Primary lateral sclerosis and the amyotrophic lateral sclerosis–frontotemporal dementia spectrum

Aim

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum of diseases.

Methods

Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n?=?27) and ALS–FTD (n?=?12). Clinical features, Addenbrooke’s Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS).

Results

Global cognition was impaired in PLS (mean total ACE score 82.5?±?13.6), similar to ALS–FTD (mean total ACE score 76.3?±?7.7, p?>?0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5?±?6.2) compared ALS–FTD (50.1?±?7.2, p?<?0.001) and ALS (62.3?±?12.6, p?=?0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4?±?22.4 months) and shortest in ALS–FTD (38.5?±?4.5 months, p?=?0.002). Bulbar onset disease (β?=???0.45, p?=?0.007) and RMT (β?=?0.54, p?=?0.001) were independent predictors of global cognition while motor scores (β?=?0.47, p?=?0.036) and SICI (β?=?0.58, p?=?0.006) were significantly associated with ALSFRS.

Conclusion

The cognitive profile in PLS resembles ALS–FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS–FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS–FTD. Overall, while these findings support the notion that PLS lies on the ALS–FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

     

Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis

Neostigmine test (NT) is a pharmacological test, demonstrating a clinical improvement in patients affected by myasthenia gravis (MG). We aim to compare clinical evaluation and neurophysiological recordings by concentric-needle single-fiber electromyography (CN-SFEMG) in response to acute administration of neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10 with ocular MG and 13 with generalized MG) were evaluated before and after 90 min neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered analysis of mean value of consecutive differences (MCD), single-pair jitter, and blocks. MGC scores significantly improved after NT in generalized MG patients (MGC 11.1?±?7.6 vs 9.1?±?6.7, p?=?0.02), whereas the improvement was not significant in the ocular group. CN-SFEMG recordings significantly improved after NT in generalized MG patients (MCD 58.9?±?18.8 vs 45.9?±?23.2 μs, p?=?0.003; single-pair jitter 49.8?±?26.9 vs 24.1?±?26.7%, p?=?0.0001; blocks 6.2?±?9.5 vs 2.6?±?7.4%, p?=?0.03) as well as in ocular MG patients (MCD 50.8?±?22.7 vs 40.1?±?22.9 μs, p?=?0.01; single-pair jitter 35.9?±?23.7 vs 20.0?±?25.1%, p?=?0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to acute administration of neostigmine in MG. Moreover, neurophysiological modifications to NT could show subclinical improvement in ocular MG better than that of the clinical scale.     

Fatigue and Its Associated Factors in Spinocerebellar Ataxia Type 3/Machado-Joseph Disease

Fatigue has been described in several neurodegenerative diseases, reducing quality of life. A systematic evaluation of this clinical feature is lacking in SCA3/MJD. The aim of this study was to evaluate the frequency and the factors associated with fatigue in SCA3/MJD. Patients with SCA3/MJD and matched healthy controls answered the Modified Fatigue Impact Scale (MFIS), Beck Inventory Depression (BDI) and Epworth Sleepiness Scale (ESS). Scale for the assessment and rating of ataxia (SARA) was used to determine ataxia severity. We used Mann-Whitney and Fisher exact tests to compare mean scores and proportions between groups. Linear regression analyses were employed to investigate factors associated with fatigue in SCA3/MJD. Seventy-four patients were included with a mean age and disease duration of 47.2?±?12.8 and 9.5?±?6.37 years, respectively. There were 38 men and 36 women. Mean (CAG)n was 72.2?±?3.8. Mean MFIS score was higher in patients with SCA3/MJD (41.4?±?16.2 vs 18.4?±?12.9, p?<?0.001). According to BDI scores, relevant depressive symptoms were found in 69.4 % of patients but only in 10.4 % of controls (p?<?0.001). The proportion of patients with ESS scores indicating excessive daytime somnolence was also higher than controls (37.5 vs 22.3 %, p?=?0.05). In the multiple regression analysis, both BDI and ESS scores were associated with fatigue (r?=?0.67, p?<?0.001 and p?=?0.01). Fatigue is frequent and strongly associated with depression and excessive daytime somnolence in SCA3/MJD.     

