Noninvasive testing, early surgery, and seizure freedom in tuberous sclerosis complex

Abstract

Background: The unambiguous identification of the epileptogenic tubers in individuals with tuberous sclerosis complex (TSC) can be challenging. We assessed whether magnetic source imaging (MSI) and coregistration of (18)fluorodeoxyglucose PET (FDG-PET) with MRI could improve the identification of the epileptogenic regions noninvasively in children with TSC.

Methods: In addition to standard presurgical evaluation, 28 children with intractable epilepsy from TSC referred from 2000 to 2007 had MSI and FDG-PET/MRI coregistration without extraoperative intracranial EEG.

Results: Based on the concordance of test results, 18 patients with TSC (64%) underwent surgical resection, with the final resection zone confirmed by intraoperative electrocorticography. Twelve patients are seizure free postoperatively (67%), with an average follow-up of 4.1 years. Younger age at surgery and shorter seizure duration were associated with postoperative seizure freedom. Conversely, older age and longer seizure duration were linked with continued seizures postoperatively or prevented surgery because of nonlateralizing or bilateral independent epileptogenic zones. Complete removal of presurgery MSI dipole clusters correlated with postoperative seizure freedom.

Conclusions: Magnetic source imaging and (18)fluorodeoxyglucose PET/MRI coregistration noninvasively localized the epileptogenic zones in many children with intractable epilepsy from tuberous sclerosis complex (TSC), with 67% seizure free postoperatively. Seizure freedom after surgery correlated with younger age and shorter seizure duration. These findings support the concept that early epilepsy surgery is associated with seizure freedom in children with TSC and intractable epilepsy.

Figure An illustrative case (patient 7, table 1) A 3-year-old girl with tuberous sclerosis complex began having seizures at age 7 weeks. She did not have infantile spasms. Her seizures consisted of 8 to 10 complex partial seizures daily, lateralized to the left hemisphere without further clear localization within that hemisphere. Many abnormal interictal findings included diffuse slowing during wakefulness, intermittent slowing over the left anterior quadrant, and spike discharges seen independently over the left central and frontal regions as well as right central, frontal, and temporal regions. Her brain MRI (A) showed greater than 20 tubers over both hemispheres, and her ¹⁸fluorodeoxyglucose PET (FDG-PET) (not shown) showed multiple focal areas of moderate to severe hypometabolism over the left occipital lobe and bilateral frontal, parietal, and temporal lobes corresponding to these tubers. Her FDG-PET/MRI coregistration (B) showed that the largest volume of hypometabolism, relative to actual MRI tuber size, was located in the left parietal lobe, not the right central tuber as may have been expected from the MRI alone. Her interictal magnetic source imaging (C) showed a large cluster of dipoles over the left parietal tuber with no dipoles elsewhere. She underwent a left craniotomy, with a group of tubers visualized over the left parietal lobe and adjacent posterior temporal lobe. Her intraoperative electrocorticography showed intermittent slowing diffusely over the temporal lobe, and continuous epileptiform discharges over the anterior parietal tuber and adjacent posterior temporal tuber, along with spikes and paroxysmal fast activity over the parietal tubers. The parietal tubers along with the posterior temporal tuber were removed, and the patient has been seizure free for more than 3 years after surgery.