Pathogenesis Of Seizures Research Articles

Epilepsy in multiple sclerosis: The role of temporal lobe damage

Background: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. Objectives: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. Methods: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. Results: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS (p< 0.05 for all comparisons). Conclusions: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed.

Zinc supplementation prolongs the latency of hyperthermia-induced febrile seizures in rats.

Some studies have shown a relationship between febrile seizures and zinc levels. The lowest dose zinc supplementation in pentylenetetrazole seizure model has a protective effect. But, zinc pretreatment has no effect in maximal electroshock model. However, it is unclear how zinc supplementation affects hyperthermia-induced febrile seizures. The aim of the present study was to investigate the effects of zinc supplementation on febrile seizures in male Sprague-Dawley rats. The rats were randomly assigned to four groups. Zinc supplementation was commenced 5 days prior to febrile seizure induction by placing the animals in a water bath at 45°C. We measured the rectal temperature and determined the febrile seizure latency, duration, and stage. In the zinc-supplemented group, both the seizure latency and the rectal temperature triggering seizure initiation were significantly higher than in the other groups. We suggest that zinc supplementation can positively modulate febrile seizure pathogenesis in rats.

PO22ELEVATED GLUTAMATE, USING MAGNETIC RESONANCE SPECTROSCOPY, IS ASSOCIATED WITH SEIZURES IN PATIENTS WITH GLIOBLASTOMAS

INTRODUCTION: Seizures are common in patients with a Glioblastoma. Although the epileptogenic mechanism remains unclear, it is suggested to be dependent upon peritumoural changes. Histological analysis of human intratumoural and peritumoural glioma tissue demonstrated that glutamate concentrations in tissue from both sites were increased in patients with seizures when compared to those without. It would be advantageous to have a non-invasive method for predicting which patients are most likely to be affected by seizures. METHOD: 80 patients with a Glioblastoma were imaged pre-operatively at 3T with sequences including anatomical and multivoxel spectroscopy. Regions of interest (ROIs) were selected in a circumferential consecutive pattern from the border of the T1-weighted enhancing region to normal appearing brain. Glutamate parameters (Glu + Gln/Cr) were calculated per voxel and expressed as a ratio to normal brain. Clinical variables were analysed in relation to tumour progression and survival. RESULTS: The mean Glu + Gln/Cr concentration remained more than 1.5 times higher compared to normal brain at a 3 cm radial distance from the T1-weighted enhancing margin in the seizure group. At this distance, the mean Glu + Gln/Cr concentration ratio had returned to 1 in the non-seizure group (Seizures 1.56 ± 0.1 vs. non-seizures 0.92 ± 0.06, p < 0.001). The presence of seizures was associated with a shorter time to progression on multivariate analysis (HR = 7.55; p = 0.01). CONCLUSION: We demonstrate that the presence of seizures is associated with elevated tumour and peritumoural glutamate concentrations and a shortened time to tumour progression in Glioblastomas. Glutamate may play a role in the pathogenesis of seizures and represent a potential biomarker for tumour progression.

An appraisal of the new operational definition of epilepsy—Then and now

The focus to define epilepsy in the newly proposed classification has shifted from the conceptual perspective to practical application thought to better reflect that which is happening to the patient. Within the new definition, a single unprovoked or reflex seizure can be considered as epilepsy if the recurrence risk is similar to that following two unprovoked seizures. Epilepsy is considered to be resolved if the individual had an age-dependent epilepsy syndrome and has passed the applicable age or if the person has remained seizure-free for the last ten years without seizure medications for the last five years. This new operational definition of epilepsy may change the epileptologist's approach regarding when and how long to treat patients with seizures. The new definition also has significant psychosocial and employment-related implications for the patients. With regard to etiology, the terms idiopathic, symptomatic, and cryptogenic have been replaced by genetic, structural/metabolic, and unknown. This reflects a better understanding of the underlying cause of epilepsy based on genetic tests and better neuroimaging. The terms ‘simple partial’ and ‘complex partial’ seizures have been replaced by ‘focal motor/sensory’ and ‘focal dyscognitive’ seizures, thereby ending the ambiguity associated with the former terms and the difficulty encountered with definitions of altered states of consciousness. These changes, reflective of a better insight into the pathogenesis of seizures and epilepsy, are expected to be more pragmatic and assist when managing patients with epilepsy.

Tumor necrosis factor-α and interleukin-6 concentrations in cerebrospinal fluid of dogs after seizures.

