- Epilepsy-causing events don't always cause epilepsy. What makes the difference?
- Italian researchers may have found the answer in a brain activity marker.
- Scientists praise grid computing as a crucial tool in their discovery.
By the time you finish reading this story, an untold number of people will have had a stroke, or have suffered a traumatic brain injury, or perhaps have been exposed to a toxic chemical agent. These events occur every day, millions of times each year. Of these victims, nearly 1 million go on to develop epilepsy.
These events — stroke, brain injury, toxic exposure, among others — are some of the known causes of epilepsy (also known as epileptogenic events), but not all who suffer from them develop epilepsy. Scientists today struggle to identify people who will develop epilepsy following the exposure to risk factors.
Even if identification were possible, there are no treatments available to prevent the emergence of epilepsy. The development of such therapeutics is a holy grail of epilepsy research, since this would reduce the incidence of epilepsy by about 40 percent.
Annual US epilepsy-related costs are an estimated $15.5 billion.
The development of anti-epileptogenic treatments awaits identification of a so-called epileptogenic marker – that is, a measurable event which occurs specifically only during the development of epilepsy, when seizures have yet to become clinically evident.
A collaboration led by Massimo Rizzi of the Mario Negri Institute for Pharmacological Research using the European Grid Infrastructure (EGI) appears to have pinpointed just such a marker. All it took was some heavy-duty grid computing and a handful of mice.
Epilepsy comes in many varieties, and is characterized as a seizure-inducing condition of the brain. These seizures result from the simultaneous signaling of multiple neurons. Considered chronic, this neurological disorder afflicts some 65 million people internationally.
Incurable at present, epileptic seizures are controllable to a large extent, typically with pharmacological agents. Changes in diet can lower seizures, as can electrical devices and surgeries. According the US National Institute of Health (NIH), annual US epilepsy-related costs are estimated at $15.5 billion.
Scientists Rizzi and his colleagues thought an alteration in brain electrical activity following the exposure to a risk factor might be a smart place to look for an epileptogenic marker. If this marker could be located, it then could be exploited to develop treatments that prevent the emergence of epilepsy.
Of mice and men
To search for the marker, Rizzi’s team focused their attention on an animal model of epilepsy. Mice developed epilepsy after exposure to a cerebral insult that mimics the effects of risk factors as they would occur in humans.
Examining the brain electrical activity of these mice, Rizzi’s team combed through 32,000 epidural electrocorticograms (ECoG), 12 seconds/4800 data points at a time, for up to an hour preceding the first epileptic seizure.
Each swath of ECoGs were run through the recurrence quantification analysis (RQA), a powerful mathematical tool specifically designed for the investigation of non-linear complex dynamics embedded in time-series readings such as the ECoG.
When the dust had settled, nearly 400,000 seconds of ECoGs revealed a telling pattern. The scientists found that high rates of dynamic intermittency accompany the development of epilepsy. In other words, the ECoGs of mice developing epilepsy from the induced trauma would rapidly alter between nearly periodic and then irregular behavior of brain electrical activity.
Noting this signal, researchers applied an experimental anti-epileptogenic treatment that successfully reduced the rate of occurrence of this complex oscillation pattern. Identification of the complex oscillation and its arrest under treatment led Rizzi and his team to confidently assert that high rates of dynamic intermittency can be considered as a marker of epileptogenesis. Their research was recently published in Scientific Reports.
Tools of the trade
Rizzi’s team made good use of the computational and storage resources at the Italian National Institute of Nuclear Physics (INFN). The INFN is a key component in the Italian Grid Infrastructure (IGI), which is integrated into the larger EGI, Europe’s leading grid computing infrastructure.
“The time required to accomplish calculations of these datasets would have taken more than two months by an ordinary PC, instead of a little more than two days using grid computing,” says Rizzi. “Considering also the preliminary settings of analytical conditions and validation tests of results, almost two years of calculations were collapsed into a couple of months by high throughput computing technology.”
From here, Rizzi hands off to pre-clinical researchers who can begin to develop interventions that will reduce and hopefully eliminate the emergence of epilepsy after exposure to risk factors. This knowledge holds out promise for use in the development of anti-epileptogenic therapies.
“This insight will help us reduce the incidence of epilepsy by approximately 40 percent,” Rizzi estimates. “Our future aim is to exploit our finding in order to improve the development of therapeutics. High throughput computer technology will keep on playing a fundamental role by significantly speeding up this field of research.”