Bimodal evoked potentials during long-term therapy with conventional or slow release preparations of carbamazepine and valproic acid in children and adolescents with epilepsy

The measurement of evoked potentials (EPs) may be particularly useful in clinical neuropharmacology for investigation of drug effects of afferent nerve conduction within CNS. The study aims at estimating the long term effects of conventional or slow release formulation (CR) of carbamazepine (CBZ) and valproid acid (VPA) on visual (VPA) and brainstem auditory (BAEP) evoked potentials. Investigation covered 125 patients 8 to 18 years old to whom both formulations of CBZ or VPA were administered in monotherapy. Everyone received a drug dosage which gave an adequate therapeutic plasma concentration and satisfactory seizure control. Antiepileptic drugs (AEDs) plasma levels were measured by means of fluorescence polarization immunoassay method aided of TDx Analyzer (Abbott, Diagnostic). EPs were registered by means of Multiliner (Toennies, Germany). A pattern of reversal stimulation for VEP was used. The latencies of N75, P100, N145 as well as interpeak amplitudes of N75/P100, P100/N145 were evaluated. The following BAEP parameters were considered: morphology of the potential, absolute latencies of waves I, III, V and I-III, III-V, I-V. EP were always performed in the same conditions and with the same equipment for the epileptic and control groups. The obtained values were compared with age-matched control group. The following BAEP abnormalities were observed: prolonged absolute latencies of waves I, III, V as well as prolonged IPLs I-III. The BAEP V/I amplitude ratio and morphology of the waves were normal in all patients. The VEPs abnormalities manifested as prolongation of P100 or N145 latencies and reduction of amplitudes N75/P100, P100/N145. Results of these electrophysiological studies with CBZ and VPA demonstrate that EP are sensitive, noninvasive reflectors of AEDs effects within the CNS.     

Acute and chronic effects of carbamazepine, phenytoin, valproate and vinpocetine on BAEP parameters and threshold in the guinea pig.

OBJECTIVE: To characterize the acute and chronic effects of the antiepileptic drugs (AEDs): carbamazepine (CBZ), phenytoin (PHT), valproic acid (VPA) and vinpocetine (VPC), at doses 20, 6, 30 and 2mg/kg, respectively, on the latencies and amplitudes of the waves of brainstem auditory evoked potentials (BAEPs) elicited by a supra-threshold stimulus alongside BAEP threshold. METHODS: BAEPs elicited by a stimulus of high (100dB nHL) intensity and BAEP thresholds were obtained at 4 and 8kHz: before, after the start of treatment, and following 28 days of a daily injection of the AEDs. RESULTS: After the start of treatment BAEPs were unchanged. After the long term treatment, CBZ and PHT increased P3 and P4 wave peak latencies and reduced P4 amplitude. Chronic VPA did not modify BAEP waves, and chronic VPC reduced P3 and P4 latencies. P1 and P2 were unchanged. BAEP thresholds at 4 and 8kHz were increased by CBZ, PHT and VPA, and decreased by VPC. CONCLUSIONS: The chronic administration of several AEDs modifies BAEP waves of retro-cochlear origin. SIGNIFICANCE: Alterations in the generators of the later waves of BAEPs underlie, in most cases, the changes in hearing sensitivity produced by the long term treatment with AEDs at therapeutic relevant doses.     

Multimodality evoked potentials in amyotrophic lateral sclerosis

Visual, brainstem auditory and somatosensory evoked potentials to medial nerve stimulation were recorded in 27 patients affected by amyotrophic lateral sclerosis. VEP N75, P100, N140, N75-P100 latencies and P100 amplitude, BAEP I-III, III-V and I-V interpeak-latencies were within normal limits in all ALS patients. Somatosensory evoked potentials were abnormally delayed in 8 patients: in 3 arms because of a delayed N9-N13 latency, in 9 arms because of a delayed N13-N19 latency.     

