Epileptogenic Activity Research Articles

Electrode location and clinical outcome in hippocampal electrical stimulation for mesial temporal lobe epilepsy

PurposeTo study the clinical outcome in hippocampal deep brain stimulation (DBS) for the treatment of patients with refractory mesial temporal lobe epilepsy (MTLE) according to the electrode location. MethodsEight MTLE patients implanted in the hippocampus and stimulated with high-frequency DBS were included in this study. Five underwent invasive recordings with depth electrodes to localize ictal onset zone prior to chronic DBS. Position of the active contacts of the electrode was calculated on postoperative imaging. The distances to the ictal onset zone were measured as well as atlas-based hippocampus structures impacted by stimulation were identified. Both were correlated with seizure frequency reduction. ResultsThe distances between active electrode location and estimated ictal onset zone were 11±4.3 or 9.1±2.3mm for patients with a >50% or <50% reduction in seizure frequency. In patients (N=6) showing a >50% seizure frequency reduction, 100% had the active contacts located <3mm from the subiculum (p<0.05). The 2 non-responders patients were stimulated on contacts located >3mm to the subiculum. ConclusionDecrease of epileptogenic activity induced by hippocampal DBS in refractory MTLE: (1) seems not directly associated with the vicinity of active electrode to the ictal focus determined by invasive recordings; (2) might be obtained through the neuromodulation of the subiculum.

High-frequency cortical activity associated with postischemic epileptiform discharges in an in vivo rat focal stroke model

The postischemic brain has greater susceptibility to epileptogenic activity than physiologically healthy tissue. Epileptiform discharges are thought to exacerbate postischemic brain function. The aim of this study was to develop an in vivo focal stroke model in rats to characterize epileptiform activity. The authors developed a parasagittal 8-channel intracortical microelectrode array to obtain recordings of cortical oscillations of local field potentials following partial middle and anterior cerebral artery occlusion. All experiments were done in urethane-anesthetized Sprague-Dawley rats. Theta runs (TRs), ranging in duration from 5 seconds to 5 minutes, were observed in 62% of animals within 1 hour of occlusion. High-frequency oscillations (HFOs) in the high gamma range (80-120 Hz) were observed 5-15 seconds before each TR and terminated at the onset of the discharge. Periodic epileptiform discharges (PEDs) were detected in 54% of rats following ischemia. The PEDs consisted of an early negative slow wave, a high-amplitude positive spike, and a short negative slow wave. Transient HFOs in the low gamma range (30-70 Hz) occurred during the first negative wave and the rising phase of the positive spike of the PED. These recordings provide the first intracortical evidence of a high-frequency component that could be an important element for diagnosis and intervention in postischemic epileptogenic activity. The early onset also suggests that HFOs could serve as a reliable method of detecting small epileptiform events and could be used as a consideration in deciding whether antiepileptic medications are appropriate as part of a patient's poststroke care.

Changes in Brain Cortex Sensitivity to Epileptogens under Conditions of Ketogenic Diet

The epileptogenic effects of applications of NMDA and kainic acid solutions to the frontal cortex were attenuated in rats receiving ketogenic diet (80% lipids, 3.3% carbohydrates, and 16.7% proteins) during 4 weeks. Spike latency increased, the power of focal epileptic activity decreased, and focus lifetime was shortened in these animals. Sodium benzylpenicillin and strychnine nitrate less markedly reduced epileptogenic activity.

