Inhibition of monoamine oxidase type A, but not type B, is an effective means of inducing anticonvulsant activity in the kindling model of epilepsy.
(1/1221)
The anticonvulsant activity of inhibitors of monoamine oxidase (MAO) was reported early after the development of irreversible MAO inhibitors such as tranylcypromine, but was never clinically used because of the adverse effects of these compounds. The more recently developed reversible MAO inhibitors with selectivity for either the MAO-A or MAO-B isoenzyme forms have not been studied extensively in animal models of epilepsy, so it is not known which type of MAO inhibitor is particularly effective in this respect. We compared the following drugs in the kindling model of epilepsy: 1) L-deprenyl (selegiline), i.e., an irreversible inhibitor of MAO-B, which, however, also inhibits MAO-A at higher doses, 2) the novel reversible MAO-B inhibitor LU 53439 (3,4-dimethyl-7-(2-isopropyl-1,3, 4-thiadiazol-5-yl)-methoxy-coumarin), which is much more selective for MAO-B than L-deprenyl, 3) the novel reversible and highly selective MAO-A inhibitor LU 43839 (esuprone; 7-hydroxy-3, 4-dimethylcoumarin ethanesulfonate), and 4) the irreversible nonselective MAO inhibitor tranylcypromine. Esuprone proved to be an effective anticonvulsant in the kindling model with a similar potency as L-deprenyl. In contrast to esuprone and L-deprenyl, the selective MAO-B inhibitor LU 53439 was not effective in the kindling model; this substantiates the previous notion that the anticonvulsant activity of L-deprenyl is not related to MAO-B inhibition, but to other effects of this drug, such as inhibition of MAO-A. Drugs inhibiting both MAO-A and MAO-B to a similar extent (tranylcypromine) or combinations of selective MAO-A and MAO-B inhibitors (esuprone plus LU 53439) had no advantage over MAO-A inhibition alone, but were less well tolerated. The data thus suggest that selective MAO-A inhibitors such as esuprone may be an interesting new approach for the treatment of epilepsy. (+info)
In vivo intracellular analysis of granule cell axon reorganization in epileptic rats.
(2/1221)
In vivo intracellular recording and labeling in kainate-induced epileptic rats was used to address questions about granule cell axon reorganization in temporal lobe epilepsy. Individually labeled granule cells were reconstructed three dimensionally and in their entirety. Compared with controls, granule cells in epileptic rats had longer average axon length per cell; the difference was significant in all strata of the dentate gyrus including the hilus. In epileptic rats, at least one-third of the granule cells extended an aberrant axon collateral into the molecular layer. Axon projections into the molecular layer had an average summed length of 1 mm per cell and spanned 600 microm of the septotemporal axis of the hippocampus-a distance within the normal span of granule cell axon collaterals. These findings in vivo confirm results from previous in vitro studies. Surprisingly, 12% of the granule cells in epileptic rats, and none in controls, extended a basal dendrite into the hilus, providing another route for recurrent excitation. Consistent with recurrent excitation, many granule cells (56%) in epileptic rats displayed a long-latency depolarization superimposed on a normal inhibitory postsynaptic potential. These findings demonstrate changes, occurring at the single-cell level after an epileptogenic hippocampal injury, that could result in novel, local, recurrent circuits. (+info)
Patient readmission and support utilization following anterior temporal lobectomy.
(3/1221)
The aim of this study was to examine factors precipitating patient readmission, following anterior temporal lobectomy (ATL) for refractory epilepsy. A second aim was to explore the use of hospital outpatient and community support services ('outpatient services') by this patient population. These aims served the more general goal of identifying patients most likely in need of services additional to those routinely provided by our Seizure Surgery Follow-up and Rehabilitation Programme. The medical records of 100 consecutive ATL patients were retrospectively examined for the incidence and diagnoses precipitating acute readmission, and the utilization of additional outpatient services. Twenty-one patients (21%) required readmission post-ATL, totalling 47 readmissions between them. Psychiatric diagnoses were the most prevalent (53%), including anxiety, depression and/or post-ictal psychosis. Epileptological diagnoses were the other main precipitant (28%). Additional outpatient services were predominantly utilized for ongoing psychological support. Of the 21 patients requiring readmission, 10(10%) also needed additional outpatient services. These patients were predominantly female or unemployed, in contrast to male or employed patients who tended to require readmission only. Seventeen patients (17%) were maintained within the community using additional outpatient services only. Characteristics of these patients included disrupted family dynamics, limited social networks, and/or a psychiatric history. These patients were also more frequently beyond the 24-month follow-up period of the programme. A profile of patients most in need of additional support services can be constructed to assist team planning of proactive management strategies for the rehabilitation phase of ATL. (+info)
Dose-related effects of single focal irradiation in the medial temporal lobe structures in rats--magnetic resonance imaging and histological study.
