Continuous Video-electroencephalography Monitoring Research Articles

Plasma neurofilament heavy chain is a prognostic biomarker for the development of severe epilepsy after experimental traumatic brain injury.

This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF-H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy. Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF-H by enzyme-linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video-electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T2 magnetic resonance imaging were performed to assess comorbidities and lesion severity. Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI-). Plasma pNF-H concentrations were higher in TBI+ rats than in TBI- rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF-H concentration distinguished TBI+ rats from TBI- rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF-H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF-H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF-H concentration on D2 correlated with greater T2 signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF-H concentration on D2 did not correlate with Morris water maze performance on D37-D39. Plasma pNF-H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.

E2730, an uncompetitive γ-aminobutyric acid transporter-1 inhibitor, suppresses epileptic seizures in a rat model of chronic mesial temporal lobe epilepsy.

More than one third of mesial temporal lobe epilepsy (MTLE) patients are resistant to current antiseizure medications (ASMs), and half experience mild-to-moderate adverse effects of ASMs. There is therefore a strong need to develop and test novel ASMs. The objective of this work is to evaluate the pharmacokinetics and neurological toxicity of E2730, a novel uncompetitive inhibitor of γ-aminobutyric acid transporter-1, and to test its seizure suppression effects in a rat model of chronic MTLE. We first examined plasma levels and adverse neurological effects of E2730 in healthy Wistar rats. Adult male rats were implanted with osmotic pumps delivering either 10, 20, or 100 mg/kg/day of E2730 subcutaneously for 1 week. Blood sampling and behavioral assessments were performed at several timepoints. We next examined whether E2730 suppressed seizures in rats with chronic MTLE. These rats were exposed to kainic acid-induced status epilepticus, and 9 weeks later, when chronic epilepsy was established, were assigned to receive one of the three doses of E2730 or vehicle for 1 week in a randomized crossover design. Continuous video-electroencephalographic monitoring was acquired during the treatment period to evaluate epileptic seizures. Plasma levels following continuous infusion of E2730 showed a clear dose-related increase in concentration. The drug was well tolerated at all doses, and any sedation or neuromotor impairment was mild and transient, resolving within 48 h of treatment initiation. Remarkably, E2730 treatment in chronically epileptic rats led to seizure suppression in a dose-dependent manner, with 65% of rats becoming seizure-free at the highest dose tested. Mean seizure class did not differ between the treatment groups. This study shows that continuous subcutaneous infusion of E2730 over 7 days results in a marked, dose-dependent suppression of spontaneous recurrent seizures, with minimal adverse neurological effects, in a rat model of chronic MTLE. E2730 shows strong promise as an effective new ASM to be translated into clinical trials.

Acute Hippocampal Damage as a Prognostic Biomarker for Cognitive Decline but Not for Epileptogenesis after Experimental Traumatic Brain Injury

It is necessary to develop reliable biomarkers for epileptogenesis and cognitive impairment after traumatic brain injury when searching for novel antiepileptogenic and cognition-enhancing treatments. We hypothesized that a multiparametric magnetic resonance imaging (MRI) analysis along the septotemporal hippocampal axis could predict the development of post-traumatic epilepsy and cognitive impairment. We performed quantitative T2 and T2* MRIs at 2, 7 and 21 days, and diffusion tensor imaging at 7 and 21 days after lateral fluid-percussion injury in male rats. Morris water maze tests conducted between 35-39 days post-injury were used to diagnose cognitive impairment. One-month-long continuous video-electroencephalography monitoring during the 6th post-injury month was used to diagnose epilepsy. Single-parameter and regularized multiple linear regression models were able to differentiate between sham-operated and brain-injured rats. In the ipsilateral hippocampus, differentiation between the groups was achieved at most septotemporal locations (cross-validated area under the receiver operating characteristic curve (AUC) 1.0, 95% confidence interval 1.0-1.0). In the contralateral hippocampus, the highest differentiation was evident in the septal pole (AUC 0.92, 95% confidence interval 0.82-0.97). Logistic regression analysis of parameters imaged at 3.4 mm from the contralateral hippocampus's temporal end differentiated between the cognitively impaired rats and normal rats (AUC 0.72, 95% confidence interval 0.55-0.84). Neither single nor multiparametric approaches could identify the rats that would develop post-traumatic epilepsy. Multiparametric MRI analysis of the hippocampus can be used to identify cognitive impairment after an experimental traumatic brain injury. This information can be used to select subjects for preclinical trials of cognition-improving interventions.

Susceptibility to epilepsy after traumatic brain injury is associated with preexistent gut microbiome profile.

We examined whether posttraumatic epilepsy (PTE) is associated with measurable perturbations in gut microbiome. Adult Sprague Dawley rats were subjected to lateral fluid percussion injury (LFPI). PTE was examined 7months after LFPI, during 4-week continuous video-electroencephalographic monitoring. 16S ribosomal RNA gene sequencing was performed in fecal samples collected before LFPI/sham-LFPI and 1week, 1 month, and 7months thereafter. Longitudinal analyses of alpha diversity, beta diversity, and differential microbial abundance were performed. Short-chain fatty acids (SCFAs) were measured in fecal samples collected before LFPI by liquid chromatography with tandem mass spectrometry. Alpha diversity changed over time in both LFPI and sham-LFPI subjects; no association was observed between alpha diversity and LFPI, the severity of post-LFPI neuromotor impairments, and PTE. LFPI produced significant changes in beta diversity and selective changes in microbial abundances associated with the severity of neuromotor impairments. No association between LFPI-dependent microbial perturbations and PTE was detected. PTE was associated with beta diversity irrespective of timepoint vis-à-vis LFPI, including at baseline. Preexistent fecal microbial abundances of four amplicon sequence variants belonging to the Lachnospiraceae family (three enriched and one depleted) predicted the risk of PTE, with area under the curve (AUC) of .73. Global SCFA content was associated with the increased risk of PTE, with AUC of .722, and with 2-methylbutyric (depleted), valeric (depleted), isobutyric (enriched), and isovaleric (enriched) acids being the most important factors (AUC = .717). When the analyses of baseline microbial and SCFA compositions were combined, AUC to predict PTE increased to .78. Whereas LFPI produces no perturbations in the gut microbiome that are associated with PTE, the risk of PTE can be stratified based on preexistent microbial abundances and SCFA content.

Incidence of Electrographic Seizures in Patients With COVID-19.

Critical illness and sepsis are commonly associated with subclinical seizures. COVID-19 frequently causes severe critical illness, but the incidence of electrographic seizures in patients with COVID-19 has been reported to be low. This retrospective case series assessed the incidence of and risks for electrographic seizures in patients hospitalized with COVID-19 who underwent continuous video electroencephalography monitoring (cvEEG) between March 1st, 2020 and June 30th, 2020. One hundred and twenty-two patients were initially identified who resulted SARS-CoV-2 nasopharyngeal RT-PCR swab positivity with any electroencephalography order placed in the EMR. Seventy-nine patients met study inclusion criteria: age ≥18 years, >1 h of cvEEG monitoring, and positive SARS-CoV-2 nasopharyngeal swab PCR. Six (8%) of the 79 patients suffered electrographic seizures (ES), three of whom suffered non-convulsive status epilepticus. Acute hyperkinetic movements were the most common reason for cvEEG in patients with ES (84%). None of the patients undergoing cvEEG for persistent coma (29% of all patients) had ES. Focal slowing (67 vs. 10%), sporadic interictal epileptiform discharges (EDs; 33 vs. 6%), and periodic/rhythmic EDs (67 vs. 1%) were proportionally more frequent among patients with electrographic seizures than those without these seizures. While 15% of patients without ES had generalized periodic discharges (GPDs) with triphasic morphology on EEG, none of the patients with ES had this pattern. Further study is required to assess the predictive values of these risk factors on electrographic seizure incidence and subsequent outcomes.

Preictal state detection using prodromal symptoms: A machine learning approach.

