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Mar Tintoré,1 Maggie Alexander,2 Kathleen Costello,3 Martin Duddy,4 David E Jones,5 Nancy Law,6 Gilmore O’Neill,7 Antonio Uccelli,8 Robert Weissert,9 Sibyl Wray10 1Multiple Sclerosis Centre of Catalonia, Hospital Vall d’Hebron, Barcelona, Spain; 2European Multiple Sclerosis Platform, Brussels, Belgium; 3National Multiple Sclerosis Society, Denver, CO, USA; 4Royal Victoria Infirmary, Newcastle-upon-Tyne, UK; 5Department of Neurology, University of Virginia, Charlottesville, VA, USA; 6Nancy Law Consulting LLC, Parker, CO, USA; 7Biogen, Cambridge, MA, USA; 8Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 9Department of Neurology, University of Regensburg, Regensburg, Germany; 10Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA Background: Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods: A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results: A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion: Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment. Keywords: health care provider survey, multiple sclerosis, patient-health care provider relationship, patient survey, treatment expectations, treatment satisfaction

Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated. A cohort Markov model based on disease progression through Expanded Disability Status Scale health states, with annual cycles and lifetime horizon, was employed to determine the cost-effectiveness of siponimod from a UK National Health Service (NHS) perspective for patients with active SPMS. Baseline characteristics, health state utility values, hazard ratios for time to 6-month confirmed disability progression, annualized relapse rate ratios and adverse events for siponimod were obtained from the phase 3 EXPAND clinical trial, supplemented by published literature. Published costs, resource use data and comparator efficacy data were obtained from the literature and, in the absence of data, reasonable assumptions were made. Quality-adjusted life years (QALYs) were greater for siponimod versus all comparators (3.45 versus 2.69–2.83). Incremental cost-effectiveness ratios (ICERs), calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY. Recognition of active SPMS and treatment of this phenotype with siponimod offers a cost-effective and clinically beneficial treatment approach compared with the continuation of oral or infused RRMS DMTs. [ABSTRACT FROM AUTHOR]

Background and purpose: Existing effectiveness models of disease‐modifying drugs (DMDs) for relapsing–remitting multiple sclerosis (RRMS) evaluate a single line of treatment; however, RRMS patients often receive more than one lifetime DMD. To develop treatment sequencing models grounded in clinical reality, a detailed understanding of the decision‐making process regarding DMD switching is required. Using a modified Delphi approach, this study attempted to reach consensus on modelling assumptions. Methods: A modified Delphi technique was conducted based on three rounds of discussion amongst an international group of 10 physicians with expertise in RRMS. Results: The panel agreed that the expected time from disease onset to Expanded Disability Status Scale 6.0 is a proxy for disease severity as well as suitable for classifying severity into three groups. A modelled clinical decision rule regarding the timing of switching should contain at least the time between relapses, magnetic resonance imaging outcomes and the occurrence/risk of adverse events. The experts agreed that the assessment of adverse event risk for a DMD is dependent on disease severity, with more risks accepted when the patient's disease is more severe. The effectiveness of DMDs conditional on their position in a sequence and/or disease duration was discussed: there was consensus on some statements regarding this topic but these were accompanied by a high degree of uncertainty due to considerable knowledge gaps. Conclusion: Useful insights into the medical decision‐making process regarding treatment sequencing in RRMS were obtained. The knowledge gained has been used to validate the main modelling concepts and to further generate clinically meaningful results. [ABSTRACT FROM AUTHOR]

