Background
Recent changes in the understanding and management of multiple sclerosis (MS) have increased the role of MRI in supporting diagnosis and disease monitoring. However, published guidelines ...on the use of MRI in MS do not translate easily into different clinical settings and considerable variation in practice remains. Here, informed by published guidelines for the use of MRI in MS, we identified a clinically informative MRI protocol applicable in a variety of clinical settings, from district general hospitals to tertiary centres.
Methods
MS specialists geographically representing the UK National Health Service and with expertise in MRI examined existing guidelines on the use of MRI in MS and identification of challenges in their applications in various clinical settings informed the formulation of a feasible MRI protocol.
Results
We identified a minimum set of MRI information, based on clinical relevance, as well as on applicability to various clinical settings. This informed the selection of MRI acquisitions for scanning protocols, differentiated on the basis of their purpose and stage of the disease, and indication of timing for scans. Advice on standardisation of MRI requests and reporting, and proposed timing and frequency of MRI scans were generated.
Conclusions
The proposed MRI protocol can adapt to a range of clinical settings, aiding the impetus towards standardisation of practice and offering an example of research-informed service improvement to support optimisation of resources. Other neurological conditions, where a gap still exists between published guidelines and their clinical implementation, may benefit from this same approach.
Cannabis and multiple sclerosis Ingram, Gillian; Pearson, Owen R
Practical neurology,
08/2019, Letnik:
19, Številka:
4
Journal Article
Recenzirano
Patients with multiple sclerosis have long turned to complementary therapies to manage symptoms that licensed products can only partially control. Around half of patients with multiple sclerosis ...admit to previous or current cannabis use for medicinal purposes and would endorse legalisation. Despite many governments worldwide relaxing regulations around medicinal cannabis, there remain many unanswered questions as to how clinicians should prescribe or recommend products, and access to pharmaceutical-grade products remains highly restricted. Here we address what adult neurologists need to know about cannabis and its use in multiple sclerosis.
Objective
Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening ...disability in this group?
Methods
We used data from the UK MS Register to characterize demographics and clinical features of late‐onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult‐onset MS (AOMS; onset 18–49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years).
Results
In the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 28.3, p < 0.001), and a higher proportion of gait‐related initial symptoms. People with LOMS were less likely to receive a high efficacy disease‐modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset‐age, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older‐onset MS patients.
Interpretation
The more progressive nature of older‐onset MS is associated with significant neurodegeneration, but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. ANN NEUROL 2024;95:471–486
Progressive disability in multiple sclerosis occurs because CNS axons degenerate as a late consequence of demyelination. In animals, retinoic acid receptor RXR-gamma agonists promote remyelination. ...We aimed to assess the safety and efficacy of a non-selective retinoid X receptor agonist in promoting remyelination in people with multiple sclerosis.
This randomised, double-blind, placebo-controlled, parallel-group, phase 2a trial (CCMR One) recruited patients with relapsing-remitting multiple sclerosis from two centres in the UK. Eligible participants were aged 18–50 years and had been receiving dimethyl fumarate for at least 6 months. Via a web-based system run by an independent statistician, participants were randomly assigned (1:1), by probability-weighted minimisation using four binary factors, to receive 300 mg/m2 of body surface area per day of oral bexarotene or oral placebo for 6 months. Participants, investigators, and outcome assessors were masked to treatment allocation. MRI scans were done at baseline and at 6 months. The primary safety outcome was the number of adverse events and withdrawals attributable to bexarotene. The primary efficacy outcome was the patient-level change in mean lesional magnetisation transfer ratio between baseline and month 6 for lesions that had a baseline magnetisation transfer ratio less than the within-patient median. We analysed the primary safety outcome in the safety population, which comprised participants who received at least one dose of their allocated treatment. We analysed the primary efficacy outcome in the intention-to-treat population, which comprised all patients who completed the study. This study is registered in the ISRCTN Registry, 14265371, and has been completed.
