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Neurology Today:
doi: 10.1097/01.NT.0000368608.85500.10
Article

Non‐Invasive Testing and Early Surgery Associated With Seizure‐Freedom in Tuberous Sclerosis Complex

FITZGERALD, SUSAN

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ARTICLE IN BRIEF

Noninvasive technologies were effectively used to assess the best candidates for resective surgery for pediatric patients with tuberous sclerosis complex.

Non-invasive testing can identify whether tuberous sclerosis complex (TSC) patients with intractable epilepsy would be good candidates for surgical resection — an approach that could spare them from having to undergo intracranial EEG monitoring prior to surgery.

Two-thirds of pediatric TSC patients whose seizure activity was evaluated using magnetic source imaging (MSI) and co-registration of fluoro-deoxyglucose PET with MRI before surgery were seizure-free postoperatively, according to a Feb. 2 study in Neurology. Moreover, the investigators reported that younger children and those patients who had had seizures for the shortest period of time were more likely to have successful surgical outcomes.

Joyce Wu, MD, a pediatric neurologist and epileptologist at the University of California-Los Angeles (UCLA), who led the study, told Neurology Today that the findings should serve to alert neurologists that it may be better to consider surgery sooner rather than later for TSC patients who do not respond to antiepileptic drugs (AEDs).

“Early consideration of surgery when medication fails would be important for these kids,” said Dr. Wu, an associate professor of pediatrics at UCLA.

Dr. Wu described the technologies used in the study in greater detail. “Magnetoencephalography studies brain function directly and non-invasively by recording outside the skull the magnetic fields induced by synchronized neuronal activity in the brain such as an epileptic spike, with millisecond temporal resolution and millimeter spatial resolution,” Dr. Wu said. MSI superimposes these magnetic fields from abnormal neuronal activity on the patient's own brain MRI to create the best cortical location of these abnormalities specific to that patient.

“The FDG-PET assesses the brain glucose metabolism, where epileptogenic brain regions will be hypometabolic compared to the normal brain regions,” she continued. “FDG-PET/MRI co-registration is then the superimposition of this metabolic pattern on the patient's own brain MRI for the best cortical location of the patient's epileptogenic region.”

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THE CHALLENGES OF TSC

Figure. A BRAIN MRI ...
Figure. A BRAIN MRI ...
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According to background information in the published study, about 90 percent of TSC patients have epilepsy. For many of the children, AEDs do little or nothing to prevent seizures, which may occur multiple times a day.

“For children whose epilepsy is medically refractory, surgical resection of the epileptogenic tubers and surrounding cerebral cortex may offer seizure freedom,” the study authors wrote. “However, the unambiguous identification of epileptogenic regions can be challenging in children with TSC. Consequently, many TSC patients require invasive EEG monitoring or are denied surgery.”

E. Steve Roach, MD, a professor of pediatrics and neurology at Ohio State University College of Medicine, told Neurology Today that the “challenge with tuberous sclerosis is trying to identify which of 20 or 30 abnormalities is causing the seizure activity.”

“If someone has two dozen abnormalities in the brain, there is no reason to assume only one of them is causing the seizures,” said Dr. Roach, who was not involved in the study.

Typically, patients who are identified as possible candidates for surgery are admitted to the hospital in advance and taken to the operating room to have electrodes directly placed on the surface of their brain, and sometimes also inserted in the depths of their brain. Electrical activity is then recorded over the course of several days in an attempt to pinpoint a precise surgical target.

“You're exposing someone to two different surgeries and you're leaving them with foreign bodies inside their head for several days,” Dr. Roach said. The process can be particularly arduous for children.

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NEW EVALUATION TESTS

The researchers focused on 28 children, 18 years old or younger, with TSC who were evaluated at UCLA's Pediatric Epilepsy Surgery Program between July 2000 and June 2007. They all had intractable epilepsy, which was defined as monthly or greater seizure frequency, and had failed to respond to at least three first-line AEDs. The 28 patients were given standardized pre-surgical evaluation consisting of inpatient video-EEG telemetry, high resolution cranial MRI, and FDG-PET.

“All children with TSC demonstrated multiple, often bi-hemispheric tubers on neuroimaging,” the study noted, but it was not possible to detect which of the tubers, which numbered at least 20, were epileptogenic. With only that inconclusive information, proceeding to surgery was not an option.

But the study took the pre-surgical evaluation further, using an expanded protocol that included obtaining MSI or FDG-PET/MRI co-registration, or both. Eighteen of the 28 patients had resective surgery, and the additional information obtained from the MSI and FDG-PET/MRI co-registration was used to target the surgical site.

There were no surgical mortalities, and no surgical complications, “including no CSF shunts, no transient or permanent motor or sensory deficit, no language deficits, and no infections,” the study author reported.

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SEIZURE RELIEF

“For the 18 children who underwent surgery, about one-third had their seizures return within weeks after surgery, about one-third were seizure-free and their AEDs were gradually weaned after surgery, and about one-third were seizure-free and were taking no AEDs,” Dr. Wu said.

The researchers said there were some notable differences between the children who became seizure-free after surgery and those who didn't. Those in the successful group were younger — on average 4.1 years old, compared to 7.9 years for those who continued to have seizures. They also had experienced seizures for a shorter period of time — 3.7 years, on average, compared to 7.6 years for the group that continued to have seizures. When the comparison was expanded to include those children who were not deemed suitable for surgery, those who did not have surgery tended to be older and had had seizures for a longer time.

Dr. Wu said the seizure-free rate of 67 percent achieved in TSC pediatric patients using the non-invasive testing was comparable to the success rate that has been documented using the standard approach of doing invasive EEG monitoring prior to surgery.

“What this is telling us is that for this group of patients — at least for seizure-free outcome after surgery — non-invasive testing is pretty comparable to invasive monitoring,” said Dr. Wu, who did the research with colleagues at UCLA and researchers at the University of California-San Francisco, and the Scripps Clinic, in La Jolla, CA. But she said more research was needed to determine if the same approach would work for patients with other types of intractable epilepsy.

Dr. Wu also noted another limitation of the research. MSI and FDG-PET/MRI co-registration are newer technologies that are not available at all medical centers. And even if they are, health insurers may not pay for the cost of the tests, especially the MSI, she said. “Parents may have to pay out of pocket. The hope is that these results would be convincing enough for the insurers to start covering the MSI over the most costly invasive recording and hospital stay,” she said.

Steven Sparagana, MD, a pediatric neurologist at Texas Scottish Rite Hospital for Children in Dallas, told Neurology Today that “the non-invasive methods described here may have some advantages over invasive EEG monitoring — this needs to be proven, as discussed by the authors.”

“Other important observations include the fact that the early age of surgery was associated with better outcome. This is an important message for pediatric neurologists who are advised to quickly establish whether a child has medically intractable epilepsy, and if so, early epilepsy surgery may be considered,” Dr. Sparagana said. “The lack of complications associated with these epilepsy surgeries was also impressive.”

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REFERENCES

• Wu KY, Salamon N, Mathern GW, et al. Non-invasive testing and early surgery linked with seizure freedom in tuberous sclerosis complex. Neurology 2010; citation info 74(5):392–398.

©2010 American Academy of Neurology

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