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The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017–2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients. [ABSTRACT FROM AUTHOR]

Purpose Clinical, experimental, and neuroimaging data all indicate that the thalamus is involved in the network of changes associated with temporal lobe epilepsy ( TLE), particularly in association with hippocampal sclerosis ( HS), with potential roles in seizure initiation and propagation. Pathologic changes in the thalamus may be a result of an initial insult, ongoing seizures, or retrograde degeneration through reciprocal connections between thalamic and limbic regions. Our aim was to carry out a neuropathologic analysis of the thalamus in a postmortem ( PM) epilepsy series, to assess the distribution, severity, and nature of pathologic changes and its association with HS. Methods Twenty-four epilepsy PM cases (age range 25-87 years) and eight controls (age range 38-85 years) were studied. HS was classified as unilateral ( UHS, 11 cases), bilateral ( BHS, 4 cases) or absent (No- HS, 9 cases). Samples from the left and right sides of the thalamus were stained with cresyl violet ( CV), and for glial firbillary acidic protein (GFAP) and synaptophysin. Using image analysis, neuronal densities ( NDs) or field fraction staining values ( GFAP, synaptophysin) were measured in four thalamic nuclei: anteroventral nucleus ( AV), lateral dorsal nucleus ( LD), mediodorsal nucleus ( MD), and ventrolateral nucleus ( VL). The results were compared within and between cases. Key Findings The severity, nature, and distribution of thalamic pathology varied between cases. A pattern that emerged was a preferential involvement of the MD in UHS cases with a reduction in mean ND ipsilateral to the side of HS (p = 0.05). In UHS cases, greater field fraction values for GFAP and lower values for synaptophysin and ND were seen in the majority of cases in the MD ipsilateral to the side of sclerosis compared to other thalamic nuclei. In addition, differences in the mean ND between classical HS, atypical HS, and No- HS cases were noted in the ipsilateral MD (p < 0.05), with lower values observed in HS. Significance Our study demonstrates that stereotypical pathologic changes, as seen in HS, are not clearly defined in the thalamus. This may be partly explained by the heterogeneity of our PM study group. With quantitation, there is some evidence for preferential involvement of the MD, suggesting a potential role in TLE, which requires further investigation. [ABSTRACT FROM AUTHOR]

Purpose Temporal lobe epilepsy ( TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI ( fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis ( HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3 T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging ( DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. Significance Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS. [ABSTRACT FROM AUTHOR]

The dynamic aspects of epilepsy, in which seizures occur sporadically and are interspersed with periods of relatively normal brain function, present special challenges for neuroanatomical studies. Although numerous morphologic changes can be identified during the chronic period, the relationship of many of these changes to seizure generation and propagation remains unclear. Mossy fiber sprouting is an example of a frequently observed morphologic change for which a functional role in epilepsy continues to be debated. This review focuses on neuroanatomically identified changes that would support high levels of activity in reorganized mossy fibers and potentially associated granule cell activation. Early ultrastructural studies of reorganized mossy fiber terminals in human temporal lobe epilepsy tissue have identified morphologic substrates for highly efficacious excitatory connections among granule cells. If similar connections in animal models contribute to seizure activity, activation of granule cells would be expected. Increased labeling with two activity-related markers, Fos and phosphorylated extracellular signal-regulated kinase, has suggested increased activity of dentate granule cells at the time of spontaneous seizures in a mouse model of epilepsy. However, neuroanatomical support for a direct link between activation of reorganized mossy fiber terminals and increased granule cell activity remains elusive. As novel activity-related markers are developed, it may yet be possible to demonstrate such functional links and allow mapping of seizure activity throughout the brain. Relating patterns of neuronal activity during seizures to the underlying morphologic changes could provide important new insights into the basic mechanisms of epilepsy and seizure generation. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the effectiveness of vagus nerve stimulation to patients with medically-refractory epilepsy, importance of magnetic resonance imaging (MRI) to detect patients with tuberous sclerosis complex (TSC) and surgical management of intractable temporal lobe epilepsy.

Overexpression of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier (BBB) is thought to be involved in pharmacoresistance in epilepsy by extruding antiepileptic drugs (AEDs) from their target site. To explore this hypothesis, positron emission tomography (PET) scans were performed with the Pgp substrate-verapamil (VPM) in animal models before and after status epilepticus (SE) and in patients with temporal lobe epilepsy (TLE) and healthy controls. In addition to baseline scans, a second VPM-PET scan was performed after administration of the Pgp inhibitor tariquidar (TQD), showing that VPM uptake at baseline and its increase after Pgp inhibition are reduced in animals following SE compared to baseline, and in refractory TLE relative to healthy controls. In animal models, brain regions with increased Pgp expression (cerebellum, thalamus, and hippocampus) showed reduced influx rate constants from blood to brain, K1, of the radiolabeled Pgp substrate relative to control animals. In human studies, preliminary findings are lower K1 values in refractory compared to seizure-free patients and attenuated increase of K1 for temporal lobe regions in patients with TLE compared to healthy controls. In summary, there is lower brain uptake of the Pgp substrate VPM in Pgp-rich areas of animals 2 days following SE, as well as lower increase in VPM brain uptake after TQD in patients with refractory TLE compared to healthy controls, supporting the hypothesis of increased cerebral Pgp function following prolonged seizures and as a mechanism contributing to drug resistance in refractory epilepsy. The observation of reduced VPM uptake in refractory compared to seizure-free patients with TLE is consistent with multiple mechanisms affecting Pgp function, including uncontrolled seizures. [ABSTRACT FROM AUTHOR]