Role of <Emphasis Type="Italic">TLR4</Emphasis> (C1196T) and <Emphasis Type="Italic">CD14</Emphasis> (C-260T) Polymorphisms in Development of Ischemic Stroke,Its Subtypes and Hemorrhagic Stroke

In the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n = 700), its subtypes and hemorrhagic stroke (n = 300) in a South Indian population from Telangana. The genotypes were determined using PCR–RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p = 0.008), other determined aetiology (p = 0.03) and undetermined aetiology (p = 0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p = 0.05, p = 0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p < 0.01). Further, analysis of the CD14 variant between the two major stroke types revealed a significant difference in genotype distribution following the co-dominant genotypic model (p = 0.01).     

Mobilization of endothelial progenitor cell in patients with acute ischemic stroke

Endothelial progenitor cells (EPCs) have important effect in tissue repair in ischemic organs. The present study was conducted to demonstrate the mobilization of EPCs and its possible mechanism after acute ischemic stroke (AIS). A total of 148 individuals were examined, including 106 patients with ischemic stroke and 42 healthy controls. Seventy-one patients with imaging-confirmed AIS were examined at days 1, 7, 14, and 21 after stroke onset. Circulating EPCs were quantified by flow cytometry using CD133 and KDR surface markers. Serum stromal cell-derived factor-1 (SDF-1) concentrations were determined by enzyme-linked immunosorbent assay. Patients with AIS had significantly lower EPC level than that in the controls (0.022 ± 0.013 vs 0.051 ± 0.020; p < 0.01). This difference did not remain significant after adjusting for risk factors at multivariate analysis. Blood pressure, triglyceride, low-density lipoprotein (LDL), and fasting blood sugar were inversely correlated with EPC levels (p < 0.01). Systolic blood pressure and LDL remained independent predictors of baseline EPC levels. The number of circulating EPCs increased on day 7 after AIS, reached a peak on day 14, and decreased on day 21. The concentration of SDF-1 had similar changes. The increment of EPCs was correlated with the infarct volume (r = 0.708; p = 0.006) and SDF-1 concentration on day 14 (r = 0.714; p < 0.001). Baseline EPC level in patients with AIS reflects the cumulative vascular endothelial damage. EPCs could be mobilized into peripheral circulation in response to stroke stress. This mobilization was associated with the increased expression of SDF-1.     

Vancomycin Pharmacokinetic Parameters in Patients with Hemorrhagic Stroke

Background

Infections are a common medical complication in hemorrhagic stroke patients, with vancomycin commonly used as empiric therapy. The purpose of this study was to evaluate the pharmacokinetic parameters of vancomycin in hemorrhagic stroke patients.

Methods

This was a retrospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted between May 2010 and February 2015 who received vancomycin. Predicted pharmacokinetic parameters based on population data were compared with calculated pharmacokinetic parameters based on serum trough concentrations.

Results

Eighty aSAH patients and 66 ICH patients met inclusion criteria. In the aSAH group, the mean dosing regimen was 17.6 ± 4 mg/kg every 12 (8–12) h. The mean measured trough concentration was lower than the predicted trough concentration (9.9 ± 4.1 vs. 19 ± 8.7 μg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.135 ± 0.04 vs. 0.092 ± 0.03 h^?1; p < 0.001), and the mean calculated half-life was lower than predicted (5.7 ± 1.8 vs. 8.3 ± 2.9 h; p < 0.001). In the ICH group, the mean dosing regimen was 15.9 ± 4.3 mg/kg every 12 (8–12) h. Similarly, the mean measured trough concentration was lower than the predicted trough concentration (10.7 ± 4.6 vs. 17.5 ± 8.5 μg/mL; p < 0.001). The mean calculated elimination rate constant was higher than the predicted value (0.106 ± 0.03 vs. 0.079 ± 0.02 h^?1; p < 0.001), and the mean calculated half-life was lower than predicted (7.2 ± 2.3 vs. 9.6 ± 3.2 h; p < 0.001).

Conclusions

Patients with hemorrhagic stroke exhibited pharmacokinetic alterations favoring increased elimination of vancomycin when compared to predicted pharmacokinetic parameters based on population data. This may result in underexposure to vancomycin, leading to treatment failure and other medical complications.

     

Quality of life and social functioning of former long-stay psychiatric patients transferred into the community: a 10 year follow up study

Purpose

Deinstitutionalisation in Ireland began following the impetus of the successful transfer of psychiatric patients into the community in other countries. This study sought to evaluate the quality of life (QoL) and social functioning (SF) of former long-stay institutionalised patients with severe and enduring mental illness who had been relocated into local community settings and followed up 10 years later.

