Development Of Seizures Research Articles

COVID-19 and seizures: Is there a link?

The rapid spread of the SARS‐CoV‐2 pandemic poses particular challenges to the management of persons with chronic disease. Reports of a possible neuroinvasiveness of SARS‐CoV‐2 as well as pathophysiological mechanisms and indirect consequences in severe COVID‐19 cases raise the question of whether the infection can be associated with an increased risk of seizure recurrence or the development of new onset and acute symptomatic seizures. Although the literature does not provide relevant evidence for seizure worsening in persons with epilepsy during the course of a SARS‐CoV‐2 infection, there are theoretical risks, for example, seizures triggered by fever. Moreover, a severe disease course and advanced disease stages can, for instance, result in hypoxic encephalopathy, cerebrovascular events, and cytokine storm, which may trigger the development of acute seizures. This is further confirmed by reports of occasional seizures in COVID‐19 patients. Although the low number of reports so far suggests that the risk may be relatively low, the reports indicate that an early neurological manifestation with seizures should not be ruled out. In the context of these cases, we discuss possible pathophysiological mechanisms that may trigger ictogenesis in patients with SARS‐CoV‐2 infection.

Blockade of Brain Adrenoreceptors Delays Seizure Development during Hyperbaric Oxygen Breathing

The main prodromal sign of seizures developing when breathing hyperbaric oxygen is a high activity of sympathetic outflow, as manifested in altered external respiration, impaired cardiac and vascular activity. We tested the hypothesis that the brain adrenergic receptors, as part of the central adrenergic system, are involved in the development of sympathetic hyperactivity and generalized seizures during hyperbaric oxygen breathing. In experiments on rats, α- and β-adrenoreceptors were blocked by non-selective and selective antagonists (propranolol, atenolol, phentolamine and prazosin) injected into the cerebral ventricles. Reactions of the CNS and autonomic nervous system to oxygen breathing at 5 ATA were evaluated. We found that in animals with intact adrenoreceptors, hyperbaric oxygen caused convulsions preceded by biphasic reactions of the cardiovascular system, external respiration and cerebral blood flow. All antagonists used in experiments attenuated visceral reactions and the development of oxygen convulsions, although propranolol showed most pronounced antihypertensive and anticonvulsant properties. The data obtained indicate the involvement of brain adrenergic receptors in the ANS reactions to hyperoxia and in the mechanisms underlying the development of oxygen seizures during hyperbaric oxygen breathing. Our results can be used to develop new methods for the prevention of seizures under extreme hyperoxia and to ensure the safe use of hyperbaric oxygen in clinical practice and diving.

Optogenetic Interrogation of ChR2-Expressing GABAergic Interneurons After Transplantation into the Mouse Brain.

This paper describes research methods to investigate the development of synaptic connections between transplanted GABAergic interneurons and endogenous neurons in the adult mouse hippocampus. Our protocol highlights methods for retroviral labeling adult-born GCs, one of the few cell types in the adult brain to be continuously renewed throughout life. By precise targeting of the retrovirus, labeling of adult-born GCs can be combined with optogenetic stimulation of the transplanted cells and electrophysiology in brain slices, to test whether the GABAergic interneurons integrate and establish inhibitory synaptic connections with host brain neurons. Modifications to adult neurogenesis are an important contributing factor in the development and severity of TLE and seizures. When combined with retroviral labeling, the approaches we describe in this chapter can be used to determine whether transplantation modifies the process of adult neurogenesis or other properties of the hippocampus. These approaches are helping to define parameters for potential cell replacement therapies to be used in patients with intractable seizure disorders.

Treatment of Low Cerebrospinal Fluid 5-Methyltetrahydrofolate With Leucovorin Improves Seizure Control and Development in PCDH19-Related Epilepsy

This six-year-old girl presented to the Neurometabolic Clinic for evaluation of medically intractable seizures, global developmental delay, and behavioral concerns. Since developing clusters of seizures at age two years, she had tried multiple medications. She had multiple seizure types, consisting primarily of focal seizures with secondary generalization, which were exacerbated by fever. Prior electroencephalographs were normal or were consistent with a right frontal seizure onset. At the time of her initial assessment, her medications were oxcarbamazepine, topiramate, valproic acid, and lacosamide.

