Impact of seizure onset zone and intracranial electroencephalography ictal characteristics on epilepsy surgery outcomes in tuberous sclerosis complex.

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1-3 was defined as good and 4-6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.

Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex.

OBJECTIVE: The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study. METHODS: Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control. RESULTS: Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (ß = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; ß = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; ß = -0.05, p = 0.482). CONCLUSIONS: Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.

Pathways to epilepsy surgery in children with tuberous sclerosis complex-associated epilepsy.

BACKGROUND: Previous studies showed the efficacy of epilepsy surgery in carefully selected children with epilepsy associated with tuberous sclerosis complex. However, how this selection is conducted, and the characteristics of the patients brought to surgery are still poorly described. By conducting a multicentric retrospective cohort study covering the practice of the last twenty years, we describe the paths leading to epilepsy surgery in children with epilepsy associated with tuberous sclerosis complex. METHODS: We identified 84 children diagnosed with tuberous sclerosis complex and epilepsy by matching two exhaustive registries of genetic diseases and subsequent medical records reviews within two French neuropediatric and epilepsy centers. Demographic, clinical, longitudinal, and diagnostic and surgical procedures data were collected. RESULTS: Forty-six percent of the children were initially drug-resistant and 19% underwent resective surgery, most often before the age of four. Stereotactic electroencephalography was performed prior to surgery in 44% of cases. Fifty-seven and 43% of patients remained seizure-free one and ten years after surgery, respectively. In addition, 52% of initially drug-resistant patients who did not undergo surgery were seizure-free at the last follow-up. The number of anti-seizure medications required decreased in 50% of cases after surgery. Infantile spasms, intellectual disability, autism spectrum disorder or severe behavioral disorders were not contraindications to surgery but were associated with a higher rate of complications and a lower rate of seizure freedom after surgery. CONCLUSION: Despite the assumption of complex multifocal epilepsy and practical difficulties in young children with tuberous sclerosis complex, successful surgery results are comparable with other populations of patients with drug-resistant epilepsy, and a spontaneous evolution to drug-sensitive epilepsy may occur in non-operated patients.

Seizure freedom but not epilepsy surgery is associated with fewer neuropsychiatric difficulties in patients with tuberous sclerosis.

BACKGROUND: Drug-resistant epilepsy (DRE) in selected individuals with the rare tuberous sclerosis complex (TSC) may benefit from resective epilepsy surgery. Furthermore, associated neuropsychiatric disorders (TAND) are common in patients with TSC; however, long-term data on how surgery affects neuropsychiatric comorbidities are sparse. MATERIALS AND METHODS: Two retrospective approaches were used to identify children with TSC and DRE with onset at < 18 years of age. The study group (surgical) was identified through the Swedish National Epilepsy Surgery Registry (n = 17), a registry with complete national coverage since 1990 and prospective patient enrolment since 1995. The reference group (non-surgical) was identified by searching medical records retrieved from the tertiary hospital of Southern Sweden (n = 52). Eligible participants were invited to complete the validated TAND lifetime checklist. Those who did not complete the checklist, never had DRE, or were aged < 7 years old were excluded from the study. The reference group was balanced with the study group for putative confounders, in the following hierarchical order: DRE at the survey, age at seizure onset, age at follow-up, and sex. RESULTS: After the balancing procedure, both groups comprised 13 participants. The median time from epilepsy onset to the survey was 18.5 (range: 7.75-40.25) and 16.0 (7.33-33.5) years in the study and reference groups, respectively. The median time from surgery to the survey was 13 years (range: 4-22). No significant differences were found in behavioural problems, autism spectrum disorder diagnosis or symptoms, or intellectual disability between the groups, regardless of surgery. Seizure-free individuals (n = 11) performed better in social skills (p = 0.016), intellectual skills (p = 0.029), and overall TAND scores (p = 0.005) than the non-seizure-free group (n = 15). CONCLUSION: This is the first study to evaluate TAND comorbidities during the long-term follow-up after epilepsy surgery in patients with TSC. We found no evidence of the adverse effects of TAND comorbidities after tuberectomy. However, a larger study that allows for a better adjustment for confounders is needed. Following previous studies, seizure-free individuals had fewer symptoms within most TAND domains compared with the group with uncontrolled epilepsy, indicating less severe symptomatology.

Kidney transplantation in patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. METHODS: This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. RESULTS: We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. CONCLUSIONS: The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

The evolution of epilepsy surgery in tuberous sclerosis in Sweden: A national registry study.

