Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
J Neurol ; 264(2): 316-326, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27896433

ABSTRACT

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p < 0.01). Lower average daily step count was associated with greater disability on the Expanded Disability Status Scale (EDSS) (p < 0.001). Within each EDSS category, substantial variability in step count was apparent (i.e., EDSS = 6.0 range 1097-7152). Step count demonstrated moderate-strong correlations with other walking measures. Lower average daily step count is associated with greater MS disability and captures important variability in real-world walking activity otherwise masked by standard disability scales, including the EDSS. These results support remote step count monitoring as an exploratory outcome in MS trials.


Subject(s)
Accelerometry/methods , Disability Evaluation , Multiple Sclerosis, Chronic Progressive/diagnosis , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Telemedicine/methods , Walking , Biomechanical Phenomena , Female , Humans , Male , Middle Aged , Monitoring, Ambulatory/methods , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Prospective Studies , Reproducibility of Results , Walking/physiology
2.
Neurology ; 76(21): 1824-30, 2011 May 24.
Article in English | MEDLINE | ID: mdl-21606454

ABSTRACT

OBJECTIVE: To evaluate whether vitamin D is associated with multiple sclerosis (MS) status and disease severity in African Americans. METHODS: Serum 25-hydroxyvitamin D was compared in a cross-sectional sample of 339 African Americans with MS and 342 African American controls. Correlations between disease severity (Multiple Sclerosis Severity Score [MSSS]) and 25-hydroxyvitamin D levels were sought. RESULTS: A total of 71% of controls and 77% of patients with MS were vitamin D deficient (<50 nmol/L; <20 ng/mL), and 93% of controls and 94% of patients with MS were vitamin D insufficient (<75 nmol/L; <30 ng/mL). Median unadjusted (29.7 vs 36.6 nmol/L, p = 0.0001) and deseasonalized (p = 0.0013) 25-hydroxyvitamin D levels were lower in the MS group. Multivariable analysis revealed that differences in latitude and ultraviolet index accounted for much of this association. The median (interquartile range) MSSS was 6.1 (4.8-8.1). There was no apparent association between the MSSS and vitamin D status. A greater proportion of European genetic ancestry, a measure of genetic admixture, was positively correlated with 25-hydroxyvitamin D (p = 0.007). CONCLUSIONS: Levels of 25-hydroxyvitamin D were lower in African Americans with MS than controls, an observation primarily explained by differences in climate and geography. There was no apparent association between vitamin D status and disease severity. These results are consistent with observations in other populations that lower 25-hydroxyvitamin D is associated with having MS, but also highlight the importance of climate and ancestry in determining vitamin D status.


Subject(s)
Black or African American , Multiple Sclerosis/blood , Multiple Sclerosis/physiopathology , Vitamin D/blood , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index , Vitamin D Deficiency/blood
3.
Neurology ; 76(8): 686-92, 2011 Feb 22.
Article in English | MEDLINE | ID: mdl-21270417

ABSTRACT

BACKGROUND: Technological advancements in neuroimaging and the increased use of these diagnostic modalities are responsible for the discovery of incidentally identified anomalies within the CNS. In addition to the identification of unanticipated brain MRI abnormalities suggestive of demyelinating disease in patients undergoing neuroimaging for a medical reason other than evaluation for multiple sclerosis (MS), asymptomatic spinal cord lesions are periodically identified. OBJECTIVE: To determine if asymptomatic spinal cord lesions are associated with clinical progression in subjects with radiologically isolated syndrome (RIS). METHODS: A retrospective review of RIS cases at the University of California, San Francisco Multiple Sclerosis Center was performed. The presence of asymptomatic cervical spinal cord MRI lesions was analyzed as a potential predictor for clinical progression. RESULTS: Twenty-five of 71 subjects with RIS possessed findings within the cervical spine that were highly suggestive of demyelinating disease. Of these subjects, 21 (84%) progressed clinically to clinically isolated syndrome (n = 19) or primary progressive multiple sclerosis (n = 2) over a median time of 1.6 years from the date of RIS identification (interquartile range 0.8-3.8). The sensitivity, specificity, and positive predictive value of an asymptomatic spinal cord lesion for subsequent development of either a first demyelinating attack or primary progressive MS were 87.5%, 91.5%, and 84%, respectively. The odds ratio of clinical progression was 75.3 (95% confidence interval 16.1-350.0, p < 0.0001). This association remained significant after adjusting for potential confounders. CONCLUSION: These findings suggest that the presence of asymptomatic spinal cord lesions place subjects with RIS at substantial risk for clinical conversion to either an acute or progressive event, a risk that is independent of brain lesions on MRI.


