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Titolo: Sclerosi multipla





Gradirei avere le piu' recenti 
news sulle ricerche per combattere questa malattia? 


 


                            
Grazie Michele



combattere questa malattia?
Salve a tutti, ciao Michele
Beh... La domanda e un po' generica. T'interessano gli studi sulle
terapie o sulla patogenesi della SM? Per quale forma di SM?
Se conosci l'inglese, questi sono gli "highlights" del convegno ACTRIMS
dell'ottobre scorso.
Per le "references", puoi anche interrogare il database di PubMed
all'indirizzo 
http://www.ncbi.nlm.nih.gov/PubMed/
Bye, Alessio
PS Per saperne di piu, 
http://www.geocities.com/Heartland/Valley/7622
From
Medscape Neurology
Conference Reports
Highlights from the Fifth Annual Meeting of the Americas Committee for
Treatment and Research in Multiple Sclerosis (ACTRIMS)
October 15, 2000
Boston, Massachusetts
Rohit Bakshi, MD
[Medscape Neurology, 2000. © 2000 Medscape, Inc.]
------------------------------------------------------------------------
The Americas Committee for Treatment and Research in Multiple Sclerosis
(ACTRIMS) celebrated its fifth anniversary at its annual meeting in
Boston, Massachusetts. ACTRIMS provides a forum for basic scientists,
clinical researchers, and clinicians to exchange information and network
with colleagues to further the science and treatment of multiple
sclerosis (MS) and related diseases. The lecture program is constructed
each year to provide information on both basic research and clinical
management issues. Hundreds of professionals came together for this
year's meeting in Boston. Recent developments pertaining to the
pathophysiology, neuroimaging findings, clinical manifestations, and
immunomodulatory treatment of MS were presented at the meeting as
highlighted in this summary. Written summaries based on these platform
presentations will be published in an upcoming issue of the journal
Multiple Sclerosis.
Keynote Address: The New Pathology of MS?
Dr. Hans Lassmann, Professor of Neuroimmunology at the University of
Vienna, Austria,[1] focused on the immunology and neuropathology of MS
and outlined the basic concepts of the pathology of MS and then
discussed newer hypotheses in this field.
Recent studies suggest heterogeneity in the patterns of inflammation,
demyelination, oligodendrocyte damage, axonal injury, and remyelination
in patients with MS. These findings raise the possibility that different
mechanisms of tissue injury may be occurring across a spectrum of
patients and thus different therapeutic approaches may be necessary.
Platform Presentations: Original Research Studies
The Role of Cannabis in Reducing Symptoms of MS
Evidence suggests that marijuana (cannabis) or related compounds may
improve the symptoms of MS through their binding to cannabinoid
receptors in the brain. One study by Consroe and colleagues[2] found
that at least one third of patients with MS reported improvement in
spasticity, pain, limb spasms, tremor, mood, appetite, fatigue, double
vision, sexual function, sphincter function, and memory after smoking
cannabis. However, a separate study[3] showed that marijuana may cause
acute worsening of posture and balance in patients with spasticity due
to MS.
Baker and colleagues,[4] from London, United Kingdom, showed compelling
evidence for the effectiveness and mechanisms of cannabinoids in a rat
model of MS (experimental allergic encephalomyelitis). First, the
investigators showed that excitation of brain cannabinoid receptors
improved tremor and spasticity in diseased animals. Second, inhibition
of these receptors worsened tremor and spasticity. Third, in areas of
tissue damage, spastic animals had elevated levels of endogenous
cannabinoid receptor ligands compared with nonspastic animals. Finally,
increasing endogenous cannabinoid levels through the use of reuptake
inhibitors improved spasticity without stimulating cannabinoid
receptors.
This work provides further insight into the mechanisms of action of
marijuana in reducing the symptoms of MS. These findings also suggest
that the disease-ameliorating potential of the cannabinoid system may be
separate from the mechanisms that cause adverse psychological effects.
This should aid in the development of drugs targeted to the appropriate
pathways that will benefit patients with MS while giving rise to only
acceptable side effects.
Cognitive Impairment in MS
Approximately 50% of patients with MS experience cognitive impairment,
and more may be affected if subtle deficits are included.[5-11] The
typical pattern of cognitive impairment includes slowing of
informational processing speed, reduction of new learning capacity, and
impaired problem solving.[7-11] Cognitive function appears to play an
important role in the quality of life (QOL) of patients with MS.
Cognitive impairment in patients with MS is associated with unemployment
and social isolation, regardless of the level of physical
disability.[12,13] Thus, it is desirable to be able to rapidly and
easily recognize cognitive dysfunction in the routine care of patients
with MS.
