Randomized, Controlled Trial Of Cannabis-Based Medicine In Central Pain In Multiple Sclerosis
Rog DJ, Nurmikko TJ, Friede T, Young CA
Neurology 2005 Sep 27;65(6):812-9
University of Liverpool, Walton Centre for Neurology and NeuroSurgery, Liverpool, United Kingdom
Central Pain in Multiple Sclerosis (MS) is common and often refractory to treatment.
We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial.
In 66 patients with MS and Central Pain States (59 Dysesthetic, seven painful spasms) of a whole-plant Cannabis-Based Medicine (CBM), containing delta-9-TetraHydroCannabinol:Cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment.
Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours.
Sixty-four patients (97%) completed the trial, 34 received CBM.
In week 4, the mean number of daily sprays taken of CBM (n = 32) was 9.6 (range 2 to 25, SD = 6.0) and of placebo (n = 31) was 19.1 (range 1 to 47, SD = 12.9). Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale.
CBM was superior to placebo in reducing the mean intensity of pain (CBM mean change -2.7, 95% CI: -3.4 to -2.0, placebo -1.4 95% CI: -2.0 to -0.8, comparison between groups, p = 0.005) and sleep disturbance (CBM mean change -2.5, 95% CI: -3.4 to -1.7, placebo -0.8, 95% CI: -1.5 to -0.1, comparison between groups, p = 0.003).
CBM was generally well tolerated, although more patients on CBM than placebo reported dizziness, dry mouth, and somnolence. Cognitive side effects were limited to long-term memory storage.
Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with Multiple Sclerosis related central Neuropathic Pain and is mostly well tolerated.
The Association Between Cognitive Impairment And Physical Disability In Multiple Sclerosis
Lynch SG, Parmenter BA, Denney DR
Mult Scler 2005 Aug;11(4):469-76
University of Kansas Medical Center, Department of Neurology, Kansas City, KS 66160, USA
The association between Cognitive Impairment and physical disability was examined in a larger, more representative sample of patients with Multiple Sclerosis (MS) than in previous studies.
Two hundred and fifty-three patients attending an MS clinic were assessed with respect to physical disability using the Expanded Disability Status Scale and Cognitive Impairment using a battery of NeuroPsychological tests.
Physical disability correlated with duration of disease; Cognitive Impairment did not. Virtually all measures derived from the Cognitive Battery were significantly correlated with physical disability.
Three measures of speeded information processing and one involving delayed recall of verbal material were unique predictors of disability status.
The relationship between Cognitive Impairment and physical disability was equivalent for patients with shorter (< 3 years) versus longer (> 10 years) disease duration.
Cognitive Impairment correlated with the rate of disability progression as reflected by the progression Index.
Cognitive Impairment is more closely associated with physical disability than most previous studies indicate.
This relationship appears to be stable throughout the duration of MS, although this conclusion is qualified by the cross-sectional design of the study. Further attention should be paid to Cognitive Impairment as a possible predictor of the rate of patients' physical decline.
The Distribution Of The Magnetic Resonance Imaging Response To Glatiramer Acetate In Multiple Sclerosis
Sormani MP, Bruzzi P, Comi G, Filippi M
Mult Scler 2005 Aug;11(4):447-9
NeuroImaging Research Unit, Scientific Institute and University Ospedale San Raffaele, 20132 Milan, Italy
We investigated the distribution of the Magnetic Resonance Imaging (MRI)-measured response to Glatiramer Acetate (GA) treatment in Multiple Sclerosis (MS) using data from a clinical trial of Relapsing/Remitting (RR) MS.
A fixed and a random effects model were used to quantify the between-patient heterogeneity in treatment response, expressed as new enhancing lesion percentage reduction.
In 95% of the patients, lesion reduction due to treatment was estimated to range between -20% and -54%, indicating a rather homogeneous effect of GA on MRI-measured disease activity in RRMS.
Physical Activity And Multiple Sclerosis: A Meta-Analysis
Motl RW, McAuley E, Snook EM
Mult Scler 2005 Aug;11(4):459-63
University of Illinois, Department of Kinesiology, 332 Freer Hall, Urbana, IL 61801, USA
Using meta-analytic procedures, this study involved a quantitative synthesis of the difference in physical activity among individuals with Multiple Sclerosis (MS).
Compared with nondiseased and diseased populations and then examined factors (i.e., moderators) that explain variation in the overall difference in physical activity.
We searched MEDLINE, PsycINFO and Current Contents Plus using the key words physical activity, exercise and physical fitness in conjunction with Multiple Sclerosis.
Conducted a manual search of bibliographies of the retrieved papers, and contacted study authors about additional studies.