A reliable identification of a high-risk state for upcoming seizures may allow for preemptive treatment and improve the quality of patients' lives. We evaluated the ability of prodromal symptoms to predict preictal states using a machine learning (ML) approach. Twenty-four patients with drug-resistant epilepsy were admitted for continuous video-electroencephalographic monitoring and filled out a daily four-point questionnaire on prodromal symptoms. Data were then classified into (1) a preictal group for questionnaires completed in a 24-h period prior to at least one seizure (n1 =58) and (2) an interictal group for questionnaires completed in a 24-h period without seizures (n2 =190). Our prediction model was based on a support vector machine classifier and compared to a Fisher's linear classifier. The combination of all the prodromal symptoms yielded a good prediction performance (area under the curve [AUC]=.72, 95% confidence interval [CI] = .61-.81). This performance was significantly enhanced by selecting a subset of the most relevant symptoms (AUC=.80, 95% CI = .69-.88). In comparison, the linear classifier systematically failed (AUCs<.6). Our findings indicate that the ML analysis of prodromal symptoms is a promising approach to identifying preictal states prior to seizures. This could pave the way for development of clinical strategies in seizure prevention and even a noninvasive alarm system.

Anticonvulsant and antiepileptogenic effects of system inactivation in chronic epilepsy models.

The cystine/glutamate antiporter system could represent a new target for antiepileptogenic treatments due to its crucial roles in glutamate homeostasis and neuroinflammation. To demonstrate this, we compared epilepsy development and seizure susceptibility in xCT knockout mice (xCT-/- ) and in littermate controls (xCT+/+ ) in different chronic models of epilepsy. Mice were surgically implanted with electrodes in the basolateral amygdala and chronically stimulated to develop self-sustained status epilepticus (SSSE); continuous video-electroencephalography monitoring was performed for 28days after SE and hippocampal histopathology was assessed. Corneal kindling was induced by twice daily electrical stimulation at 6Hz and maintenance of the fully kindled state was evaluated. Next, messenger RNA (mRNA) and protein levels of xCT and of the proteins involved in the phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase 3β (GSK-3β)/eukaryotic initiation factor 2α (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway were measured at different time points during epileptogenesis in NMRI mice treated with pilocarpine. Finally, the anticonvulsant effect of sulfasalazine (SAS), a nonselective system inhibitor, was assessed against 6Hz-evoked seizures in pilocarpine-treated mice. In the SSSE model, xCT-/- mice displayed a significant delayed epileptogenesis, a reduced number of spontaneous recurrent seizures, and less pronounced astrocytic and microglial activation. Moreover, xCT-/- mice showed reduced seizure severity during 6Hz kindling development and a lower incidence of generalized seizures during the maintenance of the fully kindled state. In pilocarpine-treated mice, protein levels of the PI3K/Akt/GSK-3β/eIF2α/ATF4 pathway were increased during the chronic phase of the model, consistent with previous findings in the hippocampus of patients with epilepsy. Finally, repeated administration of SAS protected pilocarpine-treated mice against acute 6 Hz seizure induction, in contrast to sham controls, in which system is not activated. Inhibition of system could be an attractive target for the development of new therapies with a potential for disease modification in epilepsy.

Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy.

Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.

Implementation of a Neurocritical Care Program: Improved Seizure Detection and Decreased Antiseizure Medication at Discharge in Neonates With Hypoxic-Ischemic Encephalopathy

