Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment. High-dose intravenous methylprednisolone in the treatment of multiple sclerosis: clinical-immunologic correlations. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. A randomized comparative study of short term response to blind injection versus sonographic-guided injection of local corticosteroids in patients with painful shoulder. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Prednisone therapy for acute graft-versus-host disease: short- versus long-term treatment. A prospective randomized trial. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS.
IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the impact of IVMP on T1 black holes or whole-brain atrophy.
                To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS.
                The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months.
                Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years.
                In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted. There is evidence to support both the use of intravenous methylprednisolone (IVMP) in multiple sclerosis (MS) relapse and physiotherapy in the management of MS, but no studies have investigated the combination of steroids and rehabilitation together.
                To evaluate the benefits of IVMP with planned, comprehensive multidisciplinary team (MDT) care compared to IVMP with standard care.
                In this randomised controlled trial, patients confirmed to have had a definite MS relapse severe enough to warrant IVMP (1 g daily for three days) were randomised to two groups. The control group was managed according to the standard ward routine; the treatment group received planned coordinated multidisciplinary team assessment and treatment. Baseline assessments, including demographics and Expanded Disability Status Scale (EDSS) were carried out on both groups. The primary outcome measures were Guy's Neurological Disability Scale (GNDS), and Amended Motor Club Assessment (AMCA). The secondary measures were the Barthel Index (BI), Human Activity Profile (HAP), and Short Form Item 36 Health Survey (SF-36). All measures have published data on reliability and validity. Measures were administered at one and three months.
                Forty subjects, including 27 females, completed data collection. There were no significant differences between the two groups at baseline. Results showed statistically significant differences in GNDS (p = 0.03), AMCA (p = 0.03), HAPM (p < 0.01), HAPA (p = 0.02), and BI (p = 0.02) at three months in favour of planned MDT care.
                This study indicates that combining steroids with planned MDT care is superior to administering them in a standard neurology or day ward setting. Further research is necessary in order to confirm this finding. We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement. To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients.
                In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy.
                Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured.
                Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects.
                4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS. The role of corticosteroids in the prophylaxis of graft-versus-host disease (GVHD) is not well established. We have conducted a prospective, randomized, open-label, single-center study about the effect of adding methylprednisolone (MP) to the widely used prophylactic regimen consisting of cyclosporine A and methotrexate. A total of 108 consecutive patients treated with allogeneic bone marrow transplantation from an HLA-identical sibling donor for malignant blood disease were entered into the study; 53 patients were randomized to receive and 55 were randomized not to receive prophylactic MP. The dose of MP was 0.5 mg/kg on days 14 to 20, 1 mg/kg on days 21 to 34, 0.5 mg/kg on days 35 to 48, and thereafter the dose was slowly tapered and the administration discontinued on day 110. In the group given prophylactic MP, the incidence of acute GVHD was lower (19% vs 56%, P =.0001), there was a trend toward a lower incidence of chronic GVHD among low-risk patients (P =.06), and during the first 4 months the time spent at hospital was shorter and there were fewer infections. The total amount of MP given was similar in the study groups because of a higher incidence of acute GVHD and its treatment in the group of patients not given prophylactic MP. There were no significant differences between the study groups in relapse rate or survival. In conclusion, the addition of MP to the combination of cyclosporine and methotrexate markedly reduced the incidence of acute GVHD without causing untoward effects. The timing of corticosteroid administration is probably important for the efficacy. Local corticosteroid injections, commonly accepted by rheumatologists to be effective treating painful shoulder, have shown controversial results. High frequency ultrasonography is an accurate and safe imaging modality for guiding musculoskeletal injections. We prospectively compared the short term response to randomized blind injection versus sonographic-guided injection of local corticosteroid in patients with painful shoulder.
                We studied 41 consecutive patients with painful shoulder. Patients with previous trauma or chronic inflammatory arthritis were excluded. No patient had received previous physiotherapy or local steroid injection in the shoulder. Patients were randomized to receive either a blind subacromial injection of 20 mg triamcinolone (Group 1, n = 20) or a sonographic guided injection of 20 mg triamcinolone (Group 2, n = 21) by the same rheumatologist blinded to the clinical evaluation. In both groups we recorded shoulder abnormalities and the location of the steroid postinjection by ultrasound. Each patient was clinically assessed within 5 days before injection and 6 weeks after injection by another rheumatologist without knowledge of the injection technique performed. Clinical assessment included demographic and clinical data, a visual analog scale (VAS) for pain (0-100), the Shoulder Function Assessment (SFA) scale (0-70), and postinjection adverse effects. No patient received physical therapy during the followup period. Initially, demographic, clinical, and ultrasonographic findings in both groups showed no significant differences.
                Six weeks after injection, the VAS and the SFA score showed a significantly greater improvement in Group 2 compared with Group 1 (mean VAS score change 34.9 for Group 2 vs 7.1 for Group 1, p < 0.001; and mean SFA score change 15 for Group 2 vs 5.6 for Group 1, p = 0.012). One patient in Group 1 reported mild postinjection adverse effects.
                We suggest that sonographic-guided corticosteroid injections should be indicated, at least, in patients with poor response to previous blind injection to ensure accurate medication placement in order to improve therapeutic effectiveness. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. We report the results of a controlled study in which BMT patients with moderate/severe acute graft-versus-host disease (GVHD) who responded to primary treatment with corticosteroids were prospectively randomized to short versus long taper of their steroid doses. Thirty patients with moderate/severe acute GVHD who responded by 14 days were eligible for random assignment of their steroid tapering schedule. Patients in the short taper group received a total PRED dose of 2275 mg/m2 over 86 days, whereas those in the long taper group received 6300 mg/m2 over 147 days. Patients in the long taper group achieved resolution of acute GVHD after a median of 30 days of therapy (range 6-30), whereas those receiving the short taper resolved after a median of 42 days (12-74) (P = 0.01). After 8 weeks of therapy, only 2 of 13 evaluable long taper and 3 of 13 short taper patients still had active GVHD. The median PRED dose required to achieve complete resolution of acute GVHD was not different between the two groups: 1300 mg/m2 for the long taper patients and 1800 mg/m2 for the short taper patients. Importantly, the incidence of chronic GVHD and survival at 6 months was similar in the 2 groups. The incidence of steroid-related complications was similar, as well. This study suggests that the rapid administration of high-dose PRED to a cumulative dose of 2000 mg/m2 might lead to complete and prompt resolution of acute GVHD in the majority of patients and that rapid PRED taper might provide a mechanism for minimizing steroid-related morbidity. Further investigation and formal studies of the dose-response relationships and kinetics of steroid administration may lead to improvement in the management of acute GVHD. To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse.
                Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration.
                The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a "non-inferiority effect" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms.
                Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%).
There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.