Reassessment of the Clinical Significance of Periodic Lateralized Epileptiform Discharges in Pediatric Patients

Summary: A review of clinical data from 18 pediatric patients with periodic lateralized epileptiform discharges and bilateral independent periodic lateralized epileptiform discharges (PLEDs and BIPLEDs) showed 2 with chronic neurologic illness, 6 with a history of prior seizures, 14 with depressed sensorium at the time of EEG, 5 deaths, and 8 of 13 survivors with neurologic deficits. These findings are similar to the combined data from reports involving adult patients only. Separating pediatric patients with PLEDs from those with BIPLEDs shows some influence from patients with BIPLEDs. Overall, our data do not suggest significant clinical differences for PLEDs between children and adults.     

The Effects of Remifentanil on Epileptiform Discharges during Intraoperative Electrocorticography in Patients Undergoing Epilepsy Surgery

PURPOSE: High-dose i.v. opioids (e.g., alfentanil, 50 microg/kg bolus) are known to increase the intraoperative reading of epileptiform activity during epilepsy surgery (ES), thereby facilitating localization of the epileptogenic zone (i.e., the site of ictal onset and initial seizure propagation). However, this phenomenon has not been studied with remifentanil (i.e., a novel ultra-short acting opioid). The purpose of the present study was to evaluate the effect of remifentanil on electrocorticography (ECoG) during ES. METHODS: After Institutional Review Board approval, 25 adult patients undergoing elective ECoG-guided anterior temporal corticectomy were enrolled. At the time of ECoG, anesthesia consisted of inhaled isoflurane < or =0.1% (end-tidal) in 50% N2O, and i.v. fentanyl, 2 microg/kg/h and vecuronium. Patients were maintained at normocapnia and normoxia during ECoG. After acquisition of baseline ECoG, bolus remifentanil, 2.5 microg/kg i.v., was administered. The number of epileptiform spikes occurring 5 min before and after this bolus were compared by using a one-sided sign test; p values < or =0.05 were considered statistically significant. RESULTS: When compared with baseline ECoG, bolus i.v. remifentanil significantly increased the frequency of single spikes or repetitive spike bursts in the epileptogenic zone while suppressing activity in surrounding normal brain. CONCLUSIONS: During ES, remifentanil enhanced epileptiform activity during intraoperative ECoG. Such observations facilitate localization of the epileptogenic zone while minimizing resection of nonepileptogenic eloquent brain tissue. Although not specifically evaluated in this study, we speculate that remifentanil's short elimination half-life will facilitate neurologic function testing immediately after ES. Should this be the case, we envision remifentanil has the potential to supplant other opioids (e.g., alfentanil) during ECoG-guided ES.     

Benzodiazepine Antagonists Reduce Epileptiform Discharges in Rat Hippocampal Slices

Summary: Purpose : The antiepileptic effects of benzodiaze-pine-receptor (BZR) agonists have been well documented. Surprisingly, an antiepileptic effect for the BZR antagonist, fluma-zenil, has also been described, the mechanism of which is unknown. We investigated the effects of nanomolar concentrations of flumazenil and a structurally dissimilar BZR antagonist, propyl-β-carboline-3-carboxylate (β-CCP), on normal synaptic responses and epileptiform discharges induced by a variety of methods in the CA1 region of rat hippocampal slices.
Methods : Extracellular field potentials were recorded from stratum pyramidale of the CA1 region. Orthodromic stimulation was delivered by a bipolar electrode placed in the stratum radiatum at the border of the CA2/KA3 regions. Drugs were bath applied, and epileptiform discharges were quantified by using the Coastline Bursting Index, which calculates the total length of the discharge waveform of evoked multiple population spikes. For statistical comparisons, we calculated the Coastline Bursting Index for the average of five traces at the end of the control period (20 min), drug application (20 min), and washout (20–40 min).
Results : Flumazenil was without effect on normal synaptic responses; however, flumazenil reduced epileptiform discharges evoked in the presence of high [K⁺]₀, leu-enkephalin, the BZR inverse agonist, methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), or after a cold-shock procedure. β-CCP exhibited an action similar to that observed for flumazenil, suggesting that the antiepileptic effect is due to properties common to BZR antagonists.
Conclusions : We suggest that the antiepileptic effect we observed for flumazenil and (β-CCP is mediated at the BZR and might be due to competition with endogenous BZR inverse agonists released preferentially during epileptiform activity.     

