Cortical tubers, cognition, and epilepsy in tuberous sclerosis.
ABSTRACT Tuberous sclerosis complex is an autosomal-dominant genetic disorder characterized by hamartomatous growth in various organs. Patients who have this disorder exhibit a high rate of epilepsy and cognitive problems. We investigated number of tubers, location, seizure types, and cognitive outcome, and we analyzed the relationships among them in our tuberous sclerosis patients in the Comprehensive Epilepsy Program at the University of Alberta. We also examined the seizure outcome after tuber resection. Our study cohort included 24 patients with tuberous sclerosis complex. We obtained seizure history, electroencephalogram, and neuropsychologic parameters. Magnetic resonance imaging was used to examine tuber numbers and locations. Ten patients underwent surgical removal of tubers responsible for intractable epilepsy. A negative correlation was found between the number of tubers and intelligent quotient score. Epilepsy surgery led to freedom from seizures in this patient group. We demonstrated that the total number and location of cortical tubers play a significant role in the extent of mental retardation in patients with tuberous sclerosis complex. In addition, patients with intractable seizures and well-defined epileptic focus had excellent surgical outcome.
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ABSTRACT: Background Epilepsy occurs with increased frequency in people with an intellectual disability (ID) compared to the rest of the population. A variety of research has in recent years shed light on genetic and biochemical aetiologies of epilepsy and, often in a different literature, on syndromes of ID. The aims of this annotation are to review developments in understanding of the pathophysiology of several ID syndromes in which epilepsy is a frequent co-occurrence and to relate these observations to recent advances in understanding of how these pathophysiological disturbances may lead to epilepsy. Method The ID syndromes selected for review were fragile X (FXS), Rett (RTT) and Angelman syndromes (AS) and tuberous sclerosis complex (TSC). Epilepsy is a significant aspect of these syndromes and relevant research into the genetic and biochemical pathophysiology of these four ID syndromes may be informative in establishing the association between epilepsy and ID. Employing a structured approach the authors initially searched the PubMed database for large case series describing the characteristics of epilepsy as manifested in these ID syndromes. The criteria for inclusion of the case series in the review were a sample size of greater than 50 and the description of several of the characteristic features of epilepsy, namely prevalence of seizures, age of seizure onset, seizure frequency, seizure semiology, severity and treatment. Following this, studies of the genetic and biochemical pathophysiology of these four ID syndromes were reviewed and the potential relevance of this research in understanding the association with epilepsy highlighted. Findings were considered in a focused manner in terms of effects on excitatory and inhibitory neurotransmitter systems and on glial function. Results Diverse genetic pathologies underlying several ID syndromes can lead to alterations in the functioning of the glutamatergic and GABAergic neurotransmitter systems. The mechanisms involved include transcriptional regulation in RTT, translational regulation in FXS and TSC, and UBE3A-mediated proteolysis in AS. Expression or functioning of receptor subunits, uptake sites and enzymes involved in neurotransmitter metabolism are often affected by these changes, and may lead to modifications in network excitability and neuronal plasticity that may contribute to epileptogenesis and ID. Dysfunction in astrocytes may also contribute to epileptogenesis and ID in FXS, RTT and TSC with potential mechanisms including failure of astrocytic support functions, glial inflammation and homeostatic disturbances that affect the excitability and architecture of neuronal networks. Conclusions The annotation highlights research describing disturbances in excitatory and inhibitory neurotransmitter systems, neuronal ion channel and glial functions that provide possible explanations for the co-occurrence of seizures within several ID syndromes, in some cases suggesting possible avenues for research into novel therapeutic targets. Phenotypic overlaps between syndromes may also relate to roles for the implicated genes in different disturbances in linked biochemical pathways.Journal of Intellectual Disability Research 12/2011; · 1.88 Impact Factor
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ABSTRACT: Background: The clinical phenotypes and their severity in patients with tuberous sclerosis complex can be quite variable and are sometimes never determined simply by the primary mutation. These make clinically selecting appropriate treatments and predicting disease outcome difficult. In this report, the prognostic ominous sequence was evaluated in association with clinical manifestations and gene mutations. Methods: The patients were classified by each renal lesion of angiomyolipomas and polycystic disease. The other clinical manifestations and outcomes of epilepsy, mental retardation, facial angiofibromas, subependymal giant cell astrocytoma, cortical tubers were reviewed and each gene mutations were analyzed in seven unrelated patients. Results: Two patients with multiple and large proliferative renal angiomyolipoma showed poor clinical outcome than the patients with other renal lesions. These patients presented with progressively proliferative facial angiofibroma, West syndrome, Lennox-Gastaut syndrome, severe mental retardation, subependymal giant cell astrocytoma and they were affected by TSC2 gene mutations. Conclusion: The sequence of progressively proliferative renal angiomyolipoma, facial angiofibroma, West syndrome and TSC2 gene mutations might be prognostic ominous factors.Brain & development 05/2013; · 1.74 Impact Factor
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ABSTRACT: To present a prenatal diagnosis of familial tuberous sclerosis complex (TSC). A 29-year-old woman was referred to our institution for amniocentesis at 24 weeks of gestation because of congenital anomaly. The fetus had been found to have an intrathoracic echogenic mass, suspicious of type III congenital cystic adenomatoid malformation of the lung (CCAML). The woman presented with a medical history of epilepsy and had received anticonvulsants but did not disclose the disease entity associated with the epilepsy. Amniocentesis revealed a karyotype of 46,XX. A fetal ultrasound examination at 26 weeks of gestation reported the diagnosis of type III CCAML. At 30 weeks of gestation, magnetic resonance imaging showed multiple cortical tubers in the brain along with an intracardiac mass suspicious of cardiac rhabdomyoma, and a diagnosis of fetal TSC was made. A prenatal ultrasound examination at 30 weeks of gestation revealed multiple cardiac tumors and multiple cortical tubers in the brain. The mother admitted that she had been diagnosed to have TSC. Molecular analysis of the cultured amniocytes and the parental blood showed a splicing mutation of c.2639+1G>C in the splice donor site of intron 22 of TSC2 gene in the mother and the fetus. Prenatal diagnosis of an intrathoracic lesion with a family history of parental epilepsy should raise a suspicion of fetal cardiac rhabdomyoma and TSC, and prompt magnetic resonance imaging investigation and molecular genetic analysis if necessary.Taiwanese journal of obstetrics & gynecology 09/2013; 52(3):415-9.