Advances in Pediatric Neurology & Neurosurgery

Infantile spasms syndrome is a rare form of epileptic seizures that affects children in the first two years of life during a period of rapid brain development. The seizures involve sudden muscle stiffening causing a baby’s head, arms, or legs to bend forward in a spasm lasting one to two seconds. The spasms occur in 5- to 10-minute clusters and these clusters recur throughout the day. Left untreated, infantile spasms may result in developmental delays, intellectual disability, and lifelong epilepsy.

Dr. Zachary Grinspan

“Infantile spasms may be due to underlying neurological problems,” says Zachary Grinspan, MD, MS, Interim Chief of Child Neurology and Director of the Pediatric Epilepsy Program at NewYork-Presbyterian Komansky Children’s Hospital. “However, for some, they are an isolated problem in an otherwise healthy child. Successful early treatment can result in a permanent end to seizures and a life without developmental problems.”

With this in mind, Dr. Grinspan, in collaboration with colleagues from 18 children’s hospitals across the country, conducted a study to compare the effectiveness of initial treatment – standard versus non-standard therapies – for infantile spasms. The researchers analyzed patient data from the National Infantile Spasms Consortium on 423 children with new-onset infantile spasms that began at 2 to 24 months of age who received treatment at 23 pediatric hospitals.

The study evaluated the standard therapies of adrenocorticotropic hormone (ACTH), oral steroids, and vigabatrin against non-standard therapies, such as topiramate.

“Our findings represent robust evidence in support of prescribing only recommended therapies for the treatment of infantile spasms. It’s essential to treat children with the right medications as early as possible for the best outcomes.” — Dr. Zachary Grinspan

The findings, published in the July 15, 2021, issue of Neurology, underscored a strong preference for treating infantile spasms with ACTH or oral steroids, typically prednisolone, which the researchers calculated were similarly effective. Additionally:

• The percentages of children who had no further seizures after 30 days of starting initial therapy and did not require a second treatment were 46 percent for ACTH and 44 percent for oral steroids.
• By contrast, the estimated effectiveness of non-standard therapies was only 8 percent.

The investigators estimated the comparative effectiveness for initial treatment options using advanced statistical methods and then calculated the expected improvement if children had been treated with more effective therapies. They found:

• If a child treated with a non-standard therapy had been treated instead with a recommended therapy, the estimated effectiveness of the treatment would increase significantly from 8 percent to 39 percent for ACTH and to 38 percent for oral steroids.
• Changing from vigabatrin to ACTH or oral steroids would improve estimated treatment effectiveness from 29 percent to 42 percent.

While the researchers also estimated the effectiveness of vigabatrin as less effective than ACTH or oral steroids, the medication was still better than non-standard therapies. However, vigabatrin was particularly effective for a subset of children with spasms related to tuberous sclerosis complex, a rare, multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs.

“The side effects of hormonal therapies such as ACTH and steroids can be rough on families, which is why some may shy away from them, but our research and other studies have shown that non-standard therapies are ineffective for treating infantile spasms,” says Dr. Grinspan, who is also the Nanette Laitman Clinical Scholar in Healthcare Policy and Research/Prevention and Associate Professor of Population Health Sciences and of Pediatrics at Weill Cornell Medicine. Dr. Grinspan served as first author on the study.

Initial treatment duration with any of the three recommended medications is 28 days, but they come in different formulations and have different side effects. ACTH is administered by injection into the upper thigh muscle, whereas oral steroids can be given as a liquid by mouth. The side effects of both drugs include weight gain, puffiness, mood changes, and sleep problems. Vigabatrin is a powder mixed with water and taken orally. However, due to an elevated risk of permanent vision loss, it can only be prescribed by physicians enrolled in a special program for its use.

“Our real-world study used cutting-edge statistical methods to control for potential factors that may have introduced biases. As a result, our findings represent robust evidence in support of prescribing only recommended therapies for the treatment of infantile spasms,” says Dr. Grinspan. “It’s essential to treat children with the right medications as early as possible for the best outcomes.”