PURPOSE: This study aimed to characterize the Swedish cohort of surgically treated patients with TSC and explore differences in preoperative investigation and outcome over time. METHODS: Data on patient and seizure characteristics were retrieved from the Swedish National Epilepsy Surgery Register. Two-year follow-up results were compared between the years 1997-2010 and 2011-2018. Preoperative investigations were re-evaluated. RESULTS: Eighteen tuberectomies and seven callosotomies were identified. Seizure freedom after tuberectomy was achieved in 11 % (1/9) 1997-2010 and 56 % (5/9) 2011-2018. The number of tuberectomies increased each decade. Patients operated on in 1997-2010 had higher seizure frequency (median 175 seizures/month vs. 102) and incidence of infantile spasms (4/9 vs. 1/9, none after 2011). There was a trend towards surgery at a younger age (median 86 months 1997-2010 vs. 48 months 2011-2018). None with >200 seizure/month, SEGA, or history of infantile spasms achieved seizure freedom. Two patients underwent anterior callosotomy (1992 and 1994) and became free of drop attacks. Five callosotomies were performed between 2011 and 2013, one patient became free of drop attacks. Two complications with new neurological deficits were reported. The median age at surgery was higher in the callosotomy group (14 years) than in the tuberectomy group (5 years). CONCLUSION: Seizure freedom after tuberectomy in patients with TSC has increased over time in our cohort. Signs of a heavier disease burden were more frequently observed 1997-2010 and associated with worse outcomes. Callosotomy operations were prevalent at the beginning of the 2010s.

Influence of resective extent of epileptogenic tuber on seizure outcome in patients with tuberous sclerosis complex-related epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to identify whether tuberectomy and tuberectomy plus are associated with different postoperative seizure outcomes in patients with tuberous sclerosis complex (TSC) -related epilepsy. METHODS: Electronic databases (PubMed, Embase, Cochrane, Proquest, Web of Science, Scopus, Biosis Previews) were searched without date restriction. Retrospective cohort studies of participants with TSC-associated epilepsy undergoing resective surgery that reported demographics, presurgical evaluation, extent of resection and postoperative seizure outcomes were included. Title, abstract and the full text were checked independently and in duplicate by two reviewers. Disagreements were resolved through discussion. One author extracted data which was verified by a second author using identified common standard in advance, including using a risk of bias tool we agreed on to evaluate study quality. RESULTS: Five studies, with a total of 327 participants, were included. One hundred and sixty patients received tuberectomy, and 93 of them (58.1%) achieved postoperative seizure freedom, while the other 167 patients underwent tuberectomy plus, and 128 of them (76.6%) achieved seizure freedom after adequate follow-ups (RR=0.72, 95% CI [0.60, 0.87], P<0.05). Subgroup analysis found that 40 of 63 (63.5%) patients after tuberectomy and 66 of 78 (84.6%) patients after tuberectomy plus of a single tuber achieved seizure freedom (RR = 0.71, 95% CI [0.56,0.91], P<0.05). In the multituber subrgroup, 16 of 42 (38.1%) and 21 of 31 (67.7%) patients achieved seizure freedom, after tuberectomy and tuberectomy plus, respectively (RR = 0.57, 95% CI [0.32,1.03], P = 0.06). CONCLUSIONS: Tuberectomy plus is a more effective treatment than tuberectomy for patients with TSC-related intractable epilepsy.

[Epilepsy surgery in children with tuberous sclerosis]. / Khirurgicheskoe lechenie epilepsii u detei s tuberoznym sklerozom.

Most children with tuberous sclerosis (TS) present with intractable seizures. Various factors including demography, clinical data and surgery option are mentioned to affect the outcome after epilepsy surgery in these cases. OBJECTIVE: To evaluate some demographic and clinical variables probably related to seizure outcome. MATERIAL AND METHODS: Thirty-three children, median age 4.2 ys (7.5 mths-16 ys), with TS and DR-epilepsy underwent surgery. Within overall 38 procedures (redo surgery was needed in 5 cases), tuberectomy (with or without perituberal cortectomy) was performed in 21 cases, lobectomy - 8, callosotomy - 3, various disconnections (anterior frontal, TPO and hemispherotomy) - 6 patients. Standard preoperative evaluation included MRI and video-EEG. Invasive recordings were used in 8 cases, coupled by MEG and SISCOM SPECT in some cases. ECOG and neuronavigation were used routinely during tuberectomies, and stimulation and mapping were employed in cases with lesions overlapping or near to eloquent cortex. Surgical complications: wound CSF leak (n=1) and hydrocephalus (n=2) were noted in 7.5% of cases. Postoperative neurological deficit (most frequently hemiparesis) developed in 12 patients, being temporary in majority of them. At the last FU (med 5.4 ys) favorable outcome (Engel I) has been achieved in 18 cases (54%), while 7 patients (15%) with persisting seizures reported less common attacks and their milder form (Engel Ib-III). Six patients were able to discontinue AED-treatment and 15 children resumed development and markedly improved in cognition and behavior. RESULTS AND CONCLUSION: Among different variables potentially influencing the outcome after epilepsy surgery in cases with TS, the most important one is seizure type. If prevalent, focal type may be a biomarker of favorable outcomes and probability to become free of seizures.

