Keegan M, Konig F, McClelland R, Bruck W, Morales Y, Bitsch A, Panitch H, Lassmann H, Weinshenker B, Rodriguez M, Parisi J, Lucchinetti CF
Lancet 2005 Aug 13-19;366(9485):579-82
Mayo Clinic College of Medicine, Department of Neurology, Rochester, MN 55905, USA
Early, active Multiple Sclerosis lesions show four ImmunoPathological patterns of DeMyelination. Although these patterns differ between patients, multiple active lesions from a given patient have an identical pattern, which suggests pathogenic heterogeneity.
Therapeutic Plasma Exchange (TPE) has been successfully used to treat fulminant DeMyelinating attacks unresponsive to Steroids.
We postulated that patients with Patterns II would be more likely to improve after TPE than those with other patterns since Patterns II lesions are distinguished by prominent ImmunoGlobulin deposition and Complement activation.
We retrospectively studied 19 patients treated with TPE for an attack of fulminant CNS Inflammatory DeMyelinating Disease.
All patients with Patterns II (n=10), but none with Patterns I (n=3) or Patterns III (n=6), achieved moderate to substantial functional Neurological improvement after TPE (p< 0.0001).
Patients with Multiple Sclerosis with Patterns II pathology are more likely to respond favorably to TPE than are patients with Patterns I or III.
Bittar RG, Hyam J, Nandi D, Wang S, Liu X, Joint C, Bain PG, Gregory R, Stein J, Aziz TZ
J Clin NeuroSci 2005 Aug 9
Radcliffe Infirmary, Department of NeuroSurgery, Oxford, UK; Australasian Movement Disorder and Pain Surgery (AMPS) Clinic, Melbourne, Australia; The Alfred Hospital, Department of NeuroSurgery, Melbourne, Australia; Montash University, Department of Surgery, Melbourne, Australia; Melbourne NeuroSurgery, Melbourne, Australia
Disabling intractable Tremor occurs frequently in patients with Multiple Sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable.
Thalamotomy has been the mainstay of NeuroSurgical therapy for intractable MS Tremor, however the popularization of Deep Brain Stimulation (DBS) has led to the adoption of chronic Thalamic stimulation in an attempt to ameliorate this condition.
With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS Tremor.
Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both Thalamotomy and Thalamic Stimulation produced improvements in postural and intention tremor.
The mean improvement in Postural Tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P>0.05).
Intention Tremor improved by 72% in the group undergoing Thalamotomy, a significantly larger gain than the 36% Tremor reduction following DBS (P< 0.05).
Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall.
Following Thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised Hemiparesis and Seizures. Only one patient in the Thalamic stimulation group experienced a permanent deficit (Monoparesis).
We conclude that Thalamotomy is a more efficacious surgical treatment for intractable MS Tremor, however the higher incidence of persistent Neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.
The Importance Of Measuring IFN-ß Bioactivity: Monitoring In MS Patients And The Effect Of Anti-IFN-ß AntiBodies
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.
Multicontrast MRI Of ReMyelination In The Central Nervous System
Merkler D, Boretius S, Stadelmann C, Ernsting T, Michaelis T, Frahm J, Bruck W
NMR Biomed 2005 Aug 8
Georg-August University Gottingen, Department of NeuroPathology, Germany
Although Magnetic Resonance Imaging (MRI) represents the most sensitive tool for the detection of White Matter abnormalities in patients with Multiple Sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes.
In order to identify putative MRI markers for De- and ReMyelination, we employed the cuprizone mouse model which leads to a selective and reversible DeMyelination of the Corpus Callosum with little or no axonal damage.
Apart from Histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts.
While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, DeMyelinated or ReMyelinated White Matter by one contrast alone was less specific than by Histology or electron microscopy.
However, an accurate MRI prediction of the in vivo Myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and Magnetization Transfer contrast.
With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved ReMyelination.
Copyright (c) 2005 John Wiley & Sons, Ltd.
Long-Term Clinical Outcome Of Primary/Progressive MS: Predictive Value Of Clinical And MRI Data
Sastre-Garriga J, Ingle GT, Rovaris M, Tellez N, Jasperse B, Altmann DR, Benedetti B, Stevenson VL, Cercignani M, Leary SM, Barkhof F, Brochet B, Dousset V, Filippi M, Montalban X, Kalkers NF, Polman CH, Rovira A, Miller DH, Thompson AJ
Neurology 2005 Aug 23;65(4):633-5
Institute of Neurology, UCL, Queen Square, London WC1N 3BG, UK
The authors sought to identify clinical and MRI predictors of outcome in Primary/Progressive Multiple Sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only).
At baseline, disease duration, Expanded Disability Status Scale (EDSS) and Brain Volume predicted outcome.
Adding short-term change variables, baseline EDSS, changes in T2 lesion load and Cord Area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS.
The Molecular Orchestra Of The Migration Of Oligodendrocyte Precursors During Development
de Castro F, Bribian A
Brain Res Brain Res Rev 2005 Sep;49(2):227-41
Instituto de Neurociencias de Castilla y Leon-INCyL, Universidad de Salamanca, Avda. de Alfonso X "el Sabio", s/n, E-37007-Salamanca, Spain
During development of the Central Nervous System (CNS), postmitotic cells (including Neurons and Myelin-generating cells, the Oligodendrocytes) migrate from the germinal areas of the Neural Tube where they originate to their final destination sites.
The migration of Neurons during development has been extensively studied and has been the topic of detailed reviews.
The migration of Oligodendrocyte Precursor Cells (OPCs) is also an extremely complex and precise event, with a widespread migration of OPCs across many regions to colonize the entire CNS.
Different mechanisms have been shown to direct the migration of OPCs, among them contact-mediated mechanisms (Adhesion Molecules) and long-range cues (Chemotropic Molecules).
This review provides a detailed overview and discussion of the cellular and molecular basis of OPCs migration during development.
Because it has been shown that Neuronal and Oligodendroglial lineages share some of these mechanisms, we briefly summarize similarities and differences between these two types of Neural cells.
We also summarize the changes in the normal migration of OPCs during development that would be relevant for different Neurological Diseases (including DeMyelinating Diseases, such as Multiple Sclerosis, and Glial Cancers).
We also examine the relevance of these migratory properties of the Oligondendrocytic cell lineage for the repair of Neural damage.
'Importance Sampling' In MS: Use Of Diffusion Tensor Tractography To Quantify Pathology Related To Specific Impairment
Lin X, Tench CR, Morgan PS, Niepel G, Constantinescu CS
Specific Neurological impairments in Multiple Sclerosis (MS) are dependent on the pathology in clinically eloquent areas of the Central Nervous System.
J Neurol Sci 2005 Aug 15
University Hospital, University of Nottingham, Division of Clinical Neurology, Nottingham NG7 2UH, United Kingdom
We aimed to use Diffusion Tensor fiber tracking to identify the Pyramidal Tracts and Corpus Callosum in MS patients, measure the Apparent Diffusivity within the tracts, and evaluate whether this would correlate with relevant disability scores.
Dual-Echo and Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) Brain scans were obtained from 29 patients with Relapsing/Remitting MS, and 13 age and gender matched normal controls.
Voxels from Pyramidal Tracts and Corpus Callosum were automatically identified using a tractography based algorithm. Mean Apparent Diffusion Coefficient (ADC(av)) was measured for these tracts.
Scores of Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were obtained.
The median EDSS score was 2.5 (inter-quartile range 2-3.25). The ADC(av) in the Pyramidal Tracts (p=0.02) and Corpus Callosum (p=0.0004) in patients was significantly higher than in controls.
Pyramidal Tracts ADC(av) was correlated with Pyramidal FSS (r=0.5, p=0.008).
Corpus Callosum ADC(av) was correlated with PASAT (r=-0.58, p=0.001). Global T(2) lesion volume did not correlate with the EDSS, but correlated with ADC(av) of the Pyramidal Tracts (r=0.6, p=0.0007) and Corpus Callosum (r=0.8, p< 0.0001).
T2 lesion volume within the Pyramidal Tracts and Corpus Callosum correlated with ADC(av) in the Pyramidal Tracts (r=0.6, p=0.0009) and Corpus Callosum (r=0.65, p=0.0002) respectively, but not with Pyramidal FSS or PASAT score.
DT-MRI quantifies pathology in specific White Matter Tracts and may increase the specificity of MRI in monitoring progression of Motor and Cognitive deficits in MS.