Epilepsy Center – Treatment Options
Medications are the initial treatment choice for almost all patients with multiple seizures. Some patients who only have a single seizure and whose tests do not indicate a high likelihood of seizure recurrence may not need medications. Medications are highly effective and completely control seizures in the majority (approximately 70 percent) of patients. With approximately 20 different antiepileptic drugs currently available and more likely to be available in the near future, choosing the right medication for an individual patient has become complex. The choice of medication depends on a variety of factors, some of which include the type of seizure and epilepsy, likely side effects of the medication, other medical conditions in the patient that may be improved or worsened by the medication, potential for interactions with the patient’s other medications, age, gender and cost of the medication. Our adult and pediatric epileptologists have the knowledge and experience in utilizing all available antiepileptic medications. They also have the expertise to know when to treat patients and how to choose the most appropriate medication.
The remaining 30 percent of patients whose seizures are poorly controlled with two or more medications are considered to have refractory or intractable epilepsy. Apart from additional trials of antiepileptic medications singly or in combination, currently available treatment options for these patients include surgery, vagus nerve stimulation and dietary therapy.
The comprehensive epilepsy program offers dietary therapies—including the Ketogenic Diet and Modified Atkins Diet—to help patients control seizures. The Ketogenic Diet is a special high-fat, adequate protein, and low-carbohydrate diet that is initiated over three to four days in the hospital. The Modified Atkins Diet is similar to the Ketogenic Diet but slightly less restrictive. It can be initiated as an outpatient. Both diets have been shown to reduce seizures in approximately half the patients that are identified to be appropriate candidates. These are mainly children with refractory epilepsy who are not surgical candidates.
In patients whose seizures are not controlled by medications (termed medically refractory), surgery provides the best chance of complete control of seizures. However, not all patients with refractory epilepsy are suitable candidates for surgery. In addition to being refractory, they need to have partial rather than generalized epilepsy (i.e., their epilepsy arises from a single part of the brain rather than from both sides or from all over the brain). Further, the epileptic region should be in a part of the brain that, if removed, is unlikely to result in major neurological complications. Whether or not patients are likely to benefit from surgery is determined by detailed testing (pre-surgical evaluation). As surgery offers the best hope for a cure in such patients, both adult and pediatric patients with intractable epilepsy are offered pre-surgical evaluation at Penn State Health Milton S. Hershey Medical Center.
Pre-surgical evaluation consists of a two-phase process to determine if surgery is the best option and can provide good seizure control with minimal risk. Phase I involves all noninvasive (nonsurgical) tests. Phase II testing involves invasive tests (requires surgery) that are used in select patients.
Phase I Evaluation (noninvasive tests)
Not every patient requires every test available in the Phase I evaluation. Adult and pediatric epilepsy patients are evaluated by fellowship-trained epileptologists who determine the necessary and appropriate tests on an individualized basis. The following tests may be included in the phase I evaluation:
Electroencephalography (EEG): This is the initial test performed in every patient and is usually done as an outpatient. It is used not only to diagnose epilepsy but also to determine if the epileptic seizures are coming from a small part of the brain (partial seizures) or all over the brain ( generalized). Although most patients do not have seizures when the EEG is being recorded, they often have abnormal brain activity in the EEG (spikes or sharp waves) that indicates they have a tendency to have seizures. The location of this activity allows the physician to determine whether patients have partial or generalized seizures.
Inpatient video-EEG monitoring in adult and pediatric epilepsy monitoring units: This is the most important pre-surgical test and is performed with electrodes attached to the scalp (noninvasive monitoring). Patients are admitted to the hospital for several days and the purpose is to record seizures with simultaneous video and EEG. All the data are analyzed by a trained epileptologist. Detailed analysis of the symptoms during seizures as well as the location of EEG changes during seizures (ictal EEG onset), and abnormalities noted in between seizures (interictal), indicate the likely location where seizures originate within the brain.
