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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many treatments for the epilepsies and affective disorder share the properties of seizure suppression and mood stabilization. Moreover, affective disorders and the epilepsies appear to share partially similar pathogenic mechanisms. A component of the shared predisposition appears to arise from noradrenergic and serotonergic deficits. Increasing evidence supports the hypothesis that noradrenergic and/or serotonergic elevation is a mechanism of therapeutic benefit shared by most antidepressants and many antiepileptic medications. Medication induced alterations in GABAergic, glutamatergic, and CRH (corticotropin releasing hormone) containing neurons may also contribute to the shared therapeutic properties of antidepressant and antiepileptic medications.
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PMID:Shared mechanisms of antidepressant and antiepileptic treatments: drugs and devices. 1511 61

Concepts pertaining to affective disorder and epilepsy comorbidity are contributing appreciably to improvements in patient care. Several antiepileptic treatments have become important components of the management of bipolar affective disorder. In contrast, little progress has emerged in developing clinical applications of the anticonvulsant properties of the antidepressants in the treatment of the epilepsies. The slow onset of action of the antidepressants remains a major impediment to fully effective treatment of depressive episodes. Nevertheless, studies from experimental epileptology demonstrate that the anticonvulsant effects of the antidepressants occur rapidly and as a consequence of noradrenergic and/or serotonergic activation. These studies also demonstrate that adequate initial doses of the antidepressants are essential to rapid onset of anticonvulsant action. Pharmacokinetically valid loading dose paradigms are seemingly avoided with antidepressant drugs in humans because of potential toxicities and/or patient unacceptability. However, substantial progress has been made in reducing the adverse effect liability of the antidepressants. No longer is convulsive liability considered to stem from the therapeutic mechanisms of the anti-depressants. Rather, noradrenergic and serotonergic influences have demonstrable anticonvulsant properties. Other side effects may also be separable from the anticonvulsant and antidepressive effects of antidepressive treatments. The concept that the protracted process of antidepressant-induced beta-noradrenergic down-regulation is an essential prelude to the onset of mood benefit is no longer a sustainable premise. Nevertheless, increasing evidence underlies the possibility that knowledge of serotonergic and noradrenergic regulatory processes can be used to design strategies that will hasten the onset of antidepressive action. Similar optimism pervades efforts to determine the possibility that dual inhibition of serotonin and norepinephrine transporters will hasten onset of antidepressive action. Moreover, because noradrenergic and serotonergic systems are determinants of predisposition to seizures and to dysfunctional affective episodes, augmentation strategies may also be applicable to the use of antidepressant drugs in epilepsy and to the use of antiepileptic drugs such as carbamazepine in mood disorders. Recent studies have demonstrated that, in part, the therapeutic effectiveness of carbamazepine may stem from its marked capacity to elevate serotonin concentrations in the extracellular fluid of the brain via mechanisms that differ from those of the membrane reuptake inhibitors. Evidence suggests that the epilepsies and affective disorders may arise from a multiplicity of neurobiological abnormalities. A disorder in one individual may arise via different mechanisms than a phenomenologically similar disorder in another individual. Thus, diagnostic tools are needed to make mechanistic distinctions among individuals so that treatments can be appropriately developed and selected. In terms of epileptogenesis and affective disorder progression, neuroprotective paradigms for one individual may differ from those needed for another. Moreover, diagnostic technologies that are adequate to detect genetically and/or experientially determined vulnerability before the onset of a seizure or dysfunctional affective episode may be valuable steps toward achieving goals of prevention.
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PMID:Affective disorder and epilepsy comorbidity: implications for development of treatments, preventions and diagnostic approaches. 1511 64

Valproic acid (VPA), used to treat bipolar mood disorder and seizures, also inhibits histone deacetylase (HDAC). Here, we found that VPA and other HDAC inhibitors, butyrate and trichostatin A, robustly protected mature cerebellar granule cell cultures from excitotoxicity induced by SYM 2081 ((2S, 4R)-4-methylglutamate), an inhibitor of excitatory amino-acid transporters and an agonist of low-affinity kainate receptors. These neuroprotective effects required protracted treatment and were correlated with enhanced acetylated histone levels, indicating HDAC inhibition. SYM-induced excitotoxicity was blocked by MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate), supporting that the toxicity was largely N-methyl-D-aspartate receptor dependent. SYM excitotoxicity had apoptotic characteristics and was prevented by a caspase inhibitor. SYM-induced apoptosis was associated with a rapid and robust nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a housekeeping gene previously shown to be proapoptotic. VPA pretreatment suppressed SYM 2081-induced GAPDH nuclear accumulation, concurrent with its neuroprotective effects. Chromatin immunoprecipitation (ChIP) revealed that GAPDH is copresent with acetylated histone H3, including Lys9-acetylated histone, and that VPA treatment caused a time-dependent decrease in the levels of nuclear GAPDH with a concomitant increase in acetylated histones in the ChIP complex. Our results strongly suggest that VPA protects neurons from excitotoxicity through inhibition of HDAC activity and that this protective effect may involve suppression of excitotoxicity-induced accumulation of GAPDH protein in the nucleus.
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PMID:Valproic acid inhibits histone deacetylase activity and suppresses excitotoxicity-induced GAPDH nuclear accumulation and apoptotic death in neurons. 1528 98

