Biomedical subjects

Alan J Thompson

Publications and source records attributed to Alan J Thompson.

At least 37 records · Page 2Linked to original sources

PubMed2005

Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis.

Axonal loss is thought to be a likely cause of persistent disability after a multiple sclerosis relapse; therefore, noninvasive in vivo markers specific for axonal loss are needed. We used optic neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in the macula with optical coherence tomography. We studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. Optical coherence tomography measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. There were highly significant reductions (p < 0.001) of RNFL thickness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thickness and visual acuity, visual field, color vision, and visual-evoked potential amplitude. This study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect optic nerves from axonal loss.

Adult↗

PubMed2005

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria".

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.

Humans↗

PubMed2005

Optic radiation changes after optic neuritis detected by tractography-based group mapping.

Postmortem data suggest that trans-synaptic degeneration occurs in the lateral geniculate nucleus after optic nerve injury. This study investigated in vivo the optic radiations in patients affected by optic neuritis using fast marching tractography (FMT), a diffusion magnetic resonance imaging (MRI) fiber tracking method, and group mapping techniques, which allow statistical comparisons between subjects. Seven patients, 1 year after isolated unilateral optic neuritis, and ten age and gender-matched controls underwent whole-brain diffusion tensor MR imaging. The FMT algorithm was used to generate voxel-scale connectivity (VSC) maps in the optic radiations in each subject in native space. Group maps of the left and right optic radiations were created in the patient and control group in a standardized reference frame using statistical parametric mapping (SPM99). The reconstructed optic radiations in the patient group were localized more laterally in the posterior part of the tracts and more inferiorly than in the control group. Patients showed reduced VSC values in both tracts compared with controls. These findings suggest that the group mapping techniques might be used to assess changes in the optic radiations in patients after an episode of optic neuritis. The changes we have observed may be secondary to the optic nerve damage.

Adult↗

PubMed2005

Neurorehabilitation in multiple sclerosis: foundations, facts and fiction.

PURPOSE OF REVIEW: This review of recent work in the area of neurorehabilitation of multiple sclerosis patients surveys progress and underscores the need for further work to evaluate the effectiveness of treatments. RECENT FINDINGS: Several recent review documents have summarized the current position regarding neurorehabilitation and symptomatic management in multiple sclerosis. They have highlighted the paucity of evidence underpinning current practice, thereby identifying the need for more scientifically sound studies in both neurorehabilitation and symptomatic treatment. However, as will be apparent from this review, there has been a welcome increase in studies evaluating both aspects of neurorehabilitation and specific areas such as the role of cannabinoids in spasticity and pain and new treatments for cognitive impairment. SUMMARY: Overall, there is an encouraging trend both in questioning our current practice and in designing more scientifically sound trials incorporating new and more appropriate outcome measures. There is, however, much more to be done before we are in a position to provide the expert, comprehensive, joined-up, care that is required to meet the complex, ever-changing needs of patients with multiple sclerosis.

Cognition Disorders↗

PubMed2005

Primary progressive multiple sclerosis : current and future treatment options.

Approximately 10% of patients with multiple sclerosis (MS) run a primary progressive course characterised by an accumulation of neurological deficits without relapse or remission. Designing therapeutic trials in primary progressive MS (PPMS) has presented several problems. Patient recruitment may be difficult because of the relative rarity of PPMS and historically has been hindered by the lack of specific diagnostic criteria. There has been a limited choice of validated outcome measures, although, in recent studies, the MS functional composite measure and magnetic resonance imaging measures of lesion load and atrophy have been widely used. Despite these problems, several trials have been designed specifically for PPMS, including exploratory randomised controlled trials of interferon-beta-1a and interferon-beta-1b and mitoxantrone, a phase III trial of glatiramer acetate, and an open-label study of riluzole. Patients with PPMS have also been included in randomised controlled trials of azathioprine, methotrexate, cladribine, intravenous immunoglobulin and cyclophosphamide, and open-label studies of haematopoietic stem cell transplantation and pirfenidone in progressive MS. However, no treatment has been proven definitively to modify the course of the disease. Looking to the future, therapeutic agents should aim to target the underlying pathogenic mechanisms in PPMS. As a result of the relative lack of inflammation in PPMS, neuroprotective agents that target neuronal loss directly, rather than inflammation, may be more worthwhile. However, further investigation into the pathogenic mechanisms in PPMS is required to guide the development of future therapeutic agents.

Disease Progression↗

PubMed2004

Serum S100B in primary progressive multiple sclerosis patients treated with interferon-beta-1a.