Reprint of: lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: cysts, angiomyolipomas & renal cell carcinoma.

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication. In this review, we have discussed issues relevant to clinical management based on histopathologic findings in nephrectomy specimens from patients with TSC. This includes discussions related to screening for TSC, diagnosis of PKD1/TSC2 contiguous gene deletion syndrome, the morphologic spectrum of angiomyolipoma and renal epithelium-derived neoplasia, including the risk of disease progression.

Epilepsy Surgery in Young Children With Tuberous Sclerosis Complex: A Novel Hybrid Multimodal Surgical Approach.

BACKGROUND: Surgery has become integral in treating children with tuberous sclerosis complex (TSC)-related drug-resistant epilepsy (DRE). OBJECTIVE: To describe outcomes of a multimodal diagnostic and therapeutic approach comprising invasive intracranial monitoring and surgical treatment and compare the complementary techniques of open resection and magnetic resonance-guided laser interstitial thermal therapy. METHODS: Clinical and radiographic data were prospectively collected for pediatric patients undergoing surgical evaluation for TSC-related DRE at our tertiary academic hospital. Seizure freedom, developmental improvement, and Engel class were compared. RESULTS: Thirty-eight patients (20 females) underwent treatment in January 2016 to April 2019. Thirty-five underwent phase II invasive monitoring with intracranial electrodes: 24 stereoencephalography, 9 craniotomy for grid/electrode placement, and 2 grids + stereoencephalography. With the multimodal approach, 33/38 patients (87%) achieved >50% seizure freedom of the targeted seizure type after initial treatment; 6/9 requiring secondary treatment and 2/2 requiring a third treatment achieved >50% freedom. The median Engel class was II at last follow-up (1.65 years), and 55% of patients were Engel class I/II. The mean age was lower for children undergoing open resection (2.4 vs 4.9 years, P = .04). Rates of >50% reduction in seizures (86% open resection vs 88% laser interstitial thermal therapy) and developmental improvement (86% open resection vs 83% magnetic resonance-guided laser interstitial thermal therapy) were similar. CONCLUSION: This hybrid approach of using both open surgical and minimally invasive techniques is safe and effective in treating DRE secondary to TSC. Clinical trials focused on treatment method with longer follow-up are needed to determine the optimal candidates for each approach and compare the treatment modalities more effectively.

Multiple Interventions to Thoracoabdominal Aortic Aneurysm in a Child With Tuberous Sclerosis.

Thoracoabdominal aortic aneurysms in toddlers are extremely rare. However, we experienced an extent III thoracoabdominal aortic aneurysm in a boy with tuberous sclerosis who underwent 3 open repairs and 1 endovascular aortic repair between the ages of 4 years and 18 years. This case highlights the potential for severe recurrent vascular aneurysms in the thoracic and abdominal aorta as a complication of tuberous sclerosis in children. Although aortic aneurysms in children are rare, it is vital to recognize these cases to prevent death due to rupture.

Giant Renal Angiomyolipomas and Pulmonary Lymphangioleiomyomatosis: Follow-up Report after More than a Decade.

Renal angiomyolipomas (AMLs) and pulmonary lymphangioleiomyomatosis (LAM) are two major presentations of tuberous sclerosis (TS), an autosomal dominant multisystem disorder. Renal AMLs can lead to life-threatening complications like hemorrhage and cause progressive renal failure requiring dialysis and kidney transplant. mTOR inhibitors showed promising results in TS patients with renal AMLs, LAM, and subependymal giant cell astrocytomas. This case report is a follow-up of a patient we reported in 2010 with giant AMLs and LAM who required an emergency nephrectomy for massive hemorrhage from giant left-sided AMLs.

Comparison of outcomes after stereoelectroencephalography and subdural grid monitoring in pediatric tuberous sclerosis complex.

