Clinical Neuroscience

[New antiepileptic drugs, and therapeutic considerations]


SEPTEMBER 23, 2011

Clinical Neuroscience - 2011;64(09-10)

[Epilepsy is not a singular disease, but a variety of disorders. It is affects up to 0.5% of the population. Over the past decade, the researchers have been made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced for the medication. The retigabine is a carbamic derivate, and the anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. The lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. The eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appears to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it must take some new approaches into consideration, in the therapeutic algorithm.]



Further articles in this publication

Clinical Neuroscience

[Magnetic resonance measuring and analitic methods in epilepsy]


[Neuroradiology and magnetic resonance imaging (MRI) as its leading tool play a basic role in the diagnostics of epilepsy. The result of the MRI examination is of utmost importance in patients with therapy resistent focal epilepsy possibly requiring neurosurgical intervention. Based on the continuously developing MRI techniques, we can use an optimal imaging protocol. Cerebral structures can be evaluated on a microanatomical level on high-resolution images with thin slices. The three-dimensional (3D) sequence has high spatial resolution, properly distinguishes cerebral grey and white matter, provides the possibility of surface rendering and volumetry, as well as an anatomical basis for other methods like tractography, functional MRI and neuronavigation. Diffusion weighted and diffusion tensor imaging (DWI, DTI) and tractography has an important role in differential diagnostics and tractography visualizes the main white matter tracts and their relation with brain pathologies. MR perfusion (MRP) provides help in differential diagnostics and may have a future role in the determination of the epileptogenic focus in multifocal pathologies. MR spectroscopy (MRS) is important in differential diagnostics, lateralization of focal epilepsy and in the confirmation of hippocampal sclerosis. Several of these methods need special hardware, software and expertise, but the basic MRI protocol for epilepsy can be implemented in all modern MR scanners of middle or high field strength.]

Clinical Neuroscience

[Oligoepilepsy: a real entity or the benign form of epileptic disorder?]

RAJNA Péter, SÓLYOM András

[Background and purpose - Although oligoepilepsy (OLE) is a used term in many protocols, guidelines and the everyday routine, it is found practically nowhere in the scientific literature. The aim of our study is to investigate and evaluate of the main characteristics of his subcategory of epilepsy. We try to find answer to the basic question of not only theoretical but also great practical importance whether the OLE does really exist, is it an independent entity of epilepsy or only its general benign clinical presentation. Methods - We considered OLE if the patients had two seizures maximally in the last year of their course. We counted only the two most severe clinical types, the generalized tonic-clonic and the complex partial seizures. We divided the OLE into two subtypes: those patients who had OLE from the beginning of their epilepsy (OLE1) and those ones, in whom the OLE was the result of the treatment (OLE2). We analysed retrospectively the data of 817 “OLE-suspicious” patients taken from our EPIMED database Results - We found 47 patients met the inclusion criteria (OLE1=34, OLE2=13). OLE patients did not differ from the general epileptic population according to the age and gender, the type of seizures, the electro-clinical diagnosis and the possible cause of their first seizure. But we found statistically significant differences in two measures. In OLE, far less seizure provoking factors were found in the sporadic seizures. Concerning the social conditions: while the range of employees was equal, the vast majority of OLE patients were able to work at their level of education. Conclusion - We found that more than 5% of people with epilepsy can belong to the OLE category. In the majority of OLE patients the seizure frequency is low from the beginning of the disease. The sporadic seizures in OLE are generally not provoked. The chances of OLE patients in the world of job are better for the OLE patients. In our opinion OLE rather seems to be an independent entity among epilepsy. Therefore larger prospective studies are needed to the exact description of OLE and to establish the special standards for the everyday medical practice.]

Clinical Neuroscience

[The methodology and objectives of registrating high frequency oscillation in epilepsy]


[Technological advances in digital EEG allowed the recording the full frequency band of the EEG. Activity beyond the traditional 0.3-70 Hz band reflects both physiological and pathological processes. High frequency activity recorded from the epileptic brain has been related to both epileptogenicity and epileptogenesis. The article reviews research avenues, clinical applications, and the methodology of detecting and quantifying high frequency activity.]

Clinical Neuroscience

[Congress calendar]

Clinical Neuroscience

[Role of deep brain stimulation in epilepsy]

JANSZKY József, BALÁS István, KOVÁCS Norbert

[The deep brain stimulation (DBS) is an emerging treatment option in brain disorders in which randomized multicenter trials proved its efficacy leading to licensing different DBS methods in various brain diseases. More recently more and more brain structures have become candidates for being “target” in a possible DBS treatment of epilepsy. At present, only the DBS of the anterior nucleus of the thalamus (ANT) can be considered as a proved method for epilepsy treatment. Other potential targets for DBS treatment in epilepsy are the subthalamic nuclei, and the amygdala- hippocampus complex. There are some ongoing randomized studies to investigating their therapeutical role. The therapeutical outcome of ANT-DBS treatment in drug-resistant epilepsy seems to be better than the new antiepileptic drugs, but much worse than the results of a potential epilepsy surgery. At about 10% of patients may become seizure-free and 50% of patients may have a significant improvement. Nowadays ANT-DBS should be considered as an “ultima ratio” in those adult drug-resistant epilepsy patients with normal intelligence in which neither new antiepileptic drugs nor resective epilepsy surgery are a reasonable therapeutical options.]

