Epilepsy associated tuberous sclerosis; a case report from Bangladesh.
Ontology highlight
ABSTRACT:
SUBMITTER: Shrestha AB
PROVIDER: S-EPMC9118511 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Publications
Epilepsy associated tuberous sclerosis; a case report from Bangladesh.
Shrestha Abhigan Babu AB Shrestha Sajina S Seemanta Senjuti S Pokharel Pashupati P Alam Waqar W
Annals of medicine and surgery (2012) 20220511
Tuberous sclerosis or Bourneville's disease is a rare autosomal dominant disease affecting many organs like the brain, heart, lungs, eyes, kidneys and skin. It is characterized by neurological manifestation like epilepsy, cutaneous changes and the formation of benign lesions in multiple organs. The symptoms are apparent only in late childhood, which limits the early diagnosis in infancy. Here, we report a case of a 15 year old female child with tuberous sclerosis. ...[more]
Similar Datasets
Project description:Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with different initial symptoms and complex clinical manifestations. A 14-year-old female patient presented with persistent fever and severe headache. Medical imaging examinations revealed multiple abnormal intracranial lesions. The patient had previously been misdiagnosed with "encephalitis and acute disseminated encephalomyelitis" after visiting numerous hospitals. Eventually, by combing the characteristics of the case and genetic testing results, the patient was diagnosed with TSC accompanied by Mycoplasma pneumoniae infection. The purpose of this case report and literature review is to improve understanding of the clinical diagnosis and treatment of TSC so as to avoid misdiagnosis, missed diagnosis, and overtreatment.
| S-EPMC10485941 | biostudies-literature
Project description:IntroductionTuberous sclerosis complex (TSC) is an uncommon multisystem disorder that can affect the lungs, skin, kidneys, and brain. The study highlights the importance of genetic and clinical diagnostic criteria in identifying this rare condition and the role of surveillance in preventing complications.Case presentationHerein, we report a case of 16 years old female presenting with right flank pain, hematuria, hypopigmented macule over the back, ash leaf spots over the right upper and lower limb, and a palpable mass over the right lumbar region. Laboratory tests showed low hemoglobin with plenty of red blood cells in urine. She was admitted for symptomatic management of pain and blood transfusion was done to manage anemia. After a diagnostic workup for tuberous sclerosis, she was diagnosed with the condition and is under regular follow-up.Clinical discussionTuberous sclerosis complex is one of the neurocutaneous syndromes, diagnosed based on the genetic or clinical diagnostic criteria as per the second International Tuberous Sclerosis Complex Consensus Conference 2012, which have been updated in 2021 with no changes in genetic diagnostic criteria and slight changes in clinical diagnostic criteria. After diagnosis, along with the management, surveillance is also crucial.ConclusionTuberous sclerosis runs a progressive course and can lead to various complications. Thus, early diagnosis with the help of genetic and clinical diagnostic criteria is important along with regular surveillance of different body systems to prevent debilitating complications.
| S-EPMC8844758 | biostudies-literature
Project description:BackgroundThe optimal biomarkers for early diagnosis, treatment, and prognosis of tuberous sclerosis complex (TSC)-associated epilepsy are not yet clear. This study identifies the crucial genes involved in the pathophysiology of TSC-associated epilepsy via a bioinformatics analysis. These genes may serve as novel therapeutic targets.MethodsGene chip data sets (GSE62019 and GSE16969) comprising the data of patients with TSC-associated epilepsy and healthy control participants were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in the GEO database were identified using the GEO2R gene expression analysis tool. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology function, and protein-protein interaction (PPI) network analyses were then conducted. The results were analyzed using R language, and are presented in volcano plots, Venn diagrams, heatmaps, and enrichment pathway bubble charts. A gene set enrichment analysis (GSEA), was conducted to examine the KEGG pathways and crucial genes linked to TSC-associated epilepsy. The potential genes were compared with the genes listed in the Online Mendelian Inheritance in Man (OMIM) database and analyzed against the literature to determine their clinical significance. Finally, the expression of the key genes in the TSC-associated epilepsy mice cerebral cortex was examined through immunohistochemical staining.ResultsThe intersection of the GSE62019 and GSE16969 data sets revealed 151 commonly upregulated DEGs. The KEGG enrichment analysis indicated that these DEGs affected the occurrence and development of TSC-associated epilepsy by modulating complement and coagulation cascades, glycosaminoglycans in cancer, and extracellular matrix-receptor interactions. Four high-scoring clusters emerged, and podoplanin (PDPN) was identified as a key gene through the construction of a PPI network of the common DEGs using the Cytoscape software. A GSEA of the DEGs revealed that the common DEG PDPN was enriched in both data sets in pathways related to platelet activation, aggregation, and the glycoprotein VI (GPVI)-mediated activation cascade. Immunohistochemical staining revealed a significant elevation in PDPN expression in the cerebral cortex of mice with TSC-associated epilepsy. Conversely, the control group mice did not display any significantly positive neurons.ConclusionsThe discovery of these crucial genes and signaling pathways extends understanding of the molecular processes underlying the development of TSC-associated epilepsy. Additionally, our findings may provide a theoretical basis for research into targeted clinical treatments.
