- Email: [email protected]
2-31-10 Enhanced spasticity in primary chronic MS patients treated interferon-beta-1b
Multiple with AM compared to OND and HC (p < 0.05). Interestingly, patients with MG had higher numbers of RANTES mANA expressing MNC in blood compared to OND patients and HC (p < 0.05). Taken together the present results do not indicate a strong upregulation of mRNA expression of the studied chemokines in MS, ON and MG with the exception for RANTES, which was upregulated in MG as well as AM. Ongoing studies will define the role for chemokine receptors on mononuclear cells in blood and CSF in these diseases.
12-31-07
1 The augmented numbers of cytokine mRNA expresslng mononuclear cells (YNC) in multiple sclerosis (MS) reflect a non-specific Inflammatory response
D. Matusevicius, M. Sdderstrdm l, P. Kivisakk, L. Stawiarz, H. Link. Dept. of Neurolog)! Karolinska Institute, Huddinge Hospital, Stockholm, Huddinge University
Sweden, Hospital,
’ Dept. of Opthalmologyl Stockholm, Sweden
S. Fred&son,
Universi~ Kardinska Institute,
Perfvascular accumulation of immune cells within the CNS is characteristic of MS. These cells could be involved in the pathogenesis and perpetuation of MS. They implicate the involvement of immunoregulatory cytokines, i.e. proteins which act as signals between cells of the immune system. We evaluated the T helper (Th) 1 related cytokines IFN-y and TNF-B, the Th2 cytokines 11-4, 6, 10 and 13, the macrophage derived TNFa and 11-12, and the cytotoxic perforin adopting in situ hybridization to detect and enumerate cytokine mRNA expressing mononuclear cells (MNC) in blood and CSF. All cytokines evaluated were upregulated in MS, more in CSF than systemically. The following mean frequencies of cytokine mRNA positive cells were found in MS: i/5,000 and i/500 MNC. resoectivelv, for IFN-Y: i/13.000 and i/2,800 for TNF-B; l/1.100 and l/l70 for lL-4; l/33,000 and i/10,000 for IL-6; ~1/14,000 and t/10&0 for IL-IO; i/50,000 and l/5,000 for IL-13; l/14,000 and t/2,800 for TNFa; l/33,006 and l/1,700 for IL-12; and l/5,900 and i/3,900, respectively for pedorin. Corresponding frequencies for all these cytokines in healthy subjects and controls with non-inflammatory neurological diseases were l/l 00,000 or lower. In contrast, patients with aseptic meningitis (AM) had similar mean frequencies of MNC expressing cytokine transcripts as patients with MS. This cytokine storm was also observed in patients with monosymptomatic acute unilateral optic neuritis (ON), in many cases representing very early MS. No significant relations were noticed for various clinical variables and cytokine mRNA positive cell numbers, with the exception that low disability and benign course were associated with high numbers of TGF-B mRNA expressing MNC. We conclude that increased numbers of cytokine mRNA expressing MNC in MS, ON and AM reflect the non-specific inflammatory responses occurring in these diseases.
2 31-08 The treatment Lz---J sclerosis with A. Wajgt, L. Strryiewska, Neurology,
of chronic cladrlbine
S. Ckhudfo,
SIAM, Katowice,
progressive
P. Griebb,
K. Jan&.
multiple Department
of
Poland
A 2 year, placebo-controlled, pairedmatched, double blind, crossover study was started in 1994 to evaluate cladribine R-CDA/ effect in the group of 79 patients with chronic secondary progressive multiple sclerosis A&/. In the first year patients were given P-CDA 0.06 mg/kg S.C. per day for 5 days as seven every 6 weeks courses for a total of 2.1 mg/kg body weight or placebo. During the second year patients treated with placebo in the first year were crossed over to P-cda treatment according to the same schedule. Analysis of the results revealed a favourably influence of P-CDA medication on the neurological performance scores, both in the Kurtzke extended disability status /Chi2 test p below 0.05, Wilcoxon test p = 0.013, U Mann-Withney test p = 0.030/ and in ambulation index evaluation. NMR analysis was performed in 20 cases /6 placebo, 14 subjected to therapy/ and revealed that all P-CDA treated patients had no enhancing lesions 5 months after therapy. By contast in placebo treated patients enhacing lesions were evidenced in every case. We have observed significant lowering of II-2 and soluble II-2 receptor level in the blood after 2-CDA medication/P below 0.01 and 0.05/. No serious adverse effects were observed and short term risks of cladribine seem acceptable for patients with progressive MS.