S100B belongs to a family of calcium-binding proteins implicated in intracellular and extracellular regulatory activities. This study of serum S100B in primary progressive multiple sclerosis (PPMS) is based on data obtained from a randomized, controlled trial of Interferon beta-1a in subjects with PPMS. The key questions were whether S100B levels were associated with either disability or MRI findings in primary progressive MS and whether Interferon beta-1a has an effect on their S100B levels. Serial serum S100B levels were measured using an ELISA method. The results demonstrated that serum S100B is not related to either disease progression or MRI findings in subjects with primary progressive MS given Interferon beta-1a. Furthermore there is no correlation between S100B levels and the primary and secondary outcome measures.

Adult↗

PubMed2004

A serial MRI study following optic nerve mean area in acute optic neuritis.

This study assessed optic nerve mean area on serial MRI in a cohort of patients with a first episode of acute unilateral optic neuritis to assess the effects of a single acute inflammatory demyelinating lesion. Twenty-nine patients with a median delay from onset of visual symptoms of 13 days (range 7-24 days) were recruited. After a clinical examination and visual evoked potential (VEP) measurement, each patient had their optic nerves imaged with a coronal fat-saturated short echo fast fluid-attenuated inversion recovery sequence. Twenty-one patients had serial examinations after 2, 4, 8, 12, 26 and 52 weeks. In addition, 32 control subjects had their optic nerves imaged up to three times. The mean cross-sectional area of the intra-orbital portion of each optic nerve was calculated by a blinded observer using a computer-assisted contouring technique. At baseline, the mean area of diseased optic nerves was 16.1 mm2 compared with 13.4 mm2 for healthy contralateral optic nerves (20.1% higher, P < 0.0001) and 13.6 mm2 for controls (18.4% higher, P = 0.0003). The diseased optic nerve mean area declined over time, from initial swelling to later atrophy. The mean decline at 52 weeks was -0.0018 mm2/day (95% confidence interval -0.0038 to -0.00051). At 52 weeks, the mean area of diseased optic nerves was 11.3 mm2 compared with 12.8 mm2 for healthy contralateral optic nerves (11.7% lower, P = 0.032) and 13.1 mm2 for controls (13.7% lower, P = 0.008). The 52 week diseased optic nerve mean area was not significantly affected by the baseline mean area. There was an association between baseline optic nerve mean area and logMAR visual acuity (rS = 0.46, P = 0.012) and visual field mean deviation (rS = -0.55, P = 0.002), but there was no evidence of an association between 1 year mean area and visual outcome. There was no evidence of association between baseline, rates of decline or 1 year diseased optic nerve mean areas and any of the baseline, 1 year or time-averaged VEP variables. The present study shows a consistent pattern of changes associated with individual inflammatory demyelinating lesions in the optic nerve. Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to visual impairment. Over the longer term, there was loss of tissue. The lack of association between 1 year optic nerve mean area and visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.

Acute Disease↗

PubMed2004

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus.

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.

Adult↗

PubMed2004

Exploring rating scale responsiveness: does the total score reflect the sum of its parts?

Evaluating rehabilitation requires rating scales that detect change. The authors examined Barthel Index (BI) data from 1,495 patients at a neurorehabilitation unit to determine whether total scale responsiveness accurately reflects item responsiveness. Total score effect sizes were moderate to large (0.47 to 1.09). Item-level effect sizes (0.13 to 1.16) reveal floor (3.5 to 82.3%) and ceiling (9.7 to 95.4%) effects. Results suggest BI total score effect sizes may hide item-level weaknesses and may underestimate the impact of rehabilitation.

Activities of Daily Living↗

PubMed2004

Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes.

While brain atrophy occurs early in the clinical course of multiple sclerosis, exactly how early, which tissues are affected and the rate at which early atrophy occurs are unclear. Regional brain atrophy was investigated in 58 patients recruited within 3 months of onset of a clinically isolated syndrome (CIS) suggestive of multiple sclerosis, who were followed-up for 3 years. At 3 years, 31 subjects had developed multiple sclerosis as defined by the McDonald criteria, while 27 had not (13 had MRI-visible brain lesions and 14 did not). In those who developed multiple sclerosis, the mean decrease in grey matter fractional volume (GMF, as a fraction of total intracranial volume) was -0.017 (-3.3%) and was significantly larger than in the combined lesion-positive and lesion-negative CIS subjects [-0.005 (-1.1%), P = 0.001]. No decrease in white matter fractional volumes (WMF) was seen. Change in GMF correlated only modestly with the change in T2 lesion volume from baseline to year 3 (r = -0.428, P = 0.004). These results suggest that progressive grey matter, but not white matter, atrophy is seen in the earliest clinically observable stages of relapse onset multiple sclerosis, and this is only moderately related to lesion accumulation. Longer-term follow-up is required to determine whether early grey matter atrophy is associated with subsequent disability or cognitive impairment.

