The Walton Center for Neurology and Neurosurgery

Liverpool, United Kingdom

The Walton Center for Neurology and Neurosurgery

Liverpool, United Kingdom
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Harding K.E.,University of Cardiff | Harding K.E.,University of Wales | Wardle M.,University of Wales | Moore P.,University of Cardiff | And 6 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2015

Background: A minority of patients with multiple sclerosis (MS) have primary progressive disease (PPMS). Treatment options are currently limited, but as prospects for interventional studies become more realistic, understanding contemporary outcome data will be key to successful trial design. Methods: 234 PPMS patients were identified from a population-based cohort of 2131 (11.0%) and mean follow-up of 13.1 years. Time to established disability endpoints was compared with patients with relapsing-onset MS (ROMS) using survival analysis, and Cox regression employed to explore factors contributing to disability accumulation. Results: were used to create predictive power models for clinical trials in PPMS. Results Time to fixed disability milestones was shorter than in ROMS (Expanded Disability Status Scale (EDSS) 4.0:8.1 vs 17.1 years, p<0.001; EDSS 6.0: 9.6 vs 22.1 years, p<0.001; EDSS 8.0: 20.7 vs 39.7 years, p<0.001), but there were no differences in age-related disability. Age and cerebellar symptoms at onset affected rate of progression. Modelling of these data indicated that trials employing EDSS change of 1.0 as the primary outcome measure would be powered to detect a 20% difference in progression using 600 patients with initial EDSS of 4.0 per trial arm, or 400 patients with initial EDSS of 5.0 per arm. However, trials including patients with fixed EDSS of ≤6.0 will be underpowered even with large numbers or prolonged duration. Conclusions: Disability progression in PPMS is variable and influenced by age at onset. Although progression is more rapid, age-related disability milestones are identical to relapsing-onset disease. These data offer a contemporary paradigm for clinical trial design in progressive MS.

Snell J.A.,University of Liverpool | Loh N.-H.W.,The Walton Center for Neurology and Neurosurgery | Mahambrey T.,Whiston Hospital | Shokrollahi K.,Whiston Hospital
Critical Care | Year: 2013

Between 4 and 22% of burn patients presenting to the emergency department are admitted to critical care. Burn injury is characterised by a hypermetabolic response with physiologic, catabolic and immune effects. Burn care has seen renewed interest in colloid resuscitation, a change in transfusion practice and the development of anti-catabolic therapies. A literature search was conducted with priority given to review articles, meta-analyses and well-designed large trials; paediatric studies were included where adult studies were lacking with the aim to review the advances in adult intensive care burn management and place them in the general context of day-to-day practical burn management. © 2013 BioMed Central Ltd.

Ellis R.,The Walton Center for Neurology and Neurosurgery | Brown S.,Countess of Chester | Boggild M.,Townsville Hospital
Multiple sclerosis (Houndmills, Basingstoke, England) | Year: 2015

Therapy-related acute leukaemia (TRAL) is a significant concern, when considering treatment with mitoxantrone for multiple sclerosis (MS). We re-evaluated the literature, identifying all case reports and series of > 50 patients reporting TRAL cases in MS. TRAL was diagnosed in 0.73% of the 12,896 patients identified. Median onset was 22 months following treatment. We calculated a number needed to harm of 137.5 exposed patients, significantly higher than our 2008 analysis. We found that 82.8% of patients were exposed to > 60 mg/m(2) with a relative risk of 1.85 (p = 0.018) compared to < 60 mg/m(2), strongly suggesting a relationship to dose. MS treatment regimens which limit the mitoxantrone dose to < 60 mg/m(2) reduce the risk of TRAL. © The Author(s), 2014.

Mills R.J.,The Walton Center for Neurology and Neurosurgery | Young C.A.,The Walton Center for Neurology and Neurosurgery | Pallant J.F.,University of Melbourne | Tennant A.,University of Leeds
Health and Quality of Life Outcomes | Year: 2010

Background: Fatigue is a common and debilitating symptom in multiple sclerosis (MS). Best-practice guidelines suggest that health services should repeatedly assess fatigue in persons with MS. Several fatigue scales are available but concern has been expressed about their validity. The objective of this study was to examine the reliability and validity of a new scale for MS fatigue, the Neurological Fatigue Index (NFI-MS).Methods: Qualitative analysis of 40 MS patient interviews had previously contributed to a coherent definition of fatigue, and a potential 52 item set representing the salient themes. A draft questionnaire was mailed out to 1223 people with MS, and the resulting data subjected to both factor and Rasch analysis.Results: Data from 635 (51.9% response) respondents were split randomly into an 'evaluation' and 'validation' sample. Exploratory factor analysis identified four potential subscales: 'physical', 'cognitive', 'relief by diurnal sleep or rest' and 'abnormal nocturnal sleep and sleepiness'. Rasch analysis led to further item reduction and the generation of a Summary scale comprising items from the Physical and Cognitive subscales. The scales were shown to fit Rasch model expectations, across both the evaluation and validation samples.Conclusion: A simple 10-item Summary scale, together with scales measuring the physical and cognitive components of fatigue, were validated for MS fatigue. © 2010 Mills et al; licensee BioMed Central Ltd.

Davies R.R.,The Walton Center for Neurology and Neurosurgery | Kipps C.M.,University of Southampton
Current Alzheimer Research | Year: 2011

We review the practical importance of lobar atrophy in frontotemporal dementia (FTD), for diagnosis and prognosis. We discuss specific patterns of frontotemporal atrophy that denote clinical and pathological subtypes of FTD (e.g. semantic dementia). We also discuss the unsatisfactory clinical experience of interpreting MRI scans in individual FTD cases, especially the behavioural presentations (without aphasic or motor impairments). This issue is explored by examining the FTD phenocopy concept. Lobar atrophy emerges as a key observation in defining behavioural FTD patients whose symptoms are likely to progress. In a situation where objective clinical data are few, we highlight the importance of applying caution before diagnosing FTD is the absence of visible brain atrophy. © 2011 Bentham Science Publishers Ltd.

Ando H.,Liverpool Hope University | Chakrabarti B.,University of Liverpool | Angus R.M.,University of Liverpool | Cousins R.,Liverpool Hope University | And 2 more authors.
BMJ Supportive and Palliative Care | Year: 2014

Objective: Although non-invasive ventilation (NIV) can promote quality of life in motor neuron disease (MND), previous studies have disregarded the impact of progression of illness. This study explored how patients' perceptions of NIV treatment evolve over time and how this was reflected in their adherence to NIV. Methods: Five patients with MND (male=4, mean age=59 years), from a bigger cohort who were prospectively followed, had multiple post- NIV semistructured interviews, covering more than 12 months, along with ventilator interaction data. The transcribed phenomenological data were analysed using qualitative methodology. Results: Three themes emerged: experience of NIV, influence on attitudes and perceived impact of NIV on prognosis. The ventilator interaction data identified regular use of NIV by four participants who each gave positive account of their experience of NIV treatment, and irregular use by one participant who at interview revealed a negative attitude to NIV treatment and in whom MND induced feelings of hopelessness. Conclusions: This exploratory study suggests that a positive coping style, adaptation and hope are key factors for psychological well-being and better adherence to NIV. More studies are needed to determine these relationships.

France B.D.,Bangor University | Lewis R.A.,Bangor University | Sharma M.L.,The Walton Center for Neurology and Neurosurgery | Poolman M.,Bangor University
BMJ Supportive and Palliative Care | Year: 2014

Background: Cordotomy can be effective in relieving pain for patients with mesothelioma, but the evidence to support continued provision is limited. This review forms part of the Invasive Neurodestructive Procedures in Cancer Pain pilot study: The role of cordotomy in mesotheliomarelated pain in the UK. Aim/design: We report on the results of the first comprehensive systematic review of the use of cordotomy in mesothelioma-related pain, with specific reference to effectiveness in relieving pain and safety. The review was conducted according to guidelines reported in the NHS Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses. Data sources: 14 databases from inception to March 2012 were searched, with no limitations on language or publication type. Results: Nine studies met the inclusion criteria, all of which were case series of percutaneous cervical cordotomy (PCC) involving 160 patients. All studies demonstrated good pain relief in the majority of patients. Initial post-procedure measurements showed the greatest reduction in pain. Some side effects (headache, mirror pain, motor weakness) occurred relatively frequently but were mostly transient. Respiratory dysfunction post-PCC was rare. No deaths were directly ascribed to cordotomy. Conclusions: The available evidence is significantly limited in quantity and quality. Although it seems to suggest that cordotomy might be safe and effective in this setting, more reliable evidence is needed to aid decision making on continued provision. A national registry for cordotomy would be a valuable first step in this process.

Young C.A.,The Walton Center for Neurology and Neurosurgery
Cochrane database of systematic reviews (Online) | Year: 2011

Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, is a progressive, neurodegenerative condition which may cause dysphagia, as well as limb weakness, dysarthria, emotional lability and respiratory failure. Since normal salivary production is 0.5 to 1.5 litres daily, loss of salivary clearance due to dysphagia leads to salivary pooling and sialorrhea, often resulting in distress and inconvenience to patients. To systematically review evidence on treatment of sialorrhea in MND, including medications, radiotherapy and surgery. We searched the Cochrane Neuromuscular Disease Group Specialized Register (1 October 2010), the Cochrane Central Register of Controlled Trials )(CENTRAL) (The Cochrane Library issue 3, 2010), MEDLINE (January 1966 to September 2010), EMBASE (January 1980 to September 2010), AMED (1985 to September 2010) and CINAHL Plus (January 1937 September 2010). All bibliographies of the identified randomized trials were reviewed and authors contacted as needed. Known experts in the field were contacted to identify further published and unpublished papers. We included randomized and quasi-randomised controlled studies on any intervention for sialorrhea and related symptoms, in people with MND. Review authors summarised data independently in a customised data collection form and confirmed data presented in Cochrane Review Manager software. Only one randomized controlled trial was identified. This was a well designed study of botulinum toxin B injected into parotid and submandibular glands of 20 patients, which showed positive results for four weeks (Jackson 2009). There was low risk of bias in the study and no significant adverse events reported. There is some evidence for use of botulinum toxin injections to salivary glands for the treatment of sialorrhea in MND. Further research is required on this important symptom. Data are needed on the problem of sialorrhea in MND and its measurement, both by patient self report measures and objective tests. These will allow the development of better randomized controlled trials.

Barone D.G.,The Walton Center for Neurology and Neurosurgery
The Cochrane database of systematic reviews | Year: 2014

Extent of resection is believed to be a key prognostic factor in neuro-oncology. Image guided surgery uses a variety of tools or technologies to help achieve this goal. It is not clear whether any of these, sometimes very expensive, tools (or their combination) should be recommended as part of standard care for patient with brain tumours. We set out to determine if image guided surgery offers any advantage in terms of extent of resection over surgery without any image guidance and if any one tool or technology was more effective. To compare image guided surgery with surgery either not using any image guidance or to compare surgery using two different forms of image guidance. The primary outcome criteria was extent of resection and adverse events. Other outcome criteria were overall survival; progression free survival; and quality of life (QoL). The following databases were searched, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2013), MEDLINE (1948 to March, week 10, 2013) and EMBASE (1970 to 2013, week 10). Reference lists of all identified studies were searched. Two journals, the Journal of Neuro-Oncology and Neuro-oncology, were handsearched from 1991 to 2013, including all conference abstracts. Neuro-oncologists, trial authors and manufacturers were contacted regarding ongoing and unpublished trials. Study participants included patients of all ages with a presumed new or recurrent brain tumour (any location or histology) from clinical examination and imaging (computed tomography (CT), magnetic resonance imaging (MRI) or both). Image guidance interventions included intra-operative MRI (iMRI); fluorescence guided surgery; neuronavigation including diffusion tensor imaging (DTI); and ultrasonography. Included studies had to be randomised controlled trials (RCTs) with comparisons made either with patients having surgery without the image guidance tool in question or with another type of image guidance tool. Subgroups were to include high grade glioma; low grade glioma; brain metastasis; skull base meningiomas; and sellar or parasellar tumours. Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a pre-specified pro forma. Four RCTs were identified, each using a different image guided technique: 1. iMRI (58 patients), 2. 5-aminolevulinic acid (5-ALA) fluorescence guided surgery (322 patients), 3. neuronavigation (45 patients) and 4. DTI-neuronavigation (238 patients). Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies, especially for the study using DTI-neuronavigation. All studies included patients with high grade glioma, with one study also including patients with low grade glioma. The extent of resection was increased with iMRI (risk ratio (RR) (incomplete resection) 0.13, 95% CI 0.02 to 0.96, low quality evidence), 5-ALA (RR 0.55, 95% CI 0.42 to 0.71) and DTI-neuronavigation (RR 0.35, 95% CI 0.20 to 0.63, very low quality evidence). Insufficient data were available to evaluate the effects of neuronavigation on extent of resection. Reporting of adverse events was incomplete, with a suggestion of significant reporting bias. Overall, reported events were low in most studies, but there was concern that surgical resection using 5-ALA may lead to more frequent early neurological deficits. There was no clear evidence of improvement in overall survival (OS) with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07) or DTI-neuronavigation (HR 0.57, 95% CI 0.32 to 1.00) in patients with high grade glioma. Progression-free survival (PFS) data were not available in the appropriate format for analysis.Data for quality of life (QoL) were only available for one study and suffered from significant attrition bias. There is low to very low quality evidence (according to GRADE criteria) that image guided surgery using iMRI, 5-ALA or DTI-neuronavigation increases the proportion of patients with high grade glioma that have a complete tumour resection on post-operative MRI. There is a theoretical concern that maximising the extent of resection may lead to more frequent adverse events but this was poorly reported in the included studies. Effects of image guided surgery on survival and QoL are unclear. Further research, including studies of ultrasound guided surgery, is needed.

Sathasivam S.,The Walton Center for Neurology and Neurosurgery
Singapore Medical Journal | Year: 2010

Motor neurone disease (MND) is a rapidly progressive adult-onset neurodegenerative disorder. In recent years, there has been an increased understanding regarding the epidemiology and clinical features of the different variants of MND. In addition, new diagnostic criteria have been proposed to increase the sensitivity of the diagnosis. This review highlights these new concepts and discusses the differential diagnoses of MND, highlighting the common pitfalls and misdiagnoses. It also discusses the prognostic markers for MND and a possible change in the natural history of the disease course.

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