Delayed bubble, coil and trouble: young stroke as a presentation of paradoxical embolism from previously unrecognised pulmonary arterio-venous malformation (PAVM).

Young stroke patients should be investigated thoroughly to look for cardiac and extra-cardiac sources of emboli. We present a patient who was investigated for a cardiac source of emboli following an ischemic stroke. She was found to have a small patent foramen ovale (PFO), but due to the late appearances of bubbles on the bubble study it was thought that this was an incidental finding. Further investigation confirmed a PAVM was the source of emboli causing her stroke.

Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.

Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, identifies >20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in Plasmodium parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.

Mii-vitaliSe: a pilot randomised controlled trial of a home gaming system (Nintendo Wii) to increase activity levels, vitality and well-being in people with multiple sclerosis.

OBJECTIVES: While the health and well-being benefits of physical activity are recognised, people with multiple sclerosis (MS) often face greater barriers than the general population. The Nintendo Wii potentially offers a fun, convenient way of overcoming some of these. The aim was to test the feasibility of conducting a definitive trial of the effectiveness and cost-effectiveness of Mii-vitaliSe; a home-based, physiotherapist-supported Nintendo Wii intervention. DESIGN: A single-centre wait-list randomised controlled study. SETTING: MS service in secondary care. PARTICIPANTS: Ambulatory, relatively inactive people with clinically confirmed MS. INTERVENTION: Thirty participants were randomised to receive Mii-vitaliSe either immediately (for 12 months) or after a 6-month wait (for 6 months). Mii-vitaliSe consisted of two supervised Nintendo Wii familiarisation sessions in the hospital followed by home use (Wii Sports, Sports Resort and Fit Plus software) with physiotherapist support and personalised resources. OUTCOMES: Included self-reported physical activity levels, quality of life, mood, self-efficacy, fatigue and assessments of balance, gait, mobility and hand dexterity at baseline, 6 and 12 months. Interviews (n=25) explored participants' experiences and, at study end, the two Mii-vitaliSe facilitators' experiences of intervention delivery (main qualitative findings reported separately). RESULTS: Mean (SD) age was 49.3 (8.7) years, 90% female, with 47% diagnosed with MS <6 years ago and 60% new to active gaming. The recruitment rate was 31% (95% CI 20% to 44%). Outcome data were available for 29 (97%) at 6 months and 28 (93%) at 12 months. No serious adverse events were reported during the study. Qualitative data indicated that Mii-vitaliSe was well-received. Mean Wii use across both groups over the initial 6-month intervention period was twice a week for 27 min/day. Mean cost of delivering Mii-vitaliSe was £684 per person. DISCUSSION: Mii-vitaliSe appears acceptable and a future trial feasible and warranted. These findings will inform its design. TRIAL REGISTRATION: ISRCTN49286846.

Opportunistic infections of the retina in patients with aquaporin-4 antibody disease.

IMPORTANCE: Patients with neuromyelitis optica who have aquaporin-4 antibodies are being identified and receiving immunosuppressant treatment earlier and more aggressively as a result of increasing awareness of the importance of preventing relapses responsible for the high morbidity and mortality associated with the disease. To our knowledge, opportunistic retinal infection in patients with aquaporin-4 antibodies who are receiving immunosuppressants has not been reported to date. OBSERVATIONS: We describe 2 patients with aquaporin-4 antibodies who were receiving conventional doses of first-line immunosuppressive therapy. Both patients presented with vision loss that was initially thought to be optic neuritis attacks. The subsequent diagnoses were ocular toxoplasmosis and cytomegalovirus retinitis. CONCLUSIONS AND RELEVANCE: Retinal opportunistic infections can occur in patients with aquaporin-4 antibodies who are receiving relatively low levels of immunosuppression, may mimic optic neuritis, and are a potentially reversible cause of vision loss when treated promptly.

One year follow-up of a pragmatic multi-centre randomised controlled trial of a group-based fatigue management programme (FACETS) for people with multiple sclerosis.

BACKGROUND: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS). The aim was to evaluate the effectiveness at 1-year follow-up of a manualised group-based programme ('FACETS') for managing MS-fatigue. METHODS: One-year follow-up of a pragmatic multi-centre randomised controlled trial. People with MS and significant fatigue were randomised to FACETS plus current local practice (FACETS) or current local practice alone (CLP), using concealed computer-generated randomisation. Participant blinding was not possible. Primary outcome measures were fatigue severity (Global Fatigue Severity subscale of the Fatigue Assessment Instrument), self-efficacy (MS-Fatigue Self-Efficacy) and disease-specific quality of life (MS Impact Scale). RESULTS: Between May 2008 and November 2009, 164 participants were randomised. Primary outcome data were available at 1 year for 131 (80%). The benefits demonstrated at 4-months in the FACETS arm for fatigue severity and self-efficacy largely persisted, with a slight reduction in standardised effect sizes (SES) (-0.29, p = 0.06 and 0.34, p = 0.09, respectively). There was a significant difference on the MS Impact Scale favouring FACETS that had not been present at 4-months (SES -0.24, p = 0.046). No adverse events were reported. CONCLUSIONS: Improvements in fatigue severity and self-efficacy at 4-months follow-up following attendance of FACETS were mostly sustained at 1 year with additional improvements in MS impact. The FACETS programme provides modest long-term benefits to people with MS-fatigue. TRIAL REGISTRATION: ISRCTN76517470.

Testing the feasibility and acceptability of using the Nintendo Wii in the home to increase activity levels, vitality and well-being in people with multiple sclerosis (Mii-vitaliSe): protocol for a pilot randomised controlled study.

INTRODUCTION: The benefits of physical activity for people with multiple sclerosis (pwMS) have been recognised. However, exercise regimens can be difficult to maintain over the longer term and pwMS may face unique barriers to physical activity engagement. Pilot research suggests the Nintendo Wii can be used safely at home by pwMS with minimal mobility/balance issues and may confer benefits. We have developed a home-based physiotherapist supported Wii intervention ('Mii-vitaliSe') for pwMS that uses commercial software. This is a pilot study to explore the feasibility of conducting a full scale clinical and cost-effectiveness trial of Mii-vitaliSe. METHODS AND ANALYSIS: 30 ambulatory, relatively inactive pwMS will be randomised to receive Mii-vitaliSe immediately, or after 6 months. Outcomes, measured at baseline and 6 and 12 months later, will include balance, gait, mobility, hand dexterity and self-reported physical activity levels, fatigue, self-efficacy, mood and quality of life. Interviews conducted on a purposive sample of participants will explore experiences of participation in the study and barriers and facilitators to using the Wii. Mean recruitment, adherence rate and standard deviations (SDs) of potential primary outcomes for the full trial will be estimated and precision summarised using 95% confidence intervals (CIs). Interview transcripts will be thematically analysed using a generic qualitative approach. ETHICS AND DISSEMINATION: National Health Service (NHS; ref 12/SC/0420) and university ethical approvals have been obtained as has NHS Research and Development permission from the relevant trust. A home risk assessment will be undertaken for all potential participants. All adverse events will be closely monitored, documented and reported to the study Safety Monitoring Committee. At least one publication in a peer reviewed journal will be produced and research findings presented at a national and international conference. With service users, we will coproduce a summary of the findings for dissemination on our research unit's website and elsewhere. TRIAL REGISTRATION NUMBER: ISRCTN 49286846.

A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis.

BACKGROUND: Fatigue is a common and troubling symptom for people with multiple sclerosis (MS). AIM: To evaluate the effectiveness and cost-effectiveness of a six-session group-based programme for managing MS-fatigue (Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle (FACETS)). METHODS: Three-centre parallel arm randomised controlled trial with economic evaluation. Patients with MS and significant fatigue were randomised to FACETS plus current local practice (FACETS) or current local practice alone (CLP), using concealed computer-generated randomisation. Participant blinding was not possible. Primary outcomes were fatigue severity (Fatigue Assessment Instrument), self-efficacy (Multiple Sclerosis-Fatigue Self-Efficacy) and disease-specific quality of life (Multiple Sclerosis Impact Scale (MSIS-29)) at 1 and 4 months postintervention (follow-up 1 and 2). Quality adjusted life years (QALYs) were calculated (EuroQoL 5-Dimensions questionnaire and the Short-form 6-Dimensions questionnaire). RESULTS: Between May 2008 and November 2009, 164 patients were randomised; primary outcome data were available for 146 (89%). Statistically significant differences favour the intervention group on fatigue self-efficacy at follow-up 1 (mean difference (MD) 9, 95% CI (4 to 14), standardised effect size (SES) 0.54, p=0.001) and follow-up 2 (MD 6, 95% CI (0 to 12), SES 0.36, p=0.05) and fatigue severity at follow-up 2 (MD -0.36, 95% CI (-0.63 to -0.08), SES -0.35, p=0.01) but no differences for MSIS-29 or QALYs. No adverse events reported. Estimated cost per person for FACETS is £453; findings suggest an incremental cost-effectiveness ratio of £2157 per additional person with a clinically significant improvement in fatigue. CONCLUSIONS: FACETS is effective in reducing fatigue severity and increasing fatigue self-efficacy. However, it is difficult to assess the additional cost in terms of cost-effectiveness (ie, cost per QALY) as improvements in fatigue are not reflected in the QALY outcomes, with no significant differences between FACETS and CLP. The strengths of this trial are its pragmatic nature and high external validity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76517470.

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis.

BACKGROUND: Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. METHODS/DESIGN: This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. DISCUSSION: This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76517470.

Aspergillosis of the petrous apex.

We present the case of an immunocompetent man who presented with multiple and progressive cranial nerve palsies. The cause was found to be aspergillosis of the petrous bone, arising as a result of chronic fungal otitis media. Despite treatment with local excision and systemic anti-fungal therapy, he died after suffering a subarachnoid haemorrhage. Diagnosis rests upon prompt radiological imaging and the acquisition of tissue for histological examination and culture but cannot be made without awareness of the condition.

Sudden unexplained death in epilepsy (SUDEP) following previous seizure-related pulmonary oedema: case report and review of possible preventative treatment.

We report a seizure-related death in a patient with juvenile myoclonic epilepsy 3 months following a previous generalised tonic-clonic seizure complicated by pulmonary oedema. Seizure-related pulmonary oedema is rare but may indicate an increased susceptibility to epilepsy related death. We consider possible preventative measures for patients presenting with seizure-related pulmonary oedema.