Magnetic Resonance Imaging Of Gray Matter Damage In People With MS
Filippi M, Valsasina P, Rocca M
Int MS J 2007 Mar;14(1):12-21
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit,Department of Neurology, Via Olgettina 60, 20132 Milan, Italy
The classical view of MS as an Inflammatory-DeMyelinating condition affecting the White Matter (WM) of the Central Nervous System (CNS) has recently been challenged by the results of several Magnetic Resonance Imaging (MRI) studies.
These consistently show Gray Matter (GM) involvement, which correlates only moderately with the extent of WM pathology.
Here we summarize how conventional and modern imaging-based techniques have quantified GM damage in MS, in terms of focal lesions, diffuse tissue abnormalities and irreversible tissue loss.
Results from functional MRI studies, together with these new findings, are contributing to a significant change in our MS understanding.
MS is now viewed as a global CNS condition, affecting both WM and GM, which has an early and important NeuroDegenerative component.
Does High-Field MR Imaging Improve Cortical Lesion Detection In Multiple Sclerosis?
Geurts JJ, Blezer EL, Vrenken H, van der Toorn A, Castelijns JA, Polman CH, Pouwels PJ, Bö L, Barkhof F
J Neurol 2008 Feb 4
VU University Medical Center, Dept. of Radiology, room PK 0X-112, De Boelelaan 1117, 1081, HV Amsterdam, The Netherlands
Cortical Lesions in Multiple Sclerosis (MS) are notoriously difficult to visualize with standard MR imaging (MRI) techniques.
However, the use of higher field-strengths with intrinsically higher signal-to-noise, which can partly be used to increase spatial resolution, may improve Cortical lesion detection.
Therefore, in this post mortem study, the sensitivity of high fieldstrength MRI (4.7 T) for Cortical lesions was investigated, and compared to that of standard fieldstrength (1.5 T).
At 1.5 T, dual-echo T2-weighted Spin-Echo, as well as 3D-FLAIR images of seventeen formalin-fixed coronal MS and four control Hemispheres were acquired.
At 4.7 T, the same specimens were imaged with a mainly Proton-Density (PD)- weighted sequence.
ProteoLipid Protein (PLP)-stained tissue sections (10 mum) of the same Brain slices were matched to the corresponding MR images, and Cortical Lesions were scored on all three MR sequences (blinded to Histology) and in tissue sections (blinded to MRI).
Sensitivity of the sequences for four Cortical lesion types was calculated. Additionally, an unblinded, retrospective MR scoring was performed.
Sensitivity for purely IntraCortical lesions (histological lesion Types II, III, and IV; n = 128) was below 10 % for both 1.5 T and 4.7 T MRI, while mixed Gray Matter-White Matter (Type I) lesions (n = 5) were detected in four out of five cases.
All lesion counts increased upon retrospective (unblinded) scoring. However, up to 80% of the IntraCortical lesions still remained undetected.
MRI sensitivity for post mortem detection of Cortical lesions is low, even when a higher field-strength was used. It varies, however, for different subtypes of Cortical Lesions.
Intense ImmunoSuppression In Patients With Rapidly Worsening Multiple Sclerosis: Treatment Guidelines For The Clinician
Boster A, Edan G, Frohman E, Javed A, Stuve O, Tselis A, Weiner H, Weinstock-Guttman B, Khan O
Lancet Neurol 2008 Feb;7(2):173-83
Wayne State University School of Medicine, The Multiple Sclerosis Clinical Research Center, Department of Neurology, and The Detroit Medical Center, Detroit, MI, USA
Several lines of evidence link ImmunoSuppression to inflammation in patients with Multiple Sclerosis (MS) and provide a rationale for the increasing use of ImmunoSuppressive drugs in the treatment of MS.
Treatment-refractory, clinically active MS can quickly lead to devastating and irreversible Neurological disability and treating these patients can be a formidable challenge to the clinician.