Method

One month prior to hospital closure, 87 former long-stay psychiatric patients, the majority of whom had a diagnosis of schizophrenia, were assessed on a range of QoL and SF measures. Patients were followed-up 10 years later in the community, to evaluate baseline predictors of quality of life and social functioning.

Results

Study completers (n?=?35) improved significantly on a range of QoL and SF measures over the 10 year period. Specific improvements were noted in domestic skills (t = ? 2.8, p?<?0.0008), community skills (t = ? 4.9, p?<?0.001), as well as the activity and social relations measure (t = ? 4.1, p?<?0.001). Increased social function (t = ? 6.3, p?<?0.001) and improvement on the social behaviour scale (t?=?7.6, p?<?0.001) were noted at follow-up. Linear regression analysis found that less social behaviour problems at baseline predicted QoL 10 years later (t = ? 2.6, p?<?0.02).

Conclusion

This study demonstrated that transfer into the community from an institutional environment was associated with long-term improvements in quality of life and social functioning, even in those who spent many years in the institution. Those who demonstrated the greatest improvement in QoL had less social behavioural problems at baseline assessment, providing further evidence of the success of community living for former long-stay patients.

     

Natalizumab reduces serum pro-angiogenic activity in MS patients

Angiogenesis has been implicated in the pathobiology of multiple sclerosis (MS). Osteopontin exerts a pro-angiogenetic effect and is increased in body fluid of MS patients. To evaluate the effect of 1 year natalizumab treatment on serum pro-angiogenic activity and on plasma osteopontin levels in relapsing (RR) MS patients. Ten RRMS patients scheduled for natalizumab treatment were enrolled and evaluated at baseline and after 1-year natalizumab treatment. Pro-angiogenic activity was assessed by a chick embryo chorioallantoic membrane assay (CAM), osteopontin levels were evaluated by an enzyme-linked immunosorbent assay. Plasma and serum samples of 10 treatment-naïve RRMS and 10 healthy controls (HCs) were used as controls of baseline evaluations. Both treatment-naïve and natalizumab scheduled RRMS patients had higher baseline vessel density (22.0?±?3.9 and 22.5?±?2.6, p?<?0.0001) and higher osteopontin levels (65.7?±?24.3 ng/ml and 65.9?±?16.6 ng/ml, p?=?0.019 and p?=?0.029, respectively) than HCs (9.0?±?2.2; 48.5?±?7.8 ng/ml, respectively). Baseline osteopontin levels and vessel density were significantly correlated (rs?=?0.373, p?=?0.043). After 1 year of treatment, the number of vessels and the osteopontin levels, were significantly reduced (11.9?±?2.1, p?<?0.005; 49.3?±?20.0 ng/ml, p?=?0.028). Our results suggest that natalizumab could exert its anti-inflammatory properties also by inhibiting the angiogenetic mechanisms in RRMS patients.     

Adult normative values for the PATA Rate Test

Background

During neurological evaluation, dysarthria is not rated using quantitative measures, but rather using a qualitative approach.

Objective

Aim of our study was to validate and acquire normative values for the PATA Rate Task (PRT), a quantitative test used to measure the severity of dysarthria.

Methods

For the PRT probands are invited to repeat the syllables “PA-TA” as quickly as possible during a 10-s interval. The score consists in the number of correct repetition of both syllables.

Results

We enrolled 232 healthy controls (118 males, 114 females), mean and standard deviation of the PRT was 28.84?±?6.6 (range 14–52). The PRT showed good inter-rater reliability (R?=?0.783; p?<?0.001), as well as test–retest reliability (R?=?0.927; p?<?0.001), and intra-rater reliability (R?=?0.888; p?<?0.001). Higher age correlated with lower scores (R?=?? 0.368; p?<?0.001).

Conclusions

The PRT showed good reliability and could be easily added to the evaluation of movement disorders where a speech evaluation is essential.

     

Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.     

