Epilepsy occurs in 0.5-0.7% of the population, of which 25% are children. 30% Of patients with focal epilepsy do not respond well to medication and half of them are eligible for epilepsy surgery. In recent years, the importance of early epilepsy surgery has been stressed, as successful surgery may lead seizure and medication freedom and improved social and cognitive development, especially in children. The current success rate of epilepsy surgery is around 65%; During surgery intracranial electrocorticography [acute ECoG, aECoG] is recorded in some medical centers. The presence of epileptiform brian activity, spikes, identified by clinical neurophysiologists, is used to guide the neurosurgeon in the extent of the brain tissue that needs to be resected. Spikes are considered markers of the presence of epilepsy. High Frequency Oscillations [HFOs, >80-500Hz] in the ECoG have recently been identified as a new biomarker for epileptogenic tissue. Retrospective research shows that their local presence strongly relates to the seizure onset, and removal of tissue with HFOs could predict a better surgical outcome. The area showing HFOs usually overlaps with, but is smaller than the area with spikes, and HFOs do not tend to propagate to distant sites as spikes do. The identification of HFOs is more objective than of spikes and automatic detection software exists.
A pilot study is performed to test the hypothesis : The intra-operative use of HFOs to delineate the epileptogenic cortex does not yield significantly worse outcome in seizure freedom than the current method based on spikes.
Study design is a single blinded multi-center randomized controlled trial. In two Dutch centers, the VU medical center [ Amsterdam] and University Medical Center Utrecht.
The study population [sample size 78] consists of patients of all ages with refractory epilepsy undergoing epilepsy surgery with aECoG to guide the extent of the resection.
Eligible patients are randomised, after informed consent, into group 1 [HFOs] in whom a resection guided by HFOs in the aECoG [new], or into group 2 [spikes] in whom a resection is guided by epileptiform spikes in the aECoG [current standard]. Ictiform spike patterns will always be resected.
Main study endpoint is outcome after epilepsy surgery after 1 year of follow-up dichotomized in total seizure freedom [Engel Ia&b] vs. seizure recurrence [Engel Ic-IV].
For children with refractory epilepsy whose seizures cannot be controlled by the usual medication choices, surgically removing the part of the brain most responsible for causing seizures can be curative. But in many cases, the area causing the seizures is too close to language or motor cortex, making surgery risky. Being able to map cortical regions crucial for normal function prior to undergoing surgery is vital to ensuring the best outcomes.
TMS is a noninvasive technology that creates a precise map of the eloquent cortex superimposed on a patient-specific MRI. TMS paired with neuronavigation can stimulate precise targets in the cortex, localizing functional areas with the proven accuracy of direct cortical stimulation [DCS]. The stereotactic camera provides visualization of the induced E-field, which is displayed in a 3-D rendering of the individual patient’s MRI. Placing surface electrodes on the desired muscles, the 6-channel EMG records motor-evoked potentials, amplitudes and latencies, induced by a TMS stimulus. Stimulation targets that elicit motor responses are marked as pegs color-coded as a heat scale, creating a map of the cortical somatotopy.
Language mapping is performed by inducing speech arrest or speech errors with brief trains of stimuli during a language task such as picture naming.
“Seizure
freedom is very important, but so is maintaining a child’s optimum abilities,” says CHOP pediatric neurologist Sudha Kessler, MD. “If we see that the epileptogenic zone is directly on top of or intertwined with the motor areas, we can counsel the family that there’s a high likelihood their child will be left with a weak arm or won’t be able to use their hand, etc. So the family can weigh the potential benefits of surgical
resection with the potential risk of a motor deficit.”
TMS offers a number of benefits over the standard preoperative workup, which includes inpatient electroencephalogram [EEG], magnetoencephalography [MEG], and 3 Tesla functional magnetic resonance imaging [fMRI]. It affords a level of spatial precision and accuracy these modalities lack and is more tolerable for younger patients and disabled patients who have trouble remaining still for MEG and fMRI.
“Our approach is focused on getting the best outcomes for our refractory epilepsy patients, whether that’s surgery or not,” says Kessler. “Our goal is to tailor the surgery as narrowly as possible to avoid taking out important areas that have function while still trying to disrupt the epileptic network that’s responsible for triggering seizures. TMS is an important tool in helping us get at these subtleties so we can take the big picture into account.”