Patients with refractory MS have been treated with intense ImmunoSuppression, such as Cyclophosphamide or Mitoxantrone, or with Autologous Haematopoeitic Stem Cell Transplants.
Evidence shows that intense ImmunoSuppression might be effective in patients who are unresponsive to ImmunoModulating Therapy, such as Interferon-ß and Glatiramer Acetate.
Natalizumab, a new addition to the armamentarium for treating MS, might also have a role in the treatment of this MS phenotype.
This Review describes the use of intense ImmunoSuppressant Drugs and Natalizumab in patients with rapidly worsening MS and provides clinicians with guidelines for the use of these drugs in this patient group.
Italian GITMO-Neuro Intergroup on ASCT for Multiple Sclerosis
Capello E, Saccardi R, Murialdo A, Gualandi F, Pagliai F, Bacigalupo A, Marmont A, Uccelli A, Inglese M, Bruzzi P, Sormani MP, Cocco E, Meucci G, Massacesi L, Bertolotto A, Lugaresi A, Merelli E, Solari A, Filippi M, Mancardi GL
Neurol Sci 2005 Dec;26 Suppl 4:S200-3
University of Genoa, Department of Neurological Sciences Ophthalmology and Genetics, Via De' Toni 5, I-16132, Genoa, Italy
Aggressive forms of Multiple Sclerosis (MS) represent a limited group of DeMyelinating Diseases that rapidly progress to severe disability.
Currently available therapies are poorly effective against these clinical entities.
Recently, it has been demonstrated that intense ImmunoSuppression followed by Autologous Haematopoietic Stem Cell Transplantation (AHSCT) can affect the clinical course of individuals with severe MS and completely abrogate the inflammatory activity detected by MRI.
We report the result of the Italian phase 2 GITMO study, a multicenter study in which 21 MS patients, who were rapidly deteriorating and not responding to the usual therapeutic strategies, were treated with this procedure.
The clinical effect of the treatment is long lasting, with a striking abrogation of inflammation detected by MRI findings.
These results support a role for intense ImmunoSuppression followed by ASCT as treatment in rapidly evolving MS cases unresponsive to conventional therapies.
Long-Term Benefits Of Exercising On Quality Of Life And Fatigue In Multiple Sclerosis Patients With Mild Disability: A Pilot Study
McCullagh R, Fitzgerald AP, Murphy RP, Cooke G
Clin Rehabil 2008 Mar;22(3):206-14
Trinity College Dublin, Discipline of Physiotherapy, Faculty of Health Sciences, St James' Site
To determine if exercise benefits patients with Multiple Sclerosis.
Design & Settings
A randomized controlled trial, participants exercised at home and also attended exercise classes held in a hospital physiotherapy gym.
Thirty patients, diagnosed and independently mobile, were recruited in the Dublin area.
For three months, classes were held twice-weekly and participants exercised independently once-weekly. The control group was monitored monthly and management remained unchanged.
Measurements were taken at baseline, three and six months.
The Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Impact Scale-29 (MSIS-29) and Functional Assessment of Multiple Sclerosis (FAMS) were used to measure Fatigue and Quality Of Life (QOL).
Heart Rate (HR) and the Borg's Rating of Perceived Exertion (RPE) were recorded during an incremental exercise test. The change from baseline scores between groups was compared using the Mann-Whitney U-test.
Twenty-four participants completed the program (n = 12 in each group).
Based on the change in scores at three months, the exercise group had significantly greater improvements in exercise capacity (HR: -14 [-18.5, -2.5] versus 0.5 [-4, 5.5], P= 0.009), QOL (FAMS: 23 [9.5, 42.5] versus -3.5 [-16, 5], P=0.006) and Fatigue (MFIS: -13 [-20, -3] versus 1 [-4, 4.5], P=0.02).
At six months, the difference in change scores remained significant for FAMS (19 [14, 31] versus -4.5 [-25, 8], P=0.002) and MFIS (-8.5 [-19.5, -1] versus 0.5 [-2.5, 6.5], P=0.02) only.
