Eugen Trinka

A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long‐term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1) beyond which the seizure should be regarded as “continuous seizure activity.” The second time point (t2) is the time of ongoing seizure activity after which there is a risk of long‐term consequences. In the case of convulsive (tonic–clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: name of pattern, morphology, location, time‐related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly.

Unified EEG terminology and criteria for nonconvulsive status epilepticus

The diagnosis of nonconvulsive status epilepticus (NCSE) relies largely on electroencephalography (EEG) findings. The lack of a unified EEG terminology, and of evidence‐based EEG criteria, leads to varying criteria for and ability to diagnose NCSE. We propose a unified terminology and classification system for NCSE, using, as a template, the Standardised Computer‐based Organised Reporting of EEG (SCORE). This approach integrates the terminology recently proposed for the rhythmic and periodic patterns in critically ill patients, the electroclinical classification of NCSE (type of NCSE) and the context for the pathologic conditions and age‐related epilepsy syndromes. We propose flexible EEG criteria that employ the SCORE system to assemble a database for determining evidence‐based EEG criteria for NCSE.

Nonconvulsive status epilepticus and coma.

Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. On the basis of EEG, NCSE in comatose patients may be classified as generalized or lateralized. This review aims to summarize the ongoing debate of NCSE and coma and to critically reassess the available literature on coma with epileptiform EEG pattern and its prognostic and therapeutic implications. The authors suggest distinguishing NCSE proper and comatose NCSE, which includes coma with continuous lateralized discharges or generalized epileptiform discharges (coma‐LED, coma‐GED). Although NCSE proper is accompanied by clinical symptoms suggestive of status epilepticus and mild impairment of consciousness, such as in absence status or complex focal status epilepticus, coma‐LED and coma‐GED represent deep coma of various etiology without any clinical motor signs of status epilepticus but with characteristic epileptiform EEG pattern. Hence coma‐LED and coma‐GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua–like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma‐LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.

Language Lateralization in Temporal Lobe Epilepsy: A Comparison between fMRI and the Wada Test

Summary:  Purpose: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI‐based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT).

The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on Status Epilepticus.

In this issue of Epilepsia, we present the next in our series of review, opinion, and commentary (pp. 1277–1288). Other such series, published in Gray Matters over the past couple of years, include discussions about: ethical dimensions of epilepsy genetics [2006, 47(10):1747–1756]; internet research [2007, 48(7):1415–1424]; drug resistance [2007, 48(12):2369–2374]; SCN1A mutation and sudden unexplained death in epilepsy (SUDEP) [2008, 49(2)360– 369]; and Wada testing [2008-49(4):715–727]. One reader has pointed out that we have not explained the format or purpose of these series, and so we have now added a section heading to clarify our intent. In these series, we publish a lead paper followed by commentaries that have been invited by the editors specifically to put forward different views. In commissioning such commentary, we hope to encourage discussion and debate that will lead to further research and elucidation of these still controversial issues. We hope this initiative is of interest to readers, and we invite readers to suggest new topic areas for debate within the pages of Epilepsia.

Intravenous lacosamide for treatment of status epilepticus.

Kellinghaus C, Berning S, Immisch I, Larch J, Rosenow F, Rossetti AO, Tilz C, Trinka E. Intravenous lacosamide for treatment of status epilepticus.
Acta Neurol Scand: 2011: 123: 137–141.
© 2010 John Wiley & Sons A/S.

O-(2-18F-fluoroethyl)-L-tyrosine PET predicts failure of antiangiogenic treatment in patients with recurrent high-grade glioma.

