Background and objectives: In 2008 a task force was set up to develop a revision of the European Federation of the Neurological Societies (EFNS) guideline for the diagnosis and management of ...Alzheimer’s disease (AD) and other disorders associated with dementia, published in early 2007. The aim of this revised international guideline was to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with AD. Mild cognitive impairment and non‐Alzheimer dementias are not included in this guideline.
Methods: The task force working group reviewed evidence from original research articles, meta‐analysis, and systematic reviews, published before May 2009. The evidence was classified and consensus recommendations graded (A, B, or C) according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided.
Results: The recommendations for clinical diagnosis, blood tests, neuropsychology, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) analysis, genetic testing, disclosure of diagnosis, treatment of AD, behavioural and psychological symptoms in dementia, legal issues, counselling and support for caregivers were all revised as compared with the previous EFNS guideline.
Conclusion: A number of new recommendations and good practice points are made, namely in CSF, neuropsychology, neuroimaging and reviewing non‐evidence based therapies. The assessment, interpretation, and treatment of symptoms, disability, needs, and caregiver stress during the course of AD require the contribution of many different professionals. These professionals should adhere to these guideline to improve the diagnosis and management of AD.
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Objective
To assess the risk of teratogenicity from maternal intake of the more widely used newer antiepileptic drugs, especially lamotrigine, levetiracetam and topiramate.
Materials and methods
Use ...of confidence interval and regression methods to compare risks of foetal malformation in pregnancies in women exposed (n = 1572) and in women with epilepsy not exposed (n = 153) to antiepileptic drugs in the first trimester.
Results
Compared with the foetal malformation rate in women with epilepsy who were untreated in the first trimester (3.3%), the malformation rates for lamotrigine (4.6%), levetiracetam (2.4%) and topiramate (2.4%), all in monotherapy, were not statistically significantly different. However, the malformation rates for topiramate as part of polytherapy (14.1%) and for valproate in both monotherapy (13.8%) and polytherapy (10.2%) were statistically significantly higher. Regression analysis of combined monotherapy and polytherapy data showed no statistically significant increased risk of teratogenesis associated with lamotrigine or levetiracetam, but a statistically significant and dose‐related risk for first trimester topiramate (P = 0.01) and valproate (P < 0.0001) exposure.
Conclusions
Evidence from this and other studies suggests that lamotrigine and levetiracetam have low risk for teratogenesis, but that topiramate exposure early in pregnancy may be associated with dose‐related anatomical teratogenesis, as valproate is already known to be.
Voxel-based morphometry (VBM) has already been applied to MRI scans of patients with Alzheimer’s disease (AD). The results of these studies demonstrated atrophy of the hippocampus, temporal pole, and ...insula, but did not describe any global brain changes or atrophy of deep cerebral structures. We propose an optimized VBM method, which accounts for these shortcomings. Additional processing steps are incorporated in the method, to ensure that the whole spectrum of brain atrophy is visualized. A local group template was created to avoid registration bias, morphological opening was performed to eliminate cerebrospinal fluid voxel misclassifications, and volume preserving modulation was used to correct for local volume changes. Group differences were assessed and thresholded at
P < 0.05 (corrected). Our results confirm earlier findings, but additionally we demonstrate global cortical atrophy with sparing of the sensorimotor cortex, occipital poles, and cerebellum. Moreover, we show atrophy of the caudate head nuclei and medial thalami. Our findings are in full agreement with the established neuropathological descriptions, offering a comprehensive view of atrophy patterns in AD.
Summary
The ability of Staphylococcus aureus cells to induce platelet aggregation
has long been recognized. However, despite several attempts to identify the mechanisms
involved in this interaction, ...the nature of the bacterial receptors required remains
poorly understood. Using genetic manipulation, this study for the first time provides
clear evidence that several S. aureus surface proteins participate in the
inter‐action with platelets. Mutants of S. aureus strain Newman lacking one
or more surface proteins were tested for their ability to stimulate platelet aggre‐gation.
This approach was complemented by the expression of a number of candidate proteins
in the non‐aggregating Gram‐positive bacterium Lacto‐coccus lactis. S.
aureus‐induced aggregation was monophasic and was dependent on the platelet receptor
GPIIb/IIIa. The fibrinogen‐binding proteins, clumping factors A and B and the serine‐aspartate
repeat protein SdrE could each induce aggregation when expressed in L. lactis.
Although protein A expressed in L. lactis was not capable of inducing aggregation
independently, it enhanced the aggregation response when expressed on the surface
of S. aureus. Thus, S. aureus has multiple mechanisms for stimulating platelet aggregation. Such functional redundancy suggests that this phenomenon may be important in the pathogenesis of invasive diseases such as infective endocarditis.
Background: There is considerable variability in the literature concerning the optimal treatment of acute Jones fractures.
Hypothesis: Early surgical fixation of acute Jones fractures will result in ...shorter times to union and return to athletics compared with
cast treatment.
Study Design: Randomized controlled clinical trial; Level of evidence, 1.
Methods: Eighteen patients were randomized to cast treatment, and 19 patients were randomized to screw fixation. Success of treatment
and the times to union and return to sports were calculated for each patient.
Results: Mean follow-up was 25.3 months (range, 15â42 months). Eight of 18 (44%) in the cast group were considered treatment failures:
5 nonunions, 1 delayed union, and 2 refractures. One of 19 patients in the surgery group was considered a treatment failure.
For the surgery group, the median times to union and return to sports were 7.5 and 8.0 weeks, respectively. For the cast group,
the median times were 14.5 and 15.0 weeks, respectively. The Mann-Whitney test showed a statistically significant difference
between the groups in both parameters, with P < 001.
Conclusion: There is a high incidence (44%) of failure after cast treatment of acute Jones fractures. Early screw fixation results in
quicker times to union and return to sports compared with cast treatment.
Keywords:
fifth metatarsal fracture
Jones fracture
internal fixation
intramedullary screw fixation
Abstract Data on the use in pregnancy of the new antiepileptic drugs (AED) are limited. We analysed data collected by the Australian Pregnancy Register to provide information on their relative ...teratogenicity. The database containing pregnancy outcomes from 1317 women with epilepsy (WWE) was examined for three widely used new AED in monotherapy in the first trimester – lamotrigine, levetiracetam and topiramate. This was compared with outcomes of pregnant WWE on monotherapy with three traditional AED, and with untreated women. The incidence of malformations associated with lamotrigine monotherapy was 12/231 (5.2%), with topiramate 1/31 (3.2%) and with levetiracetam 0/22 (0%). This compares with rates of 1/35 (2.9%) for phenytoin, 35/215 (16.3%) for valproate (VPA), 19/301 (6.3%) for carbamazepine and 6/116 (5.2%) for untreated women. There was no evidence of dose-dependent risks of foetal malformation, except with VPA monotherapy. We conclude that the new AED appear no more teratogenic than traditional drugs in monotherapy.
Is carbamazepine a human teratogen? Vajda, F.J.E; O’Brien, T.J; Graham, J ...
Journal of clinical neuroscience,
01/2016, Letnik:
23
Journal Article
Recenzirano
Highlights • Carbamazepine in monotherapy is associated with a two-fold increase of foetal malformations. • Carbamazepine is not an adequate comparator for the malformation risk in pregnancy. • ...Levetiracetam related risks are comparable to those of untreated women in pregnancy.
Previouscross-sectional MRI studies based on region-of-interest analyses have shown that increased cerebral atrophy is a feature of both Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). ...Relative preservation of the hippocampus and temporal lobe structures in DLB compared to AD has been reported in region-of-interest-based studies. Recently, image processing techniques such as voxel-based morphometry (VBM) have been developed to provide an unbiased, visually informative, and comprehensive means of studying patterns of cerebral atrophy. We report the first study to use the voxel-based approach to assess patterns of cerebral atrophy in DLB compared to control subjects and AD. Regional gray matter volume loss was observed bilaterally in the temporal and frontal lobes and insular cortex of patients with DLB compared to control subjects. Comparison of dementia groups showed preservation of the medial temporal lobe, hippocampus, and amygdala in DLB relative to AD. Significant gray matter loss was also observed in the thalamus of AD patients compared to DLB.
Abstract Lamotrigine (LTG) is increasingly being prescribed in pregnancy for women with epilepsy in place of valproate (VPA), because of the teratogenic risks associated with the latter. It is ...therefore important to know the teratogenic hazard associated with LTG, relative to VPA and to other commonly used antiepileptic drugs (AEDs). Data from the Australian Register of Antiepileptic Drugs in Pregnancy was examined to determine the incidence of teratogenicity determined 1 year from completion of pregnancy in women who took AEDs in monotherapy during pregnancy. Compared with a 3.4% malformation incidence in women who took no AEDs ( N = 118), the incidences for LTG ( N = 243), carbamazepine (CBZ) ( N = 302) and VPA ( N = 224) were, respectively, 4.9%, 5.3% and 15.2%, the latter statistically significantly greater than the risk for no AED therapy in pregnant women with epilepsy. Logistic regression analysis showed no tendency for foetal hazard to increase with increasing LTG dose in pregnancy, unlike the situation for VPA. However, seizure control in pregnancy tended to be not as good in the women taking LTG compared with those taking VPA, though the data examined were not adequate to permit definite conclusions regarding this matter. We conclude that LTG monotherapy in pregnancy is safer than valproate monotherapy from the point of view of foetal malformations, and no more hazardous in this regard than therapy with other commonly used AEDs.
To compare the incidence of foetal malformations (FMs) in pregnant women with epilepsy treated with different anti-epileptic drugs (AED) and doses, and the influence of seizures, family and personal ...history, and environmental factors. A prospective, observational, community-based cohort study.
Methods. A voluntary, Australia-wide, telephone-interview-based register prospectively enrolling three groups of pregnant women: taking AEDs for epilepsy; with epilepsy not taking AEDs; taking AEDs for a non-epileptic indication. Four hundred and fifty eligible women were enrolled over 40 months. Three hundred and ninety six pregnancies had been completed, with 7 sets of twins, for a total of 403 pregnancy outcomes.
Results. 354 (87.8%) pregnancy outcomes resulted in a healthy live birth, 26 (6.5%) had a FM, 4 (1%) a death
in utero, 1 (0.2%) a premature labour with stillbirth, 14 (3.5%) a spontaneous abortion and 4 lost to follow-up. The FM rate was greater in pregnancies exposed to sodium valproate (VPA) in the first trimester (16.0%) compared with those exposed to all other AEDs (16.0%
vs. 2.4%,
P<0.01) or no AEDs (16.0%
vs. 3.1%,
P<0.01). The mean daily dose of VPA taken in pregnancy with FMs was significantly greater than in those without (1975
vs. 1128 mg,
P<0.01). The incidence of FM with VPA doses ⩾1100 mg was 30.2%
vs. 3.2% with doses <1100 mg (
P<0.01).
Conclusions. There is a dose–effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs. These results highlight the need to limit, where possible, the dose of VPA in pregnancy.
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