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Objective: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME). Methods: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females. Results: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13], P, SCOPUS: ar.j, info:eu-repo/semantics/published

Arabidopsis has five phytochrome (PHY) genes for sensing the Red:Far Red (R:FR) ratio in ambient light, of which PHYA has an established role in responses to FR. To study whether and how PHYs may influence each other’s transcription, PHY-Luciferase reporter plants (pPHYA:LUC, pPHYB:LUC, pPHYC:LUC, pPHYD:LUC and pPHYE:LUC) were constructed. Subsequently, reporter lines representative for each PHY were crossed into each of the five single phy-mutant backgrounds. Reporter activities in WT and phy mutant was studied under diurnal mixed (R, B, FR), R, FR or B LED light in seedling or rosette plants. Both pPHYA:LUC and pPHYB:LUC show strong induction under FR. Full FR upregulation of both PHYA and PHYB is dependent on PHYE, identifying PHYE as a novel sensor for FR light responses. Results also show that PHYA expression is strongly suppressed by PHYD. Results were confirmed for expression of endogenous PHYA and PHYB, albeit with different dynamics compared to the LUC reporters. Profiling of pPHYA:LUC and pPHYB:LUC reporters suggest gating of FR responses. Manipulation of PHY expression levels by FR may provide a novel basis for manipulating plant growth in controlled environments.

SummaryObjective Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Methods Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Results Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Significance Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.

Objective: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. Methods: We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. Results: Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. Conclusions: AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.

Objective: Changes in anti-epileptic drug (AED) regimens may indicate unsatisfactory treatment results such as insufficient seizure control or adverse effects. This inference underlies epilepsy management and research, yet current studies often do not account for AED changes. We assessed AED change patterns and their association with quality of life (QoL), as main outcome measure, in a community-based setting. Methods: We assessed a cohort of 248 people with epilepsy identified from community pharmacy records from whom we retrieved AED dispensing history. We assessed all changes in AED use during the 2 years prior to the index date and current QoL using the validated Dutch QOLIE-31 questionnaire. Results: Thirty-one per cent had at least one AED change during the study period, either in drug type or dose. People who changed showed significantly lower QoL (QOLIE score 73 vs 79), especially those who intensified their treatment. Each additional change was associated with a further reduction of 4.9 points in QoL score. Conclusions: AED changes are common practice, even in people with long-standing epilepsy. Frequent changes, as objective measure of epilepsy severity, are associated with a progressively lower QoL. Changes, even in dose, should be monitored in daily clinical practice and used as a red flag that may require adjustments in epilepsy management. This may include earlier referral to a specialized centre for a more thorough evaluation or counselling. AED changes can also be used as an outcome marker in epilepsy research as a proxy of QoL for better translation of drug-efficacy results to general practice.

Contains fulltext : 6706.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 26982_agraco.pdf (Publisher’s version ) (Open Access) Contains fulltext : 56231.pdf (Publisher’s version ) (Open Access) This dissertation focuses on syntactic comprehension problems in patients with Broca's aphasia from an electrophysiological perspective. The central objective of this dissertation was to further explore what syntax-related event-related brain potential (ERP) effects can reveal about the nature of the deficit that underlies syntactic comprehension problems in patients with Broca's aphasia. Chapter two to four describe experiments in which event-related brain potentials were recorded while subjects (Broca patients, non-aphasic patients with a right-hemisphere lesion, and healthy elderly controls) were presented with sentences that contained either violations of syntactic constraints or were syntactically correct. Chapter two investigates ERP effects of subject-verb agreement violations in the different subject groups, and seeks to answer the following questions: Do agrammatic comprehenders show sensitivity to subject-verb agreement violations as indicated by a syntax-related ERP effect? In addition, does the severity of the syntactic comprehension impairment in the Broca patients affect the ERP responses? Chapter three describes an investigation of whether Broca patients show sensitivity to violations of word order as indicated by a syntax-related ERP effect, and whether the ERP responses in the Broca patients are affected by the severity of their syntactic comprehension impairment. Chapter four reports on ERP effects of violations of word-category. In addition, also a semantic violation condition was added to track possible dissociations in the sensitivity to semantic and syntactic information in the Broca patients. Chapter five describes the development of a paradigm in which the electrophysiological approach and the classical sentence-picture matching approach are combined. In this chapter, the ERP method is applied to study on-line thematic role assignment in Broca patients during sentence-picture matching. Also the relation between ERP effects and behavioral responses is pursued. Finally, Chapter 6 provides a summary of the main findings of the experiments and a general discussion. RU Radboud Universiteit Nijmegen, 29 september 2005 Promotor : Hagoort, P. 245 p.

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