Appearance Of Epileptiform Activity Research Articles

Ictal EEG in sunflower syndrome: Provoked or unprovoked seizures?

Sunflower syndrome (SS) is a rare, photosensitive epilepsy characterized by an attraction to light and highly stereotyped seizures with associated hand-waving (HW). It is controversial whether HW is part of the seizure or a provoking factor; therefore, we aimed to characterize the ictal electroencephalogram (EEG) in patients with SS.Video-EEG (vEEG) and charts of five patients with SS with HW during vEEG from Massachusetts General Hospital's Pediatric Epilepsy Program were reviewed and analyzed.In four out of five patients, the ictal EEG showed high amplitude (500–700 μV) 3–4 Hz generalized spike/polyspike-and-slow wave discharges, lasting 1.63–24.41 s.One hundred and twelve of 126 HW episodes, correlating to epileptiform activity (vEEG), had a lag time of less than 1.00 s (88.89%) between onset of HW and appearance of epileptiform activity. This suggests that HW does not induce seizure activity.Awareness of the ictal EEG features of this syndrome is important, as patients are frequently described as “self-inducing” their seizures.

Continuous EEG Monitoring-The Neurologist's Crystal Ball.

Time to Epileptiform Activity and EEG Background Recovery Are Independent Predictors After Cardiac Arrest Westhall E, Rose I, Rundgren M, Bro-Jeppesen J, Kjaergaard J, Hassager C, Lindehammar H, Horn J, Ullen S, Nielsen N, Friberg H, Cronberg T. Clin Neurophysiol. 2018;129:1660-1668. doi:10.1016/j.clinph.2018.05.016Objective: To investigate the temporal development of electroencephalogram (EEG) and prognosis. Methods: Prospective observational substudy of the Target Temperature Management trial. Six sites performed simplified continuous EEG monitoring (cEEG) on comatose patients after cardiac arrest, blinded to treating physicians. We determined time points of recovery of a normal-voltage continuous background activity and the appearance of an epileptiform EEG, defined as abundant epileptiform discharges, periodic/rhythmic discharges, or electrographic seizure activity. Results: One hundred thirty-four patients were included, of which 65 had a good outcome. Early recovery of continuous background activity (within 24 hours) occurred in 72 patients and predicted good outcome since 55 (76%) had good outcome, increasing the odds for a good outcome 7 times compared to a late background recovery. Early appearance of an epileptiform EEG occurred in 38 patients and 34 (89%) had a poor outcome, increasing the odds for a poor outcome 6 times compared to a late debut. The time to background recovery and the time to epileptiform activity were highly associated with outcome and levels of neuron-specific enolase. Multiple regression analysis showed that both variables were independent predictors. Conclusions: Time to epileptiform activity and background recovery are independent prognostic indicators. SIGNIFICANCE: Patients with early background recovery combined with late appearance of epileptiform activity may have a good outcome.

Time to epileptiform activity and EEG background recovery are independent predictors after cardiac arrest

ObjectiveInvestigate the temporal development of EEG and prognosis. MethodsProspective observational substudy of the Target Temperature Management trial. Six sites performed simplified continuous EEG-monitoring (cEEG) on comatose patients after cardiac arrest, blinded to treating physicians. We determined time-points of recovery of a normal-voltage continuous background activity and the appearance of an epileptiform EEG, defined as abundant epileptiform discharges, periodic/rhythmic discharges or electrographic seizure activity. Results134 patients were included, 65 had a good outcome. Early recovery of continuous background activity (within 24 h) occurred in 72 patients and predicted good outcome since 55 (76%) had good outcome, increasing the odds for a good outcome seven times compared to a late background recovery. Early appearance of an epileptiform EEG occurred in 38 patients and 34 (89%) had a poor outcome, increasing the odds for a poor outcome six times compared to a late debut. The time to background recovery and the time to epileptiform activity were highly associated with outcome and levels of neuron-specific enolase. Multiple regression analysis showed that both variables were independent predictors. ConclusionsTime to epileptiform activity and background recovery are independent prognostic indicators. SignificancePatients with early background recovery combined with late appearance of epileptiform activity may have a good outcome.