OBJECTIVE: Patients with tuberous sclerosis complex (TSC) epilepsy present with unique clinical challenges such as early seizure onset and high rates of intractability and multifocality. Although there are numerous studies about the safety and efficacy of stereoelectroencephalography (SEEG), this topic has not been studied in TSC patients who have distinct epilepsy profiles. The authors investigated subdural grid (SDG) and SEEG monitoring to determine whether these procedures lead to similar seizure and safety outcomes and to identify features unique to this pediatric population. METHODS: TSC patients who underwent SDG or SEEG placement and a second epilepsy surgery during the period from 2007 to 2021 were included in this single-center retrospective cohort analysis. Various patient, hospitalization, and epilepsy characteristics were collected. RESULTS: A total of 50 TSC patients were included in this study: 30 were included in the SDG cohort and 20 in the SEEG cohort. Baseline weekly seizure count did not significantly differ between the 2 groups (p = 0.412). The SEEG group had a greater mean baseline number of antiepileptic drugs (AEDs) (3.0 vs 2.0, p = 0.003), higher rate of previous surgical interventions (25% vs 0%, p = 0.007), and larger proportion of patients who underwent bilateral monitoring (50% vs 13.3%, p = 0.005). Despite this, there was no significant difference in seizure freedom between the SDG and SEEG cohorts. The mean reduction in seizure count was 84.9% and 47.8% of patients were seizure free at last follow-up (mean 79.4 months). SEEG trended toward being a safer procedure than SDG monitoring, with a shorter mean ICU stay (0.7 days vs 3.9 days, p < 0.001), lower blood transfusion rate (0% vs 13.3%, p = 0.140), and lower surgical complication rate (0% vs 10%, p = 0.265). CONCLUSIONS: In the comparison of the SDG and SEEG cohorts, the SEEG group included patients who appeared to receive more aggressive management and have a higher rate of multifocality, more prior surgical interventions, more AEDs at baseline, and a higher rate of bilateral invasive monitoring. Despite this, the SEEG cohort had similar seizure outcomes and a trend toward increased safety. Based on these findings, SEEG appears to allow for monitoring of a wider breadth of TSC patients given its minimally invasive nature and its relative simplicity for monitoring numerous regions of the brain.

Stereoelectroencephalography before 2 years of age.

OBJECTIVE: Stereoelectroencephalography (SEEG) is a widely used technique for localizing seizure onset zones prior to resection. However, its use has traditionally been avoided in children under 2 years of age because of concerns regarding pin fixation in the immature skull, intraoperative and postoperative electrode bolt security, and stereotactic registration accuracy. In this retrospective study, the authors describe their experience using SEEG in patients younger than 2 years of age, with a focus on the procedure's safety, feasibility, and accuracy as well as surgical outcomes. METHODS: A retrospective review of children under 2 years of age who had undergone SEEG while at Children's Hospital of Philadelphia between November 2017 and July 2021 was performed. Data on clinical characteristics, surgical procedure, imaging results, electrode accuracy measurements, and postoperative outcomes were examined. RESULTS: Five patients younger than 2 years of age underwent SEEG during the study period (median age 20 months, range 17-23 months). The mean age at seizure onset was 9 months. Developmental delay was present in all patients, and epilepsy-associated genetic diagnoses included tuberous sclerosis (n = 1), KAT6B (n = 1), and NPRL3 (n = 1). Cortical lesions included tubers from tuberous sclerosis (n = 1), mesial temporal sclerosis (n = 1), and cortical dysplasia (n = 3). The mean number of placed electrodes was 11 (range 6-20 electrodes). Bilateral electrodes were placed in 1 patient. Seizure onset zones were identified in all cases. There were no SEEG-related complications, including skull fracture, electrode misplacement, hemorrhage, infection, cerebrospinal fluid leakage, electrode pullout, neurological deficit, or death. The mean target point error for all electrodes was 1.0 mm. All patients proceeded to resective surgery, with a mean follow-up of 21 months (range 8-53 months). All patients attained a favorable epilepsy outcome, including Engel class IA (n = 2), IC (n = 1), ID (n = 1), and IIA (n = 1). CONCLUSIONS: SEEG can be safely, accurately, and effectively utilized in children under age 2 with good postoperative outcomes using standard SEEG equipment. With minimal modification, this procedure is feasible in those with immature skulls and guides the epilepsy team's decision-making for early and optimal treatment of refractory epilepsy through effective localization of seizure onset zones.

Satisfaction and seizure outcomes of epilepsy surgery in tuberous sclerosis: A Swedish population-based long-term follow-up study.

