Advantages of methohexital over amobarbital in determining hemispheric language and memory lateralization in the Wada test - A retrospective study.

OBJECTIVE: Due to supply shortage, amobarbital, the traditional anesthetic agent in Wada testing, was replaced by methohexital in many epilepsy centers. This study aimed to compare the two barbiturates to identify possible advantages or disadvantages of methohexital as compared to amobarbital with regard to the adequacy of language and memory testing during the Wada test. METHODS: Data from 75 patients with temporal lobe epilepsy who underwent bilateral Wada tests using either amobarbital (n = 53) or methohexital (n = 22) as part of presurgical work-up were analyzed retrospectively. The two subgroups were compared regarding hemispheric language and memory lateralization results and Wada testing characteristics, and the adequacy of language and memory testing was assessed. RESULTS: We observed shorter durations of motor-, speech-, and EEG recovery after each injection in patients receiving methohexital compared to amobarbital. In addition, significantly more items could be presented during effective hemispheric inactivation in the methohexital group. Moreover, significant correlations of Wada memory scores with standard neuropsychological memory test scores could be found in the methohexital group. SIGNIFICANCE: Our findings confirm that methohexital is not only equally suitable for Wada testing but has several advantages over amobarbital. Wada testing can be performed more efficiently and under more constant hemispheric inactivation using methohexital. Furthermore, the adequacy of language and memory testing during the Wada test might be affected by the anesthetic agent used.

Left temporal lobe language network connectivity in temporal lobe epilepsy.

Impairment of naming function is a critical problem for temporal lobe epilepsy patients, yet the neural correlates of the disruption of temporal lobe language networks are poorly understood. Using functional MRI, we investigated the activation and task-related functional connectivity of left temporal lobe language networks and their relation to clinical naming performance and disease characteristics. We studied 59 adult patients with temporal lobe epilepsy (35 left temporal lobe epilepsy) and 32 healthy controls with auditory and visual naming functional MRI tasks. Time series of activation maxima in the left posterior inferior temporal lobe were extracted to create a psychophysiological interaction regressor for subsequent seed-based whole-brain task-related functional connectivity analyses. Correlational analyses were performed to assess the association of functional MRI activation and functional connectivity with clinical naming scores, age of onset of epilepsy, and duration of epilepsy. Auditory naming elicited activation in the left posterior inferior temporal gyrus and visual naming in the left fusiform gyrus across all groups. Activations in the left inferior temporal gyrus, left thalamus and left supplementary motor region during auditory naming as well as left fusiform activations during picture naming correlated with better clinical naming performance. Functional connectivity analyses indicated coupling of left posterior inferior temporal regions to bilateral anterior and posterior temporal lobe regions and the bilateral inferior precentral gyrus as well as contralateral occipital cortex. Stronger functional connectivity was associated with better clinical naming performance in all groups. In patients with left temporal lobe epilepsy only, functional connectivity increased with later age of onset of epilepsy and shorter disease duration. This suggests that onset of seizures early in life and prolonged disease duration lead to disrupted recruitment of temporal lobe networks ipsilateral to the seizure focus, which might account for naming deficits in temporal lobe epilepsy.

The concept of chronotypes and its clinical importance for depressive disorders.

Chronobiology and chronobiological research deal with time-dependent physiological processes and behavioral correlates as well as their adaptation to environmental conditions. Chronobiological research is presently focused on the impact of circadian rhythms on human behavior. In the last three decades, chronobiology has established itself as an independent area of research evolving to an important field of clinical psychology and psychiatry. In this overview, the results of studies on the clinical importance of chronotypes are summarized. The main focus is on the role of chronotype in depressive disorders.

Predictors of New Cerebral Microbleeds in Patients with Antiplatelet Drug Therapy.