No Effect of Long-Term Vigabatrin Treatment on Central Nervous System Conduction in Patients with Refractory Epilepsy: Results of a Multicenter Study of Somatosensory and Visual Evoked Potentials

Summary: Purpose: In dogs, vigabatrin (VGB) has been associated with intramyelinic edema producing delayed central conduction in somatosensory and visual evoked potentials (SEP, VEP). No such effects have been reported in humans. We assessed whether abnormalities of central conduction could be detected prospectively in patients with epilepsy treated with VGB as long-term add-on medication. Methods: Two hundred one patients with refractory partial epilepsy were enrolled and monitored for as long as 2 years. VGB was added to the treatment at an average dose of 2–3g/ day. Conduction in somatosensory and visual pathways was assessed by median nerve SEP and pattern VEP recordings performed at inclusion and once every 6 months. The upper limit and test-retest variability of EP latencies were evaluated at time of enrollment in the patient group. Prolonged N13-N20 or P14-N20 SEP intervals and P100 VEP latency >2.5 SD above the baseline mean, observed on repeated runs in the same session and exceeding the test-retest variability at enrollment were considered to indicate central conduction slowing. Results: One hundred nine patients completed the 2-year study period, and 92 discontinued VGB, of whom 37 were monitored with regard to EP until the end of the study. No consistent change in SEP or VEP was observed in the entire group during VGB treatment. The number of occasional EP values outside the baseline range in patients treated with VGB similar to that in patients whose VGB treatment had been discontinued. Conclusions: We detected no evidence of changes in SEP and VEP attributable to altered neuronal conduction in the CNS during long-term VGB treatment.     

Short term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment

Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts.

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Sommario I potenziali evocati visivi (VEP) ed acustici troncoencefalici (BAEP) sono stati eseguiti in 21 pazienti affentti da sclerosi multipla (SM) in fase di poussée, prima e dopo un ciclo di trattamento con steroidi. Prima del trattamento i VEP edi BAEP sono risultati alterati in 14 e 10 pazienti rispettivamente. 4 pazienti presentavano una neurite ottica (ON) in fase acuta; in 3, dopo il trattamento, è stato rilevato un significativo miglioramento dei VEP e dell'acuità visiva. Significative, ma contrastanti, modificazioni dei VEP e BAEP, riscontrate in altri 5 pazienti, non correlate all'evoluzione clinica, sono suggestive di un interessamento subclinico, multifocale e possibilmente sequenziale, durante una poussée della SM. L'analisi per gruppi non evidenzia differenze statistiche significative tra prima e dopo il trattamento. I nostri risultati indicano che i potenziali evocati sono di limitata utilità ai fini di un monitoraggio a breve termine della SM in poussée.

     

多发性硬化患者的MRI及多种诱发电位研究

目的探讨磁共振成像(MRI)和诱发电位(EPs)在诊断多发性硬化中的价值。方法对68例多发性硬化患者的头颅MRI、脑干听觉诱发电位、视觉诱发电位以及体感诱发电位等指标进行回顾性分析和比较。结果多发性硬化患者的头颅MRI、脑干听觉诱发电位、视觉诱发电位以及体感诱发电位的异常率分别为91.2%(62/68)、80.9%(55/68)、82.4%(56/68)和77.9%(53/68),且均发现多发性硬化的亚临床病灶;两项或多项联合检查的异常率较单项检查的异常率增高,差异有统计学意义(P<0.01)。结论头颅MRI和诱发电位检查有助于临床早期确诊多发性硬化,联合应用可使其敏感性提高。     

Effects of carbamazepine and valproate on brainstem auditory evoked potentials in epileptic children

Brainstem auditory evoked potentials (BAEPs) were recorded in 18 epileptic children receiving carbamazepine and 10 epileptic children receiving valproate. BAEPs were recorded before the administration of antiepileptic drugs (AEDs) and 13 months later during which the children received AEDs. Statistical analysis of peak latencies and interpeak intervals of waves I–III–V were made. Carbamazepine treatment resulted in prolongation of peak latencies of waves I–III–V and interpeak intervals I–III and I–V. Valproate monotherapy, on the other hand, caused no consistent changes on BAEP. On the basis of these results we suggest that chronic carbamazepine therapy exerts a suppressive influence on the auditory pathways, both peripherally at the level of the cochlea and/or auditory nerve, and centrally at the brainstem.     

Brain stem auditory and visual evoked potentials in multiple sclerosis

The diagnostic value of the checkerboard pattern-reversal visual evoked potential (VEP) and the random, low rate stimulated brain stem auditory evoked potential (BAEP) was compared in 99 patients with established or suspected multiple sclerosis (MS). In normal subjects examined by both techniques no abnormal recordings were found. In 49 patients with definite MS an incidence of abnormality was found in 100% of VEP and in 84% of BAEP recordings. In 50 patients with probable or possible MS an abnormal VEP was found in 70% and an abnormal BAEP in 50%. When the two examinations were combined, the diagnostic yield increased to 100 and 80%, respectively. 22 patients had only spinal symptoms; in these the VEP gave 73%, the BAEP 55% and the combination 82% abnormalities. The combination of the two techniques was found useful for demonstrating demyelinating lesions in the central nervous system, the diagnostic value being greatest when these lesions were clinically silent.     