A three-month exercise program improved participants' exercise capacity, QOL and Fatigue, with the improvements in QOL and Fatigue lasting beyond the program.
The Effect Of Ginkgo Biloba On Functional Measures In Multiple Sclerosis: A Pilot Randomized Controlled Trial
Johnson SK, Diamond BJ, Rausch S, Kaufman M, Shiflett SC, Graves L
Explore (NY) 2006 Jan;2(1):19-24
University of North Carolina-Charlotte, Charlotte, NC
Multiple Sclerosis (MS) is a chronic DeMyelinating Neurological Disease afflicting young and middle-aged adults, resulting in problems with Coordination, Strength, Cognition, Affect, and Sensation.
The objective of this study was to determine whether a Ginkgo extract (EGb 761) improved functional performance in individuals with MS.
This study used a double-blind, placebo-controlled, parallel group design.
The end point was change between baseline (ie, preintervention) and follow-up evaluation following a regimen of four tablets per day at 60 mg per tablet for four weeks.
The study was conducted in academic and clinical-based settings.
Twenty-two individuals with MS were randomly assigned to either the treatment or control condition. Groups did not differ with respect to age, IQ, and education.
Half of the subjects received 240 mg per day of Ginkgo special extract (EGb 761), and the other half received placebo.
Main Outcome Measure
The main outcome measures assessed depression (Center for Epidemiologic Studies of Depression Scale [CES-D]), Anxiety (State-Trait Anxiety Inventory [STAI]), Fatigue (Modified Fatigue Impact Scale [MFIS]); symptom severity (Symptom Inventory [SI]) and functional performance (Functional Assessment of Multiple Sclerosis [FAMS]).
The Ginkgo group had significantly more individuals showing improvement on four or more measures with improvements associated with significantly larger effect sizes on measures of Fatigue, symptom severity, and functionality.
The Ginkgo group also exhibited less Fatigue at follow-up compared with the placebo group.
This exploratory pilot study showed that no adverse events or side effects were reported and that Ginkgo exerted modest beneficial effects on select functional measures (eg, Fatigue) among some individuals with MS.
De Stefano N, Filippi M, Hawkins C
J Neurol Sci 2008 Mar 15;266(1-2):44-50
University of Siena, Department of Neurological and Behavioral Sciences, Italy
To assess if short-term combination of Glatiramer Acetate (GA) and IV steroid in patients with Relapsing/Remitting Multiple Sclerosis (RRMS) is safe and sustains the effect of GA treatment on MRI-disease activity.
RRMS patients with >/=2 Gadolinium (Gd)-enhancing lesions on screening MRI and EDSS score < /=4.0 received GA injection (20 mg subcutaneously once daily) and monthly 1 g IV MethylPrednisolone (IVMP) for 6 months.
Afterwards, all subjects received GA injections daily alone for additional 6 months.
Neurological evaluations were performed at screening, baseline and every 3 months. Laboratory tests for safety were performed at screening, baseline, months 1, 6 and 12.
Brain MRIs were performed at screening, baseline, months 5, 6, 11, and 12 to assess the change in the number of Gd-enhancing lesions i) from baseline to month 6, and ii) from baseline to month 12 compared with the change from baseline to month 6.
89 subjects were eligible for the study. In this group, GA in combination with IVMP resulted in 65% (95% CI=0.25-0.49, p < 0.0001) reduction in the number of Gd-enhancing lesions.
This reduction was sustained for additional 6 months when patients received GA alone.
The analysis for change achieved in the second 6 month period showed no difference from the change achieved in the first six months (ratio 0.75, 90% CI=0.468-1.197).
Overall, treatment was well tolerated and adverse events reported were similar to the known safety profile of GA.
Short-term combination of GA with 1 g monthly IVMP, preceding treatment with GA alone, is safe.
MRI data suggest that this combination therapy may result in an early and sustained reduction of disease activity in RRMS patients.