But when both temporal lobes are affected the result might be complete deafness. However, many of these patients have bilateral seizure foci, or develop contralateral foci after resection, and thereby remain refractory. The degree of mossy fiber sprouting correlates with the degree of neuronal loss (Cavazos and Cross, 2006), and both pathological factors seem to contribute to the intensification of chronic seizures (Gorter et al., 2001; Zhang et al., 2002). Here, the authors used the intrahippocampal kainate model of mesial temporal lobe epilepsy and showed that hippocampal paroxysmal discharges occur frequently in male mice, but do not occur in female mice, and that only male mice demonstrate a clear latent period. The mesial temporal lobe is, as the name suggests, located on the medial aspect of the temporal lobe and is distinct from the rest of the lobe which is comprised of neocortex.. It remains an unresolved question whether granule cell dispersion is a developmental defect or the result of epileptic seizure activity. Secondly, careful pathologic analysis of temporal lobe specimens, especially from patients with seizure control following resection, has found that most contain an area of focal pathology, usually HS or mass lesions (French et al., 1993). A clear seizure-free latent period was only observed in male NMRI mice, but not in female NMRI, B6, or FVB/N mice. Dentate gyrus. A 6-year-old boy with a 5-year history of intractable complexpartial seizure was referred by his neurologist for a presurgicalevaluation of a brain locus that may have triggered the seizures.The seizures were described as starting with vocalizations thatwould quickly convert to convulsions of all four extremities.Afterward, the patient would become aphasic or dysarthric forapproximately 1 minute; then the patient would become sleepy. Mesial temporal lobe epilepsy is often associated with changes or abnormal findings on MRI (magnetic resonance imaging). Sufferers from LTLE comprise less than 10% of patients with TLE. Mesial temporal lobe lesion approaches There are several ways to safely access mesial temporal structures. • Familial mesial temporal lobe epilepsy cannot be distinguished from nonfamilial cases on the basis of clinical, EEG, or MRI findings. Recurrent excitation and the development of seizures have been associated with aberrant mossy fiber sprouting in the hippocampus. Finally, this model provides a useful platform on which to evaluate novel therapeutic strategies. By contrast, in most surgical patients with poor seizure control, no hippocampal pathology or only mild damage can be demonstrated (e.g., amygdalar sclerosis) (Mathern et al., 1995; Miller et al., 1994). [4] PMID: 32119319 The temporal lobe functions as one of the four main regions of the brain found within the cerebral cortex, and it is responsible for things like speech, memory, and facial recognition. Typical alterations that are described in temporal lobe regions involve neuronal loss (Lewis, 2005), gliosis, synaptic plasticity (Cavazos and Cross, 2006), neurogenesis (Parent and Lowenstein, 2002), inflammation (Vezzani et al., 2002), and molecular reorganization in cellular membranes and the extracellular matrix (Avanzini and Franceschetti, 2003; Perosa et al., 2002). However, confirmation that this plays a causal, rather than associative relationship, with human epilepsy awaits the results of clinical trials that specifically target tau-based mechanisms. mesial temporal sclerosis. Such asymptomatic localized disturbances may spread to recruit anatomically contiguous gray matter, creating a larger abnormality leading to the clinical manifestations of a seizure with changes in consciousness, motor control, sensory perception, behavior, and/or autonomic dysfunction (Davenport, 1998). The hallmark of AQP4 expression in the CNS is its polarized expression at astrocyte endfeet ensheathing blood vessels.40,41,140 Loss of such polarization is associated with pathology in mesial TLE as discussed above.118 During seizures, there is focal swelling in the area of the seizure focus23,74; and the putative effect of loss of the perivascular pool of AQP4 would be to slow water egress from astrocyte to capillary leading to local astrocyte swelling, ECS constriction, and increased excitability.3. Growing evidence of altered functional connectivity suggests that mesial temporal lobe epilepsy (mTLE) alters not only hippocampal networks, but also a number of resting state networks. An additional major change in the dentate gyrus is the recurrent sprouting of granule cells’ axon fibers, called mossy fibers (Buckmaster, 2012). ### Case histories. The granule cell layer (G) of the dentate gyrus (DG) sends projections, called mossy fibers, toward the CA3 layer. Hippocampal onset accounts for at least 80% of all temporal lobe seizures. The first part of this work concentrates on the concept of mesial temporal lobe epilepsy and its pathophysiology. Surgery. Thus both hilar basal dendrites and apical dendrites of granule cells contribute to additional recurrent excitatory circuitry via sprouted mossy fibers in the epileptic brain. Cell loss is evident in the hilus and pyramidal cell layers in CA3 and CA1. The temporal lobe is the main region of the brain that controls the sensation of hearing. An important way to reach this goal is to standardize the methodologies among different laboratories via the development of common data elements (CDEs) for TLE models (and other preclinical epilepsy models). One study reported no differences in the number and duration of spike-wave complexes between male and female rats with absence seizures (Coenen and Van Luijtelaar, 1987). We use cookies to help provide and enhance our service and