Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Factors associated with treatment escalation among MS specialists and general neurologists: Results from an International cojoint study.

BACKGROUND: Previous studies in multiple sclerosis (MS) showed that therapeutic inertia (TI) affects 60-90% of neurologists and up to 25% of daily treatment decisions. The objective of this study was to determine the most common factors and attribute levels associated with decisions to treatment escalation in an international study in MS care. METHODS: 300 neurologists with MS expertise from 20 countries were invited to participate. Participants were presented with 12 pairs of simulated MS patient profiles described by 13 clinically relevant factors. We used disaggregated discrete choice experiments to estimate the weight of factors and attributes affecting physicians' decisions when considering treatment selection. Participants were asked to select the ideal candidate for treatment escalation from modest to higher-efficacy therapies. RESULTS: Overall, 229 neurologists completed the study (completion rate: 76.3%). The top 3 weighted factors associated with treatment escalation were: previous relapses (20%), baseline expanded disability status scale [EDSS] (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (≤ 3%). We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-MS specialists. CONCLUSIONS: Our results provide critical information on factors influencing neurologists' treatment decisions and should be applied to continuing medical education strategies.

A study protocol for a phase II randomised, double-blind, placebo-controlled trial of sodium selenate as a disease-modifying treatment for behavioural variant frontotemporal dementia.

INTRODUCTION: Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder often neuropathologically associated with the accumulation of abnormally hyperphosphorylated tau, for which there is currently no disease-modifying treatment. Previous work by our group has shown sodium selenate upregulates the activity of protein phosphatase 2 in the brain, increasing the rate of tau dephosphorylation. The objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying treatment for bvFTD. METHODS AND ANALYSIS: This will be a multisite, phase IIb, double-blind placebo-controlled trial of sodium selenate. One hundred and twenty participants will be enrolled across 4 Australian academic hospitals. Following screening eligible participants will be randomised (1:1) to sodium selenate (15 mg three times a day) or placebo for 52 weeks. Participants will have regular safety and efficacy visits throughout the study period. The primary study outcome will be percentage brain volume change (PBVC) as measured on MRI over 52 weeks of treatment. This will be analysed with a general linear model (analysis of covariance (ANCOVA)) with the PBVC as an output, the treatment as an input and the baseline brain volume as covariate for adjustment purposes. Secondary outcomes include safety and tolerability measures, and efficacy measures; change in cerebrospinal fluid total-tau, Addenbrooke's Cognitive Examination-III and Cambridge Behavioural Inventory-Revised scores over the 52 weeks of treatment. These will also be analysed with ANCOVA where the corresponding baseline measure will be incorporated in the model. Additional exploratory outcomes will include other imaging, cognitive and biospecimen analyses. ETHICS AND DISSEMINATION: The study was approved by the Human Research and Ethics Committee of the lead site as part of the Australian Multisite Ethics approval system. The results of the study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12620000236998 .

Presentation and outcome of patients with intracranial tuberculoma in a high HIV prevalence setting.

SETTING: A referral hospital in South Africa.OBJECTIVE: To describe the clinical presentation, serial brain imaging findings during treatment and outcome of patients with intracranial tuberculoma in a high human immunodeficiency virus (HIV) prevalence setting.DESIGN: This was a retrospective observational study conducted over a 12.5-year period. Records of adults (age ≥18 years) who presented with neurological TB were screened. We included patients with tuberculoma in whom sequential brain imaging was performed.RESULTS: Of 66 patients enrolled, HIV status was known in 61; 47 (71%) were HIV-infected and 14 (21%) were non-HIV-infected. Clinical and imaging findings and outcomes were similar between these groups. Persistent tuberculoma was present at 18 months follow-up in 20/41 (49%) patients who underwent repeat imaging at that timepoint; those with persistent tuberculoma were more likely to have persisting neurological abnormalities (85% vs. 52%; P = 0.043). Larger tuberculoma size at presentation (≥3 cm) was the only factor significantly associated with tuberculoma persistence (multivariable logistic regression, OR 19.9, 95%CI 1.27-309.68; P = 0.033).CONCLUSION: Tuberculoma is a severely disabling TB manifestation regardless of HIV coinfection, with half of patients showing radiologically persistent lesions at 18 months follow-up. Large size of tuberculoma at presentation heralds lower chance of its resolution within 18 months.