Multimodal evoked potentials in spinocerebellar ataxia types 1, 2, and 3

Aims:

Spinocerebellar ataxias (SCA) are a clinically heterogeneous group of disorders that are characterized by ataxia and an autosomal dominant pattern of inheritance. The aim of our study was to describe the findings of evoked potentials (EPs) among genetically proven SCA types 1, 2, and 3 and to additionally evaluate if EPs can be used to differentiate between them.

Materials and Methods:

Forty-three cases of genetically proven SCA (SCA1 = 19, SCA2 = 13, and SCA3 = 11) were evaluated with median somatosensory-EP (mSSEP), visual-EP (VEP), and brainstem auditory-evoked response (BAER) by standard procedures and compared with normative laboratory data. An EP was considered abnormal if latency was prolonged (>mean + 3 standard deviation (SD) of laboratory control data) or the waveform was absent or poorly defined. The waves studied were as follows: mSSEP - N20, VEP - P100 and BAER - interpeak latency 1-3 and 3-5.

Results:

EPs were abnormal in at least one modality in 90.9% of patients. The most common abnormality was of BAER (86.1%) followed by VEP (34.9%) and mSSEP (30.2%). The degree of abnormality in VEP, mSSEP, and BAER among patients with SCA1 was 42.1, 41.2, and 73.3%, respectively; among patients with SCA2 was 38.5, 27.3, and 100%, respectively; and among patients with SCA3 was 18.2, 37.5, and 88.9%, respectively. The differences between the subgroups of SCAs were not statistically significant.

Conclusions:

BAER was the most frequent abnormality in SCA types 1, 2, and 3; abnormalities of mSSEP were comparable in the three SCAs; whereas, abnormality of VEP was less often noted in SCA3.     

卡马西平对诱发电位的影响及意义

目的研究长期口服卡马西平治疗癫对诱发电位的影响,并讨论其意义。方法选择尚未治疗的癫病人31例作为试验组;以性别、年龄与癫组相匹配的健康正常人26例作为对照组。两组先分别做脑干听觉诱发电位(BAEP)、事件相关电位P300、视觉诱发电位(VEP)和体感诱发电位(SEP),之后癫组开始卡马西平治疗,服药一年后再作上述各项检查。结果癫组病人治疗前各项电生理学指标与正常对照组相比无显著性差异;癫组卡马西平治疗后各项电生理指标与治疗前相比BAEP各波、P300以及VEP的P100波潜伏期均显著延长;SEP的潜伏期无显著变化。结论神经电生理学检查可以早期发现长期服用卡马西平导致的亚临床毒性。     

Brain-stem auditory evoked potentials in multiple sclerosis: the relation to VEP,SEP and CSF immunoglobulins

Summary One hundred patients with multiple sclerosis (MS) were analysed retrospectively with respect to investigations of brain-stem auditory evoked potentials (BAEP), pattern reversal visual evoked potentials (VEP), somatosensory evoked potentials (SEP), and cerebrospinal fluid immunoglobulins (CSF-IG). BAEP were abnormal in 42% of those with normal VEP and SEP examinations, and in 38% of patients with normal CSF-IG. The chance of obtaining at least one abnormal EP was lower in patients with normal CSF-IG than in patients with abnormal CSF. When a dispersion ratio was included in the criteria for BAEP abnormality, the sensitivity increased compared with conventional BAEP criteria. We recommend that BAEP should still be included in the EP test battery for patients with suspected MS.     

遗传性小脑共济失调的多形式诱发电位研究

研究遗传性小脑共济失调的诱发电位变化。方法采用多种形式诱发电位，对３６例此类疾病的患者进行检测，并与３０～４０名健康者作对比。结果全部患者至少存在１种以上的诱发电位异常。磁刺激运动诱发电位（ＭＥＰ）、脑干听觉诱发电位（ＢＡＥＰ）及胫后神经与正中神经体感诱发电位（ｔＳＥＰ、ｍＳＥＰ）的异常率分别为８３．３％、８８．９％、８０．０％和６２．５％。不同类型小脑共济失调的诱发电位异常率不同，各型ＢＡＥＰ的异常率普遍较高，橄榄－桥脑－小脑萎缩患者的ＭＥＰ与遗传性痉挛性共济失调的ｔＳＥＰ异常率也很高。ＭＥＰ测试时，刺激皮质在患者中所记录到的双峰波、多相波以及波宽增加，表明皮质运动神经元的异常放电。结论多形式诱发电位改变应列为慢性小脑变性分类学上的诊断依据     

