Cognitive And Affective Disturbances In Multiple Sclerosis
Kesselring J, Klement U
J Neurol 2001 Mar;248(3):180-3
Rehabilitation Centre, Dept of Neurology, 7317 Valens, Switzerland
PMID# 11355150; UI# 21254578
The Emotional and relationship problems associated with MS have not always been fully appreciated by the medical profession, which has tended to concentrate on the Physical aspects of this disease.
Yet the Psychological problems of MS often cause more suffering than Physical effects.
PhysioPathology And Treatment Of Fatigue In Multiple Sclerosis
Comi G, Leocani L, Rossi P, Colombo B
J Neurol 2001 Mar;248(3):174-9
Univ of Milan, Dept of NeuroScience, Scientific Institute H. San Raffaele, Via Olgettina 60, 20132 Milan, Italy
PMID# 11355149; UI# 21254577
Fatigue is a common symptom of patients with Multiple Sclerosis (MS). It is reported by about one-third of patients, and for many Fatigue is the most disabling symptom.
Fatigue may be associated with motor disturbances and/or mood disorders, which makes it very difficult to determine whether the Fatigue is an aspect of these features or a result per se of the disease.
Although peripheral mechanisms have some role in the PathoGenesis of Fatigue, in MS there are clear indications that the more important role is played by "Central" abnormalities.
NeuroPhysiological studies have shown that Fatigue does not depend on involvement of the Pyramidal Tracts and implicate impairment of volitional drive of the Descending Motor Pathways as a PhysioPathological mechanism.
Metabolic abnormalities of the Frontal Cortex and Basal Ganglia revealed by Positron-Emission Tomography and correlations between Fatigue and Magnetic Resonance Imaging lesion burden support this hypothesis.
Some recent studies also suggest that pro-inflammatory Cytokines contribute to the sense of tiredness.
No specific treatments are available. Management strategies include medications, exercise, and behavioral therapy; in most cases a combined approach is appropriate.
Hickman SJ, Miller DH
NeuroImaging Clin N Am 2000 Nov;10(4):689-704
Institute of Neurology, NMR Research Unit,
Univ, College London, Queen Square, Clinical Research Fellow, London, United Kingdom
The Spinal Cord is a common site of involvement in Multiple Sclerosis (MS), and a major cause of the disability suffered by MS patients.
High quality MRI of the Spinal Cord is therefore important for diagnosis and research. Imaging of the Spine, however, presents many technical difficulties because of the small size of the Spinal Cord and the potential for artifacts.
This article discusses technical difficulties such as pulse sequences, the use of newer imaging techniques, and the application of spinal MR imaging in clinical settings.
Major studies are underway involving Spinal Cord imaging, and clinical trials of disease-modifying agents are beginning to include Spinal Cord imaging, especially measurements of Atrophy, as part of their protocols.
In clinical practice, Spinal Cord imaging is essential for ruling out other causes of Myelopathies, particularly Spinal Cord compression.
And can help in the diagnosis of MS when Brain imaging is normal, or in older individuals in whom findings in the Brain are less specific.
Contrast Enhancement And The Acute Lesion In Multiple Sclerosis
Rovaris M, Filippi M
NeuroImaging Clin N Am 2000 Nov;10(4):705-716
Scientific Institute, Ospedale San Raffaele, NeuroImaging Research Unit, Dept of NeuroScience, Milan, Italy
Gadolinium (Gd)-enhanced MR imaging has greatly improved the understanding of the PathoPhysiology of Multiple Sclerosis (MS) and has provided robust outcome measures for monitoring MS activity.
Modest correlation between the presence and extent of enhancement and the evolution of MS probably owes to the limited sensitivity and specificity of conventional Gd-enhanced MRI.
Triple dose of Gd may enable better assessment of the presence and extent of "low-grade" MS inflammation.
Cell-specific imaging techniques and multiparametric MRI studies should increase understanding of the pathologic steps between inflammation and irreversible tissue loss.
And consequently, better define the mechanisms leading to irreversible Neurological disability in MS.
Clinical applications of Gd-enhanced MR imaging should include the diagnostic work-up of MS patients, and the assessment of their disease activity over time, in the context of natural history studies or clinical trials.
Gd-enhanced MR imaging should always be obtained at presentation in patients with Clinically Isolated Neurological Syndromes, because of its ability to show the time dissemination of lesions, and its high predictive value for subsequent evolution to Clinically Definite MS.
In patients with established MS, however, the usefulness of Gd-enhanced MR imaging should depend strictly on specific clinical settings or research questions.
Arnold DL, De Stefano N, Narayanan S, Matthews PM
NeuroImaging Clin N Am 2000 Nov;10(4):789-798
McGill University, Dept of Neurology and NeuroSurgery, Montreal, Quebec, Canada
Axonal injury in Multiple Sclerosis (MS) is Focal and diffuse, and is directly responsible for irreversible Disability.
Acute inflammatory events can be associated with reversible disability that may parallel reversible Axonal injury. This in part accounts for the remission following relapses early in the disease.
By the time there is clinical disability, substantial Axonal injury already has occurred. This provides a strong rationale for the early limitation of inflammation and its consequences.
Naturally Processed HLA Class II Peptides Reveal Highly Conserved Immunogenic Flanking Region Sequence Preferences That Reflect Antigen Processing Rather Than Peptide-MHC Interactions
Godkin AJ, Smith KJ, Willis A, Tejada-Simon MV, Zhang J, Elliott T, Hill AV
J Immunol 2001 Jun 1;166(11):6720-6727
Univ of Oxford, John Radcliffe Hospital, Institute of Molecular Medicine, Molecular Immunology Group, Nuffield Dept of Medicine;
Oxford, United Kingdom; and
Howard Hughes Medical Institute, Dept of Medicine, The Children's Hospital; and
Laboratory of Molecular Medicine, Boston, MA 02115; and
Medical Research Council Immunochemistry Unit, Dept of BioChemistry, Oxford, United Kingdom; and
Baylor College of Medicine, Dept of Neurology, Houston, TX 77030
MHC Class II heterodimers bind Peptides 12-20 aa in length. The Peptide Flanking Residues (PFRs) of these Ligands extend from a central binding core consisting of nine Amino Acids.
Increasing evidence suggests that the PFRs can alter the ImmunoGenicity of T-Cell Epitopes. We have previously noted that eluted Peptide pool sequence data derived from an MHC Class II Ag reflect patterns of enrichment.
Not only in the core binding region but also in the PFRS: We sought to distinguish whether these enrichments reflect cellular processes or direct MHC-Peptide interactions.
Using the Multiple Sclerosis-associated allele HLA-DR2, pool sequence data from naturally processed Ligands were compared with the patterns of enrichment obtained by binding SemiCombinatorial Peptide libraries to empty HLA-DR2 molecules.
Naturally processed Ligands revealed patterns of enrichment reflecting both the binding motif of HLA-DR2 (position (P)1, aliphatic; P4, bulky hydrophobic; and P6, polar).
As well as the nonbound flanking regions, including acidic residues at the N terminus and basic residues at the C terminus.
These PFR enrichments were independent of MHC-Peptide interactions.
Further studies revealed similar patterns in nine other HLA alleles, with the C-terminal basic residues being as highly conserved as the previously described N-terminal prolines of MHC Class II Ligands.
There is evidence that addition of C-terminal basic PFRs to known Peptide Epitopes is able to enhance both processing as well as T-Cell activation.
Recognition of these allele-transcending patterns in the PFRs may prove useful in Epitope identification and vaccine design.