发作间期(痫)样放电与癫(痫)患者认知功能下降有关

目的 探讨发作间期(痫)样放电(IEDs)对癫(痫)患者认知功能的影响.方法 选取6个月内无临床发作的癫(痫)患者164例,随访2年(脱落96例,剔除癫(痫)发作12例,脑电图改变4例),共计收集52例为研究对象,其中有IEDs癫(痫)36例为IED组;无IED癫(痫)16例为无IED组.于随访2年前后分别完成24 h动态脑电图及认知功能评定.IED组根据清醒期有无IED分为清醒期IED亚组和清醒期无IED亚组.采用简易精神状态量表(MMSE),ADDENBROOKE,S认知功能检查中文版(ACE-R),短延时词语记忆[AVLT(N4)及连线测试(TMT)]评价各组癫(痫)患者的认知功能情况.结果 随访前:IED组MMSE、ACE-R,AVLT(N4)及TMT与无IED组比较,均差异无显著性.随访2年后:IED组认知功能评分、ACE-R总分、语言和记忆分值均较无IED组下降,差异有统计学意义(P＜0.05);IED组TMT-B延长值与无IED组比较,差异有统计学意义(P＜0.05).清醒期IED组和清醒期无IED组认知功能测试差异无显著性.结论 IEDs是导致癫(痫)患者认知功能下降的原因之一,主要表现在语言、记忆、执行功能.未发现清醒期IEDs与癫(痫)患者的认知功能相关.     

Effect of Interictal Epileptiform Discharges on Nocturnal Plasma Prolactin Concentrations in Epileptic Patients with Complex Partial Seizures

To investigate the effect of interictal epileptiform discharges (IEDs) on plasma prolactin (PRL) level, we studied 18 epileptic patients with complex partial seizures (CPS) who did not experience clinical or subclinical ictal events during all-night monitoring with polygraphic recording and video imaging. The density of IEDs peaked during non-REM stages and was significantly reduced during REM stage. Mean plasma PRL concentrations in epileptic patients, when sampled at 30-min intervals, showed a moderate but significant elevation during non-REM (p less than 0.001) and awake stages (p less than 0.005), but not during REM stage, when compared with 10 nonepileptic control subjects studied in a similar fashion. The data obtained in this physiologically controlled environment indicate that the cumulative effect of IEDs may modify PRL regulatory mechanisms, resulting in a modest elevation of plasma concentrations independent of ictal discharges.     

Prognostic Significance of Ictal and Interictal Epileptiform Activity in Temporal Lobe Epilepsy

Summary: Long-term electrocorticograms (ECoG), recorded by chronically implanted subdural electrodes during preoperative evaluation of 59 patients with temporal lobe epilepsy (TLE) were analyzed retrospectively to assess the prognostic relevance of distribution of interictal epileptiform potentials (IEP) and seizure origin (SO) and to investigate factors affecting their lateralization. Subsequent to preoperative evaluation, a standardized two thirds anterotemporal lobectomy including subtotal hippocampectomy had been performed in all patients. The following results were obtained: (a) Only patients with 100% lateralization of SO and IEP had excellent seizure outcome (= 89% seizure-free); (b) patients with bitemporal SO were unlikely to benefit from surgical treatment (=12.5% seizure-free); (c) 40–56% patients with unilateral temporal SO and bitemporal IEP, became seizure-free irrespective of the degree of lateralization of IEP; and (d) multidimensional analysis of variance showed that lateralization of SO, presence of a magnetic resonance imaging (MRI)-detectable lesion, presence of hippocampal sclerosis, presence of febrile seizures and seizures at age ≥6 years are the five most important variables indicating abolition of seizures. Combined analysis of ECoG-recorded SO and IEP allows prediction of postoperative seizure control within close boundaries.     

