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Objective To prospectively determine the value of optical coherence tomography (OCT) as a surrogate outcome measure for the progression of myelopathy in males with adrenoleukodystrophy. Methods Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness were measured at baseline, 1‐ and 2‐year follow‐up in patients and age‐matched controls. We assessed the severity of myelopathy with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up‐and‐go. Linear mixed model analysis was used to compare changes in retinal layer thickness of patients to controls. In addition, we correlated changes in retinal layer thickness with changes in clinical parameters. Results Longitudinal data were available for 28 patients and 29 controls. Peripapillary RNFL (pRNFL) thickness decreased significantly in patients compared to controls (−1.75µm, p = 0.001), whereas change in macular GCL and RNFL was not different between groups. Analysis of the symptomatic subgroup showed that, apart from a similar decrease in pRNFL thickness, GCL thickness decreased significantly (−0.55 µm, p = 0.014). There were moderately strong correlations between changes in retinal layer thickness and changes in clinical parameters of severity of myelopathy. Interpretation This prospective study demonstrates the potential of OCT‐measured retinal neurodegeneration as a surrogate outcome measure for the progression of myelopathy in adrenoleukodystrophy. As differences were small, our findings need to be confirmed with longer follow‐up and/or in a larger patient sample.

Background In most hospitals, computed tomography angiography (CTA) is nowadays routinely performed in patients with acute ischemic stroke. However, it is unclear whether CTA is best performed before or after start of intravenous thrombolysis (IVT), since acquisition of CTA before IVT may prolong door-to-needle times, while acquisition after IVT may prolong door-to-groin times in patients undergoing endovascular treatment. Methods We performed a before-versus-after study (CTA following IVT, period I and CTA prior to IVT, period II), consisting of two periods of one year each. This study is based on a prospective registry of consecutive patients treated with IVT in two collaborating high-volume stroke centers; one primary stroke center and one comprehensive stroke center. The primary outcome was door-to-needle times. Secondary outcomes included door-to-groin times. Quantile regression analyses were performed to evaluate the association between timing of CTA and workflow times, adjusted for prognostic factors. Results A total of 519 patients received IVT during the study period (246 in period I, 273 in period II). In the adjusted analysis, we found a nonsignificant 1.13 min median difference in door-to-needle times (95% confidence interval: 1.03–3.29). Door-to-groin times was significantly shorter in period II in both unadjusted and adjusted analysis with the latter showing a 19.16 min median difference (95% confidence interval: 3.08–35.24). Conclusions CTA acquisition prior to start of IVT did not adversely affect door-to-needle times. However, a significantly shorter door-to-groin times was observed in endovascular treatment eligible patients. Performing CTA prior to start of IVT seems the preferred strategy.

Background Progressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure. Methods Sixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy. Results Patients had significantly thinner RNFL (male group, p p p p ≤ 0.002) and in pRNFL thickness (superior and temporal quadrant) in both male (p ≤ 0.02) and the female (p ≤ 0.02) groups. Neuroretinal layer thickness correlated moderately with severity of myelopathy in men (correlation coefficients between 0.29–0.55, p Conclusions These results suggest that neurodegeneration of the spinal cord in ALD is reflected in the retina of patients with ALD. Therefore, OCT could be valuable as an outcome measure for the myelopathy of ALD. Additional longitudinal studies are ongoing.

Background Neurofilament light chain is a marker of axonal damage and is of interest as a biofluid biomarker for PD. The objective of this study was to investigate whether CSF or serum neurofilament contributes to a combination of CSF biomarkers in defining the optimal biomarker panel for discriminating PD patients from healthy controls. In addition, we aimed to assess whether CSF and/or serum neurofilament levels are associated with clinical measures of disease severity. Methods We measured neurofilament light chain levels in CSF and/or serum of 139 PD patients and 52 age‐matched healthy controls. We used stepwise logistic regression analyses to test whether neurofilament contributes to a biomarker CSF panel including total, oligomeric, and phosphorylated α‐synuclein and Alzheimer's disease biomarkers. Measures of disease severity included disease duration, UPDRS‐III, Hoehn & Yahr stage, and MMSE. Results After correcting for age, CSF neurofilament levels were 42% higher in PD patients compared with controls (P

Research on the association between non-motor symptoms (NMS) of Parkinson's discasc (PD) and patients' quality of life (QoL) has given insight into the burden of NMS. Most studies investigate NMS by assessing the contribution of individual symptoms to QoL. However, symptoms could also have an interactive relationship, which might not be fully taken into account when only studying these individual contributions. Recently, a network approach has been developed that treats symptoms as nodes and associations between symptoms as edges in a network, providing the opportunity to investigate the dimensional spectrum of NMS. In the current cross-sectional study, we investigated NMS with both approaches: first, we assessed individual contributions of NMS to QoL. Second, we aimed to assess NMS using a network approach. Seventy PD patients completed questionnaires on NMS and QoL. Our primary analysis shows that the domains Mood and Pain are significant contributors to QoL. Our secondary network analysis suggests that Mood and Sleep play central roles in the NMS-network, and that Mood and Cognition are strongly related. Because of power issues, the generalizability of our explorative results is limited. However, complementary information from the network analysis does suggest that focusing on sleep problems might help both mood and pain symptoms, which negatively affect QoL. Investigating symptoms not only as individual and independent entities but rather as part of a connected network could show how treating one symptom affects other symptoms.

BackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (MethodsThe STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (p DiscussionThis statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (Trial registrationDutch National trial registerNTR4457(6 March 2014)

Visual hallucinations (VH) are common in patients with Parkinson’s disease (PD), yet the underlying pathophysiological mechanisms are still unclear. We aimed to explore the association of the presence of VH with inner retinal thinning and, secondarily, with visual acuity. To this end, we included 40 PD patients in this exploratory study, of whom 14 had VH, and 22 age- and sex-matched healthy controls. All participants were interviewed for the presence of VH by a neurologist specialized in movement disorders and underwent a thorough ophthalmologic examination, including measurement of the best-corrected visual acuity (BCVA) and optical coherence tomography to obtain macular scans of the combined ganglion cell layer and inner plexiform layer (GCL-IPL). Patients with VH had a thinner GCL-IPL than patients without VH, which persisted after correction for age, disease stage, levodopa equivalent daily dose (LED) and cognitive function. Furthermore, BCVA was lower in the PD group with VH than in the PD group without VH, although only a trend remained after correction for age, disease stage, LED and cognitive function. Taken together, in patients with PD, visual hallucinations appear to be associated with a thinning of the inner retinal layers and, possibly, with reduced visual acuity. Further research using a longitudinal design is necessary to confirm these findings and to establish the causality of these relationships.

Background: This study aimed to assess how Dutch neurologists and anesthesiologists diagnose and treat people with sciatica in secondary care and to evaluate their adherence to the newest guidelines. Methods: We conducted a cross-sectional survey. Respondents were asked about their current clinical practice related to sciatica. Three authors rated the respondents’ adherence to the guidelines on a three-point Likert scale. Results: Eighty neurologists and 44 anesthesiologists completed the questionnaire. Neurologists diagnose their sciatica patients primarily using a magnetic resonance imaging (89%). Selective diagnostic nerve blocks are considered useful by 81% of the neurologists. Neurologists primarily treat patients with pain medication, and 40% of them think epidural steroid injections are effective in 40–60% of injected patients. Twenty-nine percent of neurologists refer patients to a neurosurgeon after 4 months. Anesthesiologists consider a selective diagnostic nerve root block to have a higher diagnostic value than mapping. The most reported side effect of epidural injections is exacerbation of pain (82%). Pulse radiofrequency is applied in 9–11% of acute cases. The results also indicate that Dutch neurologists and anesthesiologists follow an evidence-based approach that is strictly or broadly in line with the guideline. Conclusions: Neurologists treat sciatica patients initially with pain medication and physiotherapy, followed by epidural steroid injections and referral for surgery. Anesthesiologists treat sciatica patients with one or more steroid injections or may perform a selective nerve root block. Imaging, selective nerve root blocks, medication, physiotherapy, and pulse radiofrequency are topics of further research.

In early-stage Parkinson&prime, s disease (PD), cognitive impairment is common, and a variety of cognitive domains including memory, attention, and executive functioning may be affected. Cerebrospinal fluid (CSF) biomarkers are potential markers of cognitive functioning. We aimed to explore whether CSF &alpha, synuclein species, neurofilament light chain, amyloid-&beta, 42, and tau are associated with cognitive performance in early-stage PD patients. CSF levels of total-&alpha, synuclein and phosphorylated-&alpha, synuclein, neurofilament light chain, amyloid-&beta, 42, and total-tau and phosphorylated-tau were measured in 26 PD patients (disease duration &le, 5 years and Hoehn and Yahr stage 1&ndash, 2.5). Multivariable linear regression models, adjusted for age, gender, and educational level, were used to assess the relationship between CSF biomarker levels and memory, attention, executive and visuospatial function, and language performance scores. In 26 early-stage PD patients, attention and memory were the most commonly affected domains. A higher CSF phosphorylated-&alpha, synuclein/total-&alpha, synuclein ratio was associated with better executive functioning (s&beta, = 0.40). Higher CSF neurofilament light was associated with worse memory (s&beta, = &minus, 0.59), attentional (s&beta, 0.32), and executive functioning (s&beta, 0.35). Reduced CSF amyloid-&beta, 42 levels were associated with poorer attentional functioning (s&beta, = 0.35). Higher CSF phosphorylated-tau was associated with worse language functioning (s&beta, 0.33). Thus, CSF biomarker levels, in particular neurofilament light, were related to the most commonly affected cognitive domains in early-stage PD. This indicates that CSF biomarker levels may identify early-stage PD patients who are at an increased risk of developing cognitive impairment.

Background Progressive myelopathy is the main cause of disability in adrenoleukodystrophy (ALD). Development of therapies is hampered by a lack of quantitative outcome measures. In this study, we investigated whether myelopathy in ALD is associated with retinal neurodegeneration on optical coherence tomography (OCT), which could serve as a surrogate outcome measure. Methods Sixty-two patients (29 men and 33 women) and 70 age-matched and sex-matched controls (33 men and 37 women) were included in this cross-sectional study. We compared retinal nerve fiber layer (RNFL), ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness between ALD patients and controls. In addition, we correlated these OCT measurements with clinical parameters of severity of myelopathy. Results Patients had significantly thinner RNFL (male group, p

