The Risk Of Relapses In Multiple Sclerosis During Systemic Infections
Correale J, Fiol M, Gilmore W
Neurology 2006 Aug 22;67(4):652-9
Raul Carrea Institute for Neurological Research (FLENI), Department of Neurology, Buenos Aires, Argentina
To assess the risk of Multiple Sclerosis (MS) relapses, MRI activity, and T-Cell responses during Systemic Infections (SI) in patients with MS.
The authors prospectively studied 60 patients with MS. Twenty patients were evaluated with sequential MRI on initial visit, and 2 and 12 weeks later.
Blood samples were collected at first infection symptom and 2, 5, 12, and 24 weeks later, and production of IL-4, IL-10, IL-12, IFN-γ, TNF-, VLA-4, LFA-1, MMP-9, and MMP-2 were measured after infectious Antigens (Ag) stimulation.
Increased risk of relapse and MRI activity were observed during SI.
Numbers of IFN-γ, TNF-, and IL-12 secreting cells, serum concentrations of MMP-9, and expression of VLA-4 and LFA-1 after PBMC Viral or bacterial Ag stimulation were higher in samples collected during exacerbations associated to SI.
Transwell analysis demonstrated that soluble factors produced during Viral stimulation have little effect on Myelin specific T-Cells activity.
In contrast, PBMC Viral stimulation in the presence of cognate Myelin Ag induces maximal effector responses at 20 to 30 times lower than the Ag alone.
There was a significant association between systemic infections and risk of MS relapse, increased MRI activity, and T-Cells activation. Furthermore, infectious agents increased Myelin specific T-Cells sensitivity to cognate Ag.
Is The Frequency Of Abnormalities On Magnetic Resonance Imaging In Isolated Optic Neuritis Related To The Prevalence Of Multiple Sclerosis? A Global Comparison
Swanton JK, Fernando K, Dalton CM, Miszkiel KA, Thompson AJ, Plant GT, Miller DH
J Neurol NeuroSurg Psychiatry 2006 Sep;77(9):1070-2
Institute of Neurology, University College London, NMR Research Unit, Queen Square, London, UK
The link between Optic Neuritis and Multiple Sclerosis is well established, as is the increased risk of conversion to Multiple Sclerosis, with lesions seen at presentation on the Magnetic Resonance Imaging (MRI) scan of the Brain.
One or more asymptomatic lesions were present in 77% of the Optic Neuritis cohort from London, UK, a higher proportion than that reported in other large cohorts studied elsewhere, where generally lower prevalence rates for Multiple Sclerosis are also reported.
These observations may support the hypothesis that Optic Neuritis is more likely to be associated with abnormalities on MRI and to be due to Multiple Sclerosis in geographical regions where Multiple Sclerosis is more common.
Regional Gray Matter Atrophy In Early Primary/Progressive Multiple Sclerosis: A Voxel-Based Morphometry Study
Sepulcre J, Sastre-Garriga J, Cercignani M, Ingle GT, Miller DH, Thompson AJ
Arch Neurol 2006 Aug;63(8):1175-80
Institute of Neurology, University College of London, 23 Queen Square, London WC1N 3BG, England
Gray Matter (GM) Atrophy has been reported in Multiple Sclerosis (MS). However, little is known about its regional distribution.
To investigate the regional distribution of GM Atrophy in clinically early Primary/Progressive MS (PPMS).
Design And Patients
Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied.
All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only.
Magnetic Resonance Images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue Atrophy on a voxel-by-voxel basis.
A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions.
A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study.
At baseline, patients with PPMS displayed bilateral Thalamic Atrophy compared with controls.
In addition, a significant association between lesion load and decreased GM volume was found for the Thalami. Loss of GM in the Putamen, Caudate, Thalami, and Cortical and InfraTentorial areas was observed in patients after 1 year of follow-up.
Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to NeuroDegeneration. Cortical and InfraTentorial Atrophy developed as the disease evolved.