PACS Integration of Semiautomated Imaging Software Improves Day-to-Day MS Disease Activity Detection.

BACKGROUND AND PURPOSE: The standard for evaluating interval radiologic activity in MS, side-by-side MR imaging comparison, is restricted by its time-consuming nature and limited sensitivity. VisTarsier, a semiautomated software for comparing volumetric FLAIR sequences, has shown better disease-activity detection than conventional comparison in retrospective studies. Our objective was to determine whether implementing this software in day-to-day practice would show similar efficacy. MATERIALS AND METHODS: VisTarsier created an additional coregistered image series for reporting a color-coded disease-activity change map for every new MS MR imaging brain study that contained volumetric FLAIR sequences. All other MS studies, including those generated during software-maintenance periods, were interpreted with side-by-side comparison only. The number of new lesions reported with software assistance was compared with those observed with traditional assessment in a generalized linear mixed model. Questionnaires were sent to participating radiologists to evaluate the perceived day-to-day impact of the software. RESULTS: Nine hundred six study pairs from 538 patients during 2 years were included. The semiautomated software was used in 841 study pairs, while the remaining 65 used conventional comparison only. Twenty percent of software-aided studies reported having new lesions versus 9% with standard comparison only. The use of this software was associated with an odds ratio of 4.15 for detection of new or enlarging lesions (P = .040), and 86.9% of respondents from the survey found that the software saved at least 2-5 minutes per scan report. CONCLUSIONS: VisTarsier can be implemented in real-world clinical settings with good acceptance and preservation of accuracy demonstrated in a retrospective environment.

Anti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study.

BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.

Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients. METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24). RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

Early magnetic resonance imaging predictors of clinical progression after 48 months in clinically isolated syndrome patients treated with intramuscular interferon ß-1a.

BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon ß-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon ß-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.

Impaired ambulation and steroid therapy impact negatively on bone health in multiple sclerosis.

BACKGROUND AND PURPOSE: The prevalence of osteopenia and osteoporosis is higher amongst patients with multiple sclerosis in comparison with the general population. In addition to the general determinants of bone health, two factors may contribute to reduced bone mineral density in multiple sclerosis: physical disability and corticosteroid therapy. The aim of this study was to examine the effect of physical disability and steroid exposure on bone health in weight-bearing bones and spine and on the incidence of low-trauma fractures in multiple sclerosis. METHODS: In this retrospective analysis of prospectively collected data, associations between bone mineral density (at the femoral neck, total femur and the lumbar spine) and its change with disability or cumulative steroid dose were evaluated with random-effect models adjusted for demographic and clinical determinants of bone health. The incidence of low-trauma fractures during the study follow-up was evaluated with Andersen-Gill models. RESULTS: Overall, 474 and 438 patients were included in cross-sectional and longitudinal analyses (follow-up 2347 patient-years), respectively. The effect of severely impaired gait was more apparent in weight-bearing bones (P ≤ 10(-15) ) than in spine (P = 0.007). The effect of cumulative steroid dose was relatively less pronounced but diffuse (P ≤ 10(-4) ). Risk of low-trauma fractures was associated with disability (P = 0.02) but not with cumulative steroid exposure and was greater amongst patients with severely impaired gait (annual risk 3.5% vs. 3.0%). Synergistic effects were found only between cumulative steroid dose in patients ambulatory without support (P = 0.02). CONCLUSIONS: Bone health and the incidence of low-trauma fractures in multiple sclerosis are more related to impaired gait than to extended corticosteroid therapy.

Multiple sclerosis susceptibility loci do not alter clinical and MRI outcomes in clinically isolated syndrome.

It has not yet been established whether genetic predictors of multiple sclerosis (MS) susceptibility also influence disease severity and accumulation of disability. Our aim was to evaluate associations between 16 previously validated genetic susceptibility markers and MS phenotype. Patients with clinically isolated syndrome verified by positive magnetic resonance imaging (MRI) and cerebrospinal fluid findings (n=179) were treated with interferon-ß. Disability and volumetric MRI parameters were evaluated regularly for 2 years. Sixteen single-nucleotide polymorphisms (SNPs) previously validated as predictors of MS susceptibility in our cohort and their combined weighted genetic risk score (wGRS) were tested for associations with clinical (conversion to MS, relapses and disability) and MRI disease outcomes (whole brain, grey matter and white matter volumes, corpus callosum cross-sectional area, brain parenchymal fraction, T2 and T1 lesion volumes) 2 years from disease onset using mixed-effect models. We have found no associations between the tested SNPs and the clinical or MRI outcomes. Neither the combined wGRS predicted MS activity and progression over 2-year follow-up period. Power analyses confirmed 90% power to identify clinically relevant changes in all outcome variables. We conclude that the most important MS susceptibility loci do not determine MS phenotype and disease outcomes.