3-Tesla Magnetic Resonance Imaging (MRI): This may detect an abnormality that could be the cause of the epilepsy (lesional epilepsy) or may be normal (nonlesional epilepsy). With more powerful MRI machines and use of special protocols and software at our center, subtle brain abnormalities are increasingly being identified.
Positron emission tomography (PET): PET scans look at the metabolic activity of the brain and allow physicians to determine if the brain is functioning normally. In patients with epilepsy, decreased brain function is seen in the region where seizures originate, when the patient is not actually having a seizure. On the other hand, if the patient has a seizure during the test, increased brain function is seen. PET scan may show abnormalities even if the brain MRI is normal. PET scans are usually done in the outpatient setting. At our center, we record an EEG during the PET scan to avoid any confusion and confirm that the patient is not having a seizure.
Single-photon emission computed tomography (SPECT): When a person has a seizure, an increased amount of blood flows to the brain region where the seizure begins. SPECT scans performed during seizures can identify the brain region where blood flow increases and thus indicate where they begin. SPECT scans are performed when the patient is admitted to the hospital for video-EEG monitoring.
Neuropsychological evaluation, functional MRI: Neuropsychological evaluation and functional MRI are used to assess cognitive functions, especially language and memory function prior to surgery, to see which side of the brain is dominant for language and to determine if there is decreased memory function in the epileptic region. This allows prediction of cognitive deficits after surgery. Functional MRI (fMRI) measures blood flow changes in areas of the brain during the performance of specific cognitive tasks.
Intracarotid amobarbital/methohexital (Wada test): This test involves the injection of a medication such as sodium amobarbital or methohexital into one carotid artery at a time, and is performed in selected cases. The medication causes temporary (1-5 minutes) paralysis of one half of the brain allowing independent testing of language and memory function in the other half. This test is also used to predict post-operative deficits in language and memory function.
Results of video-EEG monitoring are compared with those obtained from the other tests to see if they all point to the same region of the brain as being the origin of epileptic seizures. If all the test results are concordant, the patient is likely to be a good surgical candidate.
Thus, the phase I evaluation is designed to find the area of the brain that is likely to be generating the seizures (the focus), to determine if that area can be safely removed, and predict what kind of outcome might be expected with regard to seizure reduction or seizure freedom.
After the phase I evaluation, the epilepsy team meets to discuss patient management options in a multi-disciplinary setting to individualize treatments.
At this conference, based on the results of the phase I evaluation, patients may be deemed good or poor surgical candidates. In some cases, it may be unclear and more testing is needed. This additional testing is called phase II evaluation and is performed in select cases, where despite all prior tests, the seizure focus is not defined well enough for surgical treatment. Phase II evaluation involves video-EEG monitoring with electrodes that are placed inside the skull (invasive monitoring). As there is a greater risk of complications from invasive monitoring, the decision about the necessity for a phase II evaluation is made by the epilepsy team as a whole and discussed in detail with the patient.
Phase II Evaluation
There are several surgical implantation options. Each involves the implantation of electrodes ― either on the surface of the brain or within the brain. The benefit of these electrodes is that they are closer to the area producing the seizures than those simply placed on the scalp. After surgical placement of electrodes, the patients are transferred to the epilepsy monitoring unit, and epileptologists perform video-EEG monitoring in a similar fashion to the phase I monitoring.
The electrode types and implantation arrays differ and may include:
Subdural electrodes: A subdural electrode grid is a thin sheet of material with multiple small (several millimeters in size) recording electrodes implanted within it. These are placed directly on the surface of the brain and have the advantage of recording the EEG without the interference of skin, fat tissue, muscle and bone that may limit scalp EEG. Shapes and sizes of these sheets are chosen to best conform to the surface of the brain and the area of interest.
Depth electrodes: These are small wires which are implanted within the brain itself. Each wire has electrodes which surround it. These electrodes are able to record brain activity along the entire length of the implanted wire. They have the advantage of recording activity from structures deeper in the brain.
Combination: In a number of instances, it is beneficial to implant a combination of subdural electrodes and depth electrodes.