(4/1221)
The dose-related effects of single focal irradiation on the medial temporal lobe in rats were investigated by sequential magnetic resonance imaging and histological examination. Irradiation of 200 Gy as a maximum dose using 4 mm collimators with a gamma unit created an area of necrosis consistently at the target site within 2 weeks after irradiation. Irradiation of 100 Gy caused necrosis within 10 weeks, and 75 Gy caused necrosis within one year. Irradiation of less than 50 Gy did not induce necrosis consistently, although a restricted area of necrosis was created in the medial temporal structures including the intraparenchymal portion of the optic tract. 75 Gy may be the optimum dose for creating necrosis consistently in the medial temporal lobe structures. However, careful dose planning considering both dose-time and dose-volume relationships in necrosis development is necessary to avoid injury to vulnerable neural structures such as the optic tract when applying radiosurgical techniques to treat functional brain disorders in medial temporal lobe structures such as temporal lobe epilepsy. (+info)
Early and delayed MR and PET changes after selective temporomesial radiosurgery in mesial temporal lobe epilepsy.
(5/1221)
We report a patient with medically refractory mesial temporal lobe epilepsy treated by gamma knife radiosurgery. In lieu of a microsurgical procedure, an entorhinoamygdalohippocampectomy was performed with a gamma knife and low marginal doses (25 Gy). The clinical and imaging studies, including CT, MR imaging, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and long-term follow-up MR examinations, are reported. The patient has been seizure-free since the day of treatment, with no clinical complications. MR studies accurately depicted the effect on the target structures and the transient secondary changes around them. FDG-PET scans showed decreased metabolism after gamma knife surgery throughout the anteromesial part of the epileptogenic temporal lobe. This metabolic decrease was reversible in the lateral temporal cortex. Our case suggests that gamma knife surgery is a promising tool for use as a minimally invasive approach to the treatment of epilepsy. (+info)
Plasticity of language-related brain function during recovery from stroke.
(6/1221)
BACKGROUND AND PURPOSE: This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI. METHODS: Blood oxygenation level-dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes. RESULTS: The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke's and Broca's areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca's area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke's aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event. CONCLUSIONS: Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements. (+info)
Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth.
(7/1221)
A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in approximately 74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N-methyl-D-aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the hypothesis that recurrent mossy fiber growth and synapse formation increases the excitatory drive to dentate granule cells and thus facilitates repetitive synchronous discharge. Activation of NMDA receptors in the recurrent pathway may contribute to seizure propagation under depolarizing conditions. Mossy fiber-granule cell synapses also are present in normal rats, where they may contribute to repetitive granule cell discharge in regions of the dentate gyrus where their numbers are significant. (+info)
The role of the hippocampus in auditory processing studied by event-related electric potentials and magnetic fields in epilepsy patients before and after temporal lobectomy.
(8/1221)
To clarify the relationship between the hippocampus and the event-related responses in auditory information processing, we recorded event-related potentials (ERPs) and event-related magnetic fields (ERFs) associated with the auditory oddball paradigm in 12 patients with temporal lobe epilepsy before and after surgical treatment, and in eight age-matched healthy volunteers. Lesions in the patients were hippocampal sclerosis (8), cyst (2), cavernoma (1) and calcified arteriovenous malformation (1), all in the unilateral temporal lobe. Standard temporal lobectomy (8), selective amygdalohippocampectomy (2), selective hippocampectomy (1) and inferior lateral temporal resection (1) were carried out. ERPs were recorded in nine patients before surgery, in all 12 patients after surgery, and in all normal subjects. P300 was maximal at Pz in the patients both before and after surgery, and in normal subjects. The peak latency and amplitude of P300 measured at Pz in the patients either before or after surgery did not differ significantly from those in normal subjects. After surgery, only the amplitude of P300 over the anterior and mid-temporal area on the resected side was attenuated, while it was symmetric before surgery regardless of the side of epileptogenic focus. ERFs were recorded in three patients before surgery and in six normal subjects by using a whole-head neuromagnetometer. ERFs in response to the target stimuli at a latency of approximately 400 ms were recognized at the anterior, middle and posterior lateral channels on each hemisphere (M400). The latency and dipole moments for M400 did not differ significantly between the patients before surgery and the normal subjects. As a result of analysis using the time-varying multidipole model, three dipoles for M400 were estimated in two patients in whom ERFs were available before surgery for the analysis, and in normal subjects: mesial temporal area, superior temporal area and inferior parietal area on each hemisphere. After surgery, in four out of six patients in whom ERFs were recordable, M400 at the anterior temporal channels on the resected side disappeared, and the activity in the affected mesial temporal area was lost. In one patient who underwent inferior lateral temporal resection, M400 waveforms and its sources were preserved in all regions. There were no significant differences in the latency and dipole moments of the unaffected source of M400 before versus after surgery. These results suggest that the hippocampus contributes to the scalp-recorded P300 only at the corresponding anterior temporal region, and does not influence its general waveform and predominant distribution over the scalp. (+info)