| S-EPMC11319994 | biostudies-literature
Project description:In the present study, we reviewed the outcome of ketogenic diet (KD) use for the management of epilepsy in children with tuberous sclerosis complex (TSC).A total of 12 children with intractable epilepsy associated with TSC who were treated with KD at our hospital between March 1, 2008 and February 28, 2015 were retrospectively enrolled.The mean age at the time of KD initiation was 73.1 ± 38.0 months. Patients were medically refractory to a mean of 4.8 ± 1.7 antiepileptic drugs. Nine patients (75.0%) had a history of infantile spasms. At 3 months after KD initiation, 10 patients (83.3%) had > 50% seizure reduction. Moreover, 7 patients (58.3%) exhibited qualitative improvements in cognition and behavior after KD initiation, as reported by caregivers/parents. The mean duration of dietary therapy was 14.8 ± 12.8 months. Half of the patients in this study eventually underwent epilepsy surgery due to persistent seizures or seizure relapse.KD is an important non-pharmacological treatment option for patients with intractable epilepsy associated with TSC. KD may improve cognition and behavior in addition to reducing seizure frequency.
| S-EPMC5540690 | biostudies-other
Project description:ObjectivesLittle is known about the evolution of epilepsy in individuals with tuberous sclerosis complex (TSC) in adulthood. This study aims at describing the characteristics of epilepsy in adult TSC patients attending a single multidisciplinary clinic.Materials and methodsWe collected data about epilepsy (age at onset, seizure types, history of infantile spasms (IS), epilepsy diagnosis and outcome), genetic and neuroradiological findings, cognitive outcome and psychiatric comorbidities.ResultsOut of 257 adults with TSC, 183 (71.2%) had epilepsy: 121 (67.2%) were drug-resistant; 59 (32.8%) seizure-free, at a median age of 18 years. 22% of the seizure-free patients (13/59) discontinued medication. Median age at seizure onset was 9 months. Seventy-six patients (41.5%) had a history of IS. TSC2 pathogenic variants (p = 0.018), cortical tubers (p < 0.001) and subependymal nodules (SENs) (p < 0.001) were more frequent in those who developed epilepsy. Cognitive functioning was lower (p < 0.001) and psychiatric disorders more frequent (p = 0.001). We did not find significant differences regarding age, gender, mutation and tubers/SENs in seizure-free vs drug-resistant individuals. Intellectual disability (p < 0.001) and psychiatric disorders (p = 0.004) were more common among drug-resistant patients.ConclusionsEpilepsy in TSC can be a lifelong disorder, but one-third of individuals reach seizure freedom by early adulthood. In the long term, age at epilepsy onset has a crucial role in drug resistance and in developing intellectual disability, both in drug-resistant and drug-sensible patients. Patients with drug-refractory seizures tend to develop psychiatric issues, which should be recognized and adequately treated.
| S-EPMC8251624 | biostudies-literature
Project description:Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder. The TSC1 and TSC2 genes have been identified as pathogenic genes.In this report, we are discussing a novel frameshift mutation and a novel missense mutation in the TSC2 gene.The two cases discussed in this study met the latest diagnostic criteria for TSC published by the International Tuberculosis Sclerosis Complex Consensus Conference in 2012.High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were used to examine tuberous sclerosis complex (TSC)-related genes (TSC1 and TSC2) and their splicing regions using peripheral blood DNA from two probands in two families with TSC and to identify the genetic mutation sites. Amplification primers were designed for the mutation sites, and polymerase chain reaction and Sanger sequencing were used to verify the peripheral blood DNA sequences from the probands and their parents.Proband 1 had the c.1228 (exon 12)_c.1229 (exon 12) insG (p.L410RfsX11) heterozygous mutation in the TSC2 gene (chr16), which was a new frameshift mutation. Proband 2 had the c.4925G>A (exon 38) (p.G1642D) heterozygous mutation in the TSC2 gene (chr16), which was a new missense mutation.These two novel mutations may be pathogenic mutations for TSC, and their association with the disease needs to be further verified by mutant protein function cell model and animal model.
