Intractable Seizures in Children: Surgical Management at Mayo Clinic

Elaine C. Wirrell, M.D., a pediatric neurologist, and Nicholas M. Wetjen, M.D. a pediatric neurosurgeon, joined Mayo Clinic in Minnesota in 2008 and are making a difference for children with intractable seizures. Experts in pediatric epilepsy, Dr. Wirrell and Dr. Wetjen are part of the multidisciplinary epilepsy team that includes two pediatric epileptologists (Katherine C. Nickels, M.D., has also recently joined the team), neuroradiologists, neurosurgeons, and two new pediatric neuropsychologists.

One in five children with epilepsy have intractable seizures — defined as failure to respond to at least two appropriate antiseizure medications. Surgery may be an option, but the path to that decision is complex. At many institutions the evaluation process may take months. At Mayo Clinic, the surgical work-up can be done in one to two weeks and includes state-of-the art functional brain mapping and seizure locus studies. If the child is documented to be a good candidate and the family decides to proceed, surgery can then be promptly scheduled.

As Dr. Wetjen explains, "The turnaround time at Mayo is quick because the care is not fragmented and there is immediate communication among the team members. For example, a child with lesional epilepsy (e.g., tumor, cavernous malformation) may come in on a Monday; have an evaluation that includes imaging, inpatient video EEG monitoring with several recorded seizures, a SISCOM study, and a neuropsychological evaluation by Thursday; and, in some cases, be in surgery by Friday. The pace is not always that fast, however. The typical range for most epilepsy patients is two to four weeks from initial consult to surgery."

Determining Surgical Candidacy

A pediatric epileptologist determines the frequency, severity and duration of seizures and whether other conditions coexist. A scalp EEG and MRI help identify seizure etiology (e.g., cortical dysplasia, vascular malformations, arteriovenous malformation, tumor, trauma, stroke or rare metabolic conditions) and the presence or absence of a specific lesion and its focus. A pediatric neuropsychologist then evaluates baseline cognitive function and helps establish lateralization of function. Other tests to localize function may include functional MRI (fMRI) or sodium amobarbital (WADA) testing.

Technician explains EEG procedure to patient and mother

Inpatient Pediatric EEG Monitoring

EEG monitoring is offered at the Eugenio Litta Children's Hospital, an 85-bed pediatric facility located within Mayo's Saint Marys Hospital. Four rooms, as well as the pediatric intensive care unit at the children's hospital, are hard-wired with ceiling cameras for behavioral observation and continuous EEG monitoring via external or intracranial EEG leads (Figure 1).

Inpatient EEG video monitoring is needed to record several seizures by EEG and video and to minimize risks of medication withdrawal, a process that is often required to record seizures. Monitoring may take from 24 hours to several days to record at least three seizures. Digital recording allows analysis of the EEG in a number of formats.

The EEG video monitoring unit is specifically designed with children and families in mind. Child life specialists not only provide toys, movies, computer games, and other entertainment, but also help children and families through procedures that may be uncomfortable or unfamiliar. The nurses and EEG technicians are, according to Dr. Wetjen, "remarkably attentive and good at what they do." Dr. Wirrell agrees, saying, "Our EEG technologists are superb and dedicated to their patients. I have not worked with one who is not devoted to the child."

Dr. Wirrell also notes that "unlike many centers that offer monitoring, we have the ability to monitor the patient every second of the day or night, so if the patient or family member is sleeping, or the seizure is subtle, our technologists are still able to pick it up." Continuous monitoring by trained technicians not only increases safety, but can reduce the length of time a patient stays in the monitoring unit.

Localizing Seizure Focus through SISCOM

SISCOM stands for subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI. Pioneered at Mayo Clinic, it fuses the MRI image with the SPECT image, an innovation particularly useful in localizing seizure focus when seizures have a focal onset. A radioactive tracer is injected as soon as possible during a seizure. The first imaging study is performed shortly after the seizure, and the second after 24 hours of seizure freedom. Dr. Wirrell notes, "SISCOM can be very helpful in pediatric epilepsy in which the MRI frequently does not show a clear structural abnormality."

If imaging studies establish a clear focus that is not in an area of critical brain function, the child may have surgery for resection. If the focus cannot be precisely localized, or if it is in an area of eloquent cortex, intracranial electrodes may be implanted and electrical stimulation performed during an awake surgical procedure to more narrowly delineate seizure focus and to map important motor and cognitive/linguistic functions.

All the data for each case and the potential risks and benefits of surgery are reviewed at the epilepsy team conference where, according to Dr. Wirrell, "Everyone provides input, and there is always plenty of time to discuss each patient fully." The attending neurologist then meets with the family to review the recommendations.

Hemispherotomy

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Multiple Surgical Options

Depending on the nature of the problem, the patient may have surgical resection or disconnection. Resections are generally conducted for tumors, vascular malformations, and areas of cortical dysplasia. Drop attacks are often treated with cortical disconnection (corpus callosotomy).

In patients whose epilepsy arises from an entire hemisphere, Dr. Wetjen and colleagues may perform a peri-insular hemispherotomy rather than the traditional hemispherectomy. Rather than removing the entire hemisphere, a hemispherotomy involves a much smaller resection followed by image-guidance technology to disconnect the diseased hemisphere from the healthy one (Figure 2). As a result, there are fewer postoperative complications such as hydrocephalus and superficial siderosis.

Other options include endoscopic surgery for the rare patient with gelastic or laughing seizures in which there is a third ventricle hypothalamic hamartoma; radio-surgery or microsurgical resection for seizure-causing arteriovenous malformations; and neuromodulation using vagus nerve stimulation for generalized seizures.

Implanted pacemaker stimulation, another form of neuromodulation, is a future possibility. As Dr. Wetjen says, "We don't know yet if pacemaker stimulation will be effective in adults with epilepsy, but Mayo is always looking for better ways to manage patients. The infrastructure is here if those advances are appropriate."

Caring for the Whole Family

"Epilepsy impacts siblings as well as the patients and their parents. Developing long-term relationships with the whole family is important and fulfilling," says Dr. Wirrell. Adds Dr. Wetjen, "I like to spend a lot of time making the children feel comfortable. The mothers and fathers want the best possible care, and it's critical to provide extensive and effective ongoing communication throughout each patient's care. Our whole team is attentive to the ongoing mental, social and educational development of the children under our care."

Like the rest of the epilepsy team, Drs. Wetjen and Wirrell are acutely aware of the importance of the developing brain, and, as Dr. Wetjen notes, "Epilepsy is not a static situation, but an actively changing one. It's very hard to separate the problems related to continuing epilepsy from the effects of epilepsy medications, but certainly, if it is possible, stopping the seizures is best. We can't do it in every case, but that's the hope, that's the goal."