A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus

Review of 60 electroencephalograms recorded during episodes of generalized convulsive status epilepticus suggested that there are 5 identifiable EEG patterns which occur in a predictable sequence during the course of generalized convulsive status epilepticus in man: (1) discrete seizures; (2) merging seizures with waxing and waning amplitude and frequency of EEG rhythms; (3) continuous ictal activity; (4) continuous ictal activity punctuated by low voltage 'flat periods'; and (5) periodic epileptiform discharges on a 'flat' background. We confirmed our hypothesis that this sequence represents the natural history of electroencephalographic changes in untreated generalized convulsive status epilepticus by observing the same sequence in the EEGs of rats in which status epilepticus had been induced by 3 different methods: (1) systemic administration of kainic acid, (2) injection of homocysteine thiolactone to cobalt-lesioned rats; and (3) injection of lithium chloride followed 24 h later by injection of pilocarpine.     

Focal Status Epilepticus: Clinical Features and Significance of Different EEG Patterns

PURPOSE: Focal status epilepticus is typically diagnosed by the observation of continuous jerking motor activity, but many other manifestations have been described. EEG evidence of focal status may take several forms, and their interpretation is controversial. We detailed the clinical spectrum of focal status in patients diagnosed by both clinical deficit and EEG criteria and contrasted clinical manifestations in patients with different EEG patterns. METHODS: Patients were diagnosed with a neurologic deficit and discrete recurrent focal electrographic seizures or rapid, continuous focal epileptiform discharges on EEG. Clinical findings were determined by chart review. RESULTS: Of 41 patients with focal status, acute vascular disease was the cause in 21; 10 of 41 had exacerbations of prior epilepsy. A variety of clinical seizure types occurred, both before and after the EEG diagnosis, but the diagnosis was not expected in 28 patients before the EEG. Three had no obvious clinical seizures. Focal motor seizures and an abnormal mental status were the most common manifestations at the time of the EEG. With antiepileptic drugs, almost all had control of clinical seizures, and most improved in mental status. Patients with rapid continuous focal epileptiform discharges were nearly identical in presentation, likelihood of diagnosis, subsequent seizures, response to medication, and outcome to those with discrete seizures on EEG. CONCLUSIONS: Focal status epilepticus may be seen with a wide variety of clinical seizure types or without obvious clinical seizures. The diagnosis is often delayed or missed and should be considered after strokes or clinical seizures when patients do not stabilize or improve as expected. The diagnosis should be made equally whether patients have discrete electrographic seizures or continuous rapid focal epileptiform discharges on the EEG, and the same response to medications and outcome should be anticipated for the two groups.     

Temporal changes in neuronal dropout following inductions of lithium/pilocarpine seizures in the rat

Estimates of neuronal dropout for approximately 100 structures as defined by Paxinos-Watson were completed for brains of male Wistar albino rats between 1 and 50 days after status epilepticus was evoked by a single systemic injection of lithium and pilocarpine. Sample estimates of neuronal loss were strongly correlated with direct measures of cell density. The most extensive immediate damage occurred within the substantia nigra reticulata, CA1 field of the hippocampus, the piriform cortex and the reuniens and paratenial nuclei of the thalamus. Neuronal dropout continued in many other structures over a 50-day period. Structures that showed the greatest 2-deoxyglucose (2-DG) uptake during discrete seizures and waxing and waning seizures within the early stages of status epilepticus but the least 2-DG uptake at the time of late continuous spiking and fast spiking with pauses [Neuroscience 64 (1995) 1057, 1075] exhibited the most neuronal dropout. Relationships between the delay of injection of acepromazine (which facilitated survival) and the amount of damage suggested that the source of the process that results in permanent brain damage may originate within the region of the piriform cortices and its subcortices.     

