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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.\"
UNASSIGNED: 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.

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.
CONCLUSIONS: 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.

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.

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.

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.
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).
CONCLUSIONS: 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.

BACKGROUND: Tuberous sclerosis complex (TSC) and primary lymphedema (PLE) are both rare diseases, and it is even rarer for both to occur in the same patient. In this work, we have provided a detailed description of a patient\'s clinical presentation, imaging findings, and treatment. And a retrospective analysis was conducted on 14 published relevant case reports.
METHODS: A 16-year-old male came to our hospital for treatment due to right lower limb swelling. This swelling is already present from birth. The patient\'s memory had been progressively declining. Seizures had occurred 1 year prior at an unknown frequency. The patient was diagnosed with TSC combined with PLE through multimodal imaging examination: Computed tomography, magnetic resonance imaging, and lymphoscintigraphy. The patient underwent liposuction. The swelling of the patient\'s right lower limb significantly improved after surgery. Epilepsy did not occur.after taking antiepileptic drugs and sirolimus.
CONCLUSIONS: TSC with PLE is a rare and systemic disease. Imaging can detect lesions of this disease, which are important for diagnosis and treatment.

UNASSIGNED: Infantile epileptic spasms syndrome (IESS) is a common developmental and epileptic encephalopathy with poor long-term outcomes. A substantial proportion of patients with IESS have a potentially surgically remediable etiology. Despite this, epilepsy surgery is underutilized in this patient group. Some surgically remediable etiologies, such as focal cortical dysplasia and malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), are under-diagnosed in infants and young children. Even when a surgically remediable etiology is recognised, for example, tuberous sclerosis or focal encephalomalacia, epilepsy surgery may be delayed or not considered due to diffuse EEG changes, unclear surgical boundaries, or concerns about operating in this age group.
UNASSIGNED: In this review, the authors discuss the common surgically remediable etiologies of IESS, their clinical and EEG features, and the imaging techniques that can aid in their diagnosis. They then describe the surgical approaches used in this patient group, and the beneficial impact that early epilepsy surgery can have on developing brain networks.
UNASSIGNED: Epilepsy surgery remains underutilized even when a potentially surgically remediable cause is recognized. Overcoming the barriers that result in under-recognition of surgical candidates and underutilization of epilepsy surgery in IESS will improve long-term seizure and developmental outcomes.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations.
METHODS: A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5\'UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient\'s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified.
CONCLUSIONS: To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.