Resting state EEG in young children with Tuberous Sclerosis Complex.

Background: Tuberous Sclerosis Complex (TSC) manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. Methods: This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n=49, ages 12-37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. Results: Compared to matched typically developing controls, children with TSC showed significantly greater alpha and beta power in permutation cluster analyses iterated across a broad frequency range (2-50Hz). Children with TSC also showed significantly greater aperiodic offset after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, greater seizure severity was significantly related to increased periodic peak beta power. Use of GABA agonists was also independently and significantly associated with increased periodic peak beta power; the interaction between seizure severity and GABA agonist use had no significant effect on peak beta power. Conclusions: The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and mediation data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.

Beyond Benign: A Case of Subependymal Giant Cell Astrocytomas Provoking Hydrocephalus in Tuberous Sclerosis Complex.

22-year-old male diagnosed with Tuberous Sclerosis Complex (TSC), a genetic disorder characterized by benign tumors in various organs, with a focus on neurological implications. Central to the study is the development of Subependymal Giant Cell Astrocytomas (SEGAs), leading to hydrocephalus in the patient. The diagnosis of TSC was made in the patient's childhood, and he was monitored regularly. The study highlights a significant growth in a subependymal nodule, leading to monoventricular hydrocephalus. MRI scans played a crucial role in identifying the progression of SEGAs and the subsequent hydrocephalus. The treatment approach involved endoscopic surgical removal of the SEGA, with histopathology confirming the diagnosis. Post-surgical outcomes over an eight-year follow-up period showed a normalization in ventricular size and the stability of other subependymal nodules, without any complications. This case underscores the importance of regular monitoring for TSC patients, early intervention for complications like hydrocephalus, and the need for a multidisciplinary treatment approach. The case study provides valuable insights into the management of neurodevelopmental disorders and the complexities surrounding TSC and SEGAs.

Unveiling Tuberous Sclerosis in a Diagnosed Patient With Systemic Lupus Erythematosus: A Rare Coincidence.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting a variable clinical course ranging from mild to severe multiorgan dysfunction. While the exact etiology of SLE remains elusive, genetic and environmental factors are known to play crucial roles in its pathogenesis. Similarly, tuberous sclerosis complex (TSC) is a multisystem autosomal dominant genetic condition that manifests as benign hamartomatous proliferation in various organs. We present the case of a 46-year-old woman diagnosed with SLE who exhibited clinical features of TSC two decades after the initial diagnosis of SLE. The definitive diagnosis of TSC was made based on major clinical criteria, including facial angiofibroma and bilateral renal angiomyolipomas. As the patient remained asymptomatic without neurological complications, specific treatment for TSC was not initiated. The coexistence of SLE and TSC is exceedingly rare and has been scarcely reported in medical literature.

Multiparameter quantitative analyses of diagnostic cells in brain tissues from tuberous sclerosis complex.

The advent of high-dimensional imaging offers new opportunities to molecularly characterize diagnostic cells in disorders that have previously relied on histopathological definitions. One example case is found in tuberous sclerosis complex (TSC), a developmental disorder characterized by systemic growth of benign tumors. Within resected brain tissues from patients with TSC, detection of abnormally enlarged balloon cells (BCs) is pathognomonic for this disorder. Though BCs can be identified by an expert neuropathologist, little is known about the specificity and broad applicability of protein markers for these cells, complicating classification of proposed BCs identified in experimental models of this disorder. Here, we report the development of a customized machine learning pipeline (BAlloon IDENtifier; BAIDEN) that was trained to prospectively identify BCs in tissue sections using a histological stain compatible with high-dimensional cytometry. This approach was coupled to a custom 36-antibody panel and imaging mass cytometry (IMC) to explore the expression of multiple previously proposed BC marker proteins and develop a descriptor of BC features conserved across multiple tissue samples from patients with TSC. Here, we present a modular workflow encompassing BAIDEN, a custom antibody panel, a control sample microarray, and analysis pipelines-both open-source and in-house-and apply this workflow to understand the abundance, structure, and signaling activity of BCs as an example case of how high-dimensional imaging can be applied within human tissues.

A case of tuberous sclerosis complex revealed by epilepsy.