BackgroundWe report the impact of implementing continuous video electroencephalography monitoring for neonates with hypoxic-ischemic encephalopathy via a protocol in the context of neonatal neuro-critical care program. MethodsNeonates with hypoxic-ischemic encephalopathy were studied retrospectively two years before and after implementing continuous video electroencephalography for 72 hours as a care protocol. Before continuous video electroencephalography, a 60-minute routine electroencephalography was performed at the discretion of the provider. Primary outcome: electrographic seizure detection; secondary outcome: use of maintenance antiseizure medications, discharge antiseizure medications, and cumulative burden for each antiseizure medication defined as total mg/kg during hospital stay. ResultsA total of 157 patients with a median gestation of 40 weeks were analyzed; 103 (66%) underwent therapeutic hypothermia. Baseline and clinical characteristics including disease severity and cooling were similar. Before continuous video-electroencephalography (n = 86), 44 (51.2%) had clinical seizures, of those 35 had available routine electroencephalography; 12 of 35 (34%) had electrographic seizures. None of the infants without clinical seizures showed electrographic seizures. After continuous video-electroencephalography (n = 71), 34 (47.9%) had clinical seizures, of those 18 (53%) had electrographic seizures; five of 37 (14%) of infants with no clinical seizures had electrographic seizures. The introduction of continuous video-electroencephalography significantly increased electrographic seizure detection (P = 0.016). Although there was no significant difference in the initiation and maintenance use of antiseizure medications after continuous video-electroencephalography, fewer infants were discharged on any antiseizure medication (P = 0.008). Also, the mean phenobarbital burden reduced (P = 0.04), without increase in other antiseizure medications use or burden. ConclusionUse of continuous video-electroencephalography as part of the neonatal neuro-critical care program was associated with improved electrographic seizure detection, decreased phenobarbital burden, and antiseizure medication use at discharge.

P2X7 receptor antagonism reduces the severity of spontaneous seizures in a chronic model of temporal lobe epilepsy

BackgroundThe available pharmacotherapy for patients with epilepsy primarily address the symptoms and are ineffective in about 40% of patients. Brain inflammation gained support as potential target for developing new therapies, especially the P2X7 receptor (P2X7R), involved in processing of IL-1β, might be an interesting candidate. This study was designed to investigate the effect of a novel P2X7R antagonist on the severity and on the number of chronic spontaneous recurrent seizures (SRS), which was unexplored until now. MethodsAfter one-week of vehicle treatment (20% HP-β-cyclodextrin), JNJ-42253432 was administered subcutaneously for another week under continuous video-electroencephalography monitoring (n = 17) in Sprague Dawley rats 3 months after kainic acid-induced status epilepticus. The proportion of different seizure classes, as well as the number of SRS/day were calculated for the vehicle and treatment period. In addition, post-mortem microglial activation and astrogliosis were assessed. ResultsA significant decrease of the proportion of type 4–5 SRS (p < 0.05), while an increase of type 1–3 was demonstrated (p < 0.05) from the vehicle to the treatment period. There was no effect of the P2X7R antagonist on the number of SRS/day or the glial markers. ConclusionsThe P2X7R antagonist gave rise to a less severe profile of the chronic seizure burden without suppressing the SRS frequency. More studies are needed to unravel the underlying mechanisms of the beneficial effect on seizure severity and whether the administration of the compound during early epileptogenesis could induce long-term disease-modifying effects.

Epileptogenesis after traumatic brain injury in Plau-deficient mice.

Several components of the urokinase-type plasminogen activator receptor (uPAR)-interactome, including uPAR and its ligand sushi-repeat protein 2, X-linked (SRPX2), are linked to susceptibility to epileptogenesis in animal models and/or humans. Recent evidence indicates that urokinase-type plasminogen activator (uPA), a uPAR ligand with focal proteinase activity in the extracellular matrix, contributes to recovery-enhancing brain plasticity after various epileptogenic insults such as traumatic brain injury (TBI) and status epilepticus. Here, we examined whether deficiency of the uPA-encoding gene Plau augments epileptogenesis after TBI. Traumatic brain injury was induced by controlled cortical impact in the somatosensory cortex of adult male wild-type and Plau-deficient mice. Development of epilepsy and seizure susceptibility were assessed with a 3-week continuous video-electroencephalography monitoring and a pentylenetetrazol test, respectively. Traumatic brain injury-induced cortical or hippocampal pathology did not differ between genotypes. The pentylenetetrazol test revealed increased seizure susceptibility after TBI (p<0.05) in injured mice. Epileptogenesis was not exacerbated, however, in Plau-deficient mice. Taken together, Plau deficiency did not worsen controlled cortical impact-induced brain pathology or epileptogenesis caused by TBI when assessed at chronic timepoints. These data expand previous observations on Plau deficiency in models of status epilepticus and suggest that inhibition of focal extracellular proteinase activity resulting from uPA-uPAR interactions does not modify epileptogenesis after TBI.