Spinal Cord Damage in Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder caused by a CAG repeat expansion, characterized by progressive cerebellar ataxia and pyramidal signs. Non-motor and extracerebellar symptoms may occur. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are no data about cord damage in the disease and its clinical relevance. To evaluate in vivo spinal cord damage in SCA1, a group of 31 patients with SCA1 and 31 age- and gender-matched healthy controls underwent MRI on a 3T scanner. We used T1-weighted 3D images to estimate the cervical spinal cord area (CA) and eccentricity (CE) at three C2/C3 levels based on a semi-automatic image segmentation protocol. The scale for assessment and rating of ataxia (SARA) was used to quantify disease severity. The groups were significantly different regarding CA (47.26 ± 7.4 vs. 68.8 ± 5.7 mm2, p < 0.001) and CE values (0.803 ± 0.044 vs. 0.774 ± 0.043, p < 0.05). Furthermore, in the patient group, CA presented significant correlation with SARA scores (R = ?0.633, p < 0.001) and CAGn expansion (R = ?0.658, p < 0.001). CE was not associated with SARA scores (p = 0.431). In the multiple variable regression, CA was strongly associated with disease duration (coefficient ?0.360, p < 0.05) and CAGn expansion (coefficient ?1.124, p < 0.001). SCA1 is characterized by cervical cord atrophy and anteroposterior flattening. Morphometric analyses of the spinal cord MRI might be a useful biomarker in the disease.     

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n?=?272, mean duration 17.9 months) or LPV/r (n?=?173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p?<?0.001), were less likely to have AIDS (p?<?0.001) or hepatitis C virus (HCV) coinfection (p?<?0.05), had higher CD4+ T cell nadirs (p?<?0.001), had lower peak (p?<?0.001) and current (p?<?0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p?<?0.001). Overall, EFV users had worse speed of information processing (p?=?0.04), verbal fluency (p?=?0.03), and working memory (p?=?0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n?=?329), EFV users performed poorly, whereas among HCV seropositives (n?=?116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n?=?269), EFV users had worse speed of information processing (p?=?0.02) and executive functioning (p?=?0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial.     

Serum Coenzyme Q10 Is Associated with Clinical Neurological Outcomes in Acute Stroke Patients

Disruption of prooxidant-antioxidant balance may lead to oxidative stress which is known as a mechanism contributing to ischemic stroke. Coenzyme Q10 (CoQ10) is an endogenous antioxidant that could be effective in preventing oxidative stress. However, the contribution of serum levels of CoQ10 in clinical neurological outcomes following ischemic stroke has not been clearly established. This study aims at measuring serum concentration of CoQ10 along with major indicators of antioxidant and oxidant among patients within 24 h after onset of the stroke symptoms, and investigating their relation with the clinical status of patients. Serum levels of CoQ10, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured in 76 patients and 34 healthy individuals. Severity of the neurological deficit, functional disability, and cognitive status in ischemic subjects were respectively studied with the National Institutes of Health stroke scale (NIHSS), modified Rankin Scale (MRS), and Mini-Mental State Examination (MMSE). Stroke patients had significantly lower serum level of CoQ10 and SOD as compared to controls (27.34?±?35.40 ng/ml, 18.58?±?0.76 μ/ml, respectively; p?<?0.05), whereas the serum MDA level was significantly higher (38.02?±?2.61 μm, p?<?0.05). A significant negative correlation was detected between the serum CoQ10 level and scores of NIHSS and MRS. A similar association was discerned between the SOD level and the neurological deficit score. The serum MDA level was also found to be strongly correlated with all three neurological scales. These findings suggest that the serum level of CoQ10 like other antioxidant and oxidant markers can significantly change early after ischemic stroke and they are substantially associated with clinical neurological outcomes.     