Background To date, no symptomatic treatment is available for patients with vascular cognitive impairment (VCI). In the proof-of-principle study Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI), we investigated whether a single dose of a monoaminergic drug (methylphenidate) improves executive functioning and whether a single dose of a cholinergic drug (galantamine) improves memory in VCI patients. Methods STREAM-VCI is a single-center, double-blind, three-way crossover trial. We included 30 VCI patients (Mini-Mental State Examination (MMSE) ≥ 16 and Clinical Dementia Rating score 0.5–1.0) with cerebrovascular pathology on MRI. All patients received single doses of methylphenidate (10 mg), galantamine (16 mg), and placebo in random order on three separate study visits. We used the NeuroCart®, a computerized test battery, to assess drug-sensitive cognitive effects. Predefined main outcomes, measured directly after a single dose of a study drug, were (i) change in performance on the adaptive tracker for executive functioning and (ii) performance on the Visual Verbal Learning Test-15 (VVLT-15) for memory, compared to placebo. We performed mixed model analysis of variance. Results The study population had a mean age of 67 ± 8 years and MMSE 26 ± 3, and 9 (30%) were female. Methylphenidate improved performance on the adaptive tracker more than placebo (mean difference 1.40%; 95% confidence interval [CI] 0.56–2.25; p = 0.002). In addition, methylphenidate led to better memory performance on the VVLT-15 compared to placebo (mean difference in recalled words 0.59; 95% CI 0.03–1.15; p = 0.04). Galantamine did not improve performance on the adaptive tracker and led to worse performance on delayed recall of the VVLT-15 (mean difference − 0.84; 95% CI − 1.65, − 0.03; p = 0.04). Methylphenidate was well tolerated while galantamine produced gastrointestinal side effects in a considerable number of patients. Conclusions In this proof-of-principle study, methylphenidate is well tolerated and improves executive functioning and immediate recall in patients with VCI. Galantamine did not improve memory or executive dysfunction. Results might be influenced by the considerable amount of side effects seen. Trial registration http://www.clinicaltrials.gov. Registration number: NCT02098824. Registration date: March 28, 2014.

Background: Little is known about the trajectories of cognitive decline in relation to different types of vascular brain injury in patients presenting at a memory clinic with Vascular Cognitive Impairment (VCI). Methods: We included 472 memory clinic patients (age 68 (±8.2) years, 44% female, MMSE 25.9 (±2.8), 210 (44.5%) dementia) from the prospective TRACE-VCI cohort study with possible VCI, defined as cognitive complaints and vascular brain injury on MRI and at least 1 follow-up cognitive assessment (follow-up time 2.5 (±1.4) years, n = 1172 assessments). Types of vascular brain injury considered lacune(s) (≥1; n = 108 patients (23%)), non-lacunar infarct(s) (≥1; n = 54 (11%)), white matter hyperintensities (WMH) (none/mild versus moderate/severe (n = 211 patients (45%)) and microbleed(s) (≥1; n = 202 patients (43%)). We assessed cognitive functioning at baseline and follow-up, including the Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) A and B, category naming task and MMSE. The association of different types of vascular brain injury with cognitive decline was evaluated with linear mixed models, including one type of vascular brain injury (dichotomized), time and vascular brain injury*time, adjusted for sex, age, dementia status (yes/no), education (Verhage scale) and medial temporal lobe atrophy (MTA) score (dichotomized as ≥ 1.5). Results: Across the population, performance declined over time on all tests. Linear mixed models showed that lacune(s) were associated with worse baseline TMTA (Beta(SE)) (8.3 (3.8), p = .03) and TMTB (25.6 (10.3), p = .01), albeit with a slower rate of decline on MMSE, RAVLT and category naming. By contrast, patients with non-lacunar infarct(s) showed a steeper rate of decline on TMTB (29.6 (7.7), p = .00), mainly attributable to patients with dementia (62.9 (15.5), p = .00). Conclusion: Although different types of vascular brain injury have different etiologies and different patterns, they show little differences in cognitive trajectories depending on type of vascular brain injury.

Pain is an important non-motor symptom in Parkinson’s disease (PD), but its underlying pathophysiological mechanisms are still unclear. Research has shown that functional connectivity during the resting-state may be involved in persistent pain in PD. In the present cross-sectional study, 24 PD patients (both during on and off medication phase) and 27 controls participated. We assessed pain with the colored analogue scale and the McGill pain questionnaire. We examined a possible pathophysiological mechanism with resting-state fMRI using functional network topology, i.e., the architecture of functional connections. We took betweenness centrality (BC) to assess hubness, and global efficiency (GE) to assess integration of the network. We aimed to (1) assess the differences between PD patients and controls with respect to pain and resting-state network topology, and (2) investigate how resting-state network topology (BC and GE) is associated with clinical pain in both PD patients and controls. Results show that PD patients experienced more pain than controls. GE of the whole brain was higher in PD patients (on as well as off medication) compared to healthy controls. GE of the specialized pain network was also higher in PD patients compared to controls, but only when patients were on medication. BC of the pain network was lower in PD patients off medication compared to controls. We found a positive association between pain and GE of the pain network in PD patients off medication. For healthy controls, a negative association was found between pain and GE of the pain network, and also between pain and BC of the pain network. Our results suggest that functional network topology differs between PD patients and healthy controls, and that this topology can be used to investigate the underlying neural mechanisms of pain symptoms in PD.

Toxic leukoencephalopathy is an important complication of heroin abuse and has mostly been described after inhaling heroin vapor, known as “chasing the dragon syndrome” or heroin inhalation leukoencephalopathy (HIL). We present a 51 year-old male patient with toxic leukoencephalopathy following intranasal administration of heroin.