BACKGROUND: Cerebral microbleeds (CMB) are associated with an increased risk for ischemic and especially hemorrhagic stroke. The aim of the present study is to identify patients at high risk for the development of new CMB after initiation of an antiplatelet drug therapy. METHODS: Patients received magnetic resonance imaging (MRI) within 1 week after initiation of an antiplatelet drug treatment due to a first ischemic stroke (n = 58) and after a follow-up period of 6 months (n = 40). We documented the presence and the number of CMB at baseline and follow-up and analyzed the influence of possible risk factors including vascular risk factors, stroke etiology, and number of CMB at baseline using stepwise logistic regression and Spearman's correlation coefficient. We compared progression rates of CMB in relation to each risk factor using the Mann-Whitney U-test. RESULTS: The logistic regression model could correctly predict the presence of CMB in 70.7% of patients at baseline and 80% at follow-up. The model correctly identified 85% of patients with new CMB. We observed progression of CMB in 40% of the patients. The overall progression rate was .8 CMB per patient. The progression rate was significantly influenced by age more than 70 years and atherothrombotic stroke. The number of new CMB correlated significantly with the number of CMB at baseline. CONCLUSIONS: We found several predictors of CMB after initiation of antiplatelet drug therapy. The results help to identify patients who need closer monitoring and thorough control of risk factors in order to lower the risk of new CMB and associated complications.

A common SCN1A splice-site polymorphism modifies the effect of carbamazepine on cortical excitability--a pharmacogenetic transcranial magnetic stimulation study.

OBJECTIVE: SCN1A encodes the alpha subunit of the voltage-gated sodium channel and plays a crucial role in several epilepsy syndromes. The common SCN1A splice-site polymorphism rs3812718 (IVS5N+5 G>A) might contribute to the pathophysiology underlying genetic generalized epilepsies and is associated with electrophysiologic properties of the channel and the effect of sodium-channel blocking antiepileptic drugs. We assessed the effects of the rs3812718 genotype on cortical excitability at baseline and after administration of carbamazepine in order to investigate the mechanism of this association. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied in 92 healthy volunteers with the homozygous genotypes AA or GG of rs3812718 at baseline and after application of 400 mg of carbamazepine or placebo in a double-blind, randomized, crossover design. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP) were determined. RESULTS: At baseline there was no significant difference in any TMS parameter. Genotype GG was associated with a higher carbamazepine-induced increase in CSP duration as compared to AA (multivariate analysis of covariance [MANCOVA], p = 0.013). An expected significant increase in RMT was genotype independent. SIGNIFICANCE: We found that the rs3812718 genotype modifies the effect of carbamazepine on CSP duration (mainly reflecting modulation of γ-aminobutyric acid (GABA)ergic inhibition), but not on RMT (mainly reflecting modulation of voltage-gated sodium channels). This provides evidence that rs3812718 affects the pharmacoresponse to carbamazepine via an effect on GABAergic cortical interneurons. Our results also confirm that TMS is useful to investigate the effect of genetic variants on cortical excitability and pharmacoresponse.

Trends in resource utilization and prescription of anticonvulsants for patients with active epilepsy in Germany.

This study evaluated trends in the resource use of patients with active epilepsy over a 5-year period at an outpatient clinic of a German epilepsy center. Two cross-sectional cohorts of consecutive adults with active epilepsy were evaluated over a 3-month period in 2003 and 2008. Data on socioeconomic status, course of epilepsy, as well as direct and indirect costs were recorded using validated patient questionnaires. We enrolled 101 patients in 2003 and 151 patients in 2008. In both cohorts, 76% of the patients suffered from focal epilepsy, and the majority was on antiepileptic drug (AED) polytherapy (mean AED number: 1.7 (2003), 1.8 (2008)). We calculated epilepsy-specific costs of € 2955 in 2003 and € 3532 in 2008 per 3 months per patient. Direct medical costs were mainly due to anticonvulsants in 2003 (59.4% of total direct costs, 34.0% in 2008) and to hospitalization in 2008 (46.9% of total direct costs, 27.7% in 2003). The proportion of enzyme-inducing anticonvulsants and 'old' AEDs decreased between 2003 and 2008. Indirect costs of € 1689 and € 1847 were mainly due to early retirement (48.4%; 46.0% of total indirect costs in 2003; 2008), unemployment (26.1%; 24.2%), and days off due to seizures (25.5%; 29.8%). This study showed a shift in distribution of direct cost components with increased hospital costs as well as a cost-neutral increase in the prescription of 'newer' AEDs. The amount and distribution of indirect cost components remained unchanged.

The LaLiMo Trial: lamotrigine compared with levetiracetam in the initial 26 weeks of monotherapy for focal and generalised epilepsy--an open-label, prospective, randomised controlled multicenter study.

