Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vigabatrin (VGB) prevents seizures by irreversible inhibition of gamma-aminobutyric acid (GABA) transaminase and a resulting increase in GABA levels. We evaluated the cognitive and quality-of-life (QOL) effects of VGB in a double-blinded, add-on, placebo-controlled, parallel group dose-response study of patients with focal epilepsy whose complex partial seizures (CPS) were difficult to control. In a single investigation, patients were randomly assigned to placebo (n = 40), 1 g VGB (n = 36), 3 g VGB (n = 38), or 6 g VGB (n = 32), treated for 12 weeks after a 6-week dose escalation period, and tested at the end of the baseline period and at the end of the treatment period with eight cognitive measures and three tests of mood and adjustment. The patient groups were highly similar at study entry. Results at the end of the study showed substantial relief from seizures. The Digit Cancellation Test showed decreases in performance with increasing doses of VGB. Performance on no other test showed any decrement with increasing dosage. Relief from seizures was not associated with changes on the psychological tests. VGB is a useful antiepileptic drug (AED) that has little impact on tests of either cognitive abilities or QOL, even at a high dose.
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PMID:Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and quality of life in epilepsy. 782 Dec 74

Glutamate is the principal excitatory neurotransmitter in the brain and, as such, it inevitably plays a role in the initiation and spread of seizure activity. It also plays a critical role in epileptogenesis. The process of "kindling" limbic seizures in rodents by repeated electrical stimulation is dependent on activation of N-methyl-D-aspartate (NMDA) receptors. The function of these receptors is enhanced in the hippocampus of kindled rats and in the cerebral cortex of patients with focal epilepsy. Microdialysis studies show an increase in the extracellular concentration of glutamate and aspartate before or during seizure onset, suggesting that either enhanced amino acid release or impaired uptake contributes to seizure initiation. Glutamate antagonists selective for NMDA or non-NMDA receptors are potent anticonvulsants when given systemically in a wide variety of animal models of epilepsy. They are of limited efficacy against kindled seizures in rats and (on the basis of preliminary evidence) in patients with drug-refractory complex partial seizures. Cognitive side effects appear to be a significant problem with competitive, as well as noncompetitive, NMDA antagonists. Glutamate receptor antagonists provide significant protection against brain damage following global or focal cerebral ischemia or acute traumatic injury in rodent models. Anticonvulsant compounds of the lamotrigine type, which act on sodium channels and reduce ischemia-induced glutamate release, are cerebroprotective in rodent ischemia models and are free from the cognitive side effects of NMDA-receptor antagonists.
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PMID:The role of glutamate in epilepsy and other CNS disorders. 797 2

With Single Photon Emission Computed Tomography (SPECT) of regional cerebral bloodflow (rCBF) ictally and interictally, regional changes of rCBF can be detected in many cases with medically intractable complex partial seizures. Interictal SPECT shows abnormal rCBF in the epileptogenic temporal lobe in 40% to 85% of the patients. A critical survey of the methodological problems considering isotopes, scanners, data analysis and patient population is presented here as well as a few semi-quantitative studies including our own. It is concluded, that SPECT of rCBF is a useful, non-invasive method of localizing the epileptogenic zone in patients with severe partial focal epilepsy. Ictal SPECT of rCBF has a higher predictive value and is more sensitive than interictal studies for localization of the seizure focus. Interictal SPECT using a high-resolution system obtains an almost as high frequency of localization of the focus. With low resolution scanners, a minor frequency is observed. Both interictal and ictal SPECT recordings should be obtained for localization of the epileptogenic focus in presurgical cases as interictal hypoperfusion and ictal hyperperfusion demonstrated in the same focal area are highly characteristic of a seizure focus.
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PMID:Utility of interictal SPECT of rCBF for focal diagnosis of the epileptogenic zone(s). 820 33

Temporal lobe epileptogenic foci were blindly localized in 8 patients with medically refractory unilateral complex partial seizures using noninvasive in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) with 4-ml effective voxel size. The brain proton metabolite signals in 8 matched normal controls were bilaterally symmetrical within +/- 10%. The hippocampal seizure foci had 21 +/- 5% less N-acetyl aspartate signal than the contralateral hippocampal formations (p < 0.01). The focal N-acetyl aspartate reductions were consistent with pathology findings of mesial temporal sclerosis with selective neuron loss and gliosis in the surgically resected epileptogenic foci. Proton MRSI correctly localized the seizure focus in all 8 cases. By comparison, MR imaging correctly localized 7 of 8 cases and single photon emission computed tomography correctly localized 2 of 5 cases. No lactate was detected in these interictal studies. No significant changes in choline or creatine were observed. In conclusion, 1H-MRSI is a useful tool for the noninvasive clinical assessment of intractable focal epilepsy. These preliminary results suggest that 1H-MRSI can accurately localize temporal lobe epileptogenic foci.
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PMID:Neuron loss localizes human temporal lobe epilepsy by in vivo proton magnetic resonance spectroscopic imaging. 825 May 27

We evaluated the psychological effects of the antiepilepsy drug vigabatrin in a randomized multicenter double-blind placebo-controlled parallel group study that compared 3 grams oral vigabatrin with placebo as daily add-on therapy in patients with focal epilepsy whose complex partial seizures were difficult to control. Testing at baseline and after 12 weeks of vigabatrin (n = 83) or placebo (n = 85) used eight measures of cognitive abilities and three of mood and adjustment. The vigabatrin and placebo groups were highly similar at entry into the study. At the end of the study, there were no differences between the vigabatrin and placebo groups on any cognitive variable or on any measure of mood and adjustment. Analysis of the results related to relief from seizures demonstrated only chance findings. In a similar manner, there were no relationships between vigabatrin serum levels at the end of the study and changes on measures of abilities and adjustment. Vigabatrin appears to be a useful antiepilepsy drug with little impact upon tests of either cognitive abilities or quality of life.
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PMID:Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy. 825 47