Visual and auditory evoked potentials in the early diagnosis and follow-up of neurosarcoidosis

Visual and brainstem auditory evoked potentials (VEPs, BAEPs) were recorded in 23 patients with neurosarcoidosis. Eight patients (35%) had abnormal BAEPs, and 10 (43%) had abnormal VEPs. Four of the 8 patients with abnormal BAEPs had facial paresis, one had impaired memory and only 3 had symptoms and signs compatible with brainstem lesion. Seven of the patients with abnormal VEPs had no visual symptoms. These findings suggest that BAEP and VEP can reveal subclinical nervous system involvement in sarcoidosis and can also help in the early diagnosis of neurosarcoidosis. Successive recordings of 5 patients showed that BAEP and VEP were useful in the follow-up of these patients.     

Brainstem Auditory and Somatosensory Evoked Potentials in Neuro-Behqet's Syndrome

Abstract: Brainstem auditory evoked potentials (BAEPs) and somatosensory evoked potentials after median nerve stimulation (MN-SEPs) and after posterior tibial nerve stimulation (PTN-SEPs) were studied in 17 patients with neurolehget's syndrome (NB). Eleven patients (64.7%) showed an absence of wave I, III or V or a prolongation of the interpeak latency 1–111, or 111-V in BAEPs. Six patients (37.4%) showed a prolongation in the latency of cortical P37 of PTN-SEPs and/, or the interpeak latency EP-N13 or N13–N18 of MN-SEPs. The BAEP and SEP abnormalities indicated a conduction failure of the acoustic lateral lemniscus pathway and the medial lemniscus pathway in the brainstem of the patients with NB. Abnormal EPs can provide sensitive information which shows the presence of subclinical lesions in the central nervous system.     

Color vision in epileptic adolescents treated with valproate and carbamazepine.

OBJECTIVE: The aims of our study were to evaluate whether deficits in color vision exist in epileptic adolescents, to study if monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision, and to determine the possible relationship between abnormal color vision tests and AEDs dosage and their serum concentrations. PATIENTS: We examined 45 epileptic patients before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. METHODS: Color vision was evaluated with Farnsworth Munsell 100 (FM100) hue test and achromatic and short-wavelength automated perimetry (SWAP). STATISTICAL ANALYSIS: To evaluate intergroup differences we used ANOVA with Scheffe's post hoc test, when appropriate. Repeated measures ANOVA was used to evaluate the intragroup modifications of total error score (TES) and perimetric threshold during the follow-up. Pearson's correlation test was performed to correlate chromatic sense and perimetric data and AEDs dosage and serum concentrations. RESULTS: Before the beginning of therapy, there were no differences in central color vision and SWAP between controls and epileptic patients. After 1 year, patients treated with VPA or CBZ showed a deficit in FM100 hue test and SWAP parameters while no significant deficit was found in achromatic perimetry. In particular, with the FM100 hue test a higher number of errors was found in both groups of patients (CBZ patients: 166.00 +/- 27.72 TES; VPA patients: 151.19 +/- 44.09, P < 0.001) in comparison with controls (controls: 109.29 +/- 24.73) and baseline values (CBZ patients: 110.65 +/- 22.9; VPA patients 107.43 +/- 21.70). With SWAP patients of both groups showed significant variation of foveal threshold (controls: 21.07 +/- 2.01 dB; CBZ patients: 19.35 +/- 1.32, P < 0.001; VPA patients: 18.88 +/- 1.89, P < 0.001), full-field mean threshold perimetric sensitivity (controls: 18.50 +/- 1.24 dB; CBZ patients: 16.60 +/- 1.47, P < 0.001; VPA patients: 16.23 +/- 1.55, P < 0.001) and mean threshold perimetric sensitivity of the three evaluated subareas of the visual field (area 1 controls: 21.01 +/- 1.15; CBZ patients: 19.45 +/- 1.74, P = 0.001; VPA patients: 18.25 +/- 1.61, P < 0.001; area 2 controls: 18.40 +/- 1.43; CBZ patients: 16.07 +/- 1.58, P +/- 0.001; VPA patients: 16.13 +/- 1.46, P = 0.001; area 3 controls: 17.20 +/- 1.49; CBZ patients: 14.28 +/- 1.51, P < 0.001; VPA patients: 14.31 +/- 2.90, P = 0.001). CONCLUSIONS: Our study demonstrates that treatment with VPA or CBZ can affect significantly both central and paracentral color vision after a short treatment period.     