Cerebellar Contribution to Social Cognition

Emotion attribution (EA) from faces is key to social cognition, and deficits in perception of emotions from faces underlie neuropsychiatric disorders in which cerebellar pathology is reported. Here, we test the hypothesis that the cerebellum contributes to social cognition through EA from faces. We examined 57 patients with cerebellar disorders and 57 healthy controls. Thirty-one patients had complex cerebrocerebellar disease (complex cerebrocerebellar disease group (CD)); 26 had disease isolated to cerebellum (isolated cerebellar disease group (ID)). EA was measured with the Reading the Mind in the Eyes test (RMET), and informants were administered a novel questionnaire, the Cerebellar Neuropsychiatric Rating Scale (CNRS). EA was impaired in all patients (CD p?<?0.001, ID p?<?0.001). When analyzed for valence categories, both CD and ID missed more positive and negative stimuli. Positive targets produced the highest deficit (CD p?<?0.001, ID p?=?0.004). EA impairments correlated with CNRS measures of deficient social skills (p?<?0.05) and autism spectrum behaviors (p?<?0.005). Patients had difficulties with emotion regulation (CD p?<?0.001, ID p?<?0.001), autism spectrum behaviors (CD p?<?0.049, ID p?<?0.001), and psychosis spectrum symptoms (CD p?<?0.021, ID p?<?0.002). ID informants endorsed deficient social skills (CD p?<?0.746, ID p?<?0.003) and impaired attention regulation (CD p?<?0.144, ID p?<?0.001). Within the psychosis spectrum domain, CD patients were worse than controls for lack of empathy (CD p?=?0.05; ID p?=?0.49). Thus, patients with cerebellar damage were impaired on an EA task associated with deficient social skills and autism spectrum behaviors and experienced psychosocial difficulties on the CNRS. This has relevance for ataxias, the cerebellar cognitive affective/Schmahmann syndrome, and neuropsychiatric disorders with cerebellar pathology.     

Relation between lipoprotein-associated phospholipase A<Subscript>2</Subscript> mass and incident ischemic stroke severity

Background

Manifestations of ischemic stroke vary widely, and serum biomarkers may be useful for stratification of risk of severe stroke. This study evaluated the association of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) mass and initial severity.

Methods

We employed a retrospective analysis on our hospital-based registry and recruited 488 first-onset ischemic stroke patients admitted within 24 h after onset and with Lp-PLA₂ mass measured. Stroke severities evaluated by National Institutes of Health Stroke Scale (NIHSS) were compared between Lp-PLA₂ categories dichotomized by median. Multivariate logistic regression was used to detect the independent risk factors of severe stroke (NIHSS ≥?7) and receiver operator curve (ROC) was constructed to detect the value of addition of Lp-PLA₂ to the model of other risk factors for predicting severe stroke.

Results

Of the overall patients, the median admission NIHSS scores was 3 and 28.1% had severe manifestation. Admission NIHSS scores were different between patients of Lp-PLA₂ above and under the median (median NIHSS 4 vs. 3, P?<?0.001). Lp-PLA₂ levels was correlated with admission NIHSS (r?=?0.268, P?<?0.001). Logistic regression showed Lp-PLA₂ category (OR 2.37, 95%CI 1.44–3.90, P?<?0.001) and levels per 100 ng/ml (OR 1.69, 95%CI 1.35–2.11, P?<?0.001) were both independently associated with severe stroke. Addition of Lp-PLA₂ category and levels to other independent risk factors both increased the area under curves (from 0.676 to 0.718 with category and 0.734 with levels).

Conclusion

Lp-PLA2 was independently related to admission severity in ischemic stroke patients, implying a potential predictive value of Lp-PLA2 for severe stroke in prevention.

     

Impact of TLR5 rs5744174 on stroke risk,gene expression and on inflammatory cytokines,and lipid levels in stroke patients

Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case–control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real-time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFα were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: β = ? 0.14, 95 % CI: ?0.24 to ?0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population.     

Symptomatic intracranial atherosclerotic disease: an ultrasound 2-year follow-up pilot study

Introduction

The objective of this single-center pilot study was to assess if symptomatic intracranial atherosclerotic disease (ICAD) ultrasound features change through the 2 years after acute ischemic stroke or TIA, being ICAD a relevant cause of acute ischemic stroke or TIA, linked to high rates of recurrent stroke.

Methods

We consecutively enrolled 48 patients with acute ischemic stroke or TIA with symptomatic ICAD detected by transcranial color-coded duplex sonography (TCCS) and confirmed by MR-angiography and/or CT-angiography. We set a neurosonological and clinical follow-up at 3, 6, 12, and 24 months (T0, T1, T2, T3, and T4).

Results

We observed that the hemodynamic effect of the stenosis changed during the 2-year follow-up, as revealed by the modifications of Peak Systolic Velocity (PSV) (Friedman-ANOVA test, p?<?0.001). The pairwise post-hoc analysis showed a statistically significant difference between PSV at T0 and PSV at T3 (p?=?0.005) and between PSV at T0 and PSV at T4 (p?<?0.001) being PSV at T3 and T4 lower than PSV at T0. Seven patients had a new event in the first 12 months.