应用压缩谱阵检测痫样放电的初步研究

对癫痫患者以2s为单元作离线CSA分析。结果发现:CSA可显示出清醒与浅睡期散在频发中高幅放电与1s以上的阵发放电,但不能显示出散在少量与低幅放电;不同放电类型,CSA有不同的特征。表明CSA可有效地用于呈频繁放电的癫痫状态的监护,并可判断癫痫发作类型。     

Primary Generalized Seizure Disorder: Correlation of Epileptiform Discharges with Seizure Frequency

Summary: The role of routine follow-up EEG in assessment of severity of a seizure disorder is not known. This retrospective chart review study of patients with primary generalized seizure disorders explored the relation between parameters of epileptiform discharge bursts on EEG and number of seizures experienced in the preced ing months. Eighty-seven such patients were found, each with one to seven EEGs and corresponding clinical records, comprising a total of 201 clinicoelectrographic epochs. The 56 chronically attending patients (more than two attendances) differed from the 31 nonchronic attenders in receiving more antiepileptic drugs (AEDs) and having fewer EEG poly spikes; otherwise, the two groups were similar and were analyzed together. We noted a strong relation between number and maximum length of epileptiform bursts in the resting EEG record and number of absence seizures reported in the months preceding the EEG. Age did not affect this relation. After stepdown regression analysis, only the maximum length of epileptiform bursts remained significantly related to the reported number of absence seizures. These findings may prove useful in assessing clinical progress, e.g., in patients whose ability to estimate numbers of attacks is suspect. Neither number nor maximum length of epileptiform bursts in the resting EEG record had a significant relation with the number of generalized tonic-clonic seizures. Presence of polyspikes on resting or "activated" EEG had no added predictive value. The presence of epileptiform bursts after activation by sleep, hyperventilation, or photic stimulation was not associated with an increased likelihood of having had seizures.     

Defining the Role of Structural Lesions and Metabolic Abnormalities in Periodic Lateralized Epileptiform Discharges

Summary: We reviewed the EEG, clinical manifestations, computed tomography (CT) and magnetic resonance imaging (MRI) scans of 39 patients with periodic lateralized epileptiform discharges (PLEDs) or bilateral periodic lateralized epileptiform discharges (BIPLEDs) to determine the role of structural lesions (SL) and metabolic abnormalities (MA) in their pathogenesis. Thirty-eight patients had CT and 7 had MRI scans. Thirty-eight had lesions on CT or MRI. All those with PLEDs consistently had lesions on the side of the discharges, and 5 of 6 with BIPLEDs had lesions on both hemispheres. A subgroup of 23 patients with metabolic determination within 24 h of EEG all showed mild to moderate MA. They all also had SL. These findings support a primary role for SL but cannot exclude an additional role for MA.     

Effect of Seizures and Epileptiform Discharges on Cognitive Function

Summary: Several relationships have been obtained between cognitive impairment and epilepsy-related or treatment-related factors. One of these factors is treatment-related: the central cognitive side effects of the antiepileptic drugs (AEDs). The second and third factors are disease-related factors, i.e., the effect of the seizures and underlying epileptiform discharges in the brain and the localization of the epileptogenic focus in specific areas of the brain. Although most cognitive problems have a multifactorial origin and often several factors combined are responsible for the "make-up" of a cognitive problem, we have attempted to isolate one factor: the effect of seizures and epileptiform EEG discharges on cognitive function. Several studies show the impact of ictal activity, but special attention is required for the postictal and interictal effects of epilepsy on cognitive functions. This may explain substantial cognitive impairments in children with subclinical epileptiform discharges or with infrequent subtle seizures.     

