Genesis Of Epileptic Seizures Research Articles

Risk factors for preoperative and postoperative seizures in patients with glioblastoma according to the 2021 World Health Organization classification.

To identify risk factors for developing glioblastoma (GBM) related preoperative (PRS) and postoperative seizures (POS). Also, we aimed to analyze the impact of PRS and POS on survival in a GBM cohort according to the revised 2021 WHO glioma classification. We performed a single-center retrospective cohort study of patients with GBM (according to the 2021 World Health Organization Classification) treated at Mayo Clinic Florida between January 2018 and July 2022. Seizures were stratified into preoperative seizures (PRS) and postoperative seizures (POS, >7 days after surgery). Associations between patients' characteristics and overall survival with PRS and POS were assessed. One hundred nineteen adults (mean =60.9 years), 49 (41.2%) females, were identified. The rates of PRS and POS in the cohort were 35.3% (n=42) and 37.8% (n=45), respectively. Patients with PRS were younger (p = 0.035) and were likely to undergo intraoperative electrocorticography. The incidence of PRS (p = 0.049) and POS (p<0.001) was lower among patients with tumors located in the occipital location. PRS increased the risk of POS after adjusting for age and sex (RR: 2.59, CI=1.44-4.65, p = 0.001). There was no association between PRS or POS and other patient-related factors, including several tumor molecular markers (TMMs) examined. PRS (p = 0.036), POS (p<0.001), and O6-Methylguanine-DNA Methyltransferase (MGMT) promotor methylation status (p = 0.032) were associated with longer survival time. PRS and POS are associated with non-occipital tumor location and longer survival time in patients with GBM. While younger ages predicted PRS, PRS predicted POS. Well-designed prospective studies with larger sample sizes are needed to clarify the influence of TMMs in the genesis of epileptic seizures in patients with GBM.

P214 THE THERAPEUTIC IMPLICATIONS OF A FATAL COINCIDENCE

Abstract Background Factor VII deficiency is a rare, inherited disorder secondary to a reduction or absence of factor VII (FVII) of the coagulation pathway presenting with autosomal recessive transmission and caused by different types of mutation of the F7 gene. The clinical manifestations of the syndrome are highly variable: depending on the case, it can remain asymptomatic, or it can present with episodes of bleeding secondary to trauma and surgery, or it can manifest with potentially fatal spontaneous hemorrhages. It can be treated by long–term replacement prophylaxis, which consists of periodic infusions of FVII concentrates. Clinical case A 75–year–old woman presented to the emergency room in a soporose state. On the electrocardiogram, ST–segment elevation in the antero–septal and in AVR and septal akinesia affecting the left ventricle was shown. On admission, she presented with syncope, marked hypotension, and tonic–clonic spasm. Blood tests showed sodium levels of 112 mEq/L, secondary to the administration of high doses of Escitalopram and associated with the genesis of epileptic seizures. During the emergency coronary angiography, severe stenosis of mid–proximal IVA was seenand subsequently treated with PTCA/DES. Right before the procedure, therapy with Acetylsalicylic acid (ASA) 250 mg, Ticagrelor 180 mg, and Heparin sodium was administered 5000 IU + 5000 IU. Immediately after, severe anemia (5.9 Hb) and INR lengthening were demonstrated, with widespread skin hematomas. In the complete study of the coagulative state, an almost complete factor VII deficiency was found, which required infusion of factor VII concentrate. The subsequent course was further complicated by pre–renal acute renal failure and paroxysmal atrial fibrillation. Following the initial suspension of antiplatelet and anticoagulant therapy (OAT), it was possible to reintroduce, without loading dose, ASA and clopidogrel, preserving OAT for later phases. Discussion and Conclusions FVII deficiency, a rare hemorrhagic disorder, may represent a fatal coincidence in the context of myocardial infarction, due to the therapeutic implications of the pathology, which may lead to inevitable uncontrolled bleeding. This occurrence is difficult to predict in some cases, including the present one. It would be interesting to identify indicators that could prompt, even in an emergency setting, the suspicion of such a dangerous association.

The LGI1 protein: molecular structure, physiological functions and disruption-related seizures.