Tuberous sclerosis complex is a multisystem genetic disease with autosomal dominant inheritance, characterized by the development of benign tumors known as hamartomas that affect multiple organs. It is a condition with a wide phenotypic spectrum, and its clinical presentation varies over time within the same individual. Hence, the importance of early screening and rigorous monitoring of evolving clinical manifestations. Diagnosis can occur at any age. These tumors are generally benign, but their size and location can have a significant impact on the prognosis and, in some cases, even on life expectancy. Cardiac, neurological, and cutaneous manifestations are most common in childhood. The onset of early and severe epilepsy within the first year of life is associated with neurodevelopmental disorders that impact the quality of life for affected individuals and their families. We present a case of a 22-year-old female patient experiencing inaugural epileptic seizures in adulthood, with magnetic resonance imaging revealing subependymal hamartomas, cortical tubers and radial migration bands accompanied by polycystic kidney disease; the diagnosis of tuberous sclerosis complex was established based on the association of these lesions, which constitute major and minor criteria.

Increased susceptibility to kainate-induced seizures in a mouse model of tuberous sclerosis complex: Importance of sex and circadian cycle.

OBJECTIVE: Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/- mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/- mice have altered seizure susceptibility at light and dark phases. METHODS: We assessed seizure susceptibility and progression in a Tsc2+/- mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non-active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. RESULTS: We found increased seizure susceptibility in Tsc2+/- mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/- males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/- females were more susceptible during the dark and post-ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. SIGNIFICANCE: The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC-related epilepsy research. PLAIN LANGUAGE SUMMARY: Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

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.

Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis.

Cytomegalic neurons, characterized by increased size and a hyperactive mechanistic target of rapamycin complex 1 (mTORC1), are pathognomonic for tuberous sclerosis complex (TSC). To model these neurons, we recently generated a murine Tsc1 conditional knockout model in which Tsc1 deletion in late embryonic radial glia results in neuronal hypertrophy of a subset of isocortical pyramidal neurons. In the current study, we compared the cellular pathology of these cytomegalic neurons to those of the enlarged neurons in human cortical tubers. Neurons from the mice showed unique features, such as cytoplasmic vacuoles associated with Golgi complexes and the ectopic formation of perineuronal nets (PNNs), a feature of inhibitory neurons, rarely present in excitatory cortical neurons. The membranes of these vacuoles were enriched for the plasma membrane proteins CD44, KCC2, and Na+/K+ ATPase, suggesting deficits in Golgi membrane trafficking. These aberrant features in the mouse appeared only after the onset of seizures, probably due to the prolonged seizure activity in the context of constitutive mTORC1 activation. Similar PNNs and cytoplasmic vacuoles were present in the cytomegalic neurons of human cortical tubers. Our findings reveal novel pathological features of Golgi complexes and PNNs in the cytomegalic neurons in TSC.

Case report: Liver PEComa after kidney transplantation in recipient with tuberous sclerosis complex.

Introduction: Perivascular epithelioid cell tumors (PEComa) are rare tumors of mesenchymal origin that exhibit perivascular epithelioid cell phenotype. One of its most common localizations is uterus, whereas only a few studies reported PEComa localization as liver. There is a correlation between the presence of PEComa and tuberous sclerosis complex (TSC). TSC is a rare disease which leads to the development of mostly non-cancerous tumors in various organs. We would like to present a case of a kidney transplant recipient with a PEComa detected post-transplant in the liver. Case report: A 27-year-old patient, 3 years after kidney transplantation (KTx) due to chronic renal failure in the course of autosomal dominant polycystic kidney disease and concomitant TSC, was admitted to the Clinic and Department of General and Transplant Surgery for abnormal findings in computed tomography (CT). A CT scan was conducted for oncological follow-up after a kidney transplant (KTx) because before the transplantation, a small cystic lesion measuring 7 mm in diameter was removed from the donor kidney and diagnosed as papillary renal cell carcinoma (PRCC). Two tumors in the liver were detected - one 27mm in diameter in segment VII/VIII and the other 8mm in diameter in segment II/III. Because of typical radiological signs hepatocellular carcinoma was suspected, but the serum level of alpha fetoprotein was within normal limits and liver function was preserved. The intraoperative biopsy and the radiofrequency ablation (RFA) of the larger tumor were performed three months later. In the histopathological examination benign PEComa (HMB45 +, Melan A +) was detected. Conclusion: The oncological surveillance made it possible to detect liver lesion in early stage and in 3,5-year follow-up no sign of recurrence of PEComa was found. This case is the second to show RFA as treatment method of liver PEComa and first in kidney transplant recipient.

