How Is Infantile Spasms Treated?

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According to the American Academy of Neurology (AAN) and the Child Neurology Society (CNS), the goals of therapy for infantile spasms (IS) are: [3]

Many studies show that when hypsarrhythmia (chaotic brain waves) lasts for long periods of time, brain development can be damaged. However, when babies with IS are treated early in the course of the illness, they may have a better outcome.[3]

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Treatment Options

There are only two products approved by the FDA for treatment of IS. These are adrenocorticotropin hormone ACTH (H.P. Acthar® Gel [repository corticotropin injection] or Acthar) and vigabatrin (Sabril®). Other therapies are also used to treat IS, but they are not approved by the FDA for this condition. Prescription drugs used to treat IS, both FDA-approved and non-approved, may have different mechanisms of action. There are hormonal agents such as ACTH (Acthar); steroidal agents, which are prescribed under a variety of names such as prednisone; anticonvulsant medications such as vigabatrin (Sabril), zonisamide (Zonegran®), topiramate (Topamax®), valproate (Depakote®), and lamotrigine (Lamictal®); and other therapies such as pyridoxine and high-dose intravenous immunoglobulin (IVIG). The non-drug therapies used to treat IS include the ketogenic diet and surgery.

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Treatment Recommendations

When treatment of IS is effective, it should stop both the spasms and hypsarrhythmia (chaotic brain waves) in babies with IS. To determine which treatments were most effective in treating IS, experts from the AAN and the CNS, as well as experts from the Infantile Spasms Working Group (ISWG), reviewed all the studies in the medical literature. Based on their findings, they made recommendations about the order in which the treatments should be given to ensure the most effective treatments are prescribed first.

In 2004, the AAN and the CNS made recommendations about treating IS. Based on the research available, the treatments were rated in the following manner: 1) effective; 2) probably effective; 3) possibly effective; and 4) treatment unproven. None of the existing therapies were put in the effective category due to lack of scientific studies. ACTH was given the next highest rating of probably effective, vigabatrin was rated possibly effective, and there was not enough evidence to recommend any other therapies to treat IS.[6]

More recently, in 2010, a group of experts from the ISWG looked at the treatments for IS and concluded that ACTH and vigabatrin are effective as first-line therapy, meaning they should be the first drugs considered, before other treatments.[3]

If your baby is treated for IS and the treatment is successful, the spasms and hypsarrhythmia (chaotic brain waves) should disappear. If treatment is not successful after it has been given for the prescribed time, your doctor may discuss other treatment options with you.

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Hormonal Therapy

ACTH (Acthar)

ACTH (Acthar) is a prescription medication that may work by helping the body produce natural hormones such as cortisol and by having a direct effect on the brain. It is in gel form and is given as an injection into the muscle. The gel is designed to slowly release the medication into the body after it is injected.

ACTH (Acthar) is a prescription medicine that is used to treat infantile spasms in infants and babies under 2 years of age.[8] (Acthar Medication Guide) In one clinical study, 87% of subjects who received ACTH had no spasms and no hypsarrhythmia within 2 weeks.[7] (Acthar Prescribing Information, 2010)

The recommended dosage of ACTH (Acthar) for treating IS is 150 units per meter squared, divided into two daily injections of 75 units per meter squared each. After two weeks of treatment, the dose may be gradually lowered over a two-week period and then stopped.[7] (Acthar Prescribing Information, 2010) If treatment is successful, the spasms and hypsarrhythmia (chaotic brain waves) should disappear.

Side Effects

Side effects that could be serious that are associated with ACTH (Acthar) in babies with IS include:

1) Increased risk of infections

2) Effects on the adrenal gland after stopping ACTH (Acthar)

  • Your baby may not make enough of the hormone called cortisol

3) Effects on the adrenal gland while taking ACTH (Acthar)

  • Your baby may make too much of the hormone called cortisol, which may lead to Cushing’s syndrome, increased blood pressure, too much water in the body, an elevated amount of body salts, and low potassium in the blood

4) Your baby should not receive certain vaccinations during treatment with ACTH (Acthar)

5) ACTH (Acthar) may hide symptoms of other diseases or conditions

6) Increased risk for stomach and intestinal problems

7) Changes in mood or behavior

ACTH (Acthar) may also worsen certain medical conditions such as diabetes, may cause eye problems or allergic reactions, and if given long-term, may affect growth and physical development and may enlarge the heart.

The most common side effects of ACTH (Acthar) are: infections, increased blood pressure, irritability and changes in behavior, changes in appetite and weight, diarrhea, and vomiting. To see the ACTH (Acthar) Medication Guide and Prescribing Information, visit: http://www.acthar.com/

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Anticonvulsant Therapy

Vigabatrin (Sabril)

Vigabatrin (Sabril) is an anticonvulsant—a drug that can prevent seizures from recurring and stop the electrical seizure activity in the brain. It acts by increasing levels of gamma amino butyric acid (GABA) in the brain. It is believed that epileptic seizures may be the result of low levels of GABA. By increasing GABA, vigabatrin (Sabril) can lower the likelihood of an epileptic seizure.[9]

When vigabatrin (Sabril) was studied in babies with IS, 15.9% of babies were free from both spasms and hypsarrhythmia (chaotic brain waves) within two weeks.[10] (Sabril Prescribing Information, 2010)

Vigabatrin (Sabril) is a powder that you mix with water and give to your baby by mouth twice a day. According to the ISWG, vigabatrin (Sabril) is considered a drug of first choice for babies with IS who have tuberous sclerosis and is a drug of second or third choice for babies with other causes of IS.[3] The initial dosing is 50 milligrams per kilogram per day given in two divided doses and can be titrated by 25-50 milligrams per kilogram per day increments every 3 days up to a maximum of 150 milligrams per kilogram per day.[10] (Sabril Prescribing Information, 2010) However, the baby should have regular eye exams.[3]  If your baby does not show an improvement within 2 to 4 weeks, the medication should be slowly stopped due to the risk of permanent loss of peripheral vision or development of blurry vision.[10] (Sabril Prescribing Information, 2010) If treatment is successful, the spasms and hypsarrhythmia (chaotic brain waves) should disappear.

Vigabatrin (Sabril) Side Effects

1) Permanent vision damage:

  • Vigabatrin (Sabril) can damage the vision of anyone who takes it. The most noticeable loss is in your ability to see to the side when you look straight ahead (peripheral vision). If this happens, it will not get better. People who take vigabatrin (Sabril) do not lose all of their vision, but some people can have severe loss particularly to their peripheral vision. With severe vision loss you may only be able to see things straight in front of you (sometimes called ‘tunnel vision’). You may also have blurry vision.

2) Magnetic resonance imaging (MRI) changes:

  • Brain pictures taken by magnetic resonance imaging (MRI) show changes in some babies after they are given vigabatrin (Sabril). It is not known if these changes are harmful.

Stopping vigabatrin (Sabril) or any seizure medicine suddenly can cause seizures that will not stop. Vigabatrin (Sabril) may also make certain types of seizures worse. The most common side effects of vigabatrin (Sabril) are sleepiness, ear infection, and irritability. To see the vigabatrin (Sabril) Medication Guide and Prescribing Information, visit: http://www.sabril.net

Because of the risk of vision loss, vigabatrin (Sabril) is used in babies (1 month to 2 years old) with infantile spasms (IS) only when you and your doctor decide that the possible benefits of vigabatrin (Sabril) are more important than the risks[11] (Sabril Medication Guide)

Other Anticonvulsants

Several anticonvulsant therapies have been studied to see if they effectively treat IS. In their recommendations about therapies for IS, the AAN and the CNS did not recommend the use of any anticonvulsants other than vigabatrin (Sabril) in IS, concluding there was not enough evidence to determine whether these drugs were effective in treating IS.[6] Although they are not FDA-approved, some doctors prescribe these anticonvulsants for IS.

Zonisamide (Zonegran) appears to control IS in about one-fifth of patients. In one study, 5 of 25 patients with IS recovered completely within 1 to 2 weeks when zonisamide was given in doses ranging from 8 to 32 milligrams per kilogram per day.[2]

Another drug, topiramate (Topamax), given at a dose of 25 milligrams per kilogram per day, reduced spasms only in 43% of babies with IS, but 29% got worse and none became spasm-free, which does not qualify as effective therapy since the goal is not to reduce the spasms but stop them completely and to stop the hypsarrhythmia (chaotic brain waves).[2]

Valproate (Depakote) is another anticonvulsant used to treat IS. When given to children with IS in doses ranging from 25 to 100 milligrams per kilogram per day, one study found that spasms stopped in 73% of patients and hypsarrhythmia (chaotic brain waves) stopped in 91%. However, 23% of patients relapsed. The main side effect was an abnormal drop in the number of blood cells involved in forming blood clots, which occurred in one-third of patients. Liver failure is a serious risk in children under age 2. [6]

