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In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.

Events of ictal bradycardia or asystole may be of relevance in epilepsy patients presenting with ictal falls, and are a potential contributor to SUDEP. The literature on ictal bradycardia or asystole is anecdotal and consists of case reports and small case series. There are no guidelines for the care of patients with ictal arrhythmias. Insertion of cardiac pacemakers may prevent life-threatening cardiac arrest, syncope and trauma. We report the case of a 41-year-old man who presented with refractory partial seizures resulting in syncope leading to severe head trauma, as the only ictal semiology. During presurgical video-EEG monitoring, two episodes of ictal bradycardia followed by asystole and syncope were recorded. A cardiac pacemaker was implanted. At the nine-month follow-up, the patient reported no overt seizures, syncopes or traumatic falls. Our case demonstrates that implantation of a cardiac pacemaker while continuing AEDs may render a patient free from ictal symptoms and prevent ictal syncope and subsequent trauma. [Published with video sequences].

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].

Purpose: Evaluation of the loci 2q36, 3q26, 5q34 and 14q23 in a German family with autosomal dominant idiopathic generalized epilepsy (IGE)., Methods: A linkage analysis was performed including 10 family members (six affected, three unaffected, one probably affected), for the loci 2q36, 3q26, 5q34 and 14q23. Subsequently, a sequence analysis of the inward rectifier potassium channel gene KCNJ13 at 2q37 was carried out., Results: Suggestive linkage for IGE was found on 2q36-37 at D2S2308 and D2S2193. No mutations were identified in the coding or 5'-non-coding regions of the exons of candidate gene KCNJ13., Conclusions: Our results corroborate former linkage findings on 2q36-2q37 and warrant further investigation of additional candidate genes within this chromosomal area in IGE.

Background: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis., Aim: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function., Methods: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'., Results: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited., Conclusion: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.

The objective of this review was to overview published cost-of-illness (COI) studies of epilepsy and their methodological approaches. Epilepsy imposes a substantial burden on individuals and society as a whole. The mean prevalence of epilepsy is estimated at 0.52% in Europe, 0.68% in the US, and peaks up to 1.5% in developing countries. Estimation of the economic burden of epilepsy is of pivotal relevance to enable a rational distribution of healthcare resources. This is especially so with the introduction of the newer antiepileptic drugs (AEDs), the marketing of vagal-nerve stimulators and the resurgence of new surgical treatment options, which have the potential to considerably increase the costs of treating epilepsy.A systematic literature review was performed to identify studies that evaluated direct and indirect costs of epilepsy. Using a standardized assessment form, information on the study design, methodological framework and data sources were extracted from each publication and systematically reported. We identified 22 studies worldwide on costs of epilepsy. The majority of the studies reflected the costs of epilepsy in Europe (three studies each for the UK and Italy, one study each for Germany, the Netherlands, Switzerland, France and the EU) and the US (four studies), but studies were also available from India (two), Hong Kong, Oman, Burundi, Chile and Mexico. The studies utilized different frameworks to evaluate costs. All used a bottom-up approach; however, only 12 studies (55%) evaluated direct as well as indirect costs. The range for the mean annual direct costs lay between 40 International Dollar purchasing power parities (PPP-$) in rural Burundi and PPP-$4748 (adjusted to 2006 values) in a German epilepsy centre. Recent studies suggest AEDs are becoming the main contributor to direct costs. The mean indirect costs ranged between 12% and 85% of the total annual costs. Epilepsy is a cost-intensive disorder. A reliable comparison of the different COI studies in epilepsy is not easily feasible, as the evaluated studies show substantial methodological differences with respect to their patient selection criteria, diagnostic stratifications and evaluated costs. Therefore, there is an urgent need for studies that evaluate direct and indirect costs in a standardized fashion.

Pregabalin is often used for the treatment of chronic pain syndromes. We here describe two patients with chronic pain and pregabalin-induced myoclonic status epilepticus. Patients treated with pregabalin who experience sudden behavioral changes or mycloni should be investigated for this possible side effect, and pregabalin should be reduced or discontinued if myocloni or status epilepticus occurs.

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.