BACKGROUND: Of the newer antiepileptic drugs, lamotrigine (LTG) and levetiracetam (LEV) are popular first choice drugs for epilepsy. The authors compared these drugs with regard to their efficacy and tolerability in the initial monotherapy for epilepsy. METHODS: A randomised, open-label, controlled, parallel group, multicenter trial was conducted to test the superiority of the LEV arm over the LTG arm. The primary endpoint was the rate of seizure-free patients in the first 6 weeks (two-sided Fisher's exact test, α=0.05, intent-to-treat set). Furthermore, efficacy, tolerability and quality of life were evaluated. The authors included 409 patients aged ≥12 years with newly diagnosed focal or generalised epilepsy defined by either two or more unprovoked seizures or one first seizure with high risk for recurrence. Patients were titrated to 2000 mg/day of LEV or 200 mg/day of LTG reached on day 22 or 71, respectively. Two dose adjustments by 500/50 mg were allowed. RESULTS: The proportions of seizure-free patients were 67.5% (LEV) versus 64.0% (LTG) 6 weeks after randomisation (p=0.47), and 45.2% (LEV) versus 47.8% (LTG) during the whole treatment period of 26 weeks. The HR (LEV vs. LTG) for seizure-free time was 0.86 (95% CI, 0.61 to 1.22). Adverse events occurred in 74.5% (LEV) versus 70.6% (LTG) of the patients (p=0.38). Adverse events associated with study discontinuation occurred in 17/204 (LEV) versus 8/201 (LTG) patients (p=0.07). CONCLUSIONS: There were no significant differences with regard to efficacy and tolerability of LEV and LTG in newly diagnosed focal and generalised epilepsy despite more rapid titration in the LEV arm. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT00242606.

Evaluation of health-care utilization among adult patients with epilepsy in Germany.

This study evaluated the resource use of patients with epilepsy in the German district of Marburg-Biedenkopf. A cross-sectional cohort of consecutive adults with epilepsy, irrespective of seizure severity, duration of illness and epilepsy syndrome, was investigated in all health-care sectors. Costs of inpatient and outpatient treatment were derived from billing data of participating hospitals and office-based physicians. Data on socioeconomic status, course of epilepsy and further direct and indirect costs were recorded using patient questionnaires. We enrolled 366 patients from the district of Marburg-Biedenkopf and calculated annual epilepsy-specific costs of €7738 per patient. Direct costs contributed 31.1% (€2406) and indirect costs 68.9% (€5332) of the total costs. Direct medical costs were mainly due to hospitalization (33.2% of total direct costs) and anticonvulsants (26.7%). Costs of admissions were due to status epilepticus (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and seizure-related injuries (8.8%). Indirect costs were mainly due to early retirement (38.0%), unemployment (35.9%) and days off due to seizures (26.2%). The mean costs of epilepsy found in our study were lower than those found in studies conducted at European epilepsy centers due to the inclusion of patients in all health-care sectors.

Circadian preference and sleep quality in healthy controls and psychiatric inpatients with major depressive disorder - An actigraphy study incorporating morning and evening mood assessments.

Major depressive disorder (MDD) is frequently accompanied by sleep disturbance. Regarding diurnal preference (chronotype), sleep problems and low mood have been associated with evening orientation. Considering diurnal preference, we investigated subjective restorative value of sleep and actigraphy sleep parameters together with mood assessments twice a day, i.e. in the morning and evening, during weekdays and weekends in MDD psychiatric inpatients and healthy controls (HCs). The restorative value of sleep was higher during the weekend in HC, and bedtimes and risetimes were delayed during the weekend compared to weekdays in HC and MDD. Morning mood affected subjective sleep ratings in both groups, while association with symptom severity (BDI) in MDD remained insignificant. In HC, better evening mood was associated with later bedtimes. Regarding the chronotype in HC, evening orientation was associated with relatively low restorative value of sleep during weekdays, and morning orientation was associated with relatively higher actigraphy sleep efficiency during weekdays compared to weekend. In MDD, an association of evening orientation with later rise times could be observed, while no chronotype dependent effect emerged regarding the restorative value of sleep or sleep efficiency. Our results emphasize that research on sleep in MDD should incorporate weekdays as well as weekends, chronotype assessment, and measures of morning and evening mood, as these can be associated with ratings of the subjective restorative value of sleep (i.e. in our study, better morning mood was associated with higher restorative values), but also with behavioral sleep parameters (i.e. in our study, more positive evening mood was associated with later bedtimes). Potentially, the restorative value of sleep in MDD evening types can be improved by maintaining a regular sleep schedule, which needs to be investigated in an experimental design.

Interictal alterations of cytokines and leukocytes in patients with active epilepsy.

BACKGROUND: Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome. METHODS: 101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1ß, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences. RESULTS: As compared to controls, the patients showed an elevated percentage of monocytes (18.06±7.08% vs. 12.68±4.55%, p<0.001), NK cells (14.88±7.08% vs. 11.43±5.41%, p=0.019) and IL-6 concentration (3.33±3.11 pg/ml vs. 1.5±1.36 pg/ml, p=0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16±3.76% vs. 11.54±4.2%, p<0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4(+) T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8(+) T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies. CONCLUSION: Patients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment.

Wada test results contribute to the prediction of change in verbal learning and verbal memory function after temporal lobe epilepsy surgery.

In recent years, the clinical usefulness of the Wada test (WT) has been debated among researchers in the field. Therefore, we aimed to assess its contribution to the prediction of change in verbal learning and verbal memory function after epilepsy surgery. Data from 56 patients with temporal lobe epilepsy who underwent WT and subsequent surgery were analyzed retrospectively. Additionally, a standard neuropsychological assessment evaluating attentional, learning and memory, visuospatial, language, and executive function was performed both before and 12 months after surgery. Hierarchical linear regression analyses were used to determine the incremental value of WT results over socio-demographic, clinical, and neuropsychological characteristics in predicting postsurgical change in patients' verbal learning and verbal memory function. The incorporation of WT results significantly improved the prediction models of postsurgical change in verbal learning (∆R2 = 0.233, p = .032) and verbal memory function (∆R2 = 0.386, p = .005). Presurgical performance and WT scores accounted for 41.8% of the variance in postsurgical change in verbal learning function, and 51.1% of the variance in postsurgical change in verbal memory function. Our findings confirm that WT results are of significant incremental value for the prediction of postsurgical change in verbal learning and verbal memory function. Thus, the WT contributes to determining the risks of epilepsy surgery and, therefore, remains an important part of the presurgical work-up of selected patients with clear clinical indications.

Memory for public events in patients with unilateral temporal lobe epilepsy.

Memory for public events (PEs) was assessed as a marker of remote declarative memory in 36 patients with temporal lobe epilepsy (TLE) and compared with that of 19 patients with extra-TLE (ETLE), 17 patients with idiopathic generalized epilepsy (IGE), and 23 healthy volunteers. Verbal IQ, inventory-based evidence of depression, handedness, onset of illness, disease duration, and medication were obtained. Memory for PEs was reduced in all patient groups (TLE, P<0.0001; ETLE, P=0.009; IGE, P=0.008). The TLE group showed reduced memory for PEs compared with the other patients with epilepsy (P=0.001). A time gradient was observed, with worse memory for PEs of the 1990 s and for PEs that occurred after onset of illness. Our data support the key role of the temporal lobe in remote declarative memory. With patients with TLE remembering fewer PEs from the period after onset of epilepsy, the deficits can be partly attributed to unsuccessful consolidation rather than retrieval difficulties alone.

Language lateralization in children using functional transcranial Doppler sonography.

AIM: Language lateralization with functional transcranial Doppler sonography (fTCD) and lexical word generation has been shown to have high concordance with the Wada test and functional magnetic resonance imaging in adults. We evaluated a nonlexical paradigm to determine language dominance in children. METHOD: In 23 right-handed children (12 females, 11 males; age range 6-11y; mean age 8y 4mo, SD 1y 7mo) and in 22 adolescents (14 females, 8 males; age range 12-18y; mean age 14y 8mo, SD 2y 5 mo) cerebral blood flow velocity (CBFV) was measured in both middle cerebral arteries during picture description and in adolescents additionally during lexical word generation. For each individual/paradigm a lateralization index (LI; side difference in CBFV during mental activity) and its standard error of the mean (SEM; representing variability of the LI throughout task repetition) were computed. RESULTS: Fourteen of 23 children (mean LI=0.74, SD 4.22; SEM 1.05, SD 0.51) and 14 of 21 adolescents (LI=2.35, SD 4.65; SEM 1.09, SD 0.61) showed left hemispheric dominance during picture description compared with 20 of 21 adolescents during word generation (LI=3.72 SD 1.93; SEM 0.99, SD 0.41). Indicated by similarity in mean SEM, variability of the LI throughout task repetition did not differ between age groups or paradigms. INTERPRETATION: Functional TCD proved to be well tolerated in children, with similar data quality as in adolescents. However, the picture description paradigm failed to show left hemispheric dominance in a substantial number of participants. This emphasizes the need to evaluate further paradigms for fTCD language lateralization in children.