Objectives: To study the safety and efficacy of bare and covered stents in infrainguinal vein grafts after failure of PTA for treating graft stenoses.Methods: An analysis of a prospective database of all patients who underwent stenting of infrainguinal vein bypass grafts at this institution between 1 January 2008 and 31 December 2012 was carried out. The main outcome considered was primary patency, which was reported at 1, 6 and 12 months.Results: A total of 18 patients with a mean age of 73 years (range: 56 to 86) were included. The indications for stent placement were significant recoil (7, 39%), graft rupture (6, 33%), residual vein cusps (3, 17%) and aneurysmal degeneration (2, 11%). There was a high overall technical success rate of 94% (17/18) and arrest of haemorrhage was achieved in all cases of graft rupture. The primary patency at 1, 6 and 12 months was 89%, 71% and 59%, respectively.Conclusion: The use of bare and covered stents in infrainguinal vein grafts appears safe and effective. They are an excellent bail-out option for the treatment of graft rupture and give acceptable short-term results. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) has a wide spectrum of clinical courses, characterized by multifocal central nervous system (CNS) damage, postulated to be mediated by CNS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to CD1a (immature DC) and CD83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry. No CD1a-positive cells were detected in the MS or control CNS tissue blocks investigated. CD83-positive cells were not detected in tissues from any of the control cases or in the majority of perivascular cuffs in the MS tissue sections. However, in eight of the MS tissue blocks with evidence of recent demyelination, and in one block each from chronic plaque and NAWM, small numbers of distinct CD83-positive cells were present within occasional perivascular cuffs. In one area only of MS NAWM were CD83-positive cells detected in the tissue parenchyma, in an area of intense immunological activity. DC in MS tissue may originate in the peripheral circulation as monocytes or immature DC and migrate to areas of plaque in response to signals received from CNS-produced chemokines. [ABSTRACT FROM AUTHOR]

Abstract: Variant Creutzfeldt–Jakob disease (CJD) is a transmissible spongiform encephalopathy believed to be caused by the bovine spongiform encephalopathy agent, an abnormal isoform of the prion protein (PrPsc). At present there is no specific or effective treatment available for any form of CJD. Pentosan polysulphate (PPS), a large polyglycoside molecule with weak heparin-like activity, has been shown to prolong the incubation period of the intracerebral infection when administered to the cerebral ventricles in a rodent scrapie model. PPS also prevents the production of further PrPsc in cell culture models. These properties of PPS prompted its cerebroventricular administration in a young man with vCJD. Long-term continuous infusion of PPS at a dose of 11μg/kg/day for 18 months did not cause drug-related side effects. Follow-up CT scans demonstrated progressive brain atrophy during PPS administration. Further basic and clinical research is needed in order to address the issue of efficacy of PPS in vCJD and in other prion diseases. [Copyright &y& Elsevier]