Platform Session – Electroencephalography/Epilepsy: Temporal development of cEEG patterns as predictors of prognosis after cardiac arrest

Continuous EEG-monitoring (cEEG) is used to detect electrographic seizures and is a promising prognostic tool in comatose patients after cardiac arrest (CA). The objective of this study was to investigate the temporal development of epileptiform activity and EEG background activity as predictors of prognosis. In this prospective substudy of the Target Temperature Management trial six sites recorded simplified cEEG on comatose patients resuscitated after CA. The cEEG-data was blinded to the treating team and assessed, blinded to outcome and clinical data, at 12, 24, 36, 48 and 60 h after CA. The standardized EEG terminology of the American Clinical Neurophysiology Society was used. The time-points of recovery of a normal-voltage continuous background and the appearance of an epileptiform EEG were determined, the latter defined as abundant epileptiform discharges (⩾0.1 Hz), abundant periodic or rhythmic discharges or electrographic seizure activity for 30 min. The cEEG-data was not part of the multimodal prognostication protocol for decisions on withdrawal of care. Poor outcome was defined as best Cerebral Performance Category 3–5 until 180 days. 134 patients were included and 65 had a good outcome. 103 patients recovered a continuous normal-voltage background. Background recovery within 24 h occurred in 72 patients, 55 (76%) had good outcome. Among the 31 patients with background recovery beyond 24 h, 10 (32%) had good outcome. Thus a late recovery of background increased the odds for a poor outcome six times (sens 55%, spec 85%). All 31 patients that failed to recover their background within the monitoring period (60 h after CA) had a poor outcome (sens 45%, spec 100%). Appearance of an epileptiform EEG occurred in 66 patients. Among 38 patients with an epileptiform EEG within 24 h, 34 (89%) had poor outcome (sens 49%, spec 94%). 28 patients had start of an epileptiform EEG beyond 24 h, 16 had a poor outcome (sens 46%, spec 80%). Thus an early epileptiform EEG increased the odds for a poor outcome seven times. The logistic regression model showed no significant interactions between background and epileptiform activity regarding predictive ability. Thus assessing both the time to recovery of background and the time to appearance of epileptiform activity improved prognostication. 16 of the 65 patients with good outcome had an epileptiform EEG and 14 (88%) of these patients recovered their background at the same time or before the onset of epileptiform activity. Abundant periodic or rhythmic discharges were seen in 3 survivors with good outcome and all had a recovery of background within 24 h and before the onset of discharges. Time to epileptiform activity and EEG background recovery are independent prognostic indicators. Patients with early background recovery combined with late appearance of epileptiform activity may have a good prognosis.

Early electrophysiological consequences of dosed traumatic-brain injury in rats

To analyze the pathological electrical activity during the acute period after traumatic brain injury (TBI) and to search for potential morphological correlates of this activity in the neocortex and hippocampus. The study was performed on male Sprague Dawley rats. TBI was modeled using a lateral hydrodynamic impact in the sensorimotor cortex area. ECoG was continuously recorded one week before and one week after TBI. A histological analysis was performed one week after TBI. Brain slices were Nissl stained as well as immunohistochemically stained for astrocytes (GFAP) and microglia (Isolectin B4). The damage to the neocortex and hippocampus was evaluated. The slowdown of the background activity one and six hours after TBI and appearance of epileptiform activity in a half of animals one week after TBI were shown. The number of discharges was correlated with the area of astrocyte gliosis in the neocortex and with the number of dark (ischemic-like) neurons in the hippocampus. Microglial activation did not correlate with the epileptiform activity. These data are important to understanding early mechanisms of post-trauma epileptogenesis.

Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid β (Aβ) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs). Unexpectedly, we found that withholding APP overexpression until adulthood substantially delayed the appearance of epileptiform activity. Together, these findings suggest that juvenile APP overexpression altered cortical development to favor synchronized firing. Regardless of the age at which EEG abnormalities appeared, the phenotype was dependent on continued APP overexpression and abated over several weeks once transgene expression was suppressed. Abnormal EEG discharges were independent of plaque load and could be extinguished without altering deposited amyloid. Selective reduction of Aβ with a γ-secretase inhibitor has no effect on the frequency of SWDs, indicating that another APP fragment or the full-length protein was likely responsible for maintaining EEG abnormalities. Moreover, transgene suppression normalized the ratio of excitatory to inhibitory innervation in the cortex, whereas secretase inhibition did not. Our results suggest that APP overexpression, and not Aβ overproduction, is responsible for EEG abnormalities in our transgenic mice and can be rescued independently of pathology.

Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures

The extracellular matrix (ECM) plays an important role in use-dependent synaptic plasticity. Hyaluronic acid (HA) is the backbone of the neural ECM, which has been shown to modulate α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptor mobility, paired-pulse depression, L-type voltage-dependent Ca2+ channel (L-VDCC) activity, long-term potentiation and contextual fear conditioning. To investigate the role of HA in the development of spontaneous neuronal network activity, we used microelectrode array recording and Ca2+ imaging in hippocampal cultures enzymatically treated with hyaluronidase. Our findings revealed an appearance of epileptiform activity 9 days after hyaluronidase treatment. The treatment transformed the normal network firing bursts and Ca2+ oscillations into long-lasting “superbursts” and “superoscillations” with durations of 11–100 s. The changes in Ca2+ transients in hyaluronidase-treated neurons were more prominent then in astrocytes and preceded changes in electrical activity. The Ca2+ superoscillations could be suppressed by applying the L-VDCC blocker diltiazem, whereas the neuronal firing superbursts could be additionally suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione as an antagonist of AMPA/kainate receptors. These results suggest that changes in the expression of HA can be epileptogenic and that hyaluronidase treatment in vitro provides a robust model for the dissection of the underlying mechanisms.

Suppression of excitatory synaptic transmission can facilitate low-calcium epileptiform activity in the hippocampus in vivo

It has been reported that the inhibitory postsynaptic potential (IPSP) is abolished before the excitatory postsynaptic potential (EPSP) when the extracellular concentration of Ca 2+ ([Ca 2+] o) is removed gradually in hippocampal slices. However, the low-Ca 2+ nonsynaptic epileptiform activity does not appear until the [Ca 2+] o is decreased to a level sufficient to depress the excitatory synaptic transmission. This suggests the hypothesis that the suppression of excitatory synaptic transmission itself could facilitate the generation of epileptiform activity. In the present study, we tested this hypothesis and developed a new model of nonsynaptic epileptiform activity by gradually raising the neuronal excitability and blocking the synaptic transmission with high K +, zero Ca 2+ and calcium chelator ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA) in the CA1 region of hippocampus in vivo. The changes of synaptic transmission and recurrent inhibitory activity during this process were evaluated by measuring the amplitude of the population spikes (PS) in response to paired-pulse orthodromic stimulation. The results show that the epileptiform activity appeared only when the excitatory synaptic transmission was depressed by further lowering [Ca 2+] o with EGTA. Similar epileptiform activity could be induced when EGTA was replaced by the excitatory postsynaptic amino acid antagonists d-(−)-2-amino-5-phosphonopentanoic acid (APV) plus 6,7-dinitroquinoxaline-2,3-dione (DNQX) or APV alone but not DNQX alone. The combination application of APV and cadmium enhanced the epileptiform activity. These results suggest that the suppression of excitatory synaptic transmission can facilitate the appearance of epileptiform activity in solution with high K + and low Ca 2+ in vivo. These data provide new information to be considered in the development of antiepileptic drugs. They also suggest a possible mechanism to explain the fact that low-frequency electrical stimulation can suppress epileptiform activity.

