Hippocampal sclerosis

Mesial temporal lobe epilepsy (MTLE) A type of epilepsy that consists of partial seizures arising from the mesial temporal lobe of the brain. Often this type of epilepsy is associated with an anatomic change described as hippocampal sclerosis. Patients with this type of epilepsy often have excellent outcomes with surgery for epilepsy. 

Riban V, Bouilleret V, Pham-L BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112 101-111 Rudolph U, Crestani F, Benke D, Brunig I, Benson J, Fritschy JM, Martin JR, Bluethmann H, Mohler H (1999) Benzodiazepine actions mediated by specific y-aminobutyric acid A receptor subtypes. Nature 401 796-800... 

MuyUaert D, Terwel D, Kremer A, Sennvik K, Boighgraef P, Devijver H, Dewachter I, Van Leuven E (2008) Neurodegeneration and neuroinflammation in cdk5/p25-inducible mice a model for hippocampal sclerosis and neocoitical degeneration. Am J Pathol 172 470 85... 

The dentate gyrus is a major site of neuropathology in FTLD-TDP (frontotemporal lobar degeneration with transactive response DNA-binding protein of 43 kDa proteinopathy). Most laminae of the cerebral cortex are affected. CRN mutation cases are quantitatively different from sporadic cases while cases with associated hippocampal sclerosis and AD have increased densities of dystrophic neurites and abnormally enlarged neurons, respectively. There is little correlation between the subjective assessment of subtypes and the more objective quantitative data [98]. Atrophy of the corpus callosum in AD is independent of white matter lesions and may be associated with cognitive deterioration [99],... 

FIGURE 36.5 Seizure reduction per month in 6 patients with ESHC, graphs show 3-month baseline period, stimu-iation started at the fourth month (arrow) after that, 12-month stimulation follow-up. (a) Three patients with normal MRI. (b) Three patients with left hippocampal sclerosis. 

Billinton, A, Baird, VH, Thom, M, Duncan, JS, Upton, N, Bowery, NG (2001) GABA(B) receptor autoradiography in hippocampal sclerosis associated with human temporal lobe epilepsy. Br J Pharmacol, 132 475 80. 

Briellmann, RS, Newton, MR, Wellard, RM, Jackson, GD (2001) Hippocampal sclerosis following brief generalized seizures in adulthood. Neurology, 57 315-317. 

Cavazos, JE, Das, 1, Sutula, TP (1994) Neuronal loss induced in limbic pathways by kindling evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci, 14 3106-3121. 

Davies, KG, Hermann, BP, Dohan, FCJ, Foley, KT, Bush, AJ, Wyler, AR (1996) Relationship of hippocampal sclerosis to duration and age of onset of epilepsy, and childhood febrile seizures in temporal lobectomy patients. Epilepsy Res, 24 119-126. 

Fisher, PD, Sperber, EF, Moshe, SL (1998) Hippocampal sclerosis revisited. Brain Dev, 20 563-573. 

Sutula, TP, Pitkanen, A (2001) More evidence for seiziure-induced neuron loss is hippocampal sclerosis both cause and effect of epilepsy Neurology, 57 169-170. 

It is widely accepted today that prolonged seizures can selectively kill vulnerable neurons. This selective neuronal loss (diffuse cortical atrophy, unilateral hippocampal sclerosis, cerebellar atrophy) was described in the 1800s in institutionalized patients with refractory epilepsy and was assumed to be secondary to hypoxia/ischemia. In the 1970s, after experiments in primates, Meldmm and colleagues proposed that selective hippocampal and neuronal loss resulted from ischemic changes due to local seizure activity lasting 82-120 min (Meldmm, 2002). 

Many models of recurrent seizures do not demonstrate neuronal loss, and as in many, spontaneous seizures are preceded by SE, the initial neuronal loss may be attributed to SE rather than subsequent seizures (Gorier et al., 2003). Longstanding debate has centered on whether hippocampal sclerosis (neuronal loss and gliosis in CAl, CA3, and hilus of the dentate gyrus) results from seizures or is the cause of seizures. 

Prolonged seizures of around 30 min produce necrotic and apoptotic cell death in the same cell population with different time courses or in different cell populations. The current concept of the fate of a neuron is determined by many factors following an initial seizure including early gene expression with alteration of mRNA and proteins (enzymes, receptors, and ion channel subunits) modulated by calcium mediated effects. These changes alter the vulnerability of that neuron to subsequent excitotoxic stresses. Therefore, genetics influences seizure susceptibility (manifested in animal models and febrile seizures in humans) and consequences of seizures (hippocampal sclerosis). 

Changes in excitatory amino acid receptors have been documented by multiple laboratories (Mody and Heinemann, 1987 Kohr and Mody, 1994 Kraus et al., 1994). Increased mRNA levels of NMDA receptor subunits have been measured in dentate-granule cells of patients with hippocampal sclerosis and mesial temporal lobe epilepsy (Mathem et al., 1999). 

These acute changes on MRI typically show complete resolution even after SE (Salmenpera et al., 2000). However, in both children and adults, there may be evolution to atrophy in the region that showed initial swelling with an increased T2-weighted signal intensity, attributed to gliosis and neuronal cell loss (Tien and Felsberg, 1995 Meierkord et al., 1997 Perez et al., 2000). This phenomenon is typically seen with the development of hippocampal sclerosis. 

In a retrospective study of fast titration in 423 epileptic patients taking topiramate, 42 developed depression [330 °]. Rapid titration was associated with a fivefold increased risk of depression. This risk further increased in the presence of other risk factors (13-fold when rapid titration was associated with febrile seizures, 23-fold when associated with a previous history of depression, and 7.6-fold in the presence of hippocampal sclerosis). 

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