Mood disorders in patients with epilepsy are not frequently diagnosed and not treated. Because of the high prevalence of depression and the resulting high suicide rate, precise diagnosis and effective therapy are very important. Frequently, the clinical pictures of depressive syndromes in epileptics do not correspond with those described in operationalized classification systems such as ICD-10 or DSM-IV. The incidence of depressive disorders in epileptics is estimated in the literature to be 30%-70%. Multifactorial pathogenetic models include the type of seizures, the location of the epileptic focus, and neurotransmitter dysfunctions, as well as hereditary and psychosocial influences, and negative psychotropic effects of antiepileptic drugs. Despite an insufficient number of available controlled studies, based on the current data, treatment with the newer serotonergic antidepressants can be recommended for patients with epilepsy.
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PMID:Mood disorders and their treatment in patients with epilepsy. 1574 79

Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Accumulating evidence supports the notion that neuroinflammation is involved in the pathogenesis of this disease. Valproate (VPA) has long been used for the treatment of seizures and bipolar mood disorder. In vivo and in vitro studies have demonstrated that VPA has neuroprotective and neurotrophic actions. In this study, using primary neuron-glia cultures from rat midbrain, we demonstrated that VPA is a potent neuroprotective agent against lipopolysaccharide (LPS)-induced neurotoxicity. Results showed that pretreatment with 0.6 mM VPA for 48 h robustly attenuated LPS-induced degeneration of dopaminergic neurons as determined by [(3)H] dopamine uptake and counting of the number of TH-ir neurons. The neuroprotective effect of VPA was concentration-dependent and was mediated, at least in part, through a decrease in levels of pro-inflammatory factors released from activated microglia. Specifically, LPS-induced increase in the release of TNFa, NO, and intracellular reactive oxygen species was markedly reduced in cultures pretreated with VPA. These anti-inflammatory effects of VPA were time and concentration-dependent correlated with a decrease in the number of microglia. Thus, our results demonstrate that protracted VPA pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity through a reduction in levels of released pro-inflammatory factors, and further suggest that these anti-inflammatory effects may be contributed by VPA-induced reduction of microglia cell number. Taken together, our study reinforces the view that VPA may have utility in treating Parkinson's disease.
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PMID:Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. 1579 May 40

The current study was performed to determine possible gender differences among risk factors for suicidal behavior in epilepsy. A special rating scale for assessment of suicidality was designed. The risk of suicide attempt was higher in epilepsy with concomitant diagnoses of organic affective disorder (F=06.3, ICD-10) and cognitive impairment (F=07.62, ICD-10). Risk was higher among females than males. Early age of epilepsy onset and high frequency of secondary generalized, simple partial, and all seizures were risk factors for suicidality in males, whereas low frequency of complex partial seizures was the risk factor in females. Daily dose of a classic antiepileptic drug was a risk factor for males, whereas daily dose of phenobarbital was a risk factor for both genders. Daily dose of carbamazepine and valproate is inversely correlated with suicidal behaviour in women, but not in men. The results obtained are discussed in the context of a paradigm of gender dimorphism as an indicator of evolution of Homo sapiens.
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PMID:Gender differences in risk factors of suicidal behavior in epilepsy. 1582 Mar 53

There is evidence that psychogenic nonepileptic seizures (PNES) remain underdiagnosed, especially in children and adolescents. Diagnosis of such events is even more difficult in patients that do have epilepsy, leading to delayed diagnosis and treatment and, consequently, iatrogenic complications. This study aimed to evaluate possible risk factors in children with epilepsy who had PNES. Seizures and epileptic syndromes were classified according to International League Against Epilepsy guidelines. Patients were evaluated with a structured psychiatric anamnesis and classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research; and Schedule for Affective Disorders and Schizophrenia for School-Age Children--Epidemiological Version. Risk factors such as head trauma, physical, sexual and psychological abuse, and psychiatric diagnoses, among others, were investigated. Family history of epilepsy and psychiatric illness were detected by review of medical records and/or follow-up interviews. Gender was not a predictive factor, and although older children had a higher risk for PNES, younger children also presented truly psychogenic events mimicking epileptic seizures. The most common associated psychiatric diagnosis was depression. Family histories for epilepsy and psychiatric illness were a frequent finding. An inadequate family environment was more common than sexual or physical abuse. Current knowledge obtained from adults with PNES has been used to understand children with PNES. However, this study of children with epilepsy revealed some similarities and many differences. These features may help to identify predictive factors in a population in need of adequate diagnosis of and therapy for this long-lasting pathology.
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PMID:Risk factors for psychogenic nonepileptic seizures in children and adolescents with epilepsy. 1625 66