12-31-09
1 Evaluation of data base << EDMUS >> from its dally use In neurology department
P. Bernet-Bernady,
P.M. Preux, C. Preux, E. Lagrange,
CHU Dupuyfren Service Limoges, France
De Neurokqie,
2 Avenue
M. Dumas,
Martin
Luther
J.M. Vallat. King,
Multiple sclerosis (MS) is the most common idiopathic inflammatory disorder of the central nervous system. It is the most frequent cause of neurological disability in young adults. MS is defined by clinical, biological and radiological
Sclerosis
s117
criteria. There is a need to standardize morbidity records in MS patients. The use of a common language is an essential prerequisite for the establishment of a database to provide descriptive details of the disease and allow rapid identification of appropriate patients for cross studies of therapeutic trials. EDMUS, < a European Database for Multiple scferosis >-> includes both retrospective and prospective data. It is user friendly and fast to facilitate regular and long term use, even in departments with facilities. The clinical data of 199 patients with MS were recorded in EDMUS to study the differents clinical, radiological and biological variables and especially to evaluate the use of database software. Most findings in our population are in accordance with other studies: the sex ratio (0.4) the age onset (34.5 11 .O ans), the mean age (45.5 f 3.3 ans) and the event at onset. The difference with other studies is the over evaluation of the sub group with relapsing disease course (73.4%) and underevaluation of the subgroup with progressive evolution (20.1%). The aggravation of the impairment score is comparable with EDMUS impaimtent scale (EIS) and Kurtzke expanded disability status scales (EDSS) and less appreciable with ambulation index (Al). The clinical, radiological data are different between the group having disease remittent course and the group with aprogressive course. EDMUS is time saving for the clinician and gives an overview which may be used as a disease summary for any reexamination of the patient. Priority has been given, to analytical data from which interpretations such as classification of the disease progression are computer generated and reduce mistakes. But the magnetic resonance imaging data as well as genetic data are poor. Ideally, the clinical scoring scale should be objective, quantifiable, sensitive, specific and valid. EIS has the only scale requiring obligatory scoring. However, EDSS is the most widely used clinical rating method for following disease progression. Unfortunately, it does not require obligatory data. The selection windows render treatment, the EDSS and prospective or retrospective data inaccessible. The EDMUS system is a good database and it should continue to evolue.
2-31-l 0 P. Bramanti
Enhanced spastlcity in primary chronic MS patients treated Interferon-beta-lb I, C. Rifici ‘, G. D’Aleo ‘, D. Floridia ‘, L. Saltuari 2, E. Sessa ’
’ Centro per lo Studio ed il Trattamento dei Neuroiesi Lungcdegenti, Neurophysi~thofcg~ University of Messina, Ital,! 2Krankenhaus University of Innsbruck, Austria
Chair of Hochziri,
Spasticity can be a major symptom in all forms of MS, and there are anedoctical reports that this symptom can be increased during treatment of relapsing forms of MS with interferon-beta-lb (in contrast to considerable and consistent improvement of the disease burden as shown by MRI and the clinical manifestations of the disease which clearly improve). Here we report that in primary progressive MS patients undergoing compassionate treatment with the same drug spasticity appeared increased in 13 of 19 patients with primary progressive MS and this phenomenon forced us to intensify the antispastic therapy. As controls we also investigated 15 patients with clinically defined relapsing -remitting MS who had been treated with interferon-beta-lb for one year and 15 patients with clinically defined primary progressive multiple sclerosis that were not treated, in a blind therapy, with interferon-beta 1 b. In these patients no increase in spasticity it was observed. Such a possibility, that needs further investigation, should be taken into account in planning of new clinical trials in this form of MS.
2-31-11
Alpha Interferon and muftlple sclerosis.
Pilot study
J.A. Cabrera-G6mez, E. Santana, A. G6mez, A. Mir6, A. Rodriguez, J.A. Cabrera-NuAez, P. L6pez Saura, M. Casanova, 0. Vals, L. Quevedo the Group of MS IFN-alpha Trials. Departament of Neurology; Hospital Gustav0
Aldereguia,
Cienfuegos,
for
Cuba
Nine multiple sclerosis (MS) clinically definite patients (Poser et al) with one or more relapse in the 2 previous year, MRI lesions of MS, DCB in CSF and normal conduction velocity in the 4 limbs were studied. IFN alpha 2b recombinant (Hebeferon R) was administered 6 millions UI intramuscularly weekly during 3 to 48 (average 24) months. Six patients had the relapsing remitting (RR) form: 2 the relapsing-progressive (RP) and one the relapsing-remitting-stable (RRST). The whole group had considerably fewer relapses after treatment than in the 2 previous years (3 and 13 respectively) and in RR the decrease was from 11 to 3 relapses: with shorter duration and less intense. Three patients improve their score in Kurtzke scale in 1 or more points and 2 less than 1 point. All of the patients improved the Scripps scale score except the RRST patient. The treatment was intermpted in two cases: one abandoned voluntarily and the other, with RRST, it was considered not necessary. These results and others indicate that IFN alpha may be effective in MS. It is necessary to continue the research with controlled trials, some already in course.
