Epilepsy

Background

Clinical Trials SquareEpilepsy is a chronic, neurological disorder that affects the central nervous system causing an underlying tendency to have seizures. It currently affects more than 2 million people in the United States. Over one-third of these people live with uncontrollable seizures because they are unresponsive to all available treatments.

In order to be diagnosed with epilepsy, a person must have at least two unprovoked seizures (excessive electrical discharges in groups of brain cells). These seizures can be classified as either focal (restricted to one area of the brain) or generalized (involving all areas of the brain) depending on the origination of the abnormal brain activity. There are many processes that can result in a seizure, especially ones that irritate the cortex or gray matter.

Epilepsy can be fundamentally divided into focal epilepsy and generalized epilepsy, and focal epilepsy is more common. Mesial temporal lobe epilepsy (TLE) is the most frequently identified cause of medically intractable focal epilepsy in adults. It results from scaring in the mesial temporal lobe due to neuronal loss, atrophy, and gliosis within the amygdala-hippocampus. Focal epilepsy can also occasionally be due to sub-cortical lesions, located in strategic areas deep in the brain that would not normally cause seizures such as hypothalamic hamartomas , periventricular nodular heterotopia, focal nodular heterotopia, or tuberous sclerosis, and dysembryoplastic neuroepithelial tumors (DNET).

Current Treatment

Current treatment for epilepsy is successful in controlling seizures about 70% of the time. The most common method of treatment is medication.

In more severe cases, where seizures continue or only partially subside with medication, more aggressive, invasive procedures are needed. Surgery is generally an option for people who have focal epilepsy. This area may be removed to stop the seizures or at least make them easier to control with medication. When removing brain tissue is not an option, doctors can opt to make a series of lesions in the brain (multiple subpial transection) to prevent seizures from spreading. 

Other options that may be considered include tissue destruction (thermal ablation) with radiofrequency or laser probes inserted into the brain, or permanent implantation of electrodes for deep brain stimulation. Laser Interstitial Thermal Therapy (LITT) uses an implanted laser to ablate the tissue causing the seizures. Initial reports are that MRI guided LITT can be used to treat medication intractable mesial temporal lobe epilepsy, but the authors cautioned that larger, prospective studies are needed to determine the optimal ablation volume and target structures. Deep brain stimulation requires multiple surgeries and the presence of implanted foreign items in the brain carries additional risks, and the maintenance of these in patients with seizures can be an additional challenge. 

All of the options listed above are associated with the risk of surgical complications, including bleeding, infection and damage to normal brain. 

A less frequently used, but noninvasive approach is stereotactic radiosurgery, which utilizes the gamma knife or linear accelerator to deliver a high dose of radiation to destroy the targeted tissue. While this does not have the risk profile of surgery, it does have the long-term consequences of ionizing radiation and there is usually a 30-90 day delay between treatment and when a patient may experience the effects.  

Neither the invasive surgical procedures or the noninvasive radio surgical procedures are ideal.

Focused Ultrasound Treatment

Focused ultrasound is noninvasive, so it has a lower risk of adverse events compared to current treatment options. There are no incisions, no radiation, no damage to surrounding healthy tissue; and the benefits to the patients are immediate. To learn more about epilepsy, please read our focus feature.

The University of Virginia Comprehensive Epilepsy Program is conducting a research study on the use of focused ultrasound to treat deep lesions in the brain causing intractable epilepsy. The purpose of this study is to evaluate the effectiveness and safety of an investigational device that uses ultrasound waves from outside the head to treat medication-refractory seizures that are due to a small growth of abnormal cells in the middle of the brain, most commonly hypothalamic hamartomas. Some people with other lesions in the middle part of the brain will also be eligible.

We expect to open additional clinical trials in the US soon, and we will update this page as needed.   

In addition, pre-clinical research has demonstrated that with the right set of parameters, focused ultrasound can be used for neuromodulation, which is to stimulate or block brain activity in a transient and focal manner. Using the blocking effect, pre-clinical research has shown it is possible to use focused ultrasound as a means to block an ongoing seizure. UCLA is using low intensity focused ultrasound pulsations (LIFUP) to stimulate and suppress brain activity in people with temporal lobe epilepsy.

Clinical Trials

A current clinical trial is underway at the University of Virginia, for patients with medication-refractory epilepsy with subcortical focal lesions. For more information, contact Stacy Thompson at 434-982-4315 or  

A current trial is underway at the University of California Los Angeles for medication-refractory epilepsy in patients with subcortical lesions. For more information, contact Alex Korb, PhD at (323) 510-7532 or .

Notable Papers

Piper RJ, Hughes MA, Moran CM, Kandasamy J. Focused ultrasound as a non-invasive intervention for neurological disease: a review. Br J Neurosurg. 2016 Jun;30(3):286-93. doi: 10.3109/02688697.2016.1173189. Epub 2016 Apr 22.

Monteith S, Snell J, Eames M, Kassell NF, Kelly E, Gwinn R. Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. J Neurosurg. 2016 Feb 12:1-8.

Kang JY, Wu C, Tracy J, Lorenzo M, Evans J, Nei M, Skidmore C, Mintzer S, Sharan AD, Sperling MR. Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy. Epilepsia. 2016 Feb;57(2):325-34. doi: 10.1111/epi.13284. Epub 2015 Dec 24.

Quigg M, Harden C. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J Neurosurg. 2014 Dec;121 Suppl:232-40. doi: 10.3171/2014.8.GKS141608. Review.

Wynn Legon, Tomokazu F Sato, Alexander Opitz, Jerel Mueller, Aaron Barbour, Amanda Williams & William J Tyler. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nature Neuroscience (2014).

Jolesz FA, McDannold NJ. Magnetic resonance-guided focused ultrasound: a new technology for clinical neurosciences. Neurol Clin. 2014 Feb;32(1):253-69.

Dallapiazza R, McKisic MS, Shah B, Elias WJ. Neuromodulation for movement disorders. Neurosurg Clin N Am. 2014 Jan;25(1):47-58.

Click here for additional references from PubMed.

Video courtesy of InSightec

 

 
     

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