BackgroundIdiopathic and acquired epilepsy are common in dogs. Up to 30% of these dogs are refractory to pharmacological treatment. Accumulating experimental evidence indicates that brain immune response and presence of inflammatory mediators decrease the threshold for individual seizures and contribute to epileptogenesis.HypothesisDogs with seizures have higher cerebrospinal interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) concentrations compared to dogs with no seizures.MethodsA prospective double blinded study; cerebrospinal fluid (CSF) and serum IL‐6, TNF‐α and total protein (TP) concentrations were measured by a blinded investigator for the study group and CSF IL‐6 and TNF‐α levels and TP concentrations were measured in the control group (CG).AnimalsDogs presented with seizures that had enough CSF collected to allow analysis were included in the study group. Twelve apparently healthy, quarantined, stray dogs served as control (CG).ResultsCerebrospinal fluid TNF‐α and IL‐6 concentrations were significantly higher (P = .011, P = .039) in dogs with seizures (0 ± 70.66, 0.65 ± 10.93 pg/mL) compared to the CG (0 ± 19, 0.73 ± 0.55 pg/mL). When assessing cytokine concentrations of specifically the idiopathic epilepsy (IE) dogs compared to the CG, only TNF‐α concentrations (8.66 ± 62, 0 ± 19 pg/mL) were significantly higher (P = .01). CSF TP concentrations were not significantly higher in the study dogs compared to the CG.Conclusions and Clinical ImportanceHigher TNF‐α and IL‐6 concentration in the CSF of dogs with naturally occurring seizures. The higher supports the hypothesis that inflammatory processes through certain mediators play a role in the pathogenesis of seizures in dogs.

Toll-like receptor 4 is associated with seizures following ischemia with hyperglycemia

Seizures are a common sequel of cerebral ischemia, and hyperglycemia markedly increases the onset of seizures following an ischemic insult. However, the underlying mechanism of seizures is unclear. The toll-like receptor 4 (TLR4) pathway is known to be involved in temporal lobe epilepsy. The present study investigated the potential involvement of TLR4 in the pathogenesis of seizures following cerebral ischemia with hyperglycemia. Fifteen minutes of global ischemia was produced in adult Wistar rats using a 4-vessel occlusion method. Hyperglycemia was induced via an intraperitoneal injection of glucose 15min prior to ischemia. We determined that 56.7% of the hyperglycemic rats, but none of the normoglycemic rats, developed tonic-clonic seizures within 12h after ischemia. TLR4 was mildly expressed in a few cells in the control hippocampus, primarily in interneurons, and was localized in the cytoplasm. The TLR4-positive cells were significantly increased 3–12h after ischemia. In the hyperglycemic ischemia group, TLR4-positive cells were further increased in quantity and intensity, with a peak at 3h after ischemia relative to the normoglycemic group. There was no difference in the expression of TLR4 between the hyperglycemic ischemia and LPS groups or between the hyperglycemic non-ischemia and control groups. Western blot analysis consistently exhibited an increase in TLR4 protein levels in the CA3 region 3h after hyperglycemic ischemia. High mobility group box 1 (HMGB1) (an endogenous ligand of TLR4) was localized in the nucleus of neuronal cells throughout the hippocampus in the control animals. We observed a dramatic decrease in HMGB1 immunostaining at 3h after hyperglycemic ischemia that gradually returned to control levels. These results suggest that the TLR4 pathway is associated with seizures following global ischemia with hyperglycemia, which provides a new direction for the study of the pathogenesis of seizures that result from hyperglycemic ischemia.

The calcineurin inhibitor Ascomicin interferes with the early stage of the epileptogenic process induced by Latrunculin A microperfusion in rat hippocampus.

Latrunculin A microperfusion in rat hippocampus has shown to be an effective model of acute and chronic seizures for neurochemical studies. The intervention over early synaptic plasticity changes after the epileptogenesis onset represents a big challenge on the design of a suitable therapy to impair the epilepsy development. We previously suggested that receptor location might be essential for controlling neuronal excitability, and that disruption of local cytoskeletal dynamics followed by drastic changes in the synaptic/extrasynaptic ratio of NMDA, AMPA receptors and their subsequent downstream signalling may play an important role in the pathogenesis of seizures. In the present study, we performed a pharmacological intervention in the Latrunculin model by using Ascomicin (ASC) and Phenytoin (PHT). We pointed out the inhibitory action of ASC over the protein phosphatase 2B (PP2B). PP2B pathological mechanism involves changes in actin cytoskeleton and showed to avoid those subsequent changes previously observed in PSD components. On the contrary, PHT didn't seem to modify the F-actin depolymerization process induced, showing a similar redistribution pattern from the PSD towards the extrasynaptic site of several molecular components with more or less dependence on actin for their location, including glutamate receptors. Overall, we propose that the early intervention over changes on the synapse during the epileptogenic process might represent the best approach to avoid the onset of chronic refractory seizures our model. On this regard, the therapeutic potential of ASC, FK506 and derivatives should be further explored as a possible tool in the intervention over epilepsy and other brain diseases.