Objective: The pathophysiology of catamenial diseases such as epilepsy is unclear. Therefore, we investigated changes in cortical excitability during anovulatory and ovulatory cycles., Patients and Methods: Using transcranial magnetic stimulation (TMS), eight healthy women were investigated during anovulatory and 12 during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle, resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. Repeated-measures analysis of variance (anova) and nonparametric methods were used for statistical analysis., Results: A trend was seen for group by phase interaction regarding ICI (F = 2.5, P = 0.10). ICI varied during anovulatory cycles (median: 51.0% on day 8; 45.3% on day -14, 51.0% on day -7, and 28.6% on day 2; P = 0.040), mainly because of an increased inhibition on day 2. ICI was more pronounced in anovulatory cycles on day -14 (P = 0.021), -7 (P = 0.048) and 2 (P = 0.018) compared to ovulatory women who did not show intraindividual changes (P = 0.56). RMT, CSP and ICF showed no significant changes during anovulatory or ovulatory cycles., Conclusions: The results suggest fluctuations in cortical excitability during anovulatory cycles, possibly due to the withdrawal of 'excitatory' oestrogens that initiate menses in anovulatory cycles.

Epidemiologic studies of status epilepticus (SE) depend on clear definitions of terms. Such a definition is available for convulsive generalized SE, but clear definitions of nonconvulsive SE (NCSE) are lacking. This as well as clinical difficulties to diagnose NCSE are one source of underascertainment. The minimal incidence of SE in the Caucasian population of industrialized countries is about 20/100,000/year. It depends on age, ethnic background and possibly gender. Case fatality rates lie between 1.9 and 40% depending on age, etiology and duration of the SE. Effective treatment can improve and focal SE itself may impair case fatality. Clearly increased rates of long term case fatality in patients with symptomatic SE suggest that these patients should be considered a population at high risk.

Purpose: The pathophysiology of catamenial epilepsy is still unclear. Therefore, we investigated the cortical excitability of women with catamenial epilepsy during different phases of the menstrual cycle., Methods: Using transcranial magnetic stimulation, six patients suffering from catamenial epilepsy were investigated during ovulatory cycles. On days 8, -14, -7 and 2 of the cycle (day 1 being the first day of menstrual bleeding), resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. The non-parametric Friedman-test for multiple comparisons and Wilcoxon signed rank test were used for statistical analysis., Results: Five patients suffered from focal epilepsy (three right hemispheric, one bitemporal, one unknown origin) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. In the right hemispheres there was a significant change of CSP duration in the course of the menstrual cycle (chi(2)=8.3, P=0.041), due to a shorter CSP during the luteal phase (Z=-2.0, P=0.043) and menstruation (Z=-2.2, P=0.028) as compared to the follicular phase. There was no significant variation of CSP in the left hemispheres. RMT, ICI and ICF showed no significant changes in the course of the menstrual cycle., Conclusions: The CSP changes suggest a decreased inhibition involving GABA-ergic neurotransmission during the luteal phase and menstruation. These TMS alterations correlated with the clinical course of the epilepsies and were found in the hemispheres containing the majority of the epileptogenic zones.

Purpose: The aim of this study was to determine the long-term case fatality of patients with a first episode of status epilepticus (SE group) of cerebrovascular etiology, as compared with that in acute stroke patients without SE (AS group)., Methods: Patients with SE who had been prospectively admitted to an epidemiologic study were retrospectively compared with a cohort of patients from the local stroke registry. The main outcome end point was overall survival. Survival curves were generated according to the Kaplan-Meier method and compared by using the log-rank test. An extended Cox model was used to examine the impact of patient group on the risk of death. Covariates considered potential confounders included age at diagnosis, sex, type of stroke, affected hemisphere, and localization of lesions., Results: Of 166 patients who entered the study, 93 patients were in the SE group, and 73 patients were in the AS group; 53 SE patients and 35 AS patients died during the study. Patient group (SE vs. AS) showed no significant impact on survival (p=0.0832) in univariate analysis. In contrast, the results from a multivariable analysis suggest that after 6 months, patients with SE were at about twice the risk of death as were patients with AS [hazard ratio of 2.12 with 95% confidence interval, 1.04-4.32, p=0.0392]., Conclusions: The occurrence of SE in patients with cerebrovascular disease indicates a high risk of death within 3 years. In contrast, the case fatality risk attributable to recurrent status or seizures is lower.

Purpose: There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center., Methods: A "prevalence-based," cross-sectional convenience sample of adults with active epilepsy attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure-free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three-month period using questionnaires and a patient diary. Cost driving factors were identified., Results: One hundred one patients were included (40.7+/-15.2 years; disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with generalized tonic-clonic seizures). The total costs of epilepsy per patient were in average euro 2610+/-4200 over the three-month period. Direct cost contributed 39% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls, and situationally inappropriate complex behavior during or after the seizure., Conclusions: Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of poorly controlled epilepsy in this German study were above average of the European costs of epilepsy.

Little is known about the effectiveness of clinical courses as a learning environment. To accurately assess performance in these courses, equal conditions for all candidates are required. We investigated the influence of the proximity of the course to the students test taking, the students' learning styles, and their self-motivation for learning in relation to performance success. One hundred and eleven students were randomized into eight groups, each attending a 2 week course in otolaryngology with a high proportion of patient-related teaching, and a 2 week long course in neurology with a low level of patient-related teaching. All students took multiple-choice end-of-term exams to assess their knowledge in both subjects. There was a different time interval between the course participation and the test taking for each of the groups. Performance success was correlated with the different groups, as well as with the type of learning style (LIST questionnaire) and with motivation for learning (study interest questionnaire). Explorative rank variance analysis showed a significant correlation between students' performance on the written exam and the time interval between completion of the neurology course and test-taking, with the shortest interval corresponding to highest scores (P = 0.002). There was no such effect on the success rate in otolaryngology (P = 0.28). Study motivation was not the major component for performance success, but a strong correlation between the use of strategic and deep learning styles and success in the exam was observed (R = 0.62; P < 0.001). The duration of time between a clinical course with little practical teaching and the students' taking of the exam plays a significant role on performance success; this effect does not occur in a course with a high proportion of practical patient-related teaching. More studies on clinical courses are needed to establish how students can be given adequate opportunities to develop necessary skills for patient care and for objective success on assessment. With such further information, the effectiveness of clinical courses as a learning experience might be enhanced.

Functional transcranial Doppler sonography was used to study hemispheric language dominance (HLD) in 24 right-handed patients with left temporal lobe epilepsy (TLE) and a structural lesion in the left temporal lobe and in 69 healthy controls. Twenty-five percent of the patients and 4% of controls showed atypical (right or bilateral) HLD. Degree of HLD was not correlated with age, Full Scale IQ, Verbal IQ, spike frequency, seizure frequency, age at seizure onset, or duration of TLE. Atypical HLD appears to be lesion-induced, independent of epilepsy characteristics.

The purpose of this study was to evaluate the predictive value of intraoperative electro-corticography (ECoG) in patients with unilateral hippocampal sclerosis (HS) undergoing transsylvian selective amygdalohippocampectomy (sAHE). ECoG was recorded before and after resection in 22 patients with medication-resistant mesial temporal lobe epilepsy. The sAHE was performed, regardless of ECoG findings. ECoG findings recorded from the mesiobasal temporal lobe (MTL) and lateral temporal lobe (LTL) before and after the sAHE were correlated with seizure outcome 12 months later. Ten patients had right-sided and 12 left-sided HS. Average age was 37.1 years. Pre-resection spikes were restricted to the MTL in 11 patients and to the LTL in one. In three patients spikes were recorded from MTL and LTL and in seven no spikes were recorded before the resection. Fifteen patients (68%) remained completely seizure-free and 19 (86%) were in Engel's class I post-operatively. Patients with pre-resection spikes restricted to the MTL (n = 11) remained seizure-free more frequently (9/11, 82%) compared with other patients (6/11, 55%; P = 0.36). Pre-resection ECoG may be helpful in the prediction of seizure outcome in patients undergoing sAHE for mesial temporal lobe epilepsy. A larger study including more than 100 patients is needed to determine the predictive value of ECoG in patients with mesial temporal lobe epilepsy.

Objective: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery., Methods: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers., Results: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients)., Conclusion: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Background: A 38-year-old, right-handed man with late-onset right frontal epilepsy due to a ganglioglioma and atypical right hemispheric language dominance is described., Methods: Language dominance was investigated with functional transcranial Doppler sonography (fTCD), and language localization with functional magnetic resonance imaging (fMRI)., Results: During a word generation task, fTCD showed atypical right hemispheric language dominance, which was confirmed by fMRI using a semantic word comparison and a word stem completion task. This information helped to guide the resective procedure, which left the patient seizure-free and did not induce new deficits., Conclusion: Functional TCD appears to be a useful and reliable screening tool for determining hemispheric language dominance, even in patients with atypical language representation. Functional MRI may be used to confirm fTCD results and further localize eloquent cortex.

Objective: To evaluate whether genetic factors contribute to weight gain associated with valproate (VPA) therapy., Research Methods and Procedures: We retrospectively and prospectively evaluated five pairs of monozygotic twins concordant for epilepsy and treated with VPA regarding weight course., Results: In all twin pairs, both twins showed similar weight courses under therapy with VPA., Discussion: These results suggest that genetic factors may have an influence on the weight change induced by VPA. Further studies are necessary to obtain heritability estimates regarding this effect of VPA therapy and to identify the relevant genes.

The classification of status epilepticus (SE) has been a subject of discussion for many years, yet no satisfactory agreement has been reached. Due to their complexity, status episodes often defy classification according to the current international classification scheme. The semiological seizure classification (SSC) has been in use in several epilepsy centers for more than a decade, and has proven to be a valid approach to the classification of epileptic seizures. Based on the detailed analysis of more than 100 episodes of SE documented with video-EEG recordings, the authors now present a proposal for a semiological classification of status epilepticus (SCSE). The SCSE reflects the assumption implied by all modern definitions of SE that "there are as many types of status as there are types of seizures" and relies on the same principles as the SSC, focusing on the main clinical manifestations and the evolution of the status episode. The clinical manifestations of SE are subdivided into semiological components and classified along three axes: the type of brain function predominantly compromised by the seizure activity, the body part involved, and the evolution over time. Each axis contains several subcategories, so that many different levels of accuracy are possible. The SCSE, just like the SSC, is meant to be part of a comprehensive epilepsy classification which classifies as independent variables (epileptogenic zone, ictal semiology, etiology, related medical conditions) the main features of the patient's epilepsy, allowing for each variable maximum flexibility.

Purpose: Levetiracetam (LEV) is a new compound with anticonvulsive efficacy in focal and generalized epilepsies. Recent in vitro studies suggest LEV to act as a selective N-type-calcium-channel blocker., Methods: We used transcranial magnetic stimulation (TMS) in order to investigate if ion-channel blockade is relevant to the inhibitory CNS effects of LEV in vivo and if motor thresholds (MTs) are a valid TMS parameter to detect this mode of action. In a double blind, placebo-controlled, crossover study, the effects of single oral doses of 500 and 2000 mg LEV on motor thresholds, recruitment curves (REC), cortical induced silent period (CSP) and on intracortical inhibition (ICI) and facilitation (ICF) were studied in 10 healthy subjects., Results: A significant increase of motor thresholds was noticed after 2000 mg LEV as compared to placebo. The recruitment curve showed a trend towards motor evoked potential (MEP) amplitude reduction after LEV. LEV had no significant effect on CSP or on intracortical excitability as measured by inhibition and facilitation., Conclusions: We conclude that the modulation of ion-channel function, reflected by motor threshold elevation and a trend towards recruitment curve suppression, is relevant to the inhibitory CNS effects of LEV in vivo, and therefore, may contribute to the anticonvulsive efficacy of LEV. GABAergic or glutamatergic mechanisms seem to be less important in vivo as measured by TMS.

Ictal functional transcranial Doppler sonography (I-fTCD) was used to lateralize the ictal onset zone in the presurgical evaluation of two patients with temporal lobe epilepsy. In one patient, I-fTCD and ictal SPECT were performed simultaneously during EEG-monitoring. In both patients, results were concordant with the ictal SPECT findings, PET and semiology. I-fTCD seems to be an interesting new method to non-invasively lateralize the seizure onset zone with high temporal resolution. I-fTCD and SPECT may give complementary information to lateralize the seizure onset zone.

Purpose: To report that iopamidol myelography can induce status epilepticus (SE) in patients carrying the diagnosis of symptomatic epilepsy and to estimate the incidence of seizures in patients undergoing iopamidol myelography., Methods: We retrospectively identified all patients with seizures/SE associated with 1350 iopamidol myelographies during the last 5 years at our institution. The impact of cervical versus lumbar myelography was analysed., Results: Induced by iopamidol myelography two non-epileptic patients suffered from first generalised tonic-clonic seizures and a 67-year-old women with symptomatic epilepsy after a remote ischemic stroke developed a generalised tonic-clonic seizure evolving into a dialeptic and right nystagmus SE (i.e. complex focal status) of 5-hour duration. The incidence of seizures in non-epileptic patients was 0.15%. The incidence of seizure induction for lumbar myelography was lower than for myelographies that included the cervical subarachnoid space., Conclusions: Iopamidol myelography (especially if cervical) is associated with a risk of seizures in non-epileptic individuals and can induce SE in patients with epilepsy. Patients should be informed about the risk of seizure induction.