4-Aminopyridine-induced epileptogenesis depends on activation of mitogen-activated protein kinase ERK.

Extracellular signal-regulated kinases such as ERK1 [p44 mitogen-activated protein kinase (MAPK)] and ERK2 (p42 MAPK) are activated in the CNS under physiological and pathological conditions such as ischemia and epilepsy. Here, we studied the activation state of ERK1/2 in rat hippocampal slices during application of the K(+) channel blocker 4-aminopyridine (4AP, 50 micro m), a procedure that enhances synaptic transmission and leads to the appearance of epileptiform activity. Hippocampal slices superfused with 4AP-containing medium exhibited a marked activation of ERK1/2 phosphorylation that peaked within about 20 min. These effects were not accompanied by changes in the activation state of c-Jun N-terminal kinase (JNK), another member of the MAP kinase superfamily. 4AP-induced ERK1/2 activation was inhibited by the voltage-gated Na(+) channel blocker tetrodotoxin (1 micro m). We also found that application of the ERK pathway inhibitors U0126 (50 micro m) or PD98059 (100 micro m) markedly reduced 4AP-induced epileptiform synchronization, thus abolishing ictal discharges in the CA3 area. The effects induced by U0126 or PD98059 were not associated with changes in the amplitude and latency of the field potentials recorded in the CA3 area following electrical stimuli delivered in the dentate hylus. These data demonstrate that activation of ERK1/2 accompanies the appearance of epileptiform activity induced by 4AP and suggest a cause-effect relationship between the ERK pathway and epileptiform synchronization.

A Comparison of the Effects of Clozapine and Olanzapine on the EEG in Patients with Schizophrenia

Clozapine is known to induce epileptic seizures and changes in EEG-patterns, including slowing and the appearance of epileptiform activity. Olanzapine, a new antipsychotic drug, shares many pharmacological and clinical properties with clozapine. However, in patients treated with olanzapine, no case of seizure induction has been reported so far, and the EEG has not been studied systematically. We examined the EEGs of patients with schizophrenia treated with either olanzapine (N = 9) or clozapine (N = 9) prior to medication and 3 to 7 weeks afterwards. Clozapine induced significant EEG slowing present in 78% of the patients, and definite epileptiform activity appeared in 33%. Olanzapine also induced significant EEG slowing, but less frequently (in 44% of the patients) and less pronounced than clozapine. Olanzapine had no significant effect an epileptiform activity, but in one patient, an isolated sharp/slow-wave complex was observed. These preliminary data suggest that olanzapine induces EEG slowing to a lower extent than clozapine. Olanzapine's possible effect an the seizure threshold deserves further attention.

Neocortical activation: modulation by multiple pathways acting on central cholinergic and serotonergic systems.

