An LC-MS/MS method for quantification of lamotrigine and its main metabolite in dried blood spots

Background: The antiepileptic drug lamotrigine (LTG) shows high pharmacokinetic variability due to genotype influence and concomitant use of glucuronidation inducers and inhibitors, both of which may be frequently taken by elderly patients. Our goal was to develop a reliable quantification method for lamotrigine and its main glucuronide metabolite lamotrigine-N2-glucuronide (LTG-N2-GLU) in dried blood spots (DBS) to enable routine therapeutic drug monitoring and to identify altered metabolic activity for early detection of drug interactions possibly leading to suboptimal drug response. Results: The analytical method was validated in terms of selectivity, accuracy, precision, matrix effects, haematocrit, blood spot volume influence, and stability. It was applied to a clinical study, and the DBS results were compared to the concentrations determined in plasma samples. A good correlation was established for both analytes in DBS and plasma samples, taking into account the haematocrit and blood cell-to-plasma partition coefficients. It was demonstrated that the method is suitable for the determination of the metabolite-to-parent ratio to reveal the metabolic status of individual patients. Conclusions: The clinical validation performed confirmed that the DBS technique is a reliable alternative for plasma lamotrigine and its glucuronide determination

High Incidence of Sporadic Creutzfeldt-Jakob Disease in Slovenia in 2015: A Case Series

Background: Creutzfeldt-Jakob disease (CJD) is a rare fatal neurodegenerative disorder presenting with rapid cognitive decline and additional signs. The clinical characteristics of an increasing number of sporadic CJD (sCJD) patients admitted to the Ljubljana University Medical Centre are presented as well as the incidence of sCJD in Slovenia in 2015 compared to previous years. Methods: We investigated patients presenting with rapidly progressive dementia and at least one additional sign. The diagnosis was made based on clinical diagnostic criteria and an autopsy was performed in all cases. Data on definite sCJD cases in Slovenia since 1999 were obtained and its incidence was calculated. Results: Eight patients with definite sCJD died in 2015 in Slovenia (incidence: 3.89 cases per million). The long-term incidence 1999 was 1.67 per million. Conclusions: The incidence of sCJD was considerably higher in 2015. It reflects fluctuations in sporadic cases of this rare disease. The rising trend might indicate a previous underestimation and better recognition of the disease

Modulation of epileptiform EEG discharges in juvenile myoclonic epilepsy: An investigation of reflex epileptic traits

Purpose: Previous studies have suggested that cognitive tasks modulate (provoke or inhibit) the epileptiform electroencephalography (EEG) discharges (EDs) in patients with juvenile myoclonic epilepsy (JME). Their inhibitory effect was found to be especially frequent (6490%). These studies arbitrarily defined modulation as a >100% increase or >50% decrease of the EDs compared with baseline, which may not sufficiently distinguish from spontaneous fluctuations. the aim of our study was to assess the modulation of EDs and the precipitation of myoclonic seizures by cognitive tasks and by conventional provocation methods, taking into account also the spontaneous fluctuation of EDs. Method: Sixty patients with JME underwent video-EEG recordings including 50-min baseline, sleep, hyperventilation, intermittent photic stimulation (IPS), and cognitive tasks. To account for spontaneous fluctuations of the EDs we divided the baseline period into 5-min epochs and calculated the 95% confidence interval for the baseline EDs in each patient. Modulation was assumed when the number of EDs during any 5-min test period was outside the 95% confidence interval. Key Findings: Using the arbitrary method, our results were similar to previous publications: Cognitive tasks seemed to inhibit the EDs in 94% of the patients, and to provoke them in 22%. However, when the spontaneous fluctuations were accounted for, inhibition was found in only 29% of the patients and provocation in 18%. A nonspecific effect of any cognitive task seemed to account for the observed significant inhibition in two-thirds of the cases, but was observed in only one of the patients with significant provocation. Photoparoxysmal response was observed in 23% of the patients. When accounting for the spontaneous occurrence of EDs, IPS had provocative effect in 10% of the patients. Hyperventilation and sleep had provocative effect on EDs to an extent similar to the cognitive tasks (hyperventilation: 22%; sleep: 18%). the conventional provocation methods tended to be more efficient in patients who were not seizure free. Myoclonia were recorded most often during the cognitive tasks (10 patients). Significance: Spontaneous fluctuations of EDs account for most of the previously described inhibitory effect of the cognitive tasks. the provocative effect of the cognitive tasks is task-specific, whereas the inhibitory effect seems to be related to cognitive activation in general.Prof. Dr. Peter & Jytte Wolf Foundation for Epilepsy, Bielefeld (Germany)Danish Epilepsy Ctr, Dept Clin Neurophysiol, DK-4293 Dianalund, DenmarkUniv Aarhus, Aarhus, DenmarkUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, Escola Paulista Med, São Paulo, BrazilTech Univ Denmark, DK-2800 Lyngby, DenmarkAll India Inst Med Sci, Dept Neurol, New Delhi, IndiaUniv Med Ctr Ljubljana, Dept Neurol, Ljubljana, SloveniaInst Neurol, Epilepsy Sect, Montevideo, UruguayNatl Epilepsy Ctr, Shizuoka, JapanUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, Escola Paulista Med, São Paulo, BrazilProf. Dr. Peter & Jytte Wolf Foundation for Epilepsy, Bielefeld (Germany): PJWS 09/002FWeb of Scienc

