There is no need for pediatric neurosurgeons to delay brain surgery on newborns with epileptic surgery, say Israeli-led international team

Epilepsy and brain seizures can develop in any person at any age, and it is more common in young children and older people. Slightly more men than women have epilepsy. About one person in 100 will have an unprovoked seizure in their lifetime.

 

The average person doesn’t think that newborn babies can have epileptic seizures, but it can and does occur in rare cases, and the condition does not respond to medications. Drug-resistant epilepsy (DRE) during the first few months of life is challenging and requires aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental abnormalities, brain surgery to treat the condition often involves extensive tissue resections (surgery to remove tissue or part or all of an organ) or disconnection. There is little medical literature on “ultra-early” epilepsy operations to control the seizures and their safety. 

Prof. Jonathan Roth (courtesy)

Most causes of very early epilepsy leading to surgery are congenital cortical malformations such as hemimegalencephaly (which involves one side of the brain), cortical dysplasia (which occurs before a baby is born, when developing brain cells (neurons) fail to reach the parts of the brain for which they are genetically destined). As a result, those areas of the brain lack the appropriate neural connections to function properly) and cortical tubers or hamartomas (noncancerous lesions made of an abnormal mixture of normal tissues and cells from the area in which it grows). 

 

There is no clear cause of the malformations, some of which may be genetic related (usually mutations that just occur by themselves and not inherited mutations). There is no known associated with a lack of vitamins or alcohol intake by the mother. 

 

DRE can lead to epileptic encephalopathy in this age group, with the potential to cause significant developmental harm that requires aggressive treatment and often general anesthesia and mechanical ventilation. Uncontrolled seizures can lead to memory and learning impairment, and anti-seizure medications also have a major role in the neurodevelopmental outcome.

 

Until now, pediatric neurosurgeons have been reluctant to perform surgery to relieve epileptic surgery in infants up to the age of three months, even though the seizures are very upsetting and could be harmful. This reluctance to perform very-early epilepsy surgery may not be justified and may not reflect the actual safety profile of such surgeries, even in this very young population.

 

But a research study carried out by Israelis and colleagues in other countries on 64 such newborns with DRE has shown that there is no reason to postpone such surgery. The study, entitled “Epilepsy surgery in infants up to three months of age: Safety, feasibility, and outcomes: A multicenter, multinational study,” was recently published in the journal Epilepsia.

 

The infants, who suffered from cortical dysplasia (28), hemimegalencephaly (17) and cortical tubers (five) underwent 69 surgeries before the age of three months 

 

None of the infants died after surgery and the seizures were relieved. The babies’ conditions were followed up for more than three years, during which the number of antiseizure medications they were given was significantly reduced.

Prof. Shlomo Constantini (courtesy)

 

Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. This surgical treatment should not be postponed to treat DRE in very young infants based on their age, asserted Prof.  Jonathan Roth and Shlomo Constantini, pediatric neurosurgeons at the Dana Children’s Hospital at Tel Aviv Sourasky Medical Center who were among the lead researchers. 

 

“While we in Tel Aviv are a leading world center in our field, there is great importance in international collaboration on rare diseases,” commented Constantini.

 

Also participating were neurosurgery departments at Baylor College of Medicine in Texas; the Center of Excellence for Epilepsy in India; the Munari Centre for Epilepsy Surgery in Italy; the University of Utah School of Medicine, the Ribeirão Preto Medical School in Brazil; the Children’s National Medical Center in Washington, DC, the Hospital for Sick Children of the University of Toronto; the Institute for Brain Protection Sciences in St. Petersburg, Florida; Johns Hopkins University School of Medicine in Maryland; the Geisinger Commonwealth School of Medicine in Pennsylvania; the Istituto Giannina Gaslini in Italy;

Cincinnati Children’s Hospital Medical Center in Ohio; Children’s Hospital at New York University; the Cleveland Clinic; Rambam Medical Center in Haifa; Children’s Hospital of Chicago; Northwestern University in Chicago; University of California Los Angeles; the Great Ormond Street Hospital in London; and Santobono-Pausilipon Children’s Hospital in Italy. 

It is well known and accepted that the quality of life of children with epilepsy and their families, as well as the ability to maximize their developmental potential, is closely correlated with epilepsy control, and thus the important understanding that early surgery is crucial for this, said Roth, who leads the pediatric epilepsy surgical program at the Dana Children’s Hospital in Tel Aviv

 

“Delaying surgery until additional weight has been gained is not necessarily beneficial in the long run,” they wrote. “As stated previously, many of the infants awaiting surgery were taking several antiseizure medications, and often needed respiratory or systemic support to control the aggressive and frequent seizures. Thus, postponing surgery may lead to prolonged ineffective medical treatment, exposing the immature brain to endless epileptic activity, and many side effects of the various drugs. We would cautiously state that “no child is too

small or too young if seizures are severe enough…The study is a collaboration with major epilepsy centers worldwide, and also stresses the need to refer these highly complex cases to centers with vast experience in epilepsy surgery on infants,” the researchers concluded.

 


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