Leucine-rich, glioma inactivated 1 (LGI1) is a secreted glycoprotein, mainly expressed in the brain, and involved in central nervous system development and physiology. Mutations of LGI1 have been linked to autosomal dominant lateral temporal lobe epilepsy (ADLTE). Recently auto-antibodies against LGI1 have been described as the basis for an autoimmune encephalitis, associated with specific motor and limbic epileptic seizures. It is the second most common cause of autoimmune encephalitis. This review presents details on the molecular structure, expression and physiological functions of LGI1, and examines how their disruption underlies human pathologies. Knock-down of LGI1 in rodents reveals that this protein is necessary for normal brain development. In mature brains, LGI1 is associated with Kv1 channels and AMPA receptors, via domain-specific interaction with membrane anchoring proteins and contributes to regulation of the expression and function of these channels. Loss of function, due to mutations or autoantibodies, of this key protein in the control of neuronal activity is a common feature in the genesis of epileptic seizures in ADLTE and anti-LGI1 autoimmune encephalitis.

Effect of cross-fostering on seizures in adult male offspring of methamphetamine-treated rat mothers

Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory γ-aminobutyric acid (GABA) and excitatory N-methyl-d-aspartate (NMDA) systems play a role in the effect of stimulants in the genesis of epileptic seizures. Our previous studies showed that prenatal methamphetamine (MA) exposure induced long-term changes in seizure susceptibility. The aim of the present study was to investigate the effect of cross-fostering on the prenatal and postnatal MA-exposed rats, respectively, on their seizures in adulthood. Bicuculline (GABAA receptor antagonist), NMDA (NMDA receptor agonist) and flurothyl (a convulsant gas) were used to induce seizures in adult male offsprings. Female dams were injected with MA (5mg/kg daily) or physiological saline (S) for approx. 9 week [about 3 week prior to impregnation, for the entire gestation period (22 days) and in preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposure) of adult male rats were tested in each seizure test: C/C; C/S; C/MA; S/C; S/S; S/MA; MA/C; MA/S; MA/MA. The present study demonstrates that the effect of prenatal and/or postnatal MA exposure is seizure model specific. In addition, our data show that there is an effect of cross-fostering on seizures; particularly, the effect of prenatal MA exposure shown in animals fostered by control mothers is no longer apparent in animals fostered postnatally by MA-treated mothers. Such effect of postnatal treatment is not manifested in prenatal controls. In summary, it seems that: (1) prenatal MA exposure alters seizure susceptibility more than postnatal MA exposure; (2) especially in seizures induced by chemicals that affect GABAergic system (bicuculline, flurothyl) notable effect of adoption (cross-fostering) is apparent; (3) in seizure models that are associated with NMDA system (NMDA, flurothyl), effect of prenatal stress seems to play a role.

Surgical Intervention for Lumbar Spine

INTRODUCTION: The role of the insula in the genesis of epileptic seizures has been poorly documented. Few data exist from human electophysiological studies performed in vivo by direct electrical stimulation of the insular cortex due to its deep anatomical position and dense surrounding vascular network. The determination of clinical signs related to the participation of the insula permits a more accurate analysis of the electroclinical data. METHODS: This retrospective study focused on more precisely determining the anatomo-functional organization of the insula by studying the effects of intracerebral electrical stimulations during stereoelectoencephalography exploration using an oblique approach. Twenty-five epileptic patients in whom at least one electrode was used to explore the insula were selected. A total of 313 stimulations were performed in 27 insula. A presurgical three-dimensional (3D) T1-weighted magnetic resonance imaging (MRI) scan and stereotactic software were used to target the insular cortex. A postoperative contrast-enhanced 3D computed tomographic scan enabled the fusion of the resulting image with the preoperative 3D MRI in the same stereotactic referenced system. The cortical location and anatomical position could then be determined in reference to gyri and sulci. RESULTS: The stereotactic coordinates of each stimulation site were individually reported on MRI. All results were discussed in terms of their anatomic and electrical significance. Our data demonstrate a much more elaborate organization of the insular cortex in terms of sulci and gyri compared with the earlier simple distinction between the anterior and posterior insula. We have been able to identify individual areas in which direct electrical stimulation evokes language disorder, painful phenomena, or sensorimotor responses. For the latter, we have identified a somatotopy. CONCLUSION: The large sampling allowed by this exploration using an oblique approach has enabled us to draw up the first anatomo-functional insular cortex organization in terms of sulcal and gyral anatomy.