Comprehensive identification of essential pathways and transcription factors related to epilepsy by gene set enrichment analysis on microarray datasets.

Epilepsy is a common chronic neurological disorder characterized by seizures or convulsions, and is known to affect patients with primary brain tumors. The etiology of epilepsy is superficially thought to be multifactorial; however, the genetic factors which may be involved in the pathogenesis of seizures have not yet been elucidated, particularly at the pathway level. In the present study, in order to systematically investigate the gene regulatory networks involved in epilepsy, we employed a microarray dataset from the public database library of Gene Expression Omnibus (GEO) associated with tumor-induced epileptogenesis and applied gene set enrichment analysis (GSEA) on these data sets and performed candidate transcription factor (TF) selection. As a result, 68 upregulated pathways, including the extracellular matrix (ECM)-receptor interaction (P=0.004) and peroxisome proliferator-activated receptor (PPAR) signaling pathways (P=0.045), as well as 4 downregulated pathways, including the GnRH signaling pathway (P=0.029) and gap junction (P=0.034) were identified as epileptogenesis-related pathways. The majority of these pathways identified have been previously reported and our results were in accordance with those reports. However, some of these pathways identified were novel. Finally, co-expression networks of the related pathways were constructed with the significant core genes and TFs, such as PPAR-γ and phosphatidylethanolamine-binding protein. The results of our study may contribute to the improved understanding of the molecular mechanisms of epileptogenesis on a genome-wide level.

LETM1 in mitochondrial cation transport.

LETM1 in mitochondrial cation transport.

Inflammatory Mediators in Epilepsy

All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the proposed involvement of inflammation in epilepsy. Key mediators of this process include, among others: interleukin (IL) -1β, IL-6, tumor necrosis factor-α, adhesion molecules and component of complement. Recent advances suggest the involvement of specific inflammatory pathways in the pathogenesis of seizures in patients with pharmacoresistant temporal lobe epilepsy, highlighting the potential for new therapeutic strategies. This review provides an overview of the current knowledge on the relationship between inflammatory mediators and epilepsy. We also describe experimental and clinical evidence of inflammation in epilepsy with special emphasis on clinical aspects once the epileptogenic focus has been resected. Further insight into the complex role of inflammation in epileptogenesis may provide new treatment options.

Increased metalloprotease activity in the epileptogenic lesion—Lobectomy reduces metalloprotease activity and urokinase-type uPAR circulating levels

Inflammation influences the pathogenesis of seizures by boosting neuronal degeneration of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). This work aimed to determine the activity of metalloproteases (MMPs) in brain tissue fragments of TLE-HS patients and the effect of lobectomy on circulating inflammatory biomarkers. Surgical fragments (n=4) from epileptogenic focus (EF) e perilesion area (PL), and control hippocampus from autopsy (n=5) were processed for glial protein (GFAP), activated microglia (IB4) immunohistochemistry, and metalloprotease activity (MMP-2, -9). Perilesional area showed GFAP positive cells with morphology of activate astrocyte and reactive gliosis nearby the lesion. In the lesion foci, astrocytes had altered cytoarchitecture with disorganized stroma suggestive of necrosis, and numerous mononuclear cells with few projections and morphological characteristics of activate microglia. Analysis of MMP-9 and MMP-2 in the sera before and after hippocampectomy confirmed the inflammatory pattern of TLE-HS, with high MMP-9 activity; high MMP-9/TIMP-1 and urokinase uPAR plasma levels before lobectomy but low after surgery. Maintenance of MMP-2 activity indicates persistent tissue remodeling in both groups. The present work shows that patients with chronic and medically intractable TLE-HS that undergone amigdalo-hippocampectomy for removal of epileptogenic lesion had a clinical enduring benefit of lack seizure recurrence for up to a year, and consistent reduction of proteases (MMP-9 and uPAR) activation that participate as important inflammatory epileptogenic inducers.

