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ABSTRACT: We combined tract-based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract-specific short-term changes in early primary-progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty-one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM "skeleton," which represents the tracts that are "common" to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co-registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a "skeletonised" MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow-up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal-appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract-specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross-subject and tract-specific changes in MTR. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
Human Brain Mapping 04/2013; · 5.88 Impact Factor
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BMJ (Clinical research ed.). 01/2013; 346:f275.
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ABSTRACT: We characterized metabolic changes along the cortico-spinal tract (CST) in multiple sclerosis (MS) patients using a novel application of chemical shift imaging (CSI) and considering the spatial variation of metabolite levels. Thirteen relapsing-remitting (RR) and 13 primary-progressive (PP) MS patients and 16 controls underwent (1) H-MR CSI, which was applied to coronal-oblique scans to sample the entire CST. The concentrations of the main metabolites, i.e., N-acetyl-aspartate, myo-Inositol (Ins), choline containing compounds (Cho) and creatine and phosphocreatine (Cr), were calculated within voxels placed in regions where the CST is located, from cerebral peduncle to corona radiata. Differences in metabolite concentrations between groups and associations between metabolite concentrations and disability were investigated, allowing for the spatial variability of metabolite concentrations in the statistical model. RRMS patients showed higher CST Cho concentration than controls, and higher CST Ins concentration than PPMS, suggesting greater inflammation and glial proliferation in the RR than in the PP course. In RRMS, a significant, albeit modest, association between greater Ins concentration and greater disability suggested that gliosis may be relevant to disability. In PPMS, lower CST Cho and Cr concentrations correlated with greater disability, suggesting that in the progressive stage of the disease, inflammation declines and energy metabolism reduces. Attention to the spatial variation of metabolite concentrations made it possible to detect in patients a greater increase in Cr concentration towards the superior voxels as compared to controls and a stronger association between Cho and disability, suggesting that this step improves our ability to identify clinically relevant metabolic changes. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 12/2012; · 5.88 Impact Factor
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ABSTRACT: Background: Traumatic spinal cord injury (SCI) leads to disruption of axons and macroscopic tissue loss. Using diffusion tensor imaging (DTI), we assessed degeneration of the corticospinal tract (CST) in the cervical cord above a traumatic lesion and explored its relationship with cervical atrophy, remote axonal changes within the cranial CST and upper limb function.
PLoS ONE 12/2012; · 4.09 Impact Factor
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Valentina Tomassini,
Paul M Matthews, Alan J Thompson,
Daniel Fuglø,
Jeroen J Geurts,
Heidi Johansen-Berg,
Derek K Jones,
Maria A Rocca,
Richard G Wise,
Frederik Barkhof,
Jacqueline Palace
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ABSTRACT: The development of therapeutic strategies that promote functional recovery is a major goal of multiple sclerosis (MS) research. Neuroscientific and methodological advances have improved our understanding of the brain's recovery from damage, generating novel hypotheses about potential targets and modes of intervention, and laying the foundation for development of scientifically informed recovery-promoting strategies in interventional studies. This Review aims to encourage the transition from characterization of recovery mechanisms to development of strategies that promote recovery in MS. We discuss current evidence for functional reorganization that underlies recovery and its implications for development of new recovery-oriented strategies in MS. Promotion of functional recovery requires an improved understanding of recovery mechanisms that can be modulated by interventions and the development of robust measurements of therapeutic effects. As imaging methods can be used to measure functional and structural alterations associated with recovery, this Review discusses their use to obtain reliable markers of the effects of interventions.
Nature Reviews Neurology 09/2012; · 12.46 Impact Factor
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ABSTRACT: OBJECTIVE: . To investigate metabolic changes within the spinal cord using proton magnetic resonance spectroscopy ((1)H-MRS) and determine their relationship with clinical function in patients with complete brachial plexus avulsion who underwent reimplantation of the ventral roots. METHODS: . Single-voxel (1)H-MRS of the cord between C1 and C3 was performed in 10 patients with normal spinal cord on MRI, who underwent reimplantation of C5 to T1 ventral roots on average 5.5 years earlier, and 19 healthy controls. The ratios of the concentrations of the following main metabolites, with respect to total creatine levels, were obtained: total N-acetyl-aspartate, choline-containing compounds, creatine and phosphocreatine (Cr), and myo-inositol (m-Ins). Patient disability was assessed using upper limb scales. Differences in metabolite concentration ratios and their correlations with disability were investigated. RESULTS: . Patients showed increased m-Ins/Cr ratio compared with controls, which was associated with the level of function of the affected arm and time from injury. CONCLUSIONS: . The finding of increased m-Ins/Cr in patients suggests that reactive gliosis, perhaps in response to the degeneration of avulsed fibers, may occur in the spinal cord above the site of injury and be relevant to motor dysfunction. However, this pathological process appears to diminish with time. These insights underline the need to integrate metabolic imaging with structural and functional magnetic resonance imaging to obtain a complete view of spinal cord plasticity. Last, this study provides the first steps toward identifying markers to serve as outcome measures for trials comparing strategies of plexus repair following avulsion injury.
Neurorehabilitation and neural repair 09/2012; · 4.49 Impact Factor
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ABSTRACT: Rating scales are increasingly used in neurologic research and trials. A key question relating to their use across the range of neurologic diseases, both common and rare, is what sample sizes provide meaningful estimates of reliability and validity. Here, we address two questions: (1) to what extent does sample size influence the stability of reliability and validity estimates; and (2) to what extent does sample size influence the inferences made from reliability and validity testing? We examined data from two studies. In Study 1, we retrospectively reduced the total sample randomly and nonrandomly by decrements of approximately 50 % to generate sub-samples from n = 713-20. In Study 2, we prospectively generated sub-samples from n = 20-320, by entry time into study. In all samples we estimated reliability (internal consistency, item total correlations, test-retest) and validity (within scale correlations, convergent and discriminant construct validity). Reliability estimates were stable in magnitude and interpretation in all sub-samples of both studies. Validity estimates were stable in samples of n ≥ 80, for 75 % of scales in samples of n = 40, and for 50 % of scales in samples of n = 20. In this study, sample sizes of a minimum of 20 for reliability and 80 for validity provided estimates highly representative of the main study samples. These findings should be considered provisional and more work is needed to determine if these estimates are generalisable, consistent, and useful.
Journal of Neurology 06/2012; · 3.47 Impact Factor
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ABSTRACT: Traumatic spinal cord injury (SCI) leads to disruption of axonal architecture and macroscopic tissue loss with impaired information flow between the brain and spinal cord-the presumed basis of ensuing clinical impairment.
The authors used a clinically viable, multimodal MRI protocol to quantify the axonal integrity of the cranial corticospinal tract (CST) and to establish how microstructural white matter changes in the CST are related to cross-sectional spinal cord area and cortical reorganisation of the sensorimotor system in subjects with traumatic SCI.
Nine volunteers with cervical injuries resulting in bilateral motor impairment and 14 control subjects were studied. The authors used diffusion tensor imaging to assess white matter integrity in the CST, T1-weighted imaging to measure cross-sectional spinal cord area and functional MRI to compare motor task-related brain activations. The relationships among microstructural, macrostructural and functional measures were assessed using regression analyses. Results Diffusion tensor imaging revealed significant differences in the CST of SCI subjects-compared with controls-in the pyramids, the internal capsule, the cerebral peduncle and the hand area. The microstructural white matter changes observed in the left pyramid predicted increased task-related responses in the left M1 leg area, while changes in the cerebral peduncle were predicted by reduced cord area.
The observed microstructural changes suggest trauma-related axonal degeneration and demyelination, which are related to cortical motor reorganisation and macrostructure. The extent of these changes may reflect the plasticity of motor pathways associated with cortical reorganisation. This clinically viable multimodal imaging approach is therefore appropriate for monitoring degeneration of central pathways and the evaluation of treatments targeting axonal repair in SCI.
Journal of neurology, neurosurgery, and psychiatry 04/2012; 83(6):629-37. · 4.87 Impact Factor
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ABSTRACT: We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
Human Brain Mapping 02/2012; · 5.88 Impact Factor
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Peter Connick,
Madhan Kolappan,
Charles Crawley,
Daniel J Webber,
Rickie Patani,
Andrew W Michell,
Ming-Qing Du,
Shi-Lu Luan,
Daniel R Altmann, Alan J Thompson,
Alastair Compston,
Michael A Scott,
David H Miller,
Siddharthan Chandran
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ABSTRACT: More than half of patients with multiple sclerosis have progressive disease characterised by accumulating disability. The absence of treatments for progressive multiple sclerosis represents a major unmet clinical need. On the basis of evidence that mesenchymal stem cells have a beneficial effect in acute and chronic animal models of multiple sclerosis, we aimed to assess the safety and efficacy of these cells as a potential neuroprotective treatment for secondary progressive multiple sclerosis.
Patients with secondary progressive multiple sclerosis involving the visual pathways (expanded disability status score 5·5-6·5) were recruited from the East Anglia and north London regions of the UK. Participants received intravenous infusion of autologous bone-marrow-derived mesenchymal stem cells in this open-label study. Our primary objective was to assess feasibility and safety; we compared adverse events from up to 20 months before treatment until up to 10 months after the infusion. As a secondary objective, we chose efficacy outcomes to assess the anterior visual pathway as a model of wider disease. Masked endpoint analyses was used for electrophysiological and selected imaging outcomes. We used piecewise linear mixed models to assess the change in gradients over time at the point of intervention. This trial is registered with ClinicalTrials.gov, number NCT00395200.
