From infoserv-owner@infosci.org Fri Apr 21 11:27:37 1995 Received: from infosci.org (inetgate.infosci.org [194.70.23.129]) by kantti.helsinki.fi (8.6.12+Emil1.1/8.6.5) with SMTP id LAA02263 for ; Fri, 21 Apr 1995 11:26:29 +0300 Received: by infosci.org (5.65/CB-0.7) id AA17903; Fri, 21 Apr 95 08:20:34 GMT Date: Fri, 21 Apr 95 08:20:34 GMT Message-Id: <9504210820.AA17903@infosci.org> To: aapo.halko@Helsinki.FI From: infoserv@infosci.org Subject: Majordomo file: list 'ms-docs' file 'ivmp.txt' Reply-To: infoserv@infosci.org MIME-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Content-Transfer-Encoding: 7bit Status: RO -- ====================================================================== What follows is a list of abstracts covering the use of IV methylprednisolone of the treatment of MS. A few papers really refer to the treatment for optic neuritis (ON) In general, the consensus for therapy has seemed to settle on a 5 day pulse of MP at 1000mg and a shorter course of IVMP (3 day) for ON. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 95022135 Barkhof F Tas MW Frequin ST Scheltens P Hommes OR Nauta JJ Valk J Limited duration of the effect of methylprednisolone on changes on MRI in multiple sclerosis. Neuroradiology (1994 Jul) 36(5):382-7 Treatment with methylprednisolone reduces the duration and severity of clinical relapses in multiple sclerosis (MS), while reducing the number of gadolinium-enhancing lesions on T1-weighted MRI. We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium- enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. Two experienced readers in conference defined the number of active (gadolinium-enhancing and new or enlarging nonenhancing) lesions. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images, indicating persistent change such as oedema, cellular infiltration or demyelination. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks). Institutional address: Department of Diagnostic Radiology Free University Hospital Amsterdam The Netherlands. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 95016836 Kirk PF Williams JD Petersen MM Compston DA The effect of methylprednisolone on monocyte eicosanoid production in patients with multiple sclerosis. J Neurol (1994 Jun) 241(7):427-31 The in vitro effect of methylprednisolone on prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and thromboxane B2 (TXB2) synthesis by adherent monocytes was examined using samples of peripheral blood from 15 patients with multiple sclerosis and 18 normal controls. Eicosanoid production by monocytes was reduced in patients compared with controls and there was a dose-dependent inhibitory effect of methylprednisolone on eicosanoid production in both groups. In vitro production of PGE2 and TXB2 but not LTB4 was reduced in patients with multiple sclerosis following intravenous treatment with methylprednisolone compared with pretreatment samples. In a separate cohort of 20 patients with multiple sclerosis and 15 controls, the in vitro inhibition of PGE2 release by methylprednisolone was not associated with reduced pokeweed-mitogen-stimulated immunoglobulin G synthesis by peripheral blood mononuclear cells. These results suggest that methylprednisolone inhibits monocyte-macrophage function, but this effect is not specific to patients with multiple sclerosis. Institutional address: Department of Medicine University of Wales College of Medicine Heath Park Cardiff UK. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94364365 La Mantia L Eoli M Milanese C Salmaggi A Dufour A Torri V Double-blind trial of dexamethasone versus methylprednisolone in multiple sclerosis acute relapses. Eur Neurol (1994) 34(4):199-203 The efficacy of dexamethasone (DX) and methylprednisolone (MP) at high (HD) and low (LD) dose in acute multiple sclerosis (MS) relapses was evaluated by a double-blind trial in 31 patients followed for 1 year. DX and HDMP were similarly efficacious in promoting recovery, while LDMP was ineffective in the short-term outcome and was followed by an early clinical reactivation. The different outcomes seem to be related to different immunomodulating effects, mainly on cerebrospinal fluid (CSF) IgG synthesis and on peripheral blood and CSF CD4+ lymphocyte subsets. Institutional address: Department of Neurology National Institute of Neurology C. Besta Milan Italy. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94327280 Dufour A Salmaggi A La Mantia L Eoli M Nespolo A Milanese C High-dose methylprednisolone treatment-induced changes in immunological parameters in progressive MS patients. Int J Neurosci (1994 Mar) 75(1-2):119-28 The effect of High-Dose Methylprednisolone (HD-MP) treatment on Peripheral Blood (PB) and Cerebrospinal Fluid (CSF) immune parameters was investigated in 9 patients with relapsing-progressive Multiple Sclerosis (MS). Short-time effects included reduction of the percentage of CD3+, CD4+ and CD4+CD45RA+ PB lymphocytes and increase in CD3-CD56+ cells. At the end of the treatment, only increase in PB CD19+ and in CSF CD8+, CD8+CD28+ and decrease of CSF CD4+CD45RA- and serum IL2R levels were observed. No changes in CD11a+CD4+, CD18+CD14+ PB cells were observed after treatment. The results further stress the complex and multifaceted action of HD-MP on immune parameters. Institutional address: Istituto Nazionale Neurologico C.Besta Milano Italy. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94275480 Scolding NJ Lees AJ Micrographia associated with a parietal lobe lesion in multiple sclerosis. J Neurol Neurosurg Psychiatry (1994 Jun) 57(6):739-41 The occurrence of micrographia in a 52 year old women two years after an isolated episode of painful sensory disturbance led to the diagnosis of multiple sclerosis. Her handwriting returned to normal after a course of intravenous methylprednisolone. Previous reports of movement disorders occurring in the context of multiple sclerosis are briefly reviewed. The finding on MRI studies of an enhancing lesion in the dominant parietal white matter supports Kinnier Wilson's suggestion that the anatomical origin of micrographia lies in the cerebral hemisphere rather than the corpus striatum. Institutional address: National Hospital for Neurology and Neurosurgery London UK. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94160695 Funakawa I Hara K Yasuda T Terao A Intractable hiccups and sleep apnea syndrome in multiple sclerosis: report of two cases. Acta Neurol Scand (1993 Dec) 88(6):401-5 Two cases of multiple sclerosis associated with intractable hiccups (IH) and sleep apnea syndrome (SAS) are reported. Lesions were detected in the tegmentum of the medulla oblongata by magnetic resonance imaging. In one case, high dose methylprednisolone was remarkably effective for the IH. For the SAS, amitriptyline was effective in one case. The IH and SAS are thought to be important symptoms when a lesion occurs in the tegmentum of the medulla oblongata, including the paramedian and lateral reticular formations. If IH appears in conjunction with a lesion in the tegmentum of the medulla oblongata, one must be vigilant for the development of SAS. Institutional address: Department of Internal Medicine Kawasaki Medical School Japan. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94050354 Maciejek Z Niezgodzinska-Maciejek A [Prospective assessment of combined treatment with high doses of intravenous methylprednisolone and long term administration of Isoprinosine in multiple sclerosis patients] Prospektywna ocena skojarzonego leczenia wysokimi dawkami methylprednisolonu do~zylnie i przewleklego izoprinozyna u chorych na stwardnienie rozsiane. Neurol Neurochir Pol 1993 May-Jun;27(3):321-9 (Published in Polish) The authors present a prospective assessment of combined treatment with high doses of methylprednisolone intravenously and long term administration (12-18 months) of Isoprinosine. The study included 57 patients with clinically certain diagnosis of multiple sclerosis who were examined 1-5 years after treatment completion. Patients with similar degree of motor function disability served for control. Clinical improvement assessed by the motor disability scale of Kurtzke was obtained in over half the patients with various forms of the disease. The results were best in cases of multiple sclerosis of remittent course and those treated at the beginning of the disease. Institutional address: Klinicznego Oddzialu Neurologicznego 10 Wojskowego Szpitala Klinicznego z Poliklinika Bydgoszczy. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94050353 Zakrzewska-Pniewska BZ [High dose methylprednisolone therapy in patients with multiple sclerosis] Wysokie dawki methylprednisolonu w leczeniu stwardnienia rozsianego. Neurol Neurochir Pol 1993 May-Jun;27(3):313-9 (Published in Polish) A trial of high-dose pulsed intravenous methylprednisolone was carried out in 20 patients with multiple sclerosis (MS). Multimodal evoked potentials examination (visual, brainstem auditory and somatosensory evoked potentials) were evaluated before and after treatment with methylprednisolone (a single daily dose of 1000 mg was administrated for five consecutive days). Clinical improvement did not correlate well with evoked potential changes. Institutional address: Kliniki Neurologicznej Akademii Medycznej Warszawie. [5 day] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94050059 Beck RW Cleary PA Trobe JD Kaufman DI Kupersmith MJ Paty DW Brown CH The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group [see comments] N Engl J Med 1993 Dec 9;329(24):1764-9 BACKGROUND. Optic neuritis is often the first clinical manifestation of multiple sclerosis, but little is known about the effect of corticosteroid treatment for optic neuritis on the subsequent risk of multiple sclerosis. METHODS. We conducted a multicenter study in which 389 patients with acute optic neuritis (and without known multiple sclerosis) were randomly assigned to receive intravenous methylprednisolone (250 mg every six hours) for 3 days followed by oral prednisone (1 mg per kilogram of body weight) for 11 days, oral prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days. Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients. RESULTS. Definite multiple sclerosis developed within the first two years in 7.5 percent of the intravenous-methyl-prednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients). The adjusted rate ratio for the development of definite multiple sclerosis within two years in the intravenous- methylprednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-prednisone group. The beneficial effect of the intravenous-steroid regimen appeared to lessen after the first two years of follow-up. Signal abnormalities on magnetic resonance imaging (MRI) of the brain were a strong indication of risk for the development of definite multiple sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66). The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry. CONCLUSIONS. In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period. Institutional address: Jaeb Center for Health Research Tampa FL 33613. [This is the three day but it applies to ON not MS] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94045719 Alam SM Kyriakides T Lawden M Newman PK Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose. J Neurol Neurosurg Psychiatry 1993 Nov;56(11):1219-20 A randomised double-blind placebo-controlled trial of intravenous methylprednisolone versus oral methylprednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of multiple sclerosis (MS). After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of methylprednisolone for five consecutive days and with reassessment at days five and twenty-eight. There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed. In this study oral treatment with methylprednisolone was as effective as intravenous treatment in acute relapse of MS. Institutional address: Department of Neurology Middlesbrough General Hospital Cleveland UK. [5 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 94026181 Frequin ST Lamers KJ Borm GF Barkhof F Jongen PJ Hommes OR T-cell subsets in the cerebrospinal fluid and peripheral blood of multiple sclerosis patients treated with high-dose intravenous methylprednisolone. Acta Neurol Scand 1993 Aug;88(2):80-6 To determine the effects of high-dose intravenous methylprednisolone (MP) on lymphocytes and lymphocyte subpopulations in the cerebrospinal fluid (CSF) and peripheral blood (PB) in multiple sclerosis (MS) patients, we studied 67 patients with definite MS treated with MP. They were classified according to the disease course: 32 chronic progressive (CP) patients, 25 relapsing-remitting (RR) patients, and 10 patients with a chronic progressive disease course accompanied by relapses and remissions (CP + RR). MS patients were treated with 1000 mgr intravenous MP daily for 10 consecutive days. Before and after MP treatment we simultaneously studied CSF and PB CD3+, CD4+, CD8+, CD20+, and Ia1+ cell subsets. Kurtzke's Expanded Disability Status Scale (EDSS) was used for clinical evaluation. Progresson rate was defined as the ratio of EDSS to disease duration. Thirteen patients with lumbar disk herniation were investigated as controls. Before MP, we found in MS patients, especially inthe CP group, significantly lower CD4+ T-cell percentages in the PB with respect to controls (p < 0.05). The percentage of CD4+ T-cells in the CSF of MS patients was significantly higher compared with PB (p = 0.0001), and tended to be higher than in controls (p = 0.072). The CSF mononuclear cell counts were significantly correlated with higher percentages of CSF CD3+ (r = 0.40) and CD4+ (r = 0.47) T-cells and lower CSF CD8+ (r = -0.33) T- cell percentages. B-cell percentages in the CSF were significantly elevated compared with controls for all MS groups. No relation could be obtained between T- or B-cell subsets and EDSS or progression rate.(ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: Department of Neurology University Hospital Amsterdam The Netherlands. [10days!] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93263579 Whitaker JN Layton BA Herman PK Kachelhofer RD Burgard S Bartolucci AA Correlation of myelin basic protein-like material in cerebrospinal fluid of multiple sclerosis patients with their response to glucocorticoid treatment. Ann Neurol 1993 Jan;33(1):10-7 Predictors and laboratory correlates of the response of patients with multiple sclerosis to glucocorticoids are not well defined. Our study was undertaken to determine if the levels of myelin basic protein (MBP)-like material in cerebrospinal fluid (CSF) might indicate which patients with multiple sclerosis would show a short-term (5 day) or intermediate-term (40 day) improvement of at least a full-grade Kurtzke disability score after initiating treatment with glucocorticoids. A total of 62 patients received 71 courses of treatment consisting of 5 days of intravenous methylprednisolone (500 mg per day) usually followed by a 4-week tapering dose of oral prednisone. CSF was obtained before initiation of treatment and analyzed for MBP-like material by radioimmunoassay. Results were analyzed by chi 2 tests of association and by logistic regression. Individuals having a CSF MBP-like material level of ; or = 0.1 ng/ml overall showed a greater likelihood of continued improvement at day 40 (p = 0.014) or further improvement between days 5 and 40 (p = 0.003). Those in the first 15 days of worsening and with an elevated CSF MBP-like level were more likely to respond by day 5. Relapsing- remitting and relapsing- progressive forms of the disease were more likely to respond at both time points than were patients with primary or secondary chronic progressive patterns. The Kurtzke disability score at entry and the major anatomical site of the central nervous system symptomatically affected were not predictive of outcome at either time.(ABSTRACT TRUNCATED AT 250 WORDS) Institutional address: Department of Neurology University of Alabama Birmingham 35294. [5 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93206674 Bergamaschi R Versino M Raiola E Citterio A Cosi V High-dose methylprednisolone infusions in relapsing and in chronic progressive multiple sclerosis patients. One year follow-up. Acta Neurol (Napoli) 1993 Feb;15(1):33-43 Sixty Multiple Sclerosis patients hospitalized either in relapse (28) or in chronic progressive (32) phase of the disease were treated with high- dose methylprednisolone infusions (1 g/daily for 6 days). Clinical examinations, scored by Kurtzke's functional systems (FSs) and expanded disability status scale (EDSS), were performed before treatment, immediately after, and thereafter at 1,3,6 and 12 month intervals. In relapsing cases, 22 patients (78.6%) improved and EDSS mean value decreased by 1.39 points after the treatment; 8 patients had a new bout within one year. In chronic progressive cases, 18 patients (56.2%) improved and EDSS mean value decreased by 0.56 points after the treatment; 13 patients showed a new worsening throughout the follow-up period. The treatment proved to be safe and effective both in relapsing and in chronic progressive patients, determining rapid clinical improvement in most of the cases, and a slowing down of progression in some chronic patients. Institutional address: Fondazione Istituto Neurologico C. Mondino Universita di Pavia. [6 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93180952 Domzal T Zalewska B [Long-term steroid therapy in multiple sclerosis.] Dlugotrwala "pulsacyjna" terapia steroidowa w stwardnieniu rozsianym. Neurol Neurochir Pol 1992 Sep-Oct;26(5):621-5 (Published in Polish) Corticosteroids have a firm place in the treatment of ms, but as yet no generally accepted regimen of this therapy exists. It is not known either, how to achieve the greatest effectiveness of these drugs and avoid side effects. Many clinicians advocate high intravenous doses of methylprednisolone in a short time of 5-7 days. This method is more effective and leads to less adverse