Characterization of status epilepticus induced by two organophosphates in rats

Organophosphates (OPs) inhibit the enzyme cholinesterase and cause accumulation of acetylcholine, and are known to cause seizures and status epilepticus (SE) in humans. The animal models of SE caused by organophosphate analogs of insecticides are not well characterized. SE caused by OPs paraoxon and diisopropyl fluorophosphate (DFP) in rats was characterized by electroencephalogram (EEG), behavioral observations and response to treatment with the benzodiazepine diazepam administered at various stages of SE. A method for SE induction using intrahippocampal infusion of paraoxon was also tested. Infusion of 200nmol paraoxon into the hippocampus caused electrographic seizures in 43/52 (82.7%) animals tested; and of these animals, 14/43 (30%) had self-sustaining seizures that lasted 4-18h after the end of paraoxon infusion. SE was also induced by peripheral subcutaneous injection of diisopropyl fluorophosphate (DFP, 1.25mg/kg) or paraoxon (1.00mg/kg) to rats pretreated with atropine (2mg/kg) and 2-pralidoxime (2-PAM, 50mg/kg) 30min prior to OP injection. SE occurred in 78% paraoxon-treated animals and in 79% of DFP-treated animals. Diazepam (10mg/kg) was administered 10min and 30min after the onset of continuous EEG seizures induced by paraoxon and it terminated SE in a majority of animals at both time points. DFP-induced SE was terminated in 60% animals when diazepam was administered 10min after the onset of continuous EEG seizure activity but diazepam did not terminate SE in any animal when it was administered 30min after the onset of continuous seizures. These studies demonstrate that both paraoxon and DFP can induce SE in rats but refractoriness to diazepam is a feature of DFP induced SE.     

Generalized Convulsive Status Epilepticus in the Adult

Summary: Status epilepticus (SE) is denned as recurrent epileptic seizures without full recovery of consciousness before the next seizure begins, or more-or-less continuous clinical and/or electrical seizure activity lasting for more than 30 min whether or not consciousness is impaired. Three presentations of SE are now recognized: recurrent generalized tonic and/or clonic seizures without full recovery of consciousness between attacks, nonconvulsive status where the patient appears to be in a prolonged "epileptic twilight state," and continuous/repetitive focal seizure activity without alteration of consciousness. Generalized convulsive status epilepticus (GCSE) encompasses a broad spectrum of clinical presentations from repeated overt generalized tonic-clonic seizures to subtle convulsive movements in a profoundly comatose patient. Thus, GCSE is a dynamic state that is characterized by paroxysmal or continuous tonic and/or clonic motor activity, which may be symmetrical or asymmetrical and overt or subtle but which is associated with a marked impairment of consciousness and with bilateral (although frequently asymmetrical) ictal discharges on the EEG. Just as there is a progression from overt to increasingly subtle clinical manifestations of GCSE, there is also a predictable sequence of progressive EEG changes during untreated GCSE. A sequence of five patterns of ictal discharges has been observed: discrete electrographic seizures, waxing and waning, continuous, continuous with flat periods, and periodic epileptiform discharges on a relatively flat background. A patient actively having seizures or comatose who exhibits any of these patterns on EEG should be considered to be in GCSE and should be treated aggressively to stop all clinical and electrical seizure activity to prevent further neurological morbidity and mortality.     

Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study

Behavioural, electroencephalographic and neuropathological responses to increasing doses of pilocarpine (100-400 mg/kg) administered intraperitoneally to rats were studied. At the dose of 400 mg/kg pilocarpine produced a sequence of behavioural alterations including staring spells, olfactory and gustatory automatisms and motor limbic seizures that developed over 1-2 h and built up progressively into limbic status epilepticus. Smaller doses showed different threshold for these behavioural phenomena but a similar time course of development. The earliest electrographic alterations occurred in the hippocampus and then epileptiform activity propagated to amygdala and cortex. Subsequently electrographic seizures appeared in both limbic and cortical leads. The ictal periods recurred each 5-15 min and were followed by variable periods of depression of the electrographic activity. The sequence of electrographic changes correlated well with the development of behavioural phenomena. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. Neuropathological alterations were observed in the olfactory cortex, amygdaloid complex, thalamus, neocortex, hippocampal formation and substantia nigra. Pretreatment of animals with scopolamine (20 mg/kg) and diazepam (10 mg/kg) prevented the development of convulsive activity and brain damage. These results show that systemic pilocarpine in rats selectively elaborates epileptiform activity in the limbic structures accompanied by motor limbic seizures, limbic status epilepticus and widespread brain damage. It is suggested that a causative relationship between excessive stimulation of cholinergic receptors in the brain and epileptic brain damage may exist.     