Prevalence of seizures in dogs and cats with idiopathic internal hydrocephalus and seizure prevalence after implantation of a ventriculo-peritoneal shunt.

BackgroundSeizures are considered a clinical sign in dogs with internal hydrocephalus but are not found in recent studies. Seizure prevalence due to ventricular enlargement and the prevalence of postoperative seizures in animals is not known.ObjectivesTo determine seizure prevalence in dogs and cats with idiopathic internal hydrocephalus, to identify risk factors for seizure development, and to determine seizure prevalence in a 2‐year period after ventriculo‐peritoneal shunting (VPS).AnimalsRecords and MRIs of 197 animals from 2001 to December 2019 were investigated. A total of 121 animals (98 dogs and 23 cats) were included in the study.MethodsA retrospective multicenter case cohort study was conducted. Databases were searched for dogs and cats with internal hydrocephalus. MRI and CSF examinations were evaluated for signs of additional underlying disorders. Prevalence of seizures was estimated for animals showing only hydrocephalus internus. Risk factors were evaluated according to age, morphometric and morphological findings in the brain. All animals that underwent surgery were reexamined 2 years after surgery.ResultsOne hundred twenty‐one animals (98 dogs and 23 cats) with internal hydrocephalus met the inclusion criteria. Seizure prevalence in dogs and cats with internal hydrocephalus was low (1.7%; <5.8% CI 95%). Seizures were not observed in the 2‐year period after surgery.Conclusion and Clinical ImportanceSeizure prevalence in dogs and cats diagnosed with hydrocephalus internus is low. Seizures in association with VPS do not seem to be a complication of the procedure.

Brain calcification because of neurocysticercosis: a vast field to be explored.

Neurocysticercosis is the most common helminthic infection of the central nervous system caused by the larval stage of the pork tapeworm, Taenia solium. Endemic regions include Latin American countries, sub-Saharan Africa, and large regions of Asia, including the Indian subcontinent and is a global health problem. Seizures are the most common manifestation and approximately 30% of adult-onset seizures in endemic regions are attributable to NCC. Calcifications because of neurocysticercosis is the most common finding on imaging in endemic regions and are important seizure foci contributing to the burden of epilepsy. After treatment with antiparasitics for multiple viable parenchymal disease, approximately 38% of cysts that resolved after 6 months of therapy will result in residual calcifications, which represents a significant burden of residual disease. Calcified disease has been referred to as 'inactive disease', but there is accumulating evidence to suggest that calcified granulomas are actually dynamic and substantially contribute to the development and maintenance of seizures. Calcified parenchymal neurocysticercosis contributes significantly to the development and maintenance of seizures in endemic regions. Understanding the pathogenesis of the role of calcified NCC in seizure development and risk factors for development of calcifications after treatment is critical to decreasing the burden of symptomatic disease in endemic regions.

A-037 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarctions and Leukoencephalopathy: A Neuropsychological Case Review

Abstract Objectives Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarctions and Leukoencephalopathy (CADASIL) is a rare genetic disorder. It is caused by a mutation in the NOTCH3 gene on chromosome 19 which damages vascular smooth muscle cells resulting in impaired cerebral blood flow and a progressive vascular dementia. Onset typically occurs by the mid-30’s but varies widely. This case study describes a unique case of rapid disease progression. Methods The patient was a 58-year-old right-handed male. Initial symptom onset occurred at the age of 53, with blurred vision, severe headache, and difficulty speaking. Brain imaging (CT, MRI) showed significant white matter degeneration and cortical volume loss. Multiple sclerosis was hypothesized. Following the development of seizures and a right hemisphere stroke, the patient underwent genetic testing and was diagnosed with CADASIL. Initial neuropsychological evaluation revealed deficits in perceptual reasoning, working memory, processing speed, memory, and executive functioning. Serial evaluation included intelligence testing, academic achievement, the Meyers Neuropsychological Battery, and psychological functioning. Results Intellectual functioning and the overall neuropsychological test battery mean were one and a half to two standard deviations below his estimated premorbid functioning. Executive functioning declined from prior evaluation. Psychologically, the patient reported mild anger, irritability, and interpersonal difficulties. His wife endorsed significant increases in apathy and disinhibition and decline in executive functioning. The patient passed away approximately six months post-evaluation. Conclusion Findings were consistent with moderate-to-severe diffuse and lateralized deficits (RCH &amp;gt; LCH) resulting from subcortical/higher cortical vascular dementia due to CADASIL and its medical sequelae, with quite rapid symptom onset and decline.