In this cross-sectional study, the neuropsychiatric profiles of 42 patients with juvenile myoclonic epilepsy (JME) who were treated with valproate (VPA) or topiramate (TPM) in monotherapy were compared with the aim of verifying the relationship between cognitive dysfunction, psychiatric disorders, and factors related to epilepsy. Patients with JME taking VPA 500-1750 mg/day or TPM 50-175 mg/day were selected. For all patients, psychiatric profiles were evaluated with the Scheduled Clinical Interview, axes I and II (SCID I and SCID II), or the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS-PL). Neuropsychological measures included intellectual functions, attention, memory, executive functions, and language. Patients taking TPM exhibited worse neuropsychological performance on attention, short-term memory, processing speed, and verbal fluency functions related to frontal lobes, which may be dysfunctional in JME. Anxiety disorders were associated with lack of seizure control and having had more than 20 lifetime generalized tonic-clonic seizures.
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PMID:Neuropsychiatric profiles of patients with juvenile myoclonic epilepsy treated with valproate or topiramate. 1650 93

This article describes the diary of a man from 19th-century England (1829-1834) that documents the onset and course of his wife's epilepsy after a stroke. Her stroke produced aphasia and right hemiparesis, but her epilepsy was the diary's focus and caused the greatest concern. The diary documents the history of her epilepsy in detail. In addition to tonic-clonic seizures, she experienced frequent bouts of status epilepticus and complex partial seizures. The diary contains some of the earliest recorded descriptions of status epilepticus and its aftermath of delirium, mood disorder, and hysteria. It also offers some of the earliest and most detailed accounts of complex partial seizures. Bleeding by cupping was the only symptomatic or prophylactic treatment recorded. These aspects of the diary are presented, as are the historical perspectives on epilepsy, including early beliefs and stigmas, therapeutic remedies, and early European views of epilepsy.
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PMID:A diary of epilepsy in the early 1800s. 1726 88

Depressive Mood Scale (EHD) aims at assessing the various depressive mood dimensions as "blunted affect" and "lack of emotional control". It is an 18 items hetero-evaluation scale. The aim of this study was the validation of an EHD self questionnaire version. Self questionnaire items were generated from genuine scale items. As in the former version, response format was a Lickert 5 point scale. This validation study was carried out on 77 Multiple Sclerosis (MS) patients. Mood disorders are frequent during the course of MS and might be triggered or worsened by immuno-modulation therapies. Principal Component Analysis (ACP) with Varimax rotation revealed a two factors structure. The first one, corresponding to a "blunted affect" dimension, explained 33.5% of the scale variance and was composed of 7 items. The second one, corresponding to a "lack of emotional control" dimension, explained 20% of total scale variance and was composed of 4 items. The questionnaire internal coherence coefficient (Cronbach alpha) was excellent (=0.87) and the two sub-scales ones were satisfactory [0.89 for "blunted affect" dimension and 0.71 for "lack of emotional control" dimension. The questionnaire's external validity was confirmed by a positive correlation between "lack of control" sub-score and state sub-score of the Stait-Trait Anger eXpression Inventory (STAXI)] (r=0.55, p<0.01). Moreover we found a positive correlation between the total EHD autoquestionnaire score and both sub-scores on the one hand, and the Beck Depression Inventory score on the second hand (EHD/BDI: r=0.76, p<0.01; "lack of emotional control"/BDI: r=0.68, p<0.01; "blunted affect"/BDI: r=0.63, p<0.01). Test-retest reliability was good with a positive correlation between all the initial scores and their retests, a week later. Secondarily, a structural equation modeling analysis confirmed the two-factors structure model suggested by ACP. Various indicators showed a good fit between theoretical variance-covariance matrix and the observed one (chi(2)=41.55, p=0.49, ddl=42, Goodness Fit Index GFI=0.91, Root Mean Square Residual RMSEA=0.00). Thus, we proposed a well validated self questionnaire that allows the assessment of "blunted affect" and "lack of emotional control". It should be challenging to correlate those dimensions with neuro-psycho-logical testing and neuro-imagery, in patients affected by CNS diseases. Moreover, the assessment of those dimensions during interferon treatment in MS could allow a more precise evaluation of the emotional changes potentially induced by immuno-modulatory treatments.
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PMID:[Validation of EHD self questionnaire in multiple sclerosis]. 1745 94


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