Predicting outcome of epilepsy surgery in clinical practice: Prediction models vs. clinical acumen.

PURPOSE: Epilepsy surgery is an evidence-based treatment for drug-refractory focal epilepsy. We aimed to evaluate how well preoperative outcome estimates of epilepsy surgery in clinical practice correlated with postoperative outcome and to compare prediction by the clinical team with available scores (m-SFS, ESN). METHOD: Retrospective cohort study including patients with drug-refractory focal epilepsy who underwent resective epilepsy surgery at Epilepsy Center Hessen, Marburg, between 1998-2016. Patients were categorized into four groups based on their estimated chance of postoperative seizure freedom documented in preoperative medical records. Variables required for calculation of m-SFS and ESN were also extracted from presurgical medical records. Seizure outcome using Engel/ILAE classifications was extracted from postoperative medical records. RESULTS: 148 patients were included and 98 had follow-up at 5 years. 69 (70%) had Engel I and 50 (51%) ILAE 1 outcome. Observed 5-year outcome for very good candidates was 20/22 (91%) Engel I and 14/22 (64%) ILAE 1, for good candidates 29/40 (73%) Engel I and 21/40 (53%) ILAE 1, for candidates with slightly reduced chance 11/18 (61%) Engel I and 9/18 (50%) ILAE 1 and for candidates with considerably reduced chance 1/5 (20%) Engel I and 1/5 (20%) ILAE 1.There were no significant differences in discrimination or overall performance between predictions by the clinical team, ESN and m-SFS. CONCLUSIONS: Preoperative outcome estimates corresponded well with observed outcome indicating adequate patient counseling.

Serum concentrations of s100b and NSE in migraine.

BACKGROUND: The protein s100b indicates astrocytal damage as well as dysfunction of the blood-brain barrier (BBB), and neuron-specific enolase (NSE) is regarded as a marker for neuronal cell loss. Recently, s100b was shown to be a potentially useful marker for migraine in children. In this study, we investigated the levels of s100b and NSE in adult migraineurs during and after migraine attacks in order to gain some more insight into migraine pathophysiology. METHODS: Serum levels of s100b and NSE were measured in 21 migraineurs and compared with 21 healthy subjects matched by sex and age. In migraineurs, blood samples were taken during a migraine attack and following a pain-free period of 2-4 days. RESULTS: During migraine attacks elevated s100b levels could be observed. Maximal concentrations were detected in the pain-free period after 2-4 days. Regarding NSE, serum levels were decreased slightly during and after migraine bouts. CONCLUSIONS: Our data suggest a prolonged disruption of BBB during and after migraine attacks. Other possible explanations concerning the detected serum levels of s100b and NSE will be discussed; however, neuronal cell death can be ruled out by the decreased serum concentrations of NSE. With regard to the results of the present study, further research is necessary to evaluate the role of s100b and NSE in migraine.

Evening preference and poor sleep independently affect attentional-executive functions in patients with depression.

Cognitive impairments are well documented in major depressive disorder (MDD), however, they cannot be fully explained by depressive symptom severity. We investigated how diurnal preference and sleep quality affect cognitive function in MDD. In 34 inpatients with current MDD and 29 healthy controls (HC), we obtained diurnal preference (Morningness-Eveningness Questionnaire, MEQ) and subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI). Further, current mood and neuropsychological performance (Trail Making Test, TMT, part A and B) were assessed in the evening and in the following morning. Patients with MDD performed worse than HC on the TMT-B (particularly requiring executive function), but not on the TMT-A (assessing foremost visuomotor processing speed). In general, participants with evening preference (MEQ-score median split) performed poorer on the TMT than participants with morning preference. Subgroup analyses within MDD confirmed the negative effect of evening preference on the TMT. In addition, patients with severely impaired sleep quality (PSQI > 10) performed cognitively worse than patients with normal to moderately impaired sleep quality (PSQI ≤ 10). The results were largely independent of current mood state. Our findings suggest that evening preference and severely impaired sleep quality independently contribute to cognitive impairment in MDD.

