الفهرس 
INTRODUCTION
GENERALIZED EPILEPSYOnly 14 pages are availabe for public view
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Abstract
Transcranial magnetic stimulation (TMS) has been used to assess cortical disinhibition/excitation in patients with epilepsy and determine the degree of patients’ response to antiepileptic drugs (AEDs). However, the results of studies are variable and conflicting. This study was aimed to assess cortical motor excitability in adults with temporal lobe epilepsy (TLE) with impaired awareness or with bilateral tonic-clonic seizures. All patients were on treatment with antiepileptic drugs. The following TMS parameters were used for assessment: resting and active motor thresholds, cortical silent period and central motor conduction time. This study included 40 adults (males = 22; females = 18) with TLE with impaired awareness or to bilateral tonic clonic seizures with mean age of 32.50±3.38yrs and mean duration of illness of 6.15±2.02yrs). They were on regular AEDs monotherapies [valproate or VPA=15; carbamazepine or CBZ=15; levetiracetam or LEV=10]. The majority (62.5%) were seizure free for at least 1 year before TMS testing. All had normal MRI-brain except two showed atrophy and signal changes in the unilateral hippocampus. This study also included 20 healthy subjects as controls for statistical comparisons. Comparing the entire patients with controls, patients had significantly bi-hemispheric higher RMT and AMT particularly over the epileptic hemisphere and shorter CSP and CMCT in the epileptic hemisphere only. Shorter CSP and CMCT were observed with patients on VPA or CBZ and uncontrolled patients on medication (particularly epileptic hemisphere) but not in patients on LEV. Significant correlations were identified between RMT and AMT (P =0.01) and between CSP and CMCT (P = 0.001). The results of this study showed that the most prominent changes in interictal TMS parameters in our patients with TLE were the bi-hemispheric increase in MTs and the shortening of CSP and CMCT in the epileptic hemisphere compared to control subjects. The bi-hemispheric increase in MTs mainly reflect reduced cortical axonal excitability which is one of anticonvulsant mechanisms of AEDs but might not be related to ”at the moment state” of cortical excitability. The unilateral shortening of CSP and CMCT mainly reflect the asymmetrical increase in interictal cortical disinhibition/enhanced hyperexcitation despite the apparent control on AEDs which means that seizures are simply inactivated via improved control with AEDs but actually not gone (epileptogenesis) and therefore this can predict presence of pharmacoresistance and the need for life-long combined therapy with AEDs which have multiple mechanisms of action. The conflicting results among TMS studies in CSP as well as other TMS measures in patients with focal epilepsy including TLE might reflect the inter- and intra-individual dynamic epileptogenic processes and the compensatory phenomena per individual over the long disease course. For CSP, it has to be remembered that its latter part (> 75 ms) is ascribed to GABAB receptor activation. Therefore, the presence of increased or reduced CSP or lack of abnormalities in patients with epilepsy depends on whether GABAB neural substrates are involved in epileptogenesis or in interictal compensatory phenomena or not. Furthermore, the lack of increases CSP duration with VPA or CBZ suggest that the therapeutic benefits of these drugs do not involve improved GABAB mediated inhibition, however, the favorable CSP results (similar to control) with LEV suggest that LEV prohibited more pronounced alterations in cortical disinhibition and prevented the appearance of differences between patients and control groups due to its multiple anticonvulsant mechanisms of action which may indirectly involve the GABA system. Future clinical researches have to focus on paired-pulse TMS paradigms in testing pathological motor excitability in epilepsy. These paradigms are probably more closely related to the abnormal intracortical circuits and neuronal plasticity than to the excitability of the neural membrane detected by single-pulse paradigms.