| S-EPMC6086505 | biostudies-literature
Project description:BackgroundEpilepsy in tuberous sclerosis complex (TSC) typically presents with early onset, multiple seizure types, and intractability. However, variability is observed among individuals. Here, detailed individual data on seizure characteristics collected prospectively during early life were used to define epilepsy profiles in this population.MethodsChildren aged zero to 36 months were followed longitudinally. Caregivers kept daily seizure diaries, including onset and daily counts for each seizure type. Patients with >70% seizure diary completion and >365 diary days were included. Developmental outcomes at 36 months were compared between subgroups.ResultsEpilepsy was seen in 124 of 156 (79%) participants. Seizure onset occurred from zero to 29.5 months; 93% had onset before age 12 months. Focal seizures and epileptic spasms were most common. Number of seizures (for median 897 days) ranged from 1 to 9128. Hierarchical clustering based on six metrics of seizure burden (age of onset, total seizures, ratio of seizure days to nonseizure days, seizures per seizure day, and worst seven- and 30-day stretches) revealed two distinct groups with broadly favorable and unfavorable epilepsy profiles. Subpopulations within each group showed clinically meaningful differences in seizure burden. Groups with higher seizure burden had worse developmental outcomes at 36 months.ConclusionsAlthough epilepsy is highly prevalent in TSC, not all young children with TSC have the same epilepsy profile. At least two phenotypic subpopulations are discernible based on seizure burden. Early and aggressive treatments for epilepsy in TSC may be best leveraged by targeting specific subgroups based on phenotype severity.
| S-EPMC8487620 | biostudies-literature
Project description:Tuberous sclerosis complex (TSC) is an inheritable disorder characterized by the formation of benign yet disorganized tumors in multiple organ systems. Germline mutations in the TSC1 (hamartin) or more frequently TSC2 (tuberin) genes are causative for TSC. The malignant manifestations of TSC, pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipoma (AML), may also occur as independent sporadic perivascular epithelial cell tumor (PEComa) characterized by somatic TSC2 mutations. Thus, discerning TSC from the copresentation of sporadic LAM and sporadic AML may be obscured in TSC patients lacking additional features. In this report, we present a case study on a single patient initially reported to have sporadic LAM and a mucinous duodenal adenocarcinoma deficient in DNA mismatch repair proteins. Moreover, the patient had a history of Wilms' tumor, which was reclassified as AML following the LAM diagnosis. Therefore, we investigated the origins and relatedness of these tumors. Using germline whole-genome sequencing, we identified a premature truncation in one of the patient's TSC2 alleles. Using immunohistochemistry, loss of tuberin expression was observed in AML and LAM tissue. However, no evidence of a somatic loss of heterozygosity or DNA methylation epimutations was observed at the TSC2 locus, suggesting alternate mechanisms may contribute to loss of the tumor suppressor protein. In the mucinous duodenal adenocarcinoma, no causative mutations were found in the DNA mismatch repair genes MLH1, MSH2, MSH6, or PMS2 Rather, clonal deconvolution analyses were used to identify mutations contributing to pathogenesis. This report highlights both the utility of using multiple sequencing techniques and the complexity of interpreting the data in a clinical context.
| S-EPMC9059781 | biostudies-literature
Project description: Not available
| S-EPMC10593382 | biostudies-literature
Project description:ObjectiveTo evaluate the long-term benefit and safety of everolimus for the treatment of medically refractory epilepsy in patients with tuberous sclerosis complex (TSC).MethodsEverolimus was titrated over 4 weeks and continued an additional 8 weeks in a prospective, open-label, phase I/II clinical trial design. Participants demonstrating initial benefit continued treatment until study completion (48 months). The primary endpoint was percentage of patients with a ≥50% reduction in seizure frequency compared to baseline. Secondary endpoints assessed absolute seizure frequency, adverse events (AEs), behavior, and quality of life.ResultsOf the 20 participants who completed the initial study phase, 18 continued extended treatment. Fourteen of 18 (78%) participants completed the study, all but 1 of whom reported ≥50% reduction in seizure frequency at 48 months. All participants reported at least 1 AE, the vast majority (94%) of which were graded mild or moderate severity. Improvements in behavior and quality of life were also observed, but failed to achieve statistical significance at 48 months.ConclusionsImproved seizure control was maintained for 4 years in the majority of patients with TSC with medically refractory epilepsy treated with everolimus. Long-term treatment with everolimus is safe and well-tolerated in this population. Everolimus may be a therapeutic option for refractory epilepsy in TSC.Classification of evidenceThis study provides Class IV evidence that for patients with TSC with medically refractory epilepsy everolimus improves seizure control.
| S-EPMC5177677 | biostudies-literature