Krupp and associates,[14] from Stony Brook, New York, reported on their
experience with the Rey Auditory Verbal Learning Test (RAVLT) to screen
patients with MS for cognitive dysfunction. The RAVLT takes only 10
minutes to perform in the clinical setting. This team used a cutoff of a
RAVLT score at least 0.5 standard deviations below published norms to
identify cognitively impaired patients. Patients showed evidence of
impaired functioning on comprehensive neuropsychological testing.
This study indicates that the RAVLT may be a useful bedside test to
screen patients with MS for cognitive impairment. Such patients can then
be referred for neuropsychological evaluations, cognitive and vocational
therapies, and pharmacologic trials of agents that might improve
cognition, such as cholinesterase inhibitors.
QOL in MS
Physical disability assessment using the Expanded Disability Status
Scale (EDSS) is currently considered the most useful clinical measure of
MS disease activity and is the primary clinical outcome measured by
physicians. However, EDSS is strongly influenced by limb and gait
dysfunction and may be insensitive to other important clinical effects
of MS such as fatigue, depression, and sexual and cognitive
dysfunction.[15] There is a need for more sensitive clinical measures
that assess the behavioral consequences of brain lesions in patients
with MS.[16] The QOL scales are comprehensive clinical measures that
assess a variety of domains of health from a patient's perspective and
reveal a host of impairments in patients with MS compared with healthy
populations.[17-19] Miller and colleagues[20] reported results of an
interim analysis on the health-related QOL of patients enrolled in
MSTRAC, an ongoing nationwide US registry of patients with relapsing MS.
Patients completed the Multiple Sclerosis Quality of Life Inventory,
which included general disease measures, such as the 36-Item Short-Form
Health Survey, which is composed of subscales of Physical Functioning,
Role-Physical, Bodily Pain, General Health, Vitality, Social
Functioning, Role-Emotional, and Mental Health. The questionnaire was
completed by 2690 patients since 1998. Patients with MS had significant
impairment in all 8 QOL subscales compared with the general US
population or patients with hypertension or diabetes. This study shows
that many domains of QOL are adversely affected in MS, highlighting the
importance of assessing QOL in the evaluation and treatment of patients
with MS.
Gray Matter Involvement in MS: Iron Deposits Detected by Magnetic
Resonance Imaging?
Traditionally, MS is thought of as a white matter disease of
inflammatory demyelination. However, recent data indicate that MS is a
destructive process that includes axonal transection[21] and brain
atrophy.[22] It is increasingly recognized that the gray matter is
commonly involved, including hypometabolism[23] and direct plaque
formation.[24]
A growing body of evidence also indicates that the cortical and
subcortical gray matter may develop hypointensities on T2-weighted
images (black T2 lesions) that most likely represent pathologic iron
deposition.[25] One previous study[25] of 114 patients with MS showed
that, in most patients, these hypointensities were present in the
thalamus; they were also seen in the putamen, caudate, and rolandic
cortex. The degree of hypointensity was related to clinical severity of
disease as assessed by disease course, disease duration, and neurologic
function (EDSS score).[25]
Previous studies of gray matter black T2 lesions were limited by the use
of visual analysis of magnetic resonance imaging (MRI) films,
heightening the need for a quantitative study to confirm and extend
these findings. I presented results of a quantitative study done by me
and my colleagues[26] at the State University of New York at Buffalo, of
cortical and subcortical gray matter T2 signal using a computer-assisted
approach.
In 60 patients with MS and 50 healthy controls, MRI signal intensities
were obtained from T2-weighted images in various gray matter structures.
Third ventricular width (a measure of central atrophy) and total
hyperintense T2 parenchymal lesion volume were obtained from T2-weighted
fluid attenuated inversion recovery (FLAIR) images. T2 intensity was
lower in patients with MS than controls in gray matter structures
throughout the brain, including the brain stem, basal ganglia, thalamus,
and primary motor (rolandic) cortex.
Lower T2 intensity in the thalamus was associated with increasing
disease duration, and hypointensity in substantia nigra, thalamus, and
caudate was associated with secondary progressive clinical course. Lower
T2 intensity in substantia nigra, thalamus, caudate, and globus pallidus
was associated with increasing third ventricular width, and
hypointensity in substantia nigra, thalamus, caudate, putamen, rolandic
cortex, and globus pallidus was associated with increasing total
hyperintense parenchymal lesion volume. Most importantly, stepwise
regression indicated that T2 hypointensity in thalamus was the strongest
predictor of secondary progression and T2 intensity in putamen and
caudate predicted physical disability (EDSS score), but total
hyperintense parenchymal lesion volume and third ventricular width did
not predict either of these.