Enrichment and characterization of a bacterial culture that can degrade 4-aminopyridine

BackgroundThe agrichemical 4-aminopyridine is used as a bird repellent in crop fields and has an epileptogenic action in a variety of animals, including man and mouse. 4-Aminopyridine is biodegraded in the environment through an unknown mechanism.ResultsA 4-aminopyridine-degrading enrichment culture utilized 4-aminopyridine as a carbon, nitrogen, and energy source, generating 4-amino-3-hydroxypyridine, 3,4-dihydroxypyridine, and formate as intermediates. 4-Amino-3-hydroxypyridine could not be further metabolized and probably accumulated as a dead-end product in the culture. Biodegradability tests and partial sequence analysis of the enrichment culture indicated that 4-aminopyridine was mainly degraded via 3,4-dihydroxypyridine and that the metabolite is probably cleaved by 3-hydroxy-4-pyridone dioxygenase. Seven culturable predominant bacterial strains (strains 4AP-A to 4AP-G) were isolated on nutrient agar plates. Changes in the bacterial populations of 4-aminopyridine, 3,4-dihydroxypyridine, or formate/ammonium chloride enrichment cultures were monitored by denaturing gradient gel electrophoresis (DGGE) profiling of PCR-amplified 16S rRNA gene fragments. Sequence analysis of the 16S rRNA gene fragments derived from predominant DGGE bands indicated that Pseudomonas nitroreducens 4AP-A and Enterobacter sp. 4AP-G were predominant in the three tested enrichment cultures and that the unculturable strains Hyphomicrobium sp. 4AP-Y and Elizabethkingia sp. 4AP-Z were predominant in 4-aminopyridine and formate/ammonium chloride enrichment cultures and in the 3,4-dihydroxypyridine enrichment culture, respectively. Among the culturable strains, strain 4AP-A could utilize 3,4-dihydroxypyridine as a growth substrate. Although we could not isolate strain 4AP-Y on several media, PCR-DGGE analysis and microscopy indicated that the unique bi-polar filamentous bacterial cells gradually became more dominant with increasing 4-aminopyridine concentration in the medium.ConclusionsHyphomicrobium sp. 4AP-Y, P. nitroreducens 4AP-A, and Elizabethkingia sp. 4AP-Z probably play important roles in 4-aminopyridine degradation in crop fields. In the enrichment culture, 3,4-dihydroxypyridine and its metabolites including formate might be shared as growth substrates and maintain the enrichment culture, including these indispensable strains.

A robust implementation of a kurtosis beamformer for the accurate identification of epileptogenic foci

ObjectiveTo improve the accuracy and reliability of the localisation of epileptogenic activity using spatially filtered MEG data. MethodsA synthetic epileptic source was embedded in healthy brain activity in different orientations in order to estimate how reliably this signal containing high levels of kurtosis can be localised. An existing approach (SAM(g2)) was compared to a new implementation of the methodology. ResultsThe results confirm that a kurtosis beamformer is an effective tool with which to localise spontaneous epileptiform activity. However, it is crucial that the orientation of source reconstruction matches that of the true source otherwise the epileptic activity is either mis-localised or completely missed. Therefore as the original SAM(g2) implementation is restricted to the tangential plane, in certain circumstances it will perform poorly compared to the approach described here. ConclusionsA kurtosis beamformer is made more accurate and more robust if the analysis is not restricted to the tangential plane and if the optimisation routine for selecting the source orientation is performed using kurtosis rather than power. SignificanceMEG is increasingly being used for the non-invasive localisation of epileptic biomagnetic signals and the implementation described in this paper increases the clinical utility of the technique.

Diffuse cerebral language representation in tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder affecting multiple organs, including the brain, and very often associated with epileptic activity. Language acquisition and development seems to be altered in a significant proportion of patients with TSC. In the present study, we used magnetoencephalography (MEG) to investigate spatiotemporal cerebral language processing in subjects with TSC and epilepsy during a reading semantic decision task, compared to healthy control participants. Fifteen patients with TSC and 31 healthy subjects performed a lexico-semantic decision task during MEG recording. Minimum-norm estimates (MNE) were computed allowing identification of cerebral generators of language evoked fields (EF) in each subject. Source analysis of the language EF demonstrated early bilateral medial occipital activation (125ms) followed by a fusiform gyrus activation around 135ms. At 270ms post stimuli presentation, a strong cerebral activation was recorded in the left basal temporal language area. Finally, cerebral activations were measured in Wernicke's area followed by Broca's area. The healthy control group showed larger and earlier language activations in Broca and Wernicke's areas compared to TSC patients. Moreover, cerebral activation from Broca's area was greater than activation from Wernicke's area in both groups, but this difference between anterior and posterior regions was smaller in the TSC group. Finally, the activation latency difference between Broca and Wernicke's areas was greater in healthy controls than in TSC patients, which shows that activations in these areas are more serial in control subjects compared to TSC patients in whom activations occur more simultaneously. This is the first study to investigate cerebral language pattern in patients with TSC. Compared to healthy controls, atypical neuromagnetic language responses may reflect cerebral reorganization in these patients in response to early epileptogenic activity or presence at birth of multiple brain lesions.