Overall, 53 effects were retrieved from 13 studies with 2360 MS participants and yielded a weighted mean effect size (ES) of -0.60 (95% CI = -0.44, -0.77). The weighted mean ES was heterogenous, Q = 1164.11, df = 52, P < 0.0001.
There were larger effects with objective versus self-report measures of physical activity, nondiseased versus diseased populations and Primary/Progressive versus Relapsing/Remitting MS.
The cumulative evidence suggests that individuals with MS are less physically active than nondiseased, but not diseased, populations.
Relationship Between Multiple Sclerosis Intention Tremor Severity And Lesion Load In The BrainStem
Feys P, Maes F, Nuttin B, Helsen W, Malfait V, Nagels G, Lavrysen A, Liu X
NeuroReport 2005 Aug 22;16(12):1379-1382
Katholieke Belgium National Multiple Sclerosis Center, Universiteit Leuven, Leuven, Melsbroek, Belgium NeuroScience and Psychological Medicine, Imperial College London, Departments of Biomedical Kinesiology Electrical Engineering (ESAT/PSI), Radiology Neurosciences and Psychiatry, UK
Intention Tremor due to Multiple Sclerosis is clinically similar to Cerebellar Tremor. This study investigated, in 14 Multiple Sclerosis patients, the relationship between Intention Tremor severity and the lesion load in different InfraTentorial regions.
Tremor amplitude was quantified during step-tracking tasks. The lesion load was measured on Magnetic Resonance Images using an automated segmentation method.
Intention Tremor amplitude was significantly related to lesion load in the BrainStem but not in the Cerebellum.
Specifically, Tremor amplitude correlated with the lesion load in the ContraLateral Pons, and patients with more severe Tremor in both arms had a greater lesion load BiLaterally in the Pons.
These results support the view that Multiple Sclerosis Intention Tremor is related to dysfunction of Cerebellar inflow and/or outflow pathways.
Pachner AR, Dail D, Pak E, Narayan K
J NeuroImmunol 2005 Sep;166(1-2):180-8
UMDNJ-New Jersey Medical School, Department of Neurology and NeuroSciences, 185 S. Orange Ave., Newark, N.J. 07103, USA
Many Multiple Sclerosis (MS) patients treated with IFN-ß develop Anti-IFN-ß AntiBodies, which can interfere with the bioactivity of the injected Cytokine, i.e., AntiBody-mediated decreased bioactivity (ADB).
The precise levels of Anti-IFN-ß AntiBodies inducing decreased bioactivity is unknown. We repeatedly used a bioactivity measure, gene expression of MxA or GEM, and correlated bioactivity with measures of binding and Neutralizing AntiBodies.
The binding AntiBody assay was a capture ELISA, and the Neutralizing AntiBody (NAB) assay was a Cytopathic Effect (CPE) assay. 27% (17/64) of patients repeatedly sampled developed critical ADB.
Bioactivity as determined by GEM correlated negatively with NAB titer, and bioactivity that had been lost with the development of NABs returned if NAB levels diminished.
These data reveal that the GEM assay is a useful adjunct in the management of MS patients treated with IFN-ß, and that lost bioactivity returns when Anti-IFN-ß AntiBody levels diminish.
A High-Density Screen For Linkage In Multiple Sclerosis
Sawcer S, Ban M, Maranian M, Yeo TW, Compston A, Kirby A, Daly MJ, De Jager PL, Walsh E, Lander ES, Rioux JD, Hafler DA, Ivinson A, Rimmler J, Gregory SG, Schmidt S, Pericak-Vance MA, Akesson E, Hillert J, Datta P, Oturai A, Ryder LP, Harbo HF, Spurkland A, Myhr KM, Laaksonen M, Booth D, Heard R, Stewart G, Lincoln R, Barcellos LF, Hauser SL, Oksenberg JR, Kenealy SJ, Haines JL
Am J Hum Genet 2005 Sep;77(3):454-67
International Multiple Sclerosis Genetics Consortium
To provide a definitive linkage map for Multiple Sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent.
After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis.
Multipoint nonparametric linkage analysis revealed highly significant linkage in the Major Histocompatibility Complex (MHC) on Chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on Chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18).
This set of markers achieved a mean information extraction of 79.3% across the Genome, with a Mendelian inconsistency rate of only 0.002%.
Stratification based on carriage of the Multiple Sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with Genomewide significance.
However, ordered-subset analysis suggested that there may be an additional locus on Chromosome 19p13 that acts independent of the main MHC locus.
These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for Multiple Sclerosis will have to involve large sample sizes and an association-based methodology.