effects. The studied patients received prednisone (Encorton Polfa) in short course of 3 days every month. The dose of Encorton in each course depended on the clinical condition but never exceeded 200 mg. The regimen was used in 18 patients who were followed up at least one year. Evident improvement or stabilization was obtained in 11 cases. No adverse effects were noted. These results are comparable to those achieved with methylprednisolone. It may be supposed that every regimen of corticoid treatment in ms is usefull if it causes no adverse effects. The treatment by method of long-term pulse therapy with corticoids is applicable in outpatients. Institutional address: Klinika Neurologiczna CSK WAM ul. Szaserow Warszawa. [5-7 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93164665 Gerling J Kommerell G [Short-term effect of megadose steroid therapy in optic neuritis] Kurzzeiteffekt der Megadosis-Steroidtherapie bei Neuritis nervi optici. Klin Monatsbl Augenheilkd 1992 Dec;201(6):375-80 (Published in German) 15 patients with unilateral optic neuritis and 2 patients with bilateral optic neuritis were treated with 1000 mg methylprednisolone i.v. per day for 5 days. In the cases of unilateral optic neuritis, visual acuity was reduced to < or = 0.1, in those with bilateral optic neuritis to < or = 0.6 in the better eye. The treatment was started one to 70 days after the onset of the neuritis. We examined whether vision recovered rapidly during the treatment. As a rapid recovery we defined a fourfold improvement on a logarithmic scale during the 5 days of methylprednisolone medication. Such a rapid recovery was found in 11 of the 15 patients with unilateral and in 1 of the 2 patients with bilateral optic neuritis. A similar recovery was not found before and after the treatment interval. Although we did not have a control group, the correlation in time between the therapy and the rapid recovery suggests that the megadose steroids were effective in our patients. This interpretation is compatible with the results of the randomized controlled multicenter trial of Beck et al. (New Engl. J. Med. 326:81, 1992): However, the beneficial effect was seen up to 6 months only; one year after treatment, visual functions did no longer differ between the megadose and the placebo groups. Low-dose oral steroids did not improve visual function at any time and carried a higher risk for new episodes of neuritis, compared to placebo. Therefore, the "traditional" low-dose steroid therapy for optic neuritis has become obsolete. Institutional address: Abteilung Neuroophthalmologie und Schielbehandlung Universitats- Augenklinik Freiburg. [5days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93055353 Frequin ST Barkhof F Lamers KJ Hommes OR The effects of high-dose methylprednisolone on gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid measurements in multiple sclerosis. J Neuroimmunol 1992 Oct;40(2-3):265-72 Blood-brain barrier (BBB) disruption is probably the first event in the lesion development in multiple sclerosis (MS). This stage can be visualized by gadolinium-enhanced magnetic resonance (MR) imaging of the brain. Serial MR imaging studies have indicated a continuous spectrum of disease activity with waxing and waning of acute lesions, even in clinically stable MS patients. High-dose intravenous methylprednisolone (MP) has a beneficial clinical effect; reduces gadolinium enhancement, indicating improvement of BBB integrity; and, in MS patients, decreases intrathecal immunoglobulin synthesis with reduction of cerebrospinal fluid (CSF) myelin basic protein (MBP). A correlative triad is noted between gadolinium enhancement, clinical improvement, and decrease of CSF MBP following MP treatment, indicating a relationship between restoration of BBB integrity, clinical improvement and decrease of myelin breakdown. It is not clear whether MP interferes primarily with the process of demyelination or reacts non-specifically with its mediators. Institutional address: Institute of Neurology University Hospital Nijmegen Netherlands. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 93034141 Frequin ST Barkhof F Lamers KJ Hommes OR Borm GF CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after treatment with high-dose intravenous methylprednisolone. Acta Neurol Scand 1992 Sep;86(3):291-7 A total of 101 patients (62 women; 39 men) with definite MS were treated with 1000 mg methylprednisolone (MP) intravenously for 10 consecutive days. Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis) were significantly elevated. The mean CSF MBP levels were significantly higher in the relapsing-remitting (RR) and chronic progressive MS patients with relapses (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3 and 1.5 micrograms/l. A weak positive correlation was found between CSF MBP level and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels. Therefore demyelination seems to be related to intrathecal IgM production. After MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly after MP. The mean CSF MBP returned to reference values. In the RR group the decrease in CSF MBP was significantly correlated with the change in EDSS (r = 0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS. Following treatment CSF MBP was found to be related with the change in IgM index (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way indicating a relation between these 2 parameters. Institutional address: Department of Neurology University Hospital Nijmegen The Netherlands. [10 days!] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 92388910 Salle JY Hugon J Tabaraud F Boulesteix JM Vallat JM Dumas M Poser CM Improvement in motor evoked potentials and clinical course post- steroid therapy in multiple sclerosis. J Neurol Sci 1992 Apr;108(2):184-8 Motor evoked potentials (MEP) were recorded in 23 patients with definite relapsing multiple sclerosis before and after treatment with a short course of high dose of methylprednisolone. MEP were performed together with clinical examination just before treatment, and 6 and 60 days later. The following results were observed: (1) a statistically significant relationship between the corticospinal deficit and the alteration in MEP, (2) a significant improvement in latency of MEP by day 6, (3) a significant correlation between the change in the Kurtzke disability scale rating and the improvement in MEP. The results provide further evidence for the possible effectiveness of short courses of high dose corticosteroids in the treatment of relapses of multiple sclerosis and the usefulness of MEP in its assessment. Institutional address: Department of Neurology University Hospital Linoges France. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 92331330 Imamura K Hayashi F Suzumura A [Cytokine production by peripheral blood monocytes/macrophages in the patients with multiple sclerosis and its suppression by methylprednisolone] Rinsho Shinkeigaku 1992 Mar;32(3):276-80 (Published in Japanese) The production of tumor necrosis factor alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL- 6) by stimulated peripheral blood monocytes/macrophages (PBM) was assessed in patients with multiple sclerosis (MS), other neurological diseases (OND) or normal controls (NC) using enzyme-linked immunosorbent assay (ELISA). PBM obtained from acute phase of MS produced significantly higher amount of all these cytokines than those from chronic stable MS, OND or NC (TNF alpha, IL-1 alpha, IL-6: p less than 0.01, IL-1 beta: p less than 0.05). Methylprednisolone (MP) inhibited the lipopolysaccharide- induced cytokine production in a dose-dependent manner. These results suggest the possible roles of activated monocytes/macrophages in the acute exacervation of MS and suppressive effect of MP on cytokine production by activated monocytes/macrophages. Institutional address: Department of Neurology Hekinan Municipal Hospital. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 92317929 Miller DH Thompson AJ Morrissey SP MacManus DG Moore SG Kendall BE Moseley IF McDonald WI High dose steroids in acute relapses of multiple sclerosis: MRI evidence for a possible mechanism of therapeutic effect. J Neurol Neurosurg Psychiatry 1992 Jun;55(6):450-3 The integrity of the blood-brain barrier (BBB) in multiple sclerosis (MS) was monitored by serial gadolinium-(Gd)-DTPA enhanced MRI during and after the treatment of acute relapses with a three day course of high dose intravenous methylprednisolone (IVMP). During treatment there was a rapid reduction of BBB abnormalities in 96% of enhancing lesions. In spite of sustained clinical improvement, many lesions re- enhanced within a few days of stopping IVMP, and new lesions frequently appeared within one month. It is possible that the rapid, albeit transient, reversal of BBB abnormalities contributes to the accelerated recovery from relapses associated with IVMP treatment. Institutional address: Institute of Neurology London UK. [3 day] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 