An update on the role of magnetic resonance imaging in predicting and monitoring multiple sclerosis progression

INTRODUCTION: While magnetic resonance imaging (MRI) is established in diagnosing and monitoring disease activity in multiple sclerosis (MS), its utility in predicting and monitoring disease progression is less clear. AREAS COVERED: The authors consider changing concepts in the phenotypic classification of MS, including progression independent of relapses; pathological processes underpinning progression; advances in MRI measures to assess them; how well MRI features explain and predict clinical outcomes, including models that assess disease effects on neural networks, and the potential role for machine learning. EXPERT OPINION: Relapsing-remitting and progressive MS have evolved from being viewed as mutually exclusive to having considerable overlap. Progression is likely the consequence of several pathological elements, each important in building more holistic prognostic models beyond conventional phenotypes. MRI is well placed to assess pathogenic processes underpinning progression, but we need to bridge the gap between MRI measures and clinical outcomes. Mapping pathological effects on specific neural networks may help and machine learning methods may be able to optimize predictive markers while identifying new, or previously overlooked, clinically relevant features. The ever-increasing ability to measure features on MRI raises the dilemma of what to measure and when, and the challenge of translating research methods into clinically useable tools

Neurological update: non-motor symptoms in atypical parkinsonian syndromes

Among people with Parkinson’s disease (PD), non-motor symptoms (NMS) are a well-recognised cause of significant morbidity and poor quality of life. Yet, it is only more recently that NMS have been recognised to affect the lives of patients with atypical parkinsonian syndromes in a similar fashion. The aim of this article is to highlight and compare the relative prevalence of NMS among patients with atypical parkinsonian syndromes in the published literature, which largely remain underreported and unaddressed in routine clinical practice. All NMS that are recognised to occur in PD are also found to commonly occur in atypical parkinsonian syndromes. In particular, excessive daytime sleepiness is more prevalent among atypical parkinsonian syndromes (94.3%) compared to PD (33.9%) or normal controls (10.5%) (p < 0.001). Urinary dysfunction (not limited to urinary incontinence) is not only found to occur in MSA (79.7%) and PD (79.9%), but has also been reported in nearly half of the patients with PSP (49.3%), DLB (42%) and CBD (53.8%) (p < 0.001). Apathy is significantly more common among the atypical parkinsonian syndromes [PSP (56%), MSA (48%), DLB (44%), CBD (43%)] compared to PD (35%) (p = 0.029). Early recognition and addressing of NMS among atypical parkinsonian syndromes may help improve the holistic patient care provided and may encompass a range of conservative and pharmacotherapeutic treatments to address these symptoms

Correction to: Neurological update: non-motor symptoms in atypical parkinsonian syndromes

The original version of this article unfortunately contained a mistake. The corrected detail is provided below: In section “CBD”, fourth paragraph, which previously read: Visual dysfunction appears to be another common problem among patients with CBD [37, 42, 45, 48, 51, 55, 56], and is included in the diagnostic criteria for the disease [51, 57, 58]. Although several studies [37, 45, 48] did not find any gross visual impairment on formal testing, one review [41] discussed how this might be due to confounding factors such as limb apraxia, motor deficits or co-existent executive dysfunction which could limit the ability to formally test visuospatial function. Should read: Visuospatial dysfunction appears to be another common problem among patients with CBD [37, 42, 45, 48, 51, 55, 56], and is included in the diagnostic criteria for the disease [51, 57, 58]. Although several studies [37, 45, 48] did not find any gross visual impairment on formal testing, one review [41] discussed how this might be due to confounding factors such as limb apraxia, motor deficits or co-existent executive dysfunction which could limit the ability to formally test visuospatial function

Delivery of urethral sphincter botulinum toxin injections for treating urinary retention during the COVID19 pandemic

Aims: Urethral sphincter botulinum toxin injections is an alternative treatment for urinary retention in women with Fowler’s syndrome and when access to health services were curtailed during the Covid19 pandemic, we continued to offer treatment to prevent increased demand on catheter services due to a recurrence of urinary retention. We describe our experience delivering safe and timely treatment during this period of lockdowns and restricted access to healthcare. // Methods: We retrospectively reviewed the records of all women with Fowler’s syndrome treated with transperineal urethral sphincter botulinum toxin injection between 23rd March 2020 and 31st December 2021 in a tertiary university hospital and clinical outcomes were recorded. // Results: 15 women (mean age 35.6 ± 10.1 years) received 100U OnabotulinumtoxinA injected into the external urethral sphincter as an out-patient procedure adopting hospital infection control guidelines. 41 injections were administered in total, and 8 (53%) patients received more than 1 injection (median 2 injections/patient, median inter-injection interval 108.5 days). 10 (66.7%) patients reported improvements in urinary symptoms across 31/41 (75.6%) of injections. Side effects were reported after 21.4% of injections which were mild and transient. No patients developed Covid19 within 4 weeks of the hospital visit. // Conclusion: Real-world data shows that transperineal urethral sphincter botulinum toxin injections could be continued safely and effectively during the Covid19 pandemic. This essential outpatient service played an important role in treatment and quality of life for women with Fowler’s syndrome, and avoided an additional burden on the NHS at the time of a health crisis

The evolving contribution of MRI measures towards the prediction of secondary progressive multiple sclerosis

BACKGROUND: In multiple sclerosis (MS), both lesion accrual and brain atrophy predict clinical outcomes. However, it is unclear whether these prognostic features are equally relevant throughout the course of MS. Among 103 participants recruited following a clinically isolated syndrome (CIS) and followed up over 30 years, we explored (1) whether white matter lesions were prognostically more relevant earlier and brain atrophy later in the disease course towards development of secondary progressive (SP) disease; (2) if so, when the balance in prognostic contribution shifts and (3) whether optimised prognostic models predicting SP disease should include different features dependent on disease duration. METHODS: Binary logistic regression models were built using age, gender, brain lesion counts and locations, and linear atrophy measures (third ventricular width and medullary width) at each time point up to 20 years, using either single time point data alone or adjusted for baseline measures. RESULTS: By 30 years, 27 participants remained CIS while 60 had MS (26 SPMS and 16 MS-related death). Lesions counts were prognostically significant from baseline and at all later time points while linear atrophy measure models reached significance from 5 years. When adjusted for baseline, in combined MRI models including lesion count and linear atrophy measures, only lesion counts were significant predictors. In combined models including relapse measures, Expanded Disability Status Scale scores and MRI measures, only infratentorial lesions were significant predictors throughout. CONCLUSIONS: While SPMS progression is associated with brain atrophy, in predictive models only infratentorial lesions were consistently prognostically significant

Long-term Outcomes of Periurethral Sphincter Botulinum Toxin in Female Chronic Urinary Retention

Purpose Nonneurogenic chronic urinary retention is an uncommon problem in young female individuals, and a well characterised causes is Fowler syndrome (primary disorder of urethral sphincter relaxation). Intermittent catheterisation is often challenging, and gold standard treatment sacral neuromodulation is not widely available. Urethral sphincter botulinum toxin injection has been shown to be effective cross-sectionally, however little is known about long-term outcomes. Methods Female individuals presenting with urinary retention due to Fowler syndrome were reviewed retrospectively from a single tertiary referral centre over an 11-year period (2010–2021). One hundred units of onabotulinum toxin A (BoTX-A) was injected into the striated urethral sphincter in a divided dose by the periurethral approach. Efficacy and side effects were assessed 4 weeks after injection. Results Thirty-three female individuals with a mean age of 40.1±14.1 years received 165 unique urethral sphincter BoTX-A injections over 11 years. Nineteen individuals (57.6%) presented in acute urinary retention, and 28 (84.8%) were reliant on catheterisation. Twenty-one individuals (64%) responded to BoTX-A injections and had a significantly raised baseline maximum urethral closure pressure (MUCP), compared to nonresponders (114.6 cm H2O, P=0.012). Side effects were reported following 19 injections (11.5%) however, were mild and transient. Fifteen individuals received more than 1 botulinum toxin injection (median, 3 injections), with a median interval of 112 days (interquartile range) and efficacy persisted following repeat injections and no safety concerns were seen. Conclusions Sphincter botulinum toxin through the periurethral approach is safe and effective following repeat injections, and offers a low-cost, minimally invasive alternative to managing female chronic urinary retention due to Fowler syndrome, particularly when there was a high baseline MUCP

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT

BACKGROUND: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. OBJECTIVE: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. DESIGN: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. SETTING: Usual NHS care. PARTICIPANTS: Patients undergoing elective/non-elective abdominal surgery, including caesarean section. INTERVENTIONS: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'. MAIN OUTCOME MEASURES: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. DATA SOURCES: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals. RESULTS: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. LIMITATIONS: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. CONCLUSIONS: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks. TRIAL REGISTRATION: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1)

Validation of the Bluebelle Wound Healing Questionnaire for assessment of surgical-site infection in closed primary wounds after hospital discharge

BACKGROUND: Accurate assessment of surgical‐site infection (SSI) is crucial for surveillance and research. Self‐reporting patient measures are needed because current SSI tools are limited for assessing patients after leaving hospital. The Bluebelle Wound Healing Questionnaire (WHQ) was developed for patient or observer completion; this study tested its acceptability, scale structure, reliability and validity in patients with closed primary wounds after abdominal surgery. METHODS: Patients completed the WHQ (self‐assessment) within 30 days after leaving hospital and returned it by post. Healthcare professionals completed the WHQ (observer assessment) by telephone or face‐to‐face. Questionnaire response rates and patient acceptability were assessed. Factor analysis and Cronbach's α examined scale structure and internal consistency. Test–retest and self‐ versus observer reliability assessments were performed. Sensitivity and specificity for SSI discrimination against a face‐to‐face reference diagnosis (using Centers for Disease Control and Prevention criteria) were examined. RESULTS: Some 561 of 792 self‐assessments (70·8 per cent) and 597 of 791 observer assessments (75·5 per cent) were completed, with few missing data or problems reported. Data supported a single‐scale structure with strong internal consistency (α greater than 0·8). Reliability between test–retest and self‐ versus observer assessments was good (κ 0·6 or above for the majority of items). Sensitivity and specificity for SSI discrimination was high (area under the receiver operating characteristic (ROC) curve 0·91). CONCLUSION:The Bluebelle WHQ is acceptable, reliable and valid with a single‐scale structure for postdischarge patient or observer assessment of SSI in closed primary wounds