Comparisons Of Patient Self-Report, Neurologic Examination, And Functional Impairment In MS
Hoogervorst EL, van Winsen LM, Eikelenboom MJ, Kalkers NF, Uitdehaag BM, Polman CH
Neurology 2001 Apr 10;56(7):934-937
Academic Hospital, Free University, Depts of Neurology, and Clinical Epidemiology and Biostatistics, Amsterdam, the Netherlands
To compare the recently developed Guy's Neurologic Disability Scale (GNDS), based on patient self-report, with both Neurologist rating of Neurologic Examination abnormalities.
Using the Expanded Disability Status Scale (EDSS) and observations of functional impairment on the Multiple Sclerosis Functional Composite (MSFC) in the assessment of disease impact in MS.
Two hundred ninety MS patients were recruited at an outpatient clinic. Impairment and Disability were assessed using GNDS, EDSS, and MSFC.
Correlations between GNDS, EDSS, MSFC, and their corresponding components were studied for the total population, MS phenotypes, and three disability strata.
Mean scores were 4.6 (SD, 2.0) for EDSS, 0.0 (SD, 0.8) for MSFC, and 14.6 (SD, 7.9) for GNDS.
Good correlations were found between GNDS and EDSS (r = 0.73), between GNDS and MSFC (r = -0.68), and between different subcategories of the GNDS and EDSS, MSFC, and their corresponding components.
Remarkably good correlations were found between lower limb function and all three scales. Poor correlations were also found, especially between different measurements focusing on Cognitive function.
The good correlations between GNDS and both EDSS and MSFC were mainly due to the importance of Spinal Cord-related Neurologic functions in all three scoring systems.
A marked discrepancy was found for the assessment of Cognition between objective measurements and subjective complaints.
Because patients' self-reporting correlates well with results of physical examination, GNDS can offer a valuable way to measure disease impact in MS. However, GNDS is not an adequate screen of Cognitive Dysfunction.
A Case Of Multiple Sclerosis With Granulomatous Uveitis In Japan-Use Of The AntiLipoArabinoMannan (LAM)-B Test In Differential Diagnosis
Inoue K, Numaga J, Joko S, Izumi S, Kato S, Kawashima H, Fujino Y
Am J Ophthalmol 2001 Apr;131(4):524-526
Univ of Tokyo School of Medicine, Branch Hospital, Dept of Ophthalmology, Tokyo, Japan
To report a patient with Multiple Sclerosis and associated with Granulomatous Uveitis, and how AntiLipoArabinoMannan (LAM)-B AntiBody can play a key role in differential diagnosis.
A 35-year-old Japanese woman with Multiple Sclerosis, diagnosed 3 years ago, presented with blurred vision in her left eye.
Ophthalmological examinations revealed Granulomatous Iridocyclitis in her left eye and Retinal Periphlebitis in both eyes.
The diagnosis of Tuberculosis was suspected because of a positive Tuberculin skin test. However, a further examination by an anti-LAM-B AntiBody test excluded active Tuberculosis.
Her clinical findings were thought most likely to be caused by Multiple Sclerosis and treated with CorticoSteroids.
We should consider the possibility of Multiple Sclerosis as the underlying origin in patients with Granulomatous Uveitis.
A measurement of anti-LAM-B AntiBody titer may be useful in the differential diagnosis of Granulomatous Uveitis.
Anergy Induction By Dimeric TCR Ligands
Appel H, Seth NP, Gauthier L, Wucherpfennig KW
J Immunol 2001 Apr 15;166(8):5279-5285
Dana-Farber Cancer Institute, Dept of Cancer Immunology & AIDS, and Harvard Medical School, Dept of Neurology, Boston, MA 02115
T-Cells that recognize particular self Ags are thought to be important in the PathoGenesis of AutoImmune Diseases. In Multiple Sclerosis, susceptibility is associated with HLA-DR2, which can present Myelin-derived peptides to CD4+ T-Cells.
To generate molecules that target such T-Cells based on the specificity of their TCR, we expressed a soluble dimeric DR2-IgG fusion protein with a bound peptide from Myelin Basic Protein (MBP).
Soluble, dimeric DR2/MBP Peptide complexes activated MBP-specific T-Cells in the absence of signals from costimulatory or Adhesion Molecules.