12-31-07
1 The augmented numbers of cytokine mRNA expresslng mononuclear cells (YNC) in multiple sclerosis (MS) reflect a non-specific Inflammatory response
D. Matusevicius, M. Sdderstrdm l, P. Kivisakk, L. Stawiarz, H. Link. Dept. of Neurolog)! Karolinska Institute, Huddinge Hospital, Stockholm, Huddinge University
Sweden, Hospital,
’ Dept. of Opthalmologyl Stockholm, Sweden
S. Fred&son,
Universi~ Kardinska Institute,
Perfvascular accumulation of immune cells within the CNS is characteristic of MS. These cells could be involved in the pathogenesis and perpetuation of MS. They implicate the involvement of immunoregulatory cytokines, i.e. proteins which act as signals between cells of the immune system. We evaluated the T helper (Th) 1 related cytokines IFN-y and TNF-B, the Th2 cytokines 11-4, 6, 10 and 13, the macrophage derived TNFa and 11-12, and the cytotoxic perforin adopting in situ hybridization to detect and enumerate cytokine mRNA expressing mononuclear cells (MNC) in blood and CSF. All cytokines evaluated were upregulated in MS, more in CSF than systemically. The following mean frequencies of cytokine mRNA positive cells were found in MS: i/5,000 and i/500 MNC. resoectivelv, for IFN-Y: i/13.000 and i/2,800 for TNF-B; l/1.100 and l/l70 for lL-4; l/33,000 and i/10,000 for IL-6; ~1/14,000 and t/10&0 for IL-IO; i/50,000 and l/5,000 for IL-13; l/14,000 and t/2,800 for TNFa; l/33,006 and l/1,700 for IL-12; and l/5,900 and i/3,900, respectively for pedorin. Corresponding frequencies for all these cytokines in healthy subjects and controls with non-inflammatory neurological diseases were l/l 00,000 or lower. In contrast, patients with aseptic meningitis (AM) had similar mean frequencies of MNC expressing cytokine transcripts as patients with MS. This cytokine storm was also observed in patients with monosymptomatic acute unilateral optic neuritis (ON), in many cases representing very early MS. No significant relations were noticed for various clinical variables and cytokine mRNA positive cell numbers, with the exception that low disability and benign course were associated with high numbers of TGF-B mRNA expressing MNC. We conclude that increased numbers of cytokine mRNA expressing MNC in MS, ON and AM reflect the non-specific inflammatory responses occurring in these diseases.
2 31-08 The treatment Lz---J sclerosis with A. Wajgt, L. Strryiewska, Neurology,
of chronic cladrlbine
S. Ckhudfo,
SIAM, Katowice,
progressive
P. Griebb,
K. Jan&.
multiple Department
of
Poland
A 2 year, placebo-controlled, pairedmatched, double blind, crossover study was started in 1994 to evaluate cladribine R-CDA/ effect in the group of 79 patients with chronic secondary progressive multiple sclerosis A&/. In the first year patients were given P-CDA 0.06 mg/kg S.C. per day for 5 days as seven every 6 weeks courses for a total of 2.1 mg/kg body weight or placebo. During the second year patients treated with placebo in the first year were crossed over to P-cda treatment according to the same schedule. Analysis of the results revealed a favourably influence of P-CDA medication on the neurological performance scores, both in the Kurtzke extended disability status /Chi2 test p below 0.05, Wilcoxon test p = 0.013, U Mann-Withney test p = 0.030/ and in ambulation index evaluation. NMR analysis was performed in 20 cases /6 placebo, 14 subjected to therapy/ and revealed that all P-CDA treated patients had no enhancing lesions 5 months after therapy. By contast in placebo treated patients enhacing lesions were evidenced in every case. We have observed significant lowering of II-2 and soluble II-2 receptor level in the blood after 2-CDA medication/P below 0.01 and 0.05/. No serious adverse effects were observed and short term risks of cladribine seem acceptable for patients with progressive MS.