Metabolic Alterations Predispose to Seizure Development in High-Fat Diet-Treated Mice: the Role of Metformin.

The link between epilepsy and type 2 diabetes (T2DM) and/or metabolic syndrome (MetS) has been poorly investigated. Therefore, we tested whether a high-fat diet (HFD), inducing insulin-resistant diabetes and obesity in mice, would increase susceptibility to develop generalized seizures induced by pentylentetrazole (PTZ) kindling. Furthermore, molecular mechanisms linked to glucose brain transport and the effects of the T2DM antidiabetic drug metformin were also studied along with neuropsychiatric comorbidities. To this aim, two sets of experiments were performed in CD1 mice, in which we firstly evaluated the HFD effects on some metabolic and behavioral parameters in order to have a baseline reference for kindling experiments assessed in the second section of our protocol. We detected that HFD predisposes towards seizure development in the PTZ-kindling model and this was linked to a reduction in glucose transporter-1 (GLUT-1) expression as observed in GLUT-1 deficiency syndrome in humans but accompanied by a compensatory increase in expression of GLUT-3. While we confirmed that HFD induced neuropsychiatric alterations in the treated mice, it did not change the development of kindling comorbidities. Furthermore, we propose that the beneficial effects of metformin we observed towards seizure development are related to a normalization of both GLUT-1 and GLUT-3 expression levels. Overall, our results support the hypothesis that an altered glycometabolic profile could play a pro-epileptic role in human patients. We therefore recommend that MetS or T2DM should be constantly monitored and possibly avoided in patients with epilepsy, since they could further aggravate this latter condition.

GM-CSF induces noninflammatory proliferation of microglia and disturbs electrical neuronal network rhythms in situ

BackgroundThe granulocyte-macrophage colony-stimulating factor (GM-CSF) (or CSF-2) is involved in myeloid cell growth and differentiation, and, possibly, a major mediator of inflammation in body tissues. The role of GM-CSF in the activation of microglia (CNS resident macrophages) and the consequent impacts on neuronal survival, excitability, and synaptic transmission are widely unknown, however. Here, we focused on electrical neuronal network rhythms in the gamma frequency band (30–70 Hz). Gamma oscillations are fundamental to higher brain functions, such as perception, attention, and memory, and they are exquisitely sensitive to metabolic and oxidative stress.MethodsWe explored the effects of chronic GM-CSF exposure (72 h) on microglia in male rat organotypic hippocampal slice cultures (in situ), i.e., postnatal cortex tissue lacking leukocyte invasion (adaptive immunity). We applied extracellular electrophysiological recordings of local field potential, immunohistochemistry, design-based stereology, biochemical analysis, and pharmacological ablation of microglia.ResultsGM-CSF triggered substantial proliferation of microglia (microgliosis). By contrast, the release of proinflammatory cytokines (IL-6, TNF-α) and nitric oxide, the hippocampal cytoarchitecture as well as the morphology of parvalbumin-positive inhibitory interneurons were unaffected. Notably, GM-CSF induced concentration-dependent, long-lasting disturbances of gamma oscillations, such as slowing (beta frequency band) and neural burst firing (hyperexcitability), which were not mimicked by the T lymphocyte cytokine IL-17. These disturbances were attenuated by depletion of the microglial cell population with liposome-encapsulated clodronate. In contrast to priming with the cytokine IFN-γ (type II interferon), GM-CSF did not cause inflammatory neurodegeneration when paired with the TLR4 ligand LPS.ConclusionsGM-CSF has a unique role in the activation of microglia, including the potential to induce neuronal network dysfunction. These immunomodulatory properties might contribute to cognitive impairment and/or epileptic seizure development in disease featuring elevated GM-CSF levels, blood-brain barrier leakage, and/or T cell infiltration.

