The routine clinical integration of individualised objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multi-centre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3-6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65 - 5.41, p = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012-0.049, p = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared to using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalised objective disease activity monitoring for those living with amyotrophic lateral sclerosis.

A minority (10%–15%) of cases of amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease (MND), are currently attributable to pathological variants in a single identifiable gene. With the emergence of new therapies targeting specific genetic subtypes of ALS, there is an increasing role for routine genetic testing for all those with a definite diagnosis. However, potential harm to both affected individuals and particularly to asymptomatic relatives can arise from the indiscriminate use of genetic screening, not least because of uncertainties around incomplete penetrance and variants of unknown significance. The most common hereditary cause of ALS, an intronic hexanucleotide repeat expansion in C9ORF72, may be associated with frontotemporal dementia independently within the same pedigree. The boundary of what constitutes a possible family history of MND has therefore extended to include dementia and associated psychiatric presentations. Notwithstanding the important role of clinical genetics specialists, all neurologists need a basic understanding of the current place of genetic testing in MND, which holds lessons for other neurological disorders.

Background: Quidditch is a fast growing, physically intense, mixed-gender full-contact sport. Originally adapted from Harry Potter novels, quidditch was first played in 2005 in the USA but is now played worldwide. It is essential to elucidate patterns of injury for the safety and growth of the sport of quidditch. It also provides a unique opportunity to study injury patterns in mixed-gender full-contact sport, an area of increasing importance with the developing culture of transition from single-gender to mixed-gender sports.Purpose: The purpose of this investigation was to examine the types of injuries sustained while playing quidditch in terms of their incidence, anatomical distribution and severity, and gender distribution.Methods: An anonymous self-reporting questionnaire was distributed to all active quidditch players in the UK. Data collection included player demographics, type of injury, mechanism of injury, player position, experience and treatment required, relating to the previous 12 months.Results: A total of 348 participants of 684 eligible athletes responded to the questionnaire representing a 50.87% response rate. There were 315 injuries reported by 180 athletes in total, with an overall incidence of 4.06 injuries per 1,000 hours. A statistically significantly different rate of concussion was observed with female athletes sustaining more concussion than males (p=0.006). The overall rate of concussion was 0.651/1000hrs in males and 1.163/1000hrs in females (0.877/1000 hours overall). Conclusions:This study provides the first quantitative description of injury rates in quidditch. The overall injury rates are no higher than those reported in other recreational contact sports. Female athletes were found to have a higher rate of concussion, which needs further investigation. These findings are relevant to players concerned about safety in quidditch and to governing bodies regarding governance of the sport.

Background and aims:Imaging studies have relied on the ‘overall’ volumetric quantification of perivascular adipose tissue. We sought to assess the relationship of circumferential distribution between perivascular adipose tissue and adjacent wall thickness of carotid and aortic arteries using dedicated magnetic resonance imaging sequences.Methods:Vessel wall and perivascular adipose tissue were acquired using magnetic resonance imaging (1.5 T). Co-registered images were segmented separately, and measurements of both perivascular adipose tissue and vessel wall were obtained along radii of the vessel spaced at angles of 5° each.Results:In total, 29 patients were recruited. Perivascular adipose tissue thickness of the aorta was 3.34 ± 0.79 mm with specific pattern of ‘double peaks’ distribution, while carotid perivascular adipose tissue had no identifiable pattern with thickness of 0.8 ± 0.91 mm. Although statistically significant, the correlation between perivascular adipose tissue thickness and wall thickness in carotid arteries with normal (r = 0.040, p = 0.001) or with abnormal wall thickness (r = –0.039, p = 0.015) was merely nominal. Similarly, perivascular adipose tissue of the aorta had very weak correlation with normal aortic wall thickness (r = 0.010, p = 0.008) but not with the abnormal ones (r = −0.05, p = 0.29).Conclusion:Dissociation between the spatial distribution of perivascular adipose tissue and arterial wall thickening in the aorta and carotid arteries does not support that perivascular adipose tissue has a causal role in promoting atherosclerotic plaque via a paracrine route. Yet, perivascular adipose tissue functional properties were not examined in this study.