This initial signaling through the TCR rendered the T-Cells unresponsive (Anergic) to subsequent activation by peptide-pulsed APCs.
Fluorescent labeling demonstrated that anergic T-Cells were initially viable, but became susceptible to late Apoptosis due to insufficient production of Cytokines.
Dimerization of the TCR with bivalent MHC Class II/Peptide complexes therefore allows the induction of anergy in human CD4+ T-Cells with a defined MHC/Peptide specificity.
ApoLipoProtein A-I Inhibits The Production Of InterLeukin-1beta And Tumor Necrosis Factor-alpha By Blocking Contact-Mediated Activation Of Monocytes By T-Lymphocytes
Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK 3rd, Roux-Lombard P, Burger D
Blood 2001 Apr 15;97(8):2381-2389
Tumor Necrosis Factor-alpha (TNF-) and InterLeukin-1beta (IL-1ß), essential components in the PathoGenesis of ImmunoInflammatory Diseases, are strongly induced in Monocytes by direct contact with stimulated T-Lymphocytes.
This study demonstrates that adult Human Serum (HS) but not fetal calf or Cord blood Serum displays inhibitory activity toward the contact-mediated activation of Monocytes by stimulated T-Cells, decreasing the production of both TNF- and IL-1ß.
Fractionation of HS and N-terminal MicroSequencing as well as Electroelution of material subjected to preparative Electrophoresis revealed that ApoLipoProtein A-I (apo A-I), a "negative" acute-phase protein, was the inhibitory factor.
Functional assays and flow cytometry analyzes show that high-density LipoProtein (HDL)-associated Apo A-I inhibits contact-mediated activation of Monocytes by binding to stimulated T-Cells, thus inhibiting TNF- and IL-1ß production at both protein and messenger RNA levels.
Furthermore, apo A-I inhibits Monocyte inflammatory functions in peripheral blood MonoNuclear Cells activated by either specific Antigens or Lectins without affecting cell proliferation.
These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions.
Therefore, because HDL has been shown to bind and neutralize LipoPolySaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation.
The novel anti-inflammatory function of Apo A-I reported here might lead to new therapeutic approaches in inflammatory diseases such as Rheumatoid Arthritis, Multiple Sclerosis, Systemic Lupus Erythematosus, and AtheroSclerosis.
He J, Grossman RI, Ge Y, Mannon LJ
AJNR Am J NeuroRadiol 2001 Apr;22(4):664-669
Hospital of the Univ of Pennsylvania, Dept of Radiology, 3400 Spruce Street, Philadelphia, PA 19104-4283
Background And Purpose
Contrast enhancement on MR images of patients with Multiple Sclerosis (MS) is known to be associated with abnormalities of the Blood-Brain Barrier (BBB).
However, little is known about diagnostic patterns and common features of enhanced MS lesions. This study was designed to evaluate initial enhancement patterns, changes in these enhancing patterns, and duration of enhancement in a cohort of patients with MS.
Twenty-five patients with Clinically Definite MS were studied retrospectively. The appearance of enhancing lesions and sequential changes in the appearance on Axial contrast-enhanced Spin-Echo images were evaluated.
The enhancing lesions were classified as Nodular, Ringlike, or "other" (eg, Arclike).
Of 301 new enhancing lesions, 205 (68%) showed Nodular enhancement, 70 (23%) a Ring pattern, and 26 (9%) a pattern neither Nodular nor Ringlike (eg, Arclike).
Two hundred eighty (93%) of 301 enhancing lesions disappeared within 6 months, and seven (2%) lesions showed persistent enhancement longer than 6 months.
The other 14 (5%) lesions, which disappeared by the time of the next scan, were excluded, because the course between two examinations was longer than 6 months.
Of nine persisting Nodular enhancing lesions on the follow-up images, seven were decreased in size, whereas all of two persisting Ringlike enhancing lesions on the follow-up images were larger than before.
Nodular enhancement is the predominant enhancement pattern for new MS lesions, and the temporal course of enhancement is usually shorter than 6 months.
The appreciation of the evolution of MS-enhanced lesions aids in both identifying new MS lesions and distinguishing these lesions from other pathologic entities. This may be helpful in clinically evaluating the stage of MS Lesions.