Between Jan 17, 2017, and May 17, 2019, 52 participants were randomly assigned to receive either bexarotene (n=26) or placebo (n=26). Participants who received bexarotene had a higher mean number of adverse events (6·12 SD 3·09; 159 events in total) than did participants who received placebo (1·63 SD 1·50; 39 events in total). All bexarotene-treated participants had at least one adverse event, which included central hypothyroidism (n=26 vs none on placebo), hypertriglyceridaemia (n=24 vs none on placebo), rash (n=13 vs one on placebo), and neutropenia (n=10 vs none on placebo). Five (19%) participants on bexarotene and two (8%) on placebo discontinued the study drug due to adverse events. One episode of cholecystitis in a placebo-treated participant was the only serious adverse event. The change in mean lesional magnetisation transfer ratio was not different between the bexarotene group (0·25 percentage units pu; SD 0·98) and the placebo group (0·09 pu 0·84; adjusted bexarotene–placebo difference 0·16 pu, 95% CI –0·39 to 0·71; p=0·55).
We do not recommend the use of bexarotene to treat patients with multiple sclerosis because of its poor tolerability and negative primary efficacy outcome. However, statistically significant effects were seen in some exploratory MRI and electrophysiological analyses, suggesting that other retinoid X receptor agonists might have small biological effects that could be investigated in further studies.
Multiple Sclerosis Society of the United Kingdom.
Carbon and nitrogen stable isotopes (δ
13
C and δ
15
N) were used to examine trophic niche dynamics of three co-occurring predators in The Bahamas. Variable estimates of core trophic niche width and ...total trophic niche overlap were observed between nurse sharks (
Ginglymostoma cirratum
), southern stingrays (
Hypanus americanus
), and Atlantic chupare stingrays (
Styracura schmardae
). Nurse sharks exhibited little trophic overlap with either species of stingray and exhibited higher δ
15
N values, suggesting limited potential resource competition. Southern and Atlantic chupare stingrays exhibited higher total trophic niche overlap, highlighting higher levels of resource competition. Nurse sharks exhibited the broadest δ
13
C range, implying utilization of multiple resource pools to facilitate energetic requirements, compared with southern stingrays and Atlantic chupare stingrays. Southern stingrays exhibited the smallest core trophic niche width, highlighting reliance upon a narrower range of resource pools, likely supported by a single habitat type. We postulate that the persistence of the three sub-sampled predator populations is supported by potential resource partitioning and utilization of multiple trophic resource pools. Further information regarding trophic niche dynamics and patterns of resource use is required for data-poor species to identify how populations and communities may respond to the adverse effects of exploitation, such as fisheries impacts, habitat alteration, and pollution.
Background:
People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor ...psychological wellbeing during the pandemic.
Objective:
To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom.
Methods:
This is a community-based, prospective longitudinal cohort and cross-sectional case–control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS.
Results:
The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58–2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04–1.80) reported worse social support (OR: 1.90, 95% CI: 1.18–3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18–2.32) during the outbreak than controls.
Conclusion:
Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.
The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. ...Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys median (IQR) 5.03 (3.71, 6.34), MSWS-12 median (IQR) 5.28 (3.62, 6.94) and HADS-Depression median (IQR) 0.71 (0.47, 0.96) scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.
We present a crystallography chip enabling in situ room temperature crystallography at microfocus synchrotron beamlines and X-ray free-electron laser (X-FEL) sources. Compared to other in situ ...approaches, we observe extremely low background and high diffraction data quality. The chip design is robust and allows fast and efficient loading of thousands of small crystals. The ability to load a large number of protein crystals, at room temperature and with high efficiency, into prescribed positions enables high throughput automated serial crystallography with microfocus synchrotron beamlines. In addition, we demonstrate the application of this chip for femtosecond time-resolved serial crystallography at the Linac Coherent Light Source (LCLS, Menlo Park, California, USA). The chip concept enables multiple images to be acquired from each crystal, allowing differential detection of changes in diffraction intensities in order to obtain high signal-to-noise and fully exploit the time resolution capabilities of XFELs.
Neurologists increasingly use anti-CD20 therapies, including for women of childbearing age, despite these medications being unlicensed for use in pregnancy. Current evidence suggests that women can ...safely conceive while taking anti-CD20 therapy. Women should not be denied treatment during pregnancy when it is clinically indicated, although they should be counselled regarding live vaccinations for their infant. Women receiving regular ocrelizumab for multiple sclerosis should preferably wait 3 months before trying to conceive. There are few data around ofatumumab in pregnancy, and while there is probably a class effect across all anti-CD20 therapies, ofatumumab may need to be continued during pregnancy to maintain efficacy. We recommend that anti-CD20 therapies can be safely given while breast feeding. It is important to make time to discuss treatments with women of childbearing age to help them choose their most suitable treatment. Outcomes should be monitored in pregnancy registries.
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