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Treatment with Medications

There are two treatments for infantile spasms approved by the Federal Drug Administration (FDA) in the USA.  Vigabatrin was approved in 2009 and ACTHar Gel was approved in 2010.  These two treatments, as well as other treatment options, are described below.

Vigabatrin
Vigabatrin is a medication that blocks the breakdown of GABA (gamma aminobutyric acid) transaminase, which is responsible for the metabolism of GABA, a major inhibitory neurotransmitter in the brain. Consensus from the NIH Tuberous Sclerosis Complex Consensus Conference in 2000 was that vigabatrin is the drug of choice to treat infantile spasms in children with TSC (Hyman and Whittemore, 2000).  There are several peer-reviewed publications that report convincing evidence of the effectiveness of vigabatrin in treating children with infantile spasms, especially those with TSC (Chiron et al., 1991, 1997; Elterman et al., 2001, 2010; Lux et al., 2002; Mackay et al., 2002; Mikati et al., 2002; Mackay et al., 2004; Thiele, 2004).

The major advantages of vigabatrin are:

  • The ability to quickly increase the dosage when the drug is started.
  • It works quickly.
  • The drug can be used outside the hospital for long term treatment. 
  • It's usually tolerated well with only minor side effects, except for possible visual field loss (Nabbout, 2001). 

Vigabatrin (Sabril®) was approved for use in the USA by the Food and Drug Administration (FDA) in 2009. For more information about the drug or help getting the medication: 

Visual Field Loss Associated with Vigabatrin: Visual problems in people taking vigabatrin were first reported in 1997 in adults (Eke et al, 1997; Russell-Eggit et al, 2000; Besch et al, 2002) and later in some children (Harding et al., 2002).  

  • The vision problems consist of losing peripheral vision, or not being able to see to the far left or far right of the visual fields. A recent study indicates that loss of peripheral visual fields may be more common in adults than in children, with 44% and 34% exhibiting loss of visual fields respectively (Macquire et al., 2010). 
  • The safety of vigabatrin in children with infantile spasms is of particular concern because these children could have other vision problems unrelated to vigabatrin (Iinuma K et al. 1994; Castano G et al. 2000; Brooks BP et al. 2002; Hammoudi DS et al. 2005). 
  • The FDA requires that any physician who prescribes vigabatrin for their patients must be registered. Visual testing must also be done on any person who uses vigabatrin. Health care providers may indicate that an individual is not able to perform the visual field testing on the form when they prescribe vigabatrin if testing is not feasible for a specific individual.

It can be hard to determine the risk-benefit ratio of vigabatrin in children with infantile spasms and to know who may do best with this drug. 

  • In many cases, the patient may not be aware that they have the visual field loss because it develops slowly and does not affect central vision.  The visual problem is confirmed by perimetric testing, a special type of vision testing.
  • In children, especially in the young or disabled, it is difficult to detect the visual field loss. We don't yet know if children are at higher or lower risk for this adverse effect compared to adults. 
  • Children younger than 9 years old usually are unable to cooperate for perimetry or vision studies.   
  • MRI changes have also been found in very young children taking vigabatrin. These were first seen in 2009 (Pearl,  et al, 2009).  The changes were in the central structures of the brain.  It was not clear that there were any clinical consequence, and, when the vigabatrin was discontinued, all of the changes resolved.  A similar MRI abnormality was seen in a TS patient treated for IS, and, when the vigabatrin was stopped, the abnormality disappeared. (Hsieh, 2010)
  • Because of the risk of vision loss, and the MRI abnormalities, generally vigabatrin is used in babies (1 month to 2 years of age) with infantile spasms only when you and your doctor decide that the possible benefits of vigabatrin are more important than the possible risks.
  • It is very important to understand the developmental consequences of continued IS when making these decisions. 
  • Children who are first treated with vigabatrin, but who do not achieve a good response, may consider using ACTH.

Adrenocorticotropic Hormone (ACTH; marketed as Acthar® Gel)
ACTH has been used for many years as a treatment for infantile spasms, and was approved by the FDA as Acthar® Gel in October 2010. 

  • The benefits of ACTH in infantile spasms could be related to how it affects the release of adrenocorticosteroids and neurosteroids. 
  • For some children with TSC, ACTH is effective in treating infantile spasms when vigabatrin does not work, and the reverse is also true.
  • Side effects related to ACTH in infants, includes: increased pressure in the eyes (Friling et al., 2003), immunosuppression and possible increase in the size of cardiac rhabdomyomata, the heart tumors associated with TSC (Hishitani et al., 1997; Hiraishi et al., 2000).
  • Parents should talk with their child's health care providers about possible risks and benefits of this treatment.  

For more information about Acthar® Gel and the ACTHar Support and Access Program (A.S.A.P.): 

  • Go to www.acthar.com 
  • Call 1-888-435-2284, Monday-Friday from 8:00 am-8:00 pm ET.

Oral Medictions

One of the ongoing questions is whether steroids given by mouth may be helpful in treating IS, rather than Acthar® Gel which must be given by injection.  There are no studies that compare these treatments and answer the question definitively, but some clinicians are using oral prednisone or prednisolone instead of ACTH (Lux, 2002).  Most clinicians use vigabatrin as the first drug, but if it is not successful then a trial of ACTH or prednisolone could be tried.  However, it should be noted that prednisolone has not been approved by the FDA for treatment of IS. 

Clinical trials reporting the efficacy of other medications (zonisamide, topirmate) for the treatment of infantile spasms have shown some promise in small studies, but failed to effectively treat infantile spasms in larger, multi-center clinical trials.  It is likely that the initial success with these medications reflects the spontaneous remission rate of 20-25% of all individuals with infantile spasms. These new antiepileptic drugs represent a potential nonhormonal approach for infantile spasms, but additional studies are needed to verify their safety and effectiveness. Future studies will hopefully identify other anti-epileptic drugs that control infantile spasms and minimize the risk on the development of the brain.

Other Treatment Options

Dietary therapy

The ketogenic diet has been reported to be a safe, well-tolerated and possibly effective alternative treatment in some children with infantile spasms who do not respond to standard seizure medications (Kossoff et al. 2002; Hong et al., 2010). A few tips to consider about dietary therapy: 

  • Children on the diet must be carefully selected, monitored, and followed.
  • The diet needs to be followed strictly and requires a comprehensive team approach. Parents must be integrally involved in this treatment.
  • The ketogenic diet generally provides sufficient nutrition to keep growth within normal parameters over a defined period. Kosoff and colleagues (2002) reported 50% of the children with hypsarrhythmia and follow-up EEGs had EEG improvement. 
  • Diet-related side reactions (nephrolithiasis, gastroesophageal reflux) should be monitored.

Surgery  

Some children with TSC continue to have spasms and experience psychomotor regression, despite medication or dietary treatments. Some of these children may be candidates for surgery and should be evaluated by a team experienced in epilepsy surgery for children with TSC (Chugani et al., 2010). A number of studies have shown that surgery can be helpful for some children with TS and infantile spasms (Asarnow et al., 1997; Asano et al., 2001; Curatolo et al., 2001; Chugani et al., 2010, Wu, 2010) by improving seizure control and developmental outcomes (Chugani & Pinard, 1999; Jonas et al, 2005). Indications for surgical treatment of a child with TS and infantile spasms include: 

  • Intractability of seizures.  The infant’s seizures should be refractory to appropriate trials of medications (one cannot use “all” because it is not possible to try “all” of the medications).  
  • Focal features on EEG.  Focal abnormalities should be present on interictal and/or ictal EEGs of potential surgical candidates.  
  • Focal abnormalities on neuroimaging.  All infants should have a structural change in the brain (by CT/MRI/MEG) or an area of functional change (by PET/SPECT scan). 

The most appropriate time to consider surgery has not been clearly defined. Providers and families must consider the potential risks of waiting too long versus having unnecessary surgery too early. Some professionals proposed that, in addition to evaluation of seizures, developmental assessment be a key factor in the surgical decision (Shields et al, 1999). If a child with infantile spasms has met developmental milestones even though he or she has infantile spasms, the potential benefits of surgery should be carefully weighed with the potential risks.  

In summary:

  • Infantile spasms should be treated as soon as the diagnosis is made. 
  • The drug of choice for treatment of infantile spasms in children with TSC is vigabatrin.  If the seizures are not controlled with vigabatrin at a high enough dose, then ACTH or prednisolone should be considered.  Children with TSC may also be candidates for other treatments such as diet or surgery. 
  • It is important to avoid treating children with TSC with medications that may induce or make infantile spasms worse. Medications such as phenobarbital, phenytoin, carbamazepine and tiagabine should not be used in children and especially in infants with TSC (Dulac, 2001).
  • Treatment with valproate or one of the newer antiepileptic medications, such as topiramate, rather than with phenobarbital, carbamazepine or phenytoin, is recommended when the diagnosis of infantile spasms has not yet been made (Dulac, 2001), even in small children and infants. 
  • Surgery should be carefully considered in young children with TS and infantile spasms who do not respond to appropriate medical treatments for infantile spasms and who meet other critieria for surgery. 
Reviewed by: Patricia O. Shafer RN MN on 12/2013
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