Stereoelectroencephalography: In rare instances, it may be best to approach invasive monitoring with a stereoelectroencephalography approach (stereoEEG). With this approach, multiple depth electrodes are implanted in a specific pattern that is individualized to the patient. The three-dimensional space covered by the depth electrodes is designed to encompass the seizure focus.
Functional mapping: Functional mapping is usually performed in patients with implanted subdural electrodes while they are in the Epilepsy Monitoring Unit. After a sufficient number of seizures are recorded, brief electrical stimulation is provided through each electrode separately to determine the normal function of the part of the brain underneath the electrode. This procedure is painless. The purpose is to map out critically important areas of the brain, such as those necessary for motor, sensory and language functions, and determine if there is any overlap with the seizure-generating regions. This allows tailoring of surgical resections to minimize the risk of major neurological deficits after surgery.
Surgery for the treatment of epilepsy involves resection, disconnection, stereotactic radiosurgery or implantation of neuromodulation devices. Within these categories are multiple options, depending on the clinical scenario.
Surgical resections: Surgical resection (removal of abnormal tissue) for epilepsy may fall into the following broad categories:
Lesionectomy: A lesion is a generic term for brain abnormalities that show up on imaging. Some types of lesions — such as cavernous malformations (blood vessel abnormality) and tumors — are prone to cause seizures. When preoperative testing indicates that these lesions are the cause of the epilepsy, they can be removed surgically.
Lobectomy: Each hemisphere, or half, of the brain is divided into four main lobes—the frontal, temporal, parietal and occipital. Seizures may arise within any of the lobes. A lobectomy is an operation to remove a lobe of the brain. Removal of one of the temporal lobes — called a temporal lobectomy — is the most common type of epilepsy surgery performed. Other types of lobectomies may rely on more specialized testing and surgery to prove a lack of vital function, such as speech, memory, vision or motor function.
Multilobar resection: A multilobar resection involves removal of parts or all of two or more lobes of the brain. It is reserved for more widespread abnormalities causing seizures, providing that no vital functions are in those regions.
Hemispherectomya: The brain is divided into a left and right hemisphere. In rare instances, children may have severe, uncontrollable and devastating seizures that can be associated with weakness on one side of the body. This may occur with a large amount of damage or injury to one of the hemispheres. Surgery to remove or disconnect a hemisphere, a hemispherectomy, may be curative. There are many subtypes of this surgery. The two main divisions are anatomic and functional hemispherectomy.
- Anatomic hemispherectomy involves removing the entire half of the brain that is injured and is generating the debilitating seizures. This includes the four lobes of the hemisphere — frontal, temporal, parietal and occipital.
- Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection.
These surgeries involve cutting and dividing fiber bundles that connect portions of the brain. The rationale is to separate the area of the brain that is generating the seizures from the normal brain.
Corpus callosotomy: The corpus callosum is one of the main fiber bundles that connect the two hemispheres. When debilitating generalized seizures or falling-type seizures start on one side of the brain and quickly spread to the other, patients may be candidates for this procedure. A large part of this fiber bundle may be cut. The procedure is palliative, meaning that although seizures may improve, they usually do not disappear.
Functional hemispherectomy: Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection.
Stereotactic radiosurgery: Stereotactic radiosurgery involves the delivery of a focused beam of radiation to a specific target area. Gamma Knife radiosurgery, one of the most common forms of radiosurgery, uses gamma rays to target the area to be treated. In epilepsy, it is generally reserved for small, deep-seated lesions that are visible on MR imaging.
Vagus nerve stimulation: The vagus nerve stimulator (VNS) is an FDA-approved device for the treatment of epilepsy that is not controlled with antiepileptic medications. It involves the surgical placement of electrodes around the vagus nerve in the neck and a generator placed below the collar bone in the upper chest region. It requires two separate incisions, but is an outpatient procedure. Subsequently, a programmer can be used by the epileptologist (from outside the skin) to change the intensity, duration and frequency of stimulation to optimize seizure control. Vagus nerve stimulation rarely cures seizures but may decrease the frequency and severity of seizures. It is an option for those who are not candidates for other types of surgery.