All articles in the issue

Related contents

Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]


[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]

Clinical Neuroscience

Effects of valproate, carbamazepine and levetiracetam on Tp-e interval, Tp-e/QT and Tp-e/QTc ratio


Aim - To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods - A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results - Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusions - It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.

Clinical Neuroscience

EEG-based connectivity in patients with partial seizures with and without generalization

DÖMÖTÖR Johanna, CLEMENS Béla, EMRI Miklós, PUSKÁS Szilvia, FEKETE István

Objective - to investigate the neurophysiological basis of secondary generalization of partial epileptic seizures. Patients and methods - inter-ictal, resting-state EEG functional connectivity (EEGfC) was evaluated and compared: patients with exclusively simple partial seizures (sp group) were compared to patients with simple partial and secondary generalized seizures (spsg group); patients with exclusively complex partial seizures (cp group) were compared to patients with cp and secondary generalized seizures (cpsg group); the collapsed sp+cp group (spcp) was compared to those who had exclusively secondary generalized seizures (sg group). EEGfC was computed from 21-channel waking EEG. 3 minutes of waking EEG background activity was analyzed by the LORETA Source Correlation (LSC) software. Current source density time series were computed for 23 pre-defined cortical regions (ROI) in each hemisphere, for the 1-25 Hz very narrow bands (1 Hz bandwidth). Thereafter Pearson correlation coefficients were calculated between all pairs of ROI time series in the same hemisphere. Z-scored correlation coefficients were compared at the group level (t-tests and correction for multiple comparisons by local false discovery rate, FDR). Results - Statistically significant (corrected p<0.05) EEGfC differences emerged at specific frequencies (spsg > sg; cpsg > cp), and at many frequencies (sg > spcp). The findings indicated increased coupling between motor cortices and several non-motor areas in patients with partial and sg seizures as compared to patients with partial seizures and no sg seizures. Further findings suggested increased coupling between medial parietal-occipital areas (structural core of the cortex) and lateral hemispheric areas. Conclusion - increased inter-ictal EEGfC is associated with habitual occurrence of secondary generalized seizures.

Clinical Neuroscience

[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]


[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

Clinical Neuroscience

Relationship between Status Epilepticus Severity Score and etiology in adult NCSE patients

GENC Fatma, ERDAL Abidin, AKCA Gizem, KARACAY Ertan, GÖKSU Özaydın Eylem, KUTLU Gülnihal, GÖMCELI Bicer Yasemin

Purpose - Nonconvulsive status epilepticus (NCSE) is a heterogeneous, severe neurological disorder of different etiologies. In this study, the outcomes of NCSE episodes was assessed in a large series of adult patients. Our objective was to evaluate relationship between Status Epilepticus Severity Score (STESS) and etiology and the role of etiological factors on predicting the outcomes. Method - In this retrospective study, the medical records of 95 patients over 18 years of age who were diagnosed with NCSE between June 2011 and December 2015 were reviewed. Their treatment and follow-up for NCSE was performed at the Epilepsy Unit in Department of Neurology, Antalya Research and Training Hospital. Etiological factors thought to be responsible for NCSE episodes as well as the prognostic data were retrieved. The etiological factors were classified into three groups as those with a known history of epilepsy (Group 1), primary neurological disorder (Group 2), or systemic/unknown etiology (Group 3). STESS was retrospectively applied to patients. Results - There were 95 participants, 59 of whom were female. Group 1, Group 2, and Group 3 consisted of 11 (7 female), 54 (33 female), and 30 (19 female) patients, respectively. Of the 18 total deaths, 12 occurred in Group 2, and 6 in Group 3. The negative predictive value for a STESS score of ≤ 2 was 93.88% (+LR 2.05 95% CI: 1.44-2.9 and -LR 0.3 95% CI 0.10-0.84 ) in the overall study group. While the corresponding values for Group 1 (patients with epilepsy), Group 2 (patients with primary neurological disorder), and group 3 (patients with systemic or unknown etiology) were 100%, 92.59% (+LR 2.06 95%CI: 1.32-3.21 and -LR 0.28 95% CI 0.08-1.02 ) 83.33% (+LR 1.14 95%CI: 0.59-2.9 and -LR 0.80 95% CI 0.23-2.73). Conclusions - This study included the one of the largest patients series ever reported in whom STESS, a clinical scoring system proposed for use in patients with status epilepticus, has been implemented. Although STESS appeared to be quite useful for predicting a favorable outcome in NCSE patients with epilepsy and primary neurological disorders, its predictive value in patients with systemic or unknown etiology was lower. Further prospective studies including larger NCSE samples are warranted.