New AAN/CNS Guideline on Infantile Spasms

June 15, 2012 — The American Academy of Neurology and the Child Neurology Society have released new guidelines on the medical management of infantile spasms in children.

The guideline updates the last version, released in 2004. Among the major changes are a recommendation that low-dose adrenocorticotrophic hormone (ACTH) may be considered for use, and that both ACTH and vigabatrin can be useful short-term treatment options, although ACTH is preferred to vigabatrin.

"We also want to highlight that early diagnosis and treatment of infantile spasms could lead to better long-term development outcomes," first author Christine Y. Go, MD, from the Hospital for Sick Children in Toronto, Ontario, Canada, told Medscape Medical News.

"I think that's one of the more important messages, because a lot of families, sometimes they're not sure if it's a seizure or not, and they kind of miss the boat," she said. "The child doesn't get treated until 3 to 4 months into the spasms, and by that time, their developmental outcomes are much worse."

The guideline update, jointly prepared by the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society, is published in the June 12 issue ofNeurology.

Epilepsy Syndrome

Infantile spasms are a "unique, age-specific epilepsy syndrome of early infancy, characterized by epileptic spasms often accompanied by neurodevelopmental regression and an EEG [electroencephalogram] finding of hypsarrhythmia," the authors write. "When all 3 components are present, the eponym 'West syndrome' is commonly used."

For the earlier 2004 Practice Parameter, the evidence for treatment suggested that ACTH and vigabatrin were "possibly effective" for short-term treatment (Level C) of infantile spasms and for children with tuberous sclerosis (Level C), the authors note. Information on long-term outcomes was not conclusive.

"Since 2004, there have been a lot of studies published, mainly using other agents as well, to see if they can also be used in infantile spasms, and also a few long-term studies, so now we have some information to make a recommendation," Dr. Go noted.

With this new guideline update, the committees concentrated on 5 major questions:

1. "Are other forms of corticosteroids as effective as ACTH for short-term treatment of infantile spasms?" The authors conclude that data are insufficient to recommend the use of prednisolone, dexamethasone, and methylprednisolone as being as effective as ACTH for short-term treatment of infantile spasms (Level U).
2. "Are low-dose ACTH regimens effective for short-term treatment of infantile spasms?" Evidence from Class I and Class II studies suggests that low-dose ACTH is "probably" as effective as high-dose treatment, so they have recommended that low-dose ACTH "should be considered as an alternative to high-dose ACTH for treatment of infantile spasms (Level B)."
3. "Is ACTH more effective than [vigabatrin] for short-term treatment of infantile spasms?" Two studies have demonstrated that ACTH is more effective than vigabatrin, including the recent United Kingdom Infantile Spasms Study (UKISS), but other smaller studies showed no difference. The authors recommend that ACTH (Level B) or vigabatrin (Level C) may be offered for short-term treatment of infantile spasms. "Evidence suggests that ACTH may be offered over [vigabatrin] (Level C)."
4. "Is there a role for the ketogenic diet or for AEDs [antiepileptic drugs] other than [vigabatrin] in managing infantile spasms?" For this question, they concluded that there is insufficient evidence to recommend any of these other therapies at this time (Level U).
5. "Does the successful short-term treatment of infantile spasms lead to long-term improvement of neurodevelopmental outcomes or a decreased epilepsy incidence?" One Class II study indicated that hormonal therapy with ACTH or prednisolone, relative to vigabatrin, leads to better neurodevelopmental outcomes in children with crytogenic spasms, they note. One previous Class III study and a more recent Class II study showed that a shorter lag time to treatment improves long-term cognitive outcomes. They recommend, therefore, that hormonal therapy with ACTH or prednisolone may be considered in preference to vigabatrin in infants with cryptogenic spasms to possibly improve developmental outcome (Level C). They further conclude that a shorter lag time to treatment with either hormonal therapy or vigabatrin may be considered to improve long-term cognitive outcomes (Level C).

"Clinicians have always known this, but we didn't have the evidence, and now we actually have studies to show that if you treat them early — and both studies showed less than 1 month from the onset of spasm to treatment, if the patients can be treated quickly and the spasms and the hypsarrhythmia pattern are successfully resolve — then you have better long-term developmental outcomes," Dr. Go said. "They may still have other seizures, but at least their developmental outcomes are better."

Future Research

A number of questions still remain unanswered with the current evidence, Dr. Go notes. One ongoing trial, the International Collaborative Infantile Spasms Study (ICSS), a multicenter randomized trial, is comparing hormonal therapy plus vigabatrin vs hormonal therapy alone. "I'm really looking forward to the results of that study," she said.

Other studies are needed to look at other issues, such as the optimal dose and duration of treatment with ACTH. "Some centers have a short-term, maybe 3-week course of ACTH, while other centers treat longer," she said. "For example, at Sick Kids, we actually have a 12-week, every other day injection of ACTH. That's our protocol, so that's a long time to be on ACTH."

The longer children are treated, the more common are the adverse events associated with treatment, so defining the optimal duration of treatment would be useful, Dr. Go added.

The guideline was developed with financial support from the American Academy of Neurology and the Child Neurology Society. None of the authors received reimbursement, honoraria, or stipends for their participation in the guideline development. Dr. Go has disclosed no relevant financial relationships. Disclosures for coauthors are outlined in the publication.