Since the advent of magnetic resonance imaging, there has been renewed interest in disorders of cortical migration in the cause of focal epilepsy. The function of dysplastic cortex is poorly understood. We report a 46-year-old woman in whom this was assessed by intraoperative stimulation. This left-handed patient had a 30-year history of complex partial seizures with secondary generalization. Prolonged electroencephalographic recordings documented an epileptic focus in the right lateral and inferomesiotemporal lobe. Computed tomographic scanning and angiography suggested a right posterotemporal hamartoma. Amytal testing showed major speech representation in the right hemisphere. At craniotomy, an ivory-colored, posterotemporal lesion originating 5 cm from the temporal tip and 4 cm in diameter occupied the posterotemporal region. Electrical stimulation of this lesion produced speech interference. A histological examination of the resected anterotemporal lobe, amygdala, and hippocampus and biopsy specimens of the lesion showed extensive multifocal cortical microdysgenesis and gliovascular and cortical hamartoma. This case shows that grossly dysplastic cortex can remain functional. Cortical mapping under local anesthesia should be performed before resection of dysplastic lesions in putatively functional areas in patients with intractable epilepsy.
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PMID:Retained language in dysgenic cortex: case report. 855 50

This study compared the efficacy and tolerability of vigabatrin 3/day as add-on therapy with that of placebo in patients with focal epilepsy whose complex partial seizures were difficult to control with established antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 placebo; 92 vigabatrin) received drug therapy under double-blind conditions. We increased the daily dosage to 2.5 g/day during a 4-week titration segment and maintained it at 3 g/day during the 12-week maintenance segment. By analyses we found a statistically significant lower frequency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo. The median monthly frequency was reduced by three seizures per 28 days in the placebo group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic success (a 50% reduction from baseline in mean monthly seizure frequency) was attained in 40 of the vigabatrin patients (43%) compared with 17 of those treated with placebo (19%) (p < 0.001). Vigabatrin significantly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 micrograms/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the elimination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vigabatrin treatment. The results of this study indicate that 3 g/day vigabatrin is more effective than placebo as add-on therapy. Vigabatrin was well tolerated, compliance was high with twice-daily administration, and therapy did not result in clinically relevant drug interactions.
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PMID:A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort. 855 21

The diagnosis of non-epileptic seizures (NES) is problematic. Although diagnosis can be achieved by videotelemetry, these facilities are expensive and not widely available. HMPAO SPECT studies show focal hypoperfusion interictally in focal epilepsy. SPECT has not been studied in any detail in NES previously. Two groups (10 patients each) were studied, one with NES and one with complex partial seizures and localisation related epilepsy. SPECT scans were normal in 7 of 10 (70%) NES patients, while showing clear focal hypoperfusion in 8 of 10 patients (80%) with epilepsy. In the NES group, 1 patient showed hypoperfusion indistinguishable from that seen in epilepsy, while 2 patients in the epilepsy group showed only equivocal focal hypoperfusion. The remaining 2 patients in the NES group showed bifrontal and equivocal focal hypoperfusion. A normal HMPAO SPECT study supports the diagnosis of NES in patients with seizures of uncertain aetiology.
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PMID:HMPAO SPECT in non-epileptic seizures: preliminary results. 889 Oct 51

Tiagabine blocks the uptake by neurons or glia of synaptically released GABA resulting in prolonged GABAergic activity and decreased likelihood of epileptic seizures. We evaluated the cognitive and quality of life effects of tiagabine in a double-blind, add-on, placebo-controlled, parallel, multicenter, dose-response efficacy study in patients with focal epilepsy whose complex partial seizures were difficult to control. One hundred sixty-two patients provided cognitive and quality of life data for the analyses and received the following treatments: placebo (n = 57), 16 mg/d tiagabine (n = 34), 32 mg/d tiagabine (n = 45), or 56 mg/d tiagabine (n = 26) at a fixed-dose for 12 weeks after a 4-week dose titration period. Eight cognitive tests and three measures of mood and adjustment were administered during the baseline period and again during the double-blind period near the end of treatment (or at the time of dropout). The patient groups were similar at entry into the study. Results showed no clinically important changes with the addition of tiagabine on the test battery. Although this is an encouraging finding, it remains for future investigations to determine the cognitive and behavioral effects of tiagabine either as monotherapy or in relation to other antiepileptic drugs.
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PMID:Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. 910 94

Our patient underwent right anteromesial temporal resection at 17 years of age for intractable complex partial seizures due to hippocampal sclerosis, and then developed juvenile myoclonic epilepsy after a change in medication. Postoperative seizures ceased after a change to valproate monotherapy. Our patient reminds us to remain aware that generalized and focal epilepsy may coexist as an unusual cause for surgical failure. We feel that these patients may still be favorable candidates for epileptic surgery, as long as the focal epileptogenic zone is amenable to resection and the generalized epilepsy appears to be readily controllable.
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PMID:Worsening seizures after surgery for focal epilepsy due to emergence of primary generalized epilepsy. 978 52


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