The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

Hemodynamic Differences in Intracranial Aneurysms before and after Rupture

BACKGROUND AND PURPOSE:Rupture risk of intracranial aneurysms may depend on hemodynamic characteristics. This has been assessed by comparing hemodynamic data of ruptured and unruptured aneurysms. However, aneurysm geometry may change before, during, or just after rupture; this difference causes potential changes in hemodynamics. We assessed changes in hemodynamics in a series of intracranial aneurysms, by using 3D imaging before and after rupture.MATERIALS AND METHODS:For 9 aneurysms in 9 patients, we used MRA, CTA, and 3D rotational angiography before and after rupture to generate geometric models of the aneurysm and perianeurysmal vasculature. Intra-aneurysmal hemodynamics were simulated by using computational fluid dynamics. Two neuroradiologists qualitatively assessed flow complexity, flow stability, inflow concentration, and flow impingement in consensus, by using flow-velocity streamlines and wall shear stress distributions.RESULTS:Hemodynamics changed in 6 of the 9 aneurysms. The median time between imaging before and after rupture was 678 days (range, 14–1461 days) in these 6 cases, compared with 151 days (range, 34–183 days) in the 3 cases with unaltered hemodynamics. Changes were observed for flow complexity (n = 3), flow stability (n = 3), inflow concentration (n = 2), and region of flow impingement (n = 3). These changes were in all instances associated with aneurysm displacement due to rupture-related hematomas, growth, or newly formed lobulations.CONCLUSIONS:Hemodynamic characteristics of intracranial aneurysms can be altered by geometric changes before, during, or just after rupture. Associations of hemodynamic characteristics with aneurysm rupture obtained from case-control studies comparing ruptured with unruptured aneurysms should therefore be interpreted with caution.

Intracranial aneurysms are found in 1%–5% of the adult population.^1,2 For ruptured intracranial aneurysms, case morbidity and fatality rates are high.^1,3 However, 50%–80% of all intracranial aneurysms do not rupture during an individual''s lifetime.¹ More commonly, unruptured aneurysms are incidentally found due to increasing use of imaging.^4,5 The risk of rupture should be balanced against the risk of treatment when deciding whether an aneurysm should be treated. In clinical practice, the location and size of the aneurysm are the most important parameters for determining the risk of rupture.^1,6 However, these geometric predictors are insufficient for optimal treatment selection. Therefore, the search for better predictors for rupture continues.^7–9 Previous studies have associated intra-aneurysmal flow patterns and wall shear stress (WSS) distributions with aneurysm rupture status.^7,8,10 However, these results are still controversial. For example, both high and low aneurysmal WSS were separately associated with aneurysm growth and rupture.^11,12 In these risk-assessment studies, potential changes in hemodynamics due to the rupture itself were systematically neglected. Recently, 2 studies have shown changes in aneurysm geometry after rupture.^13,14 These rupture-associated geometric changes may result in differences in hemodynamic characteristics as well.In this study, we had the opportunity to use high-quality 3D imaging data of 9 patients with intracranial aneurysms, obtained before and after rupture, to assess potential differences in hemodynamic characteristics associated with rupture.     

Randomized double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers

PURPOSE: This study aimed at investigating the cognitive and mood effects of lamotrigine (LTG) versus valproate (VPA) and placebo (PBO). METHODS: By studying the effects in healthy volunteers, it is possible to separate the genuine effects of LTG from the cognitive improvements, caused by better seizure control. The study used a pretest-posttest comparison of 50 mg LTG, 900 mg VPA, or PBO in a double-blind single-dummy parallel-group design with 30 healthy volunteers. Study duration was 12 days (with a last control on day 13). Outcome measures included cognitive tests (FePsy neuropsychological test battery), mood scales (ASL; mood-rating scale), and a scale for subjective complaints (ABNAS Neurotoxicity scale). Total sleep time was controlled with actigraphic recordings. The results were analyzed by comparing the change over time (pretest with posttest) for the three treatments with Student's t tests. RESULTS: COGNITIVE TESTS: significant differences between the treatments were found for measurements of cognitive activation (i.e., three of the four simple reaction-time measurements showed statistically significant differences in change between PBO and LTG in favor of LTG (p=0.03; 0.03; 0.04); two of four tests showed statistically significant differences in change between LTG and VPA, both in favor of LTG (p=0.03; 0.05). SUBJECTIVE COMPLAINTS: the ABNAS-neurotoxicity scale reveals a significant reduction of drug-related cognitive complaints for the subjects taking LTG, relative to VPA (p=0.02). MOOD RATING: significant changes were found on the scale assessing "tiredness," showing increased tiredness/sedation for VPA relative to PBO (p=0.02) and on the "timid scale" for LTG reporting "being more at ease" compared with both PBO and VPA (p=0.02; 0.02). The general direction of change for the mood scales was toward "activation" for LTG (five of six scales improved), whereas for VPA, the reverse effect was found (four of six scales showed a change in the direction of "tiredness/sedation"). CONCLUSIONS: Short-term treatment in normal volunteers with a low dose of LTG resulted in improved cognitive activation on simple reaction-time measurements, a more positive subjective report about the impact of drug treatment relative to VPA, and mood changes concurring with the activating effect demonstrated by the cognitive tests.     

Effects of psychotherapy on hippocampal volume in out-patients with post-traumatic stress disorder: a MRI investigation

BACKGROUND: Magnetic resonance imaging (MRI) studies have especially reported smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD), most of them war or sexual abuse victims. The present study compares the hippocampal volumes of out-patients with PTSD who had low co-morbidity rates to those of trauma-exposed control subjects without PTSD, and measures hippocampal volume changes in these patients after brief eclectic psychotherapy. We hypothesized that smaller hippocampal volumes are specific to PTSD and that hippocampal volume changes after effective psychotherapy would be measurable. METHOD: Eighteen patients with PTSD and 14 traumatized control subjects were examined with MRI. In a randomized clinical trial, the PTSD patients were assigned to treatment (n = 9) or waiting-list group (n = 9). After the former received psychotherapy for 4 months, the MRI was repeated on both PTSD groups. Three temporal lobe structures were manually segmented: hippocampus, amygdala, and parahippocampal gyrus. Volumetric analysis was used to measure grey matter, white matter, and cerebrospinal fluid. RESULTS: PTSD patients had significantly smaller hippocampal volumes at baseline (total 13.8%, right 13.5%, left 14.1%) compared to the control subjects. After effective psychotherapy, however, no volume changes were found in the smaller hippocampi. CONCLUSIONS: We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of out-patients who experienced different types of traumas, reducing co-morbidity to a minimum. Smaller hippocampal volumes did not change after effective psychotherapy, even while symptoms resolved.     

Peroxisomal biogenesis disorder: comparison of conventional MR imaging with diffusion-weighted and diffusion-tensor imaging findings

BACKGROUND AND PURPOSE: Peroxisomal biogenesis disorders (PBDs) refer to a group of disorders of peroxisomal biogenesis causing neuronal migration disorder, delayed myelination, and demyelination. The aim of this study was to evaluate the added value of diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) compared with that of conventional T2-weighted imaging in assessing the extent of white matter damage in patients with PBDs. METHODS: Three patients (aged 12, 16, and 80 months) with PBD (type 1 protein targeting sequence [PTS1]) and three age-matched control subjects underwent MR imaging on a 1.5-T system. The protocol included axial T2-weighted, DWI, and DTI sequences. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) changes were calculated using regions of interest at several predefined white matter areas and compared with those of age-matched control subjects. Color-coded maps were obtained to visualize the range of FA values. RESULTS: On the T2-weighted images, one patient revealed severe hypomyelination throughout the brain; the two other patients showed focal abnormal high-signal-intensity areas. All patients had significantly decreased FA values in white matter areas that appeared abnormal on the T2-weighted images. In two of the three patients, significant FA reduction was also found in normal-appearing white matter. The ADC values of the patients were significantly increased compared with those of the age-matched controls. CONCLUSION: Although based on a small number of patients, our data suggest that DWI and DTI can be used to characterize and quantify white matter tract injury in patients with PBD-PTS1. Furthermore, our data suggest that these techniques have the potential to identify neurodegenerative changes not yet visible on T2-weighted images.     

Functional magnetic resonance imaging for neurosurgical planning in neurooncology

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that is widely available and can be used to determine the spatial relationships between tumor tissue and eloquent brain areas. Within certain limits, this functional information can be applied in the field of neurosurgery as a pre-operative mapping tool to minimize damage to eloquent brain areas. In this article, we review the literature on the use of fMRI for neurosurgical planning. The issues addressed are: (1) stimulation paradigms, (2) the influence of tumors on the blood oxygenation level-dependent (BOLD) signal, (3) post-processing the fMRI time course, (4) integration of fMRI results into neuronavigation systems, (5) the accuracy of fMRI and (6) fMRI compared to intra-operative mapping (IOM).