Spread of epileptiform potentials in the neocortical slice: recordings with voltage-sensitive dyes

The spread of epileptiform potentials in guinea pig neocortical slices was investigated by use of voltage sensitive dyes and a fast optical recording technique. Epileptiform activity was induced in a perfusion medium containing 10–20 μM bicuculline-methiodide and by single pulse stimulation of layer I or the white matter. The location of minimal and maximal amplitudes, the shape of the potentials at specific sites and the velocity of spread were independent from the specific stimulation site. The expression of epileptiform activity appeared to depend on specific, possibly geometrical, properties of the tissue.     

A method for detecting epileptic seizures.

A simple instrument for detecting seizures is described. Vibrations of the bed due to movements of the patient were converted to electrical oscillations by movement of a loudspeaker coil in reversed mode as transducer. To distinguish between normal movements and those caused by a seizure, three criteria were used--the amplitude of the oscillations, the time interval between them, and the duration of a burst of oscillations, each parameter compared with a reference value for each patient.     

Predictors of seizures during pregnancy in women with epilepsy

We aimed to characterize the seizure pattern during pregnancy in a large cohort of women with epilepsy (WWE) and identify possible predictors of seizure relapse during pregnancy. We recorded the antiepileptic drug (AED) use and seizure frequency for WWE during the prepregnancy month and pregnancy. The seizure profile was correlated with the clinical details and seizure type as abstracted from the clinical records maintained in the registry. Of the 1,297 pregnancies in WWE with complete seizure data, 47.8% were seizure-free during pregnancy. Seizure relapse was highest during the three peripartum days. Women with partial seizures-had higher risk of relapse (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0) than those with generalized seizures. They had two peaks of seizure relapse (second to third month and sixth month). Those with generalized seizures had one peak at first trimester. Those who were on polytherapy had increased risk of seizures (OR 2.98, 95% CI 2.3-3.9) when compared to those on monotherapy. Those who had seizures in the prepregnancy month had higher risk (OR 15, 95% CI 9-25.1) of seizures during pregnancy when compared to those who were seizure-free during that period. On multiple logistic regression, prepregnancy seizure was the most important predictor of seizures during pregnancy.     

Optical recording of cortical activity after in vitro perfusion of cerebral arteries with a voltage-sensitive dye

Cortical neuronal architecture and connectivity can be analyzed with high-resolution optical imaging after staining the in vitro isolated guinea pig brain preparation by circulating the voltage-sensitive dye RH795 via the arterial system. To establish this new technique, electrical field potentials evoked in the piriform and entorhinal cortices by lateral olfactory tract stimulation were correlated to the optical signal. The depth analysis of the optical response was performed by evaluating the contribution of the mono- and poly-synaptic components of the signal generated in different layers after applying a pair-pulse stimulation protocol. The tangential propagation of neuronal activity in olfactory cortices was evaluated by gathering several 4.2 x 4.2 mm images recorded from adjacent cortical areas. The real-time optical imaging technique applied to the isolated guinea pig brain can be successfully utilized to study the integrative properties of cortical neurons ensembles.     

Characteristics and clinical significance of subclinical seizures

Purpose: To define characteristics of subclinical seizures (SCS) and their prognostic significance after epilepsy surgery. Methods: Reports from intracranial video‐EEG monitoring were reviewed for patients who had epilepsy surgery between 1989 and 2003. Relationships between SCS and clinical seizures were categorized as either: complete colocalization (Group A), when both SCS and clinical seizures originated from the same single focus, or incomplete and no colocalization (Group B), when some or all SCS and clinical seizures originated from different foci in different lobes or hemispheres. Results: A total of 111 patients were included in this review. Seventy‐one (64%) patients had 2,821 SCS and most SCS came from the mesial temporal lobe. The mean duration of SCS was shorter than complex partial seizures and generalized tonic–clonic seizures but similar to simple partial seizures. SCS rarely propagated beyond the site of origin and the majority of SCS had the same area of origin as clinical seizures. Sixty‐five patients had both SCS and clinical seizures and underwent resective surgery. Group A patients had a higher seizure‐free outcome rate (77.5%) than Group B patients (37.5%). The colocalization rate of SCS and clinical seizures may impact seizure‐free outcome. The presence or absence of SCS, SCS duration, and extent of propagation of SCS did not influence surgical outcome. Conclusion: SCS commonly originate from the same cortical area as clinical seizures and are related to postsurgical outcome. These findings suggest they should be viewed as having similar significance in the surgical decision process as clinical seizures.     