This study provides convincing evidence that patients with MS have
widespread gray matter T2 hypointensity that is associated with physical
disability, clinical course, central atrophy, and total hyperintense
parenchymal lesion volume. Further study is warranted to determine the
pathologic significance of the black T2 lesions, including the cellular
localization of iron deposits that may be correlated with the MRI
findings. It would also be of interest to determine if the black T2
lesions worsen over time in patients with MS who are accumulating
disability.
Whether the black T2 lesions will be helpful in diagnosing MS and
predicting long-term outcome is not known. If iron deposition plays a
direct role in the pathogenesis of MS, then this would open a new avenue
for the development of therapies.
Featured Speakers Sessions
Manipulating the Bone Marrow: Potential Benefit in MS?
Dr. Mark Freedman,[27] from Ottawa, Ontario, discussed how the immune
system contributes to the pathogenesis of MS. He first outlined the
various targets for immunotherapy in MS: T cells, macrophages/microglia,
natural killer cells, and B cells. Immunosuppressive therapies, such as
total body irradiation, cyclophosphamide, and mitoxantrone, are limited
by their toxic effects and inability to induce complete remission.
Because autoimmune processes are thought to play an important role in
the pathogenesis of MS and because the immune system arises from
hematopoietic cells in the bone marrow, there is rationale for the use
of stem cell therapy. He discussed the procedures involved in stem cell
transplantation, including harvesting, immunoablation, and
reconstitution.
Dr. Richard Burt,[28] from Chicago, Illinois, gave an overview of the
role of stem cell therapy in the treatment of experimental and human MS.
Dr. Burt's group began the study of autologous hematopoietic stem cell
transplantation (HSCT) in MS in 1993. Before performing this treatment,
stem cells must be harvested from the patient's bone marrow or
peripheral blood. The peripheral blood collection may be necessary to
enrich the cells that are obtained from bone marrow. The infusion of the
stem cells is preceded by high-dose chemotherapy and/or radiation
therapy to maximally suppress the patient's immune cells.
Experimental MS in animals (experimental autoimmune encephalomyelitis)
can be cured by HSCT if the treatment is started early in the disease
process. Dr. Burt has used HSCT in 18 patients with secondary
progressive MS and high disability. The treatment was not associated
with mortality or significant morbidity. Results are preliminary at this
time, but the findings suggest a significant reduction in MRI
progression and a slight slowing of clinical progression. Dr. Burt
cautioned that, although the results are encouraging, further study is
necessary to fully evaluate the role of HSCT in MS.
Dr. Athanasios Fassas,[29] from Thessalonika, Greece, discussed his
group's experience with the use of HSCT in 24 patients with progressive
forms of MS who had moderate to severe disability. Most of the patients
remained clinically stable or improved after HSCT, whereas 5 continued
to progress. However, most patients eventually developed relapse or
progression months or years after initial improvement, indicating that
HSCT had only a temporary benefit.
Dr. Fassas concluded that further studies are warranted to evaluate bone
marrow transplantation strategies in patients with MS. The panel agreed
that multicenter, randomized, double-blind,
controlled trials will be necessary to fully appreciate the role of HSCT
and that patients with less severe forms of MS should be considered for
these studies.
References
[1] Lassmann H. The new pathology of MS [keynote address]. Program and
abstracts of the Fifth Annual Meeting of the Americas Committee for
Treatment and Research in Multiple Sclerosis (ACTRIMS); October 15,
2000; Boston, Massachusetts.
[2] Consroe P, Musty R, Rein J, et al. The perceived effects of smoked
cannabis on patients with multiple sclerosis. Eur Neurol. 1997;38:44-48.
[3] Greenberg HS, Werness SAS, Pugh JE, et al. Short-term effects of
smoking marijuana on balance in patients with multiple sclerosis and
normal volunteers. Clin Pharmacol Ther. 1994;55:324-328.
[4] Baker D, Pryce G, Croxford JL, et al. Cannabinoids control tremor
and spasticity in experimental multiple sclerosis. Program and abstracts
of the Fifth Annual Meeting of the Americas Committee for Treatment and
Research in Multiple Sclerosis (ACTRIMS); October 15, 2000; Boston,
Massachusetts. Abstract 3.
[5] Rao SM. Neuropsychology of multiple sclerosis. Curr Opin
Neuropsychol. 1995;8:216-220.
[6] Pelosi L, Geesken JM, Holly M, et al. Working memory impairment in
early multiple sclerosis: evidence from an event-related potential study
of patients with clinically isolated myelopathy. Brain.
1997;120:2039-2058.
[7] Beatty WW. Memory and "frontal lobe" dysfunction in multiple
sclerosis. J Neurol Sci. 1993;115(suppl):S38-S41.
[8] Beatty WW, Monson N. Picture and motor sequencing in multiple
sclerosis. J Clin Exp Neuropsychol. 1994;16:165-172.