24. LOCAL TUMOR PROGRESSION IS A RISK FACTOR FOR POSTOPERATIVE SEIZURES IN PATIENTS WITH BRAIN METASTASIS

PURPOSEBrain tumor-related epilepsy (BTRE) occurs in 20–35% of patients with brain metastases (BM) and influences morbidity, mortality as well as quality of life. Several factors associated with seizure risk have been identified, including incomplete resection and supratentorial localization of BM. In primary brain tumors like lower grade glioma, tumor growth is associated with seizures. However, it remains to be elucidated whether this holds also true for patients with BM. METHOD: We identified 295 patients who had been diagnosed with BM between 2004 and 2014 by review of our electronic chart system. Occurrence of new onset of postoperative seizures dependent on BM progression was tested during the clinical course as well as pattern of progression and previously described predictors of postoperative seizures. Chi-square test was used for univariate analysis, a Cox-regression model for multivariate testing.RESULTSPostoperative seizures were observed in 49 of 295 patients (16.6%). Supratentorial localization (p=0.043, OR 4.45, 95% CI 1.1–19.3) and incomplete resection (p=0.018, OR 3.68, 95% CI 1.4–10.9), along with intracranial (p=0.038, OR 1.4, 95% CI 1.4–5.8) but not extracranial progression (p=0.729, OR 0.90, 95% CI 0.4–1.7) were confirmed as factors independently associated with postoperative seizures. Furthermore, there was a significantly higher rate of postoperatives seizures in patients with local progression (18 of 84 patients, 21.4 %) compared to those with distant brain progression (12 of 93 patients, 12.9%, p=0.042, Chi-square test).CONCLUSIONHere we define tumor progression as a risk factor for the development of postoperative seizures in a well defined cohort of BM patients. Extracranial tumor recurrence seems to be not significant for seizure risk. Subgroup analysis indicates that patients with local progression of BM are more prone to seizures than those with new, distant BM lesions. Patients with local tumor recurrence might thus be candidates for primary prophylaxis with antiepileptic drugs.

The potential role of micro-RNA-211 in the pathogenesis of sleep-related hypermotor epilepsy

Sleep-related hypermotor epilepsy (SHE) is a rare epileptic syndrome characterized by epileptic seizures which occur during the non-rapid eye movement (NREM) stage of sleep. It manifests with hypermotor semiology resembling violent limb movements and an asymmetric tonic-dystonic posture. The genes which are responsible for the autosomal dominant form of SHE (ADSHE) and whose function is to code the sub-unit of the neuronal acetylcholine receptor are well known. Considering that ADSHE is a prototype of SHE, it is thought that the dysfunction of the cortico-subcortical cholinergic network, which regulates the cycle of sleep, has a key role in the epileptogenesis of this syndrome. Namely, studies to date, have shown that the hypercholinergic activity is sufficient for the development of epileptic seizures, even though the exact mechanism remains to be elucidated. NREM parasomnias are sleep disorders that are the most difficult to differentiate from SHE due to a similar clinical presentation. Considering the clinical similarities, NREM occurrence and probable genetic connection, it is considered that fundamentally, both of these conditions share a common pathophysiological mechanism i.e. cholinergic dysfunction. The main difference between SHE and NREM parasomnias are the genuine epileptic seizures that are responsible for the semiology in SHE. These genuine seizures are not present in NREM parasomnias. Why this is so, remains to be elucidated. Considering that animal studies have shown that dynamic changes and the decreased levels of microRNA-211 contribute to epileptic seizures and to changes in cholinergic pathways, our hypothesis is that epileptic seizures and the development of epileptogenesis in SHE are a consequence of cholinergic dysfunction and decreased levels of microRNA-211 as opposed to NREM parasomnias where there is a stable level of microRNA-211, preventing epileptogenesis despite the cholinergic system dysfunction.

IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy.

Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes increase absence epileptic activity. In order to study the central effects of TCZ, we investigated whether administration of this anti-IL-6R antibody could modulate the lipopolysaccharide (LPS) or IL-6-evoked changes in absence epileptic activity in WAG/Rij rats. Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6months of age (1month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. Decreased absence seizure development at 6months of age was also accompanied by reduced comorbid depressive-like behavior, whereas no effects were observed on anxiety-related behavior. Acute treatment with TCZ, at 30mg/kg, had anti-absence properties lasting ~25h. The co-administration TCZ with i.c.v. LPS or IL-6 showed that TCZ inhibited the worsening of absence seizures induced by both proinflammatory agents in the WAG/Rij rats, supporting a central anti-inflammatory-like protective action. These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity.

The Influence of Ionizing Radiation on Proneness to Audiogenic Seizure and Behavior in Krushinsky–Molodkina Rats

We studied the effects of whole body gamma-radiation (4 Gy, dose rate 0.6 Gy/min) and proton-beam head irradiation (with an energy of 150 meV, 4 Gy and a dose rate of 0.8 Gy/min) on the intensity and timing of audiogenic seizures in rats of the Krushinsky–Molodkina selected strain. In experiments using gamma rays the rat behavior was tested in the open field, elevated plus maze, and Morris water maze tests. No changes in audiogenic tonic–clonic seizures (originating in the brain stem) were found during the first exposure to sound after gamma-irradiation. Slower development of seizures and larger latency of the tonic seizure phase were found following serial daily exposure to sound in rats after proton irradiation. It was also noted that audiogenic myoclonic seizures (which developed in the forebrain) in irradiated rats that were exposed daily to sound had shorter durations, while the intensity of these seizures was at a maximum in all groups. The behavioral tests revealed a moderate increase in anxiety after radiation exposure.

Pharmaco-genetic inhibition of pyramidal neurons retards hippocampal kindling-induced epileptogenesis.

AimsPharmaco‐genetics emerges as a new promising approach for epileptic seizures. Whether it can modulate epileptogenesis is still unknown.MethodsHere, parvalbumin neurons and pyramidal neurons of the seizure focus were transfected with engineered excitatory Gq‐coupled human muscarinic receptor hM3Dq and engineered inhibitory Gi‐coupled human muscarinic receptor hM4Di, respectively. And their therapeutic value in mouse hippocampal kindling‐induced epileptogenesis was tested.ResultsPharmaco‐genetic activating parvalbumin neurons limitedly retarded the progression of behavioral seizure stage and afterdischarge duration (ADD) during epileptogenesis induced by kindling. Activating parvalbumin neurons delayed seizure development only in the early stage, but accelerated it in late stages. On the contrary, pharmaco‐genetic inhibiting pyramidal neurons robustly retarded the progression of seizure stages and ADDs, which greatly delayed seizure development in both early and late stages. Although both pharmaco‐genetic therapeutics efficiently alleviated the severity of acute kindling‐induced seizures, pharmaco‐genetic inhibiting pyramidal neurons were able to reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco‐genetic activating parvalbumin neurons.ConclusionOur results demonstrated that pharmaco‐genetic inhibiting pyramidal neurons retard hippocampal kindling‐induced epileptogenesis and reverse the enhanced synaptic plasticity during epileptogenesis, compared with that of pharmaco‐genetic activating parvalbumin neurons. It suggests that pharmaco‐genetics targeting pyramidal neurons may be a promising treatment for epileptogenesis.

