[Epilepsy in the elderly. Special clinical features and treatment strategies]. / Epilepsie im höheren Lebensalter. Klinische Besonderheiten und Therapiestrategien.

BACKGROUND: With increasing life expectancy, the incidence rate of epilepsy in the elderly has considerably increased in recent decades. This leads to new diagnostic and therapeutic challenges. OBJECTIVES: Recognition of the special clinical features of epilepsy in the elderly is essential for diagnosis, therapy and prognosis. Special consideration is placed on comorbidity and drug interactions. METHODS: The literature and new developments in this field are reviewed and discussed. RESULTS: Epilepsy often presents in patients older than 60 years for the first time. The etiology of epilepsy in the elderly is heterogeneous with most belonging to symptomatic epilepsies that are associated with an underlying structural lesion of the brain. Epilepsy in the elderly is distinguished from that in other age groups by its clinical presentation. The treatment of seizures in the elderly is a particular challenge because not only due to comorbidity and co-medication but also because of metabolic changes in this age group. CONCLUSION: Epilepsy in the elderly has diagnostic and therapeutic features that require careful clinical assessment and differentiated therapy.

Intravenous lacosamide for treatment of status epilepticus.

OBJECTIVES: Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. METHODS: We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. RESULTS: Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. CONCLUSIONS: Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Visual field defect during therapy with valproic-acid.

Visual field defect because of antiepileptic drug (AED) treatment has been widely reported during the clinical application of vigabatrin. But other gamma-aminobutyric acid (GABA)-ergic and non-GABA-ergic AEDs could also affect the visual field with different mechanisms of action. Here we report a case of a 22-year-old female patient, who suffered from bilateral concentric visual field defect during the long-term therapy with valproic-acid (VPA). A VPA-related metabolic dysfunction was found through blood and urine examination. Reduced B-waves were shown by electroretinography and a bilateral concentric visual field defect was confirmed by both manual and automated perimetry. In conclusion, the concentric visual field defect related to VPA treatment is rare but possible.

Influence of levetiracetame on ictal and postictal EEG in patients with partial seizures.

To investigate the influence of levetiracetame (LEV) treatment on the interhemispheric seizure pattern propagation and postictal recovery of electroencephalography (EEG) background activity. Twenty-three adult patients (age > 16 years) with pharmacoresistant focal epilepsies presenting at the Epilepsy Center Erlangen for pre-surgical evaluation were enrolled in the study. Those eligible patients receiving only one antiepileptic drugs were recruited to the 48-h baseline phase and, after at least two seizures, were randomized to the 7-day treatment phase with either LEV (n = 11) or placebo (n = 12). All participants were submitted to continuous day-and-night video-EEG monitoring. The daily dose of LEV was 1000 mg (500 mg bid.) on the first treatment day and was increased to 2000 mg (1000 mg bid.) from the second day onward. The EEG changes relating to the time delay of the interhemispheric seizure pattern propagation and to the postictal recovery of the background activity were analysed by computerized video-EEG recording and compared using the non-parameter Mann-Whitney U-exact test (alpha = 0.05). A prolonged latency of the contralateral seizure pattern propagation was observed in the LEV group, whereas a more rapid propagation was observed in the placebo group (P = 0.009). Postictal generalized slowing of the background activity was recorded in 21 patients during the baseline phase. More rapid postictal recovery of the EEG background activity was observed in the LEV, but not in the placebo group (P = 0.03). This study demonstrated that LEV not only prevented the seizure pattern propagation but also helped the speedy recovery of the postictal background activity in the EEG.

Changes of seizures activity during rapid withdrawal of lamotrigine.

Quantitatively evaluating the rapid withdrawal effects of lamotrigine (LTG) and carbamazepine (CBZ) on seizure activity during pre-surgical evaluation in patients with pharmacoresistant complex partial epilepsy. The duration and frequency of seizure activities and electrographic seizure onset of 41 patients totally withdrawing from CBZ monotherapy (n = 20), LTG monotherapy (n = 10) and CBZ + LTG combined therapy (n = 11) were intensively studied by therapeutic intensive seizure analysis (TISA) method. Study phases ran from the baseline phase to the antiepileptic drug (AED) withdrawal phase until the AED free phase, 3 days for each phase. Seizure duration and frequency obviously increased during the withdrawal process in each group (P < 0.05). The duration of secondarily generalized clonic signs markedly increased with the tapering of each drug; tonic signs, however, only in the AED free phase (P < 0.05). The frequency of secondary tonic and clonic signs only increased in the CBZ and CBZ + LTG group. Intergroup comparisons of all variables were insignificant (P > 0.05). There was no change of ictal EEG localization during all withdrawal protocols. All patients experienced more severe seizures during the withdrawal processes. An earlier aggravation of the clonic signs than the tonic signs was observed in each group. Difference between the withdrawal effects of LTG and CBZ monotherapy and LTG + CBZ polytherapy was mainly in the frequency change of ictal signs. The withdrawal process did not influence the ictal EEG localization. This study justified the withdrawal in pre-surgical localization, rationalized precautions for possible accompanying risks, and also aroused attentions in clinical anticonvulsant trials and substitutions involving withdrawal process.