Application of pattern plastic plate and red color stimulation in continuous video-electroencephalography monitoring

Objective To evaluate the clinical efficiency of intermittent photic stimulation (IPS) with pattern and red color plastic plates in video-electroencephalography(EEG). Methods Three hundred and fifty-eight patients hospitalized in Wuhan Children's Hospital from March 2013 to March 2014 were selected, and they were exa-mined by using stroboscope with a red plastic plate, a dots printed plastic plate, and ordinary white flicker for photic driving response (PDR), photoparoxysmal responses (PPR), photoconvulsive response (PCR). The results of patients with PDR, PPR, PCR were analyzed. Results The PDR synchronously evoked by the three flickering patterns were in 29 cases, and the amplitude of photic drivings evoked by ordinary white flicker and red flicker were higher than that of flickering dot pattern[(30.294±7.767)μV, (31.103±8.920)μV vs(24.436±8.075)μV], and there were significant differences(t=2.983, 2.815, P=0.003, 0.008). However, there was no significant difference between ordinary white flicker and red flicker (t=0.368, P=0.710). The PPR evoked were in 17 cases, and 16 cases (94.12%) of them were evoked by red color, while 10 cases (58.82%) were evoked by white light, and 1 case only evoked by flic-kering dot pattern.However, stronger intensity and longer duration time of PPR were evoked by red color than by white light.In 3 patients with positive PCR, the epileptic seizure was more likely to be evoked by red color or pattern plastic plate. Conclusions IPS with red and pattern plastic plate is more potent in eliciting photosensitive epilepsy in video-EEG than the ordinary white light.Moreover, it could reduce the discomfort of eyes without influencing PDR in comparison to the ordinary white light. Key words: Intermittent photic stimulation; Video-electroencephalography; Photosensitive epilepsy; Red color plastic plate; Pattern plastic plate

Application of continuous video-electroencephalographic monitoring in patients with consciousness disorders in intensive care unit

To evaluate the application value of continuous video-electroencephalographic (cVEEG) monitoring in patients with consciousness disorders in intensive care unit (ICU). Retrospective analyses were conducted for applying cVEEG in the clinical diagnosis and outcome evaluation of 54 patients with consciousness disorders in intensive care unit (ICU) at our hospital from January 2008 to April 2014. The most common cause was cerebrovascular disease (46.3%) followed by ischemic-hypoxic encephalopathy after cadio-pulmonary resuscitation (18.5%). And 49 cases (90.7%) showed an abnormal background on initial cVEEG, 19 cases (35.2%) had epileptic discharge and 8 cases (14.8%) were diagnosed with nonconvulsive status epilepticus (NCSE). Among 6 cases of convulsive patients, only 1 had epileptic discharge patterns of isoelectric, invariable low amplitude. Burst-suppression, persistent θ rhythm-like background activity, persistent diffuse epileptic discharge and periodic waves had high mortality rate. Stroke is a major cause of consciousness disorders. And continuous VEEG monitoring is beneficial for clinical diagnosis, differential diagnosis and outcome evaluation.

Seizure burden is independently associated with short term outcome in critically ill children