[9] Rao SM, Hammeke TA, McQuillen MP, et al. Memory disturbance in
chronic progressive multiple sclerosis. Arch Neurol. 1984;41:625-631.
[10] DeLuca J, Johnson SK, Natelson BH. Information processing
efficiency in chronic fatigue syndrome and multiple sclerosis. Arch
Neurol. 1993;50:301-304.
[11] Filley CM, Heaton RK, Nelson LM, et al. A comparison of dementia in
Alzheimer's disease and multiple sclerosis. Arch Neurol.
1989;46:157-161.
[12] Rao SM, Leo GJ, Ellington L, et al. Cognitive dysfunction in
multiple sclerosis, II: impact on employment and social functioning.
Neurology. 1991;41:692-696.
[13] Franklin GM, Nelson LM, Filley CM, et al. Cognitive loss in
multiple sclerosis: case reports and review of the literature. Arch
Neurol.
1989;46:162-167.
[14] Krupp L, Christodoulou C, Elkins L, et al. Designing clinical
trials for treating MS associated cognitive impairment. Program and
abstracts of the Fifth Annual Meeting of the Americas Committee for
Treatment and Research in Multiple Sclerosis (ACTRIMS); October 15,
2000; Boston, Massachusetts. Abstract 4.
[15] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an
Expanded Disability Status Scale (EDSS). Neurology. 1983;33:1444-1452.
[16] Rudick R, Antel J, Confavreux C, et al. Recommendations from the
National Multiple Sclerosis Society Clinical Outcomes Assessment Task
Force. Ann Neurol. 1997;42:379-382.
[17] Vickrey BG, Hays RD, Genovese BJ, et al. Comparison of a generic to
disease-targeted health-related quality-of-life measures for multiple
sclerosis. J Clin Epidemiol. 1997;50:557-569.
[18] Vickrey BG, Hays RD, Harooni R, et al. A health-related quality of
life measure for multiple sclerosis. Qual Life Res. 1995;4:187-206.
[19] Janardhan V, Bakshi R. Quality of life and its relationship to
brain lesions and atrophy on magnetic resonance images in 60 patients
with multiple sclerosis. Arch Neurol. 2000;57:1485-1491.
[20] Miller DM, Jacobs L, Lacy JR, et al. Quality of life of patients
enrolled in MSTRAC: a registry of multiple sclerosis treatment and care.
Program and abstracts of the Fifth Annual Meeting of the Americas
Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS);
October 15, 2000; Boston, Massachusetts. Abstract 5.
[21] Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in
the lesions of multiple sclerosis. N Engl J Med. 1998;338:278-326.
[22] Losseff NA, Wang L, Lai HM, et al. Progressive cerebral atrophy in
multiple sclerosis: a serial MRI study. Brain. 1996;119:2009-2019.
[23] Bakshi R, Miletich RS, Kinkel PR, et al. High-resolution
fluorodeoxyglucose positron emission tomography shows both global and
regional cerebral hypometabolism in multiple sclerosis. J Neuroimaging.
1998;8:228-234.
[24] Kidd D, Barkhof F, McConnell R, et al. Cortical lesions in multiple
sclerosis. Brain. 1999;122:17-26.
[25] Bakshi R, Shaikh ZA, Janardhan V. MRI T2 shortening ("black T2") in
multiple sclerosis: frequency, location, and significance. Neuroreport.
2000;11:15-21.
[26] Bakshi R, Dmochowski J, Bermel RA, et al. T2 hypointensity in gray
matter of MS patients: a quantitative study. Program and abstracts of
the Fifth Annual Meeting of the Americas Committee for Treatment and
Research in Multiple Sclerosis (ACTRIMS); October 15, 2000; Boston,
Massachusetts. Abstract 6.
[27] Freedman MS. The immunological rationale for bone marrow
transplantation in multiple sclerosis. Program and abstracts of the
Fifth Annual Meeting of the Americas Committee for Treatment and
Research in Multiple Sclerosis (ACTRIMS); October 15, 2000; Boston,
Massachusetts.
[28] Burt RK. Hematopoietic stem cell therapy for multiple sclerosis.
Program and abstracts of the Fifth Annual Meeting of the Americas
Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS);
October 15, 2000; Boston, Massachusetts.
[29] Fassas A. High-dose, myeloimmunoablative chemotherapy followed by
autologous stem cell transplantation in the treatment of MS. Program and
abstracts of the Fifth Annual Meeting of the Americas Committee for
Treatment and Research in Multiple Sclerosis (ACTRIMS); October 15,
2000; Boston, Massachusetts.
------------------------------------------------------------------------
Rohit Bakshi, MD, 
http://www.drbakshi.com/
, is a staff neurologist and
multiple sclerosis specialist at the State University of New York at
Buffalo.
------------------------------------------------------------------------
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