Naming fMRI predicts the effect of temporal lobe resection on language decline.

OBJECTIVE: To develop language functional MRI (fMRI) methods that accurately predict postsurgical naming decline in temporal lobe epilepsy (TLE). METHODS: Forty-six patients with TLE (25 left) and 19 controls underwent two overt fMRI paradigms (auditory naming and picture naming, both with active baseline conditions) and one covert task (verbal fluency). Clinical naming performance was assessed preoperatively and 4 months following anterior temporal lobe resection. Preoperative fMRI activations were correlated with postoperative naming decline. Individual laterality indices (LI) were calculated for temporal (auditory and picture naming) and frontal regions (verbal fluency) and were considered as predictors of naming decline in multiple regression models, along with other clinical variables (age at onset of seizures, preoperative naming scores, hippocampal volume, age). RESULTS: In left TLE patients, activation of the left posterior inferior temporal gyrus during auditory naming and activation of left fusiform gyrus during picture naming were related to greater postoperative naming decline. Activation LI were the best individual predictors of naming decline in a multivariate regression model. For picture naming, an LI of higher than 0.34 gave 100% sensitivity and 92% specificity (positive predictive value (PPV) 91.6%). For auditory naming, a temporal lobe LI higher than 0.18 identified all patients with a clinically significant naming decline with 100% sensitivity and 58% specificity (PPV: 58.3%). No effect was seen for verbal fluency. INTERPRETATION: Auditory and picture naming fMRI are clinically applicable to predict postoperative naming decline after left temporal lobe resection in individual patients, with picture naming being more specific.

Seizures induced by the sight of moving water.

The most frequent precipitants of photic- or pattern-induced seizures are television and discotheque lighting effects. Seizure induction by reflection of bright sunlight on water surfaces has also been reported. We report a patient with seizures induced by the sight of moving water in the absence of bright sunlight. [Published with video sequences].

High-frequency rTMS of the motor cortex does not influence the nociceptive flexion reflex but increases the unpleasantness of electrically induced pain.

The aim of this study was to investigate whether a 10-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex, using a stimulus paradigm employed for pain control in chronic pain, affects acute electrically induced pain. We investigated whether rTMS modulates the nociceptive flexion reflex (NFR) in addition to subjective pain perception. Pain threshold, NFR threshold, supra-threshold NFR response, and the concomitant pain intensity and pain unpleasantness visual analogue scale (VAS) scores were compared before and after 20 min of rTMS. Effects of 20 trains of 5 s' duration (55 s intertrain interval) of 10-Hz rTMS at 80% of the resting motor threshold (RMT) applied over the dominant motor cortex were compared to sham rTMS in 12 healthy volunteers. Supra-threshold NFR stimulation significantly increased pain unpleasantness VAS scores with real rTMS compared to sham rTMS (F(1,10)=6.91; P=0.025). There was no significant effect of 10-Hz rTMS on the subjective pain threshold or on the NFR, neither at threshold nor at supra-threshold noxious stimulation. The rTMS paradigm used to control chronic pain is not suitable for controlling Adelta fiber-mediated acute experimentally induced pain since the effects on pain perception were only marginal, with an increase in the VAS unpleasantness scores but with no effect on the NFR. The increased activity of cortico-thalamic projections might modulate the perception of Adelta fiber-mediated pain within the lateral pain pathway. The type of fiber that is stimulated and neuroplastic changes in chronic pain and are thought to be critical for rTMS to have an effect.

Lack of differences of motorcortical excitability in the morning as compared to the evening in juvenile myoclonic epilepsy--a study using transcranial magnetic stimulation.

We used transcranial magnetic stimulation (TMS) in patients with juvenile myoclonic epilepsy (JME) and healthy controls to characterise motorcortical excitability in the morning as compared to the evening. Intra- and interindividual comparisons in JME-patients and controls showed no significant differences of any TMS parameter. The expected rise of the resting motor thresholds (RMT) in JME-patients taking anticonvulsants could not be detected which may indicate a decreased RMT in JME-patients.