Subject(s)
Brain/pathology , Functional Laterality/physiology , Magnetic Resonance Imaging , Spinal Cord Injuries/diagnosis , Spinal Cord/pathology , Adult , Aged , Cohort Studies , Disease Progression , Female , Humans , Logistic Models , Male , Middle Aged , Predictive Value of Tests , ROC Curve , Retrospective Studies , Spinal Cord Injuries/physiopathology , Young Adult
4.
J Neurol Neurosurg Psychiatry ; 80(9): 1002-5, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19465415

ABSTRACT

PATIENTS AND METHODS: This is a cross sectional study comparing the retinal features of optic neuritis (ON) between 20 multiple sclerosis (MS) and 16 neuromyelitis optica (NMO) patients with a history of ON (visual acuity at time of attack >20/100) matched for age and gender using optical coherence tomography (OCT) and fundoscopy. RESULTS: Compared with MS, NMO patients often had: (1) vascular changes, including attenuation of the peripapillary vascular tree (3/40 MS eyes, 22/32 NMO eyes; p = 0.001) and focal arteriolar narrowing (0/40 MS eyes and 9/32 NMO eyes; p<0.0001), (2) a lower average nerve fibre layer (NFL) thickness (59.2 microm compared with 82.0 microm in MS; p = 0.004) and (3) nearly twice the NFL thinning after controlling for final visual acuity (32.1 vs 17.6 microm; p = 0.004). Patients with NMO had more severe and diffuse axonal injury of the NFL compared with MS. CONCLUSION: These NFL and fundoscopic findings suggest that some of the injury seen in NMO may be vascularly mediated. These inner retinal vascular changes are reminiscent of blood vessel wall thickening previously reported in the optic nerve and spinal cord at autopsy. If the retinal changes share a common pathology to those in the spinal cord and optic nerve, these observations suggest that vascular changes may be detectable during life.


Subject(s)
Nerve Fibers/pathology , Neuromyelitis Optica/pathology , Optic Neuritis/pathology , Retina/pathology , Retinal Vessels/pathology , Adult , Arterioles/pathology , Axons/pathology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Ophthalmoscopy , Optic Disk/pathology , Tomography, Optical Coherence , Visual Acuity
5.
Brain ; 132(Pt 1): 250-9, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19022862

ABSTRACT

Genetic susceptibility to multiple sclerosis (MS) is associated with the human leukocyte antigen (HLA) DRB1*1501 allele. Here we show a clear association between DRB1*1501 carrier status and four domains of disease severity in an investigation of genotype-phenotype associations in 505 robust, clinically well characterized MS patients evaluated cross-sectionally: (i) a reduction in the N-acetyl-aspartate (NAA) concentration within normal appearing white matter (NAWM) via (1)HMR spectroscopy (P = 0.025), (ii) an increase in the volume of white matter (WM) lesions utilizing conventional anatomical MRI techniques (1,127 mm(3); P = 0.031), (iii) a reduction in normalized brain parenchymal volume (nBPV) (P = 0.023), and (iv) impairments in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT-3) performance (Mean Z Score: DRB1*1501+: 0.110 versus DRB1*1501-: 0.048; P = 0.004). In addition, DRB1*1501+ patients had significantly more women (74% versus 63%; P = 0.009) and a younger mean age at disease onset (32.4 years versus 34.3 years; P = 0.025). Our findings suggest that DRB1*1501 increases disease severity in MS by facilitating the development of more T2-foci, thereby increasing the potential for irreversible axonal compromise and subsequent neuronal degeneration, as suggested by the reduction of NAA concentrations in NAWM, ultimately leading to a decline in brain volume. These structural aberrations may explain the significant differences in cognitive performance observed between DRB1*1501 groups. The overall goal of a deep phenotypic approach to MS is to develop an array of meaningful biomarkers to monitor the course of the disease, predict future disease behaviour, determine when treatment is necessary, and perhaps to more effectively recommend an available therapeutic intervention.


Subject(s)
HLA-DR Antigens/genetics , Multiple Sclerosis/genetics , Adolescent , Adult , Aged , Brain/pathology , Cognition Disorders/etiology , Female , Genetic Predisposition to Disease , Genotype , HLA-DRB1 Chains , Heterozygote , Histocompatibility Testing/methods , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Male , Middle Aged , Multiple Sclerosis/pathology , Multiple Sclerosis/psychology , Neuropsychological Tests , Phenotype , Prospective Studies , Young Adult
6.
Genes Immun ; 7(4): 310-5, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16625214

ABSTRACT

Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene-gene interactions and disease susceptibility in a well-characterized African-American case-control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76% accuracy (P<0.01). These results demonstrate the importance of exploring both main effects and gene-gene interactions in the study of complex diseases.


Subject(s)
Black or African American/genetics , Genetic Predisposition to Disease , Lipopolysaccharide Receptors/genetics , Multifactorial Inheritance , Multiple Sclerosis/genetics , Receptors, Interleukin-4/genetics , Receptors, Interleukin/genetics , Case-Control Studies , Epistasis, Genetic , Female , Gene Deletion , Genotype , Humans , Interleukin-5 Receptor alpha Subunit , Male , Multiple Sclerosis/immunology , Polymorphism, Genetic , Polymorphism, Single Nucleotide
7.
Arch Neurol ; 62(9): 1345-56, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16157741

ABSTRACT

Major advancements have been achieved in our ability to diagnose multiple sclerosis (MS) and to commence treatment intervention with agents that can favorably affect the disease course. Although MS exacerbations and the emergence of disability constitute the more conspicuous aspects of the disease process, evidence has confirmed that most of the disease occurs on a constitutive and occult basis. Disease-modifying therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive stage of the disease. Therapeutic strategies currently used for MS primarily target the inflammatory cascade. Several potential mechanisms appear to be involved in the progression of MS. Characterizing these mechanisms will result in a better understanding of the various forms of the disorder and how to effectively treat its clinical manifestations. It is our objective within this 2-part series on progression in MS to offer both evidence-based observations and hypothesis-driven expert perspectives on what constitutes the cause of progression in MS. We have chosen areas of inquiry that appear to have been most productive in helping us to better conceptualize the landscape of what MS looks like pathologically, immunologically, neuroscientifically, radiographically, and genetically. We have attempted to advance hypotheses focused on a deeper understanding of what contributes to the progression of this illness and to illustrate new technical capabilities that are catalyzing novel research initiatives targeted at achieving a more complete understanding of progression in MS.


Subject(s)
Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Multiple Sclerosis/physiopathology , Disease Progression , Genetics , Humans , Immune System/physiopathology , Models, Biological , Multiple Sclerosis/genetics , Neurosciences
8.
Neurology ; 64(7): 1270-2, 2005 Apr 12.
Article in English | MEDLINE | ID: mdl-15824362

ABSTRACT

Eight patients with worsening neuromyelitis optica were treated with rituximab to achieve B cell depletion. Treatment was well tolerated. Six of eight patients were relapse free and median attack rate declined from 2.6 attacks/patient/year to 0 attacks/patient/year (p = 0.0078). Seven of eight patients experienced substantial recovery of neurologic function over 1 year of average follow-up. The pretreatment median Expanded Disability Status Scale score was 7.5, and at follow-up examination was 5.5 (p = 0.013).


Subject(s)
Antibodies, Monoclonal/administration & dosage , Immunologic Factors/administration & dosage , Neuromyelitis Optica/drug therapy , Adult , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Disability Evaluation , Female , Humans , Immunologic Factors/adverse effects , Lymphocyte Count , Male , Myelitis, Transverse/drug therapy , Myelitis, Transverse/immunology , Myelitis, Transverse/physiopathology , Neuromyelitis Optica/immunology , Neuromyelitis Optica/physiopathology , Optic Nerve/drug effects , Optic Nerve/immunology , Optic Nerve/physiopathology , Optic Neuritis/drug therapy , Optic Neuritis/immunology , Optic Neuritis/physiopathology , Recovery of Function/drug effects , Recovery of Function/immunology , Rituximab , Secondary Prevention , Spinal Cord/drug effects , Spinal Cord/immunology , Spinal Cord/physiopathology , Treatment Outcome
9.
Neurology ; 63(11): 2039-45, 2004 Dec 14.
Article in English | MEDLINE | ID: mdl-15596747

ABSTRACT

BACKGROUND: African American (AA) individuals are thought to develop multiple sclerosis (MS) less frequently than Caucasian American (CA) individuals. OBJECTIVE: To compare the clinical characteristics of AA and CA patients with MS. METHODS: The clinical features of MS were compared in a large retrospective cohort of AA (n = 375) and CA (n = 427) subjects. RESULTS: The proportion of women to men was similar in AA and CA subjects (81% [AA] vs 77% [CA]; p = 0.122). There were no differences in the proportions of subjects with relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing MS. The median time to diagnosis was 1 year after symptom onset in AA subjects and 2 years after symptom onset in CA subjects (p = 0.0013). The age at onset was approximately 2.5 years later in AA than CA subjects (33.7 vs 31.1 years; p = 0.0001). AA subjects presented with multisite signs and symptoms at disease onset more often than CA subjects (p = 0.018). Clinical involvement restricted to the optic nerves and spinal cord (opticospinal MS) occurred in 16.8% of AA patients compared with 7.9% of CA patients (p < 0.001). Transverse myelitis also occurred more frequently in AA subjects (28 vs 18%; p = 0.001). Survival analysis revealed that AA subjects were at higher risk for development of ambulatory disability than CA subjects. After adjusting for baseline variations and differences in therapeutic interventions, AAs were at 1.67-fold greater risk for requiring a cane to ambulate than CA patients (p < 0.001). There was a trend suggesting that AAs were also at greater risk for development of wheelchair dependency (p = 0.099). Adjusted Cox proportional hazard models showed that this effect was in part attributable to the older age at onset in AAs (p < 0.001). CONCLUSIONS: Compared with multiple sclerosis (MS) in Caucasian Americans, African American patients with MS have a greater likelihood of developing opticospinal MS and transverse myelitis and have a more aggressive disease course.


Subject(s)
Black or African American , Multiple Sclerosis/ethnology , White People , Adult , Age of Onset , Canes/statistics & numerical data , Cohort Studies , Female , Gait Disorders, Neurologic/ethnology , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/therapy , Health Services Accessibility/statistics & numerical data , Humans , Male , Multiple Sclerosis/complications , Multiple Sclerosis/therapy , Myelitis, Transverse/ethnology , Myelitis, Transverse/etiology , Optic Nerve Diseases/ethnology , Optic Nerve Diseases/etiology , Proportional Hazards Models , Retrospective Studies , Spinal Cord/physiopathology , Survival Analysis , United States/epidemiology , Wheelchairs/statistics & numerical data
SELECTION OF CITATIONS
SEARCH DETAIL
...