Idiopathic intracranial hypertension: expanding our understanding.

PURPOSE OF REVIEW: Idiopathic intracranial hypertension (IIH) affects predominantly overweight women of childbearing age, causing chronically-disabling headaches and visual loss. Weight loss remains the most effective management strategy, but innovative treatments and randomized control trials (RCTs) remain few. This paper will review recent IIH research. RECENT FINDINGS: Pregnancy-related complications, but not losses, are increased in IIH, while symptom severity is not affected. Weight loss of 24% results in normalization of intracranial pressure (ICP) and improvement in papilledema. Prolonged periods of papilledema result in delayed thinning of the ganglion cell layer. Less-invasive telemetry has improved understanding of the positional effects on ICP with rises seen in the supine and lateral positions. Exenatide, a GLP-1 agonist, may reduce ICP and improve symptoms. Venous sinus stenting is increasingly popular but its benefits over CSF diversion remain unclear. SUMMARY: Early involvement of obstetric care is recommended with pregnancy in IIH. Early intervention is required to avoid chronic papilledema that confers worse visual outcomes. Positional changes may affect ICP readings. The use of novel ICP telemetric devices has significant potential in future disease monitoring. The dual benefits of weight loss and ICP reduction with exenatide have significant potential in IIH management. Surgical RCTs are still required.

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The impact of smoking cessation on multiple sclerosis disease progression.

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.

Risk factors for perianeurysmal vasogenic oedema (pavo) following embolization therapy: literature review.

Perianeurysmal vasogenic oedema (PAVO) is a rare complication associated post-embolisation of intracranial aneurysms. The prevalence, risk factors predisposing to susceptibility, and pathologic mechanisms underlying this process are not clearly understood. Since this complication may be associated with poor clinical outcomes, the authors designed this study to describe possible risk factors, underlying mechanisms, and management of PAVO through published case reports. Developing a priori protocol according to PRISMA guidelines, we searched MEDLINE/PubMed, Embase and Web of Science to identify case studies and reports of adult patients with intracranial aneurysms who developed perianeurysmal oedema following coil embolization therapy. Data extracted from these studies included patient demographics, aneurysm characteristics, coil type, PAVO characteristics, treatment, and outcomes. Quality was assessed using a standardized tool. 21 eligible studies of acceptable quality were identified, comprising 40 unique cases from 9 countries. The mean patient age was 56.4 years and 25 (62.5%) were female. Aneurysm size ranged from 6 to 30 mm, with a mean size of 15.2 mm; only 6 (15%) of cases were giant intracranial aneurysm (≥ 25 mm). The more frequent locations of intracranial aneurysms associated with PAVO were the ICA (50%) and posterior circulation (32.5%), with 7.5% and 10% of cases occurring in MCA and anterior circulation, respectively. 16 cases (40%) were treated with bare platinum coils, and 14 (35%) with a combination of BPCs and bioactive coils; in 10 cases (25%), the coil type was not mentioned. PAVO presented between 0 days and 8 years of coil embolization, with 23 (57.5% cases) presenting symptomatically in relation to brain region affected. Management strategies for PAVO included conservative, steroids, re-embolization, clipping, stenting, parent artery occlusion either as monotherapy or as combination therapy. Of reported studies, 26 treated cases (65%) resolved, with 8 (20%) remaining stable, and 4 (10%) deteriorating. PAVO can be associated with small or large intracranial aneurysms, bare and bioactive platinum coils, and all regions of the intracranial circulation. The understanding of the risk factors of this complication lies in the underlying mechanisms, which will ultimately guide appropriate patient follow-up and subsequent optimal management.

Discovering patterns in outpatient neurology appointments using state sequence analysis.

BACKGROUND: Outpatient services in the UK, and in particular outpatient neurology services, are under considerable pressure with an ever-increasing gap between capacity and demand. To improve services, we first need to understand the current situation. This study aims to explore the patterns of appointment type seen in outpatient neurology, in order to identify potential opportunities for change. METHODS: We use State Sequence Analysis (SSA) on routinely collected data from a single neurology outpatient clinic. SSA is an exploratory methodology which allows patterns within sequences of appointments to be discovered. We analyse sequences of appointments for the 18 months following a new appointment. Using SSA we create groups of similar appointment sequence patterns, and then analyse these clusters to determine if there are particular sequences common to different diagnostic categories. RESULTS: Of 1315 patients 887 patients had only one appointment. Among the 428 patients who had more than one appointment a 6 monthly cycle of appointments was apparent. SSA revealed that there were 11 distinct clusters of appointment sequence patterns. Further analysis showed that there are 3 diagnosis categories which have significant influence over which cluster a patient falls into: seizure/epilepsy, movement disorders, and headache. CONCLUSIONS: Neurology outpatient appointment sequences show great diversity, but there are some patterns which are common to specific diagnostic categories. Information about these common patterns could be used to inform the structure of future outpatient appointments.

Uncommon causes of ischaemic stroke: how to approach the diagnosis.

Stroke is a common neurological emergency and although most cases are associated with traditional vascular risk factors leading to cerebral ischaemia by well-recognised pathophysiological mechanisms, around 4% of ischaemic strokes are due to rare conditions. These are important to recognise due to their different management, which is often specific and effective, and due to their different prognosis from otherwise cryptogenic ischaemic strokes. We outline a practical approach to identifying uncommon causes of ischaemic stroke by highlighting diagnostic 'red flags' and propose a structured approach to investigating them.

Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.

Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.

Optimising rehabilitation and recovery after a stroke.

Stroke can cause significant disability and impact quality of life. Multidisciplinary neurorehabilitation that meets individual needs can help to optimise recovery. Rehabilitation is essential for best quality care but should start early, be ongoing and involve effective teamwork. We describe current stroke rehabilitation processes, from the hyperacute setting through to inpatient and community rehabilitation, to long-term care and report on which UK quality care standards are (or are not) being met. We also examine the gap between what stroke rehabilitation is recommended and what is being delivered, and suggest areas for further improvement.

International Multicenter Analysis of Brain Structure Across Clinical Stages of Parkinson's Disease.

BACKGROUND: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated. OBJECTIVE: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging. METHODS: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score. RESULTS: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (dmax  = -0.20, dmin  = -0.09). The bilateral putamen (dleft  = -0.14, dright  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures. CONCLUSIONS: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Late-onset epilepsy predicts stroke: Systematic review and meta-analysis.

OBJECTIVE: Late-onset epilepsy (LOE) is closely associated with cerebrovascular disease, acting as both a marker of cerebrovascular disease (CVD) and occurring as a direct consequence. Despite this, our understanding of LOE as a cerebrovascular phenomenon is in its infancy. LOE also appears to be a harbinger of dementia. METHODS: A systematic review was performed to identify publications relating to LOE and identified observational studies, clinical studies, and radiological studies. RESULTS: A meta-analysis of observational studies demonstrated that patients presenting with LOE experience an increased risk of subsequent stroke (weighted OR 3.88 (95% CI 2.76-5.46)). The additional studies demonstrated clinical and radiological evidence to support the premise that LOE is likely to reflect underlying cerebrovascular disease. SIGNIFICANCE: Cerebrovascular disease risk factors convey increased risk of LOE and LOE can precede stroke and dementia, acting as an early marker for cerebrovascular risk. This may represent a potential point for intervention. There are a number of suggested mechanisms relating LOE to stroke; however, there is limited understanding of the natural history of LOE. Current data support the need for prospective research in order to understand the natural history of LOE and modify disease, in order to reduce the apparent sequelae of stroke and dementia.

Routinely collected patient data in neurology research: a systematic mapping review.

BACKGROUND: This review focuses on neurology research which uses routinely collected data. The number of such studies is growing alongside the expansion of data collection. We aim to gain a broad picture of the scope of how routine healthcare data have been utilised. METHODS: This study follows a systematic mapping review approach which does not make a judgement on the quality of the papers included in the review, thereby enabling a complete overview of the field. RESULTS: Of 4481 publications retrieved, 386 met the eligibility criteria for this study. These publications covered a wide range of conditions, but the majority were based on one or only a small number of neurological conditions. In particular, publications concerned with three discrete areas of neurological practice - multiple sclerosis (MS), epilepsy/seizure and Parkinson's disease - accounted for 60% of the total. MS was the focus of the highest proportion of eligible studies (35%), yet in the recent Global Burden of Neurological Disease study it ranks only 14th out of 15 neurological disorders for DALY rates. In contrast, migraine is the neurological disorder with the highest ranking of DALYs globally (after stroke) and yet it was represented by only 4% of eligible studies. CONCLUSION: This review shows that there is a disproportionately large body of literature pertaining to relatively rare disorders, and a correspondingly small body of literature describing more common conditions. Therefore, there is potential for future research to redress this balance.

Seizures in the context of occult cerebrovascular disease.

There is an important bidirectional relationship between seizures and cerebrovascular disease (CVD). Aside from poststroke epilepsy, Occult CVD is an important cause of late-onset seizures (LOS) and late-onset epilepsy (LOE). Late-onset seizures/LOE are associated with a threefold increased risk of subsequent clinical stroke. This relationship exists not only in later life, but with 'late-onset' seizures or epilepsy occurring from the fourth decade of life onwards. There is increasing evidence for the importance of hypertension and cerebral small vessel disease (SVD) in epileptogenesis, but there is a considerable need for further work to elucidate underlying mechanisms. There may be a disproportionately increased risk of intracerebral hemorrhage (ICH) after LOS/LOE; this too requires further study. There is also a bidirectional relationship between LOS/LOE and cognitive impairment/dementia: it is likely that there are important interactions between vascular and neurodegenerative pathological processes mediating LOE, stroke, and dementia. There is a pressing need for better epidemiological and natural history data as well as elucidation of epileptogenic mechanisms, in order to progress our understanding and to better inform clinical practice.

GLP-1 receptor agonists for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD. OBJECTIVES: To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. SEARCH METHODS: We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author. MAIN RESULTS: Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The difference in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no effect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no effect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8). AUTHORS' CONCLUSIONS: Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persist for some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying effect. SAEs were unlikely to be related to treatment. The effectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists.

Periprocedural antithrombotic management for lumbar puncture: Association of British Neurologists clinical guideline.

Lumbar puncture (LP) is an important and frequently performed invasive procedure for the diagnosis and management of neurological conditions. There is little in the neurological literature on the topic of periprocedural management of antithrombotics in patients undergoing LP. Current practice is therefore largely extrapolated from guidelines produced by anaesthetic bodies on neuraxial anaesthesia, haematology groups advising on periprocedural management of antiplatelet agents and anticoagulants, and by neuroradiology on imaging-guided spinal procedures. This paper summarises the existing literature on the topic and offers recommendations to guide periprocedural antithrombotic management for LP, based on the consolidation of the best available evidence. ​.

Integrating acute stroke telemedicine consultations into specialists' usual practice: a qualitative analysis comparing the experience of Australia and the United Kingdom.

BACKGROUND: Stroke telemedicine can reduce healthcare inequities by increasing access to specialists. Successful telemedicine networks require specialists adapting clinical practice to provide remote consultations. Variation in experiences of specialists between different countries is unknown. To support future implementation, we compared perceptions of Australian and United Kingdom specialists providing remote acute stroke consultations. METHODS: Specialist participants were identified using purposive sampling from two new services: Australia's Victorian Stroke Telemedicine Program (n = 6; 2010-13) and the United Kingdom's Cumbria and Lancashire telestroke network (n = 5; 2010-2012). Semi-structured interviews were conducted pre- and post-implementation, recorded and transcribed verbatim. Deductive thematic and content analysis (NVivo) was undertaken by two independent coders using Normalisation Process Theory to explore integration of telemedicine into practice. Agreement between coders was M = 91%, SD = 9 and weighted average κ = 0.70. RESULTS: Cross-cultural similarities and differences were found. In both countries, specialists described old and new consulting practices, the purpose and value of telemedicine systems, and concerns regarding confidence in the assessment and diagnostic skills of unknown colleagues requesting telemedicine support. Australian specialists discussed how remote consultations impacted on usual roles and suggested future improvements, while United Kingdom specialists discussed system governance, policy and procedures. CONCLUSION: Australian and United Kingdom specialists reported telemedicine required changes in work practice and development of new skills. Both groups described potential for improvements in stroke telemedicine systems with Australian specialists more focused on role change and the United Kingdom on system governance issues. Future research should examine if cross-cultural variation reflects different models of care and extends to other networks.

Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

BACKGROUND: Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. METHODS: A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. RESULTS: Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline's PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. CONCLUSIONS: The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV.

'It was like he was in the room with us': patients' and carers' perspectives of telemedicine in acute stroke.

BACKGROUND: Telemedicine can facilitate delivery of thrombolysis in acute stroke. The aim of this qualitative study was to explore patients' and carers' views of their experiences of using a stroke telemedicine system in order to contribute to the development of reliable and acceptable telemedicine systems and training for health-care staff. METHOD: We recruited patients who had, and carers who were present at, recent telemedicine consultations for acute stroke in three hospitals in NW England. Semi-structured interviews were conducted using an interview guide based on normalization process theory (NPT). Thematic analysis was undertaken. RESULTS: We conducted 24 interviews with 29 participants (16 patients; 13 carers). Eleven interviews pertained to 'live' telemedicine assessments (at the time of admission); nine had mock-up telemedicine assessments (within 48 h of admission); four had both assessments. Using the NPT domains as a framework for analysis, factors relating to coherence (sense making) included people's knowledge and understanding of telemedicine. Cognitive participation (relational work) included interaction between staff and with patients and carers. Issues relating to collective action (operational work) included information exchange and support, and technical matters. Findings relating to reflexive monitoring (appraisal) included positive and negative impressions of the telemedicine process, and emotional reactions. CONCLUSION: Although telemedicine was well accepted by many participants, its use added an additional layer of complexity to the acute stroke consultation. The 'remote' nature of the consultation posed challenges for some patients. These issues may be ameliorated by clear information for patients and carers, staff interpersonal skills, and teamworking.

Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.

OBJECTIVE: Titin gene (TTN) mutations have been described in eight families with hereditary myopathy with early respiratory failure (HMERF). Some of the original patients had features resembling myofibrillar myopathy (MFM), arguing that TTN mutations could be a much more common cause of inherited muscle disease, especially in presence of early respiratory involvement. METHODS: We studied 127 undiagnosed patients with clinical presentation compatible with MFM. Sanger sequencing for the two previously described TTN mutations in HMERF (p.C30071R in the 119th fibronectin-3 (FN3) domain, and p.R32450W in the kinase domain) was performed in all patients. Patients with mutations had detailed review of their clinical records, muscle MRI findings and muscle pathology. RESULTS: We identified five new families with the p.C30071R mutation who were clinically similar to previously reported cases, and muscle pathology demonstrated diagnostic features of MFM. Two further families had novel variants in the 119th FN3 domain (p.P30091L and p.N30145K). No patients were identified with mutations at position p.32450. CONCLUSIONS: Mutations in TTN are a cause of MFM, and titinopathy is more common than previously thought. The finding of the p.C30071R mutation in 3.9% of our study population is likely due to a British founder effect. The occurrence of novel FN3 domain variants, although still of uncertain pathogenicity, suggests that other mutations in this domain may cause MFM, and that the disease is likely to be globally distributed. We suggest that HMERF due to mutations in the TTN gene be nosologically classified as MFM-titinopathy.

The challenges of implementing a telestroke network: a systematic review and case study.

BACKGROUND: The use of telemedicine in acute stroke care can facilitate rapid access to treatment, but the work required to embed any new technology into routine practice is often hidden, and can be challenging. We aimed to collate recommendations and resources to support telestroke implementation. METHODS: Systematic search of healthcare databases and the Internet to identify descriptions of the implementation of telestroke projects; interviews with key stakeholders during the development of one UK telestroke network. Supporting documentation from existing projects was analysed to construct a framework of implementation stages and tasks, and a toolkit of documents. Interviews and literature were analysed with other data sources using Normalisation Process Theory as described in the e-Health Implementation Toolkit. RESULTS: 61 telestroke projects were identified and contacted. Twenty projects provided documents, 13 with published research detailing four stages of telestroke system development, implementation, use, and evaluation. Interviewees identified four main challenges: engaging and maintaining the commitment of a wide range of stakeholders across multiple organisations; addressing clinicians perceptions of evidence, workload, and payback; managing clinical and technical workability across diverse settings; and monitoring how the system is used and reconfigured by users. CONCLUSIONS: Information to guide telestroke implementation is sparse, but available. By using multiple sources of data, sufficient information was collated to construct a web-based toolkit detailing implementation tasks, resources and challenges in the development of a telestroke system for assessment and thrombolysis delivery in acute care. The toolkit is freely available online.

Calibrated fMRI during a cognitive Stroop task reveals reduced metabolic response with increasing age.

fMRI studies of aging have revealed increased blood oxygenation level dependent (BOLD) response to tasks of executive function with advancing age, which is generally interpreted as increased neural activity. However, changes in the cerebrovascular system with age can alter the BOLD signal, complicating this interpretation. Arterial spin labeling (ASL) allows simultaneous acquisition of BOLD and cerebral blood flow (CBF) information and can be used to quantify the component parts of the BOLD signal. We used this calibrated BOLD approach in 58 healthy participants over an age range of 18-71 years to determine the relative vascular and neuronal contributions to the age-related BOLD changes in response to a Stroop task. The percentage BOLD response increased significantly with increasing age but the percentage CBF response did not alter, such that the BOLD increase is attributed to a significant reduction in the oxygen metabolism response with increasing age. Hence, in this study, the BOLD increase with age should be interpreted as a reduction in neural activity. The greatest percentage BOLD increases with age were found in the left and right medial frontal gyri and the primary motor cortex and were again linked to a reduction in oxygen metabolism. On separating the participants into three groups (young, old high performers and old low performers), age-related differences in percentage BOLD response and oxygen metabolism response could be attributed to the low performing old group. This study demonstrates the need to take into account alterations in vascular-metabolic coupling and resting blood volume when interpreting changes in the BOLD response with aging.