-
Tidsskrift For Den Norske Laegeforening... Jan 2023The temporal lobes are the part of the brain most likely to give rise to epileptic seizures. Seizures originating in the temporal lobes vary greatly in character; some...
The temporal lobes are the part of the brain most likely to give rise to epileptic seizures. Seizures originating in the temporal lobes vary greatly in character; some may be so unusual that they are not even recognised as epileptic. For patients who have been diagnosed with hippocampal sclerosis and whose seizures cannot be controlled with drugs, epilepsy surgery may be a good treatment option. In this brief clinical review, we summarise the key features of epilepsy and highlight the importance of accurate and early diagnosis for achieving good clinical outcomes.
Topics: Humans; Epilepsy, Temporal Lobe; Seizures; Epilepsy; Temporal Lobe; Brain; Hippocampus; Electroencephalography
PubMed: 36718887
DOI: 10.4045/tidsskr.22.0369 -
Epilepsia Feb 2020Mesial temporal lobe epilepsy (mTLE) is a neurological disorder in which patients suffer from frequent consciousness-impairing seizures, broad neurocognitive deficits,... (Review)
Review
Mesial temporal lobe epilepsy (mTLE) is a neurological disorder in which patients suffer from frequent consciousness-impairing seizures, broad neurocognitive deficits, and diminished quality of life. Although seizures in mTLE originate focally in the hippocampus or amygdala, mTLE patients demonstrate cognitive deficits that extend beyond temporal lobe function-such as decline in executive function, cognitive processing speed, and attention-as well as diffuse decreases in neocortical metabolism and functional connectivity. Given prior observations that mTLE patients exhibit impairments in vigilance, and that seizures may disrupt the activity and long-range connectivity of subcortical brain structures involved in vigilance regulation, we propose that subcortical activating networks underlying vigilance play a critical role in mediating the widespread neural and cognitive effects of focal mTLE. Here, we review evidence for impaired vigilance in mTLE, examine clinical implications and potential network underpinnings, and suggest neuroimaging strategies for determining the relationship between vigilance, brain connectivity, and neurocognition in patients and healthy controls.
Topics: Arousal; Brain Mapping; Epilepsy, Temporal Lobe; Humans; Nerve Net; Neuroimaging
PubMed: 31901182
DOI: 10.1111/epi.16423 -
Nature Communications Oct 2020Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To...
Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.
Topics: Adolescent; Adult; Biopsy; Case-Control Studies; Cell Nucleus; Datasets as Topic; Drug Resistant Epilepsy; Epilepsy, Temporal Lobe; Female; Glutamic Acid; Humans; Magnetic Resonance Imaging; Male; Microdissection; Middle Aged; Models, Genetic; Nerve Net; Neurons; RNA-Seq; Receptors, AMPA; Receptors, Glutamate; Signal Transduction; Single-Cell Analysis; Temporal Lobe; Transcription, Genetic; Transcriptome; Up-Regulation; Young Adult
PubMed: 33028830
DOI: 10.1038/s41467-020-18752-7 -
Proceedings of the National Academy of... Nov 2022Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy, yet approximately one-third of patients are refractory to current anticonvulsive drugs, which...
Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy, yet approximately one-third of patients are refractory to current anticonvulsive drugs, which target neurons and synapses. Astrocytic and microglial dysfunction is commonly found in epileptic foci and has been shown to contribute to neuroinflammation and hyperexcitability in chronic epilepsy. Accumulating evidence points to a key role for glial hemichannels in epilepsy, but inhibiting both connexin (Cx) gap junctions and hemichannels can lead to undesirable side effects because the former coordinate physiological functions of cell assemblies. It would be a great benefit to use an orally available small molecule to block hemichannels to alleviate epileptic symptoms. Here, we explored the effect of D4, a newly developed compound that inhibits the Cx hemichannels but not Cx gap junctions using the pilocarpine mouse model of TLE. In vitro application of D4 caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity. Moreover, preadministration of D4 in vivo effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate. Posttreatment with a single dose of D4 in vivo has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine. Collectively, these results indicate that targeting Cx hemichannels by D4 is an effective and promising strategy for treating epilepsy in which neuroinflammation plays a critical role.
Topics: Animals; Mice; Connexins; Epilepsy, Temporal Lobe; Pilocarpine; Neuroinflammatory Diseases; Epilepsy
PubMed: 36322757
DOI: 10.1073/pnas.2213162119 -
Science (New York, N.Y.) Dec 2022The large diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct...
The large diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the visual system can each be defined by unique combinations of on average 10 continuously expressed transcription factors. We show that targeted modifications of this terminal selector code induce predictable conversions of neuronal fates that appear morphologically and transcriptionally complete. Cis-regulatory analysis of open chromatin links one of these genes to an upstream patterning factor that specifies neuronal fates in stem cells. Experimentally validated network models describe the synergistic regulation of downstream effectors by terminal selectors and ecdysone signaling during brain wiring. Our results provide a generalizable framework of how specific fates are implemented in postmitotic neurons.
Topics: Animals; Drosophila Proteins; Gene Expression Regulation, Developmental; Neurons; Transcription Factors; Neurogenesis; Drosophila melanogaster; Neural Stem Cells; Optic Lobe, Nonmammalian
PubMed: 36480601
DOI: 10.1126/science.add1884