The P2X7 receptor in activated microglia promotes depression- and anxiety-like behaviors in lithium -pilocarpine induced epileptic rats

Depressive and anxious behaviors are the most common psychiatric symptoms of epilepsy, and may aggravate the epileptic condition and affect the patient's quality of life. Accumulating data obtained from both experimental animal models and patients have convincingly shown a critical role of P2X7 receptor (P2X7R) during depression and anxiety. Our study showed for the first time that the P2X7R is involved in promoting depression- and anxiety-like behaviors in lithium pilocarpine-induced epileptic rats. More importantly, direct anti-depressive and anti-anxiety effects were produced by the P2X7R antagonist Brilliant Blue G (BBG) is in this study, and the effect was similar to that of the classic anti-depressant and anti-anxiety drug fluoxetine. We also found that BBG did not affect the development of spontaneous recurrent seizures (SRS) and had a neuroprotective effect via inhibition of microglial activation after status epilepticus (SE). Thus, our data provide evidence that the P2X7R in activated microglia promotes depression- and anxiety-like behaviors in lithium-pilocarpine induced epileptic rats. Since previous studies have indicated that some anti-depression and anti-anxiety drugs may exacerbate seizures, our data support that the P2X7R is a promising therapeutic target for epilepsy associated with depression and anxiety.

Clavulanic acid improves ethanol withdrawal symptoms in rats.

Objective(s):Ethanol withdrawal following chronic use, is an important challenge clinically. In this study, the effect of clavulanic acid was evaluated on the symptoms of ethanol withdrawal in rats. Materials and Methods:Alcohol dependence was induced by the gavage of ethanol (10% v/v, 2 g/kg), twice daily for 10 days. Clavulanic acid (10, 20, 40, and 80 mg/kg) was administered concurrently with ethanol (sub-acute study), or a single dose after ethanol withdrawal (acute study). Six hours after the last dose of ethanol, anxiety was assessed by the elevated plus-maze (EPM). Seizure-like behavior was evaluated by a sub-convulsive dose of pentylenetetrazol (PTZ, 25 mg/kg/IP). Locomotor activity and motor coordination were measured by the open field and rotarod tests, respectively. Lipid peroxidation marker and antioxidant content were assessed through measuring malondialdehyde (MDA) and glutathione (GSH), respectively.Results:The number of entries and time spent on the open arms of EPM decreased during the withdrawal state. Motor coordination and locomotor activity were significantly decreased. In the sub-acute study, clavulanic acid 80 mg/kg increased time spent and the number of entries to the open arms of EPM, in withdrawn animals. Both motor incoordination and locomotor activity reduction were normalized by clavulanic acid (10, 20, 40 and 80 mg/kg). Withdrawal-induced PTZ kindling seizure was also suppressed by all of the doses. MDA increased, while GSH decreased after withdrawal. Clavulanic acid attenuated such changes.Conclusion:Clavulanic acid could prevent the development of alcohol withdrawal-induced anxiety and seizure. Alcohol withdrawal causes oxidative stress which can be prevented by clavulanic acid.

Association between Foramen Size and Febrile Seizure Status in the Pediatric Population: A Two-Center Retrospective Analysis.

Objective Febrile seizures have been shown to occur in 2 to 5% of children between the ages of 6 months and 5 years, making them the most common seizures of childhood. Multiple risk factors for febrile seizures have been identified; however, no investigation has been conducted to explore foramen size and associated venous drainage as a potential risk factor for experiencing febrile seizures. Of particular interest are the parietal foramen and the condylar canal, which conduct the parietal emissary vein and the occipital emissary vein, respectively. Emissary veins lack valves, allowing them to play a crucial role in selective brain cooling via a bidirectional flow of blood from the head’s evaporating surface. Narrowed cranial apertures conducting these veins may lead to reduced cerebral venous outflow and delayed brain cooling, creating favorable conditions for a febrile event. This study seeks to explore the association between cranial aperture area and febrile seizure status. Methods A retrospective cross-sectional medical record review study from January 2011 to December 2017 was conducted at a 500-bed academic hospital and a 977-bed private hospital in Lubbock, Texas, United States. A total of 101 complex febrile seizure patients were compared with a similarly aged group of 75 trauma patients representing the normal population. Parietal foramen area and condylar canal area were electronically measured and defined as having “normal” or “below normal” area. Statistical Analysis Independent t -tests were used to compare foramen and canal areas by febrile seizure status. Logistic regression analyses were conducted to determine the association of small cranial aperture area with febrile seizure status. Results Below normal parietal foramen area had a strong association with febrile seizures in our patient population. Male sex, white race, and complete vaccination status were also found to have significant associations with febrile seizure status. Conclusion Our findings indicated that narrowed parietal foramen may be considered as a risk factor for febrile seizure development.

