Association between migraine and HLA–DRB1 gene polymorphisms

We examined the distribution of HLA–DRB1 alleles in a cohort of 255 Italian migraine patients and in a control group of 325 healthy subjects. The frequency of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with migraine while the DRB1*16 allele was significantly increased (p=0.04) in comparison with controls. When the patients were divided into disease subgroups (migraine with and without aura), HLA–DRB1**16 allele was significantly increased (p<0.05) only in migraine without aura patients. We conclude that, in Italian patients, migraine is associated with different alleles of the HLA–DRB1 locus. Our data suggest the presence of a genetic susceptibility factor for migraine within the HLA region

Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: Ne-PAL a pilot randomized controlled study

Background This study analysed the impact on palliative care outcomes of a new specialist palliative care service for patients severely affected by amyotrophic lateral sclerosis (ALS/MND), multiple sclerosis, Parkinson's disease and related disorders (multiple system atrophy progressive supranuclear palsy, MSA-PSP). Methods The design followed the Medical Research Council Framework for the evaluation of complex interventions. A phase II randomised controlled trial (RCT) was undertaken comparing an immediate referral to the service (FT, fast track) to a 16-week wait (standard track (ST), standard best practice) using a parallel arm design. The main outcome measures were Quality of Life (measured with Schedule for the Evaluation of Individual Quality of Life Direct Weight, SEIQoL-DW) and burden of the carers (Caregivers Burden Inventory, CBI), with secondary outcomes of symptoms, psychosocial and spiritual issues. Results 50 patients severely affected by neurodegenerative conditions and their informal family carers were randomised: 25 FT, 25 ST. At baseline (T0), there were no differences between groups. 4 patients died during the follow-up (2 FT, 2 ST) and 2 FT patients dropped out before the end of the study. After 16?weeks (T1), FT participants scored significant improvement in the SEIQoL-DW index, pain dyspnoea sleep disturbance and bowel symptoms. Conclusions This exploratory RCT provides evidence that no harm was experienced by SPCS for patients severely affected by neurodegenerative disorders. There was an improvement in quality of life and physical symptoms for neurological patients in palliative care. Caregiver burden was not affected by the service

Frailty Syndromes in Persons With Cerebrovascular Disease: A Systematic Review and Meta-Analysis

Background: Frailty can change the prognosis and treatment approach of chronic diseases. Among others, frailty has been associated with cerebrovascular diseases such as stroke. However, the extent to which the two conditions are related is unclear, and no systematic review of the literature has been conducted. Objectives: To conduct a systematic review and meta-analysis assessing the association of cerebrovascular diseases and frailty, as well as prefrailty, in observational studies. The project was carried out on behalf of the Joint Action ADVANTAGE WP4 group. Methods: The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-26/05/2019. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic. Publication bias was assessed with Egger's and Begg's tests. Results: Of 1027 studies searched, 18 studies were included (n = 48,009 participants). Stroke was the only cerebrovascular disease studied in relation to frailty syndromes. All studies except one reported an association between stroke and prefrailty or frailty. However, most studies were not of high quality and there was heterogeneity between results. The pooled prevalence of prefrailty and frailty in stroke patients was 49% (95% CI = 42–57) and 22% (95% CI = 16–27), respectively. The prevalence of frailty was 2-fold in persons with stroke compared to those without stroke (pooled odds ratio = 2.32, 95% CI = 2.11–2.55). Only two studies longitudinally examined the association between stroke and frailty, producing conflicting results. Conclusions: Frailty and prefrailty are common in persons with stroke. These results may have clinical implications, as they identify the need to assess frailty in post-stroke survivors and assess how it may affect prognosis. Better quality, longitudinal research that examines the temporal relationship between stroke and frailty are needed, as well as studies on other types of cerebrovascular disease

MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis

Objective: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon b treatment as response indicators in multiple sclerosis (MS). Methods: Patients with relapsing–remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing T1 lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres >20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months. Results: 147 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN) 52% (34–69%), specificity (SP) 80% (65–91%), negative predictive value (NPV) 73% (58–77%), positive predictive value (PPV) 62% (42–79%), p=0.002; NAb positivity, SN 71% (45–88%), SP 66% (55–76%), NPV 92% (82–97%), PPV 29% (16– 45%), p=0.01; active scan and NAb positivity, SN 71% (38–91%), SP 86% (73–94%), NPV 94% (86–98%), PPV 50% (29–70%), p=0.0003. Conclusions: MRI activity and NAb occurrence during the first 6 months of interferon b treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests

The OPTimization of Interferon for MS study : 375 mug interferon beta-1b in suboptimal responders

We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFNβ-1b) 375 μg (subcutaneously [sc] every other day [eod]) in relapsingremitting multiple sclerosis (RRMS) patients with a suboptimal response to IFNβ-1b 250 μg, i.e., with MRI activity or relapses. The OPTimization of Interferon for MS (OPTIMS) study was a prospective multicenter randomized phase 2 trial comprising a 6-month run-in phase (to identify suboptimal responders) and a 6-month randomized phase of open-label clinical and blinded MRI follow-up. During run-in all patients were treated with IFNβ-1b 250 μg sc eod; during the study phase suboptimal treatment responders were randomized either to IFNβ-1b 250 or 375 μg sc eod. Primary outcome was the proportion of patients without MRI activity during study Months 9–12 according to the intention-totreat principle. 216 RRMS patients entered the study: 83 suboptimal responders were identified and randomized, 7 refused to continue treatment, 76 were included in the analysis. More patients treated with 375 μg had no MRI activity at Months 9–12 (30/36 vs.16/40; relative risk, 0.28; 95 % confidence interval, 0.08–0.47; p = 0.0001). Sensitivity analysis (“worst case scenario”) confirmed the results. No new or unexpected adverse events were observed, but there was a trend towards more withdrawals in the 375 μg group. Increasing the dose of IFNβ-1b from 250 μg to 375 μg is a successful strategy for reducing subclinical signs of disease activity in RRMS patients. Further studies are needed to show whether this dose may also improve clinical efficacy

The palliative care needs of people severely affected by neurodegenerative disorders:a qualitative study

Specialist palliative care services are often involved in the care of people with progressive neurological disease, in particular amyotrophic lateral sclerosis. However, the particular needs of people with advanced and progressive neurological disease are not well known. A qualitative approach was used, interviewing people with advanced amyotrophic lateral sclerosis/motor neurone disease (ALS/MND), multiple sclerosis (MS), Parkinson's disease (PD), and multiple systems atrophy (MSA) and their family carers to ascertain their particular needs. Focus groups of health and social care professionals allowed a professional view of the needs. People with progressive disease have many, difficult and distressing symptoms: physical, including pain, movement issues, swallowing and speech problems, psychological, feelings of being abandoned and of anxiety and depression, social, of isolation, of being a burden and of financial issues, and spiritual, of loss of hope and the meaning of life as they approach death. These issues could be helped by the development of a palliative care approach and the involvement of a specialist palliative care team, which was supported by patients, carers, and professionals