Evaluation of the Possible Epileptogenic Activity of Ciprofloxacin: The Role of Nigella sativa on Amino Acids Neurotransmitters

The neuroprotective effect of Nigella sativa (NS) on amino acid neurotransmitters alteration in pentylenetetrazole (PTZ) and ciprofloxacin (CFX) treated rats in different brain regions was examined. The oral administration of NS induced an elevation in aspartate and glutamate contents, whereas the levels of GABA and glycine were decreased. Furthermore, the treated groups with PTZ and CFX caused a decrease in aspartate, glutamate and total antioxidant capacity levels, while the concentrations of GABA and glycine were increased after 14 days. Moreover, the pre- and post-treatment with NS in PTZ and CFX treated rats return the levels of these parameters near control values. So, it could be concluded that the treatment with CFX induced imbalance between the excitatory and the inhibitory amino acids which may lead to the initiation of epileptic seizures and the treatment with NS was found to ameliorate these neurological defects which reflect its potent antiepileptic activity.

Wernicke Encephalopathy in a Non-Alcoholic Patient With Metastatic CNS Lymphoma and New-Onset Occipital Lobe Seizures

Back to table of contents Previous article Next article LettersFull AccessWernicke Encephalopathy in a Non-Alcoholic Patient With Metastatic CNS Lymphoma and New-Onset Occipital Lobe SeizuresJeremy Gregory, M.D., Kemuel Philbrick, M.D., and Amit Chopra, M.D.Jeremy GregorySearch for more papers by this author, M.D., Kemuel PhilbrickSearch for more papers by this author, M.D., and Amit ChopraSearch for more papers by this author, M.D.Published Online:1 Oct 2012https://doi.org/10.1176/appi.neuropsych.11110344AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A 51-year-old man with no psychiatric or alcohol use history was treated for high-grade B-cell lymphoma involving the bowel, liver, and bone marrow, achieving complete remission with systemic chemotherapy. Six months later, he developed severe headaches secondary to relapsed CNS lymphoma.He presented with confusion, bilateral ophthalmoplegia, non-reactive pupils, and ptosis. MRI showed leptomeningeal enhancement along the temporal and occipital lobes bilaterally with adjacent parenchymal infiltration and expansion of the cavernous sinuses. On admission, high-dose intravenous methotrexate was initiated, and the psychiatry department was consulted because of concern for delirium. On mental status exam, he was noted to be confused, with florid visual hallucinations (seeing animals in his room, sparkles dancing on his skin, and the blood coursing through his veins).Wernicke encephalopathy (WE) was suspected, and, after one dose of intravenous thiamine, he became fully oriented, and his symptoms of ophthalmoplegia improved, but visual hallucinations persisted. EEG showed epileptogenic activity over the left occipital region consistent with simple partial occipital lobe seizures. Visual hallucinations resolved with initiation of levetiracetam.DiscussionThiamine deficiency leads to breakdown of the blood–brain barrier, neuronal necrosis, and irreversible brain damage in susceptible areas, including the medial thalamus and periaqueductal gray matter.1 Despite thiamine administration, WE patients (as high as 80%) may progress to Korsakoff syndrome, a chronic condition characterized by anterograde amnesia and confabulations.2 Coma and death may ensue, with 17% mortality for untreated WE.2The incidence of WE in the general cancer population is unknown. In one autopsy series, 8 of 24 patients with leukemia or lymphoma had pathologic findings suggestive of WE, none of which were recognized clinically.3,4 Cancer patients are at high risk of WE due to chronic malnutrition, chemotherapy-induced nausea and vomiting, and consumption of thiamine by rapidly-growing tumors such as hematological malignancies and sarcoma.1Brain MRI is the imaging procedure of choice5 because of high specificity (93%), although it cannot exclude WE because of low sensitivity (53%). MRI findings in alcoholic patients with acute WE may reveal atrophy of the mamillary bodies, infratentorial regions, supratentorial cortex, and corpus callosum, whereas atrophic changes are generally absent in nonalcoholic patients.5Diagnosis of WE is difficult in cancer patients because there are multiple reasons for confusional states, including hypoxia, infection, electrolyte imbalances, organ failure, opioid and sedative medications, chemotherapy, and brain and meningeal metastases.1 WE is a neurological emergency, and thiamine (500 mg 3 times daily) should be initiated immediately, either intravenously or intramuscularly, to ensure adequate absorption.4ConclusionsCancer patients are at high risk of developing WE, and it should be urgently treated with parenteral thiamine to prevent permanent neurologic damage and death. Thiamine prophylaxis should be considered in cancer patients to prevent WE.Dept. of Neurology, Mayo Clinic, Rochester, MNDept. of Psychiatry and Psychology, Mayo Clinic, Rochester, MNCorrespondence: chopra.[email protected]eduReferences1 Kuo SH, Debnam JM, Fuller GN, et al.: Wernicke’s encephalopathy: an underrecognized and reversible cause of confusional state in cancer patients. Oncology 2009; 76:10–18Crossref, Medline, Google Scholar2 Victor M, Adams RD, Collins GH: The Wernicke-Korsakoff syndrome. A clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol Ser 1971; 7:1–206Medline, Google Scholar3 De Reuck J, Sieben G, De Coster W, et al.: Prospective neuropathologic study on the occurrence of Wernicke’s encephalopathy in patients with tumours of the lymphoid-hemopoietic systems. Acta Neuropathol Suppl 1981; 7:356–358Crossref, Medline, Google Scholar4 Fernandez M, Barceló M, Muñoz C, et al.: Anaphylaxis to thiamine (vitamin B1). Allergy 1997; 52:958–960Crossref, Medline, Google Scholar5 Antunez E, Estruch R, Cardenal C, et al.: Usefulness of CT and MR imaging in the diagnosis of acute Wernicke’s encephalopathy. AJR Am J Roentgenol 1998; 171:1131–1137Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byEpileptic seizures in nonalcoholic Wernicke’s encephalopathy: a case report and literature review6 September 2017 | Metabolic Brain Disease, Vol. 32, No. 6Wernicke encephalopathy as initial presentation of lymphomaThe Korean Journal of Internal Medicine, Vol. 32, No. 6Supportive Care in Cancer, Vol. 24, No. 1Neuro-Oncology Practice, Vol. 3, No. 3 Volume 24Issue 4 Fall 2012Pages E53-E53 Metrics PDF download History Published online 1 October 2012 Published in print 1 October 2012

