Brain MRI, CSF examination, and evoked potentials in patients affected by optic neuritis: their diagnostic and prognostic role

Comparison

of 4 putative

MR imaging marbra in MS plaques.

of matrixdestruction

Brain

MRI,

affected

CSF examination.

by optic A. Ghezzi,

Centro

Studi

neuritis:

and evoked their

potentials

diwnostic

in patients

and prognostic

role.

V. Toni*, A. Zlbetti, S. Baldini, M. 7affaroni

Sclemsc Multipta (Gallsrate)

and ‘lstiiuto M. Negri (Milan), Italy

0-w 1- to evaluate the diagnostic role of brain MRI, CSF examination (intrathecel IgG synthesis) and multimodal evoked potentials in patients with optic neuritis (ON); 2- to evaluate their prognostic role in reltin to the development of multiple sclerosis (MS). Suqhcts end r@wlts - 100 patients affected by ON (74 females, 26 males, mean age 28.9). Most of them were submittad to the diagnostic procedures mentioned above, 82 were included in a follow up study (mean duration 5.3 ys): of these, 49 presented complete laboratory data. Motor EP+ 3146 (6.5%)

Visual Brainstem Sornatosens. EP +’ EP+ EP+ 5189 61181 54192 22190 4190 (5.6%) (75.3%) (58.7%) (24.4%) (4.4%) ‘VEP abnormal: if delayed in the clinically unaffected eye MRI +

follow up results: 13/49 patiints showed signs of CNS outside the optic nerve, after a mean follow up of 5.3 ys.

(SRC&= 0 8386. p < 0 Oool) Tlus correlatm” & eve” stron@r when NAWM valws were mchukd (SRCC = -0 8905, p c 0 Oool). strmp oorrelat~m~ we alw fcnmd b&wee” sqmal m”te”say. normaIced to CSF. and hoth T I relaxatxmtune(SRCC=-08357,pr0.0001)andh4TR(SRCC=07455.p<00001)and hctwccn m@nal interwty, nonnalizd to NAWM. snd both T I relaxation tmx (SRCC = 08495.p~00001)andMTR(SRCC=07822.p~00001) DiYcIusinn. The putawe parameters, wblch are Sug&ested to be relatively SpeclfiC lndlcators for mstnxdeshucuon, are strooply &ted to each other Both sqal lntens~t~ ncmnallzed to CSF and qnal ~“kn%ty d to NAWhi @ve dmmt equal mfamatnm to T I relaxatm” mneand~imd~heprefared”verTlrelaxaumtunewd~a*theyaremucheas~er to acqum and analyze

TGF-fil-MEDIATED PROLIFERATION INTERRUPTED

AND BY IFNr

INHIBITION OF DOWN-REGULATION

B.-G. Xiao, G.-X. Zhang, C.-G. Ma and Neurology, Karolinska Institute, Huddinge Sweden.

MRI+ MS+(13) I

MS-

13 (36)

25

EP= other evoked

MRI-

CSF+

CSF-

09 11 15 potential

VEP+ 34

excluding

15 10

VEP-

involvement EP+

EP-

92

10

25 5

301

VEP

Co~~cludonr: MRI is confirmed to be the most relevant tool in diagnostic and prognostic evaluation of ON patients; CSF study is less relevant but useful to better sustain the suspicion of an inflammatory demyelinating disease, specially in cases with normal MRI or few lesions; EPs give no additive diagnostic or prognostic help.

CEREBROSPINAL FLUID FROM MULTIPLE SCLEROSIS PATIENTS PROMOTES NEURONAL AND OLIGO-DENDROCYTE DAMAGE BY DELAYED PRODUCTION OF NITRIC OXIDE IN VITRO

GLIAL CELL OF ICAMIS H. Link. Hospital,

CSF+

Division of Stockholm,

B.-G. Xiao, G.-X. Zhang, C.-G. Ma and Neurology and Karolinska MS Center, Huddinge Hospital, Stockholm, Sweden

H. Link. Division of Karolinska Institute,

Microglia-induced cytotoxicity on oligodendrocytes is mediated through nitric oxide (NO) in vitro. Elevated NO synthetase was reported in regions of demyelination in MS brains. NO could thus be involved in myelin and oligodendrocyte injury in MS. Because NO secreted from brain cells is short-lived and difficult to measure, the exact mechanisms of NO production and possible cytotoxic effects of NO in the MS brain have not been elucidated. We examined the effects of MS and control patients’ CSF on neurons cultured from rat brains at embryonic day 18 (mixed neuronal cultures) and oligodendrocyte from cerebral cortices of newborn rats (mixed glial cultures). NO production detected on day 20 in supematants of mixed neuronal cultures treated with MS CSFs was markedly higher than after treatment with CSF from patients with other inflammatory neurological diseases or tension headache (TH). The increased NO production was paralleled by increased LDH release. Oligodendrocyte loss in MS-CSF treated mixed glial cultures was more evident than in TH CSF-treated cultures on day 14 of treatment. Excessive NO in MS CSF seems to represent a mechanism for oligodendrocyte losses and lesion formation in MS.

The immune response-downregulating cytokine TGF-f3 has a protective effect against EAE that is exerted at the level of the vascular CNS endothelium rather than through direct effects on lymphoid cells. The proinflammatory 1FN-y upregulates EAE. To analyze the effects of TGF-01 on proliferation and ICAM-l/LFA-1 expression, and the antagonistic events between TGF-Pl and IFN-y in vitro, we used (1) Lewis rat glial cells activated by intracerebral injection of MBP (in vivo activated glial cells); (2) in vitro MBP-stimulated glial cells; and (3) in vitro MBP-stimulated microglia and (4) astrocytes. TGF-Pl inhibited proliferation of activated and stimulated glial cells, and especially of separated microglia and astrocyte cultures. TGF-PI strongly inhibited ICAMexpression measured by FACScan on activated glial cells but had no effect on ICAMexpression on astrocytes. TGF-@l did not affect LFA-1 expression. In contrast, 1FN-y had an antagonistic, upregulating effect on ICAMexpression, but inhibited the proliferative response on stimulated glial cells. In the presence of IFN-y TGF-!31 was unable to inhibit glial cell proliferation until high doses were added. Similarly, IFN-yInduced ICAMexpression was not downregulated by TGF-el until TGF-Pl was added at very high concentrations. The observations implicate that TGF-Pl effects are dose-dependent and related to presence or absence of other cytokines or mediators in the local microenvironment.

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