Acute symptomatic seizures following intracerebral hemorrhage in the rat collagenase model

Background and purposeIntracerebral hemorrhage (ICH) is a known risk factor for the development of seizures, but little is known about the pathophysiology of seizures in the acute phase post-ICH and their influence on functional outcome. With the use of an animal model, the underlying pathophysiology could be further unraveled. The aim of our study was to optimize the rat collagenase stroke model for the detection of acute symptomatic seizures using video-EEG monitoring. MethodsMale Sprague-Dawley rats were implanted with scalp electrodes and a craniotomy was made for later injection of collagenase. After one week of baseline video-EEG recording, rats were injected with 0.6 U collagenase in 0.7 μL saline in left striatum, in close proximity of the piriform cortex, and immediately reconnected to the video-EEG setup for 7 days. Occurrence of clinical and electrographic seizures was assessed and functional deficits were evaluated on several time points using the cylinder test, Neurological Deficit Scale (NDS) and forelimb placing test. At day 7 post-ICH, animals were euthanized. The volume and cortical involvement of the hemorrhage were assessed by histological examination of the brain tissue, using Cresyl violet stain. ResultsCollagenase injection induced ICH in all animals with a mean volume of 27 mm³ (SEM 7 mm³, range 4–92 mm³). Functional deficits were present in all animals injected with collagenase (pre-ICH vs post-ICH, p < 0.001). Epileptic seizures occurred in 5/11 animals and started between 1 and 61 h after ICH induction. Behavioral changes were observed in 13/15 seizures. ConclusionsInjecting rats with 0.6 U of collagenase is a useful model to study the occurrence of acute symptomatic seizures post-ICH as it results in ICH in all animals without mortality, 45% incidence of ICH-induced acute symptomatic seizures and measurable functional deficits.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15mg/kg, 30min intervals, i.p.) 7days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100mg/kg), LEV (50mg/kg), GBP (100mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50mg/kg LEV and 100mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Seizures in patients with respiratory disease - a retrospective single center study.

Seizures are a neurological condition commonly experienced during the follow-up period after systemic or metabolic disorders. The aim of the present study was to determine the etiological factors of seizures in patients at a tertiary care chest clinic. We reviewed all neurology consultations that were requested due to seizures in inpatient clinics in a tertiary care hospital specializing in respiratory disorders between January 2011 and January 2018 were retrospectively reviewed. The present study included 705 of 2793 (25.2%) patients who requested consultations for seizures during the study period. The mean age of the sample was 64.05±17.19 years. Of the 705 patients, 307 (43.5%) had a previous history of epilepsy (Group I) and 398 (56.5%) had a first-time seizure and were considered to have symptomatic seizures (Group II). Multiple factors played roles in the development of seizures in 54.8% of the patients. In most patients, metabolic causes, systemic infections, and drug use were identified and an intracranial metastatic mass lesion was the major cause in patients with lung cancer. Rates of hypoxemia and respiratory acidosis were significantly higher in patients with symptomatic seizures (Group II) than in patients with primary epilepsy (Group I). Blood gas changes such as hypoxemia and respiratory acidosis were among the factors statistically associated with the development of symptomatic seizures in patients with respiratory diseases. Additionally, hypoxemia, hypercapnia, and respiratory acidosis were correlated with mortality in patients hospitalized for respiratory system diseases who requested consultations for seizures.