Background: The brain reserve hypothesis posits that larger maximal lifetime brain growth (MLBG) may confer protection against physical disability in multiple sclerosis (MS). Larger MLBG as a proxy for brain reserve, has been associated with reduced progression of physical disability in patients with early MS; however, it is unknown whether this association remains once in the secondary progressive phase of MS (SPMS). Our aim was to assess whether larger MLBG is associated with decreased physical disability progression in SPMS., Methods: We conducted a post hoc analysis of participants in the MS-Secondary Progressive Multi-Arm Randomisation Trial (NCT01910259), a multicentre randomised placebo-controlled trial of the neuroprotective potential of three agents in SPMS. Physical disability was measured by Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT) and 25-foot timed walk test (T25FW) at baseline, 48 and 96 weeks. MLBG was estimated by baseline intracranial volume (ICV). Multivariable time-varying Cox regression models were used to investigate the association between MLBG and physical disability progression., Results: 383 participants (mean age 54.5 years, 298 female) were followed up over 96 weeks. Median baseline EDSS was 6.0 (range 4.0-6.5). Adjusted for covariates, larger MLBG was associated with a reduced risk of EDSS progression (HR 0.84,95% CI:0.72 to 0.99;p=0.04). MLBG was not independently associated with time to progression as measured by 9HPT or T25FW., Conclusion: Larger MLBG is independently associated with physical disability progression over 96 weeks as measured by EDSS in SPMS. This suggests that MLBG as a proxy for brain reserve may continue to confer protection against disability when in the secondary progression phase of MS., Trail Registration Number: NCT01910259., Competing Interests: NJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speakers honoraria from Merck and congress sponsorship covering registration and travel from Novartis. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Schering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. CAGW-K has received research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon 2020, NIHR/MRC, MRC and is a shareholder of Queen Square Analytics. In the last 3 years, JC has received support from the Efficacy and Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership and the Health Technology Assessment (HTA) Programme (NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He is supported in part by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre, London, UK. He has been a local principal investigator for a trial in MS funded by the Canadian MS Society. A local principal investigator for commercial trials funded by: Actelion, Biogen, Novartis and Roche; has received an investigator grant from Novartis; and has taken part in advisory boards/consultancy for Azadyne, Biogen, Celgene, Janssen, MedDay, Merck, NervGen, Novartis and Roche., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Tremor is a disabling symptom of multiple sclerosis (MS), with limited treatment modalities. Thalamic ventral-intermediate-nucleus (VIM) deep brain stimulation (DBS) is a method of neuromodulation. We describe the long-term outcomes of our carefully selected patients who underwent VIM DBS for their MS-associated tremor., Methods: Patients were referred from the regional neurology units. Pre-operative assessments included suitability for anesthesia, tremor quantification by the Fahn-Tolosa-Marin scores, and quality-of-life (EQ5D) measures. Exclusion criteria included prominent cerebellar symptoms such as ataxia and dysmetria, intracranial pathology such as ventriculomegaly, cerebellar plaques and thalamic abnormality, and comorbid psychiatric symptoms. Seven patients (3M:4F) underwent DBS for MS-associated tremor between September 2013 and February 2019. Mean age was 42 years (±SD 8 years). DBS was performed at a mean of 13 years (±SD 9 years) after diagnosis of MS., Results: There were no postoperative surgical complications. All patients showed improvement in FTM tremor scores, by up to 61% at 6 months postoperatively. There was an improvement of 30-175% in quality-of-life scores at 6 months. Improvement of tremor and quality of life, over baseline, was sustained over a long period of follow-up (mean 26.6 months ± SD 20.7 months), including our longest duration at 72 months., Conclusion: With careful selection, DBS is a safe, efficacious intervention for MS-tremor and can positively impact on tremor and quality of life, with effects over a long period. As patients live longer with MS and the advent of new therapies, DBS should be considered for selected patients.

Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (-22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (-18.81 ml; 95% CI: -29.60 to -8.03 ml; p < 0.001), putamen (-0.40 ml; 95% CI: -0.69 to -0.10 ml; p = 0.008) and acumbens (-0.09 ml; 95% CI: -0.15 to -0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p < 0.001). Neurophysiological data showed reduced lower-limb maximum voluntary force production (-19.23 N; 95% CI: -35.93 to -2.53 N; p = 0.02) and an attenuation of upper-limb (-5.77%; 95% CI:-8.61 to -2.93%; p < 0.0001) and lower-limb (-2.16%; 95% CI:-4.24 to -0.07%; p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (-5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934., (© 2021. The Author(s).)

It is increasingly common for secondary care to provide advice to primary care without an outpatient appointment. Even before the increased telemedicine during COVID-19, many hospital services gave advice alone for some referrals, yet there are few published data about patient outcomes. Does advice and guidance alter outpatient numbers or simply mean that patients are seen later? Which neurological conditions can we manage at a distance? Do complaints increase from either primary care or patients? Do clinics become more complex and time consuming? Our department has developed an advice and guidance service embedded within the English electronic referral system since 2017, allowing detailed analysis of the outcome of 6500 patients over 2.5 years. We suggest ways to set up and run a neurology advice and guidance service, looking at the potential benefits and the barriers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit-risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society., (© 2021. The Author(s).)