In vivo modulation of hippocampal epileptiform activity with radial electric fields

PURPOSE: Electric field stimulation can interact with brain activity in a subthreshold manner. Electric fields have been previously adaptively applied to control seizures in vitro. We report the first results from establishing suitable electrode geometries and trajectories, as well as stimulation and recording electronics, to apply this technology in vivo. METHODS: Electric field stimulation was performed in a rat kainic acid injection seizure model. Radial electric fields were generated unilaterally in hippocampus from an axial depth electrode. Both sinusoidal and multiphasic stimuli were applied. Hippocampal activity was recorded bilaterally from tungsten microelectrode pairs. Histologic examination was performed to establish electrode trajectory and characterize lesioning. RESULTS: Electric field modulation of epileptiform neural activity in phase with the stimulus was observed in five of six sinusoidal and six of six multiphasic waveform experiments. Both excitatory and suppressive modulation were observed in the two experiments with stimulation electrodes most centrally placed within the hippocampus. Distinctive modulation was observed in the period preceding seizure-onset detection in two of six experiments. Short-term histologic tissue damage was observed in one of six experiments associated with high unbalanced charge delivery. CONCLUSIONS: We demonstrated in vivo electric field modulation of epileptiform hippocampal activity, suggesting that electric field control of in vivo seizures may be technically feasible. The response to stimulation before seizure could be useful for triggering control systems, and may be a novel approach to define a preseizure state.     

Predicting psychogenic nonepileptic seizures with the Personality Assessment Inventory and seizure variables

Early identification of likely cases of psychogenic nonepileptic seizures may prompt earlier and more appropriate diagnosis and treatment. This study investigated the validity of multiple independent self-report variables in predicting psychogenic nonepileptic versus epileptic seizures. One hundred forty-three patients with psychogenic nonepileptic seizures and 129 patients with epileptic seizures were compared with the Personality Assessment Inventory, age at seizure onset, years since first seizure, and length of seizures. Diagnostic prediction was made by analyses of variance and logistic regressions. Cut scores were developed for the multivariate predictors with maximal sensitivity and specificity. The Personality Assessment Inventory conversion subscale (SOM-C), years since first seizure, and length of seizures provided 84% correct classification. Ninety-six percent of patients meeting cut scores of SOM-C ≥ 70, years since first seizure ≤ 8, and length of seizures ≥ 3 minutes were diagnosed with psychogenic nonepileptic seizures. Results demonstrated good ability to identify likely cases of psychogenic nonepileptic seizurs by multiple predictors that are easily and cost-effectively obtainable.     

The experience of earthquakes by patients with epileptic and psychogenic nonepileptic seizures

PURPOSE: We sought to understand better the experience of seizures by studying differences in the subjective experience of being in an earthquake between patients with epileptic (EP) and nonepileptic (NES) seizures. METHODS: Forty-eight patients with CCTV/EEG-documented EP or NES who were in the Seattle metropolitan area during the February 28, 2001 Nisqually earthquake were randomly selected for telephone interviews on their earthquake experiences, including whether they thought they were having a seizure during the event. RESULTS: Twenty-three percent of EP patients spontaneously volunteered that they initially thought they were having a seizure during the earthquake as compared with none of the NES individuals (p = 0.03). However, 35% of EP and 23% of NES patients thought they were having a seizure during it when asked directly (p = 0.37). The most common reasons given, regardless of seizure type, were shaking and feelings of losing control. Of those responding negatively, 100% of EP and 47% of NES patients said that movement of their environment indicated that it was not a seizure (p = 0.001). EP patients took an average of 42 s to realize that the earthquake was not a seizure compared with 105 s for the NES group (p = 0.06). The earthquake precipitated seizures in both groups (11.5% EP, 9.1% NES). CONCLUSIONS: EP patients were more likely to mistake the earthquake spontaneously for a seizure. This indicates these two experiences are similar and provides a glimpse into the subjective experience of a seizure for those who have never had one but have experienced an earthquake.     

A reduction of sleep spindles heralds seizures in focal epilepsy

ObjectivesSleep has profound effects on epilepsy. It may alter the occurrence of interictal discharges (IEDs) and seizures. Vice versa, an active epilepsy changes sleep. Sleep spindles are typically associated with an increase of IEDs. We examined whether seizures change the number and power of spindles preceding nightly seizures.MethodsWe retrospectively examined the nightly EEG recordings of presurgical epilepsy patients from our EEG-video-monitoring unit. We evaluated the 200 s before the EEG seizure onset for spindle density (spindles per minute) and spindle power and compared that to the interictal baseline sleep.ResultsThe spindle density and the spindle power decreased significantly before the first seizure. The reduction before secondarily generalized seizures (8.7 ± 2.5; p = 0.001) was more pronounced than before focal seizures (10.5 ± 2.5; p = 0.003) compared to baseline (12.2 ± 2.7). This finding was more pronounced in extratemporal lobe epilepsies than in temporal lobe epilepsies. The reduction of spindle power was also significant and was more pronounced in XTLE. These results were consistent for all other seizures during sleep, the mean spindle density decreased significantly in all focal (10.2 ± 1.9; p = 0.001) and generalized preictal period (8.8 ± 2.4; p = 0.001) compared to the mean interictal period (12.1 ± 2.1). These were also more significant in XTLE than TLE group.ConclusionsOur data demonstrate that the occurrence of seizures and propensity of seizure generalisation in focal epilepsy is modulated by specific characteristics of light sleep such as sleep spindles.SignificanceThis study supports the notion that changes in the epileptic network precede the seizure onset and have an influence on seizure generation and termination.     