Evolution of cortical and thalamus atrophy and disability progression in early relapsing-remitting MS during 5 years.

BACKGROUND AND PURPOSE: Pathologic changes in GM have an important role in MS. We investigated the association between SDGM and cortical volume changes and disability progression in early RRMS. MATERIALS AND METHODS: One hundred eighty patients with RRMS had clinical assessment during 5 years and were divided into those with or without SDP at 5 years by the usual definition in treatment trials. The number of available MR imaging scans at various time points was the following: at baseline, 178; and at 6 months, 172; at 12 months, 175; at 24 months, 155; at 36 months, 160; at 48 months, 158; and at 60 months, 162, respectively. Longitudinal changes in cortical, GM, and WM volume were calculated by using the direct method. RESULTS: At 5 years, 90 patients with RRMS experienced SDP and 90 had stable disease. At baseline, patients with SDP had longer disease duration, greater T2-lesion volume, and smaller whole-brain, WM, cortical, and SDGM volume (P < .01). At 5 years, patients with SDP had significantly greater percentage decreases from baseline compared with those without SDP in the volume of the whole brain (P < .0001), cortex (P = .001), GM (P = .003), and thalamus (P = .01). In patients who developed SDP at 5 years and those who did not, mixed-effect models, adjusted for age, disease duration, and change of the treatment status, showed significant interactions between SDP status at 5 years and changes with time in whole-brain, cortical, lateral ventricle (all P < .001), thalamus (P = .006), and total SDGM (P = .0095) volume. CONCLUSIONS: SDP is associated with progression of cortical, central, and thalamic atrophy in early RRMS during 5 years.

Corpus callosum atrophy--a simple predictor of multiple sclerosis progression: a longitudinal 9-year study.

AIM: To determine whether corpus callosum atrophy predicts future clinical deterioration in multiple sclerosis. METHODS: In 39 multiple sclerosis patients the area of corpus callosum in the sagittal plane, T2 and T1 lesion volumes, brain parenchymal fraction and brain atrophy were determined at baseline and 1 year after treatment initiation. Non-parametric and multiple regression models were built to identify the most reliable predictors of disability and of its changes over 9 years. RESULTS: Corpus callosum atrophy during the first year of treatment was the best predictor of disability (r = -0.56) and of its increase at 9 years (r = 0.65). Corpus callosum atrophy of at least 2% predicted increase in disability with 93% sensitivity and 73% specificity (odds ratio = 35). CONCLUSION: Corpus callosum atrophy is a simple and accurate predictor of future disability accumulation and is feasible for routine clinical practice.

Microsatellite polymorphism in haem oxygenase 1 gene promoter in multiple sclerosis.

Previous studies suggested that increased activity of haem oxygenase 1 may ameliorate autoimmune neuroinflammation in experimental models of multiple sclerosis. This increased activity is associated with an augmented number of GT repeats (≥ 25) within the HMOX1 gene promoter. Here we examined 338 patients with multiple sclerosis to determine the influence of their HMOX1 gene promoter (GT)n polymorphism and other individual characteristics on the course of the disease. The patients were divided into those with "rapid" or "delayed" course, based on reaching expanded disability status scale step 4 within nine years of disease onset, and the correlations between the disease course and the investigated characteristics were sought using logistic regression analysis. No statistically significant effect of HMOX1 gene promoter (GT)n polymorphism on the rate of disability progression was found (P = 0.9). This was confirmed by Cox regression analysis, which did not find any difference in the cumulative risk of reaching expanded disability status scale step 4 between the patients with long and short HMOX1 gene promoter (P = 0.7). In contrast, covariates significantly associated with the faster disability progression were: progressive course of multiple sclerosis, shorter duration of disease-modifying treatment and older age at disease onset (P ≤ 0.04). The observed absence of effect of the HMOX1 promoter (GT)n polymorphism could be attributed to its known dualistic role in the pathogenesis of autoimmune disorders. As a secondary outcome, we have seen that disease-modifying drugs have the potential to delay disability progression in patients with multiple sclerosis.