12-31-09
1 Evaluation of data base << EDMUS >> from its dally use In neurology department
P. Bernet-Bernady,
P.M. Preux, C. Preux, E. Lagrange,
CHU Dupuyfren Service Limoges, France
De Neurokqie,
2 Avenue
M. Dumas,
Martin
Luther
J.M. Vallat. King,
Multiple sclerosis (MS) is the most common idiopathic inflammatory disorder of the central nervous system. It is the most frequent cause of neurological disability in young adults. MS is defined by clinical, biological and radiological
Sclerosis
s117
criteria. There is a need to standardize morbidity records in MS patients. The use of a common language is an essential prerequisite for the establishment of a database to provide descriptive details of the disease and allow rapid identification of appropriate patients for cross studies of therapeutic trials. EDMUS, < a European Database for Multiple scferosis >-> includes both retrospective and prospective data. It is user friendly and fast to facilitate regular and long term use, even in departments with facilities. The clinical data of 199 patients with MS were recorded in EDMUS to study the differents clinical, radiological and biological variables and especially to evaluate the use of database software. Most findings in our population are in accordance with other studies: the sex ratio (0.4) the age onset (34.5 11 .O ans), the mean age (45.5 f 3.3 ans) and the event at onset. The difference with other studies is the over evaluation of the sub group with relapsing disease course (73.4%) and underevaluation of the subgroup with progressive evolution (20.1%). The aggravation of the impairment score is comparable with EDMUS impaimtent scale (EIS) and Kurtzke expanded disability status scales (EDSS) and less appreciable with ambulation index (Al). The clinical, radiological data are different between the group having disease remittent course and the group with aprogressive course. EDMUS is time saving for the clinician and gives an overview which may be used as a disease summary for any reexamination of the patient. Priority has been given, to analytical data from which interpretations such as classification of the disease progression are computer generated and reduce mistakes. But the magnetic resonance imaging data as well as genetic data are poor. Ideally, the clinical scoring scale should be objective, quantifiable, sensitive, specific and valid. EIS has the only scale requiring obligatory scoring. However, EDSS is the most widely used clinical rating method for following disease progression. Unfortunately, it does not require obligatory data. The selection windows render treatment, the EDSS and prospective or retrospective data inaccessible. The EDMUS system is a good database and it should continue to evolue.
2-31-l 0 P. Bramanti
Enhanced spastlcity in primary chronic MS patients treated Interferon-beta-lb I, C. Rifici ‘, G. D’Aleo ‘, D. Floridia ‘, L. Saltuari 2, E. Sessa ’
’ Centro per lo Studio ed il Trattamento dei Neuroiesi Lungcdegenti, Neurophysi~thofcg~ University of Messina, Ital,! 2Krankenhaus University of Innsbruck, Austria
Chair of Hochziri,
Spasticity can be a major symptom in all forms of MS, and there are anedoctical reports that this symptom can be increased during treatment of relapsing forms of MS with interferon-beta-lb (in contrast to considerable and consistent improvement of the disease burden as shown by MRI and the clinical manifestations of the disease which clearly improve). Here we report that in primary progressive MS patients undergoing compassionate treatment with the same drug spasticity appeared increased in 13 of 19 patients with primary progressive MS and this phenomenon forced us to intensify the antispastic therapy. As controls we also investigated 15 patients with clinically defined relapsing -remitting MS who had been treated with interferon-beta-lb for one year and 15 patients with clinically defined primary progressive multiple sclerosis that were not treated, in a blind therapy, with interferon-beta 1 b. In these patients no increase in spasticity it was observed. Such a possibility, that needs further investigation, should be taken into account in planning of new clinical trials in this form of MS.
2-31-11
Alpha Interferon and muftlple sclerosis.
Pilot study
J.A. Cabrera-G6mez, E. Santana, A. G6mez, A. Mir6, A. Rodriguez, J.A. Cabrera-NuAez, P. L6pez Saura, M. Casanova, 0. Vals, L. Quevedo the Group of MS IFN-alpha Trials. Departament of Neurology; Hospital Gustav0
Aldereguia,
Cienfuegos,
for
Cuba
Nine multiple sclerosis (MS) clinically definite patients (Poser et al) with one or more relapse in the 2 previous year, MRI lesions of MS, DCB in CSF and normal conduction velocity in the 4 limbs were studied. IFN alpha 2b recombinant (Hebeferon R) was administered 6 millions UI intramuscularly weekly during 3 to 48 (average 24) months. Six patients had the relapsing remitting (RR) form: 2 the relapsing-progressive (RP) and one the relapsing-remitting-stable (RRST). The whole group had considerably fewer relapses after treatment than in the 2 previous years (3 and 13 respectively) and in RR the decrease was from 11 to 3 relapses: with shorter duration and less intense. Three patients improve their score in Kurtzke scale in 1 or more points and 2 less than 1 point. All of the patients improved the Scripps scale score except the RRST patient. The treatment was intermpted in two cases: one abandoned voluntarily and the other, with RRST, it was considered not necessary. These results and others indicate that IFN alpha may be effective in MS. It is necessary to continue the research with controlled trials, some already in course.