Abnormalities in evoked potentials associated with abnormal glycemia and brain injury in neonatal hypoxic-ischemic encephalopathy

ObjectiveTo investigate how functional integrity of ascending sensory pathways measured by visual and somatosensory evoked potentials (VEP & SEP) is associated with abnormal glycemia and brain injury in newborns treated with hypothermia for hypoxic-ischemic encephalopathy (HIE).MethodsFifty-four neonates ≥ 36 weeks gestational age with HIE underwent glucose testing, VEPs, SEPs, and magnetic resonance imaging (MRI) the first week of life. Minimum and maximum glucose values recorded prior to evoked potential (EP) testing were compared with VEP and SEP measures using generalized estimating equations. Relationships between VEP and SEP measures and brain injury on MRI were assessed.ResultsMaximum glucose is associated with decreased P200 amplitude, and increased odds that N300 peak will be delayed/absent. Minimum glucose is associated with decreased P22 amplitude. Presence of P200 and N300 peaks is associated with decreased odds of brain injury in the visual processing pathway, with delayed/absent N300 peak associated with increased odds of brain injury in posterior white matter.ConclusionsDeviations from normoglycemia are associated with abnormal EPs, and abnormal VEPs are associated with brain injury on MRI in cooled neonates with HIE.SignificanceGlucose is a modifiable risk factor associated with atypical brain function in neonates with HIE despite hypothermia treatment.     

Multimodal evoked potentials in neuro-Behçet: a longitudinal study of two cases

Two neuro-Behçet patients have been studied, over a period of several months, by means of peroneal and median somatosensory- (SEP), brainstem auditory- (BAEP), and visual- (VEP) evoked potentials. In both patients, peroneal SEP showed evidence of a pathological reduction in the central conduction velocity without a related deep sensation impairment, while VEP changes were consistent with the visual disorders. Conversely, BAEP and median SEP findings did not show disease-related abnormalities. The observed anomalies were detectable irrespective of the clinical phase of the disease. Thus, evoked potential assessment is useful in providing objective evidence for evaluating and monitoring CNS damage in neuro-Behçet's syndrome.     

Evoked potentials and CSF-immunoglobulins in MS: relationship to disease duration, disability, and functional status

In 100 MS patients, BAEP and tibial SEP abnormality rates increased significantly with disease duration and clinical disability. VEP correlated non-linearly with disease duration, and median nerve SEP correlated with disability. In multifactorial analysis, however, BAEP correlated significantly only with clinical brainstem and cerebellar signs. These results suggest that evoked potentials correlate more strongly with neurological status of the functional subsystems than either overall disability or disease duration. These findings indirectly suggest that evoked potentials may be useful monitors during large therapeutical trials in MS patients.     

Laser evoked potentials and carbamazepine in epileptic patients.

AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve conduction; reports on conventional somatosensory evoked potentials and CBZ are controversial. In a previous study, assessing laser-evoked potentials (LEPs) in CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs were dampened even after stimulation of the non-painful side, with a strong correlation between LEP latency and daily CBZ dose. No other study investigated the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20 patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although the trigeminal LEP mean latency was slightly longer in epileptic patients (P=0.11), we did not find significant differences between epileptic patients and controls for any LEP data. LEP data did not correlate with the daily CBZ dose, CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to large-fibre, might be less susceptible to AED's toxic effect. Although the TN patients in our previous study were older than the epileptic patients in the present study, a possible combined effect induced by drug and age in patients with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ-induced effect in patients with trigeminal neuralgia is possibly related to pathophysiological changes specific to this disease.     

The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism.

OBJECTIVE: To investigate the effect of vigabatrin (VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with 18F-fluorodeoxyglucose (FDG) PET and 15O water PET. BACKGROUND: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. METHODS: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline 18F-FDG and 15O water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. RESULTS: No statistically significant difference in age, duration of epilepsy, or CBZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1+/-6.5% and global CBF by 13.1+/-10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48+/-1.06 versus 4.03+/-4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R2 = 0.82, p < 0.01). CONCLUSIONS: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBF) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism.