Modern Epilepsy Treatment 
Modalities Gain Momentum

HILTON HEAD—New or improved epilepsy treatments that can reduce seizure frequency or eliminate seizures altogether include MRI-guided laser ablation, responsive neurostimulation, and the investigational drug brivaracetam. Bassel W. Abou-Khalil, MD, Professor of Neurology and Director of the Epilepsy Center at Vanderbilt University in Nashville, expounded on these treatment modalities at 
the university’s 38th Annual Contemporary Clinical Neurology 
Symposium.

A New Era in Ablation Treatment

Brain tissue ablation, a technique developed in the 1980s, is not new, but recent technological improvements have made the procedure safer and more feasible. “Real-time monitoring of tissue heating through the use of MRI was an important development,” Dr. Abou-Khalil pointed out. The advent of laser technology and the use of cooling catheters also have been important advances, he added. “With laser ablation, the idea is to produce time-dependent thermal damage, not vaporization. Temperatures between 44 °C and 59 °C can produce this thermal damage, [thus] resulting in cell death.”

The Visualase thermal ablation system, which was approved by the FDA in 2010, and the NeuroBlate MRI-guided laser ablation system, approved in 2013, have proprietary computer software to help the surgeon identify the target tissue and create a surgical plan to treat the target while avoiding healthy surrounding tissue. In both systems, a stereotactic device holds the patient’s head in place while an entry is made in the skull. The laser applicator is then inserted into the target. The diameter of the Visualase laser applicator is 1.65 mm, while that of Neuroblate is 2.2 mm or 3.3 mm. The patient is then placed in the MRI and imaged to confirm the correct positioning of the laser for precise ablation of the target.

The Visualase system’s probe tip heats in a diffusing, circumferential manner, while the NeuroBlate system has a directional, “side-firing” tip option. Both systems can be used along with a standard 1.5-T or 3-T MRI system. The laser heats up the target tissue, then cooling prevents unwanted damage to surrounding tissue. Both NeuroBlate and Visualase use MR thermography for real-time monitoring of the procedure and visualization of the results.

Dr. Abou-Khalil cited a 2014 study of 13 adult patients with intractable mesial temporal lobe epilepsy who underwent computer-controlled laser ablation with continuous real-time MRI guidance. After five to 26 months of follow-up, 77% of patients achieved meaningful seizure reduction, and 54% were free of disabling seizures. Six of the nine patients with mesial temporal sclerosis achieved seizure freedom. The only significant complication was a visual field deficit resulting from deviated insertion of a stereotactic aligning rod, which was corrected before ablation. “Open surgery remains an option if laser ablation fails,” Dr. Abou-Khalil noted.

Stopping Seizures at Initiation

The FDA approved the NeuroPace Responsive Neurostimulation (RNS) system in 2013 as an adjunctive therapy for adults with refractory partial-onset epilepsy. The system works like a cardiac defibrillator. A small, battery-powered device, or neurostimulator, is surgically implanted in the skull. Leads connected to the neurostimulator are placed at seizure-onset zones on the surface of or inside the brain. The neurostimulator monitors and detects abnormal electrical activity and delivers electrical stimulation to onset zones to abort electrical seizure activity before it develops into a clinical seizure.

A multicenter pivotal trial randomized 191 patients one month after implantation to receive stimulation or sham stimulation. There was a 37.9% reduction in seizures in the treatment group, compared with a 17.3% reduction in the sham group, a statistically significant difference. “The closer the stimulation to abnormal brain activity, the better the outcome was,” Dr. Abou-Khalil added. No deaths occurred as a result of implantation or stimulation. At two years, there was a 53% median reduction in seizure frequency. Open follow-up treatment results showed that the benefit was sustained over a mean follow-up of 5.4 years.

DBS to Prevent
Seizures From Spreading

The anterior thalamus may play a role in seizure propagation. Deep brain stimulation of the anterior thalamus is another stimulation therapy being considered for FDA approval. Unlike RNS, this type of stimulation has an open-loop design.

In a multicenter trial, 110 adults with refractory partial seizures were randomized to bilateral stimulation or no stimulation of the anterior nuclei of the thalamus through an implanted neurostimulator during a three-month blinded phase. After the three-month period, all subjects received unblinded stimulation. During the last month of the blinded phase, the stimulated group had a 29% greater reduction in seizure frequency, compared with controls. The stimulated group was more likely to report depression (14.8% vs 1.8%) or memory problems (13% vs 1.8%) as adverse events. At two years, there was a 56% median reduction in seizure frequency, with 14 patients having been seizure-free for six months or more.

New Drug on the Horizon

Brivaracetam is a pharmaceutical treatment for epilepsy that may receive FDA approval in the near future, Dr. Abou-Khalil said. Brivaracetam is chemically related to levetiracetam. In a phase III study presented last year at the 68th Annual Meeting of the American Epilepsy Society, 768 patients with epilepsy and partial-onset seizures were randomized to adjunctive brivaracetam (ie, 100 or 200 mg/day) or placebo for 12 weeks. Both brivaracetam doses demonstrated statistically significant percent reductions in partial-onset seizure frequency per 28 days, compared with placebo. The 50% responder rates for brivaracetam 100 and 200 mg/day were 38.9% and 37.8%, respectively, compared with 21.6% for placebo, a statistically significant finding. The most frequent treatment-emergent adverse events were somnolence, dizziness, and fatigue.

—Adriene Marshall

HILTON HEAD—New or improved epilepsy treatments that can reduce seizure frequency or eliminate seizures altogether include MRI-guided laser ablation, responsive neurostimulation, and the investigational drug brivaracetam. Bassel W. Abou-Khalil, MD, Professor of Neurology and Director of the Epilepsy Center at Vanderbilt University in Nashville, expounded on these treatment modalities at 
the university’s 38th Annual Contemporary Clinical Neurology 
Symposium.

A New Era in Ablation Treatment

Brain tissue ablation, a technique developed in the 1980s, is not new, but recent technological improvements have made the procedure safer and more feasible. “Real-time monitoring of tissue heating through the use of MRI was an important development,” Dr. Abou-Khalil pointed out. The advent of laser technology and the use of cooling catheters also have been important advances, he added. “With laser ablation, the idea is to produce time-dependent thermal damage, not vaporization. Temperatures between 44 °C and 59 °C can produce this thermal damage, [thus] resulting in cell death.”

The Visualase thermal ablation system, which was approved by the FDA in 2010, and the NeuroBlate MRI-guided laser ablation system, approved in 2013, have proprietary computer software to help the surgeon identify the target tissue and create a surgical plan to treat the target while avoiding healthy surrounding tissue. In both systems, a stereotactic device holds the patient’s head in place while an entry is made in the skull. The laser applicator is then inserted into the target. The diameter of the Visualase laser applicator is 1.65 mm, while that of Neuroblate is 2.2 mm or 3.3 mm. The patient is then placed in the MRI and imaged to confirm the correct positioning of the laser for precise ablation of the target.

The Visualase system’s probe tip heats in a diffusing, circumferential manner, while the NeuroBlate system has a directional, “side-firing” tip option. Both systems can be used along with a standard 1.5-T or 3-T MRI system. The laser heats up the target tissue, then cooling prevents unwanted damage to surrounding tissue. Both NeuroBlate and Visualase use MR thermography for real-time monitoring of the procedure and visualization of the results.

Dr. Abou-Khalil cited a 2014 study of 13 adult patients with intractable mesial temporal lobe epilepsy who underwent computer-controlled laser ablation with continuous real-time MRI guidance. After five to 26 months of follow-up, 77% of patients achieved meaningful seizure reduction, and 54% were free of disabling seizures. Six of the nine patients with mesial temporal sclerosis achieved seizure freedom. The only significant complication was a visual field deficit resulting from deviated insertion of a stereotactic aligning rod, which was corrected before ablation. “Open surgery remains an option if laser ablation fails,” Dr. Abou-Khalil noted.

Stopping Seizures at Initiation

The FDA approved the NeuroPace Responsive Neurostimulation (RNS) system in 2013 as an adjunctive therapy for adults with refractory partial-onset epilepsy. The system works like a cardiac defibrillator. A small, battery-powered device, or neurostimulator, is surgically implanted in the skull. Leads connected to the neurostimulator are placed at seizure-onset zones on the surface of or inside the brain. The neurostimulator monitors and detects abnormal electrical activity and delivers electrical stimulation to onset zones to abort electrical seizure activity before it develops into a clinical seizure.

A multicenter pivotal trial randomized 191 patients one month after implantation to receive stimulation or sham stimulation. There was a 37.9% reduction in seizures in the treatment group, compared with a 17.3% reduction in the sham group, a statistically significant difference. “The closer the stimulation to abnormal brain activity, the better the outcome was,” Dr. Abou-Khalil added. No deaths occurred as a result of implantation or stimulation. At two years, there was a 53% median reduction in seizure frequency. Open follow-up treatment results showed that the benefit was sustained over a mean follow-up of 5.4 years.

DBS to Prevent
Seizures From Spreading

The anterior thalamus may play a role in seizure propagation. Deep brain stimulation of the anterior thalamus is another stimulation therapy being considered for FDA approval. Unlike RNS, this type of stimulation has an open-loop design.

In a multicenter trial, 110 adults with refractory partial seizures were randomized to bilateral stimulation or no stimulation of the anterior nuclei of the thalamus through an implanted neurostimulator during a three-month blinded phase. After the three-month period, all subjects received unblinded stimulation. During the last month of the blinded phase, the stimulated group had a 29% greater reduction in seizure frequency, compared with controls. The stimulated group was more likely to report depression (14.8% vs 1.8%) or memory problems (13% vs 1.8%) as adverse events. At two years, there was a 56% median reduction in seizure frequency, with 14 patients having been seizure-free for six months or more.

New Drug on the Horizon

Brivaracetam is a pharmaceutical treatment for epilepsy that may receive FDA approval in the near future, Dr. Abou-Khalil said. Brivaracetam is chemically related to levetiracetam. In a phase III study presented last year at the 68th Annual Meeting of the American Epilepsy Society, 768 patients with epilepsy and partial-onset seizures were randomized to adjunctive brivaracetam (ie, 100 or 200 mg/day) or placebo for 12 weeks. Both brivaracetam doses demonstrated statistically significant percent reductions in partial-onset seizure frequency per 28 days, compared with placebo. The 50% responder rates for brivaracetam 100 and 200 mg/day were 38.9% and 37.8%, respectively, compared with 21.6% for placebo, a statistically significant finding. The most frequent treatment-emergent adverse events were somnolence, dizziness, and fatigue.

—Adriene Marshall

HILTON HEAD—New or improved epilepsy treatments that can reduce seizure frequency or eliminate seizures altogether include MRI-guided laser ablation, responsive neurostimulation, and the investigational drug brivaracetam. Bassel W. Abou-Khalil, MD, Professor of Neurology and Director of the Epilepsy Center at Vanderbilt University in Nashville, expounded on these treatment modalities at 
the university’s 38th Annual Contemporary Clinical Neurology 
Symposium.

A New Era in Ablation Treatment

Brain tissue ablation, a technique developed in the 1980s, is not new, but recent technological improvements have made the procedure safer and more feasible. “Real-time monitoring of tissue heating through the use of MRI was an important development,” Dr. Abou-Khalil pointed out. The advent of laser technology and the use of cooling catheters also have been important advances, he added. “With laser ablation, the idea is to produce time-dependent thermal damage, not vaporization. Temperatures between 44 °C and 59 °C can produce this thermal damage, [thus] resulting in cell death.”

The Visualase thermal ablation system, which was approved by the FDA in 2010, and the NeuroBlate MRI-guided laser ablation system, approved in 2013, have proprietary computer software to help the surgeon identify the target tissue and create a surgical plan to treat the target while avoiding healthy surrounding tissue. In both systems, a stereotactic device holds the patient’s head in place while an entry is made in the skull. The laser applicator is then inserted into the target. The diameter of the Visualase laser applicator is 1.65 mm, while that of Neuroblate is 2.2 mm or 3.3 mm. The patient is then placed in the MRI and imaged to confirm the correct positioning of the laser for precise ablation of the target.

The Visualase system’s probe tip heats in a diffusing, circumferential manner, while the NeuroBlate system has a directional, “side-firing” tip option. Both systems can be used along with a standard 1.5-T or 3-T MRI system. The laser heats up the target tissue, then cooling prevents unwanted damage to surrounding tissue. Both NeuroBlate and Visualase use MR thermography for real-time monitoring of the procedure and visualization of the results.

Dr. Abou-Khalil cited a 2014 study of 13 adult patients with intractable mesial temporal lobe epilepsy who underwent computer-controlled laser ablation with continuous real-time MRI guidance. After five to 26 months of follow-up, 77% of patients achieved meaningful seizure reduction, and 54% were free of disabling seizures. Six of the nine patients with mesial temporal sclerosis achieved seizure freedom. The only significant complication was a visual field deficit resulting from deviated insertion of a stereotactic aligning rod, which was corrected before ablation. “Open surgery remains an option if laser ablation fails,” Dr. Abou-Khalil noted.

Stopping Seizures at Initiation

The FDA approved the NeuroPace Responsive Neurostimulation (RNS) system in 2013 as an adjunctive therapy for adults with refractory partial-onset epilepsy. The system works like a cardiac defibrillator. A small, battery-powered device, or neurostimulator, is surgically implanted in the skull. Leads connected to the neurostimulator are placed at seizure-onset zones on the surface of or inside the brain. The neurostimulator monitors and detects abnormal electrical activity and delivers electrical stimulation to onset zones to abort electrical seizure activity before it develops into a clinical seizure.

A multicenter pivotal trial randomized 191 patients one month after implantation to receive stimulation or sham stimulation. There was a 37.9% reduction in seizures in the treatment group, compared with a 17.3% reduction in the sham group, a statistically significant difference. “The closer the stimulation to abnormal brain activity, the better the outcome was,” Dr. Abou-Khalil added. No deaths occurred as a result of implantation or stimulation. At two years, there was a 53% median reduction in seizure frequency. Open follow-up treatment results showed that the benefit was sustained over a mean follow-up of 5.4 years.

DBS to Prevent
Seizures From Spreading

The anterior thalamus may play a role in seizure propagation. Deep brain stimulation of the anterior thalamus is another stimulation therapy being considered for FDA approval. Unlike RNS, this type of stimulation has an open-loop design.

In a multicenter trial, 110 adults with refractory partial seizures were randomized to bilateral stimulation or no stimulation of the anterior nuclei of the thalamus through an implanted neurostimulator during a three-month blinded phase. After the three-month period, all subjects received unblinded stimulation. During the last month of the blinded phase, the stimulated group had a 29% greater reduction in seizure frequency, compared with controls. The stimulated group was more likely to report depression (14.8% vs 1.8%) or memory problems (13% vs 1.8%) as adverse events. At two years, there was a 56% median reduction in seizure frequency, with 14 patients having been seizure-free for six months or more.

New Drug on the Horizon

Brivaracetam is a pharmaceutical treatment for epilepsy that may receive FDA approval in the near future, Dr. Abou-Khalil said. Brivaracetam is chemically related to levetiracetam. In a phase III study presented last year at the 68th Annual Meeting of the American Epilepsy Society, 768 patients with epilepsy and partial-onset seizures were randomized to adjunctive brivaracetam (ie, 100 or 200 mg/day) or placebo for 12 weeks. Both brivaracetam doses demonstrated statistically significant percent reductions in partial-onset seizure frequency per 28 days, compared with placebo. The 50% responder rates for brivaracetam 100 and 200 mg/day were 38.9% and 37.8%, respectively, compared with 21.6% for placebo, a statistically significant finding. The most frequent treatment-emergent adverse events were somnolence, dizziness, and fatigue.

—Adriene Marshall