Purpose: To evaluate the relative impact of 3 and 5 min of hyperventilation (HV) and different sleep stages on the sensitivity of the interictal EEG in focal epilepsy., Methods: We examined 20 patients with temporal lobe epilepsy (TLE, 85%) or extratemporal epilepsy during EEG-monitoring. We compared 6 min EEG (12 epochs of 30s) during/after each: (a) waking; (b) 5 or 3 min of HV; (c) sleep stages 1, 2, 3/4 and REM regarding the frequency of epileptiform discharges (ED). The Wilcoxon matched pairs signed rank test was used. The main endpoint was the comparison of 5 min of HV with sleep stage 2., Results: During sleep stage 2, ED were more frequent than during/after 5 min of HV (P=0.002). Compared to the waking EEG, all NREM-sleep stages activated ED. Sleep stage 2 was associated with the strongest activation. There was no difference between the waking state and REM-sleep. Compared to the waking EEG, neither 3 nor 5 min of HV showed an activation of ED., Conclusion: In patients with TLE, sleep stage 2 shows a significantly higher sensitivity for ED than 5 min of HV. Compared to the waking EEG, HV showed no activating effect on ED. These results suggest that in patients with the clinical diagnosis of TLE (and possibly other focal epilepsies) measures to record sleep stage 2 (such as sleep deprivation) should be increased whereas HV appears to be dispensable in this setting.

This study prospectively investigates whether noninvasive functional transcranial Doppler sonography (fTCD) is a useful tool to determine hemispheric language lateralization in the presurgical evaluation of patients with medically intractable temporal lobe epilepsy (TLE). fTCD results were compared with the Wada test as the gold standard. Wada test and fTCD were performed in 13 patients suffering from TLE. fTCD continuously measured blood flow velocities in both middle cerebral arteries, while the patient was performing a cued word generation task. During the Wada test, spontaneous speech, comprehension, reading, naming, and repetition were investigated. A laterality index (LI) was obtained by both procedures. Due to a lack of an acoustic temporal bone window, fTCD could not be performed in two patients (15%). In 9 of the remaining 11 patients hemispheric language dominance was found on the left side, in 1 patient on the right side, and 1 patient showed bihemispheric language representation. In all patients fTCD and the Wada test were in good agreement regarding hemispheric language lateralization, and the LI of both techniques were highly correlated (r = 0.776, P = 0.005). fTCD gives predictions of hemispheric language dominance consistent with the Wada test results even in children, patients with low IQ, and nonnative speakers. It is an alternative to the Wada test in determining language lateralization in patients with temporal lobe epilepsy.

Focal clonic seizures are a frequent epileptic phenomenon. However, there are few data about their pathogenesis. Eleven patients with focal epilepsy who experienced focal clonic seizures during prolonged video-EEG monitoring were included in this study. Nine patients had subdural electrodes on the precentral gyrus and one patient had additional bilateral subthalamic nucleus (STN) depth electrodes. In five patients, the EEG was co-registered with the EMG of muscles which were involved in the clonic seizures. The frequency, pattern and evolution of the ictal EEG were analysed and their relationship to STN and EMG activity was studied. Focal clonic seizures were always associated with a polyspike-wave pattern in the EEG of the primary motor area (frequency range 1.6-3.4 Hz), while neighbouring electrodes not overlying the precentral gyrus showed different EEG patterns. At seizure onset, the ictal EEG derived from the precentral gyrus consisted of repetitive spiking for 8-28 s (median 19.5 s), accompanied by a continuous increase in muscle tone. This evolved to a pattern of polyspike-wave complexes which were associated with clinical clonus and lasted for 14-202 s (median 30.5 s). The clonic muscle contractions consisted of bursts of compound muscle action potentials (CMAPs) which occurred synchronously in agonistic and antagonistic muscles and were separated by periods of complete muscle relaxation. Each series of CMAPs followed the polyspikes in the EEG with a latency of 17-50 ms. The periods of muscle relaxation occurred during the EEG slow waves. Only some of the cortical spikes were followed by ipsilateral STN spikes. CMAPs followed the cortical polyspikes independently of whether or not STN spikes were seen. The study suggests that focal clonic seizures are focal tonic-clonic seizures. The epileptic clonus consisted of simultaneous contractions of agonistic and antagonistic muscles at regular intervals and was generated by localized polyspike-wave activity in cortical primary motor areas. Activation of the STN did not appear to be an essential component of clonic seizures.

Bismuth (Bi) is used for the treatment of different gastrointestinal symptoms and disorders such as gastric ulcers. In Germany, Bi medication is available without prescription as over-the-counter-medication even though it can cause severe myoclonic encephalopathy if ingested chronically in high doses. We report a 49 year-old woman with chronic gastric ulcers and 5 years of Bi abuse who developed the typical clinical course of Bi encephalopathy. She presented with progressive dementia, dysarthria and myoclonic jerks one week after increasing the Bi dosage. The EEG showed generalized spike-wave complexes suggesting that the myoclonus was epileptic in nature. Bi intake was stopped and valproate was given, which decreased the frequency of the myoclonic jerks. Administration of the metal chelator D,L-2,3-dimercaptopropane- 1-sulfonic acid (DMPS) led to increased urine excretion of Bi, but was accompanied by a clinical deterioration which resulted in it being discontinued. The subsequent clinical recovery of the patient was documented over 40 days by EEG, video and neuropsychological testing. A time lag of two weeks was observed between falling plasma levels and clinical improvement. In conclusion, Bi-induced encephalopathy is a differential diagnosis for myoclonic encephalopathies. Treatment with metal chelators may aggravate the encephalopathy. The over-the-counter availability of medications containing Bi should be questioned. (Published with video sequence.)