173 Long-term Follow-up After Multiple Hippocampal Transection (MHT)

INTRODUCTION: The conventional procedure of hippocampectomy can impair memory. Furthermore, the hippocampus is the main source of stem cells. On the other hand, multiple hippocampal transection (MHT) can disrupt seizure circuits without loss of function or stem cells. In this presentation therefore, the authors will present long term outcomes in patients who had MHT for unilateral temporal lobe epilepsy. METHODS: There were 15 patients with a male/female ratio of 2-to-1; follow-up of 24 to 60 months (median of 41 months); and ages between 25 and 60 years. Preoperative electrocorticography (ECoG) was done using subdural and depth electrodes. All patients had multiple subpial transection (MST) on the neocortex and MHT on the hippocampus. Access to the hippocampus was gained through the middle temporal gyrus. Transverse cuts were made in the hippocampus at 4 mm intervals. The fimbria and entorhinal cortex were left intact. Amygdala was removed if it was epileptogenic (10 patients). Intraoperative ECoG was then done. If recordings showed epileptogenic activity, transections were repeated. If this activity persisted, the involved neocortex was resected. RESULTS: Based on intraoperative ECoG, repeat transections were needed in every case; though the second pass was over a much smaller area. Resection of temporal tip (1-2.5 cm diameter) was needed in 11 patients. There were no permanent neurological complications. Fourteen patients (94.7%) are Seizure free (Engel's class I) and 1 (6%) has rare seizures (class II). Neuropsychological studies showed that verbal memory was preserved. CONCLUSION: Although the series is small the long-term follow-up is adequate to draw preliminary conclusions. The results show that the seizure outcome with MHT is better than those reported with standard temporal lobectomy. The study also shows that intraoperative ECoG is important in order to conclude adequacy of the procedure. These conclusions indicate that this procedure needs to be persued as an alternate to hippocampectomy.

Magnetoencephalography in fronto-parietal opercular epilepsy

To clarify the clinical and neurophysiological profiles of fronto-parietal opercular epilepsy in which epileptic spikes are detected with magnetoencephalography (MEG) but not with scalp electroencephalography (EEG). Four patients presented with epileptic spikes localized to the fronto-parietal opercular cortex, which were only appreciated following MEG recordings. In all cases, seizure semiology suggested early activation of the operculum and lower peri-rolandic cortex consistent with the somatotopic organization of this region, i.e. tingling sensation involving the throat and hemi-face or contralateral upper limb, and spasms of the neck and throat. MEG spikes were localized in the fronto-parietal operculum. Three of the four patients underwent invasive electrocorticography and/or stereo-EEG recordings, and spikes were confirmed to arise from the estimated area of MEG dipole localization. Two patients remained seizure-free for over 1 year after resection of the epileptogenic region; the other patient declined resective surgery due to proximity to the language cortex. This study demonstrates the usefulness of MEG in localizing spikes arising from within the fronto-parietal opercular regions, and implies that MEG may provide localizing information in patients with symptoms suggestive of opercular epilepsy, even if scalp EEG recordings fail to disclose any epileptogenic activities.

Efficacy of Vagal Nerve Stimulation (VNS) after Multiple Subpial Transection (MST) for Extra-Temporal Seizure Foci (P01.056)

Objective: To evaluate seizure outcome with vagal nerve stimulation after multiple subpial transection in patients with extra temporal seizure foci. Background Though there are reports on seizure outcome of vagal stimulation (VNS) following failed major resective surgeries there are no studies on its effect following multiple subpial transections (MST). Design/Methods: 24 patients between the ages of 10-55 years were followed up for 24-148 months (median of 115 months). Seizure foci were bilateral in 11 patients, multi-lobar (unilateral) in 12 patients and single-lobar(unilateral) in 1 patient. MST was performed over broad areas in and around the seizure foci. Minimal topectomies were done in areas in which intra-operative EEG recording showed epileptogenic activity after 2-3 MST passes. VNS implant was done when the response from first surgery was poor (2 patients) or there was recurrence of seizures (24 patients). The interval between MST and VNS was 1 month-3years (median of 2 years). Results: There were no complications from VNS implant. The seizure outcome after VNS implant is: 15/24(62.5%) Engle9s class I, 8/24 (33.3%) class II and 1/24 (4%) class III. Conclusions: The results show that VNS improves seizure outcome in patients who have previously had MST. Based on literature search these results are better than those reported in patients who had VNS implant alone (with a 50 % responder rate in 30-40 percent); or had VNS implant after major resective surgery (with no significant benefit) or those who had major resective surgery alone. This difference may be because MST is performed over a large area of the brain; so that satellite foci in distant areas also get treated. Furthermore, it is possible that the pruning of the inter-neuronal connections that occurs in MST makes VNS signals reaching the cortical neurons more intense (and therefore more effective) by reducing its peripheral spread. Disclosure: Dr. Patil has nothing to disclose. Dr. Antony has nothing to disclose. Dr. Andrews has nothing to disclose.

