Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium (Li) reduces brain inositol levels by inhibiting the enzyme inositol monophosphatase. The enzyme inositol-1-phosphatase was measured in human red blood cells of controls, Li-free bipolar patients, and Li-treated bipolar patients and was found to be reduced by 80% in Li-treated bipolars, thus supporting the concept that chronic Li at therapeutic concentrations inhibits this enzyme. Two behaviors in rats caused by Li, reduction of rearing, and Li-pilocarpine seizures, are reversed by intracerebroventricular replenishment of inositol. The reversal is stereospecific to the naturally occurring myo-inositol; whereas the stereoisomer L-chiro-inositol is ineffective. The reversal is dose-dependent, requiring a dose consistent with known quantities of brain inositol depletion; and is time-dependent, as inositol must be given 1-8 h before stimulation. High-dose peripheral inositol also reverses the limbic seizures induced by Li-pilocarpine, and using gas chromatography was shown to increase brain inositol levels that had been reduced by Li treatment. Low-dose inositol could be shown to reverse a peripheral Li-induced side effect, polyuria/polydipsia, in rats and in patients treated with Li. A higher dose of inositol markedly reduced Hamilton Depression Ratings in 9 of 11 unipolar major depressive disorder patients previously unresponsive to tricyclics, in an open design, but had no effect on chronic schizophrenics in a controlled double-blind randomized crossover trial. A new inositol monophosphatase inhibitor, a fungal product originally discovered as a complement inhibitor, was found to act like Li and lower the seizure threshold for subconvulsant doses of pilocarpine. These data suggest that inositol monophosphatase inhibition is a key mechanism of Li's therapeutic action and that design of new inositol monophosphatase inhibitors may be a practical strategy to create new compounds with Li-like therapeutic effects.
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PMID:Ziskind-Somerfeld Research Award 1993. Biochemical, behavioral, and clinical studies of the role of inositol in lithium treatment and depression. 811 Sep 11

Fifteen patients with major depression who were being treated with bilateral electroconvulsive treatment (ECT) were investigated before and 45 min after a single ECT using split-dose Single Photon Emission Tomography (SPET or SPECT) with 99mTc-Exametazime. All patients suffered from unipolar depressive illness and were rated on the Newcastle scale and with the 17-item Hamilton scale. They completed tests of orientation and verbal memory on the day of ECT. For comparison, verbal memory was also tested on the preceding day. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Significant decreases in tracer uptake were confined to the inferior anterior cingulate cortex. The changes were correlated with the severity of depressive symptoms and more weakly with decrements of memory function produced by ECT; there was no significant correlation with stimulus intensity or electroencephalographic measures of seizure duration.
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PMID:Short-term effects of electroconvulsive treatment on the uptake of 99mTc-exametazime into brain in major depression shown with single photon emission tomography. 815 Oct 46

The effects of the anesthetic agents propofol and methohexital on seizure duration, clinical outcome, recovery, and memory in electroconvulsive therapy (ECT) were studied in a double-blind trial. The study comprised 53 patients, 47 patients with major depression and six patients with other diagnoses according to DSM-III. Several recent clinical studies with a crossover design have shown a reduced seizure duration for anesthesia with propofol in comparison with both methohexital and thiopental. Propofol significantly reduced the seizure duration in this study without reducing the therapeutic outcome as measured by the Montgomery-Asberg Depression Rating Scale. Propofol did not significantly alter the length of the course of ECT; however, a slightly prolonged course for women cannot be completely ruled out. There were no significant differences between the two agents in effects on recovery times after anesthesia and on anterograde memory. In general, it seems that propofol is as effective as methohexital as an induction agent for ECT.
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PMID:A comparison of propofol and methohexital as anesthetic agents for ECT: effects on seizure duration, therapeutic outcome, and memory. 817 18

The effect of pulse unilateral electroconvulsive therapy (ECT) on heart rate, blood pressure and the product of heart rate and systolic blood pressure, an index of myocardial oxygen consumption, was studied during 48 ECT sessions in 7 patients with major depression. Intra-individually, hyperventilation-induced hypocapnia compared with normocapnia markedly augmented the ECT-induced increase in heart rate (47% vs 28%) and the product of heart rate and systolic blood pressure (82% vs 60%). Over all ECT seizures, the maximum and increase in heart rate and the product of heart rate and systolic blood pressure were significantly correlated with seizure duration as determined by electroencephalography. However, significant correlations were only present for the seizures during hypocapnia and not during normocapnia. Combining measures of magnitude and length of ECT-induced tachycardia to motor responses may increase the potential for clinical seizure evaluation.
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PMID:Cardiovascular response and seizure duration as determined by electroencephalography during unilateral electroconvulsive therapy. 837 92