Coregistrating magnetic source and magnetic resonance imaging for epilepsy surgery in focal cortical dysplasia

Background Epilepsy surgery for focal cortical dysplasia type II (FCD II) offers good chances for seizure freedom, but remains a challenge with respect to lesion detection, defining the epileptogenic zone and the optimal resection strategy. Integrating results from magnetic source imaging from magnetoencephalography (MEG) with magnetic resonance imaging (MRI) including MRI postprocessing may be useful for optimizing these goals. Methods We here present data from 21 adult FCD II patients, investigated during a 10 year period and evaluated including magnetic source imaging. 16 patients had epilepsy surgery, i.e. histopathologically verified FCD II, and a long follow up. We present our analysis of epileptogenic zones including MEG in relation to structural data according to MRI data and relate these results to surgical outcomes. Results FCD II in our cohort was characterized by high MEG yield and localization accuracy and MEG showed impact on surgical success-rates. MEG source localizations were detected in 95.2% of patients and were as close as 12.3 ± 8,1 mm to the MRI-lesion. After a mean follow up of >3 years, we saw >80% Engel I outcomes, with more favourable outcomes when the MEG source was completely resected (Fishers exact test 0,033). Conclusion We argue for a high value of conducting a combined MEG-MRI approach in the presurgical workup and the resection strategy in patients with FCD II related epilepsy

The provision of epilepsy care across Europe 2017:a 17-year follow-up survey

\u3cp\u3eObjective: To assess the resources available in the provision of epilepsy care across Europe and the developments since the International League Against Epilepsy (ILAE) survey published in 2003 (data collected in 2000). Methods: An updated online version of the European Epilepsy Services Inventory was distributed to all European chapters of the ILAE (N = 47) and responses were obtained from 33 chapters (response rate 70%). To assess trends and allow comparisons with the survey published in 2003, the responding countries were divided into 4 groups (Western, Central, Southern, and Eastern). Responses from European Union (EU) member states are reported as a subgroup (N = 23), since the current survey is a part of the EU-funded European Study on the Burden and Care of Epilepsy (ESBACE, www.esbace.eu). Results: The total number of physicians involved in epilepsy care had increased since 2000, with the largest increase seen for neurologists. The gap between the best- and the least-provided areas with regard to the competence of the providers had diminished. However, the density of comprehensive multidisciplinary epilepsy teams had not changed to any greater degree. The main problems reported by the chapters were to a large extent the same as in 2000 and included lack of specialists and specialist care, lack or underuse of epilepsy surgery, and problems regarding financing and resource allocation. Several chapters also highlighted problems with healthcare structure and organization. Significance: Although there have been some improvements concerning the availability of care for people with epilepsy in Europe over the last 17 years, there are still a number of problem areas with little improvement or where there are important regional differences.\u3c/p\u3