Interferon, azathioprine and corticosteroids in multiple sclerosis: 6-year follow-up of the ASA cohort.

OBJECTIVE: To evaluate long-term effects of 2-year treatment with interferon beta combined with low-dose azathioprine and prednisone in multiple sclerosis. METHODS: In the original 2-year ASA study, 181 patients with early relapsing-remitting multiple sclerosis were randomised into 3 treatment arms: those treated with interferon beta (n=60), with interferon beta and low-dose azathioprine (n=58), and interferon beta, azathioprine and low-dose prednisone (n=63). Of these, 172 were included in this 4-year non-study extension. Three monthly clinical controls and annual MRI scans were carried out. The primary endpoint was annual relapse activity. The secondary endpoints were disability and quantitative MRI parameters. RESULTS: Nine patients were lost to follow-up and 172 were included in the analyses. None of relapse activity, disability accumulation or MRI parameters differed significantly between the groups over 6 years. Only 5.5% and 0.6% of patients were free from disease activity at year 2 and year 6 of the treatment initiation. CONCLUSION: The tested combined therapeutic regimen does not improve long-term outcomes in patients with multiple sclerosis. Furthermore, interferon is not able to completely abolish disease activity.

Early predictors of non-response to interferon in multiple sclerosis.

OBJECTIVE: To identify early clinical and MRI predictors of non-response to interferon (IFN) treatment in multiple sclerosis (MS). METHODS: In 172 patients with relapsing-remitting MS treated with IFNß, we evaluated prediction of future treatment non-response. Candidate predictors comprised disability and its sustained progression, relapse score (combining frequency and severity of relapses), brain volume change, brain parenchymal fraction, number of new T2 lesions, and T2 and T1 lesion volume within the initial year of treatment. Treatment non-response was evaluated as confirmed disability progression or overall average annual relapse score exceeding 1 over the following 5 years. Logistic regression model was adjusted for patient age, gender, disease duration and changes in treatment. RESULTS: Ninety patients (52%) reached the status of IFN non-responders in years 2-6. Patients with ≥1 new T2 lesion and relapse score ≥2 (odds ratio ≥5.7) or those with ≥3 new T2 lesions regardless of the relapse score (odds ratio = 3) were in a significantly higher risk of future treatment non-response. CONCLUSIONS: In patients with MS treated with IFNß for 1 year, number of new T2 lesions and annualized relapse score predict individual risk of treatment non-response over the following 5 years.

Cost of multiple sclerosis in the Czech Republic: the COMS study.

BACKGROUND: Information about cost of multiple sclerosis (MS) is available from a number of European countries, but no data from the Czech Republic have been published so far. OBJECTIVE: The objective of this study was to establish the cost of MS in the Czech Republic, overall and by level of disease severity. METHODS: Data on demographics, disease history, resource consumption and production losses were collected from 909 patients recruited in 7 MS centres in the Czech Republic. Annual costs were estimated in the societal perspective, using 2007 unit costs. To evaluate the relationship between disability and costs, patients were stratified into those with mild (67%), moderate (27%) and severe (10%) disability using the Expanded Disability Status Scale. RESULTS: Mean total annual costs per patient were €12,272, of which 51% were direct medical costs, 4% direct non-medical costs and 45% indirect costs. The average annual costs in patients with mild, moderate and severe disability amounted to €9905, €14,064 and €22,880, respectively. CONCLUSION: The total costs of MS in the Czech Republic are estimated at €208.6 million per year. Consistent with other studies, the costs increase significantly with the severity of MS.

Influence of magnesium sulphate on evoked activity of rat brain after exposure to short-term hypoxia.

Young Wistar rats (aged 12, 25 and 35 days) were exposed to short-term (60 min) hypobaric hypoxia of 41 kPa. Cortical afterdischarges (ADs) were evoked by repeated direct stimulation of the sensorimotor cortex and the duration of ADs was monitored to examine the influence of magnesium sulphate injection (0.3 g/kg b.w.). In 12-day-old hypoxia-exposed rats, an increase of the mean duration of ADs after the repeated stimulation appeared. This effect was prevented by magnesium administration. In 25- and 35-day-old rats exposed to hypoxia a shortening of ADs was registered but no specific effect of magnesium sulphate pretreatment was observed. The brain susceptibility and ability to terminate evoked seizures is discussed.