Nonlinear dynamic characteristics of electroencephalography in a high-dose pilocarpine-induced status epilepticus model

We applied nonlinear analysis to the results of electroencephalography (EEG) in a pilocarpine-induced status epilepticus (SE) model to characterize nonlinear dynamics according to SE phase. Nine male Sprague-Dawley rats weighing 150-250 g were used. EEG was classified into four phases in addition to baseline EEG (phase 0) as follows: phase 1, discrete seizures; phase 2, continuous ictal discharges; phase 3, early periodic epileptiform discharges (PEDs); and phase 4, late PEDs. High-dose diazepam was administered at phase 4 to terminate SE. Diazepam controlled SE in five rats (group 1), while it failed to stop SE in the rest (group 2). The presence of nonlinearity was determined by time reversal asymmetry statistics using a surrogate data set. The correlation dimension (D(2)) was calculated to characterize the dimensional complexity of each phase of SE. EEG of later phases of SE showed strong nonlinearity, whereas no or only weak nonlinearity was noted at phases 0 and 1. D(2) showed the highest value at phase 0 and decreased progressively. Considering therapeutic responsiveness, D(2) showed significant differences between the two groups at phases 2 and 4. These results suggest that nonlinear dynamic changes in the later SE phases reflect underlying pathophysiological changes that contribute to determining therapeutic responsiveness in the pilocarpine-induced SE model.     

Treatment of late lithium-pilocarpine-induced status epilepticus with diazepam

PURPOSE: It is well known that status epilepticus (SE) becomes increasingly difficult to control over time. Previous studies have indicated that the electroencephalographic pattern at the time of intervention is predictive of the probability of successful treatment. However, these findings are based on studies limited to the first 2h of SE onset. Little data is available on the efficacy of treating SE at later time points. METHODS: The aim of the present study was to investigate the efficacy of diazepam (DZP) treatment given at two different phases of SE in a lithium-pilocarpine rat model: during continuous ictal discharges (CIDs, phase 3), and during late periodic epileptiform discharges (late PEDs, phase 5). Changes in cortical and hippocampal electroencephalographs (EEGs) were observed continuously during the phases of SE, as well as at 24, 36, 48, and 72h after SE onset. The effects of DZP treatment during CIDs or during late PEDs were compared to control DZP-untreated rats. RESULTS: In all three groups, hippocampal and cortical EEGs displayed five distinct phases of SE. There were no statistical differences in the duration of phases 1 and 2 among the three groups. Although DZP administration during CIDs did not terminate CIDs in most rats, it did significantly shorten the duration of phases 3 and 4 of SE. Importantly, DZP given during phase 5 successfully ended behavioral and electrographic seizures in most rats. CONCLUSIONS: Hippocampal and cortical EEGs displayed five distinct phases of SE that were similarly responsive to DZP treatment. Termination of electrographic seizures with DZP treatment was more effective in the last phase of SE (late PEDs) than in phase 3 (CIDs). These findings suggest that previous reports of DZPs decrease in efficacy over time may not be applicable to DZP treatment at 4h-post onset.     

A potential model of pediatric posttraumatic epilepsy

Preclinical models of pediatric posttraumatic epilepsy (PTE) are lacking. We hypothesized that traumatic brain injury (TBI), induced by controlled cortical impact, in immature rats would cause electroencephalographic (EEG) epileptiform activity and behavioral seizures. TBI or sham craniotomy was performed on postnatal day 17. Using video-EEG monitoring 4–11 months post-TBI, most TBI rats (87.5%) showed EEG spiking and one had spontaneous, recurrent seizures. Controls showed neither EEG spikes nor electrographic/behavioral seizures. Late seizures were rare after TBI, but EEG spiking was common and may represent a surrogate for PTE.     

The EEG and Prognosis in Status Epilepticus

Summary: Purpose: To examine the relation between specific EEG features and clinical outcome, determine whether a predictable sequence of EEG patterns exists during status epilepticus (SE), and examine the relation between periodic epileptiform discharges (PEDs) and SE.
Methods: EEG records of 50 patients with SE admitted to Graduate Hospital between January 1990 and July 1995 were reviewed. Ictal EEGs were available in 72%; 28% had only postictal EEGs. Poor outcome was defined as death or persistent vegetative state, and good outcome as all others. Fisher's Exact test, x², and t tests were performed for data analysis.
Results: Of 50 patients, 72% had a good outcome and 28%, a poor outcome. If PEDs were present at any time during or after SE, outcome tended to be worse (p = 0.053). With PEDs, eight (44%) of 18 had a poor outcome; without PEDs, six (19%) of 32 had a poor outcome. Etiologies for SE did not substantially differ in patients with or without PEDs, and structural abnormalities were not more associated with the presence of PEDs. PEDs were seen both early and late, during and after SE. Other EEG characteristics (lateralized vs. bilateral symmetric ictal EEG, discrete vs. continuous ictal activity, and postictal focal slowing) did not relate to outcome. No predictable sequence of EEG changes was found during SE.
Conclusions: PEDs are the only EEG feature related to outcome in SE and are associated with poor outcome independent of etiology.     