Hub GABA Neurons Mediate Gamma-Frequency Oscillations at Ictal-like Event Onset in the Immature Hippocampus

Gamma-frequency oscillations (GFOs, >40Hz) are a general network signature at seizure onset at all stages of development, with possible deleterious consequences in the immature brain. At early developmental stages, the simultaneous occurrence of GFOs in different brain regions suggests the existence of a long-ranging synchronizing mechanism at seizure onset. Here, we show that hippocamposeptal (HS) neurons, which are GABA long-range projection neurons, are mandatory to drive the firing of hippocampal interneurons in a high-frequency regime at the onset of epileptiform discharges in the intact, immature septohippocampal formation. The synchronized firing of interneurons in turn produces GFOs, which are abolished after the elimination of a small number of HS neurons. Because they provide the necessary fast conduit for pacing large neuronal populations and display intra- and extrahippocampal long-range projections, HS neurons appear to belong to the class of hub cells that play a crucial role in the synchronization of developing networks.

Traumatic Brain Injury Causes an FK506-Sensitive Loss and an Overgrowth of Dendritic Spines in Rat Forebrain

Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.

Intra-Arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients with Moderate to Severe Middle Cerebral Artery Acute Ischemic Stroke

Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0-1 in patients with NIHSS 8-14, or modified Rankin Scale scores 0-2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.

Metabolic differences in the contralateral hippocampus of concordant and discordant mesial temporal sclerosis (MTS) patients: evaluation with proton magnetic resonance spectroscopy (1H-MRS)

PURPOSE: Patients with mesial temporal sclerosis (MTS) are clinically classified as concordant or discordant according to the extent of epileptogenic activity. The aim of this study is to determine whether the metabolic changes in the hippocampus are different in the two groups. MATERIALS AND METHODS: 33 patients diagnosed with MTS, 23 concordant (33±9 years old) and 10 discordant (33±10 years old) and 28 controls (33±10 years old) were evaluated. We obtained magnetic resonance spectroscopy of both hippocampi (ipsilateral and contralateral) on a 3T scanner with single voxel PRESS sequence with TE/TR=135/1500ms. The main metabolites were quantified with LC Model. For comparison between groups statistical tests were performed with a significance level of 0.05. RESULTS: In all patients a reduction of NAAipsi and Cr ipsi was observed, when compared to the contralateral side, but this difference was only significant for the group of concordant patients. In comparison with controls a significant reduction of Cr ipsi and NAAipsi was observed for both groups and for Naa/Cr ipsi in the group of concordant patients while NAA/Cr contra was reduced only in the group of discordant patients. CONCLUSION: Our findings suggest a stronger decline of NAA/Cr ipsi in the group of concordant patients and of NAA/Cr contra in discordant patients, suggesting a slightly different metabolic pattern for both groups. However, we need to increase the sample size to confirm these findings.

Abdominal epilepsy in chronic recurrent abdominal pain.