Subpial resection of epileptogenic tubers: operative nuances and lessons learned.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder. Tubers of the central nervous system are a hallmark of the disorder and often cause epilepsy. Many TSC patients fail to achieve seizure control with medication alone. Several case series have demonstrated high seizure freedom rates after resective surgery. However, the technique for the resection of epileptogenic tubers has largely been unreported. Here the authors present 2 cases to illustrate their multistage approach for localizing and resecting the seizure onset zone in patients with TSC. At their institution, they have excellent seizure outcomes and a low complication rate with this technique. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2411.

Vitamin D in tuberous sclerosis complex-associated tumors.

Mammalian target of rapamycin inhibitors (mTORi) have been used to treat pediatric tuberous sclerosis complex (TSC)-associated tumors, particularly in cases with contraindications to surgery or difficulties in complete tumor resection. However, some patients experience side effects and tumor regression after discontinuation of the treatment. Therefore, there is an urgent need to develop drugs that can be used in combination with mTORi to increase their efficacy and minimize their side effects. 1,25-Dihydroxyvitamin D3 (1,25-D), which has anticancer properties, may be a promising candidate for adjuvant or alternative therapy because TSC and cancer cells share common mechanisms, including angiogenesis, cell growth, and proliferation. Vitamin D receptor-mediated signaling can be epigenetically modified and plays an important role in susceptibility to 1,25-D. Therefore, vitamin D signaling may be a promising drug target, and in vitro studies are required to evaluate the efficacy of 1,25-D in TSC-associated tumors, brain development, and core symptoms of psychiatric disorders.

A 23-year bibliometric analysis of the development of global research on hereditary renal carcinoma.

Objectives: Medical research continues to be extensively devoted to investigating the pathogenesis and treatment approaches of hereditary renal cancer. By aspect including researchers, institutions, countries, journals, and keywords, we conduct a bibliometric analysis of the literature pertaining to hereditary renal cancer over the last 23 years. Methods: From the Web of Science Core Collection, we conducted a search for publications published between January 1, 2000 and November 28, 2023. Reviews and original articles were included. Results: A cumulative count of 2,194 publications met the specified criteria for inclusion. The studies of the included articles involved a collective of 2,402 institutions representing 80 countries. Notably, the United States exhibited the highest number of published documents, constituting approximately 45.49% of the total. The preeminent institution in this discipline is the National Cancer Institute (NCI), which maintains a publication volume of 8.98%. In addition to being the most prolific author (125 publications), Linehan WM's works received the highest number of citations (11,985). In a comprehensive count, 803 journals have published related articles. In the top 10 most recent occurrences were the terms "hereditary leiomyomatosis" and "fumarate hydratase." Conclusion: This is the first bibliometric analysis of the literature on hereditary renal cancer. This article offers a thorough examination of the present status of investigations concerning hereditary renal cancer during the previous 23 years.

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.

Effectiveness and safety of liposomal rapamycin for the treatment of facial angiofibromas in tuberous sclerosis.

AIM: Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease. METHOD: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment. RESULTS: Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable. CONCLUSIONS: After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.

The extent of kidney involvement in paediatric tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis (TSC)-associated kidney disease is a leading cause of mortality in adults with TSC. This study aimed to understand TSC features in children, particularly kidney involvement, to inform clinical care for this specific group. METHODS: This retrospective cohort study included all paediatric (< 19 years) TSC cases at a large tertiary paediatric nephrology centre. Relevant data were collected from patients' records, statistical analyses were performed to identify associations between variables, survival probabilities were estimated with Kaplan‒Meier curves, and log-rank tests were conducted to assess survival differences among genetic mutations. RESULTS: A total of 182 children with TSC were included. Among the 145 children with available kidney imaging data, 78.6% (114/145) exhibited kidney lesions. Angiomyolipomas (AMLs) were significantly more prevalent in the TSC2 mutation group (p = 0.018). Children with TSC2 mutations generally had poorer lesion-free survival than those with TSC1 mutations, but this difference was only significant for AMLs (p = 0.030). The change in size of largest AMLs increased with age and doubled in children above 9 years; a similar pattern was observed when stratified by genetic mutation. In contrast, kidney cysts exhibited two peaks: one in children under 5 years (2.31 mm/year) and the second in children between 15-19 years (2.82 mm/year). Chronic kidney disease was observed in 12.3% (10/81) of children, and high-risk AMLs above 3 cm were observed in 9% (13/145). CONCLUSIONS: While TSC kidney disease emerges later in the disease course than neurological features, our findings emphasise the importance of kidney surveillance during childhood, including routine kidney imaging, kidney function, and blood pressure monitoring.

Incidence and Characteristics of Cerebellar Atrophy/Volume Loss in Children with Confirmed Diagnosis of Tuberous Sclerosis Complex.

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC). Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism. Results: Cerebral tubers were present in 97/98 cases. In total, 97/98 had subependymal nodules, 15/98 had SEGA, 8/98 had ventriculomegaly and 4/98 had hippocampal sclerosis. Cerebellar tubers were found in 8/98 patients (8.2%), whereas cerebellar atrophy was described in 38/98 cases (38.8%). In 37/38 patients, cerebellar volume loss was mild and diffuse, and only one case presented with left hemi-atrophy. Briefly, 32/38 presented with seizures and were treated with anti-seizure drugs. In total, 8/38 (21%) presented with behavioral disorders, 10/38 had autism and 2/38 presented with seizures and behavioral disorders and autism. Conclusions: Several studies have demonstrated cerebellar involvement in patients with TSC. Cerebellar tubers differ in shape compared with cerebral tubers and are associated with cerebellar volume loss. Cerebellar atrophy may be focal and diffuse and one of the primary cerebellar manifestations of TSC, especially if a TSC2 mutation is present. Cerebellar degeneration may, however, also be secondary/acquired due to cellular damage resulting from seizure activity, the effects of anti-seizure drugs and anoxic-ischemic injury from severe seizure activity/status epilepticus. Further, prospective studies are required to identify and establish the pathogenic mechanism of cerebellar atrophy in patients with TSC.

Exploring Cardiovascular Involvement in Tuberous Sclerosis: Insights for Pediatric Clinicians.

Tuberous sclerosis is a rare genetic disorder involving mainly the nervous and cardiovascular systems. The early recognition of the cardiovascular manifestations by the pediatrician allows an appropriate management and therefore enhances the quality of life of the affected children. Cardiac rhabdomyomas and the associated arrhythmias are the first cardiac features and they might represent a diagnosis challenge given their wide spectrum of clinical manifestations. We aimed to provide the paediatric practitioners with current knowledge regarding the cardiovascular complications in children with tuberous sclerosis. We overviewed the antenatal and postnatal evolution of cardiovascular manifestations, the systematic screening and long-term follow-up strategy of cardiac rhabdomyomas and arrhythmias in children with tuberous sclerosis.

Eosinophilic Solid and Cystic Renal Cell Carcinoma-A Systematic Review and Meta-Analysis.

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a distinct entity in the WHO 2022 kidney tumor classification. Previously known as "unclassified RCC", followed by "tuberous sclerosis complex (TSC)-associated RCC", ESC-RCC is now a distinct category of kidney tumor, with its own name, with specific clinical manifestations, and a unique morphological, immunohistochemical and molecular profile. Due to its recent introduction and the limited available data, the diagnosis of ESC-RCC is still a complex challenge, and it is probably frequently misdiagnosed. The secret of diagnosing this tumor lies in the pathologists' knowledge, and keeping it up to date through research, thereby limiting the use of outdated nomenclature. The aim of our case-based review is to provide a better understanding of this pathology and to enrich the literature with a new case report, which has some particularities compared to the existing cases.

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.