Comparison of clonidine to sleep deprivation in the potential to induce spike or sharp-wave activity.

OBJECTIVE: This study aimed to investigate previously observed side effects, i.e. increased epileptic activity during clonidine medication. The safety and effectiveness of clonidine as spike inducing agent compared to sleep deprivation were tested. METHODS: Patients suffering from drug-resistant localization related epilepsy took part in 3 magnetoencephalography (MEG) sessions. One session was recorded without any activating measures. The other two sessions were either performed after sleep deprivation or after medication with clonidine. Target parameter was the number of spikes or sharp-waves during a 30 min recording period. RESULTS: About 67% of the patients showed increased spike activity after clonidine, whereas sleep deprivation increased the number of spikes in 33%, and 29% of the patients did not show any activation at all. Clonidine was most effective in temporal lobe epilepsy, when the focus was located in the right hemisphere, and when clonidine serum concentrations were ranging between 0.6 and 1.0 ng/ml. CONCLUSIONS: This study showed for the first time that clonidine can be considered an effective spike or sharp-wave inducing drug that is superior to the potency of sleep deprivation. SIGNIFICANCE: The administration of clonidine increases the probability of recording ictal and interictal epileptic activity during limited acquisition time.

Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases.

Epilepsy surgery is based upon the minute assessment of brain tissue generating epileptic activity. A number of diagnostic methods are employed in the process of presurgical evaluation, supplying information on various morphological and functional aspects, ultimately integrated into the general result fundamental to the final treatment decision. Magnetic source imaging (MSI), combining structural (MRI) and functional (MEG) data, has been playing an increasingly important role among the tools of presurgical epilepsy evaluation. However, in spite of a considerable number of publications, the samples used have hardly exceeded 50 cases. Therefore, we present a synopsis of 455 epilepsy patients who underwent MSI investigations. Analysis of this substantial data revealed that the average sensitivity of MEG for specific epileptic activity was 70%. Among 131 patients who underwent surgical therapy in addition to antiepileptic drug medication, MSI identified the lobe to be treated in 89%, with results for extratemporal cases being even superior to those with temporal lobe surgery. Introducing a measure to quantify the contribution of MSI to the general result of presurgical evaluation that was applied to 104 patients, the results showed that MSI supplied additional information in 35% and information crucial to final decision making in 10%. Accuracy as well as contribution findings underlined MSI appropriateness even for extratemporal epilepsies, which otherwise frequently prove difficult with respect to focus localization.

Ictal onset localization of epileptic seizures by magnetoencephalography.

OBJECTIVES: The aim of this study was to localize the ictal onset zone of focal epileptic seizures by magnetoencephalography (MEG) and to compare the results with interictal MEG localizations, ictal and interictal electroencephalography (EEG) results and magnetic resonance imaging (MRI) in epilepsy surgery candidates. MATERIALS AND METHODS: Data of 13 patients with partial seizures during MEG recording were analysed. Measurements were performed with a Magnes II dual unit system. RESULTS: In six of 13 cases, the ictal onset zone could be localized by MEG, with all interictal MEG findings being confirmed by ictal MEG results. In four cases, the ictal MEG localization results were corresponding to the ictal EEG localization results. In two cases, EEG yielded no comparable information. CONCLUSION: Ictal onset localization is feasible with MEG. Both interical and ictal MEG contribute valuable information to the presurgical assessment of epilepsy patients.

[Pharmacological treatment of epilepsies: progress during the last 10 years]. / Antikonvulsive Pharmakotherapie: Entwicklung in den letzten 10 Jahren.

The pharmacological treatment of epilepsies represents an important domain of neurological therapeutical strategies and is not only important for specialized epilepsy centres, but for all hospital -and office-based neurologists. The choice of the right anticonvulsive drug is not always simple since the development of new drugs during the last 10 years offers a broad range of possibilities. Therefore, pharmacological treatment has become more sophisticated than it was with relatively few anticonvulsive drugs before. The new drugs are better tolerated and have less side effects, but more knowledge is required about the specific aspects of each drug. Pharmacology, pharmacocinetics, indication, dosage and side effects of the substances will be summarized and discussed.

Magnetoencephalography in extratemporal epilepsy.

Epilepsy surgery candidates with extratemporal foci represent a particular diagnostic and therapeutic challenge, because of anatomic and functional features of the pertaining areas. In the last decade, novel developments in the field of electrophysiological techniques have offered new approaches to detailed localization of specific epileptic discharges as well as eloquent regions. Magnetoencephalography, in combination with neuroimaging data and simultaneously recorded EEG, yields promising results to clarify centers of epileptic activity and their relationship to structural abnormalites and functionally significant areas. Examples are given to illustrate the range of applications of this method as a contribution to routine presurgical evaluation.