Original ArticleSISCOM in Children with Tuberous Sclerosis Complex-Related Epilepsy
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.
Section snippets
Patients
Children 18 years and younger were identified from the EEG report database at Mayo Clinic Rochester for prolonged scalp EEG monitoring during which SISCOM was performed between 1996 and 2008. Patients were selected for study if they had a clinical diagnosis of tuberous sclerosis complex and underwent resective epilepsy surgery. Clinical charts were reviewed for number of seizure types, seizure semiology, age at seizure onset, developmental status, number of antiepileptic drug trials before
Patient information
Six patients with tuberous sclerosis complex underwent focal resective epilepsy surgery from a series of 252 consecutive pediatric patients who had undergone SISCOM for presurgical evaluations. Five patients met criteria for definite tuberous sclerosis complex [44]. One patient had possible tuberous sclerosis complex based on multiple hypopigmented macules, but other available supporting evidences included positive family history and multiple presumed tubers present on fluorodeoxyglucose and α-
Discussion
Patients with tuberous sclerosis complex have an increased incidence of medically intractable epilepsy [7], [45]. Although multiple tubers are observed on imaging, only some of these are epileptogenic. Therefore, structural imaging frequently fails to provide the information necessary to identify the epileptogenic focus in these patients. Scalp EEG can be useful in identifying focal ictal onset; however, it is often nonlocalizing in young children in whom generalized discharges are observed
References (51)
- et al.
Tuberous sclerosis complex: a review of neurological aspects
Eur J Paediatr Neurol
(2002) - et al.
Vagal nerve stimulation in tuberous sclerosis complex patients
Pediatr Neurol
(2001) - et al.
Magnetic source imaging and reactivity to rhythmical stimulation in tuberous sclerosis
Brain Dev
(1998) Role of neuroimaging in the management of seizure disorders
Mayo Clin Proc
(2002)- et al.
The practical utility of performing peri-ictal SPECT in the evaluation of children with partial epilepsy
Pediatr Neurol
(1998) - et al.
Epidemiology of tuberous sclerosis
Ann N Y Acad Sci
(1991) - et al.
Neuropsychiatric aspects of tuberous sclerosis
Ann N Y Acad Sci
(1991) Tuberous sclerosis and multiple tubers: localizing the epileptogenic zone
Epilepsia
(2004)- Muzykewicz DA, Costello DJ, Halpern EF, Thiele EA. Infantile spasms in tuberous sclerosis complex: prognostic utility...
- et al.
Tuberous sclerosis complex: a review of the management of epilepsy with emphasis on surgical aspects
Childs Nerv Syst
(2006)
Seizure remission and antiepileptic drug discontinuation in children with tuberous sclerosis complex
Arch Neurol
On the incidence of fits and mental retardation in tuberous sclerosis
J Med Genet
Surgical treatment of epilepsy in tuberous sclerosis: strategies and results in 18 patients
Neurology
Epilepsy surgery outcome in children with focal epilepsy due to tuberous sclerosis complex
Neuropediatrics
On the surgical treatment of refractory epilepsy in tuberous sclerosis complex
Pediatr Neurosurg
Surgical management and seizure outcome in patients with tuberous sclerosis
J Neurosurg
Surgical treatment for epilepsy in cerebral tuberous sclerosis
Epilepsia
Epilepsy surgery in children with tuberous sclerosis complex: presurgical evaluation and outcome
Epilepsia
Identification of candidates for epilepsy surgery in patients with tuberous sclerosis
Neurology
Epilepsy surgery in tuberous sclerosis: a systematic review
Epilepsia
Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex
J Child Neurol
Managing epilepsy in tuberous sclerosis complex
J Child Neurol
Long-term outcome of epilepsy surgery in patients with tuberous sclerosis
Neurology
Multiple seizure foci and multiple tuberectomy for intractable partial epilepsy in tuberous sclerosis
Epilepsia
Epilepsy surgery in young children with tuberous sclerosis: results of a novel approach
Pediatrics
Cited by (35)
Presurgical Evaluation Strategies for Intractable Epilepsy of Childhood
2021, Seminars in Pediatric NeurologyLongitudinal correspondence of epilepsy and scalp EEG fast (40–200 Hz) oscillations in pediatric patients with tuberous sclerosis complex
2020, Brain and DevelopmentCitation Excerpt :It is observed in approximately 1 in 6000 individuals, representing one of the most significant genetic causes of epilepsy [1,2]. Epilepsy is a particularly prevalent manifestation of the disorder, affecting approximately 80% of individuals with TSC [3–5]; over 60% have seizures that tend to be severe and refractory [3,6,7]. The characteristic feature of epilepsy related to TSC is age-dependent expansion of the epilepsy network and worsening seizures.
Resective surgery in tuberous Sclerosis complex, from Penfield to 2018: A critical review
2019, Revue NeurologiqueCitation Excerpt :All patients underwent surgical resection without invasive EEG monitoring. Three patients were seizure free at two-year follow-up and seizure freedom correlated with the complete resection of SISCOM abnormalities in two cases [32]. Koh et al. described the results of ictal SPECT in 15 TSC patients.
Distinctive MRI features of the epileptogenic zone in children with tuberous sclerosis
2014, European Journal of RadiologyLocalization of the epileptogenic tuber with electric source imaging in patients with tuberous sclerosis
2014, Epilepsy ResearchCitation Excerpt :However, in a subsequent study of the same center, the coregistration of FDG-PET/MRI was non-localizing in 16/28 TSC patients, as no single tuber or group of tubers showed increased hypometabolism relative to their actual MRI volume (Wu et al., 2010). The yield of ictal SPECT and of SISCOM analysis in TSC has been investigated in two small studies (Aboian et al., 2011; Koh et al., 1999). Their results are in agreement with our data, showing that a majority of patients had a dominant hyperperfusion, correlating with the results of other investigations (EEG, MRI) or with seizure outcome.