Prevalence of Epilepsy in the Parsi Community of Bombay

A door-to-door survey was carried out to screen a community of 14,010 people (Parsis living in colonies in Bombay, India) for possible neurologic diseases. High school graduates, social workers, and medical students administered a screening questionnaire that in a pilot survey had a sensitivity of 100% for identifying persons with epilepsy. Neurologists used defined diagnostic criteria to evaluate individuals positive on the screening survey. Sixty-six persons (43 males, 23 females) suffered from epilepsy (4.7 cases/1,000). Of those, 50 (34 males, 16 females) had active epilepsy (3.6 cases/1,000). The age-specific prevalence ratios remained fairly constant for each age group except for a small peak in the group aged 20-39 years for all epilepsy cases combined. Age-adjusted prevalence ratios were higher for males. The most common seizure type was partial (36 cases). The most frequently associated conditions were cerebral palsy and mental retardation. The majority of individuals were receiving medication as of prevalence day (47 cases).     

Seizure-Related Injuries in Multihandicapped Patients with Therapy-Resistant Epilepsy

A prospective study on seizure-related inju ries in Norway's two nursing homes for persons with ep ilepsy was conducted. Sixty-two multihandicapped pa tients with mostly difficult-to-treat epilepsy were as sessed for 13 months: 6,889 seizures, 2,696 with ensuing falls, resulted in 80 injuries. The seizure-related injury risk was 1.2%. The most frequent injuries were mild soft tissue injuries with and without cuts. Six serious injuries were recorded: two leg fractures, one mandibular fracture, one neck of the femur fracture, one skull fracture, and one subdural hematoma. A 71-year-old woman with subdural hematoma died during operation for the he matoma. Seizure types most often causing injury were atonic and tonic-clonic seizures. Prophylactic measures can be taken. Because the seizure-induced injury risk was slight, we concluded that even persons with refractory epilepsy should be encouraged to lead active lives.     

Left Hemispheric Dominance of Epileptiform Discharges

Summary: Purpose: We reviewed 1,360 EEG reports for all patients studied in two different neurophysiology laboratories during 1 calendar year to determine whether epileptiform discharges have a hemispheric dominance.
Methods: Both inpatients and outpatients, with or without epilepsy, were included.
Results: Ninety-four records (6.9%) demonstrated generalized epileptiform activity. Of 95 EEG reports indicating spikes solely from one hemisphere, spikes arose from the left in 61 and from the right in 34. Among 50 other records with bilateral independent spikes with lateralization, 40 were left hemisphere'dominant and 10 were right hemisphere dominant.
Conclusions: These findings raise the possibility that the left cerebral hemisphere may generate focal epilepsy more frequently than the right.     

Interictal Epileptiform Discharges in Temporal Lobe Epilepsy Due to Hippocampal Sclerosis Versus Medial Temporal Lobe Tumors

PURPOSE: It remains controversial whether a specific pattern of interictal epileptiform activity exists that may help to differentiate temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) from other forms of TLE. In this study, we characterized the distribution of interictal epileptiform discharges in TLE due to HS as compared with those in patients with tumors restricted to the medial temporal lobe structures. METHODS: The study included 21 adult patients with unilateral HS who remained seizure free (>1 year) after anterior temporal lobectomy with amygdalohippocampectomy. Patients with "dual pathology" were excluded. The comparison group consisted of nine patients with tumors restricted to the amygdala and hippocampus. All patients underwent video-EEG monitoring preoperatively by using 39 scalp electrodes (including the 10-10 system over both temporal regions) and bilateral sphenoidal electrodes. RESULTS: The HS patient group showed a significantly higher percentage of ipsilateral epileptiform discharges maximal at anterior temporal electrodes (median, 97.0%; sphenoidal electrode alone, 88.1%), as compared with the tumor group (median, 72.1%; p<0.001; sphenoidal electrode alone, 24.8%; p<0.001). The HS group had significantly fewer extratemporal spikes/sharp waves (median, 0.0), as compared with the tumor group (10.0%; p<0.001). At least 90% of the interictal discharges were located in the anterior temporal region in 20 (95.2%) of 21 HS patients, but in none of the tumor patients (p<0.001). Bilateral temporal discharges were found in nine (42.9%) of 21 patients with HS and in two (22.2%) of nine tumor patients (p = 0.42). CONCLUSIONS: We conclude that ipsilateral interictal epileptiform discharges outside the anterior temporal region are rare (<10%) in adults with intractable TLE due to unilateral HS. Frequent posterior or extratemporal sharp waves may detract from the certainty of this diagnosis in complicated cases. These restricted epileptiform discharges suggest a smaller irritative zone in HS as compared with medial tumors, or a more organized activity associated with intrinsic hippocampal disease. Bilateral epileptiform discharges were not uncommon in both groups.     