We isolated, expanded, characterised, and administered mesenchymal stem cells in ten patients. The mean dose was 1·6×10(6) cells per kg bodyweight (range 1·1-2·0). One patient developed a transient rash shortly after treatment; two patients had self-limiting bacterial infections 3-4 weeks after treatment. We did not identify any serious adverse events. We noted improvement after treatment in visual acuity (difference in monthly rates of change -0·02 logMAR units, 95% CI -0·03 to -0·01; p=0·003) and visual evoked response latency (-1·33 ms, -2·44 to -0·21; p=0·020), with an increase in optic nerve area (difference in monthly rates of change 0·13 mm(2), 0·04 to 0·22; p=0·006). We did not identify any significant effects on colour vision, visual fields, macular volume, retinal nerve fibre layer thickness, or optic nerve magnetisation transfer ratio.
Autologous mesenchymal stem cells were safely given to patients with secondary progressive multiple sclerosis in our study. The evidence of structural, functional, and physiological improvement after treatment in some visual endpoints is suggestive of neuroprotection.
Medical Research Council, Multiple Sclerosis Society of Great Britain and Northern Ireland, Evelyn Trust, NHS National Institute for Health Research, Cambridge and UCLH Biomedical Research Centres, Wellcome Trust, Raymond and Beverly Sackler Foundation, and Sir David and Isobel Walker Trust.
The Lancet Neurology 02/2012; 11(2):150-6. · 23.46 Impact Factor
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ABSTRACT: Traumatic spinal cord injury (SCI) leads to disruption of axons and macroscopic tissue loss. Using diffusion tensor imaging (DTI), we assessed degeneration of the corticospinal tract (CST) in the cervical cord above a traumatic lesion and explored its relationship with cervical atrophy, remote axonal changes within the cranial CST and upper limb function.
Nine cervical injured volunteers with bilateral motor and sensory impairment and ten controls were studied. DTI of the cervical cord and brain provided measurements of fractional anisotropy (FA), while anatomical MRI assessed cross-sectional spinal cord area (i.e. cord atrophy). Spinal and central regions of interest (ROI) included the bilateral CST in the cervical cord and brain. Regression analysis identified correlations between spinal FA and cranial FA in the CST and disability.
In individuals with SCI, FA was significantly lower in both CSTs throughout the cervical cord and brain when compared with controls (p≤0.05). Reduced FA of the cervical cord in patients with SCI was associated with smaller cord area (p = 0.002) and a lower FA of the cranial CST at the internal capsule level (p = 0.001). Lower FA in the cervical CST also correlated with impaired upper limb function, independent of cord area (p = 0.03).
Axonal degeneration of the CST in the atrophic cervical cord, proximal to the site of injury, parallels cranial CST degeneration and is associated with disability. This DTI protocol can be used in longitudinal assessment of microstructural changes immediately following injury and may be utilised to predict progression and monitor interventions aimed at promoting spinal cord repair.
PLoS ONE 01/2012; 7(12):e51729. · 4.09 Impact Factor
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ABSTRACT: Functional imaging studies, using blood oxygen level-dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS) to non-invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1-weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma-related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor-evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r(2) ≥ 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.
European Journal of Neuroscience 11/2011; 34(11):1839-46. · 3.63 Impact Factor
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ABSTRACT: Intravenous steroids are routinely used to treat disabling relapses in multiple sclerosis (MS). Theoretically, the infusion could take place at home, rather than in hospital. Findings from other patient populations suggest that patients may find the experiences of home relapse management more desirable. However, formal comparison of these two settings, from the patients' point of view, was prevented by the lack of a clinical scale. We report the development of a rating scale to measure patient's experiences of relapse management that allowed this question to be answered confidently.
Scale development had three stages. First, in-depth interviews of 21 MS patients generated a conceptual model and pool of potential scale items. Second, these items were administered to 160 people with relapsing-remitting MS. Standard psychometric techniques were used to develop a scale. Third, the psychometric properties of the scale were evaluated in a randomised controlled trial of 138 patients whose relapses were managed either at home or hospital.
A preliminary conceptual model with eight dimensions, and a pool of 154 items was generated. From this we developed the MS Relapse Management Scale (MSRMS), a 42-item with four subscales: access to care (6 items), coordination of care (11 items), information (7 items), interpersonal care (18 items). The MSRMS subscales satisfied most psychometric criteria but had notable floor effects.
The MSRMS is a reliable and valid measure of patients' experiences of MS relapse management. The high floor effects suggest most respondents had positive care experiences. Results demonstrate that patients' experiences of relapse management can be measured, and that the MSRMS is a powerful tool for determining which services to develop, support and ultimately commission.