American Clinical Neurophysiology Society's standardized critical care EEG terminology: Interrater reliability and 2012 version

American Clinical Neurophysiology Society's standardized critical care EEG terminology: Interrater reliability and 2012 version

Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: A case of mesial temporal lobe epilepsy with hippocampal sclerosis

IntroductionHippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS). DesignWe report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood. ResultsIn total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles. DiscussionWe present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy.

Non-Convulsive Status Epilepticus Associated With Glutamic Acid Decarboxylase Antibody

Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis.

Association Between Seizures and Diabetes Mellitus: A Comprehensive Review of Literature

Epilepsy or seizures are often observed in patients with diabetes mellitus (DM), and an emerging association between the two diseases is more than coincidental based on recent research. Approximately 25% of patients with DM experience different types of seizures. Furthermore, diabetic patients who experienced episodes of DKA also have seizures more frequently. The precise pathogenesis of seizures in the diabetes patient remains undetermined. Currently, the leading hypotheses in the literature suggest that multiple physiological factors, such as immune abnormalities, microvascular lesions in the brain, local brain damage, metabolic factors and gene mutation, may contribute to this condition. To date, there are no international criteria for the diagnosis and treatment of this condition. Although it is commonly assumed that antiepileptic drugs are necessary, most of the partial epilepsy patients with non-ketotic diabetes are resistant to frequently used antiepileptic drugs. In contrast, partial status epilepticus can be treated by diazepam, and carbamazepine is reported to be effective to some DM patients with epilepsy. However, anti-diabetic drugs are considered to be the most important factors in the treatment of this condition. When the blood glucose levels gradually return to normal levels, patients can no longer generate seizures even when antiepileptic drugs are discontinued.

Cation-chloride cotransporters in the nervous system

Maintenance of intracellular chloride (Cl−) concentration ([Cl−]i) is critical for volume regulation and determines the effects of γ-aminobutyric acid (GABA) and glycine-mediated neurotransmission. Cation-chloride cotransporters (CCC) transport Cl− together with sodium (Na+), potassium (K+), or both, across plasma membranes and have an important role in maintenance [Cl−]i. The CCC in the nervous system include the Na–K–2Cl cotransporter NKCC1, which mediates Cl− influx, and various K–Cl cotransporters, such as KCC2 and KCC3, that extrude Cl− from the cell. NKCC1 mediates regulatory volume increase in response to cell shrinkage; KCC3 primarily mediates regulatory volume decrease in response to cell swelling. The precise balance between NKCC1 and KCC2 activity and their effect on [Cl−]i determines the consequences of GABAergic and glycinergic signaling in the nervous system. In immature neurons, the predominant effects of NKCC1 renders the effects of GABA and glycine depolarizing, which is important for development of neuronal circuits. In the adult nervous system, the predominant KCC2 action is critical for the inhibitory effects of GABA and glycine in most synaptic circuits. Increased activity of NKCC1 contributes to cerebral edema and excitotoxicity in the setting of traumatic or ischemic brain injury, whereas impaired activity of KCC2 renders GABAergic inhibition ineffective and contributes to the pathogenesis of seizures and pain. The molecular physiology of the CCC and their role in neurologic disorders have been the subjects of several comprehensive reviews.1–11 BDNF= : brain-derived neurotrophic factor; CCC= : cation-chloride cotransporters; [Cl–]i= : intracellular chloride concentration; DRG= : dorsal root ganglion; ECl= : Cl− equilibrium potential; GABA= : γ-aminobutyric acid; GABAAR= : GABAA receptors; GlyR= : glycine receptor; KCC= : K-Cl cotransporters; NCC= : Na-Cl cotransporters; NKCC= : Na-K-2Cl cotransporters; TLE= : temporal lobe epilepsy; TMZ= : temozolomide

Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse andDrosophilaGenetic Models of Epilepsy