Tetanus toxin-induced seizures in infant rats and their effects on hippocampal excitability in adulthood

A new experimental model of developmental epilepsy is reported. Behavioral and EEG features of seizures produced by unilateral intrahippocampal injection of tetanus toxin in postnatal day 9–11 rats, are described. Within 24–72 h of tetanus toxin injection, rat pups developed frequent and often prolonged seizures which included combinations of repetitive wet dog shakes, and wild running-jumping seizures. Intrahippocampal and cortical surface EEG recordings showed that coincident with these behaviors, electrographic seizures occurred not only in the injected hippocampus, but also in the contralateral hippocampus and bilaterally in the neocortex. Analysis of the interictal EEG revealed multiple independent spike foci. One week following tetanus toxin injection, the number of seizures markedly decreased; however, interictal spiking persisted. After injection rats were allowed to mature some were observed to have unprovoked behavioral seizures and/or epileptiform EEG activity. Mature animals were also studied using in vitro slice techniques. Recordings from hippocampal slices demonstrated spontaneous epileptiform burst discharges in the majority of rats which had tetanus toxin induced seizures as infants. These events occurred in area CA3 and consisted of interictal spikes and intracellularly recorded paroxysmal depolarization shifts (PDSs). On rarer occasions, electrographic seizures were recorded. The use of the tetanus toxin model in developing rats may facilitate a better understanding of the unique features of epileptogenesis in the developing brain and the consequences early-life seizures have on brain maturation and the genesis of epileptic conditions in later life.     

Aphasic status epilepticus: electroclinical correlation

Purpose: Aphasic status epilepticus (ASE) in otherwise awake patients is a rare phenomenon. We present a series of nine consecutive patients with ASE to characterize clinical, electrophysiologic, and imaging findings. Methods: Nine patients in ASE were identified between July 2006 and December 2009 at our institution. Each was evaluated by the neurology service and monitored with video‐electroencephalography (EEG) for at least 24 h. Thorough, repeated language testing was correlated with EEG findings. Key Findings: All nine patients were right‐handed with subacute or chronic left hemispheric lesions on magnetic resonance imaging (MRI). All patients had mixed aphasia, three presenting with persistent aphasia from onset and six with episodic speech impairment, which became persistent in five of the six. The initial 30‐min EEG demonstrated electrographic seizure in only five patients (56%), despite the presence of aphasia during the recording. Left hemispheric periodic lateralized epileptiform discharges (PLEDS) were seen in two patients, and left hemispheric slowing in two patients. Continuous video‐EEG monitoring confirmed electrographic seizure activity in all nine patients. Peak electrographic seizure frequency varied from continuous to once every 2 h and was not associated with fluctuations in the speech deficit. EEG seizures resolved abruptly in three patients and gradually over up to 4 days in six patients. Clinical improvement was delayed in eight of the nine patients, and four patients retained some aphasia at discharge, 2–4 days after EEG seizure resolution. Significance: Standard EEG is sensitive for detection of abnormalities in the dominant hemisphere in patients with ASE. However, continuous EEG is necessary to confirm the diagnosis and monitor treatment, since clinical symptoms do not correlate with electrographic seizure activity and do not provide sufficient information to guide treatment decisions.     

Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801, diazepam, or MK-801 plus diazepam

Pharmacologic control of refractory status epilepticus has been little-studied in experimental models. In this experiment, rats in status epilepticus induced by lithium and pilocarpine were treated with MK-801 alone, diazepam alone or MK-801 plus diazepam, with treatment begun at a time when this model of status is refractory to anticonvulsant drugs. EEG samples were digitized before and for two hours after treatment, and the digitized samples subjected to computerized frequency analysis. MK-801 plus diazepam halted all manifestations of status epilepticus. Although neither MK-801 alone nor diazepam alone stopped the ongoing electrographic status epilepticus, both drugs diminished motor seizures and total EEG power. MK-801 treatment prevented the progression of changes in EEG pattern which normally occurs in this model of status epilepticus, while diazepam did not. MK-801, with and without diazepam, allowed the rats to survive the episode of status epilepticus, but rats treated with MK-801 alone required several days to recover completely, while the MK-801 plus diazepam rats appeared normal the next day. MK-801 may be a useful agent for treatment of human refractory status epilepticus, because of its neuroprotective action as well as its ability to potentiate GABAergic drugs.     