Background:Abdominal epilepsy (AE) is an uncommon cause for chronic recurrent abdominal pain in children and adults. It is characterized by paroxysmal episode of abdominal pain, diverse abdominal complaints, definite electroencephalogram (EEG) abnormalities and favorable response to the introduction of anti-epileptic drugs (AED). We studied 150 children with chronic recurrent abdominal pain and after exclusion of more common etiologies for the presenting complaints; workup proceeded with an EEG. We found 111 (74%) children with an abnormal EEG and 39 (26%) children with normal EEG. All children were subjected to AED (Oxcarbazepine) and 139 (92%) children responded to AED out of which 111 (74%) children had an abnormal EEG and 27 (18%) had a normal EEG. On further follow-up the patients were symptom free, which helped us to confirm the clinical diagnosis.Context:Recurrent chronic abdominal pain is a common problem encountered by pediatricians. Variety of investigations are done to come to a diagnosis but a cause is rarely found. In such children diagnosis of AE should be considered and an EEG will confirm the diagnosis and treated with AED.Aims:To find the incidence of AE in children presenting with chronic recurrent abdominal pain and to correlate EEG findings and their clinical response to empirical AEDs in both cases and control.Settings and Design:Krishna Institute of Medical Sciences University, Karad, Maharashtra, India. Prospective analytical study.Materials and Methods:A total of 150 children with chronic recurrent abdominal pain were studied by investigations to rule out common causes of abdominal pain and an EEG. All children were then started with AED oxycarbamezepine and their response to the treatment was noted.Results:111 (74%) of the total 150 children showed a positive EEG change suggestive of epileptogenic activity and of which 75 (67.56%) were females and 36 (32.43%) were male, majority of children were in the age of group of 9-12 years. Temporal wave discharges were 39 (35.13%) of the total abnormal EEG's. All the children were started on AEDs and those with abnormal EEG showed 100% response to treatment while 27 (18%) children with normal EEG also responded to treatment. Twelve (8%) children did not have any improvement in symptoms.Conclusions:A diagnosis of AE must be considered in children with chronic recurrent abdominal pain, especially in those with suggestive history, and an EEG can save a child from lot of unnecessary investigations and suffering.

Posterior reversible encephalopathy syndrome (PRES): electroencephalographic findings and seizure patterns

To better describe seizure type, frequency, and electroencephalographic (EEG) findings in posterior reversible encephalopathy syndrome (PRES) and correlate these data with clinical and magnetic resonance imaging (MRI) data, we retrospectively assessed medical charts and EEG studies of patients with PRES treated between 2004 and 2011. Data collected included patients' underlying pathology, lesion distribution by MRI, seizure type and frequency, EEG pathologic background activity, focal pathology, and epileptogenic activity. Thirty-eight of 49 adults with PRES suffered from seizures; 17 underwent EEG and were included in the analysis. Perpetuating factors were similar to those reported in the literature. In 15 of 17 patients, MRI showed widespread involvement rather than purely occipital lesions. Nine patients had subcortical and cortical involvement. Seizures were single short grand mal (GM) in 11, serial GM in 2, recurrent GM in 2, and additional focal seizures in 2. No seizures were noted beyond the first day. After discontinuation of antiepileptic medication, no patients experienced seizure recurrence during 6-month follow-up. EEG showed diffuse theta/delta slowing in 13 patients and epileptogenic activity with focal sharp-wave and periodic lateralizing epileptiform discharges in 2 patients. Seizures in PRES are most commonly single GM and are usually of limited duration. EEG shows variable theta/delta slowing. Focal EEG pathology is seen in patients with focal seizures. Seizures occur early after disease onset and terminate spontaneously or under therapy during the first 24h. Seizure recurrence beyond 24h and chronic epilepsy were not seen. Seizures in PRES are frequent but appear to be uncomplicated and do not herald worse prognosis. EEG is helpful in evaluating the degree of encephalopathy and monitoring epileptic activity. Long-term antiepileptic medication does not appear to be warranted.