Long-Term Clinical Experience With Weekly Interferon-ß-1a In Relapsing Multiple Sclerosis
Coppola G, Lanzillo R, Florio C, Orefice G, Vivo P, Ascione S, Schiavone V, Pagano A, Vacca G, De Michele G, Morra VB
Eur J Neurol 2006 Sep;13(9):1014-21
Federico II University, Department of Neurological Sciences, Naples, Italy
Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of Interferon-beta-1a (IFN-ß-1a) therapy in Multiple Sclerosis (MS) patients.
The goals of this study were to:
- Assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFN-ß-1a therapy in a large cohort of patients
- Suggest possible predictors of therapeutic response
A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months.
Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of Cholesterol levels.
After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline.
The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively.
These results confirm the safety and suggest a sustained effectiveness of i.m. IFN-ß-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.
Interferon-ß-1a Treatment In Childhood And Juvenile-Onset Multiple Sclerosis
Tenembaum SN, Segura MJ
Neurology 2006 Aug 8;67(3):511-3
Hospital de Pediatria, Department of Neurology, Buenos Aires, Argentina
The authors studied the safety and tolerability of subcutaneous Interferon-beta-1a at different doses in 24 children with clinically definite Multiple Sclerosis.
After a mean treatment period of 44 months, Interferon-ß-1a was well tolerated in 22 patients, although two experienced possible serious adverse events.
Although effectiveness cannot be inferred from this study, the authors did observe a significant reduction in the relapse rate at 22 mug, three times weekly, in the Relapsing/Remitting subgroup.
Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Bruck W, Lucchinetti C, Lassmann H
Brain 2006 Dec;129(Pt 12):3165-72
Center for Brain Research, Medical University of Vienna, Vienna, Austria
Although spontaneous ReMyelination does occur in Multiple Sclerosis lesions, its extent within the global population with this disease is presently unknown.
We have systematically analyzed the incidence and distribution of completely ReMyelinated lesions (so-called Shadow Plaques) or partially ReMyelinated lesions (shadow plaque areas) in 51 autopsies of patients with different clinical courses and disease durations.
The extent of ReMyelination was variable between cases. In 20% of the patients, the extent of ReMyelination was extensive with 60-96% of the global lesion area ReMyelinated.
Extensive ReMyelination was found not only in patients with Relapsing Multiple Sclerosis, but also in a subset of patients with Progressive disease.
Older age at death and longer disease duration were associated with significantly more ReMyelinated lesions or lesion areas.
No correlation was found between the extent of ReMyelination and either gender or age at disease onset.
These results suggest that the variable and patient-dependent extent of ReMyelination must be considered in the design of future clinical trials aimed at promoting CNS repair.
Clinical And MRI Features Of Japanese Patients With Multiple Sclerosis Positive For NMO-IgG
Nakashima I, Fujihara K, Miyazawa I, Misu T, Narikawa K, Nakamura M, Watanabe S, Takahashi T, Nishiyama S, Shiga Y, Sato S, Weinshenker BG, Itoyama Y
J Neurol NeuroSurg Psychiatry 2006 Sep;77(9):1073-5
Tohoku University School of Medicine, Department of Neurology, Sendai 980-8574, Japan
This study investigates the relation between the serological status of NMO (NeuroMyelitis Optica)-IgG and the clinical and MRI features in Japanese patients with Multiple Sclerosis.
Serum NMO-IgG was tested in 35 Japanese patients diagnosed with Multiple Sclerosis, including 19 with the Optic-Spinal form of Multiple Sclerosis (OSMS), three with the Spinal form of Multiple Sclerosis (SMS), and 13 with the conventional form of Multiple Sclerosis (CMS), which affects the brain.
NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 Vertebral segments) Spinal Cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS.
The two patients having CMS with NMO-IgG had unusual Brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS.
This newly discovered Serum AutoAntiBody was markedly associated with longitudinally extensive Spinal Cord lesions and with complete blindness, suggesting severe Optic-Spinal disease.