Circadian Rhythmicity and Epilepsy: the Significance of Chronobiological Time

Stam, C.J. [Promotor]Weerd, A.W. de [Copromotor

Headache in epilepsy patients: The (un)awareness of this phenomenon among Dutch neurologists

AbstractPurposeHeadache is a frequently heard complaint that can strongly influence quality of life. This is probably even more so in people with a chronic illness. Knowing that headache, and especially migraine, is more frequent among epilepsy patients, the knowledge concerning this problem has been studied among Dutch neurologists.MethodsSeven hundred and seventy two neurologists, working in 89 hospitals and two tertiary epilepsy clinics were asked to participate. Using a questionnaire, neurologists were surveyed on different subjects, e.g. whether they thought current headaches are more frequent in people with epilepsy than in the general population, their interest for epilepsy and how many patients with epilepsy visited their polyclinic per month.ResultsIn total, 334 questionnaires were returned (response rate of 43%) of which 18 were excluded. One third of neurologists responded affirmatively that current headaches are more prevalent among people with epilepsy and eight percent knows that this is, more specified, migraine. The number of years of experience does not influence knowledge on headaches in epilepsy patients. The interest in epilepsy and the number of epilepsy patients per month on the polyclinic does.ConclusionsThese results show that the occurrence of headache in people with epilepsy is underestimated by Dutch neurologists. This leaves an often bothersome and potentially treatable condition underexposed

BSI versus the Eye: EEG Monitoring in Carotid Endarterectomy

Carotid endarterectomy is a common procedure as an important secondary prevention of stroke. For selective shunting, continuous EEG monitoring is a standard technique, with visual assessment to track possible ischemia. Recently, the extended BSI was proposed as a pair of quantitative features to support the visual interpretation. Here, we further evaluate its potential clinical use using a large data set. The extended BSI (consisting of a spatial and temporal symmetry measure, sBSI and tBSI, respectively) was calculated retrospectively from a group of 111 patients who underwent a carotid endarterectomy in our hospital. EEG recordings were visually assessed to determine shunt placement and compared to the calculated BSI-values. All unilateral changes in the EEG found by visual assessment are reflected by ∆-sBSI ≥ 0.060 and all diffuse changes by ∆-tBSI ≥ 0.065. In EEGs with both unilateral and diffuse changes, ∆-sBSI ≥ 0.060 and ∆-tBSI ≥ 0.065. This study extends and confirms our previous pilot results, that the sBSI and tBSI correlate strongly with the visual assessment of the EEG, as performed by experienced neurophysiologists. The extended BSI supports the visual intraoperative EEG monitoring during carotid endarterectomics and assists in a more reliable decision for selective shunting

Morningness and eveningness: When do patiens take their antiepileptic drugs?

Almost one-third of epilepsy patients continue to have seizures despite adequate drug treatment. Chronotherapy (based on dynamic changes in drug pharmacology and disease-related processes) could be a promising treatment option. We aimed to explore whether different circadian types adjust administration times of anti-epileptic drugs (AEDs) as a step in exploring chronotherapeutic possibilities. We performed a questionnaire-based study to compare behavior of different circadian types in relation to times of taking drugs. Circadian type was determined by the Morningness–Eveningness Questionnaire. Results clearly show that morning types are taking their AEDs significantly earlier than do evening types on free days. Times of taking AEDs in the morning on work days also differ significantly between morning and evening types. Regardless of circadian type, drugs on free days are taken later than on working days. In conclusion, our study shows that patients adapt times of taking medication to their circadian typ

Timing of temporal and frontal seizures in relation to the circadian phase: A prospective pilot study

There is strong evidence that epileptic seizures occur in diurnal or 24-h patterns. A study in rat models of partial epilepsy showed circadian seizure patterns, and in humans circadian rhythmicity in interictal discharges has been found, suggesting that circadian rhythm may play a role in epilepsy. Circadian influences on human seizure patterns have not been investigated. We performed a pilot study to ascertain influences of the circadian rhythm on seizure occurrence. We prospectively outlined circadian rhythms of patients admitted for long term EEG and video monitoring, using measurement of the dim light melatonin onset (DLMO). Seizures during admission were recorded with continuous EEG and video monitoring. The DLMO ranged from 18:46h to 23:13h (mean 21:22h). One hundred and twenty-four seizures of 21 patients were analysed. Seizures of temporal lobe origin occurred mainly between 11:00 and 17:00 h and frontal seizures were seen mostly between 23:00 and 05:00 h. When correlating seizure timing to the individual's circadian phase as measured by the DLMO, the following was seen: temporal seizures occurred most frequently in the 6 h before DLMO and frontal seizures mainly in 6-12 h after the DLMO. The results of this pilot study suggest that temporal and frontal seizures occur in a non-random fashion synchronized to a hormonal marker of the circadian timing system. (C) 2011 Elsevier B.V. All rights reserved

Mutations in a TGF-β Ligand, TGFB3, Cause Syndromic Aortic Aneurysms and Dissections

BACKGROUND Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-b signaling. OBJECTIVES This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. METHODS We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. RESULTS Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-b signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-b signaling in association with up-regulation of the expression of TGF-b ligands. CONCLUSIONS Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk