Liverpool, United Kingdom
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Goebel A.,University of Liverpool | Goebel A.,Walton Center
Autoimmunity Reviews | Year: 2013

Complex regional pain syndrome (CRPS) is a painful condition, which arises in a limb after trauma. CRPS can profoundly affect patients' quality of life, and there is no cure. CRPS is associated with limb-confined sensory, motor, skin, bone and autonomic abnormalities. Recent research has shown that some patients respond to treatment with immunoglobulins, and that a majority have IgG serum-autoantibodies directed against, and activating autonomic receptors. CRPS serum-IgG, when transferred to mice elicits abnormal behaviour. These results suggest that CRPS is associated with an autoantibody-mediated autoimmune process in some cases. CRPS has unusual features, including a non-destructive, and regionally-confined course. We propose that CRPS constitutes a prototype of a new kind of autoimmunity, which we term 'IRAM' (injury-triggered, regionally-restricted autoantibody-mediated autoimmune disorder with minimally-destructive course). Understanding autoimmune contribution to CRPS should allow the exploration of novel treatment modalities in the future. Additional 'functional' disorders, painful or painless may be autoimmune in nature. © 2013 Elsevier B.V.


Wong S.H.,Moorfields Eye Hospital | Das K.,Walton Center | Javadpour M.,Walton Center
BMJ Case Reports | Year: 2013

We presented a case of a 62-year-old man whose initial clinical picture was suggestive of bacterial meningitis, but instead had pituitary apoplexy. We highlighted how pituitary apoplexy can mimic bacterial meningitis, learning points on how clinical assessment can aid earlier diagnosis and the importance of considering this differential diagnosis, particularly with the associated morbidity and mortality if missed. Copyright 2013 BMJ Publishing Group. All rights reserved.


Freedman M.S.,Ottawa Hospital Research Institute | Bar-Or A.,Montreal Neurological Institute | Oger J.,University of British Columbia | Traboulsee A.,University of British Columbia | And 8 more authors.
Neurology | Year: 2011

Objective: To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2 + or DR4 +). Methods: This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5-6.5, stratified according to baseline EDSS score (3.5-5.0, or 5.5-6.5) and HLA haplotype (DR2 + or DR4 +, or DR2 -/DR4 -). Upon entry of 100 DR2 -/DR4 + subjects, further study enrollment was limited to DR2 + or DR4 + subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life. Results: There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified. Conclusion: In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. Classification of evidence: This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2 + or DR4 +. Copyright © 2011 by AAN Enterprises, Inc.


Chadwick D.,Walton Center | Almond S.,Royal Liverpool Hospital
Practical Neurology | Year: 2010

The differential diagnosis of episodes of transient loss of consciousness can be straightforward but can also present some of the greatest diagnostic diffi culties. In most circumstances, when there is uncertainty, usually when there have been only one or a few poorly observed events, it may be reasonable to admit to that uncertainty and await any further events to clarify the diagnosis. We have reason to know from bitter experience that this is not always the case and that more rigorous consideration of investigation may be justifi ed rather than allowing the passage of time to clarify the diagnosis.


Maramattom B.V.,Lourdes Hospital | Jacob A.,Walton Center
Annals of Indian Academy of Neurology | Year: 2011

A large proportion of "encephalitis" is caused by unknown agents. Of late, a new category of disorders, "autoimmune encephalitis," has been described, which present with features similar to viral encephalitides. A well-delineated and common entity among this group is the recently described anti-NMDAR encephalitis (NMDARE). Although this entity was initially described in young women harboring ovarian teratomas, it is now characterised as well in children and men. Approximately 60% of the patients have an underlying tumor, usually an ovarian teratoma. In 40% of the patients, no cause can be found (idiopathic NMDARE). NMDARE typically presents with psychiatric features followed by altered level of consciousness, severe dysautonomia, hyperkinetic movement disorders, seizures and central hypoventilation. Orofacial dyskinesias resulting in lip and tongue mutilation are quite common. Seizures, are common and may be difficult to treat. The disease can be confirmed by serum and cerebrospinal fluid anti-NMDAR antibodies. Titers of these antibodies can also guide response to treatment. Tumor removal is necessary if identified, followed by immunological treatment. Intravenous methylprednisolone and immunoglobulins aim to suppress/modulate immune response while plasma exchange attempts to remove antibodies and other inflammatory cytokines. Rituximab and cyclophosphamide aim to suppress antibody production. Recovery is slow and often with neurological deficits if treatment is delayed. With many distinctive clinical features, a specific antibody that aids diagnosis, and early effective treatment with commonly available drugs leading to good outcomes, NMDARE is a diagnosis that should be considered early in any case of "unexplained encephalitis".


Versteegh M.M.,Erasmus University Rotterdam | Leunis A.,Erasmus University Rotterdam | Luime J.J.,Rotterdam University | Boggild M.,Walton Center | And 2 more authors.
Medical Decision Making | Year: 2012

Background. Responses on condition-specific instruments can be mapped on the EQ-5D to estimate utility values for economic evaluation. Mapping functions differ in predictive quality, and not all condition-specific measures are suitable for estimating EQ-5D utilities. We mapped QLQC30, HAQ, and MSIS-29 on the EQ-5D and compared the quality of the mapping functions with statistical and clinical indicators. Methods. We used 4 data sets that included both the EQ-5D and a condition-specific measure to develop ordinary least squares regression equations. For the QLQ-C30, we used a multiple myeloma data set and a non-Hodgkin lymphoma one. An early arthritis cohort was used for the HAQ, and a cohort of patients with relapsing remitting or secondary progressive multiple sclerosis was used for the MSIS-29. We assessed the predictive quality of the mapping functions with the root mean square error (RMSE) and mean absolute error (MAE) and the ability to discriminate among relevant clinical subgroups. Pearson correlations between the condition-specific measures and items of the EQ-5D were used to determine if there is a relationship between the quality of the mapping functions and the amount of correlated content between the used measures. Results. The QLQ-C30 had the highest correlation with EQ-5D items. Average %RMSE was best for the QLQ-C30 with 10.9%, 12.2% for the HAQ, and 13.6% for the MSIS-29. The mappings predicted mean EQ-5D utilities without significant differences with observed utilities and discriminated between relevant clinical groups, except for the HAQ model. Conclusions. The preferred mapping functions in this study seem suitable for estimating EQ-5D utilities for economic evaluation. However, this research shows that lower correlations between instruments lead to less predictive quality. Using additional validation tests besides reporting statistical measures of error improves the assessment of predictive quality.


Zhao S.,Walton Center | Mutch K.,Walton Center | Elsone L.,Walton Center | Nurmikko T.,Walton Center | Jacob A.,Walton Center
Multiple Sclerosis Journal | Year: 2014

Though pain in neuromyelitis optica (NMO) has been described in two recent reports, the proportion with true neuropathic pain (NP), its features, impact on activities of daily living (ADL) and quality of life has not been well characterised. A cross-sectional study of 50 NMO patients with transverse myelitis was performed using Douleur Neuropathique 4, Brief Pain Inventory, Extended Disability Status Scale and Short Form 36. NP was identified in 62% of patients. Pain was constant in 68% affecting most ADL. Pain was associated with significant reduction of the SF36 Mental Composite Score. The high prevalence of NP and associated disability necessitates an in-depth enquiry in patients with NMO. © The Author(s) 2014.


Eldridge P.,Walton Center
Anaesthesia and Intensive Care Medicine | Year: 2016

Neurosurgical treatments for pain can be classified into three categories: treatment of the cause, neuromodulation and neuroablative techniques in order of preference of application. In general, it is important to be able offer all treatments in a pluripotential context. All of these treatments are now delivered in a multidisciplinary context, with other adjunctive treatments including pain medicine, cognitive techniques and pain management programmes. There is increasing emphasis on outcome measurement in all categories, using both condition-specific and generic assessment tools such as the EuroQuol-5D. In this context, it is longer term outcomes that are important – meaning several years. © 2016


Chandran A.,Walton Center | Puthuran M.,Walton Center | Eldridge P.R.,Walton Center | Nahser H.C.,Walton Center
Journal of NeuroInterventional Surgery | Year: 2016

A stable guide catheter position within the intracranial vasculature is critical for safe, successful endovascular treatment. Objective To present ourinitial experience with the 0.071inch inner diameter Benchmark guide catheter used in the treatment of intracranial cerebrovascular pathologies, demonstrating its safety and efficacy. Methods We retrospectively reviewed use of the Benchmark guide catheter from September through December 2014 in the management of various neuroendovascular intracranial pathologies. Clinical performance and complication rates were evaluated, with particular consideration of vessel tortuosity. A total of 62 Benchmarks were used, 47 in the anterior circulation, 10 in the posterior circulation, 4 in the external carotid, and 1 in the venous sinus. The five cases with access to the external carotid and venous sinus were excluded. Results The Benchmark was able to cross at least one 90° turn in 49 (86%) of the 57 patients. Reversal of the catheter was seen in 15% of 47 anterior circulation cases (4 at one 90° turn; 3 at two 90° turns). We report no complications of dissection or thromboembolic events. All guide catheter positions were safely achieved over a 0.035 Terumo stiff glidewire without need for an inner smaller lumen guide catheter for navigation. Conclusions Benchmark is a new guide catheter, with an ideal combination of both hyperflexible, atraumatic distal tip and optimized proximal shaft support to provide stable 6F primary access for a successful neurointerventional procedure. Benchmark can be easily, safely, and consistently positioned in a desired location within intracranial arteries providing a stable position for intervention and adequate angiography. © 2016 Published by the BMJ Publishing Group Limited.


Barone D.G.,Walton Center | Czosnyka M.,University of Cambridge
The Scientific World Journal | Year: 2014

The ability to measure reliably the changes in the physical and biochemical environment after a brain injury is of great value in the prevention, treatment, and understanding of the secondary injuries. Three categories of multimodal brain monitoring exist: direct signals which are monitored invasively; variables which may be monitored noninvasively; and variables describing brain pathophysiology which are not monitored directly but are calculated at the bedside by dedicated computer software. Intracranial pressure (ICP) monitoring, either as stand-alone value or study of a dynamic trend, has become an important diagnostic tool in the diagnosis and management of multiple neurological conditions. Attempts have been made to measure ICP non-invasively, but this is not a clinical reality yet. There is contrasting evidence that monitoring of ICP is associated with better outcome, and further RCTs based on management protocol are warranted. Computer bedside calculation of "secondary parameters" has shown to be potentially helpful, particularly in helping to optimize "CPP-guided therapy." In this paper we describe the most popular invasive and non invasive monitoring modalities, with great attention to their clinical interpretation based on the current published evidence. © 2014 D. G. Barone and M. Czosnyka.

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