Seizures are common among critically ill children, but their relationship to outcome remains unclear. We sought to quantify the relationship between electrographic seizure burden and short-term neurological outcome, while controlling for diagnosis and illness severity. Furthermore, we sought to determine whether there is a seizure burden threshold above which there is an increased probability of neurological decline. We prospectively evaluated all infants and children admitted to our paediatric and cardiac intensive care units who underwent clinically ordered continuous video-electroencephalography monitoring over a 3-year period. Seizure burden was quantified by calculating the maximum percentage of any hour that was occupied by electrographic seizures. Outcome measures included neurological decline, defined as a worsening Paediatric Cerebral Performance Category score between hospital admission and discharge, and in-hospital mortality. Two hundred and fifty-nine subjects were evaluated (51% male) with a median age of 2.2 years (interquartile range: 0.3 days-9.7 years). The median duration of continuous video-electroencephalography monitoring was 37 h (interquartile range: 21-56 h). Seizures occurred in 93 subjects (36%, 95% confidence interval = 30-42%), with 23 (9%, 95% confidence interval = 5-12%) experiencing status epilepticus. Neurological decline was observed in 174 subjects (67%), who had a mean maximum seizure burden of 15.7% per hour, compared to 1.8% per hour for those without neurological decline (P < 0.0001). Above a maximum seizure burden threshold of 20% per hour (12 min), both the probability and magnitude of neurological decline rose sharply (P < 0.0001) across all diagnostic categories. On multivariable analysis adjusting for diagnosis and illness severity, the odds of neurological decline increased by 1.13 (95% confidence interval = 1.05-1.21, P = 0.0016) for every 1% increase in maximum hourly seizure burden. Seizure burden was not associated with mortality (odds ratio: 1.003, 95% confidence interval: 0.99-1.02, P = 0.613). We conclude that in this cohort of critically ill children, increasing seizure burden was independently associated with a greater probability and magnitude of neurological decline. Our observation that a seizure burden of more than 12 min in a given hour was strongly associated with neurological decline suggests that early antiepileptic drug management is warranted in this population, and identifies this seizure burden threshold as a potential therapeutic target. These findings support the hypothesis that electrographic seizures independently contribute to brain injury and worsen outcome. Our results motivate and inform the design of future studies to determine whether more aggressive seizure treatment can improve outcome.

Sleep-Wake Cycling in a Neonate Admitted to the NICU

This retrospective case study describes the sleep-wake cycles of an infant in the neonatal intensive care unit. We analyzed video-electroencephalographic recording of the term infant monitored during treatment with therapeutic hypothermia for hypoxic-ischemic encephalopathy. The continuous video-electroencephalographic recording over a 4-day period also allowed us to describe the following dimensions of daily care in relation to the infant's sleep-wake states: (1) handling by professional and parent caregivers and (2) stress, pain, and analgesia. Physical contact constituted 17% to 36% of each 24-hour period. The infant's care was fragmented, with a mean of 3 to 4 physical contacts per hour. As a result, the structure of infant sleep was altered by the increased amount of awake and quiet sleep. The number of painful procedures ranged from 5 to 24 per day. Nurses were the main care providers. Parents had more contact after the infant was rewarmed. This case study suggests that neonatal intensive care unit infants are exposed to frequent handling and stress as well as altered sleep. The cumulative negative impact of frequent handling and sleep fragmentation may go unnoticed by caregivers focused on episodes of care. Continuous video-electroencephalographic monitoring is a useful tool for longitudinal evaluation of infant sleep and responses to caregiving in the neonatal intensive care unit.

Benign Rolandic Epilepsy—Perhaps Not So Benign: Use of Magnetic Source Imaging as a Predictor of Outcome

The purpose of this study was to evaluate children with benign rolandic epilepsy, a childhood epilepsy characterized by centrotemporal/rolandic spike-wave discharges with infrequent partial seizures that may secondarily generalize. Recently, some investigators have questioned whether benign rolandic epilepsy is indeed "benign" or whether long-term cognitive outcome may be adversely affected. We initiated an ongoing study to identify children with benign rolandic epilepsy. The children were evaluated in the Texas Comprehensive Epilepsy Program using outpatient or continuous video-electroencephalographic monitoring, brain magnetic resonance imaging, magnetoencephalography, and neuropsychological testing. Neuropsychological testing revealed fine motor dysfunction, visuomotor integration deficits, dyscalculia, and/or expressive language deficits in all of the 9 patients evaluated, reaffirming that benign rolandic epilepsy is not necessarily a benign disorder. Our study shows a high concordance of motor and cognitive deficits in benign rolandic epilepsy, as others have previously suggested. Furthermore, magnetic source imaging shows a higher resolution of dipole localization compared with conventional electroencephalography, which may ultimately improve prediction of deficits. This reaffirms that magnetoencephalography is a valuable diagnostic tool in the evaluation of children with benign rolandic epilepsy.