Neurotransmitter actions in the thalamus and cerebral cortex.

The postsynaptic actions of glutamate, gamma-aminobutyric acid (GABA), acetylcholine, norepinephrine, serotonin, and histamine in the cerebral cortex and thalamus and their relevance to the control of thalamocortical activity are reviewed. Excitatory and inhibitory amino acids (such as glutamate and GABA) are proposed to form the neurotransmitters by which the executative neural networks of the neocortex and thalamus process synaptic information. In contrast, the more slowly acting neurotransmitters, acetylcholine, norepinephrine, serotonin, and histamine, are proposed to control the state of activity and excitability of thalamic and cortical neurons and thereby modulate the state of thalamocortical activity. Specific examples of the involvement of fast and slow transmitter actions in the genesis of epileptic seizures and the determination of sleep-wake cycles are given.

Calcium antagonist nimodipine in intractable epilepsy.

The influx of Ca2+ into the neuron seems to play an important role in the genesis of epileptic seizures, and current research suggests that calcium entry blockers may have anticonvulsant activity. We used nimodipine, a calcium antagonist with high central nervous system affinity at a fixed dosage of 30 mg, t.i.d., in 21 patients with intractable epilepsy caused by organic brain lesions in addition to basal antiepileptic drug (AED) therapy. After a 12-week treatment period 14 patients (67%) showed a decrease in seizure frequency, four patients had no change, and three had an increase. In eight patients (38%) seizure frequency decreased by greater than 40%. The p value with one-tailed t-test was 0.0491. No significant modifications in AED or electrolyte serum levels were found. One patient had a lowering of blood pressure at this dosage.

Examination of the potential antiepileptic activity of calcium antagonists with different sites of action

1. 1. Calcium is proposed to play a role in the genesis of epileptic seizures, and a number of established antiepileptic drugs limit the transport of extracellular calcium into neuronal cells. 2. 2. The aim of the present study was to explore the potential antiepileptic activity of three calcium antagonists: nifedipine (20 mg/kg i.p.), which blocks the calcium channel at its outer mouth; verapamil (30 mg/kg i.p.), which blocks the calcium channel at its inner mouth; and propyl-methylenedioxyindene (pr-MDI; 68, 100 and 120 mg/kg i.p.), which acts intracellularly to inhibit calcium mobilization from the endoplasmic reticulum. 3. 3. In the maximal electroshock test, none of the calcium antagonists provided protection against tonic seizures in mice. Phenytoin (20 mg/kg i.p.), on the other hand, afforded complete protection. 4. 4. In the pentylenetetrazol-induced seizure test, the order of effectiveness of the three calcium antagonists in attenuating the severity of the clonic and tonic seizures in mice was: nifedipine > verapamil > pr-MDI. All three calcium antagonists were less effective than ethosuximide (200 mg/kg i.p.). 5. 5. These findings indicate that the calcium antagonists would be of no value in the treatment of grand mal epilepsy, while only those agents acting at the outer side of the membrane would have limited usefulness at best against petit mal seizures.

Convulsive attacks due to antidepressant drug overdoses: Case reports and discussion

Antidepressant drug overdoses have been reported to induce seizures, but the etiology of this phenomenon is still unclear. Recently we treated three patients who suffered from epileptic seizures after acute overdoses of three antidepressant drugs: (a) Dibenzepin HCl (Noveril), (b) Maprotiline HCl (Ludiomil), and (c) Clorimipramine (Anafranil). After a review of the pertinent literature, the possible role of antidepressant drugs in the genesis of epileptic seizures is discussed.

Kynurenines and seizures.

Recent data and concepts concerning the convulsant effects of kynurenines, neuroactive metabolites of tryptophan, in mice, rats, and frogs are reviewed. Myoclonic seizures of the hindlegs are induced in mice by l- and d,l-kynurenine. Both l- and d,l-kynurenine exhibit a selective synergism with strychnine. The convulsant effect of l-kynurenine is selectively antagonized by taurine, less selectively by l-glycine, and not at all by gamma-aminobutyric acid (GABA) or the GABA agonist muscimol. Derivatives of GABA and some standard anticonvulsant drugs alter seizures induced by l-kynurenine and quinolinic acid in different ways. The involvement of brian kynurenines in the genesis of epileptic seizures is suggested.