Health and Quality of Life Outcomes 09/2011; 9:80. · 2.11 Impact Factor
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ABSTRACT: Nearly 100 cases of atopic myelitis have been reported in Japan. However, it has only been described in two non-Japanese patients, both from Western Europe. We report a European individual who developed cervical myelitis while resident in Japan. This showed a partial response to corticosteroids. There was no clinical or radiological dissemination for over 5 years, at which time she had a brainstem relapse caused by a new lesion in the medulla oblongata. The patient had high serum total IgE with evidence of allergy to several antigens, including house dust mite and soya. It is possible that the incidence of atopic myelitis may be underestimated where it is not standard practice to measure serum IgE levels in patients with myelopathy. Such cases will instead be subsumed into the diagnostic category of clinically isolated syndrome. However, it remains uncertain whether atopic myelitis is a distinct disease or falls within the spectrum of demyelinating diseases. Further studies are required to fully elucidate the relationship between atopy and the incidence and severity of CNS inflammatory disorders.
Journal of neurology, neurosurgery, and psychiatry 09/2011; 82(9):1022-4. · 4.87 Impact Factor
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ABSTRACT: The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.
Brain 06/2011; 134(Pt 6):1610-22. · 9.46 Impact Factor
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Peter Connick,
Madhan Kolappan,
Rickie Patani,
Michael A Scott,
Charles Crawley,
Xiao-Ling He,
Karen Richardson,
Kelly Barber,
Daniel J Webber,
Claudia A M Wheeler-Kingshott, [......],
Rebecca S Samson,
David L Thomas,
Ming-Qing Du,
Shi L Luan,
Andrew W Michell,
Daniel R Altmann, Alan J Thompson,
David H Miller,
Alastair Compston,
Siddharthan Chandran
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ABSTRACT: No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach".
MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway.
Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm.
In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability.
ClinicalTrials.gov (NCT00395200).
Trials 03/2011; 12:62. · 2.02 Impact Factor
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Chris H Polman,
Stephen C Reingold,
Brenda Banwell,
Michel Clanet,
Jeffrey A Cohen,
Massimo Filippi,
Kazuo Fujihara,
Eva Havrdova,
Michael Hutchinson,
Ludwig Kappos,
Fred D Lublin,
Xavier Montalban,
Paul O'Connor,
Magnhild Sandberg-Wollheim, Alan J Thompson,
Emmanuelle Waubant,
Brian Weinshenker,
Jerry S Wolinsky
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ABSTRACT: New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.
Annals of Neurology 02/2011; 69(2):292-302. · 11.09 Impact Factor
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ABSTRACT: Non-arteritic anterior ischaemic optic neuropathy (NA-AION) can cause disabling visual loss and traditionally, visual prognosis has been considered poor, although recent studies have demonstrated improvements in visual acuity in about 30% of patients over time. The aim of the study was to determine whether there was significant cortical reorganisation with functional MRI (fMRI) after acute NA-AION by comparing affected individuals with healthy controls.
9 patients with NA-AION were studied acutely and then after 1, 2, 3 and 6 months. 23 healthy volunteers underwent scanning at least twice. At each time point, patients were assessed clinically and with fMRI. For the fMRI experiments, subjects underwent monocular visual stimulation (wearing goggles with flashing LED displays).
When stimulating the affected eye, occipital activation was reduced in patients compared with controls. Also, within the NA-AION group, activation in the right Brodmann areas (BA) 44 and 45 was seen during the early phase of the condition. The same areas were activated within the NA-AION group several months later for fellow eye stimulation. When the NA-AION and healthy control groups were formally compared however, these areas (BA 44/45) were not significantly different. NA-AION subjects did show greater activation in visual related areas compared with controls when stimulating the fellow eye. Visual acuity was correlated with more occipital cortex activation when stimulating the affected eye.
There is cortical re-organisation of the fMRI response in extra-visual areas, seen when both affected and fellow eyes are stimulated after NA-AION.
Journal of neurology, neurosurgery, and psychiatry 02/2011; 82(8):905-13. · 4.87 Impact Factor
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Annals of Neurology 01/2011; 69(1):11-2. · 11.09 Impact Factor
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ABSTRACT: Management of symptoms in multiple sclerosis (MS) has received little attention compared with disease-modifying treatments. However, the effect of these symptoms on quality of life can be profound. Clinical trials of pharmacological drugs to treat symptoms of MS have often been underpowered and have used inappropriate measures of outcome. Many currently used symptomatic drugs were introduced decades ago, when study quality was considerably below current standards. Therefore, the evidence base on which to make clinical decisions is less than adequate. Interest in pharmacological treatment of symptoms in MS has increased in recent years, and several large randomised controlled trials have been reported. Pharmacological strategies are a core component of the treatment of these symptoms, but it is imperative to remember that a multidisciplinary rehabilitation approach is needed for effective management.
The Lancet Neurology 12/2010; 9(12):1182-99. · 23.46 Impact Factor