tailor content and ads. It is believed that in an epileptic brain there is an alteration of brain function that facilitates hypersynchronous neuronal activity. Thus in this chapter we refer to MTLE when we describe TLE, unless otherwise stated. However, we recently reported that the latent period after kainate-induced SE before onset of spontaneous recurrent seizures varies as a function of mouse strain and sex (Twele et al., 2016a). The second part addresses the clinical characteristics, in particular the natural evolution of the illness, the different aetiologies and the diagnostic relevance of the ictal semiology. It is both a cause and an effect of temporal lobe epilepsy. Group I metabotropic glutamate receptors generate two types of intrinsic membrane oscillations in hippocampal oriens/alveus interneurons. Although temporal lobe seizures are always partial, they can become secondarily generalized and result into tonic–clonic seizures (Mathern et al., 1996). As in the DG, axon fibers of pyramidal cells in both CA3 and CA1 are known to sprout in TLE and contribute to increased connectivity between local pyramidal cells (Long et al., 2014; Siddiqui and Joseph, 2005). Difficulty speaking 3.4. Extensive loss of pyramidal neurons is seen in CA1 and CA3 layers while pyramidal neurons in CA2 and granule cell neurons in DG are relatively spared. Temporal lobe seizures begin in the temporal lobes of your brain, which process emotions and are important for short-term memory. see Temporal lobe epilepsy surgery. Mesial temporal lobe epilepsy (MTLE) affects the inner part of the temporal lobe manifesting in the hippocampus, parahippocampal gyrus and the amygdala. For the first time in this context, a pathologic process in the medial temporal lobes, leading to hippocampal atrophy, is unequivocally documented. While these guidelines span all disciplines of preclinical research, according to a NIH analysis of public comments, “neurobiology and neurological disorders” was one of the top-cited areas of science that would benefit from considering SABV (The National Institutes of Health, 2015). They represent the typical complex partial seizure. In line with this theory we found that ablation of adult neurogenesis using focal brain irradiation is associated with accelerated, kindling epileptogenesis in the rat-kindling model for TLE (Raedt et al., 2007). This process is called mossy fiber sprouting, and is most probably the result of the loss of appropriate targets of the mossy fibers, e.g., hilar polymorphic neurons and CA3 neurons, during the epileptogenic process (Cavazos and Cross, 2006). Moreover, the mesial temporal lobes tend to be the site of origin of close to 80% of all TLEs. Note that there are fewer GAD67 mRNA-positive cells in the stratum oriens in pilocarpine-treated rats, compared with control. Some people remain aware of what's happening, but during more-intense s… Up to a third of patients with established refractory temporal lobe epilepsy have a history of seizures in childhood at the time of fever 3. HS is frequently the result of a previous status epilepticus, complicated febrile convulsions, encephalitis, or an ischemic insult (French et al., 1993). Age at onset Late childhood or adolescence. Because of the advantages of the intrahippocampal kainate mouse model for drug testing, this model is currently being evaluated as a mouse model of therapy-resistant mesial TLE by the Anticonvulsant Screening Program (ASP) of the University of Utah, sponsored by the NIH National Institute of Neurological Disorders and Stroke (NINDS). TLE can be categorized in two groups: those with seizures originating in the mesial temporal lobe structures (mesial temporal lobe epilepsy, MTLE) and those with seizures beginning elsewhere in the temporal lobe (e.g., lateral temporal lobe epilepsy, LTLE). As some authors pointed out, “cells are often identified by staining for cellular markers, and the loss of marker-stained cells could be subsequent to changed expression of that marker rather than cell death” (Alexander et al., 2016); published studies have limitations regarding the identification of interneuron subtypes in TLE. Temporal lobe epilepsy is one of 20 different kinds of epilepsy. What is Mesial Temporal Sclerosis? Furthermore, pharmacologically targeting p-tau expression has been found to be both antiseizure and antiepileptogenic in a variety of acquired epilepsy models (Jones et al., 2011; Liu et al., 2016). Recurrent excitation and the development of seizures have been associated with aberrant mossy fiber sprouting in Here, we established the efficacy of optogenetic and electrical low-frequency stimulation (LFS) in interfering with seizure generation in a mouse model of MTLE. Interestingly, a similar loss of AQP4 polarization has been observed in distinct models of neurological diseases. Along with three other lobes – the occipital lobe, the frontal lobe, and the parietal lobe – it makes up the cerebrum. Abnormal neurogenesis in response to seizures seems not to be limited to animal models for TLE. Euphoria 1.3. The rodent estrous cycle can also affect epilepsy-related phenotypes. Mesial temporal lobe epilepsy (MTLE), the most common epilepsy in adults, is generally intractable and is suspected to be the result of recurrent excitation or inhibition circuitry. Gyrus What is mesial temporal sclerosis acute models from the perspective of modeling epilepsy receive synaptic input from sprouted fibers. In CA3 and CA1 ping Zheng,... Jeanne T. Paz, in models of neurological Diseases for. And thereby remain refractory anatomy involves specific structures frequently implicated as a cause for seizures in the anterior has. 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