Adolescent↗

PubMed2004

Specificity of Barkhof criteria in predicting conversion to multiple sclerosis when applied to clinically isolated brainstem syndromes.

BACKGROUND: Barkhof criteria have been adopted to demonstrate dissemination in space in the new multiple sclerosis diagnostic criteria because of their high specificity for predicting conversion to multiple sclerosis. One of the 4 Barkhof criteria is the presence of an infratentorial lesion. In clinically isolated syndromes (CIS) of the brainstem (CISB), the infratentorial criterion does not demonstrate dissemination in space, raising the possibility that the criteria may be less specific in CISB, as compared with specificity in other CIS, in which all 4 criteria demonstrate dissemination in space. OBJECTIVE: To compare the validity indices of Barkhof criteria in CISB with those in other CIS. DESIGN: Inception cohort with median follow-up of 34 months for CISB and 40 months for other CIS. SETTING: Institutional ambulatory referral center. PATIENTS: A sample of 51 patients with CISB and 102 patients with other CIS (46 with myelitis and 56 with optic neuritis) was analyzed. Barkhof criteria, with a cutoff of 3 of 4, were applied to magnetic resonance imaging performed at baseline. Four combinations each containing 3 parameters were also applied, with a cutoff of 2 of 3. MAIN OUTCOME MEASURE: Specificity of unmodified Barkhof criteria and of the 4 combinations to predict conversion to clinically definite multiple sclerosis. RESULTS: The specificity of the criteria in CISB was 61% against 73% in other CIS. The combinations that retained the infratentorial lesion parameter had lower specificities in the CISB group; in analysis of the group with other CIS, no such differences were found. CONCLUSION: The infratentorial lesion criterion is responsible for the lower specificity of Barkhof criteria in CISB.

Adolescent↗

PubMed2004

The influence of time after stroke on brain activations during a motor task.

After stroke, the pattern of brain activation during performance of a motor task is related to outcome. Here, we compare this relationship in the early (10-14 days) and late (at least 3 months) phases after first-ever stroke. A negative linear relationship between task-related brain activation, as measured by functional magnetic resonance imaging, and outcome is seen in several identical primary and nonprimary motor regions that is independent of time after stroke. In other words, patients with poorer outcome scores recruit more widely within motor-related regions in both the early or late poststroke phase. However, in contralesional middle intraparietal sulcus, contralesional cerebellum, and ipsilesional rostral premotor cortex, this relationship is seen only in the early poststroke phase. Thus, patients with poorer outcome scores recruit these areas in only the early and not the late poststroke phase. These results suggest that there are differences in the cerebral implementation of action in patients with poor outcome that are dependent on the time since stroke. Thus, in those patients with the most to gain from rehabilitation, different therapeutic approaches may be required at different stages after stroke.

Adult↗

PubMed2004

Patient-based outcomes of cervical dystonia: a review of rating scales.

Decisions on treatment choice for patients are based on trials and outcome studies that are wholly dependent upon the scientific quality of the rating scales used. This study reviewed rating scales used in cervical dystonia outcome research to determine the extent that they satisfy recommended criteria for rigorous measurement.

Humans↗

PubMed2004

Visual recovery following acute optic neuritis--a clinical, electrophysiological and magnetic resonance imaging study.

This study reports the prospective follow-up of a cohort of patients with acute optic neuritis examined with serial visual tests, visual evoked potentials (VEPs), conventional and triple-dose gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) to examine which factors are important in visual recovery. Thirty-three patients were recruited with acute unilateral optic neuritis. A clinical and VEP assessment was performed on each. Optic nerve MRI was performed using fast spin echo (FSE) (on all) and triple-dose Gd-enhanced T1-weighted sequences (n = 28). Optic nerve lesion lengths were measured. Serial assessments were performed on 22 of the patients up to one-year. Serial Gd-enhanced optic nerve imaging was performed on 15 of the patients until enhancement ceased. The final 30-2 Humphrey visual field mean deviation (MD) was 2.55 dB higher in patients in the lowest quartile of initial Gd-enhanced lesion length compared with the other quartiles (p < 0.01) but recovery was not related to the duration of enhancement. The initial recovery of Humphrey MD was 4.60 dB units per day in patients with good eventual recoveries (MD > -6.0 dB) and 0.99 dB per day in poor-recovery patients (p = 0.02).Good-recovery patients had mean central field VEP amplitudes 2.29 microV higher during recovery than poor-recovery patients (p = 0.047). The results suggest that factors which are associated with a better prognosis are: having a short acute lesion on triple-dose gadolinium enhanced imaging, higher VEP amplitudes during recovery and a steep gradient of the initial improvement in vision.

Adult↗

PubMed2004

Patient dissatisfaction: insights into the rehabilitation process.

