COVID-19 leukoencephalopathy with subacute magnetic resonance imaging findings of vasculitis and demyelination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) commonly results in a respiratory illness in symptomatic patients; however, those critically ill can develop a leukoencephalopathy. We describe two patients who had novel subacute MRI findings in the context of coronavirus disease 2019 (COVID-19) leukoencephalopathy, which we hypothesize could implicate a potent small-vessel vasculitis, ischemic demyelination and the presence of prolonged ischemia. Recent evidence of the direct neuroinvasiness of SARS-CoV-2 leading to ischemia and vascular damage supports this hypothesis.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

[18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis.

PURPOSE: We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [18F]florbetapir PET-MR imaging. METHODS: We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [18F]florbetapir PET-MR and both a clinical and cognitive assessment. [18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70-90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling. RESULTS: [18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = -0.15, P < 0.001, coeff. = -0.12, P < 0.001 and coeff. = -0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (-10.9%, P = 0.005). SUV70-90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26). CONCLUSION: Our findings demonstrate that [18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG. METHODS: Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records. RESULTS: All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events. CONCLUSION: Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.

Best Methods of Communicating Clinical Trial Data to Improve Understanding of Treatments for Patients with Multiple Sclerosis.

BACKGROUND: Patients' understanding of treatment risks and benefits is a prerequisite for shared decision making. Yet, patients with multiple sclerosis (MS) do not accurately understand treatment information provided in regular clinical consultations. OBJECTIVES: To identify the best methods of communicating clinical trial data to improve the understanding of treatments among patients with MS and to also examine the relationship between patients' understanding with decisional conflict, individual traits, and MS symptoms. METHODS: A repeated-measures study was used. A sample of relapsing-remitting patients with MS was recruited from National Health Service sites in the United Kingdom. Patients were presented with hypothetical treatment risks and benefits from faux clinical trials. Treatments were communicated using absolute terms, relative terms, and numbers needed to treat/harm. The presence of baseline information with each method was also manipulated. Patients' understanding and conflict in treatment decisions were assessed. Individual traits and MS symptoms were also recorded. RESULTS: Understanding was better when treatments were communicated in absolute terms (mean 3.99 ± 0.93) compared with relative terms (mean 2.93 ± 0.91; P < 0.001) and numbers needed to treat/harm (mean 2.89 ± 0.88; P < 0.001). Adding baseline information to all methods significantly improved understanding (mean 5.04 ± 0.96) compared with no baseline information (mean 1.50 ± 0.74; P < 0.001). Understanding was not related to conflict in treatment decisions (r = -0.131; P = 0.391). Numeracy, IQ, and cognitive impairments were significantly related to patients' understanding of treatments. CONCLUSIONS: Treatment risks and benefits should ideally be communicated using absolute terms, alongside baseline information. Patients with MS with low numeracy, low IQ, and reduced cognitive skills should be supported during treatment education.

How integrated are neurology and palliative care services? Results of a multicentre mapping exercise.

BACKGROUND: Patients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services interact. This study aimed to map the current level of connections and integration between these services. METHODS: The mapping exercise was conducted in eight centres with neurology and palliative care services in the United Kingdom. The data were provided by the respective neurology and specialist palliative care teams. Questions focused on: i) catchment and population served; ii) service provision and staffing; iii) integration and relationships. RESULTS: Centres varied in size of catchment areas (39-5,840 square miles) and population served (142,000-3,500,000). Neurology and specialist palliative care were often not co-terminus. Service provisions for neurology and specialist palliative care were also varied. For example, neurology services varied in the number and type of provided clinics and palliative care services in the settings they work in. Integration was most developed in Motor Neuron Disease (MND), e.g., joint meetings were often held, followed by Parkinsonism (made up of Parkinson's Disease (PD), Multiple-System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP), with integration being more developed for MSA and PSP) and least in Multiple Sclerosis (MS), e.g., most sites had no formal links. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (range: 9-88 MND, 3-25 Parkinsonism, and 0-5 MS). CONCLUSIONS: This mapping exercise showed heterogeneity in service provision and integration between neurology and specialist palliative care services, which varied not only between sites but also between diseases. This highlights the need and opportunities for improved models of integration, which should be rigorously tested for effectiveness.

The impact of health anxiety in patients with relapsing remitting multiple sclerosis: Misperception, misattribution and quality of life.

OBJECTIVES: Multiple sclerosis (MS) is a progressive disease with an unpredictable prognosis. Previous studies have reported health anxiety within the MS population. This study examines the effect of health anxiety on MS patients' quality of life (QoL) and evaluates the potential contribution of cognitive factors in maintaining health anxiety. METHODS: A total of 84 patients with relapsing remitting multiple sclerosis (RRMS) were screened for health anxiety. From this sample, a group with relatively high and another group with low anxiety (n = 21 in each group) were identified. A further 21 healthy controls were recruited for comparison. A measure of QoL was then completed. Cognitive biases were investigated by measuring perception and attribution of common bodily symptoms as well as appraisal of performance on neuropsychological and physical fatigue tests. RESULTS: The high health anxiety group reported poorer QoL relative to the other groups, independent of level of disability. They were also more likely to misattribute common bodily changes to MS, and perceive their (objectively intact) performance on tests of cognition and fatigue as being impaired, attributing the cause of impairment to MS. CONCLUSION: Health anxiety may be a factor in mediating the psychosocial impact of MS. Skilled psychological treatment which changes misperception and misattribution may significantly benefit patients with MS and elevated health anxiety. PRACTITIONER POINTS: Clinical implications Health anxiety impacts on quality of life in patients with MS even when disability and other measures of psychological distress are taken into account. High levels of health anxiety distort perceptions of symptoms in patients with MS in line with the predictions made by the cognitive model of health anxiety. Limitations of study This study is limited to patients with RRMS within the relatively early stages of their disease and is based on a small sample size. Health anxiety is correlated with measures of generalized anxiety, depression, and worry, although it is found to have a unique impact on quality of life in patients with MS.

'It feels like someone is hammering my feet': understanding pain and its management from the perspective of people with multiple sclerosis.

BACKGROUND: Pain affects around 63% of people with multiple sclerosis (pwMS). Biomedical treatments demonstrate limited efficacy. More research is needed to understand pain from the individual's perspective in order to better inform a patient-centred approach that improves engagement, self-management and outcome. OBJECTIVE: The objective of this paper is to explore pwMS' experience and responses to pain, and their perspectives on pain management. METHODS: Twenty-five in-depth, semi-structured telephone interviews were conducted. Interviews were audiotaped, transcribed and analysed using an inductive thematic analysis approach with elements of grounded theory. RESULTS: Key themes included vivid descriptions of pain and beliefs that pain is unpredictable, a sign of damage and may worsen. Anger was a common emotional response. Two dominant pain management themes emerged: one related to pain reduction and another to acceptance. Those focusing on pain reduction appeared to engage in cycles in which they struggled with symptoms and experienced continued distress. CONCLUSION: Findings identify pain-related beliefs, emotional reactions and disparate pain-management attitudes. All may influence pwMS' responses to pain and what they ask of their clinicians. Uncovering pwMS' personal beliefs about pain, and introducing a broader biopsychosocial understanding of pain in the clinical context, may provide opportunities to rectify potentially unhelpful management choices and enhance pain acceptance.

Exploring meanings of illness causation among those severely affected by multiple sclerosis: a comparative qualitative study of Black Caribbean and White British people.

BACKGROUND: Illness attributions, particularly for those living with life limiting illnesses, are associated with emotional adjustment or psychological distress. Few studies have examined attributions among people severely affected by multiple sclerosis (PwMS), and specifically among from diverse communities. This study aimed to explore and compare the presence and construction of meanings among Black Caribbean and White British PwMS. METHODS: Cross sectional qualitative interviews were conducted among Black Caribbean (BC) and White British (WB) PwMS with an EDSS of ≥6.0 (severe disease). Data were analysed using the framework approach. RESULTS: 15 BC and 15 WB PwMS were interviewed. Attributions were complex with most PwMS reporting multiple explanations. Uncertainty, represents the first theme surrounding the aetiology of MS where participants constantly rehearsed the "why me?" question in relation to their illness, a number expressing considerable frustration. The second theme, 'logical and scientific', was voiced more often by WB PwMS and accounts for a range of genetic/viral influences, stress, environmental and lifestyle factors. Third, the 'supernatural' illness attribution theme departs from a biomedical perspective and was reported often among BC PwMS. This theme included the sub-categories of tests of faith and divine punishment, a view although exclusive to BC participants but was sometimes in conflict with notions of modernity. CONCLUSION: Our findings identify evidence of cross-cultural and intra-group diversity in relation to MS causation. A greater professional awareness of the processes used by PwMS from diverse communities to make sense of their situation will enable health care professionals to facilitate effective support for those in their care and channel relevant psychosocial resources to them. This requires heightened skills in communication and cultural competency.

Efficacy and safety of autologous haematopoietic stem cell transplantation versus alemtuzumab, ocrelizumab, ofatumumab or cladribine in relapsing remitting multiple sclerosis (StarMS): protocol for a randomised controlled trial.

INTRODUCTION: Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, 'Multiple Sclerosis International Stem Cell Transplant, MIST', showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS. METHODS AND ANALYSIS: StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve 'no evidence of disease activity' during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs. ETHICS AND DISSEMINATION: The study was approved by the Yorkshire and Humber-Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN88667898.

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

INTRODUCTION: There remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. METHODS AND ANALYSIS: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. ETHICS AND DISSEMINATION: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBERS: NCT03387670; ISRCTN82598726.

Place of death, and its relation with underlying cause of death, in Parkinson's disease, motor neurone disease, and multiple sclerosis: a population-based study.

BACKGROUND: Little is known about place of death in chronic neurological diseases. Mortality statistics are ideal for examining trends in place of death, but analyses are limited by coding rule changes. AIM: To examine the relationship between place of death and underlying cause of death in Parkinson's disease, multiple sclerosis and motor neurone disease and the impact of coding rule changes on analysis of place of death. DESIGN: Population-based study. Proportion ratios for death in hospice, home, care home and hospital were calculated according to underlying cause of death, using multivariable Poisson regression. PARTICIPANTS: Deaths in England (1993-2010) with any mention of Parkinson's disease, multiple sclerosis or motor neurone disease as a cause of death, identified from national mortality data. RESULTS: In this study, 125,242 patients with Parkinson's disease, 23,501 with multiple sclerosis, and 27,030 with motor neurone disease were included. Home deaths ranged from 9.7% (Parkinson's disease) to 27.1% (motor neurone disease), hospice deaths ranged from 0.6% (Parkinson's disease) to 11.2% (motor neurone disease) and hospital deaths ranged from 43.4% (Parkinson's disease) to 55.8% (multiple sclerosis). In Parkinson's disease and multiple sclerosis, cancer as underlying cause of death increased likelihood of hospice death (proportion ratio (PR): 18.8, 95% confidence interval (CI) = 16.1-22.0; 8.88, 95% CI = 7.49-10.5) and home death (PR: 1.91, 95% CI = 1.80-2.04; 1.71, 95% CI = 1.56-1.88). Dementia as underlying cause of death increased likelihood of care home death in Parkinson's disease (PR: 1.25, 95% CI = 1.19-1.32), multiple sclerosis (PR: 1.73, 95% CI = 1.22-2.45) and motor neurone disease (PR: 2.36, 95% CI = 1.31-4.27). CONCLUSIONS: Underlying cause of death has a marked effect on place of death. The effects of coding rule changes are an essential consideration for all research using underlying cause of death to study place of death.

A Novel approach using O-CVP to treat paraneoplastic NMO spectrum disorder associated with follicular lymphoma.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neuroinflammatory disorder of the central nervous system that very rarely may be a paraneoplastic phenomenon. We describe the case of a woman with a longitudinally extensive transverse myelitis (LETM). We identified a previously undiagnosed, follicular lymphoma and she was treated with the immunochemotherapy regime (obinutuzumab, cyclophosphamide, vincristine and prednisolone; O-CVP) for paraneoplastic NMOSD. Following two cycles, there was almost complete radiological remission of the myelitis and the patient showed some improvement in her neurological function. This case illustrates the heterogeneous aetiology that LETM may have and that O-CVP may be used as therapeutic option in patients with NMOSD driven by follicular lymphoma.

Key demographics and psychological skills associated with adjustment to progressive Multiple Sclerosis early in the diagnosis.

Background/purpose: Being diagnosed with a progressive type of multiple sclerosis (MS) has been associated with worse psychological outcomes compared to relapsing-remitting type. Previous studies of adjustment to MS have primarily focused on relapsing-remitting type MS. The present study aims to examine psychological adjustment for people newly diagnosed with progressive multiple sclerosis. Methods: This was a multicenter cross-sectional survey of 189 people newly diagnosed with progressive MS. A composite measure of psychological adjustment was created from questionnaires measuring psychological distress, positive affect, perceived-stress, life satisfaction and self-concept. Predictor variables included coping strategies, social support, relationship with partner, psychological vulnerability, MS-related beliefs, and responses to symptoms. Data were analysed using a regularised regression model to indicate which group of all variables are associated with adjustment. Results: People who were older (b = 0.17(0.07), p = 0.02), in employment (b = 0.40 (0.17), p = 0.01), and with lower illness severity (b = -0.24 (0.08), p = 0.001) showed better adjustment. Based on a Lasso regression, the most important psychological and demographic variables associated with lower adjustment (out-of-sample cross-validation R 2 = 62.6%) were lower MS self-efficacy and higher avoidance, cognitive vulnerability, embarrassment avoidance, conflict, helplessness, and secondary progressive MS type. Conclusions and implications: Helping newly diagnosed people to find ways to tolerate anxiety-causing situations by encouraging acceptance may help people adjust to progressive MS by lowering their avoidance. Further, building confidence in managing the illness and addressing relationship issues are key focus areas in psychological interventions for people with progressive multiple sclerosis.

"I wanna live and not think about the future" what place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study.

BACKGROUND: Little is known about how people with multiple sclerosis (MS) and their families comprehend advance care planning (ACP) and its relevance in their lives. AIM: To explore under what situations, with whom, how, and why do people with MS and their families engage in ACP. METHODS: We conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families. Twenty-seven people with MS and 17 family members were interviewed between June 2019 and March 2020. Interviews and the ethical discussion group were audio-recorded and transcribed verbatim. Data were analysed using the framework approach. RESULTS: Participants' narratives focused on three major themes: (i) planning for an uncertain future; (ii) perceived obstacles to engaging in ACP that included uncertainty concerning MS disease progression, negative previous experiences of ACP discussions and prioritising symptom management over future planning; (iii) Preferences for engagement in ACP included a trusting relationship with a health professional and that information then be shared across services. Health professionals' accounts from the ethical discussion group departed from viewing ACP as a formal document to that of an ongoing process of seeking preferences and values. They voiced similar concerns to people with MS about uncertainty and when to initiate ACP-related discussions. Some shared concerns of their lack of confidence when having these discussions. CONCLUSION: These findings support the need for a whole system strategic approach where information about the potential benefits of ACP in all its forms can be shared with people with MS. Moreover, they highlight the need for health professionals to be skilled and trained in engaging in ACP discussions and where information is contemporaneously and seamlessly shared across services.

Evaluation of a new model of short-term palliative care for people severely affected with multiple sclerosis: a randomised fast-track trial to test timing of referral and how long the effect is maintained.

AIMS: In this randomised fast-track phase II trial, the authors examined (1) whether the timing of referral to short-term palliative care (PC) affected selected outcomes, and (2) the potential staff-modifying effect of the short-term PC intervention (whether the effects were sustained over time after PC was withdrawn). METHODS: PC comprised a multiprofessional PC team that provided, on average, three visits, with all care completed by 6 weeks. Recruitment commenced in August 2004 and continued for 1 year. Follow-up was performed for 6 months in both groups. Outcomes were a composite measure of five key symptoms (pain, nausea, vomiting, mouth problems and sleeping difficulty) using the Palliative care Outcome Scale-MS Symptom Scale, and care giver burden was measured using the Zarit (Care Giver) Burden Interview (ZBI). RESULTS: 52 patients severely affected by multiple sclerosis were randomised to receive PC either immediately (fast-track group) or after 12 weeks (control group). Patients had a high level of disability (mean Expanded Disability Status Scale: 7.7; median: 8; SD: 1). Following PC, there was an improvement in Palliative care Outcome Scale-MS Symptom Scale score and ZBI score. A higher rate of improvement in ZBI score was seen in the fast-track group. After withdrawal of PC, effects were maintained at 12 weeks, but not at 24 weeks. CONCLUSIONS: Receiving PC earlier has a similar effect on reducing symptoms but greater effects on reducing care giver burden, compared to later referral. In this phase II trial, the authors lacked the power to detect small differences. The effect of PC is maintained for 6 weeks after withdrawal but then appears to wane.

Progressive bulbar symptomatology due to vascular brainstem compression.

Symptomatic brainstem compression from vertebral artery dolichoectasia is rare. There are no recognised diagnostic or treatment criteria to guide management of this disease. We report a case of medullary compression and cerebral ischaemia from an enlarged and tortuous vertebral artery. Our patient developed progressive dysphonia and dysphagia. Cerebral MRI revealed compression of the medulla oblongata by a right ectatic vertebral artery and a right occipital lobe infarct. Other causes of bulbar dysfunction were ruled out. He was treated with anticoagulation and underwent percutaneous endoscopic gastrostomy. We review selected literature on the presentation, diagnosis and management of this rare neurologic condition.