The present experiments examined the central systems which mediate the electrocorticographic activation induced by electrical stimulation of forebrain and midbrain areas known to play a role in cerebral activation. In urethane-anesthetized rats, 100-Hz electrical stimulation of the amygdaloid cmplex or dorsal raphe changed neocortical electrocorticographic activity from large irregular slow activity (LISA; 1-6 Hz, up to 2 mV) to low voltage fast activity (LVFA; less than 0.5 mV, including frequencies above 10 Hz). The LVFA during amygdala stimulation, but not that during dorsal raphe stimulation, was completely abolished and replaced by LISA after administration of the anti-muscarinic agent scopolamine (5 mg/kg, i.p.), confirming previous work suggesting that neocortical LVFA is maintained by two distinct neurochemical inputs to the cortex that can be dissociated using anti-muscarinic drugs. Electrical stimulation of the locus coeruleus area or of the superior colliculus also suppressed LISA and induced LVFA. The LVFA during stimulation of the locus coeruleus area was abolished by the anti-muscarinic drug atropine (50 mg/kg, i.p.), whereas the LVFA during superior colliculus stimulation was atropine-resistant but could be abolished by the serotonergic antagonists methiothepin (5 mg/kg, i.p.) or ketanserin (5 mg/kg, i.p.). Stimulation of 44% of electrode sites in the orbitofrontal cortex produced neocortical LVFA which was reduced by atropine and completely abolished by additional administration of methiothepin. Stimulation of the entorhinal or cingulate cortex was ineffective in producing LVFA and often resulted in the appearance of epileptiform activity. Single-pulse electrical stimulation of those sites that effectively induced atropine-sensitive LVFA (amygdala, locus coeruleus area) produced excitation of over 65% of those extracellularly recorded basal forebrain neurons that fired at higher rates during the presence of neocortical LVFA relative to LISA. About 80% of basal forebrain cells that were more active during LISA relative to LVFA were inhibited by single-pulse stimulation of the amygdala or locus coeruleus area. The present results suggest that widely distributed neuronal systems can produce electrocorticographic activation by acting through mechanisms sensitive to anti-muscarinic or anti-serotonergic drugs, suggeting that these activating influences involve the release of acetylcholine and/or serotonin. Those neural systems that produce atropine-sensitive (i.e., putative cholinergic) LVFA, believed to be dependent on the cholinergic innervation of the cortex arising in the basal forebrain, may produce electrocorticographic activation by exciting basal forebrain cells that appear to contribute to neocortical LVFA, while concurrently inhibiting cells that may contribute to LISA.

Epileptic patterns induced by some biogenic amines injected in the rat brain

Summary The biogenic quaternary amines leptodactiline, candicine and murexine, when injected into the third ventricle of rat brain, produced desynchronizing pattern followed by the appearance of epileptiform activity in both cortical and subcortical structures (caudate nucleus and reticular formation). Application of atropine abolished the induced epileptic activity. The injection of leptodactiline and candicine but not that of murexine into the caudate nucleus caused activity changes which first appeared there. The present results, confirming previous data observed in molluscan nerve cells, suggest that the trymethylammonium group present in all the tested molecules plays an important role in inducing the observed patterns.

Cerebral cortical cholesterol changes in cobalt-induced epilepsy.

The present study was designed to elucidate cerebral cortical cholesterol changes observed earlier in cobalt-induced epilepsy in the rat. This model is produced by insertion of cobalt metal rods into the cerebral cortex. Seven days after implantations of cobalt (or other metals), measurements of cerebral cortical lipid concentrations were made in the direct area of metal implantation (lesion area) and in the nonnecrotic tissue immediately adjacent to the lesion site (adjacent area). The cortical concentration of free cholesterol decreased and the concentrations of cholesterol esters (CE) greatly increased in the adjacent area of rats implanted with epileptogenic metals (cobalt and nickel) but not in those implanted with nonepileptogenic metals (copper and stainless steel). Differences in the fatty acid compositions of CE from plasma and those from cobalt-lesioned cortex indicated that the accumulated CE originated in the brain rather than from the plasma CE pool. A time course study revealed that changes in the cortical concentrations of free and esterified cholesterol precedes the first appearance of epileptiform activity as measured by electrocorticography. The reduction of free cholesterol levels most likely reflects increased cholesterol metabolism in the cobalt-lesioned cortex. A major portion of this free cholesterol appears to be converted to CE, but not to bile acid or neutral sterol (potential products of cholesterol metabolism). The concentration of free fatty acids, the other substrate of CE formation, was decreased in the lesion site. The increased metabolism of cholesterol could not be explained by changes in the activities of CE synthetase and hydrolase(s). Since cholesterol in the brain is found almost exclusively in membranes, it is likely that these sterol changes reflect membrane alterations or disintegration. However, the exact relationship of these changes to the epileptogenic effect of cobalt remains unclear.