Background: Recognising the transition from relapsing remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) in clinical practice can be challenging. With disease-modifying therapies (DMTs) commonly used for RRMS accepted to be less efficacious once progression has occurred, treatment options for progressive forms of MS have been limited. Emergence of new DMTs in SPMS are changing the treatment landscape. There is a need to better understand current practice and the factors underlying it, to facilitate consensus on the overall management of SPMS and optimise diagnostic and management decisions. This survey project aimed to assess current practices for the diagnosis and management of patients with SPMS in the UK., Methods: Healthcare professionals (HCPs) involved in the management of patients with SPMS from geographically distributed MS neurology centres in the UK participated in face-to-face or telephone interviews, facilitated by a semi-structured questionnaire. The survey data were descriptively analysed using quantitative and qualitative methods., Results: Fifty-nine HCPs (41 neurologists, 15 specialist nurses and 3 'other'), from 59 UK centres took part. Sixty-one percent (n = 36/59) of respondents applied a specific definition for SPMS, although only 6% of these (2/36) used the Lublin 2014 phenotype criteria. Expanded Disability Status Scale (EDSS) score increase with an absence of relapses was an important consideration for SPMS diagnosis for 83% (n = 49/59) of respondents, and 36% (n = 21/59) considered this to be the most important piece of evidence that they look for when they suspect a patient is transitioning from RRMS to SPMS. The median (interquartile range [IQR]) estimated time between first suspicion and diagnosis of SPMS was 12 months (12-24 [n = 45/59]), with concerns over withdrawing DMTs and the psychological impact of a diagnosis on patients the most commonly reported reasons for reluctance to diagnose. Seventy-three percent (n = 43/59) of respondents followed specific guidelines for DMT management of patients transitioning from RRMS to SPMS, with most (86%, n = 37/43) using the NHS England algorithm. Ninety-eight percent (n = 58/59) use DMTs to treat patients they suspect may be transitioning to SPMS, and 51% (n = 30/59) reported using DMTs for newly diagnosed SPMS patients. Approximately 1 in 5 HCPs may consider continuing DMTs beyond EDSS 7.0 in certain circumstances., Conclusion: The survey highlighted variation across the UK in SPMS definition, diagnosis and reported real-world management. Disparity in practice may result in unnecessary variations in treatment patterns and consequently outcomes. HCPs should be equipped to make timely and accurate decisions, which will be important in improving access to appropriate therapies for patients with SPMS., (Copyright © 2021. Published by Elsevier B.V.)

Background: Infections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS., Methods: The COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms., Results: Fifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection., Conclusion: COVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

The transition from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS) remains a clinical challenge owing to the heterogeneous course of the disease, indistinct disease progression and lack of availability of validated biomarkers and diagnostic tools. This article summarizes the outcomes from an international expert group meeting conducted to validate the preliminary research findings gathered through interviews with primary healthcare stakeholders and pharmaceutical representatives, and to understand the current and future patient journey of SPMS across seven European countries. We highlight the uncertainty in SPMS diagnosis and management and, consequently, the need for uniform assessment guidelines, enhanced awareness and a collaborative effort between the stakeholders associated with SPMS patient care and the pharmaceutical industry.

Background and Aims: The management of persistent type II endoleaks (T2E) is often problematic for the endovascular specialist, with a lack of clear evidence for the best approach for embolization. The aim of this study was to evaluate the safety and efficacy of translumbar embolization (TLE) for T2E following endovascular aneurysm repair (EVAR)., Methods: This retrospective review included 27 embolizations performed on 23 patients with a median age of 78 (range 67-94 years; male: female 15:9), during the period September 2006 to July 2018. Primary outcome was freedom from aneurysm sac growth defined as <2 mm sac diameter increase on subsequent computed tomography., Results: The initial technical success rate was 100%, with complete "on table" embolization of the T2E on fluoroscopy; however, 4 (15%) patients needed repeat TLE due to persistent endoleak identified on follow-up computed tomography or because of further sac expansion. Satisfactory stasis was achieved in these 4 cases following a second embolization. The mean volume of embolic injected was 7.4 mL per case. Feeding vessels were identified on angiography in all cases; the nidus was supplied by lumbar branches in 21 cases, by the inferior mesenteric artery in 1 case and by both in a further 5 cases. Freedom from aneurysm sac growth (defined as < 2 mm) following 1 or 2 separate TLE was achieved in 18 (78%) and 20 (86%) patients, respectively. The major complication rate was <5% with one case of psoas abscess presenting 7 months following embolization; there were 2 minor complications in the form of intraprocedural transient abdominal pain., Conclusion: The translumbar approach is a safe and effective technique to treat T2E, as evidenced by the low complication and reintervention rate.

Background: Abdominal aortic aneurysm (AAA) repair in patients with organ transplant remains a challenge. We looked at AAA repair in patients with organ transplants at our tertiary liver and kidney transplant unit., Methods: A retrospective analysis of a prospectively maintained database was undertaken from January 2008 to July 2018. We looked at patient demographics, type of repair, and technical success including reinterventions, perioperative transplant organ function, and 30-day and 1-year survival rate. Eight of 662 patients who underwent AAA repair had a solid organ transplant. Of these, 5 were kidney transplants, 2 liver transplants, and 1 had kidney and liver transplant; 75% were male; and average age was 63.4 (range: 49-83). All patients had asymptomatic AAAs, and 6 were treated with standard endovascular repair, 1 standard repair with iliac branch device, and 1 open repair. Adjunctive techniques such as CO 2 angiograms, deployment of main body through contralateral iliac, low-profile sheaths, custom-made stent grafts, and temporary axillo-femoral shunting were used to protect transplant organs. Thirty-day survival was 100% with 1 death at 5 months from liver failure, and 1 patient has a persistent type-2 endoleak 3 years after the procedure., Conclusion: Abdominal aortic aneurysm repair in patients with organ transplants can be undertaken using adjunctive endovascular and open surgical techniques.

Recent studies have linked cell-free mitochondrial DNA (ccf-mtDNA) to neurodegeneration in both Alzheimer's and Parkinson's disease, raising the possibility that the same phenomenon could be seen in other diseases which manifest a neurodegenerative component. Here, we assessed the role of circulating cell-free mitochondrial DNA (ccf-mtDNA) in end-stage progressive multiple sclerosis (PMS), where neurodegeneration is evident, contrasting both ventricular cerebral spinal fluid ccf-mtDNA abundance and integrity between PMS cases and controls, and correlating ccf-mtDNA levels to known protein markers of neurodegeneration and PMS. Our data indicate that reduced ccf-mtDNA is a component of PMS, concluding that it may indeed be a hallmark of broader neurodegeneration., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: Because multiple sclerosis (MS) is a chronic disease causing disability over decades, it is crucial to know if the short-term effects of disease-modifying therapies reported in randomised controlled trials reduce long-term disability. This 10-year prospective observational study of disability outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue., Methods: The outcomes of the UK treated patients were compared with a modelled untreated control based on the British Columbia MS data set to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multilevel model (MLM) and a continuous Markov model., Results: 4862 patients with MS were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by 28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by 31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility worsening was reduced by 23%-24% in the total cohort and by 24%-31% in the RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores., Conclusions: This study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. However the waning effect noted requires further study., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Previous reports have suggested higher periprocedural complications after ipsilateral antegrade femoral arterial access (AA). We looked at a contemporary series comparing complication rates between AA and contralateral retrograde femoral arterial access (RA) for femoropopliteal angioplasty., Method: A prospective review of all cases between 2010 and 2015 in a United Kingdom tertiary vascular center. Demographical and procedural data were obtained for those undergoing percutaneous femoropopliteal angioplasty. The primary outcome looked at periprocedural complications including retroperitoneal hematoma, pseudoaneurysm, hematoma requiring transfusion, arteriovenous fistulation, and surgical intervention. Secondary outcomes included contrast and radiation doses in addition to procedural failure leading to major amputation., Results: A total of 556 (66% male) patients underwent femoropopliteal angioplasty, 461 (82%) via AA. Groups were of comparable age, sex, comorbidity, and symptomatology. AA patients had a lower body mass index, 26 versus 29 ( P = .005). No significant difference was seen in periprocedural (15.8% AA vs 11.6% RA; P = 0.292) or access site complications (3.7% AA vs 1.1% RA; P = 0.186). There was less need for a closure device, 40.3% AA vs 73% RA ( P < .01), less contrast, 94 mL AA: 114 mL RA ( P < .001), and less radiation, 3487 cGy cm 2 AA: 9697 cGy cm 2 RA ( P < .001). Arterial access was also associated with greater technical success of 83.8%: 73.3% RA ( P = .002)., Conclusions: Arterial access is associated with higher technical success and reduced contrast/radiation doses with no significant difference in complications compared to RA contrary to previous reports.

Importance: Antibodies to myelin oligodendrocyte glycoprotein IgG (MOG-IgG) are increasingly detected in patients with non-multiple sclerosis-related demyelination, some of whom manifest a neuromyelitis optica (NMO) phenotype. Cortical involvement, encephalopathy, and seizures are rare in aquaporin 4 antibody (AQP4-IgG)-related NMO in the white European population. However, the authors encountered several patients with seizures associated with MOG-IgG disease., Objective: To compare incidence of seizures and encephalitis-like presentation, or both between AQP4-IgG-positive and MOG-IgG-positive patients., Design, Setting, and Participants: Retrospective case series of all patients who were seropositive for MOG-IgG (n = 34) and the last 100 patients with AQP4-IgG disease (NMO spectrum disorder) seen in the NMO service between January 2013 and December 2016, and analysis was completed January 4, 2017. All patients were seen in a tertiary neurological center, The Walton Centre NHS Foundation Trust in Liverpool, England., Main Outcomes and Measures: The difference in seizure frequency between the AQP4-IgG-positive and MOG-IgG-positive patient groups was determined., Results: Thirty-four patients with MOG-IgG disease (20 female) with a median age at analysis of 30.5 years (interquartile range [IQR], 15-69 years), and 100 AQP4-IgG-positive patients (86 female) with a median age at analysis of 54 years (IQR, 12-91 years) were studied. Most patients were of white race. Five of the 34 patients with MOG-IgG (14.7%) had seizures compared with 1 patient with AQP4-IgG (2-sided P < .008, Fisher test). On magnetic resonance imaging, all 5 MOG-IgG-positive patients had inflammatory cortical brain lesions associated with the seizures. In 3 of the 5 MOG-IgG-positive patients, seizures occurred as part of the index event. Four of the 5 presented with encephalopathy and seizures, and disease relapsed in all 5 patients. Four of these patients were receiving immunosuppressant medication at last follow-up, and 3 continued to take antiepileptic medication. In contrast, the only AQP4-IgG-positive patient with seizures had a diagnosis of complex partial epilepsy preceding the onset of NMO by several years and experienced no encephalitic illness; her magnetic resonance imaging results demonstrated no cortical, subcortical, or basal ganglia involvement., Conclusions and Relevance: Patients with MOG-IgG-associated disease were more likely to have seizures and encephalitis-like presentation than patients with AQP4-IgG-associated disease.

Objective: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab., Methods: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers., Results: Nine patients were identified. Median disease duration to alemtuzumab treatment was 94 (39-215) months and follow-up from time of first alemtuzumab cycle 20 (14-21) months. Following first alemtuzumab infusion cycle, 8 patients were identified by at least 1 clinical relapse and radiologic disease activity and 1 by significant radiologic disease activity alone., Conclusions: We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of patients with MS most in need of disease control. We suggest that significant and unexpected subsequent disease activity after alemtuzumab induction results from prolonged sequestration of autoreactive lymphocytes following fingolimod withdrawal, allowing these cells to be concealed from the usual biological effect of alemtuzumab. Subsequent lymphocyte egress then provokes disease reactivation. Further animal studies and clinical trials are required to confirm these phenomena and in the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens.

Objective: Graft angioplasty combines the durability and ability of surgical bypasses to treat long arterial occlusions with the minimally invasive nature of endovascular procedures. The purpose of this study was to evaluate the efficacy of single and repeated graft angioplasty in revising failing infrainguinal vein bypass grafts and to determine predictors of medium- and long-term freedom from revision after graft angioplasty., Method: This was a retrospective analysis from a prospectively maintained database. Consecutive endovascular revisions of graft-threatening lesions identified by duplex ultrasound surveillance were reviewed from 2003 to 2010. Patients were followed up until death, major amputation, or the end of follow-up, with the data last updated on January 1, 2013., Results: 178 graft angioplasty procedures performed in 114 bypass grafts in 103 limbs from 98 patients were studied. At 5 years, freedom from revision was 22.6%, graft survival was 45.8%, amputation-free survival was 57.9%, and patient survival was 64.9%. Analysis of repeated angioplasties found no evidence that effectiveness diminishes significantly with the number of previous angioplasties performed (p=.892). Higher Rutherford Grade of ischemia and longer time interval from index surgery to first angioplasty were significant positive predictors of medium- and long-term patency., Conclusion: Percutaneous transluminal angioplasty of infrainguinal vein grafts is safe and effective in the treatment of failing grafts identified by duplex surveillance. Graft angioplasties do not lose effectiveness when repeated and have shown cumulative benefit in prolonging graft survival. Treatment of claudicants and time interval from graft implantation of more than 6 months at the time of first angioplasty are positive predictors of at least medium-term patency after graft angioplasty., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aim of this study was to assess the durability of superficial femoral artery (SFA) stents and factors that affect stent patency., Methods: A retrospective assessment of 214 SFA stent procedures between 2003 and 2012 was conducted from a prospectively compiled database. Patency rates and patient outcomes were compiled from case notes and computerized records. Stent patency was confirmed by either duplex scan or clinical examination (palpable distal pulse). Survival and patency were compared across a range of factors using Kaplan-Meier plots and log-rank tests. Factors found to be significant were further assessed by Cox regression models., Results: Data were analyzed for 214 limbs in 205 patients. Inclusion criteria included those patients who received an SFA stent for treatment of claudication or critical limb ischemia (CLI) with follow-up data. This gave a study group of 151 limbs divided into 76 claudicant and 75 patients with CLI (male-female ratio = 103:48, mean age 71 years, standard deviation 11.7). Seventy-one percent of procedures were elective and 29% were emergency procedures; 53% of procedures were carried out on a day case basis. Median follow-up was 11 months (range 1 day-89 months). Patency was significantly worse for patients with CLI (P = .009), with a 1- and 3-year patency of 63% and 34% compared to 79% and 60% in patients with claudication. Significant factors associated with patency included oral therapy controlled diabetes (P = .003), lesions located in either the mid-SFA (P = .029) or the mid-popliteal (P = .013), and periprocedural complications (P = .005). There was no significant difference in patency rates between insulin-dependent and nondiabetic patients (hazard ratio: 1.0, 95% confidence interval: 0.4-5.6, P = .983). The overall amputation rate for the total study group was 5%. Patients with 1- and 3-year survival were 98% and 96% in the claudication group and 74% and 51%, respectively, in the CLI group., Conclusion: SFA stents have superior outcomes in claudicants. Patency is related to severity of disease, diabetes, and location of disease., (© The Author(s) 2015.)

The Loeys-Dietz syndrome is a multisystem connective tissue disorder characterized by aortopathy, arterial tortuosity, peripheral aneurysms, and skeletal features. The peripheral arteriopathy is an important cause of morbidity and potential mortality. This report presents 2 cases: the first demonstrating a 5-cm pseudoaneurysm of the right internal mammary artery and the second demonstrating a 2.3-cm aneurysm of the left internal mammary artery, each following aortic root surgery. These were successfully treated with percutaneous techniques. No complications were seen at follow-up as long as 2 years. Patients with Loeys-Dietzs syndrome require comprehensive long-term vascular follow-up and are likely to require percutaneous vascular interventions., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)