Medical Professional Publications

Targeting Early Remission for Infantile Spasms

(From the January 2014 Issue of PediatricsOnline)

A type of seizure called infantile spasms can often be treated effectively with a short course of a hormone therapy known as ACTH. According to a study by pediatric neurologists at Nationwide Children’s Hospital, the response to ACTH is nearly always determined within two weeks of starting treatment. The findings, presented recently at the American Epilepsy Society annual meeting in Washington, D.C., have prompted the researchers to advocate that clinicians consider changing therapies if ACTH fails to resolve infantile spasms quickly.

Infantile spasms (IS) are seizures commonly associated with West syndrome—a severe infantile epileptic encephalopathy often accompanied by poor developmental outcomes. Although they often involve clusters of sudden vigorous muscle contractions of the neck, arms, legs and trunk, the spasms can also present as mild contractions of the abdominal muscles or subtle movements of the eyes, head or shoulders. The seizures usually begin between 3 and 12 months of age, with peak onset at 6 months. Although IS can be associated with many different conditions, the exact cause of the disorder is unknown.

One of the most common treatments for the disorder is a drug called adrenocorticotropic hormone (ACTH). Although many patients respond well to ACTH, experts often disagree about how long treatment should continue, says John Mytinger, MD, director of the Infantile Spasms Clinic at Nationwide Children’s and lead researcher on this new study.

“There continues to be debate, even among experts, about the best dose—high versus low—or duration of treatment—short or long, which has resulted in the use of widely variable ACTH regimens that often differ even within a single institution,” Dr. Mytinger says. “The goal of our study was to provide additional insight into the best duration of treatment with ACTH.”

Clinician researchers analyzed data from patients treated for IS at Nationwide Children’s from January 2009 to September 2013, looking specifically at the time to remission following ACTH treatment. Two high-dose ACTH protocols were used during the study period. Prior to September 2012, a long course (typically 12 weeks) was used, and after this date the protocol was modified to a short course (typically four weeks). Patients were said to be in remission if they had no IS for 28 days or longer.

“When we looked back at all of our cases since 2009, response was determined in nearly all patients by two weeks,” Dr. Mytinger says, adding that the findings were similar to those of two small studies conducted at other institutions. “Given that early remission is so critical for optimal developmental outcome, we believe that an alternative treatment should be considered if there is no response to ACTH within two weeks.”

If ACTH is unsuccessful, clinicians can turn to either oral corticosteroids or an anti-seizure medication such as vigabitrin. In some cases, surgery or a ketogenic diet is needed to treat the underlying cause of the seizures.

There has been some concern among clinicians that a short course of ACTH may contribute to the rate of relapse. But in this new study, only four of the 23 responders to ACTH suffered a relapse, and only one of these patients was in the short-course group.

“We were surprised at our low rate of relapse overall, given that roughly one-third of children experience a recurrence of infantile spasms after an initial remission,” says Dr. Mytinger, who also is an assistant professor of clinical pediatrics and neurology at The Ohio State University College of Medicine. “Although our study is small and not powered to address this concern, the low rate of relapse after a short course of ACTH did not appear to justify ongoing treatment.”

Researchers are planning to continue their studies, expanding their focus to include the question of whether low-dose ACTH is as effective as high-dose ACTH. “There is considerable national interest among pediatric neurologists in this issue,” Dr. Mytinger says.

Recent presentations and publications:
Mytinger JR, Weber A, Heyer GL. The response to ACTH is determined early in the treatment of infantile spasms. Poster session presented at: American Epilepsy Society 2013 Annual Meeting; 2013 Dec 6-10; Washington, D.C.

Related Citation:
Mytinger JR, Joshi S. Pediatric Epilepsy Research Consortium, Section on Infantile Spasms. The current evaluation and treatment of infantile spasms among members of the Child Neurology Society. Journal of Child Neurology. 2012 Oct, 27(10):1289-94. Epub 2012 Aug 21.

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