Background This systematic review focusses on inflammation as an underlying pathogenic mechanism in sciatica. We addressed two questions in particular: (1) what inflammatory biomarkers have been identified in patients with sciatica in the literature so far? 2) is there an association between the level of inflammatory activity and clinical symptoms? Methods The search was conducted up to December 19th 2018 in MEDLINE, EMBASE, CENTRAL and Web of Science. The study selection criteria: (1) observational cohort studies, cross-sectional studies and randomized clinical trials (RCT), (2) adult population (≥ 18 years) population with sciatica, (3) concentrations of inflammatory biomarkers measured in serum, cerebrospinal fluid (CSF) or biopsies, and (4) evaluation of clinically relevant outcome measures (pain or functional status). Three reviewers independently selected studies and extracted data regarding the study characteristics and the outcomes. Risk of Bias was evaluated using an adjusted version of the Quality in Prognosis Studies (QUIPS) tool. Results In total 16 articles fulfilled the criteria for inclusion: 7 cross sectional observational studies and 9 prospective cohort studies that included a total of 1212 patients. With regard to question 1) the following markers were identified: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-21, tumor necrosis factor-α (TNF-α), phospholipase A2, high sensitivity C-reactive protein (hsCRP), C-X-C motif chemokine 5 (CXCM5), CX3CL1, CCL2, epidermal growth factor (EGF), and monocyte chemotactic protein 4 (MCP-4). With regard to question 2) several positive correlations were found in longitudinal studies: a strong positive correlation between inflammatory mediators or byproducts and pain (measured by visual analogue scale, VAS) was found for IL-21 in two studies (r > 0,8), and moderate positive correlations for TNF-a in both serum (r = 0,629) and biopsy (r = 0.65); severe pain (VAS > 4) is associated with increased hsCRP levels among patients with sciatica (adjusted OR = 3.4 (95% CI, 1.1 to 10). Conclusion In this systematic review there was considerable heterogeneity in the type of biomarkers and in the clinical measurements in the included studies. Taking into account the overall risk of bias of the included studies there is insufficient evidence to draw firm conclusions regarding the relationship between inflammation and clinical symptoms in patients with sciatica. Electronic supplementary material The online version of this article (10.1186/s12891-019-2541-0) contains supplementary material, which is available to authorized users.

Introduction: Approximately 20% of patients with Parkinson’s disease (PD) experience diplopia; however, the cause of the diplopia is unclear. We aimed to explore the association of diplopia, and its subtypes, with oculomotor abnormalities, impaired vision, and visual hallucinations, in patients with PD. Methods: This exploratory study included 41 PD patients, recruited from two general hospitals, of whom 25 had diplopia and 16 did not have diplopia, as well as 23 healthy controls (HCs). We defined subtypes of diplopia as selective diplopia, i.e., diplopia of single objects, and complete diplopia, i.e., diplopia of the entire visual field. All participants underwent a full orthoptic and ophthalmologic examination. Results: PD patients with diplopia had a high prevalence of oculomotor abnormalities (84%), impaired vision (44%), and visual hallucinations (44%), compared to PD patients without diplopia (33%, 6%, and none, respectively, p < 0.01), and compared to HCs (23%, 9%, and none, respectively, p < 0.01). Oculomotor abnormalities were equally prevalent in both subtypes of diplopia (selective and complete), whereas impaired vision was predominantly found in patients with selective diplopia. Moreover, only patients with selective diplopia had visual hallucinations. Conclusions: In PD patients, diplopia may be indicative of oculomotor or visual impairments. Hence, it is worthwhile to refer PD patients with diplopia to an orthoptist and an ophthalmologist for evaluation and, possibly, treatment of diplopia. Furthermore, in the case of selective diplopia, the neurologist should consider the presence of visual hallucinations, which may require the adjustment of the patient’s medication.

Contains fulltext : 203664.pdf (Publisher’s version ) (Open Access) Atrophy of the medial temporal lobe of the brain is key to memory function and memory complaints in old age. While age and some morbidities are major risk factors for medial temporal lobe atrophy, individual differences remain, and mechanisms are insufficiently known. The largest combined neuroimaging and whole genome study to date indicates that medial temporal lobe volume is most associated with common polymorphisms in the GRIN2B gene that encodes for the 2B subunit (NR2B) of the NMDA receptor. Because sleep disruption induces a selective loss of NR2B from hippocampal synaptic membranes in rodents, and because of several other reports on medial temporal lobe sensitivity to sleep disruption, we hypothesized a contribution of the typical age-related increase in sleep-wake rhythm fragmentation to medial temporal lobe atrophy. Magnetic resonance imaging and actigraphy in 138 aged individuals showed that individual differences in sleep-wake rhythm fragmentation accounted for more (19%) of the variance in medial temporal lobe atrophy than age did (15%), or any of a list of health and brain structural indicators. The findings suggest a role of sleep-wake rhythm fragmentation in age related medial temporal lobe atrophy, that might in part be prevented or reversible. 7 p.

Background: Delirium is frequently unrecognised. EEG shows slower frequencies (i.e. below 4 Hz) during delirium, which might be useful in improving delirium recognition. We studied the discriminative performance of a brief single-channel EEG recording for delirium detection in an independent cohort of patients. Methods: In this prospective, multicentre study, postoperative patients aged ≥60 yr were included (n=159). Before operation and during the first 3 postoperative days, patients underwent a 5-min EEG recording, followed by a video-recorded standardised cognitive assessment. Two or, in case of disagreement, three delirium experts classified each postoperative day based on the video and chart review. Relative delta power (1–4 Hz) was based on 1-min artifact-free EEG. The diagnostic value of the relative delta power was evaluated by the area under the receiver operating characteristic curve (AUROC), using the expert classification as the gold standard. Results: Experts classified 84 (23.3%) postoperative days as either delirium or possible delirium, and 276 (76.7%) non-delirium days. The AUROC of the relative EEG delta power was 0.75 [95% confidence interval (CI) 0.69–0.82]. Exploratory analysis showed that relative power from 1 to 6 Hz had significantly higher AUROC (0.78, 95% CI 0.72–0.84, P=0.014). Conclusions: Delirium/possible delirium can be detected in older postoperative patients based on a single-channel EEG recording that can be automatically analysed. This objective detection method with a continuous scale instead of a dichotomised outcome is a promising approach for routine detection of delirium. Clinical trial registration: NCT02404181.

Epidural injection with corticosteroids is a common treatment option for patients with lower back pain or sciatica. In this paper we review its origin and evolution. The first injections were given around 1900 in Paris by Jean Sicard (1872-1929) and Fernand Cathelin (1873-1945), who worked independently. They both injected small volumes of cocaine into the sacral hiatus. After a slow start, the epidural treatment of back pain and sciatica gradually spread to other parts of Europe and Northern America. In the early 1950s, corticosteroids were introduced for epidural use. Since the 1970s, there have been numerous clinical trials that show a significant, although small, effect of epidural corticosteroid injections compared with placebo for leg pain in the short term. Despite an ongoing debate about effectiveness and safety, epidural injections remain popular.

Thinning of the retinal nerve fiber layer (RNFL) is a recently discovered feature of Parkinson’s disease (PD). Its exact pathological mechanism is yet unknown. We aimed to determine whether morphological changes of the RNFL are limited to RNFL thinning or also comprise an altered internal structure of this layer. Therefore, we investigated RNFL thickness and applied the RNFL attenuation coefficient (RNFL-AC), a novel method derived from optical coherence tomography, in PD patients and healthy controls (HCs). In this pilot study, we included 20 PD patients and 20 HCs matched for age, sex, and ethnicity. An ophthalmologist investigated all participants thoroughly, and we acquired retinal images from both eyes of each participant with a Spectralis optical coherence tomography system. We obtained both the RNFL-AC and RNFL thickness from peripapillary RNFL scans for the entire RNFL, as well as for each quadrant separately. We found no significant differences in the average RNFL-AC or the RNFL-AC of the separate retinal quadrants between PD patients and the HC group. However, compared to the HC group, PD patients had a significantly thinner RNFL in the temporal retinal quadrant. RNFL thinning was found in the temporal quadrant in PD patients without a corresponding change in the RNFL-AC. These findings suggest a reduction in the number of RNFL axons (atrophy) without other major changes in the structural integrity of the remaining RNFL.

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = −.004 (95% CI −.007; −.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

BackgroundTransforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However there is much debate about their safety and effectiveness. It is important to identify patients that benefit most from TESI and only few trials have yet evaluated the effects in patients with acute sciatica.MethodsWe describe a prospective, randomized controlled trial (RCT), with the aim to evaluate the hypothesis that TESI plus Levobupivacaine (TESI-plus) added to oral pain medication is more effective compared to pain medication alone or compared to transforaminal injection with a local anesthetic of short duration among patients with acute sciatica. We will recruit a total of 264 patients with sciatica (DiscussionA clinically relevant outcome in favor of TESI-plus implies that future patients with acute sciatica should be recommended TESI-plus within the first few weeks rather than being treated with pain medication alone in order to relieve pain and improve their functioning. In case of a negative result (no relevant differences in outcome between the three study arms), pain medication will remain the mainstay of treatment in the acute stages of sciatica.Trial registrationDutch National trial register:NTR4457(March, 6th, 2014)

Background: Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction due to vascular brain injury, as a single cause or in combination with other, often neurodegenerative, etiologies. VCI is a broad construct that captures a heterogeneous patient population both in terms of cognitive and noncognitive symptoms and in terms of etiology and prognosis. This provides a challenge when applying this construct in clinical practice. Objective: This paper presents the rationale and design of the TRACE-VCI study, which investigates the clinical features and prognosis of VCI in a memory clinic setting. Methods: The TRACE-VCI project is an observational, prospective cohort study of 861 consecutive memory clinic patients with possible VCI. Between 2009 and 2013, patients were recruited through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC) (N=665) and the outpatient memory clinic and VCI cohort of the University Medical Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients with a primary etiology other than vascular brain injury or neurodegeneration were excluded. Patients underwent an extensive 1-day memory clinic evaluation including an interview, physical and neurological examination, assessment of biomarkers (including those for Alzheimer-type pathologies), extensive neuropsychological testing, and an MRI scan of the brain. For prognostic analyses, the composite primary outcome measure was defined as accelerated cognitive decline (change of clinical dementia rating ≥1 or institutionalization) or (recurrent) major vascular events or death over the course of 2 years. Results: The mean age at baseline was 67.7 (SD 8.5) years and 46.3% of patients (399/861) were female. At baseline, the median Clinical Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini-Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at baseline was dementia in 52.4% of patients (451/861), mild cognitive impairment in 24.6% (212/861), and no objective cognitive impairment in the remaining 23.0% (198/861). Conclusions: The TRACE-VCI study represents a large cohort of well-characterized patients with VCI in a memory clinic setting. Data processing and collection for follow-up are currently being completed. The TRACE-VCI study will provide insight into the clinical features of memory clinic patients that meet VCI criteria and establish key prognostic factors for further cognitive decline and (recurrent) major vascular events. [JMIR Res Protoc 2017;6(4):e60]

Background: Despite the beneficial effect of cardiac rehabilitation after myocardial infarction, a rehabilitation program to improve cardiorespiratory fitness and influence secondary prevention has not been implemented for ischemic stroke and transient ischemic attack (TIA). Objective: To investigate the safety and feasibility of a post-stroke care including an exercise program after minor ischemic stroke or TIA. Methods: In a randomised controlled trial, 20 patients with a recent minor stroke or TIA without cardiac contraindications were randomly assigned to one of the two interventions; post-stroke care without exercise or post-stroke care with exercise. Patients were evaluated at baseline, 6 and 12 months. Results: Eighteen patients completed the intervention. In none of the patients cardiopulmonary contraindications for the maximal exercise test and exercise program were found. No cardiovascular events occurred during the maximal exercise tests and exercise program. After one year, significantly more patients in the post-stroke care with exercise group achieved the composite endpoint of optimal medical therapy. Conclusions: Post-stroke care including an exercise program is safe and feasible in the acute phase after minor stroke or TIA and might be a way to increase effectiveness of secondary stroke prevention. We are currently conducting a larger trial to validate these results. © 2014 - IOS Press and the authors. All rights reserved.

Rationale, aims, and objectives How to clarify the implications of complexity thinking for decision making in the intensive care unit (ICU)? Method Retrospective qualitative empirical research. Practitioners in an ICU were interviewed on how their decisions were made regarding a particular patient in a difficult, clinical situation. Transcriptions of these interviews were coded and retrieved in Maxqda, a software program. Assisted by complexity thinking, researchers focused on the decision-making process and the shift from analytic approaches to complex approaches. Results Originally, practitioners took their decisions with negligible transdisciplinary interactivity, drawing on analytical knowledge. Later on, they shifted to transdisciplinary practices, paying attention to more participation in their decision-making processes within their complex environment. Conclusions Complexity thinking demonstrates that this is a better model towards understanding transdisciplinary decision making then most analytical methodologies.

Background and Purpose— Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events. The purpose of this systematic review and meta-analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of (1) preventing recurrent cardiovascular events, (2) reducing mortality, and (3) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke. Methods— For this systematic review and meta-analysis, we systematically searched PubMed, Embase, PsycInfo, and the Cochrane Library from the start of the database to May 7, 2015. Subgroup analyses were conducted to explore the influence of therapy-related factors. Results— Twenty-two randomized controlled trials were identified with a total of 2574 patients. Pooling showed a significant reduction in systolic blood pressure by the lifestyle interventions applied, compared with usual care (mean difference, −3.6 mm Hg; 95% confidence interval, −5.6 to −1.6, I 2 =33%). No significant effect was found on cardiovascular events, mortality, diastolic blood pressure, or cholesterol. In the subgroup analyses, the trials with cardiovascular fitness interventions, trials with an intervention that lasted longer than 4 months, and interventions that used >3 behavior change techniques were more effective in reducing systolic blood pressure. Conclusions— We found that lifestyle interventions are effective in lowering systolic blood pressure. About other end points, this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality, diastolic blood pressure, or total cholesterol.

Introduction.Pain is an important nonmotor symptom of Parkinson’s disease (PD). Brain areas such as the hippocampus and the prefrontal cortex play an important role in the processing of pain. Since these brain areas are also involved in cognitive functioning, for example, episodic memory and executive functions, respectively, we examined whether a relationship exists between cognitive functioning and spontaneous pain in PD.Methods. Forty-eight patients with PD and 57 controls participated. Cognitive functioning was measured by a comprehensive battery of neuropsychological tests. Both the sensory-discriminative aspect and the motivational-affective aspect of pain were assessed. Multiple linear regression analyses were performed to assess a relation between cognition and pain.Results. Cognition was related to neither the sensory nor the affective aspect of pain in our sample of PD patients. Variance in pain measures was primarily explained by symptoms of depression and anxiety.Discussion. The difference between the affective and the sensory aspect of pain might be due to the neuropathology of PD, which is mainly present in areas processing the affective aspect of pain. Pain treatment might improve when mood is taken into account. We provide several explanations for the lack of an association between pain and cognition.

Item does not contain fulltext OBJECTIVE: This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR). METHODS: This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34 degrees C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months. RESULTS: Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not. INTERPRETATION: In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP. 01 februari 2012

The aim of this work was to determine the value of stroking the lateral dorsal border of the foot, in addition to stroking the sole in patients with a suspected pyramidal tract lesion. In addition, we studied the differences in interpretation between neurologists, residents, and medical students. We included subjects who had weakness of at least one leg and in whom a pyramidal tract lesion was suspected. After testing muscle power, tone, reflexes, and foot tapping, a decision on the presence of a pyramidal syndrome had to be made by each observer. After stimulating the sole as well as the lateral border of the foot, observers made a decision about the presence of a pyramidal syndrome again. Twenty-two legs of 18 patients were examined. Testing the plantar reflex (according to both methods) led to a change of opinion on the presence of a pyramidal syndrome in 45 of 69 (65 %) observations. On analysis according to level of experience, a change of opinion occurred in 19 (86 %) observations by medical students, 15 (65 %) by residents, and 11 (46 %) by neurologists. On eight occasions, the change was prompted by stimulation of the lateral border; in five of these cases the examiner (three medical students and two residents) found a new pathological response. Consecutively stroking the sole and the lateral border may be of added value, especially for less-experienced physicians. It seems that more-experienced physicians need fewer tests in the physical examination in order to identify a pyramidal syndrome of the leg.

Item does not contain fulltext Cardiac output and cerebral perfusion are reduced in patients with advanced stages of heart failure. Our aim was to determine whether cerebral blood flow velocity measured by transcranial Doppler ultrasonography was reduced in outpatients with mild heart failure in comparison to controls and, if so, whether this reduction was related to cognitive performance and abnormalities of the brain diagnosed by magnetic resonance imaging. 5 p.

OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates. DESIGN: Case-control study. SETTING: Outpatient clinic in a community hospital. PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated. MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z-scores for five cognitive domains and mean z-score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z-score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis. RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent (P=.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E e4 allele. CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF.

Background: Heart failure (HF) and cognitive impairment are common medical conditions that are becoming increasingly prevalent in theaging Western population. They are associated with frequent hospitalisation and increased mortality, particularly when they occursimultaneously. Evidence from a number of studies suggests that HF is independently associated with impairment in various cognitivedomains.Aims: This systematic literature review evaluates the relation between cognitive deterioration and heart failure.Methods: We searched electronic databases from 1966 to May 2006 for studies that investigated cognitive function in HF patients. Twenty-two controlled studies that met the inclusion criteria were selected for analysis. Study characteristics and data on global cognitiveperformance, memory scores, psychomotor speed and depression scores were extracted and analysed using the Cochrane Review Managersoftware.Results: Pooled analysis shows diminished neuropsychological performance in HF patients, as compared to control subjects. In a pooledsample of 2937 heart-failure patients and 14,848 control subjects, the odds ratio for cognitive impairment was 1.62 (95% confidenceinterval:1.48–1.79, pb0.0001) among subjects with HF.Conclusion: This review confirms the relationship between HF and cognitive impairment, but it also stresses the need for additionalsystematic neuropsychological data and adequate neuro-imaging from representative populations of HF patients.© 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Background: Exact mechanisms underlying cognitive dysfunction in diabetes mellitus (DM) remain unclear. Imaging studies of the brain could help to identify possible structural brain lesions underlying cognitive dysfunction. Objective: To describe a detailed neuropsychological profile in patients functioning independently with type 2 DM. Secondly, correlations were studied between cognitive impairment and brain lesions on magnetic resonance imaging (MRI), i.e. periventricular hyperintensities (PVH), deep white matter lesions (DWML), medial temporal lobe atrophy (MTA), cerebral atrophy and lacunar infarcts. In addition, the influence of relevant disease variables of DM was studied. Methods: 92 patients withtype 2 DM (mean age 73.2±5.7 years, mean duration 13.8±10.8 years) and 44 control subjects (mean age 72.9±5.3 years) were included and underwent an extensive neuropsychological test battery and an MRI of the brain. Results: Neuropsychological scores were worse for each cognitive domain except for memory functions after adjustment for hypertension in a group of elderly patients with type 2 DM compared to healthy control subjects. Only PVH were independently associated with motor speed, whereas all other MRI measures were not independently associated with cognitive impairment. Interactions between the different MRI measures were not present. Glycosylated haemoglobin (HbA1c) and duration of DM were significantly associated with cognitive dysfunction. Conclusions: The data of this cross-sectional study show that type 2 DM is associated with diminished cognitive function in different cognitive domains, while memory is less affected after adjustment for hypertension. The association of cognitive impairment with MRI measures is equivocal, whereas HbA 1 c and duration of DM were significantly associated with cognitive dysfunction.

Background/Aims: We purposed to investigate the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure (HF). Methods: In 58 patients with HF neuropsychological assessment was performed including tests of mental speed, executive functions, memory, language and visuospatial functions. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated on MRI of the brain. Correlations between MRI findings and the cognitive measures were calculated. Results: MTA correlated with memory (r = –0.353, p < 0.01), with executive functions (r = –0.383, p < 0.01) and the Mini Mental State Examination (r = –0.343, p < 0.05). Total WMH and deep WMH were found to correlate with depression and anxiety scores, but not with cognitive measures. Age, estimated premorbid intelligence and MTA were independent predictors of diminished cognitive performance. Conclusions: In HF patients, MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH was related to depression and anxiety.

Traditionally, multiple sclerosis (MS) is considered to be a disease primarily affecting the white matter (WM). However, the development of some clinical symptoms such as cognitive impairment cannot be fully explained by the severity of WM pathology alone. During the past decades it became clear that gray matter (GM) damage of the brain is also of major importance in patients with MS. Thanks to improved magnetic resonance imaging techniques, the in vivo detection of GM pathology became possible, enabling a better understanding of the manifestation of various clinical symptoms, such as cognitive impairment. Using higher field strengths and specific sequences, detection of cortical lesions was increased. However, despite these improvements, visualization of cortical MS lesions remains difficult (only about 30-50% of histopathologically confirmed lesions can be detected at 7 Tesla magnetic resonance imaging (MRI)). Furthermore, more research is needed to understand the exact interplay of cortical lesions, GM atrophy and WM pathology in the development of clinical symptoms. In this review, we summarize the historical background that preceded current research and provide an overview of the current knowledge on clinical consequences of GM pathology in MS in terms of disability, cognitive impairment and other clinically important signs such as epileptic seizures.

Diabetes is associated with impaired cognitive functioning and an increased risk of dementia (1,2). Patients with type 1 diabetes may show mild to moderate slowing of mental speed and diminished mental flexibility, whereas learning and memory are relatively spared (3). In patients with type 2 diabetes, cognitive impairment may be relatively more pronounced, particularly affecting verbal memory or complex information processing (4,5). The pathogenesis is still uncertain, but chronic hyperglycemia, vascular disease, repeated hypoglycemic episodes, and possibly direct effects of insulin on the brain have been implicated (6). Brain imaging studies can help to clarify the pathogenesis. An increasing number of studies report both focal vascular and more global (e.g., atrophy) cerebral changes, but the results are not always consistent. Our aim was to systematically review brain imaging studies in patients with diabetes. Data on the relation of imaging with cognition and with relevant disease variables were also recorded. Medline and EMBASE (1966 to February 2006) were searched with the following medical subject heading terms: computed tomography (CT) and magnetic resonance imaging (MRI) studies: white matter, leukoaraiosis, lacunar infarction, subcortical, periventricular, brain, cerebral, hippocampus, atrophy, MRI, magnetic resonance imaging, CT, and tomography; magnetic resonance spectroscopy (MRS) studies: magnetic resonance spectroscopy, MRS, brain, and cerebral; positron emission tomography (PET), single-photon emission CT (SPECT), and Xenon-enhanced CT studies: cerebral blood flow, glucose metabolism, brain, cerebral, PET, SPECT, Xenon, positron emission tomography, single-photon emission tomography, and tomography; all combined with “diabetes.” The abstracts were screened and potentially relevant articles retrieved. These articles were included if they met the following four criteria: 1 ) original article, written in English, on brain imaging in adult patients with diabetes in comparison with control subjects; 2 ) diagnostic criteria for diabetes specified; 3 ) sample size of at least 20 diabetic patients, or a total sample …

Objective: The event-related potential (ERP) evoked by the auditory oddball paradigm has been investigated mainly in patients with Alzheimer’s disease and in patients with different causes of subcortical dementia. Subcortical ischemic vascular disease (SIVD) seems to be an important cause of vascular cognitive impairment (VCI) frequently not fulfilling the criteria for dementia. Recognition of VCI is needed in order to provide adequate care and therapy. The aim of this study was to investigate the diagnostic value of the different elements of this response (N1, N2 complex and P3 latencies) in a group of elderly patients with VCI caused by SIVD. Methods: The study population consisted of patients with a clinical and neuropsychological diagnosis of VCI caused by SIVD (n = 38) and healthy control subjects (n = 53) aged 60 years or older. The mean Mini Mental State Examination score of both groups was 27.6, and the mean HIV Dementia Scale score was 6.1 in the patient group and 12.3 in the control group. In all subjects, the ERP was recorded under standardized conditions, and the latencies and amplitudes of N1, N2 and P3 were analyzed by two clinical neurophysiologists in consensus. Both were blinded to the diagnosis. Results: The N2 latency was significantly longer in patients with VCI than in age-matched controls, whereas the latencies of the P3 and N1 were not significantly different. The peak-to-peak amplitude of the N2 complex to the P3 wave was significantly lower in the patient group. White matter abnormalities on MRI were not significantly correlated with the N2 latency. Conclusion: Our findings suggest that the latency of the N2 complex is prolonged and the peak-to-peak amplitude of the N2 complex to the P3 wave is lowered in patients with VCI caused by SIVD.

Background and Purpose: Diabetes mellitus (DM) type 2 has been associated with poor cognitive performance and dementia, particularly in elderly patients. The exact mechanisms underlying the cognitive dysfunction in DM remain unclear. Imaging studies of the brain could be helpful to give more insight into possible structural brain lesions underlying these cognitive dysfunctions. Therefore, we performed a study in independently living patients with DM type 2 in order to investigate the association between DM and brain imaging abnormalities. Methods: The study population consisted of 45 patients with DM type 2 without hypertension (mean age 73.4 ± 5.1 years, mean duration 16.5 ± 11.5 years), 45 patients with DM type 2 and hypertension (mean age 73.5 ± 6.1 years, mean duration 11.9 ± 9.2 years) and 44 control subjects (mean age 73.1 ± 5.4 years). All patients and control subjects underwent an MRI of the brain. White matter lesions (WML), cerebral atrophy and medial temporal lobe atrophy were rated by a standardized visual rating scale. Lacunar infarcts were defined as focal hypo-intensities on fluid-attenuated inversion recovery sequences with a hyperintense rim around it. Results: WML occurred more frequently in diabetic patients with hypertension as well as without hypertension. Significantly more deep WML were found in DM patients with and without hypertension when compared to control subjects, whereas no difference was found in the occurrence of periventricular hyperintensities. In all 3 groups, lacunar infarcts occurred sporadically. A trend towards higher atrophy scores was seen in patients with DM compared to control subjects. Conclusions: The data of this cross-sectional study suggest that type 2 DM is an independent risk factor for deep WML in the independently living elderly patients.