Conclusions

The high rate of recurrent stroke or death among ICAD patients seems to be independent of progressive arterial narrowing. A wide multicenter follow-up study is needed in order to identify the factors that, alongside the hemodynamic features, contribute to the high risk of recurrent stroke among patient with symptomatic ICAD.

     

Psychiatric Morbidity in Dependent Z-Drugs and Benzodiazepine Users

Zolpidem/zopiclone (Z-drugs) and benzodiazepines (BDZs) have different profiles of comorbidity, but studies have seldom explored these differences. This study examined psychiatric comorbidity in patients dependent on Z-drugs or BDZs attending substance abuse clinics in Hong Kong. In this retrospective chart review, the medical records of 207 patients (117 on Z-drugs and 90 on BDZs) treated between January 2008 and August 2012 were analysed. Demographic data, patterns of substance misuse and comorbid psychiatric diagnoses were recorded. Patients dependent on Z-drugs were younger (40.5?±?10.4 vs. 46.8?±?11.6; p?<?0.001), had an earlier age of onset of drug misuse (p?=?0.047) and were more likely to currently use cough syrup (29.5?±?12.1 vs. 33.6?±?14.5; p?=?0.009) than the BDZs dependent patients. Overall, the Z-drugs and BDZs groups had a similar frequency of comorbid psychotic disorders, mood disorders and anxiety disorders. Mood disorders were the most common comorbid psychiatric disorders. The zopiclone group had a significantly higher percentage of psychotic disorders than the zolpidem group (25.5 % vs. 0; p?=?0.022). To summarize, patients with Z-drugs or BDZs dependence have similar psychiatric comorbidities, with depressive disorder the most common comorbidity. Zopiclone is more likely to be associated with psychotic disorders than zolpidem.     

The Diagnosis and Natural History of Multiple System Atrophy,Cerebellar Type

The objective of this study was to identify key features differentiating multiple system atrophy cerebellar type (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. Twelve patients had definite MSA-C, 53 had possible/probable MSA-C, and 12 had ILOCA. Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p?=?0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p?<?0.01). REM sleep behavior disorder (RBD) occurred early in possible/probable MSA-C (p?<?0.01). Late MSA-C included pathologic laughing and crying (PLC, p?<?0.01), bradykinesia (p?=?0.01), and corticospinal findings (p?=?0.01). MRI distinguished MSA-C from ILOCA by atrophy of the brainstem (p?<?0.01) and middle cerebellar peduncles (MCP, p?=?0.02). MSA-C progressed faster than ILOCA: by 6 years, MSA-C walker dependency was 100 % and ILOCA 33 %. MSA-C survival was 8.4?±?2.5 years. Mean length of ILOCA illness to date is 15.9?±?6.4 years. A sporadic onset, insidiously developing cerebellar syndrome in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of the cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs, and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.     

Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task

Previous research suggests that a history of early life stress (ELS) impacts working memory (WM) in adulthood. Despite the widespread use of WM paradigms, few studies have evaluated whether ELS exposure, in the absence of psychiatric illness, also impacts WM-associated brain activity in ways that might improve sensitivity to these ELS effects or provide insights into the mechanisms of these effects. This study evaluated whether ELS affects WM behavioral performance and task-associated activity by acquiring 3T functional images from 27 medication-free healthy adults (14 with ELS) during an N-back WM task that included 0- and 2-back components. Whole brain voxel-wise analysis was performed to evaluate WM activation, followed by region of interest analyses to evaluate relationships between activation and clinical variables. ELS was associated with poorer accuracy during the 2-back (79 %?±?19 vs. 92 %?±?9, p?=?0.049); accuracy and response time otherwise did not differ between groups. During the 0-back, ELS participants demonstrated increased activation in the superior temporal gyrus/insula, left inferior parietal lobule (IPL) (both corrected p?<?0.001), and middle temporal and parahippocampal gyrus (MTG/PHG)(corrected p?<?0.010). During the 2-back, ELS was associated with greater activation in the IPL, MTG/PHG and inferior frontal gyrus (corrected p?<?0.001), with a trend towards precuneus activation (p?=?0.080). These findings support previous research showing that ELS is associated with impaired neurobehavioral performance and changes in brain activation, suggesting recruitment of additional cognitive resources during WM in ELS. Based on these findings, ELS screening in future WM imaging studies appears warranted.