The vital dye Evans blue mimics limbic seizures induced by kainate or pilocarpine

Evans blue dye, given i.c.v. in rats in a dose of 208 nmol, causes electrical and behavioural seizures which resemble those induced by the glutamate analogue, kainate, or by electrical kindling of the amygdala. Chicago sky blue, 201 nmol i.c.v., produces similar seizures. The principal elements of the seizures are wet-rat-shakes, facial and forelimb clonus, rearing and spike-and-waves in the EEG. A non-NMDA receptor antagonist, GYKI 52466 and a benzodiazepine, diazepam, significantly delay the onset to the occurrence of the first forelimb clonus. The cholinergic antagonist, scopolamine, significantly reduces the delay to onset of first facial clonus. The competitive NMDA receptor antagonist, d-CPPene, the non-specific dopamine antagonist, haloperidol, and the purinergic agonist, 2-chloroadenosine, have no effect on the measured parameters. During the induction of seizures by Evans blue, the average extracellular glutamate concentration in hippocampus or cortex does not increase statistically significantly in comparison to pre-seizure values. Histological examination of limbic areas indicates that the moderate to severe Evans blue-induced cell damage is similar to that seen after limbic seizures induced by pilocarpine and in the hippocampus is partially preventable by d-CPPene but not by diazepam or GYKI 52466. It is proposed that Evans blue-induced seizures may be useful as a new model for studying the mechanisms of intractable epilepsy of the complex partial seizure type. © 1997 Elsevier Science B.V. All rights reserved.     

Brief seizures cause dendritic injury

Seizures may directly cause brain injury by disrupting the structure and function of synapses. Previous studies using in vivo time-lapse imaging have demonstrated an acute beading of dendrites and loss of dendritic spines immediately following status epilepticus, but the effects of brief seizures and the long-term evolution of this dendritic injury are unknown. Here, we examined the effects of seizures of varying durations on dendritic structure over several weeks using in vivo multiphoton imaging with kainate-induced seizures in mice. The degree of dendritic injury was directly dependent on the duration of the seizures, with seizures lasting more than 30 min (status epilepticus) resulting in a greater than 75% spine loss. However, even brief seizures (< 5 min) induced moderate dendritic beading and spine loss. The dendritic injury from brief seizures usually recovered within 2 weeks, whereas status epilepticus-induced injury only partially reversed. These studies demonstrate that seizures of all durations may trigger at least transient neuronal injury.     

Adult-onset seizures in a patient with Down syndrome and portosystemic shunt

Objective: The prevalence of epilepsy in patients with Down syndrome (DS) is 5–13%, which is higher than the prevalence in the general population. Transient hyperammonemia is often observed following seizure, but it typically resolves within a day. Here, we describe the case a 37-year-old woman who had DS and a history of adult-onset epilepsy and was admitted to our hospital with recurrent seizures. After admission, her ammonia levels fluctuated without any apparent cause, and dynamic computed tomography revealed a portosystemic shunt. The findings suggest that her seizures possibly precipitated from hyperammonemia secondary to a portosystemic shunt, and we reviewed the relevant literature. Methods: We conducted PubMed, Web of Science, and EMBASE searches without language restrictions for articles published between 1970 and February 2013. Results: In addition to the present case, 7 cases were ultimately included in this review. Four patients were newborns, 2 patients were 1 month old, and 1 patient was 3 years old. No adult cases were described until now. Conclusion: Adult patients with DS diagnosed with epilepsy are not routinely assessed for portosystemic venous shunts. Measuring ammonia levels in patients with DS the day after admission would help detect portosystemic shunts, even if the patients have been previously diagnosed with epilepsy. Practice Implications: If ammonia levels fluctuate without any apparent cause after seizure, dynamic computed tomography should be performed, especially for patients with DS, whether or not they have been previously diagnosed with epilepsy.     