Expression profiling of synaptic microRNAs from the adult rat brain identifies regional differences and seizure-induced dynamic modulation

In recent years, microRNAs or miRNAs have been proposed to target neuronal mRNAs localized near the synapse, exerting a pivotal role in modulating local protein synthesis, and presumably affecting adaptive mechanisms such as synaptic plasticity. In the present study we have characterized the distribution of miRNAs in five regions of the adult mammalian brain and compared the relative abundance between total fractions and purified synaptoneurosomes (SN), using three different methodologies. The results show selective enrichment or depletion of some miRNAs when comparing total versus SN fractions. These miRNAs were different for each brain region explored. Changes in distribution could not be attributed to simple diffusion or to a targeting sequence inside the miRNAs. In silico analysis suggest that the differences in distribution may be related to the preferential concentration of synaptically localized mRNA targeted by the miRNAs. These results favor a model of co-transport of the miRNA–mRNA complex to the synapse, although further studies are required to validate this hypothesis. Using an in vivo model for increasing excitatory activity in the cortex and the hippocampus indicates that the distribution of some miRNAs can be modulated by enhanced neuronal (epileptogenic) activity. All these results demonstrate the dynamic modulation in the local distribution of miRNAs from the adult brain, which may play key roles in controlling localized protein synthesis at the synapse.

Phenotypic differences between fast and slow methionine sulfoximine-inbred mice: Seizures, anxiety, and glutamine synthetase

Seizures induced by the convulsant methionine sulfoximine (MSO) resemble human "grand mal" epilepsy, and brain glutamine synthetase is inhibited. We recently selected two inbred lines of mice: sensitive to MSO (MSO-Fast) and resistant (MSO-Slow). In the present study, the selection pressure was increased and consanguinity established. To gain insight into the mechanisms of epileptogenesis, we studied the behaviour of MSO-Fast and MSO-Slow mice based on their responses to various convulsants and anticonvulsants, and also the kinetics of glutamine synthetase. The results show that increasing the number of generations of sib-crossings resulted in an increase in the differences between MSO-Fast and MSO-Slow mice. The dose-response curve of MSO-dependent seizures demonstrated that the MSO-Slow mice were highly insensitive to MSO-dependent seizures compared with MSO-Fast inbred mice that were highly sensitivity. The MSO-Slow were resistant to convulsions induced by various convulsants having different mechanisms of action, whereas those in the MSO-Fast line were more sensitive to kainic acid-induced seizures. These data, in addition to the effects of anticonvulsant, strongly suggest that glutamatergic pathways are most likely involved in MSO-dependent seizures, rather than GABAergic ones. This hypothesis is corroborated by the glutamine synthetase activity, which is more elevated in the MSO-Slow line. Behaviour tests showed that MSO-Slow were less anxious than MSO-Fast. Collectively, these results showed that glutamatergic pathways could be involved in the epileptogenic action of MSO, which may be related to the glutamate/glutamine cycle in the brain.

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

The present study shows interactive effects of pentoxifylline (PTX) as a phosphodiesterase (PDE) inhibitor, H-89 as a protein kinase A (PKA) inhibitor and bucladesine (db-cAMP) as a cAMP agonist on pentylenetetrazol (PTZ)-induced seizure in mice. Different doses of pentoxifylline (25, 50, 100 mg/kg), bucladesine (50, 100, 300 nM/mouse), and H-89 (0.05, 0.1, 0.2 mg/100g) were administered intraperitoneally (i.p.), 30 min before intravenous (i.v.) infusion of PTZ (0.5% w/v). In combination groups, the first and second components were injected 45 and 30 min before PTZ infusion. In all groups, the control animals received an appropriate volume of vehicle. Single administration of PTX had no significant effect on both seizure latency and threshold. Bucladesine significantly decreased seizure latency and threshold only at a high concentration (300 nM/mouse). Intraperitoneal administration of H-89 (0.2 mg/100g) significantly increased seizure latency and threshold in PTZ-treated animals. All applied doses of bucladesine in combination with PTX (50 mg/kg) caused a significant reduction in seizure latency. Pretreatment of animals with PTX (50 and 100 mg/kg) attenuated the anticonvulsant effect of H-89 (0.2 mg/100g) in PTZ-exposed animals. H-89 (0.05, 0.2 mg/100g) prevented the epileptogenic activity of bucladesine (300 nM) with significant increase of seizure latency and seizure threshold. In conclusion, we showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters.