The clinical utility of routine electroencephalography (EEG) after a first unprovoked seizure remains uncertain. Its diagnostic accuracy in identifying adults and children with new onset epilepsy was examined. A systematic review and meta‐analysis of studies examining individuals who underwent routine EEG after a first unprovoked seizure and were followed for seizure recurrence for at least 1 year was performed. A ‘positive’ test was defined by the presence of epileptiform discharges (ED). Pooled sensitivity and specificity estimates were calculated using a bivariate random effects regression model. In all, 3096 records were reviewed, from which 15 studies were extracted with a total of 1799 participants. Amongst adult studies, the sensitivity and specificity (95% confidence interval) of routine EEG were 17.3% (7.9, 33.8) and 94.7% (73.7, 99.1), respectively. Amongst child studies, the pooled sensitivity and specificity were 57.8% (49.7, 65.6) and 69.6% (57.5, 79.5), respectively. Based upon our positive likelihood ratios, and assuming a pre‐test probability of 50%, an adult with ED on routine EEG after a first unprovoked seizure has a 77% probability of having a second seizure, whilst a child with similar findings has a 66% probability. Further studies are required to examine the impact of patient characteristics and EEG features on the diagnostic accuracy of routine EEG for new onset epilepsy.

Abstract

Our aim was to determine the prevalence of migraine amongst university students. Migraine is highly prevalent amongst university students, but the exact frequency remains inconsistent between studies. PubMed, Embase and Google Scholar databases were used to identify studies dealing with the prevalence of migraine amongst university students published between 1 January 1988 and 31 August 2014. The pooled migraine prevalence was calculated using DerSimonian and Laird's random‐effects model. Heterogeneity of the results was investigated using subgroup analysis and the trend of migraine prevalence according to the publication year and sample size was determined by cumulative analysis. Data were combined from 56 independent studies, analysing a total of 34 904 students. The pooled migraine prevalence was 16.1% [95% confidence interval (CI) 13.6%–18.9%]: 11.3% (95% CI 8.8%–14.4%) amongst male students and 21.7% (95% CI 18.0%–25.8%) amongst female students. Subgroup analysis revealed that diagnostic criteria (<0.0001) and gender distribution (=0.004) significantly affected migraine prevalence. Cumulative analysis found that the 95% CI became narrower with ascending publication year and sample size. Many studies agree that migraine is highly prevalent amongst university students, but diverse methodologies lead to substantial heterogeneity in the results. It is shown that gender and diagnostic criteria significantly influence the migraine prevalence and may partially explain the heterogeneity between studies.

Background

To investigate the effect of drug withdrawal on the course of relapsing−remitting multiple sclerosis (RR‐MS).

Methods

An observational cohort retrospective study was performed to compare the time to relapse of patients who discontinued disease‐modifying therapy (1a or 1b beta‐interferons or glatiramer acetate) with the patients who did not. One hundred and twenty‐eight RR‐MS patients were investigated using a time‐dependent approach.

Results

Over a median follow‐up of 108 months, 60 patients discontinued treatment and 89 relapses were observed. The time to relapse was shorter in patients who discontinued treatment compared with those who did not ( < 0.001), median times being 31.1 months (95% confidence interval 10.4–50.8) and 85.8 months (95% confidence interval 58.6–106.3), respectively, whilst the baseline covariates (gender, Expanded Disability Status Scale at diagnosis) did not significantly affect the prognosis.

Conclusions

It was found that stopping treatment strongly reduces the time to relapse and this information may be useful in patient management.

Background and purpose

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain.

Methods

MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out‐of‐hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed.

Results

Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs.

Conclusions

A multimodal algorithm composed of neurological examination, EEG‐based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA.

Abstract

Click to view the accompanying paper in this issue.

Background and purpose

Recent large series studies have demonstrated that dehydration is common amongst stroke subjects and is associated with poor outcome. However, the effects of hydration status on the development of collaterals have never been discussed. In this study, the hypothesis that hydration status is an important factor for developing collaterals after acute middle cerebral artery (MCA) infarction was tested.

Methods

Eighty‐seven patients with acute infarction due to occlusion of the MCA were enrolled. Two collateral markers, posterior cerebral artery (PCA) laterality and fluid‐attenuated inversion recovery hyperintense vessels (HVs) were assessed from magnetic resonance imaging. Dehydration status was defined by a nitrogen to creatinine ratio ≧ of 15. The associations between dehydration status and the development of collaterals were estimated.

Results

Sixty‐one of 87 patients (70.1%) were identified as dehydrated. The development of PCA laterality and HVs shows a significant difference between dehydrated and euhydrated patients. A serum nitrogen to creatinine ratio <15, diastolic blood pressure and the presence of a dense MCA on computed tomography were significantly associated with the development of PCA laterality. A serum nitrogen to creatinine ratio <15, the initial National Institutes of Health Stroke Scale score, the presence of a dense MCA and calcifications of the internal carotid artery on computed tomography were significantly associated with the development of HVs. Dehydration remained an independent negative predictor for the development of PCA laterality and HVs in the multivariate analysis.

Conclusions

Hydration status is associated with the development of collateral flow after acute MCA occlusion. This preliminary study provides an imaging clue that hydration status and early hydration therapy could be important for acute stroke management.

Background and purpose

Subacute and chronic peripheral neuropathies (PNP) have been reported in Parkinson's disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (LCIG), although several aspects of their incidence and pathogenesis still remain to be clarified. This study main objective is to prospectively report the 2‐year incidence of PNP in patients treated with LCIG.

Methods and results

The clinical, hematological, nutritional and electrophysiological assessments of 33 consecutive patients have been prospectively collected and evaluated. At baseline (before the start of LCIG therapy), 3/33 (9%) patients showed symptomatic PNP and 7/33 (21%) subclinical PNP. During a follow‐up of 24.36 ± 12.18 months, 2/23 patients with normal baseline clinical‐electrophysiological assessment developed a subacute PNP, 2/23 developed a chronic PNP and 7/23 developed a subclinical PNP. LCIG was immediately halted in the subacute cases, while the infusion therapy was not interrupted in chronic and subclinical forms. All PNP were supplemented with vitamin B1 and B12, showing a clinical improvement and/or substantial stability at the following evaluations. Higher levodopa‐equivalent daily dose (: 0.024) and homocysteine levels (: 0.041) were found in chronic PNP, while no correlations were observed with vitamin B12, folate and UPDRS values. A trend towards BMI reduction was observed in both PNP and unaffected subjects and one patient developed a symptomatic PNP associated with a relevant weight loss.

Conclusions

Serial clinical‐electrophysiological evaluations are mandatory in patients treated with LCIG, given the possible risk of subacute and chronic PNP. No clear causative factors has been recognized in the subacute forms, whilst homocysteine‐mediated neurotoxicity seems to underlie the pathogenesis of chronic forms.

Background and purpose

The differences in gait abnormalities from the earliest to the later stages of dementia and in the different subtypes of dementia have not been fully examined. This study aims to compare spatiotemporal gait parameters in cognitively healthy individuals, patients with amnestic mild cognitive impairment (MCI) and non‐amnestic MCI, and patients with mild and moderate stages of Alzheimer's disease (AD) and non‐Alzheimer's disease (non‐AD).

Methods

Based on a cross‐sectional design, 1719 participants (77.4 ± 7.3 years, 53.9% female) were recruited from cohorts from seven countries participating in the Gait, Cognition and Decline (GOOD) initiative. Mean values and coefficients of variation of spatiotemporal gait parameters were measured during normal pace walking with the GAITRite system at all sites.

Results

Performance of spatiotemporal gait parameters declined in parallel with the stage of cognitive decline from MCI status to moderate dementia. Gait parameters of patients with non‐amnestic MCI were more disturbed compared to patients with amnestic MCI, and MCI subgroups performed better than demented patients. Patients with non‐AD dementia had worse gait performance than those with AD dementia. This degradation of gait parameters was similar between mean values and coefficients of variation of spatiotemporal gait parameters in the earliest stages of cognitive decline, but different in the most advanced stages, especially in the non‐AD subtypes.

Conclusions

Spatiotemporal gait parameters were more disturbed in the advanced stages of dementia, and more affected in the non‐AD dementias than in AD. These findings suggest that quantitative gait parameters could be used as a surrogate marker for improving the diagnosis of dementia.

Background and purpose

It is known that underlying diabetes mellitus (DM) can affect the clinical and electrophysiological pattern of coexisting peripheral neuropathies of other etiologies. The aim of this study was to identify the effect of underlying DM on the clinical and electrophysiological features of Guillain–Barré syndrome (GBS) and on the prognosis of GBS with regard to functional outcome.

Methods

This study prospectively included 27 GBS patients with DM (GBS‐DM+) and 58 GBS patients without DM (GBS‐DM−) from two university‐based hospitals. The clinical and electrophysiological findings were compared between the two groups. The functional outcomes were quantified by measuring the Hughes grade, whose values were compared between the groups at 3 months after symptom onset.

Results

All three sudden deaths that occurred during the acute stage of GBS were GBS‐DM+ patients. GBS‐DM+ patients had a tendency toward more frequent sensory involvement, and specific electrophysiological patterns and calculated indices disclosed a distal accentuation of conduction abnormalities in these patients. In addition, multivariate analysis identified history of mechanical ventilation (odds ratio 10.057, 95% confidence interval 2.057−49.164, = 0.04) and DM (odds ratio 9.049, 95% confidence interval 2.152−38.044, = 0.003) as independent factors for poor functional outcome at 3 months.

Conclusions

The findings of this study suggest that DM exacerbates the clinical and electrophysiological features of GBS and influences long‐term disability. Both chronic inflammation and nerve ischaemia in DM may intervene in the disease course of GBS, which is a prototype of acute inflammatory neuropathy.

Background and purpose

Patients with myotonic dystrophy (DM) are at high risk of brain cancer. This study describes the spectrum of brain neoplasms in DM patients.

Methods

Data from 1119 DM patients identified from the National Swedish Patient Register between 1987 and 2007 were linked to the National Cancer and the Cause of Death Registers. Standardized incidence ratios (SIRs) and cumulative incidence to quantify the relative and absolute risks of brain neoplasms were calculated and the Kaplan–Meier estimator was used for survival analysis. Patient follow‐up started at birth or the age at the start of Swedish cancer registration (1 January 1958) and ended at the age of brain neoplasm diagnosis, death or on 31 December 2007.

Results

Twenty patients developed brain neoplasm during follow‐up {median age 53, range 2–76 years, accounting for a five‐fold excess risk of brain tumors during the patient lifetime [SIR = 5.4, 95% confidence interval (CI) 3.4–8.1, = 1 × 10]}. Astrocytoma was the most common histological subtype ( = 16, 80%), and almost all cases ( = 19) developed after age 20. No statistically significant differences in gender‐specific risks (SIR in men 6.3 and in women 3.8, ‐heterogeneity 0.46) were observed. After accounting for competing mortality related to DM, the cumulative incidence of brain neoplasms reached 2.9% (95% CI 1.8%–4.7%) by age 70. Five‐year survival after brain tumor diagnosis was 52% (95%CI 29%–75%) overall (number at risk 8) and 34% (95% CI 26%–47%) for malignant neoplasms (number at risk 5).

Conclusion

Despite the high relative risk of DM‐related brain tumors, the absolute risk is modest. Nonetheless, careful evaluation of DM patients with new central nervous system symptoms is warranted.

Background

Successful return to work after stroke may improve economic circumstances, quality of life and overall life satisfaction, but not all stroke survivors are able to return to work.

Aim

Our aim was to determine what proportion of previously employed patients return to work after an acute stroke resulting in mild to moderate disability and to examine factors associated with a successful return to work.

Methods

Patients 18–60 years of age who were previously employed and who had a first‐ever stroke 3 months to 2 years previously resulting in mild to moderate disability (modified Rankin score ≤3) were recruited. Socio‐demographic and clinical information was collected and anxiety, depression and social support were assessed using previously validated instruments. Multivariate logistic regression was used to assess factors associated with a successful return to work.

Results

Of 141 patients (mean age ± SD 48 ± 8.8 years), 74 (52.5%) returned to work after stroke. Multivariate analysis demonstrated that a lower modified Rankin scale at 3 months [odds ratio (OR) 3.70, 95% confidence interval (CI) 1.77–7.76], younger age (OR 2.24, 95% CI 1.07–4.67) and a professional or business job (OR 3.02, 95% CI 1.44–6.34) were significantly associated with successful return to work and revealed that anxiety, depression and social support score did not affect patients' decision to return to work ( = 0.17, 0.61 and 0.27, respectively).

Conclusions

Amongst patients with mild to moderate disability after stroke, almost half do not return to work, and this is determined by functional disability and type of job rather than psychosocial factors such as anxiety and depression.

Background and purpose

Dementia is a leading cause of dependence amongst the aged population. Early identification of cognitive impairment could help to delay advanced stages of dependence. This study aimed at assessing the performance of three neuropsychological tests to detect cognitive disorders in elderly subjects with memory complaints.

Methods

The EVATEM study is a prospective multicentre cohort with a 1‐year follow‐up. Subjects with memory complaints were selected during preventive health examinations, and three neuropsychological tests (five‐word, cognitive disorders examination, verbal fluency) were administered. Two groups were identified in memory clinics: (i) cognitively healthy individuals (CHI) and (ii) mild cognitive impairment or demented individuals (MCI‐DI). Cross‐sectional analyses were performed on data at inclusion. The relationship between the diagnosis of MCI‐DI/CHI and the neuropsychological tests was assessed using logistic regressions. The performance of the neuropsychological tests, individually and combined, to detect cognitive disorders was calculated.

Results

Of 585 subjects, 31.11% had cognitive disorders (MCI, 176 subjects; DI, six subjects). Amongst the three tests studied, the odds ratio for MCI‐DI was higher for the five‐word test <10 [odds ratio 3.2 (1.81; 5.63)]. The best performance was observed when the three tests were combined: specificity 90.5% and sensitivity 42.4% compared to respectively 89.2% and 28.3% for the five‐word test.

Conclusions

Despite the poor sensitivity of the five‐word test, it seems to be the most adapted for the diagnosis of MCI‐DI in older adults with a memory complaint, in prevention centres, taking into account its high specificity and its rapid administration compared to the other tests.

Background

Gating of sensory evoked potentials (SEPs) around the onset of a voluntary movement is a physiological phenomenon with centripetal and central components, and may reflect sensorimotor integration required for normal movement control.

Objective

Our objective was the investigation of SEP suppression at the onset of movement and the interaction between SEP suppression and vibration of the limb.

Methods

Fourteen patients with primary focal/segmental dystonia and 17 age‐matched healthy volunteers were studied. SEPs were elicited after electrical stimulation of the median nerve at the wrist. Electroencephalograms (EEGs) were recorded over the scalp at three sites according to the International 10–20 System (F3, C3 and P3). SEPs were recorded in four conditions: at rest, at the onset of movement (a self‐paced abduction movement of the right thumb), both in the absence and in the presence of vibration of the limb.

Results

Repeated measures revealed that there was a significant main effect of group [(1, 11.1) = 0.471, = 0.002]. exploration of this effect revealed it to be due to an absence of SEP suppression at movement onset in patients (mean ratio SEP movement onset/rest 1.15 at F3, 1.13 at C3, 1.01 at P3) compared to controls, who had SEP suppression at movement onset (mean ratio SEP movement onset/rest 0.79 at F3, 0.78 at C3, 0.77 at P3). With vibration, SEP suppression reduced in both patients and controls to a similar extent.

Conclusion

These results demonstrate abnormal SEP suppression at the onset of movement in patients with primary dystonia, and in addition that vibration of the limb reduces SEP suppression in patients and controls.

Background and purpose

Olfactory bulb atrophy is associated with cognitive dysfunction in Parkinson's and Alzheimer's disease, and with major depression. It has been suggested that olfactory bulb atrophy or dysfunction is therefore a marker of neurodegeneration. Multiple sclerosis (MS) is now also recognized as having a significant neurodegenerative component. Thus, the aim of this study was to investigate associations between physical and cognitive disability, depression and olfactory bulb volume in MS.

Methods

In total, 146 patients with MS (mean age 49.0 ± 10.9 years, disease duration 21.2 ± 9.3 years, median Expanded Disability Status Scale (EDSS) score 3.0 (range 0–7.5), 103 relapsing−remitting, 35 secondary progressive and eight primary progressive MS) underwent a standardized neurological examination, comprehensive neuropsychological testing and magnetic resonance imaging (MRI); data of 27 healthy people served as age‐ and gender‐matched control subjects. The olfactory bulb was semi‐automatically segmented on high‐resolution three‐dimensional T1‐weighted MRI.

Results

Mean olfactory bulb volume was lower in MS patients than healthy controls (183.9 ± 40.1 vs. 209.2 ± 59.3 μl; = 0.018 adjusted to intracranial volume). Olfactory bulb volume was similar across clinical disease subtypes and did not correlate with cognitive performance, EDSS scores or total proton density/T2 white matter lesion volume. However, in progressive MS, the mean olfactory bulb volume correlated with depression scores (Spearman's rho = −0.38, < 0.05) confirmed using a multivariate linear regression analysis including cognitive fatigue scores. This association was not observed in relapsing−remitting MS.

Conclusion

Olfactory bulb volume was lower in MS than in healthy controls. Olfactory bulb volume does not seem to mirror cognitive impairment in MS; however, it is associated with higher depression scores in progressive MS.

Background and purpose

To date the role of mutations beyond α‐synucleinopathies in the parkinsonism−dementia spectrum is still unclear. The aim of the study was to screen for mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD).

Methods

In all, 303 patients with a clinical diagnosis of PSP ( = 157), CBS ( = 39), PPA ( = 35) and bvFTD ( = 72) and 587 neurologically healthy controls were screened for the most common mutations.

Results

mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP ( = 1), probable CBS ( = 2) and PPA ( = 1, with concomitant C9orf72 expansion). Overall the prevalence of mutations was low in non‐α‐synucleinopathies but significantly higher in the CBS subgroup compared to controls.

Conclusion

Although numbers are small, our findings indicate that the clinical phenotype of ‐associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying α‐synucleinopathies. This may be of relevance, once causal therapeutic strategies for ‐associated neurodegenerative disease are developed.

Abstract

Click to view the accompanying paper in this issue.

Background and purpose

The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial.

Methods

A systematic review and meta‐analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS.

Results

Thirty‐five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%–74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%–50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%–18.9%) and 19.5% (16.6%–22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%–18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63–2.54, < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%–8.3%)] and spontaneous echo contrast [3.8% (2.3%–6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%–0.7%)]. Significant heterogeneity was identified ( > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut‐off of 50 years, PFO was significantly ( = 0.001) more prevalent in younger than in older patients.

Conclusion

Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Background and purpose

Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific antibodies directed to aquaporin 4 (AQP4‐IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4‐IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG‐IgG). Our objective was to investigate whether the clinical characteristics of these patients differ.

Methods

Using a cell‐based assay, samples of 61 AQP4‐IgG seronegative patients and 41 AQP4‐IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG‐IgG. Clinical characteristics of the AQP4‐IgG, MOG‐IgG seropositive and double seronegative NMOSD patients were compared.

Results

Twenty of the 61 AQP4‐IgG seronegative patients tested MOG‐IgG seropositive (33%). MOG‐IgG seropositive patients were more frequently males in contrast to AQP4‐IgG seropositive patients (55% vs. 15%, < 0.01) and Caucasians (90% vs. 63%, = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, = 0.02) and had a monophasic disease course (70% vs. 29%, < 0.01). AQP4‐IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG‐IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2–4.7). AQP4‐IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow‐up ( < 0.01).

Conclusion

Antibodies directed to MOG identify a subgroup of AQP4‐IgG seronegative NMO patients with generally a favourable monophasic disease course.

Background and purpose

Differential diagnosis of sporadic inclusion body myositis (s‐IBM) and polymyositis (PM)/dermatomyositis (DM) is difficult and can affect proper disease management. Detection of heterogeneous muscular involvement in s‐IBM by muscle sonography could be a unique diagnostic feature.

Methods

Sonography of the lower leg and forearm was performed in patients with s‐IBM, PM/DM and control subjects ( = 11 each). Echo intensities (EIs) of the adjacent muscles [medial head of the gastrocnemius versus soleus and the flexor digitorum profundus (FDP) versus flexor carpi ulnaris (FCU)] were scored by three blinded raters. The mean EIs of these muscles were compared using computer‐assisted histogram analysis.

Results

Both evaluation methods showed high echoic signals in the gastrocnemius of patients with s‐IBM. EIs were significantly different between the gastrocnemius and soleus in patients with s‐IBM, but not in those with DM/PM and the controls. In the forearm, although the EI of the FDP was higher in the s‐IBM group than in the other groups, the EI differences between the FDP and FCU did not differ significantly between disease groups. The difference in area under the curves to differentiate between s‐IBM and DM/PM was greatest between the gastrocnemius−soleus EIs (0.843; = 0.006).

Conclusions

High echoic signals in the medial gastrocnemius compared with those of the soleus are suggestive of s‐IBM over PM/DM.

Background and purpose

Haemorrhagic transformation (HT) is common after acute ischaemic stroke. Whether liver function plays a role in HT remains an open question.

Methods

Acute ischaemic stroke patients within 7 days from stroke onset were included. Baseline data including liver function tests were collected. An independent association between liver function and HT was identified by multivariate regression analysis for stroke overall and stroke subtypes.

Results

A total of 2788 patients were included. HT occurred in 277 patients (9.9%), with 32 patients (1.1%) with symptomatic HT and 245 patients (8.8%) with asymptomatic HT. On multivariate regression analysis, aspartate aminotransferase (AST) and bilirubin (BILI) were independently associated with HT for stroke overall. In different stroke subtypes, AST was independently associated with HT for cardioembolic stroke, BILI for stroke of undetermined aetiology, and no liver function indicators for stroke of large‐artery atherosclerosis and small‐artery occlusion.

Conclusions

Liver function played an uneven role in HT for different stroke subtypes. Indicators of liver function independently associated with HT were AST for cardioembolic stroke, BILI for stroke of undetermined aetiology and none for stroke of large‐artery atherosclerosis and small‐artery occlusion.

Background and purpose

Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed.

Methods

Clinical Coma Recovery Scale – Revised (CRS‐R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome ( = 26) patients, minimally conscious state ( = 7) patients and healthy controls ( = 25).

Results

A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients’ etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor‐related activity in the orbitofrontal cortex and CRS‐R scores.

Conclusions

It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.

Abstract

Click to view the accompanying paper in this issue.

Background and purpose

In many cardioembolic strokes (CSs), the specific embolic source is uncertain. Despite the high mortality of CS, not enough attention is paid to its potential source. Although atrial fibrillation (AF) is the most common source of embolism, more complex and dynamic multiplicities may influence CS. The aim of this study was to evaluate novel indicators of transthoracic echocardiography (TTE) that have additional value for detecting CS.

Methods

In total, 1878 patients with acute ischaemic stroke who had TTE during admission were identified. Of the patients with undetermined etiology, 93 patients with incomplete evaluations were excluded. Thereafter, two stroke neurologists reviewed all of the magnetic resonance images to assess cardioembolic lesion patterns. The patients were classified into two groups: potential cardioembolic stroke (PCS) and non‐PCS.

Results

Amongst a total of 1601 patients, 518 (32.4%) had PCS. About half of the patients with PCS had AF. Patients with PCS were more likely to have larger left ventricular (LV) end‐diastolic diameters, larger LV end‐systolic diameters, larger left atrial sizes, increased / ratios and reduced LV ejection fractions. After adjusting for multiple clinical and TTE variables including AF, an / ratio ≥1.5 had a significant predictive value for PCS (odds ratio 2.89, 95% confidence interval 1.57–5.31, 0.01).

Conclusion

An / ratio ≥1.5 is independently associated with PCS after adjusting for multiple covariates including AF and provides incremental prognostic information for detecting PCS.

Background and purpose

The aim was to analyse the clinical profiles and outcomes of patients with anti‐ ‐methyl‐‐aspartate receptor (anti‐NMDAR) encephalitis in China.

Methods

A retrospective study of anti‐NMDAR encephalitis in China was performed between June 2011 and June 2014. The clinical characteristics and predictors of poor outcome were determined.

Results

A total of 51 patients with a definitive diagnosis of anti‐NMDAR encephalitis were included in this study. Four of them were surgically confirmed to have a neoplasm. Thirty‐two patients, amongst whom 24 were female, presented with psychiatric disorder as the initial symptom, whereas 14 patients, of whom nine were male, presented with seizure as the initial symptom ( = 0.011). Twenty‐nine patients (56.86%) were initially misdiagnosed with psychosis, viral encephalitis or other diseases, and 58.8% of the patients experienced at least one type of complication. It typically took 3 weeks before these patients were admitted to our hospital and another 2 weeks before the correct diagnosis was made. Forty‐one patients (80%) reached a good outcome; 10 patients (20%) had a poor outcome. Older age, extended hospital stay, memory deficits, decreased consciousness, central hypoventilation, complications and abnormal cerebrospinal fluid results were associated with poor outcome ( < 0.05).

Conclusions

Female patients more frequently initially present with psychiatric disorder but male patients more frequently initially present with seizure. Patients with anti‐NMDAR encephalitis in China have a lower incidence of neoplasm. Nevertheless, this study reveals several challenges in treating anti‐NMDAR encephalitis in China that may contribute to poor outcome.

Abstract

Click to view the accompanying paper in this issue.

Background and purpose

Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression. The aim of this study was to analyze the influence of disease‐related factors, BDNF Val66Met polymorphism and perception of disease on the severity of depression in MS.

Method

In total, 136 MS patients (88 women) were recruited and genotyped for BDNF rs6265 polymorphism at nucleotide 196 (G/A) using ‘high resolution melting’. Depressive symptoms were assessed by the Multiple Sclerosis Depression Rating Scale. Perception of health status was assessed using the SF‐36 questionnaire.

Results

A multivariable linear regression model showed that the best predictors of depression were the SF‐36 General health ( = −0.209; = 0.013), Mental health ( = −0.410; < 0.001) and Social activity ( = −0.195; = 0.035) scores; physical disability (assessed by the Extended Disability Status Scale score) was directly correlated to depression severity on univariate analysis, but it was not a relevant predictor of depression on multivariate analysis; other variables directly related to the disease (treatment, annual relapsing rate) and the BDNF Val66Met polymorphism were not significantly associated with depression.

Conclusion

Perception of the health status is the principal predictor of depressive symptoms in our sample. This result supports the hypothesis that the subjective interpretation of the disease's consequences is one of the main factors in determining depression in MS.

Background and purpose

The involvement of metabolic factors in the development of dementia has received much attention. However, previous studies have yielded conflicting results regarding how blood adipocytokine level impacts cognitive decline and dementia. This study aimed to clarify whether serum high‐molecular‐weight (HMW) adiponectin level is related to incident dementia.

Methods

Data were from 466 patients (mean age 67.8 years, male 57%) – who had normal cognitive function and received brain magnetic resonance imaging – from amongst the 1106 patients in the Osaka Follow‐up Study for Carotid Atherosclerosis, Part 2, a prospective cohort study of cardiovascular events and dementia amongst patients with vascular risk factors enrolled between 2001 and 2009. Baseline HMW adiponectin levels were measured using frozen serum. Dementia occurrence was examined in June 2013.

Results

Serum HMW adiponectin level was 4.33 ± 2.95 μg/ml; the levels were lower in men than in women and negatively correlated with body mass index. During the follow‐up period (median 6.9 years), 47 patients had incident dementia including Alzheimer's disease dementia (27), vascular dementia (13), mixed dementia (four), other dementia (three). Risks of dementia in patients with high versus low HMW adiponectin levels were almost identical ( = 0.689). No association was found between adiponectin levels and Alzheimer's disease dementia or vascular dementia in the whole group or amongst men and women separately.

Conclusions

This study demonstrated that serum HMW adiponectin level has little association with future dementia. Determination of metabolic factors involved in dementia requires evaluation of other biomarkers or parameters.

Background and purpose

Stroke is a leading cause of death and severe disability worldwide. Serum biomarkers play a critical role in the assessment of the severity and prognosis in stroke patients.

Methods

In this prospective cohort study, the measurement of serum progranulin (PGRN) was conducted in 316 participants, including 216 patients with an identified diagnosis of acute ischaemic stroke and 100 normal control subjects. The primary end‐point was defined as all‐cause mortality for a short‐term follow‐up of 6 months. Adverse functional outcome (modified Rankin Scale score ≥3) was considered as the secondary end‐point.

Results

The median value of serum PGRN for patients with acute ischaemic stroke was 64.2 ng/ml (interquartile range 54.6–73.7), which was significantly higher than the control group [59.7 (54.4–64.4) ng/ml; < 0.001]. Multivariable linear regression suggested that PGRN levels were significantly correlated with body mass index, alcohol consumption, fasting blood glucose, total cholesterol, National Institutes of Health Stroke Scale (NIHSS) score and high‐density lipoprotein cholesterol. Serum PGRN concentrations were independently associated with increased risks of all‐cause mortality and adverse functional outcome after adjustment for clinical variables. In Cox proportional hazards models, PGRN levels were associated with the risk of mortality (hazard ratio 1.090, 95% confidence interval 1.033–1.150, = 0.002). The net reclassification improvement of the model with added PGRN was 0.1902 ( = 0.0234) after adjustment for the variables in the Cox regression model for predicting all‐cause mortality, and the integrated discrimination improvement was 0.1052 ( < 0.001).

Conclusions

Serum PGRN levels independently predicted all‐cause mortality and adverse functional outcome in the short term in stroke patients. The discriminative power was improved by PGRN on the basis of NIHSS score.

Background and purpose

Mixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small‐vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin‐6 (IL‐6), C‐reactive protein (CRP) and gene variants increase dementia risk.

Methods

In a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL‐6, CRP levels, gene variants [interleukin‐6 receptor (IL‐6R), rs2228145; IL‐6, rs2097677; CRP, rs3093059] and incident all‐cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial‐temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein Eε4, education, cerebrovascular events, vascular risk factors and MRI findings.

Results

Of 803 subjects (mean 67.0 ± 8.5 years, males 59%), during a mean of 7.5 ± 3.2 years follow‐up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed‐type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL‐6R variant (rs2228145), IL‐6 levels (relative risk 1.68, = 0.048) or highest tertile (relative risk 2.38, = 0.031) for all‐cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL‐6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia.

Conclusions

The deleterious effect of higher IL‐6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL‐6R variant.

Background

Early neurological improvement (ENI) after fibrinolysis for ischaemic stroke is strongly associated with recanalization and favourable outcome. However, it remains unknown why some patients recover within the first hour after treatment (very ENI, VENI) whereas others recover later within 24 h.

Aim

The factors associated with the timing of ENI were assessed.

Methods

Consecutive stroke patients treated with intravenous recombinant tissue plasminogen activator (rt‐PA) within 4.5 h after onset in four stroke centres of our geographical area were retrospectively studied. VENI assessed at 1 h and ENI assessed at 24 h post‐treatment were defined by National Institutes of Health Stroke Scale (NIHSS) improvement by 40% from baseline.

Results

Of 421 patients, 65 (15%) had VENI and 110 (26%) had ENI. Patients with VENI had significantly lower serum creatinine level than patients with ENI (79 ± 19 vs. 91 ± 35 μmol/l; = 0.01). After adjustment for age, sex, baseline NIHSS, hypertension and blood glucose level, patients with low serum creatinine level were more likely to have VENI (lowest tertile, odds ratio 3.8, 95% confidence interval 1.5–9.7; intermediate tertile, odds ratio 1.8, 95% confidence interval 0.8–4.3; for trend <0.01). VENI patients were as likely as ENI patients to have a modified Rankin scale score ≤2 at 3 months.

Conclusions

Low serum creatinine levels are associated with VENI, suggesting that swiftness of the efficacy of rt‐PA or of neurological recovery may depend on renal function.

Background and purpose

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN‐mediated gait improvement.

Methods

Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks.

Results

Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark.

Conclusions

The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN‐mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance.

Amyotrophic lateral sclerosis (ALS) is the most common adult‐onset motor neuron disease. Alongside identification of aetiologies, development of biomarkers is a foremost research priority. Metabolomics is one promising approach that is being utilized in the search for diagnosis and prognosis markers. Our aim is to provide an overview of the principal research in metabolomics applied to ALS. References were identified using PubMed with the terms ‘metabolomics’ or ‘metabolomic’ and ‘ALS’ or ‘amyotrophic lateral sclerosis’ or ‘MND’ or ‘motor neuron disorders’. To date, nine articles have reported metabolomics research in patients and a few additional studies examined disease physiology and drug effects in patients or models. Metabolomics contribute to a better understanding of ALS pathophysiology but, to date, no biomarker has been validated for diagnosis, principally due to the heterogeneity of the disease and the absence of applied standardized methodology for biomarker discovery. A consensus on best metabolomics methodology as well as systematic independent validation will be an important accomplishment on the path to identifying the long‐awaited biomarkers for ALS and to improve clinical trial designs.