The objective of this study was to compare MRI response assessment with metabolic O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET response evaluation during antiangiogenic treatment in patients with recurrent high-grade glioma (rHGG). Methods: Eleven patients with rHGG were treated biweekly with bevacizumab–irinotecan. MR images and 18F-FET PET scans were obtained at baseline and at follow-up 8–12 wk after treatment onset. MRI treatment response was evaluated by T1/T2 volumetry according to response assessment in neurooncology (RANO) criteria. For 18F-FET PET evaluation, an uptake reduction of more than 45% calculated with a standardized uptake value of more than 1.6 was defined as a metabolic response (receiver-operating-characteristic curve analysis). MRI and 18F-FET PET volumetry results and response assessment were compared with each other and in relation to progression-free survival (PFS) and overall survival (OS). Results: At follow-up, MR images showed partial response in 7 of 11 patients (64%), stable disease in 2 of 11 patients (18%), and tumor progression in 2 of 11 patients (18%). In contrast, 18F-FET PET revealed 5 of 11 metabolic responders (46%) and 6 of 11 nonresponders (54%). MRI and 18F-FET PET showed that responders survived significantly longer than did nonresponders (10.24 vs. 4.1 mo, P = 0.025, and 7.9 vs. 2.3 mo, P = 0.015, respectively). In 4 patients (36.4%), diagnosis according to RANO criteria and 18F-FET PET was discordant. In these cases, PET was able to detect tumor progression earlier than was MRI. Conclusion: In rHGG patients undergoing antiangiogenic treatment, 18F-FET PET seems to be predictive for treatment failure in that it contributes important information to response assessment based solely on MRI and RANO criteria.

Polycystic ovaries, obesity and insulin resistance in women with epilepsy. A comparative study of carbamazepine and valproic acid in 105 women.

Abstract. In order to investigate the possible role of valproic acid therapy in the development of obesity, hyperinsulinism and polycystic ovaries (PCOs), we have studied metabolic parameters and ovarian morphology in epileptic women. A total of 105 women, who were treated for at least 2 years with valproate (n = 52) or carbamazepine monotherapy (n = 53), were included in the examination. Menstrual disturbances were reported by 29 (28 %) of the women, 12 (11 %) of the VPA treated women, and 17 (16 %) in the CBZ group. On ultrasound scan polycystic ovaries were found in 28 patients (27 %) of the whole study population, of whom 13 (12 %) received VPA and 15 (14 %) CBZ. The mean body mass index (BMI) was significantly higher in the VPA group (24.4 kg/m2± 4.1) than in CBZ treated patients (22.9 kg/m2± 2.4;p < 0.022), and serum triglycerides tended to be increased, while total cholesterol values (178.9 ± 30.5) and LDL-cholesterol values (92.6 ± 27.4) were significantly lower in the valproate group, than in the carbamazepine group (207.1 ± 43.0 vs 115.1 ± 42.0; p < 0.001). Postprandial insulin, C-peptide and proinsulin levels were significantly higher in VPA treated patients compared with those treated with CBZ, while no differences could be found in the fasting state. In conclusion we could thus demonstrate that the frequency of PCOs in 27 % of epileptic women seems to be similar to that in the general population with a frequency of 20–30 %. The development of PCOs did not reveal a difference with the administration of VPA or CBZ. With respect to the metabolic side-effects of VPA therapy our data indicate that VPA increases glucose stimulated pancreatic insulin secretion, which might be followed by an increase in body weight.

[18F]-fluoro-ethyl-l-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma

BACKGROUND To assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases. METHODS We retrospectively evaluated (18)F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense). RESULTS Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions. CONCLUSIONS (18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

Lacosamide as a new treatment option in status epilepticus.

Status epilepticus is among the most common neurologic emergencies, with a mortality rate of up to 20%. The most important therapeutic goal is fast, effective, and well‐tolerated cessation of status epilepticus. Intravenous phenytoin/fosphenytoin, phenobarbital, or valproate is the current standard treatment after failure of benzodiazepines. Lacosamide as a new antiepileptic drug has been available as an intravenous solution since 2009. To date, PubMed lists 19 studies (10 single case reports and 9 case series), reporting a total of 136 episodes of refractory status epilepticus (50% nonconvulsive status epilepticus, 31% focal status epilepticus, and 19% convulsive status epilepticus) treated with lacosamide. The most often used bolus dose was 200–400 mg over 3–5 min. The overall success rate was 56% (76/136). Adverse events (AEs) were reported in 25% (34/136) of patients: mild sedation in 25 cases, 1 patient with possible angioedema, 2 with allergic skin reaction, 4 with hypotension, and 1 with pruritus. One patient developed a third‐degree atrioventricular (AV) block and paroxysmal asystole. Overall, the rate of AEs was low. Current evidence on the use of intravenous lacosamide in acute seizures and status epilepticus is restricted to retrospective case reports and case series (class IV). Further prospective studies to inform clinicians are necessary.