Alcohol and Marijuana: Effects on Epilepsy and Use by Patients with Epilepsy

We review the safety of alcohol or marijuana use by patients with epilepsy. Alcohol intake in small amounts (one to two drinks per day) usually does not increase seizure frequency or significantly affect serum levels of antiepileptic drugs (AEDs). Adult patients with epilepsy should therefore be allowed to consume alcohol in limited amounts. However, exceptions may include patients with a history of alcohol or substance abuse, or those with a history of alcohol-related seizures. The most serious risk of seizures in connection with alcohol use is withdrawal. Alcohol withdrawal lowers the seizure threshold, an effect that may be related to alcohol dose, rapidity of withdrawal, and chronicity of exposure. Individuals who chronically abuse alcohol are at significantly increased risk of developing seizures, which can occur during withdrawal or intoxication. Alcohol abuse predisposes to medical and metabolic disorders that can lower the seizure threshold or cause symptoms that mimic seizures. Therefore, in evaluating a seizure in a patient who is inebriated or has abused alcohol, one must carefully investigate to determine the cause. Animal and human research on the effects of marijuana on seizure activity are inconclusive. There are currently insufficient data to determine whether occasional or chronic marijuana use influences seizure frequency. Some evidence suggests that marijuana and its active cannabinoids have antiepileptic effects, but these may be specific to partial or tonic-clonic seizures. In some animal models, marijuana or its constituents can lower the seizure threshold. Preliminary, uncontrolled clinical studies suggest that cannabidiol may have antiepileptic effects in humans. Marijuana use can transiently impair short-term memory, and like alcohol use, may increase noncompliance with AEDs. Marijuana use or withdrawal could potentially trigger seizures in susceptible patients.     

Prevalence of Epilepsy in a Rural Community of Guatemala

Summary: We conducted a cross-sectional epidemiological study to assess the prevalence and patterns of epilepsy in a small rural village of Guatemala (population 2,111); 1,882 subjects (97.3%) were surveyed. By administering the World Health Organization (WHO) standard questionnaire and performing neurological examinations, we detected 16 cases of epilepsy. The crude prevalence rate for this community was 8.5 in 1,000 general population. Eleven cases were further classified as active epilepsy, giving a prevalence rate of 5.8 in 1,000 general population for this form. The most common type of seizure was generalized tonicclonic seizures (GTCS, 50%), followed by complex partial seizures (CPS, 37.5%), simple partial seizures (SPS, 6.2%) and generalized atonic seizures (6.2%). The age-specific prevalence ratio was highest among the group aged 20–29 years, although the difference between that group and the other age groups was not statistically significant ( z < 2, p > 0.05). Fourteen persons (87.5%) had sought medical care for their seizures at least once in their lifetime, 5 (31.25%) were receiving an antiepileptic drug (AED), and 9 (56.25%) had previously received treatment and 2 (12.5%) had never been treated for their illness. Phenobarbital was the most common AED prescribed; 7 persons had positive family history of epilepsy, 5 reported a history of significant head trauma, 4 had history of central nervous system disease, and 1 had a history of chronic alcohol intake.