional therapies are started.
Fortunately, 75% of children with Down syndrome respond to 1 course of hormonal treatment. But a little over half (about 57%) may need more than 1 course of therapy. In children who don’t respond to treatment with steroids, other seizure medications can be used.
What are the long-term outcomes?
Developmentally, children with Down Syndrome are at an increased risk for cognitive impairment and autism, though having a history of infantile spasms does not seem to increase that risk. In general, infantile spasms can result in developmental delay, cognitive impairment and epilepsy. However, kids with Down Syndrome tend to do better than children with spasms due to other causes.
How do infantile spasms in Down syndrome contrast from infantile spasms in typical children?
In general, children with Down Syndrome and infantile spasms, respond well to treatment. The occurrence of epilepsy is slightly higher in Down Syndrome, and infantile spasms is a significant portion of the seizure types that occur. Recognizing the symptoms early leads to a quick diagnosis and early treatment positively impacts developmental and seizure outcomes.