Thirty patients with major depressive disorder of melancholic subtype were randomly allocated to receive ECT either twice or thrice a week. Double-blind ratings on the Hamilton Scale for Depression and Clinical Global impression showed no differences in the outcome through 4 weeks of trial as well as at 6-month follow-up. Cumulative seizure duration was higher in the thrice weekly group but not significantly so in spite of having received a significantly greater number of ECTs. The results indicate that ECT given thrice a week conferred no advantage over ECT given twice a week.
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PMID:Twice versus thrice weekly ECT in melancholia: a double-blind prospective comparison. 850 27

The first detailed case report of recurrent common migraine after electroconvulsive therapy (ECT) is presented; it involves a 52-year-old woman with major depressive disorder. The migraine symptoms corresponded to those of the infrequent spontaneous migraine attacks she had. After a change to propofol as the anesthetic because of methohexital intolerance, the migraine attacks ceased, apparently due to seizure generalization being inhibited by propofol. In patients with migraine, ECT may be expected to trigger a migraine attack, probably in the same way as spontaneous seizures. The possible reasons and significance are discussed.
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PMID:Migraine after electroconvulsive therapy. 852 66

Tiagabine (TGB) hydrochloride is a potential new antiepileptic drug (AED) undergoing clinical development. Experience in humans amounts to 1,810 patient-years of exposure. TGB was found to be tolerated in an integrated safety analysis of five double-blind, add-on therapy trials involving approximately 1,000 patients with epilepsy with difficult-to-control seizures with existing AEDs. Discontinuation resulting from adverse events were infrequent, occurring in 15% of patients receiving TGB compared to 5% receiving placebo. The most frequently reported adverse event was dizziness, which was usually transient and did not require medical intervention. Adverse events that were statistically significantly more common with TGB than placebo were dizziness, asthenia, nervousness, tremor, diarrhea, and depression (not major depression). Adverse events were usually mild to moderate in severity and transient, and most were associated with dose titration. The incidence, type, and severity of adverse events in long-term studies were comparable with those in short-term studies. Serious adverse events were uncommon and no idiosyncratic events were reported.
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PMID:Tiagabine: the safety landscape. 859 87

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (+/- S.D.) was 8.4 +/- 3.4 micrograms/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 +/- 9.4 micrograms/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 +/- 11.5 micrograms/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.
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PMID:Increased serum levels of neuron-specific enolase in epileptic patients and after electroconvulsive therapy--a preliminary report. 871 37

Titration of the electroconvulsive therapy (ECT) stimulus to the patient's convulsive threshold is the only way to directly assess the patient's seizure threshold. This technique is presently practiced by 39% of ECT providers, according to a recent survey. Because multiple variables influence the seizure threshold in patients, multivariate statistical methods may provide a useful strategy to determine which variables exert the most influence on convulsive threshold. A multivariate ordinal logistic model of seizure threshold was developed on an experimental group of 66 consecutive patients undergoing titrated right unilateral (RUL) ECT for major depression. The accuracy of the model was cross-validated on a second group of 40 patients undergoing similar RUL ECT procedures. The final multivariate ordinal logistic regression model for the seizure threshold level (STL) was significant (Likelihood ratio chi 2 = 54.115; p < 0.0001:R2 = 0.313). Increasing age, African-American race, and longer inion-nasion distances (p < 0.06) predicted higher STL. Female gender was associated with a lower STL. The ability of the final model to accurately predict STL for the validation group was fair (pairwise correlation was 0.576; p < 0.001). The model did well for predicting lower STL, but fared poorly for higher STL. In conclusion, modeling STL may help establish the relative contribution of variables thought to be important to seizure threshold. However, STL models remain impractical for clinical applications in estimating seizure threshold at this time, and empirical stimulus titration should be used.
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PMID:A statistical model predicting the seizure threshold for right unilateral ECT in 106 patients. 877 50

Twenty-two patients with major depression received a course of right unilateral ECT. The convulsive threshold (CT) was determined on the first treatment. Subsequent treatments were approximately 2.25 times CT. Seizure morphology for treatments 2-6 were rated for regularity (0-6 scale; low-high) and postictal suppression (0-3; low-high). Ratings of postictal suppression were log transformed to improve the approximation to a normal distribution. A preliminary analysis of variance with CT as the independent variable compared the seizure ratings at low, mid, and high CT. Second, linear regression models for the mean values of seizure regularity and postictal suppression were determined using age, gender, and the CT as predictor variables. The degree of postictal suppression varied inversely with age, male gender, and CT in this study. Our results suggested that CT made the greatest contribution to the model. Future studies examining the predictive value of seizure morphology parameters to clinical outcome should include measurement of CT.
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PMID:Relationship of seizure morphology to the convulsive threshold. 887 2


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