Prediction of Seizures in Asphyxiated Neonates: Correlation With Continuous Video-Electroencephalographic Monitoring

After perinatal asphyxia, predicting which infants will develop significant hypoxic-ischemic encephalopathy and neonatal seizures remains a difficult task. High-risk markers (Apgar score, acidosis, nucleated red blood cells, and resuscitation) have been used to predict neonatal seizures with varying success. The "3 strikes" of Apgar score of <5 at 5 minutes, pH <7.00, and need for intubation have been cited as having a positive predictive value of 80%. We examined whether the predictive values of these markers would be increased if early continuous electroencephalographic monitoring allowed us to accurately identify all neonatal seizures and to grade the encephalopathy. We recruited term infants with perinatal asphyxia. Continuous video electroencephalography was commenced soon after birth and continued for 24 to 72 hours. The abilities of high-risk markers to predict electroencephalographic seizures, background electroencephalographic activity, and Sarnat grade were examined. Forty-nine infants were suitable for analysis. Electrographic seizures occurred in 11 of the 49 infants. Encephalopathy was scored by using Sarnat grade (6, severe; 18, moderate; 25, mild) and electroencephalographic findings (4 inactive, 4 major abnormalities, 16 moderate abnormalities, and 25 normal/mildly abnormal). Apgar score of <5 at 5 minutes, pH <7.0, and the need for intubation had positive predictive values for neonatal seizures of 18%, 16%, and 21%, respectively. Combining these markers gave a positive predictive value of 25% and a negative predictive value of 77%. Substituting base deficit or lactate for pH in the 3-strikes model did not improve its predictive value. Apgar score of <5 at 5 minutes, nucleated red blood cells, and a base deficit less than -15 mEq/L showed some association with Sarnat grade. Only 5-minute Apgar score was significantly associated with both Sarnat grade and electroencephalographic grade. After perinatal asphyxia, neither the condition at birth nor the degree of metabolic acidosis reliably predict neonatal seizures.

Effect of lamotrigine treatment on epileptogenesis: an experimental study in rat

Prevention of epileptogenesis in patients with acute brain damaging insults like status epilepticus (SE) is a major challenge. We investigated whether lamotrigine (LTG) treatment started during SE is antiepileptogenic or disease-modifying. To mimic a clinical study design, LTG treatment (20 mg/kg) was started 2 h after the beginning of electrically induced SE in 14 rats and continued for 11 weeks (20 mg/kg per day for 2 weeks followed by 10 mg/kg per day for 9 weeks). One group of rats ( n=14) was treated with vehicle. Nine non-stimulated rats with vehicle treatment served as controls. Outcome measures were occurrence of epilepsy, severity of epilepsy, and histology (neuronal loss, mossy fiber sprouting). Clinical occurrence of seizures was assessed with 1-week continuous video-electroencephalography monitoring during the 11th (i.e. during treatment) and 14th week (i.e. after drug wash-out) after SE. LTG reduced the number of electrographic seizures during SE to 43% of that in the vehicle group ( P<0.05). In the vehicle group, 93% (13/14), and in the LTG group, 100% (14/14) of the animals, developed epilepsy. In both groups, 64% of the rats had severe epilepsy (seizure frequency >1 per day). The mean frequency of spontaneous seizures, seizure duration, or behavioral severity of seizures did not differ between groups. The severity of hippocampal neuronal damage and density of mossy fiber sprouting were similar. In LTG-treated rats with severe epilepsy, however, the duration of seizures was shorter (34 versus 54 s, P<0.05) and the behavioral seizure score was milder (1.4 versus 3.4, P<0.05) during LTG treatment than after drug wash-out. LTG treatment started during SE and continued for 11 weeks was not antiepileptogenic but did not worsen the outcome. These data, together with earlier studies of other antiepileptic drugs, suggest that strategies other than Na +-channel blockade should be explored to modulate the molecular cascades leading to epileptogenesis after SE.