Purpose: Topiramate (TPM) is a novel drug with broad antiepileptic effect in children and adults. In vitro studies suggest activity as sodium-channel blocker, as gamma-aminobutyric acid type A (GABAA)-receptor agonist and as non-N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist., Methods: With transcranial magnetic stimulation (TMS), we evaluated which of the mechanisms of action of TPM detected in vitro are relevant for the modulation of human motor cortex excitability. In a double-blind, placebo-controlled, crossover study design, we investigated the effect of single oral doses of 50 mg and 200 mg TPM on motor thresholds, cortical silent period (CSP), and on intracortical inhibition (ICI) and intracortical facilitation (ICF) in 20 healthy subjects., Results: A significant dose-dependent increase of ICI was noticed after 200 mg TPM as compared with placebo at short interstimulus intervals of 2 to 4 ms. TPM had no effect on motor thresholds or the CSP., Conclusions: We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion-channel blockade or GABAB-receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.

Focal clonic seizures are a frequent epileptic phenomenon. However, there are little data about their pathomechanism. In four patients with focal epilepsy and subdural electrodes, focal clonus was elicited by electrical stimulation of the motor cortex. Three additional patients underwent intraoperative stimulation of the spinal cord. Rhythmic clonic muscle responses were elicited by cortical stimulation with 20-50 Hz. The clonus consisted of simultaneous trains of compound muscle action potentials (CMAP) in agonistic and antagonistic muscles alternating with periods of muscular silence despite continuous stimulation. Clonus frequency decreased from 4.0-8.0 Hz at 50 Hz stimulation to 3.0-3.5 Hz at 20 Hz paralleled by a prolongation of the trains of CMAP. The stimulation frequency correlated with the number of stimuli blocked during relaxation. During the stable stimulation periods, the clonus frequency decreased over time. The number of stimuli which formed a train of CMAP and which were blocked during relaxation increased towards the end of the stimulation periods. Increasing intensity of stimulation at the same frequency converted a clonic to a tonic response. There was always an 1:1 relationship between stimulus and CMAP during spinal cord stimulation. We hypothesize that during cortical stimulation, clonus is elicited by synchronous activation of pyramidal tract (PT) neurons which results in excitation of intracortical GABA(B)ergic interneurons by recurrent axon-collaterals. This leads to stepwise hyperpolarization of PT neurons intermittently suppressing the output of PT neurons despite continuous stimulation. This mechanism can explain our finding that temporal and spatial summation of the stimuli were needed for clonus generation., (Copyright 2002 Elsevier Science B.V.)

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of the primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.

Objective: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes., Methods: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997., Results: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization., Conclusions: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

This report reviews the lateralising and localising signs of epileptic seizures in respect to the differential diagnosis of epilepsy. The lateralising value of epileptic signs and symptoms can frequently be derived from the neuroanatomy. Focal clonic, focal tonic, and versive seizures as well as ictal unilateral dystonia are associated with a seizure onset zone in the contralateral hemisphere. Postictal nose wiping is performed with the hand ipsilateral to the epileptogenic zone. Similarly, unilateral blinking points to an ipsilateral seizure onset. Automatisms with preserved consciousness, ictal speech, and vomiting correlate to an epileptogenic zone in the non-dominant hemisphere, while postictal dysphasia is produced by seizures arising from the dominant hemisphere. Lateralising and localising signs and symptoms of epileptic seizures are of great help in the differential diagnosis of epilepsy from the first diagnosis of epileptic events to presurgical video-EEG monitoring.

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down's syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down's syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic-tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down's syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer's disease (AD) and Unverricht-Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged., (Copyright 2001 BEA Trading Ltd.)