The EEG of status epilepticus.

SUMMARY: Gastaut noted that there are as many forms of status epilepticus (SE) as there are seizure types. The pleomorphic EEG patterns reflect this wide variety of clinical types. The different electroclinical types of status epilepticus share EEG characteristics including rhythmic activity, epileptiform discharges, and often a waxing and waning evolution. Gray zones of interpretation exist in the form of runs of epileptiform periodic discharges, typically of lower frequency, and lesser temporal variability. In diagnosing SE, clinical correlation and response to parenteral anti-epileptic drugs (AEDs) are of particular importance. Accurate diagnosis of electroclinical SE type is essential, because it determines prognosis and dictates the intensity of therapeutic management. Some patients with benign forms of SE may benefit from nonparenteral treatment, and be followed up clinically and by spot EEGs. Conversely, intensive care unit management with anesthesia and continuous monitoring, and parenteral AEDs may be required for refractory convulsive SE.     

Treatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466

Purpose:  Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine-sensitive GABA_A receptors are progressively internalized with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad-spectrum anticonvulsants, could be more effective treatments for status epilepticus. We assessed the ability of the noncompetitive AMPA receptor antagonist GYKI 52466 to protect against kainic acid–induced status epilepticus in mice.
Methods:  Groups of animals treated with kainic acid received GYKI 52466 (50 mg/kg followed in 15 min by 50 mg/kg) or diazepam (25 mg/kg followed in 20 min by 12.5 mg/kg) beginning at 5 min of continuous seizure activity or 25 min later. The duration of seizure activity was determined by EEG recording from epidural cortical electrodes.
Results:  Both GYKI 52466 and diazepam rapidly terminated electrographic and behavioral seizures when administered early. However, diazepam-treated animals exhibited more seizure recurrences. With late administration, GYKI 52466 also rapidly terminated seizures and they seldom recurred, whereas diazepam was slow to produce seizure control and recurrences were common. Although both treatments caused sedation, GYKI 52466-treated animals retained neurological responsiveness whereas diazepam-treated animals did not. GYKI 52466 did not affect blood pressure whereas diazepam caused a sustained drop in mean arterial pressure.
Discussion:  Noncompetitive AMPA receptor antagonists represent a promising approach for early treatment of status epilepticus; they may also be effective at later times when there is refractoriness to benzodiazepines.     

The susceptibility of rats to pilocarpine-induced seizures is age-dependent

Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydrochloride were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral patterns in developing rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoclonic movements of the limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense behavioral signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12-day-old-rats. The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocampus and cortex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings during the second week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pilocarpine, 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered in 15-21-day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to motor limbic seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased susceptibility to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs, and an increased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced convulsions high voltage fast activity superposed over hippocampal theta-rhythm, progressed into high voltage spiking and spread to cortical records. The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morphological analysis of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage or an attenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological breakdown was seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in the substantia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was present in 4-5-week-old rats.(ABSTRACT TRUNCATED AT 400 WORDS)     

Potentiation of kainic acid epileptogenicity and sparing from neuronal damage by an NMDA receptor antagonist

The time course and severity of the excitotoxic syndrome induced in rats by s.c. injection of 10 mg/kg kainic acid (KA) was modified by pretreatment with MK801, a non-competitive inhibitor of the NMDA receptor, at doses of 0.1, 1 and 10 mg/kg. A dose-dependent increase in the severity of the KA-induced electrographic (EEG) manifestations of epilepsy was seen after MK801. This consisted of an earlier appearance and higher number of EEG seizures, longer time spent in seizures, and an earlier onset of status epilepticus. In contrast, behavioral seizures were increased only in the 0.1 mg/kg MK801 group, but abolished by higher doses. On the contrary, wet dog shakes were progressively reduced with increasing doses of MK801. Four of the 9 animals receiving KA-only group and 3 of the 10 animals in the 1 and 10 mg MK801 groups were sacrificed 5 days after KA. The brain of the KA-only rats presented diffuse gross and microscopic evidence of hemorrhagic necrosis and neuronal damage; the MK801 rats showed only minimal neuronal loss in the CA3 hippocampal sector. This study demonstrates that neuronal damage and epileptiform activity can be dissociated. Furthermore, it confirms the protective effect of MK801 against neuronal damage caused by multiple factors. Lastly, it emphasizes the need for EEG monitoring in order to accurately assess any epileptic/antiepileptic effect.     

Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats.

Lithium is known to potentiate the ability of pilocarpine to induce status epilepticus in rats. The goal of this study was to determine whether lithium could potentiate pilocarpine-induced seizures in developing animals. Behavioral, electroencephalographic (EEG), and histopathological changes induced by systemic administration of lithium (3 meq/kg) followed 20 h later by pilocarpine (3, 10, 30, 60 mg/kg) were studied in 3-30-day-old rats. Lithium followed by pilocarpine (30 and 60 mg/kg) induced hyperactivity, tremor, loss of postural control and scratching but no electrographic seizures in 3-8-day-old rats. In the 7-10-day-old animals pretreatment with lithium and pilocarpine 60 mg/kg induced status epilepticus with sustained myoclonus and continuous bilateral synchronous spike and sharp wave, but doses of pilocarpine lower than 60 mg/kg had no effect. The susceptibility to lithium-pilocarpine-induced status epilepticus increased markedly during the third postnatal week of life. During this time period, rats treated with lithium (3 meq/kg) plus pilocarpine 10 mg/kg exhibited behavioral and EEG manifestations of status epilepticus. The same combination of lithium and pilocarpine failed to induce status epilepticus either before or after the third week of life. Histopathological analysis of the brains of the animals used in these studies failed to demonstrate the widespread damage reported in adult rats that have undergone lithium-pilocarpine-induced status epilepticus.     

Different behavioral and electrographic effects of acoustic stimulation and dibutyryl cyclic AMP injection into the inferior colliculus in normal and in genetically epilepsy-prone rats

The behavioral and electrographic effects of acoustic stimulation (100 dB) and injection of dibutyryl cyclic AMP (cAMP, 10 nmol) into the inferior colliculus were studied in normal and genetically epilepsy-prone (GEPR-9) rats. Acoustic stimulations induced behavioral seizures only in GEPR-9 rats; the seizures were associated with electrographic epileptiform discharges recorded from the inferior colliculus. Injections of dibutyryl cAMP into the inferior colliculus caused wild running episodes resembling the initial phase of audiogenic seizures in both groups. However, in GEPR-9 rats these episodes progressed to significantly more severe seizures than in normal rats and the convulsions culminated into status epilepticus. During drug-induced seizures, epileptiform activity was present in the inferior colliculus in both groups. The seizure generalization latency was markedly shorter in GEPR-9 rats than in normals. Furthermore, in GEPR-9 rats, the seizure generalization latency was in the same range with either acoustic stimulation-induced or dibutyryl cAMP-induced seizures. The data suggest that the increased susceptibility of genetically epilepsy-prone rats to acoustic stimuli may be related to a malfunction of the cyclic AMP system within the inferior colliculus.     

Continuous EEG predictors of outcome in patients with altered sensorium

PurposeTo evaluate EEG predictors of outcome in patients with altered sensorium suspected to have seizure and to assess whether short term EEG is as effective as long term continuous EEG (cEEG) in predicting the outcome of patients with altered sensorium due to neurological causes.MethodsWe identified 99 consecutive critically ill patients with altered sensorium in whom nonconvulsive seizures were suspected. They underwent cEEG. Functional outcome was assessed with the modified Rankin Scale (mRS) at 4 weeks, discharge or death. We compared efficacy of short term EEG and long term continuous EEG in recording the abnormal patterns on EEG. Logistic regression analysis was performed to identify EEG findings associated with poor outcome, defined as mRS 4–6 (dead or moderately to severely disabled).ResultsPoor outcome was associated with nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), periodic lateralized epileptiform discharges (PLEDS), PLEDS plus, generalized periodic epileptiform discharges (GPEDS) and abnormal EEG background. Short term EEG can detect seizure activity and other electrographic markers of poor outcome but the values are statistically insignificant.ConclusioncEEG monitoring provides independent prognostic information in patients with altered sensorium and suspected seizures. Unfavorable findings include nonconvulsive seizures, periodic epileptiform discharges and abnormal background. Short term EEG is ineffective in detecting seizures on EEG in patients with altered sensorium and should not be used as substitute for Long term EEG