PURPOSE: We conducted a cross-sectional study to evaluate long-term outcomes of epilepsy surgery in tuberous sclerosis complex (TSC) in a Swedish population. METHODS: Demographic and seizure data was retrieved from the Swedish National Epilepsy Surgery Registry and medical records. Patient reported outcome measurements (PROM) were determined by telephonic interviews at long term follow-up. RESULTS: Median follow-up was 6 y 8 m (range, 3-15 y 1 m) for tuberectomies (n = 15) and 3 y 6 m (range 2-10 y) for callosotomies (n = 7). Eight of the 15 tuberectomy participants were seizure-free. Four out of seven callosotomies were free from drop attacks. PROMs were provided by caregivers of 18/20 participants (data missing for two callosotomies). In the tuberectomy group, 6/8 patients were seizure-free and 3/7 had continued seizures; surgery was considered satisfactory and beneficial. Overall, satisfaction was high, even among patients who did not achieve remission; 13/15 tuberectomy responders recommended surgery to others with TSC and refractory epilepsy. None of the patients considered the surgery harmful. In the callosotomy group, satisfaction was low and congruent with the seizure outcome. All patients with continued drop attacks were unsatisfied; one considered surgery to be harmful. One participant, who would not recommend surgery to others, still perceived the surgery to be beneficial. CONCLUSIONS: This study confirmed that both tuberectomy and callosotomy are effective treatment options for TSC. Factors other than seizure outcomes seemed to have a major influence on satisfaction and perception of the benefit of surgery.

Lessons from histopathologic examination of nephrectomy specimens in patients with tuberous sclerosis complex: cysts, angiomyolipomas, and renal cell carcinoma.

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved understanding of histopathologic findings in TSC patients and associated clinicopathologic correlates has significant implications not just in establishing a diagnosis of TSC, but also in the recognition of sporadic tumors occurring secondary to somatic alterations of TSC1/TSC2/MTOR pathway genes and accurate prognostication. In this review, we have discussed issues relevant to clinical management based on histopathologic findings in nephrectomy specimens from patients with TSC. This includes discussions related to screening for TSC, diagnosis of PKD1/TSC2 contiguous gene deletion syndrome, the morphologic spectrum of angiomyolipoma and renal epithelium-derived neoplasia, including the risk of disease progression.

Subependymal giant-cell astrocytoma: A surgical review in the modern era of mTOR inhibitors.

INTRODUCTION: Surgical removal has been the historical treatment for subependymal giant-cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) patients. In the past decade, mTOR inhibitors have shown efficacy in the treatment of SEGA, significantly reducing tumor size. The aim of this study was to assess the safety and efficacy of surgical treatment at a time when mTOR inhibitors have changed standard treatment. MATERIAL AND METHODS: We conducted a single-center retrospective study including all patients treated by surgery for SEGA from October 2003 to September 2019, with a review of all SEGA surgical case series, following PRISMA guidelines. Research focused on demographics, surgical indications, surgical approach, use of CSF shunt, morbidity and mortality, resection quality, recurrence rate and treatment of recurrence, follow-up and long-term clinical status. RESULTS: Eleven patients were included, with a median age at surgery of 16.0 years. Gross total resection was achieved in 8 patients (72%), with no permanent morbidity. One patient needed further surgery for tumor recurrence. Eighteen studies were reviewed, totaling 263 TSC patients affected by SEGA and 286 surgical procedures. Gross total resection was achieved in 81.1% of cases, mortality was 4.9% and permanent morbidity 6.1%. Tumor recurrence occurred in 11.5% of cases, and was secondary to partial tumor resection at first surgery in the majority of cases. CONCLUSION: Surgical treatment of SEGA is still a valid and effective option. Morbidity is low and complete disappearance of SEGA can be achieved in selected cases.

A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification.

Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

Limited utility of structural MRI to identify the epileptogenic zone in young children with tuberous sclerosis.

BACKGROUND AND PURPOSE: The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC. METHODS: We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12 months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, transmantle sign). They selected lesions suspect for the EZ based on structural MRI, and reselected after unblinding to seizure onset location on electroencephalography (EEG). RESULTS: None of the tuber characteristics and FCD features were distinctive for the EZ, indicated by resected lesions in seizure-free children. With structural MRI alone, the EZ was identified out of 10 lesions in 31%, and with addition of EEG data, this increased to 48%. However, rates of identification of resected lesions in non-seizure-free children were similar. Across 251 lesions, interrater agreement was moderate for large size (κ = .60), and fair (κ = .24) for all other features. CONCLUSIONS: In young children with TSC, the utility of structural MRI features is limited in the identification of the epileptogenic tuber, but improves when combined with EEG data.