Purpose: To determine the incidence and case-fatality rate of status epilepticus (SE) in adults in Hessen, Germany, we performed a prospective, population-based study from July 1997 through June 1999., Methods: All adult patients residing within the zip-code area 35 (area-35) with SE were included. Area-35 had 743.285 adult inhabitants, including 123.353 adult inhabitants of the primary service area of the University Hospital Marburg (PS-area). Patients were reported by 16 hospitals in the area and were prospectively identified and carefully reviewed within 5 days by one of the authors. Based on the crude annual incidence of SE and a rate of underascertainment of 10% determined for the PS-area, the corrected, age-adjusted incidence of SE in area 35, more representative of the population of Germany, was calculated., Results: The crude annual incidence in the PS-area was 15.8/100,000 [95% confidence interval (CI), 11.2-21.6]. The calculated, corrected, age-adjusted incidence of SE in area 35 was 17.1/100,000. It was higher for men compared with women (26.1 vs. 13.7) and for those aged 60 years and older (54.5 vs. 4.2/100,000, p < 0.0001). The etiology was mainly remote symptomatic due to cerebrovascular disease. Epilepsy was previously diagnosed in only 50% of the patients. The case-fatality rate was 9.3%., Conclusions: Based on our data, at least 14,000 patients would be affected by SE in Germany, associated with approximately 1,300 deaths annually. The incidence of SE in Germany is similar to that found in the white United States population. Furthermore, this study confirms the higher incidence of SE in male patients and in the elderly population. This may be due to a higher incidence of cerebrovascular disease in these subpopulations.

Purpose: The 18q- deletion syndrome (18qDS) is frequently associated with cardiac anomalies. Patients with this syndrome may also have epilepsy, which presents certain diagnostic difficulties. This case report aims to illustrate these diagnostic problems, document the usefulness of heart rate-based seizure detection algorithms in this setting, and define the epilepsy syndrome associated with 18qDS., Methods: Closed-circuit video electroencephalogram (EEG) monitoring using a heart rate-based seizure detection software was used to identify the event in question and to establish the diagnosis of epilepsy. Chromosomal analysis and magnetic resonance imaging (MRI) were used to further define the epilepsy syndrome., Results: We report on a patient with an atrial septal defect, enlargement of the right heart, and incomplete right bundle branch block, who developed episodes of tachycardia, loss of consciousness, and pallor, for which he was amnesic. Chromosomal analysis demonstrated karyotype 46,XY,del(18)(q21.3). ish del(18)(wcp18+,D18Z1+) with a loss of the gene for myelin basic protein. MRI revealed multifocal dysmyelination. Video-EEG monitoring using an electrocardiogram (ECG)-triggered seizure detection software proved to be indispensable in detecting an autonomic seizure and establishing the correct diagnosis; the procedure also allowed for the definition of the epilepsy syndrome. The patient was treated with carbamazepine and remained seizure-free., Conclusions: Video-EEG monitoring using a heart rate-based seizure detection software can be helpful in diagnostically differentiating autonomic seizures from syncope. Dysmyelination due to loss of the myelin basic protein gene on 18q and cortical dysgenesis may be of pathogenic relevance.

Purpose: Identification of risk factors for unsuccessful testing during intracarotid amobarbital procedure (IAP) in preadolescent children., Methods: A pediatric IAP protocol was attempted in 42 candidates for epilepsy surgery (5-12 years old; mean, 10 years) based on the ability to pass a practice test. Language dominance was defined by marked asymmetry until first verbal response and paraphasic errors. Intact hemispheric memory was defined by recall of >/=60% of test items. The odds ratios of baseline variables (age at IAP, Full-Scale IQ, side of disease, age at seizure onset, amobarbital dose) were calculated for various IAP outcomes., Results: IAPs were accomplished in 40 children. Language dominance was established in 25 (62.5%) of 40 patients: all 21 focal resection candidates were left language dominant; four hemispherectomy candidates had intact language after injection of the damaged hemisphere. In 12 (30%) of 40 patients, language testing failed because of agitation or obtundation. Compared with the 21 children with language dominance established by bilateral IAP, these 12 children had lower mean Full-Scale IQ (66.4 vs. 87.9; p = 0.014), and more frequently, the epileptogenic lesion in the left hemisphere (presumed dominant by right-handedness; 78 vs. 33%; p = 0.04). Excluding hemispherectomy candidates (intentionally only one injection), memory testing could not be completed in 13 (36%) of 36 children because of obtundation or agitation. These children were significantly younger than the 23 (64%) of 36 with successful bilateral memory testing (mean age, 107.6 vs. 128.7 months; p = 0. 006). The eight (25%) of 32 children with failing retention scores after ipsilateral injection had lower Full-Scale IQ than did the 24 (75%) patients who passed (mean, 59.6 vs. 81.7 months; p = 0.03)., Conclusions: The IAP successfully established hemispheric language dominance and memory representation for just under two thirds of the preselected preadolescent children. Risk factors for unsuccessful testing included low Full-Scale IQ (especially <80), young age (especially <10 years), and seizures arising from the left hemisphere presumed dominant by right-handedness.

Two adult patients with focal epilepsy who tolerated valproate (VPA) well in different combinations of anticonvulsants developed hyperammonemic encephalopathy when treated with VPA in combination with topiramate (TPM). Topiramate may contribute to the increased ammonia level by its inhibition of carbonic anhydrase and cerebral glutamine synthetase, thereby facilitating VPA/TPM hyperammonemic encephalopathy. Recovery occurred after withdrawal of VPA or TPM.

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.

Several medications such as baclofen, amitriptyline and even antiepileptic drugs such as carbamazepine or vigabatrin are known to induce absence status epilepticus in patients with generalized epilepsies. Tiagabine (TGB) is effective in patients with focal epilepsies. However, TGB has also been reported to induce non-convulsive status epilepticus in several patients with focal epilepsies and in one patient with juvenile myoclonic epilepsy. In animal models of generalized epilepsy, TGB induces absence status with 3-5 Hz spike-wave complexes. We describe a 32-year-old patient with absence epilepsy and primary generalized tonic-clonic seizures since 11 years of age, who developed her first absence status epilepticus while treated with 45 mg of TGB daily. Administration of lorazepam and immediate reduction in TGB dosage was followed by complete clinical and electroencephalographic remission. This case demonstrates that TGB can induce typical absence status epilepticus in a patient with primary generalized epilepsy., (Copyright 1999 BEA Trading Ltd.)

Purpose: Few data are available concerning symptomatology of epileptic seizures in infants., Methods: We reviewed 296 videotaped seizures from 76 patients aged 1-35 months (mean, 15.1 months) who underwent video-EEG monitoring at our institution from 1988 to 1998. Seizure symptomatology was first classified based on observable behavioral and motor manifestations and then correlated with ictal EEG., Results: Four seizure types accounted for 81% of all seizures seen in this group: epileptic spasms (24%), clonic seizures (20%), tonic seizures (17%), and hypomotor seizures (20%; characterized by arrest or significant decrease of behavioral motor activity with indeterminate level of consciousness). The remaining seizures included small numbers of myoclonic, atonic, and versive seizures. All 12 focal motor seizures and all five versive seizures were associated with focal EEG seizure patterns, seen in the contralateral hemisphere in all but one patient with versive seizures. Generalized motor seizures (clinically generalized at onset) were accompanied either by focal (19 of 51; 37%) or generalized (32 of 51; 63%) EEG seizures. Hypomotor seizures also were associated with focal (14 of 20; 70%) or generalized (six of 20; 30%) EEG seizures. Four patients with generalized epileptic spasms had generalized EEG seizures in the setting of focal epilepsy based on neuroimaging, interictal EEG, and in two cases also on postresection seizure freedom. Seizure types not seen in this age group included auras, seizures with prominent automatisms (except in one case), and classic generalized tonic-clonic seizures., Conclusions: The repertoire of seizure manifestation in the first 3 years of life appears to be limited. In infants, focal motor seizures are reliably associated with focal EEG seizures in the contralateral hemisphere, whereas generalized motor and hypomotor clinical seizures may be either focal or generalized on EEG. Epileptic spasms may be seen in focal as well as generalized epilepsies. Video-EEG monitoring and neuroimaging may be critical for clarifying the focal or generalized nature of the epilepsy in infants.

We report three consecutive patients with hypersensitivity syndrome (HSS) due to phenytoin and carbamazepine and successful treatment with gabapentin. HSS is a rare but potentially fatal reaction to multiple drugs including several anticonvulsants. Cross-reactivity among drugs may occur. Immediate withdrawal of the offending drug is the most important step in treatment. Benzodiazepines acutely and, after resolution of the hepatitis, valproic acid have been successfully used for seizure control in patients with HSS. Our cases indicate that gabapentin is also a safe anticonvulsant in HSS., (Copyright 1999 BEA Trading Ltd.)

Anticonvulsant hypersensitivity syndrome, a potentially fatal but rare reaction, manifests as rash, fever, tender lymphadenopathy, hepatitis, and eosinophilia. To manage hypersensitivity syndrome successfully, one must recognize the symptoms early, stop the offending drug immediately, and substitute a safe, alternative anticonvulsant medication. Hypersensitivity syndrome has not been described in patients taking benzodiazepines or the newer anticonvulsants gabapentin or topiramate, and these appear to be safe substitutes for drugs that cause the reaction.