92131313 Barkhof F Frequin ST Hommes OR Lamers K Scheltens P van Geel WJ Valk J A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing multiple sclerosis patients treated with high-dose intravenous methylprednisolone. Neurology 1992 Jan;42(1):63-7 In a prospective study, we compared the number of gadolinium-DTPA (Gd- DTPA) enhancing lesions on MRI with the CSF and clinical findings before and after a total of 20 courses of high-dose intravenous methylprednisolone in relapsing multiple sclerosis patients. Before treatment, there was a significant correlation of Gd-DTPA enhancement (seen on 16 of 20 scans) and CSF myelin basic protein (MBP). If enhancement with Gd-DTPA represents inflammation and CSF-MBP indicates myelin breakdown, the amount of inflamed tissue should correlate with the amount of myelin being damaged. Clinical improvement occurred following 15 of 20 courses, and decrease of Gd- DTPA enhancement in 12 of 16 scans; the mean CSF-MBP level was the only CSF variable to return to reference values. There was a significant correlative triad of decrease in CSF-MBP, Gd-DTPA enhancement, and clinical disability. Thus, the clinical effect of methylprednisolone might be accompanied by a reduction of inflammation and myelin breakdown. Institutional address: Free University Hospital Department of Diagnostic Radiology Amsterdam The Netherlands. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 92131074 Beck RW Cleary PA Anderson MM Jr Keltner JL Shults WT Kaufman DI Buckley EG Corbett JJ Kupersmith MJ Miller NR et al A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group [see comments] N Engl J Med 1992 Feb 27;326(9):581-8 BACKGROUND AND METHODS. The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. RESULTS. Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did not differ from that in the placebo group. In addition, the rate of new episodes of optic neuritis in either eye was higher in the group receiving oral prednisone, but not the group receiving intravenous methylprednisolone, than in the placebo group (relative risk for oral prednisone vs. placebo, 1.79; 95 percent confidence interval, 1.08 to 2.95). CONCLUSIONS. Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis. Institutional address: Department of Ophthalmology University of South Florida College of Medicine Tampa 33612. [3 days for ON] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 91367308 Burnham JA Wright RR Dreisbach J Murray RS The effect of high-dose steroids on MRI gadolinium enhancement in acute demyelinating lesions. Neurology 1991 Sep;41(9):1349-54 Gadolinium (Gd) enhancement of brain lesions by MRI is a marker of active blood-brain barrier damage secondary to an inflammatory process. We studied the effects of high-dose (1,000 mg/d) intravenous (IV) methylprednisolone (Mp) for 4 to 8 days on Gd-enhancing lesions in seven patients with acute demyelinating diseases and compared pretreatment brain MRIs with studies obtained 1 to 4 days after treatment. Five patients had complete suppression, and two had significant suppression of Gd enhancement following treatment. In addition, six of seven patients had Gd-enhancing lesions that explained their clinical signs; in five of six of these patients, suppression of the Gd-enhanced lesions temporally correlated with clinical improvement. Thus, short courses of high-dose IV Mp suppress Gd enhancement in acute demyelinating lesions, and this correlates with clinical improvement. Institutional address: Colorado Neurological Institute Denver. [4-8 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- MEDECINE***** 91320077 Beer S Kesselring J [Steroid therapy in multiple sclerosis] Steroidtherapie bei Multipler Sklerose. Schweiz Med Wochenschr 1991 Jun 29;121(26):961-9 (Published in German) Since the 1950s steroids have been known to have a beneficial effect on recovery from acute exacerbations of multiple sclerosis. The main effect is a more rapid improvement after acute relapses due to resolution of edema in the central nervous system. Long-term steroid therapy showed no benefit in patients with a progressive course and involves dangerous side effects (Cushing's habitus, hyperglycemia, increased susceptibility to infections, peptic ulcers, osteoporosis, cataract). Intrathecal steroid administration offered no advantage over the conventional i.v. route. On the basis of a multicentre trial, ACTH therapy became the standard regime in the treatment of acute exacerbations. Recent reports have demonstrated a beneficial effect of therapy with high-dose methylprednisolone. Taking into account the restrictions and possible side effects, this therapy is a safe and efficient alternative to the standard ACTH regimen in the treatment of acute exacerbations in multiple sclerosis. Institutional address: Klinik fur Neurologie Abteilung fur klinische Neurophysiologie Kantonsspital St. Gallen. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 91021899 Miro J Amado JA Pesquera C Lopez-Cordovilla JJ Berciano J Assessment of the hypothalamic-pituitary-adrenal axis function after corticosteroid therapy for MS relapses [see comments] Acta Neurol Scand 1990 Jun;81(6):524-8 Doses of corticosteroids usually given for relapses of MS are able to suppress the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated HPA axis function using rapid ACTH stimulation and rapid overnight metyrapone tests, just after cessation of regular oral prednisone therapy for relapses in 14 MS patients. Nine additional patients treated with i.v. boluses of methylprednisolone before beginning conventional oral therapy were also evaluated. Sixteen patients had normal response to both tests and 6 patients had only a discordant response to one test. These data indicate that most patients had normal HPA axis function, which make corticosteroid replacement unnecessary after cessation of therapy for relapses. Institutional address: Service of Neurology National Hospital Marques de Valdecilla University of Cantabria Santander Spain. -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 91326243 Barkhof F Hommes OR Scheltens P Valk J Quantitative MRI changes in gadolinium-DTPA enhancement after high- dose intravenous methylprednisolone in multiple sclerosis. Neurology 1991 Aug;41(8):1219-22 In 12 patients with definite multiple sclerosis who received a total of 21 courses of high-dose (1 gram daily for 10 consecutive days) intravenous methylprednisolone, we performed MRI of the brain with and without gadolinium-DTPA before and after treatment. On the initial MRI, there was a total of 98 enhancing lesions, 93 of which were also represented on the unenhanced images. After treatment, 13 patients improved clinically, and 78 of the lesions lost enhancement but remained visible on the unenhanced images. There were six new enhancing lesions on the second MRI. Thus, the blood-brain-barrier integrity improved after high-dose IV methylprednisolone, which correlated well with the clinical improvement. The lesions remaining visible on the unenhanced images indicate an incomplete histologic recovery at the time of the second scan, and also demonstrate that unenhanced MRI alone is not sufficient to monitor disease activity in the short term in multiple sclerosis. Institutional address: Department of Diagnostic Radiology Free University Hospital Amsterdam The Netherlands. [10 days!] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- 91151312 Anderson TJ Donaldson IM Sheat JM George PM Methylprednisolone in multiple sclerosis exacerbation: changes in CSF parameters. Aust N Z J Med 1990 Dec;20(6):794-7 Twenty-six patients with multiple sclerosis (MS) received a total of 45 courses of intravenous methylprednisolone daily for seven days, for acute neurological deterioration. Changes in CSF parameters and clinical status following methylprednisolone were determined and first and repeat courses were compared. There were significant reductions in CSF IgG, CSF albumin, serum IgG and serum albumin levels and CSF IgG synthesis rate in the first and repeat treatment groups. CSF IgG index fell significantly with initial methylprednisolone treatment but not with subsequent courses. Oligoclonal bands disappeared in three patients. Definite clinical improvement followed 30 methylprednisolone courses, possible improvement followed six and no change followed seven. Clinical response was not predicted by pre- treatment CSF IgG synthesis status and did not correlate with its degree of reduction. Institutional address: Christchurch Hospital New Zealand. [7 days] -=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- -Richard Korejwo r.korjwo@GENIE.GEIS.COM You may copy and distribute verbatim copies of the text files above in any medium, provided that you publish the copyright notice and discaimer if that text file contains one, also you may not charge any fee for doing so without permission of the author or authors of any text file. In those cases without copyright notice the author, authors or source must be acknowledged.