Epilepsia
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The mechanisms of drug resistance in epilepsy are only incompletely understood. According to a current concept, overexpression of drug efflux transporters at the blood-brain barrier may reduce levels of antiepileptic drugs (AEDs) in epileptogenic brain tissue. Increased expression of drug efflux transporters such as P-glycoprotein has been found in brain tissue surgically resected from patients with medically intractable epilepsy, but it is not known whether this leads to decreased extracellular (interstitial) AED concentrations in affected brain regions. This prompted us to measure concentrations of AEDs in the extracellular space of human neocortical tissue by using intraoperative microdialysis (IOMD) in those parts of the brain that had to be removed for therapeutic reasons. For comparison, AED levels were determined in brain tissue, subarachnoid CSF, and serum. ⋯ The data demonstrate that AED concentrations show a considerable intraindividual and interindividual variation in the ECS of cortical regions. Furthermore, the ECS concentration of several AEDs is significantly lower than their CSF concentration in patients with intractable epilepsy. However, in the absence of data from nonepileptic tissues, it is not possible to judge whether the present findings relate to overexpression of multidrug transporters in the brain. Instead, the present study illustrates the methodologic difficulties involved in performing IOMD studies in patients and may thus be helpful for future approaches aimed at elucidating the role of multidrug transporters in epilepsy.
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Randomized Controlled Trial Comparative Study
Onset of action of levetiracetam: a RCT trial using therapeutic intensive seizure analysis (TISA).
To correlate the onset of clinical effects of add-on levetiracetam (LEV) therapy with daily serum LEV concentration, in pharmaco-resistant focal epilepsies, using the TISA method. ⋯ The present study objectively quantified the correlation between the anticonvulsant effects of LEV in focal epilepsies and the peak serum concentration of the drug. For the first time, direct measurement was used to demonstrate the onset of action of LEV to be two days after drug initiation.
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Comparative Study
Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed.
Considering the epileptogenic effect of cavernoma-surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin-stained brain tissue. ⋯ Our study suggests that complete removal of cavernoma-surrounding hemosiderin-stained brain tissue may improve epileptic outcome after resection of cavernous malformations.
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Comparative Study
Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbazepine.
Evidence suggests that enzyme-inducing antiepileptic drugs (AEDs) may decrease serum 25-hydroxyvitamin D (25-OHD) levels and increase bone turnover. We sought to determine whether these are affected by treatment with carbamazepine (CBZ) or oxcarbazepine (OXC). ⋯ Epilepsy patients taking OXC or CBZ have significantly lower 25-OHD than do normal controls, with a pattern of changes in other bone biomarkers suggestive of secondary hyperparathyroidism. It may be prudent for patients taking CBZ or OXC to be prescribed 25-OHD replacement.
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Comparative Study
Seizure recurrence and risk factors after antiepilepsy drug withdrawal in children with brain tumors.
To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence. ⋯ AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.