SISCOM in Children with Tuberous Sclerosis Complex-Related Epilepsy

Abstract

Identification of a single epileptogenic focus in patients with tuberous sclerosis complex is a challenge. Noninvasive imaging modalities, including subtraction ictal single-photon emission computed tomography coregistered to magnetic resonance imaging (SISCOM), have been used to determine the dominant epileptogenic focus for surgical resection. We assessed whether complete resection of SISCOM hyperperfusion abnormality correlates with seizure-free outcome in 6 children with tuberous sclerosis complex-related epilepsy. The median seizure onset age was 4 months (range 1 day to 16 months). The age at surgery ranged from 8 months to 13 years. A dominant SISCOM hyperperfusion focus was identified in 5 patients with multiple tubers. SISCOM provided additional localizing information for epilepsy surgery in 3 patients with nonlocalizing or discordant electrophysiologic and neuroimaging findings. At a minimum of 2 years’ follow-up, 3 patients were free of seizures overall. Freedom from seizures was associated with complete resection of SISCOM abnormality in 2 patients. These findings demonstrate that SISCOM can be useful in identifying the epileptogenic zone and in guiding the location and extent of epilepsy surgery in children with tuberous sclerosis complex and multifocal abnormalities. In children with tuberous sclerosis complex and intractable epilepsy, complete resection of the SISCOM hyperperfusion abnormality is associated with freedom from seizures.

Introduction

Over 90% of children with tuberous sclerosis complex develop epilepsy at an early age, with over 80% of these progressing to medically refractory epilepsy [1], [2], [3], [4], [5], [6], [7], [8]. Seizure-free outcome in children with tuberous sclerosis complex undergoing epilepsy surgery is reported to be 22-69% [9], [10], with more favorable outcomes in patients who have a single tuber on magnetic resonance imaging (MRI), focal preoperative electroencephalographic (EEG) abnormalities, and focal seizure semiology [9], [10], [11], [12], [13], [14], [15]. Tonic seizures and low intellectual quotient have been reported to be negative predictive factors [16].

Identification of a focal epileptogenic region in children with tuberous sclerosis complex is frequently a challenge because of multiple tubers on neuroimaging, multiple seizure semiologies, and nonlocalizing, generalized, or multifocal epileptiform abnormalities [2], [17]. As a result, many patients are offered ketogenic diet or palliative procedures such as corpus callosotomy or vagus nerve stimulation as opposed to focal cortical resection procedures [6], [9], [12], [13], [14], [18], [19], [20]. Several reports have documented the effectiveness of resection of multiple tubers on seizure outcome [4], [21], [22].

Novel imaging methods to localize the epileptogenic focus are of increasing importance when MRI and EEG are discordant or nonlocalizing. Potential modalities reported to be of use include diffusion weighted imaging [23], fluorodeoxyglucose and α- [¹¹C]methyl-l-tryptophan positron emission tomography [24], [25], [26], [27], [28], [29], [30], magnetoencephalography [29], [31], [32], [33], functional MRI [34], and ictal single-photon emission computed tomography [14], [35], [36]. Jansen et al. suggested that multifocal findings on ictal single-photon emission tomography correlate with negative outcome after epilepsy surgery [16].

Subtraction ictal single-photon emission computed tomography coregistered to MRI (SISCOM) improves the conventional interpretation of ictal single-photon emission computed tomography. Intensity differences more than 2 standard deviations between interictal and ictal images are coregistered onto the individual patient’s MRI. This technique produces semiquantitative maps of cerebral perfusion differences between ictal and interictal states and places that information in the context of the patient’s own anatomy [37]. SISCOM has been found to be more sensitive and specific than either ictal or interictal single-photon emission computed tomography [38], [39]. Resection of SISCOM focus has been described as an independent positive predictive factor of long-term outcome after epilepsy surgery in adults [38]. In children with intractable epilepsy, SISCOM has also demonstrated promise in identifying the epileptogenic region, but whether complete resection of SISCOM lesion affects postsurgical outcome is still unknown [39].

In this study, we analyzed whether complete resection of the SISCOM foci was predictive of outcome in children with intractable epilepsy due to tuberous sclerosis complex with either multiple tubers or nonlocalizing MRI findings.