A pediatric case of transient periictal MRI abnormalities after repeated seizures

BackgroundTransient periictal MRI abnormalities (TPMA) are caused by seizures, and may completely or partially reverse within a few days following seizure. Although TPMA are usually observed in patients with status epilepticus (SE), they have also been rarely reported after isolated/recurrent seizures not fulfilling the criteria for SE. Herein, we present a case of a 1-year-old girl with TPMA.CaseA 1-year-old girl with Apert syndrome and epilepsy showed MRI abnormalities in the cortico-subcortical areas of the left temporal, occipital and parietal lobes, as well as the left thalamus. These abnormalities showed as a hyperintense signal on diffusion-weighted imaging and a hypointense signal on apparent-diffusion coefficient maps. On follow-up MRI after 3 days, the abnormal signals were completely reversed. We confirmed TPMA after eliminating other possibilities. When treatment was withdrawn, the patient regained consciousness immediately and did not show any abnormality on subsequent MRI.ConclusionTPMA may occur in young children; recognizing this possibility is important for making the diagnosis and conducting appropriate treatment. As a previous study revealed, the distribution of signal changes in cortico-subcortical areas and the ipsilateral thalamus may be a characteristic feature of TPMA.     

The diagnostic value of oral lacerations and incontinence during convulsive "seizures"

Purpose: Oral lacerations and urinary incontinence have long been considered useful clinical features for the diagnosis of epileptic seizures; however, both are also reported in patients with psychogenic nonepileptic seizures (PNES). The aims of the study were (1) to investigate whether the presence and nature of oral lacerations or incontinence during convulsive seizures of patients with epilepsy differed from those with PNES, and (2) whether the side of the oral laceration has any correlation with the epilepsy syndrome or lateralization.
Methods: Eighty-four consecutive patients who experienced at least one convulsive event during video-EEG monitoring (VEM) were questioned and examined for oral lacerations and incontinence. Seizure classification was determined by a team of epileptologists based on the VEM findings and other clinical and investigational data, blinded to the oral laceration and incontinence information.
Results: The presence of oral lacerations among patients with epileptic seizures was 26% (17/66), in contrast it was 0% (0/18) with PNES (p = 0.01). Of the oral lacerations sustained by patients during an epileptic seizure, 14 were to the side of the tongue, one to the tip of the tongue, two to the cheek, and three to the lip. No significant relationships were observed between seizure lateralization and oral lacerations. Incontinence occurred in 23% (15/66) of epilepsy patients and 6% (1/18) of PNES patients (p = 0.09). There was no relationship between epilepsy type or lateralization and the prevalence of incontinence.
Conclusions: Despite frequent reports of oral lacerations and incontinence by patients with PNES, objective evidence for this is highly specific to convulsive epileptic seizures.     

Epileptic seizures in thrombotic stroke

Summary Epileptic seizures due to thrombotic cerebral infarction were studied in 118 patients. The occurrence of seizures had a bimodal distribution with one peak period within 2 weeks and another peak period from 6 to 12 months after stroke. Four patients had seizures preceding stroke, while 23 patients without a history of previous stroke had silent infarct on the CT scan. Fifteen patients (13%) had status epilepticus. Simple partial seizures occurred in 56% of patients, complex partial seizures in 24% and generalized tonic-clonic seizures in 4%. Epilepsy developed in 35% of patients with early seizures and in 90% of patients with late seizures.     

The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis

PURPOSE: Mesial temporal sclerosis (MTS) is the most common and important pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance imaging (MRI) scans is strongly correlated with a successful surgical outcome. Despite the general assumption that patients with MTS respond poorly to medication, the long-term prognosis for such patients has not yet been investigated. We studied the overall clinical prognosis of patients with MTS and analyzed the factors related to the degree of medical responsiveness. METHODS: Case patients were actively followed up at the Yonsei Epilepsy Clinic in Seoul, Korea, for >2 years. A structured interview and a thorough clinical evaluation were conducted. MRI scans, at the field strength of 1.0 or 1.5 Tesla, were performed with T1- and T2-weighted coronal and axial spin-echo images. All coronal slices were < or = 5-mm thick with no gap. Two neurologists and one radiologist determined the presence of MTS in MRIs by visual analysis. RESULTS: The MTS group consisted of 104 patients. Of these, 26 (25%) were completely controlled with adequate therapy, and 40 (38%) were intractable, despite aggressive anticonvulsant polytherapy. The remaining 37% had their seizure frequencies reduced by > or = 50%, but were not seizure free. The age of seizure onset was significantly younger in the intractable group than in the well-controlled group. Patients with a history of febrile convulsions or with epileptiform discharges in their electroencephalogram (EEG) had poorer seizure control (p < 0.05) than those who did not. Among the 16 patients who had no previous treatment, five (31%) became seizure free, and two were intractable. CONCLUSIONS: Not all patients with MTS are medically intractable; 25% of the patients in our study achieved complete control while receiving medication. Poor seizure control was related to an early age of seizure onset, a history of febrile convulsions, and epileptiform discharges on the EEG.