Lamotrigine (Lamictal) controlled IS to some degree when given at a dose of 6 to 10 milligrams per kilogram per day. However, due to the risk of rash, the dose must be increased slowly, which is not optimal for the treatment of IS.[2]


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Steroids and Other Drug Therapies

Steroidal Agents

There are many different brands of steroidal (corticosteroid) medications your doctor may prescribe for IS. Three different types of steroids used for IS are prednisone, prednisolone, and methylprednisolone. Prednisone is taken by mouth and comes under the brand names: Meticorten®, Orasone®, Prednicen-M®, Sterapred®, Sterapred DS®, and Deltasone®. Prednisolone, which is taken by mouth, is also called Orapred®, Prelone®, and MillipredTM. Methylprednisolone is given intravenously and comes under the brand names A-Methapred®, Depo-Medrol®, Medrol®, and Solu-Medrol®.

In two studies that used prednisone to treat IS, spasms stopped in about one-third of children who were treated for 2 to 6 weeks at a dose of 2 milligrams per kilogram per day.[3]

All three of the steroidal agents used in IS are man-made corticosteroids that have the effect of suppressing the immune system and reducing inflammation. Some of the side effects of corticosteroids may be serious. The most common side effects of the corticosteroids are infection, high blood pressure, irritability, and weight gain, especially around the face.[6]

Pyridoxine

In rare cases, IS can be caused by pyridoxine (vitamin B6) dependency. Some doctors may give a trial of 100 milligrams of pyridoxine intravenously.[2] If the EEG becomes normal, the cause of IS may be pyridoxine-dependent epilepsy.

Intravenous Immunoglobulin (IVIG)

Although it is used by some doctors, high-dose IVIG was not recommended by the AAN or CNS because there was not enough evidence to show it was effective in treating IS.[6]

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Non-drug Therapies

There are also non-drug therapies that can be used to treat IS: the ketogenic diet and surgery.

The ketogenic diet is a high-protein, low-carbohydrate diet. When given in a study to infants with IS who had not responded to other therapies, the diet reduced the number of spasms in 36% of infants and completely stopped the spasms in 19%. However, this study did not look at hypsarrhythmia (chaotic brain waves).[12] Side effects of the diet can include kidney stones, nausea, vomiting, and fatty liver.[3] The Infantile Spasms Working Group recommended the diet should not be used as first-line therapy, but should be tried as an alternative if ACTH and vigabatrin fail.[3]

Surgery is an additional option that may be considered when babies have not responded to medical therapy and/or have brain abnormalities that can be identified on brain scans. Some of the conditions that may be considered for surgery include cortical dysplasia, porencephaly, or tuberous sclerosis. In such cases, this approach may control seizures and improve developmental outcomes.[2][3]

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Reimbursement

Questcor, the makers of Acthar, started the Acthar Support & Access Program (A.S.A.P.) http://www.acthar.com/ispatient/getting-started-acthar

Lundbeck Inc., the maker of vigabatrin (Sabril) has a program called SHARE® (Support, Help, And Resources for Epilepsy).
http://www.sabril.net/ShareProgram.aspx


Prescription Products Discussed:

ACTH
H.P. Acthar® Gel is a registered trademark of Questcor Pharmaceuticals, Inc.

Lamotrigine
Lamictal® is a registered trademark of GlaxoSmithKline.

Methylprednisolone
A-Methapred® is a registered trademark of Hospira, Inc.
Depo-Medrol® is a registered trademark of Pharmacia & Upjohn Company Corp.
Medrol® is a registered trademark of Pharmacia & Upjohn Company Corp.
Solu-Medrol® is a registered trademark of Pfizer Inc.

Prednisolone
Orapred® is a registered trademark of Medicis Pediatrics, Inc.
Prelone® is a registered trademark of Muro Pharmaceutical, Inc.
MillipredTM is a registered trademark of Laser Pharmaceuticals, LLC.

Prednisone
Meticorten® is a registered trademark of Schering Corp.
Orasone® is a registered trademark of Solvay Pharma Properties, Inc.
Prednicen-M® is a registered trademark of Central Pharmaceuticals, Inc.
Sterapred® is a registered trademark of Merz, Inc.
Sterapred® DS is a registered trademark of Merz, Inc.
Deltasone® is a registered trademark of Upjohn Company.

Topiramate
Topamax® is a registered trademark of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Valproate
Depakote® is a registered trademark of Abbott Laboratories.

Vigabatrin
Sabril® and SHARE® are registered trademarks of Lundbeck, Inc.

Zonisamide
Zonegran® is a registered trademark of Dainippon-Sumitomo Pharma Co., Ltd.




















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