Neuronal network hyperexcitability underlies the pathogenesis of seizures and is a component of some degenerative neurological disorders such as Alzheimer's disease (AD). Recently, the microtubule-binding protein tau has been implicated in the regulation of network synchronization. Genetic removal of Mapt, the gene encoding tau, in AD models overexpressing amyloid-β (Aβ) decreases hyperexcitability and normalizes the excitation/inhibition imbalance. Whether this effect of tau removal is specific to Aβ mouse models remains to be determined. Here, we examined tau as an excitability modifier in the non-AD nervous system using genetic deletion of tau in mouse and Drosophila models of hyperexcitability. Kcna1(-/-) mice lack Kv1.1-delayed rectifier currents and exhibit severe spontaneous seizures, early lethality, and megencephaly. Young Kcna1(-/-) mice retained wild-type levels of Aβ, tau, and tau phospho-Thr(231). Decreasing tau in Kcna1(-/-) mice reduced hyperexcitability and alleviated seizure-related comorbidities. Tau reduction decreased Kcna1(-/-) video-EEG recorded seizure frequency and duration as well as normalized Kcna1(-/-) hippocampal network hyperexcitability in vitro. Additionally, tau reduction increased Kcna1(-/-) survival and prevented megencephaly and hippocampal hypertrophy, as determined by MRI. Bang-sensitive Drosophila mutants display paralysis and seizures in response to mechanical stimulation, providing a complementary excitability assay for epistatic interactions. We found that tau reduction significantly decreased seizure sensitivity in two independent bang-sensitive mutant models, kcc and eas. Our results indicate that tau plays a general role in regulating intrinsic neuronal network hyperexcitability independently of Aβ overexpression and suggest that reducing tau function could be a viable target for therapeutic intervention in seizure disorders and antiepileptogenesis.

Cortico-juxtacortical involvement increases risk of epileptic seizures in multiple sclerosis

Previous studies have reported an increased risk for epileptic seizures in multiple sclerosis (MS) patients. However, data on the pathogenesis of seizures remain inconclusive. The aim of our study is to evaluate prevalence, clinical and paraclinical features of epileptic attacks in our MS cohort and to search MS-specific risk factors for epileptic seizures. In this cohort of 428 MS patients, 13 patients were identified with epileptic seizures occurring at any point during the course of MS including at MS onset. As a control group, we selected 26 MS patients without seizures and matched for gender, age and date of MS onset. We compared demographic features and clinic-radiological findings between the both groups. Thirteen patients (3%) were identified as having epileptic attacks. Ten patients (77%) experienced focal seizures, half of whom had confirmed secondary generalization. We did not find an association between seizures and disease course. Most patients had a single or few (2-5) seizures. MS patients with seizures had a significantly higher number of cortical and juxtacortical lesions on T2-weighted/fluid attenuation inversion recovery magnetic resonance imaging than control group [OR = 2.6 CI95% (1.0-6.5); P = 0.047]. Our findings support a credible role of cortical and juxtacortical involvement in the development of epileptic seizures in MS.

Increased Seizure Susceptibility in a Mouse with Diacylglycerol Kinase &amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt; Deficiency

Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. Several DGK isoforms have been implicated in the pathogenesis of seizure, but the role of DGKβ in seizure is unknown. In the present study, we investigated the involvement of DGKβ in seizure using DGKβ knockout (KO) mice. Seizures were more severe in DGKβ KO mice than in wild-type (WT) mice after pentylenetetrazol (PTZ) treatment and after kainic acid treatment, but there were no differences in latency to seizure. The expression levels of DGKβ in the hippocampal CA1, CA3, or DG areas did not differ between PTZ (60 mg/kg) treatment and saline treatment. There were fewer parvalbumin-positive interneurons in the hippocampal CA3 area in DGKβ KO mice than in control WT mice, which might partly account for the increased seizure susceptibility displayed by DGKβ KO mice. These results suggest that DGKβ may play a pivotal role in the development of the relevant interneurons, and that on inherent deficiency of DGKβ increases the animal’s sensitivity to seizure-inducing stimuli.

Angioarchitecture of Brain AVM Determines the Presentation with Seizures: Proposed Scoring System

Seizures are a common presentation in patients with brain arteriovenous malformations, but the pathogenesis of seizures remains poorly understood. The purpose of our study was to analyze various morphologic and hemodynamic characteristics of unruptured BAVMs presenting primarily with seizures and, on the basis of these, to propose a scoring system to predict seizures in patients with BAVMs. In a retrospective review of our BAVM data base from 2000 to 2009, after excluding patients with ruptured BAVMs, we classified patients into 2 groups, those with and without seizures at presentation. Clinical, angiographic, and hemodynamic characteristics on cerebral angiograms of all these patients were studied. The association between various angioarchitectural variables and seizure presentation was examined, and these results were used to guide the development of criteria to predict presentation with seizures. Of 1299 patients in our data base, we finally analyzed 33 patients with unruptured BAVMs with seizures and 45 patients with unruptured AVMs without seizures. Location, fistulous component in the nidus, venous outflow stenosis, and the presence of a long pial course of the draining vein were identified as the strongest predictors of seizures. The proposed scoring system had good predictability of presentation with seizures. Specific angioarchitectural characteristics of unruptured BAVMs may predict occurrence of seizures and may help in targeted treatment.