Texas Children’s researchers discover a noninvasive method to locate seizure foci in Infantile Spasms/West Syndrome patients
A recent study from Texas Children’s Hospital and Baylor College of Medicine finds high-frequency activity (HFA) measured with regular electroencephalogram (EEG) recordings can serve as a surrogate clinical biomarker to precisely locate areas of the brain that generate epileptic spasms in infantile spasms (IS)/West syndrome patients. In those children that are candidates for epilepsy surgery, this discovery should make it significantly easier for neurosurgeons to precisely map the abnormal region that needs to be removed. The study appeared in the journal Epilepsia.
Epileptic spasms are brief seizures that are the hallmark of catastrophic childhood seizure disorder called infantile spasms or West Syndrome. Early diagnosis and treatment of infantile spasms is urgent. If left untreated, these spasms can halt brain development and cause permanent long-term cognitive and motor damage. A type of hormonal therapy and vigabatrin in conjunction with ketogenic diet are used to manage these spasms. If a child fails to respond to these frontline drug treatments and continues to experience frequent spasms, then the last resort can be the surgically removal the brain region from where the spasms originate. Not all children are candidates for epilepsy surgeries because the affected brain area may control important functions such as speech and its removal would have unacceptable consequences. Accurate and precise mapping of the area from where spasms originate is therefore critical for a successful outcome. Currently, neurosurgeons rely on a variety of imaging and neurophysiological techniques to map epileptic regions but newer approaches could aid them in this endeavor.
In a previous study, researchers in the laboratory of Dr. John Swann, director of the Cain Foundation Laboratories for Pediatric Neurology, co-director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and professor at the Baylor College of Medicine, showed infantile spasms originate in the neurons of the neocortex. Furthermore, they discovered that the “up” states of the well-orchestrated ‘up’ and ‘down’ states of brain activity produced spasms. The researchers were able to identify the different brain states using the well-established experimental procedure called multiunit activity (MUA) recordings wherein electrical activity multiple nerve cells is measured simultaneously using advanced state-of-the art neurophysiological equipment.
“While MUA is an amazing experimental tool for neuroscientists, it is not suitable for routine neurological evaluation of patients since it is too invasive and requires specialized technical and surgical methods,” Dr. Swann said. “We wanted to extend our previous findings to clinical settings to help IS patients. So, we set out to find an easy-to-measure clinical biomarker that could be used in lieu of MUA for accurate identification of the area of brain from where spasms originate.”
West syndrome is diagnosed using a combination of clinical features and a characteristic EEG recording that can be best described as chaotic and disorganized with a high-amplitude slow wave called hypsarrhythmia that occurs between the spasms. Interestingly, Swann lab researchers found that a type of epilepsy-associated high-frequency activity (HFA) that can be easily identified using routine EEG also overlaps with hypsarrhythmia in their animal model of infantile spasms. This led them to wonder if HFAs could be used as a clinical biomarker for the pathological “up” state associated with infantile spasms.
To test this possibility, they performed a side-by-side comparison of the temporal and rhythmicity patterns of HFA versus MUA during neocortical ‘up’ and ‘down’ brain states and during spasm generation in rodents. They found the electrophysiological signatures of HFA closely mimicked the MUA patterns before, after and during the seizures, lending strong support for the use of HFA as a surrogate clinical biomarker to pinpoint specific foci from where spasms originate in IS patients.
“We are very excited by the potential clinical implications of our findings for IS patients. We hope that neurologists and neurosurgeons will find it easy to use HFA for early diagnosis and to identify specific brain locations that need to be targeted for epilepsy surgeries. In fact, they could just perform regular EEG using the equipment that is already available in most hospitals and clinics and analyze the high-frequency activity data, which is currently often discarded or ignored. Since this methodology uses existing equipment and technical know-how, it can be adopted fairly rapidly to clinical settings. We are hopeful that early implementation of the practice of analyzing HFAs from routine EEGs can significantly reduce the long-term cognitive and motor disabilities and thereby, improve clinical and quality of life outcomes for those IS patients who are surgical candidates.” Swann concluded.
Other authors include Dr. Chih-Hong Lee and John T. Le. Both are affiliated to the Cain Foundations laboratory for Pediatric Neurology at Texas Children’s Hospital and Baylor College of Medicine. The study was supported by grants from the NIH and CURE.