Most patients admitted for inpatient rehabilitation find it beneficial even when there is little change in physical disability. The aim of this study was to determine the characteristics of patients who felt that they had not benefited from inpatient rehabilitation and to delineate the underlying reasons for this perception. From a database of 331 patients admitted to a neurological rehabilitation unit over a three-year period, we ascertained those with a low score (< 5) on a self-rated visual analogue scale (VAS) regarding their perception of the benefit of rehabilitation. We investigated their disability outcomes, aspects of the rehabilitation process through analysis of integrated care pathways, and from inspection of the multidisciplinary record identified specific adverse factors which might contribute to dissatisfaction. Low VAS scores were detected in 6% of patients (n = 19). These did not correlate with baseline demographic factors or disability levels, but were associated with unresolved external problems regarding community care and accommodation, and conflicts between patients and therapists. We conclude that from the patients' perspective, successful inpatient rehabilitation depends on adequate attention given to community-based issues and health care professionals recognising patients' needs. When these two conditions are not fulfilled, patients are more likely to express a lack of satisfaction with their rehabilitation.

Humans↗

PubMed2004

Functional significance of the ipsilateral hemisphere during movement of the affected hand after stroke.

Previous fMRI observations have suggested increased task-related activation of the ipsilateral cerebral motor cortex in patients recovering from stroke. This is generally taken to infer an increased output from this area, although the functional relevance of this has been questioned. Here, we use directed EEG coherence to reveal whether there is increased informational flow from the ipsilateral motor cortex following motor stroke, and through correlation with degree of recovery, establish that this pattern of activity is associated with limited functional improvement. Unrecovered (n = 14), recovered (n = 11) patients and healthy subjects (n = 16) performed an isometric grip task with either hand that corresponded to 25% of individual maximum force, while EEG was recorded. For unrecovered stroke patients, most task-related information flow between the sensorimotor cortices in the low beta band of the EEG came from the ipsilateral (undamaged) hemisphere during grip with the affected hand. This was not the case when they gripped with their unaffected hand, when cortical activity was driven from the contralateral sensorimotor cortex. The latter pattern was also seen in recovered patients and controls. These findings suggest a functional role for the ipsilateral hemisphere in organizing movement of the impaired limb following stroke, but only in those patients that do not make a good functional recovery. Patients making a fuller recovery organize movement-related cortical activity from the hemisphere contralateral to movement.

Adolescent↗

PubMed2004

Characterizing function-structure relationships in the human visual system with functional MRI and diffusion tensor imaging.

A key objective in neuroscience is to improve our understanding of the relationship between brain function and structure. We investigated this in the posterior visual pathways of healthy volunteers by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) with tractography. The optic radiations were segmented using the Probabilistic Index of Connectivity (PICo) tractography algorithm and extracted at several thresholds of connection confidence. The mean fractional anisotropy (FA) of the estimated tracts was found to correlate significantly with fMRI measures of visual cortex activity (induced by a photic stimulation paradigm). The results support the hypothesis that the visual cortical fMRI response is constrained by the external anatomical connections of the subserving optic radiations.

Adult↗

PubMed2004

Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis.

BACKGROUND: There is little information available on grey and white matter (GM and WM) atrophy in primary progressive multiple sclerosis (PPMS) and on their relationships with clinical and other magnetic resonance imaging (MRI) measures. AIM: To evaluate disease progression in the early phase of PPMS, focusing on axonal loss as assessed by volumetric MRI measures of WM and GM, and to determine their relationships with clinical outcomes and lesion load measures. METHODS: Forty-three patients with PPMS within 5 years of symptom onset and 45 control subjects were studied. Three-dimensional brain scans were acquired and segmented into WM, GM, and cerebrospinal fluid (CSF) using SPM99. Brain parenchymal (BPF), WM (WMF), and GM fractions (GMF) normalized against total intracranial volumes were estimated. T2-weighted (T2) and enhancing lesion loads were also determined. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were recorded in all patients. RESULTS: There were significant differences between patients and controls in BPF, WMF, and GMF values (P < 0.001). BPF (r = -0.469; P = 0.002) and WMF (r = -0.532; P < 0.001) but not GMF (r = -0.195; P = 0.2) correlated with EDSS scores. BPF (r = 0.518; P = 0.001), WMF (r = 0.483; P = 0.001), and GMF (r = 0.337; P = 0.031) correlated with MSFC scores. Correlations with enhancing lesion and T2 loads were only significant for BPF and WMF. CONCLUSIONS: Brain atrophy is seen in the early stages of PPMS and affects both GM and WM. WM atrophy appears more closely related to clinical outcome and WM focal damage than GM atrophy in this patient group.

Adult↗