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Background Natalizumab (NTZ) and ocrelizumab (OCR) can be used for the treatment of relapsing–remitting multiple sclerosis (RRMS). In patients treated with NTZ, screening for JC virus (JCV) is mandatory, and a positive serology usually requires a change in treatment after 2 years. In this study, JCV serology was used as a natural experiment to pseudo-randomize patients into NTZ continuation or OCR. Methods An observational analysis of patients who had received NTZ for at least 2 years and were either changed to OCR or maintained on NTZ, depending on JCV serology status, was performed. A stratification moment (STRm) was established when patients were pseudo-randomized to either arm (NTZ continuation if JCV negativity, or change to OCR if JCV positivity). Primary endpoints include time to first relapse and presence of relapses after STRm and OCR initiation. Secondary endpoints include clinical and radiological outcomes after 1 year. Results Of the 67 patients included, 40 continued on NTZ (60%) and 27 were changed to OCR (40%). Baseline characteristics were similar. Time to first relapse was not significantly different. Ten patients in the JCV + OCR arm presented a relapse after STRm (37%), four during the washout period, and 13 patients in the JCV-NTZ arm (32.5%, p = 0.701). No differences in secondary endpoints were detected in the first year after STRm. Conclusions The JCV status can be used as a natural experiment to compare treatment arms with a low selection bias. In our study, switching to OCR versus NTZ continuation led to similar disease activity outcomes.

Transcranial direct current stimulation (tDCS) can change the excitability of the central nervous system and contribute to motor recovery of stroke patients. The aim of our study was to examine the short- and long-term effects of real versus sham bihemispheric tDCS combined with repetitive peripheral nerve stimulation in patients with acute stroke and a severe motor impairment.The study was prospective, randomized, double blind, and placebo controlled. Nineteen acute stroke patients (ischemic and hemorrhagic) with upper limb Fugl-Meyer mean score of19 were randomized in two groups: one group received five consecutive daily sessions of anodal tDCS over the affected hemisphere and cathodal over unaffected hemisphere combined with repetitive peripheral nerve stimulation and the other received sham tDCS associated to repetitive peripheral nerve stimulation. Clinical and neurophysiological assessment was applied before tDCS, 5 days after tDCS, and 3, 6, and 12 months after tDCS.There were significant time-related changes in both groups of patients in motor evoked potentials, somatosensory evoked potentials, Hmax:Mmax ratio, upper limb Fugl-Meyer scores, and Modified Ashworth scales scores ( P0.05). However, no significant differences between groups were present at any time ( P0.05).Bihemispheric tDCS and repetitive peripheral nerve stimulation with the parameters of our study did not add significant short- or long-term clinical improvement or change in neurophysiological data in severe acute stroke patients in comparison to sham stimulation. The severity of motor impairment in stroke patients may influence a possible response to an interventional tDCS treatment.

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) most commonly experience their first symptoms between 20 and 40 years of age. The objective of this study was to investigate how the age at which the first symptoms of RRMS occur has changed over the past decades. Methods: Patients who were followed up in our unit after an initial diagnosis of RRMS using the Poser or McDonald criteria and who experienced their first symptoms between January 1970 and December 2019 were included in the study. The cohort was divided into five groups according to the decade in which the first symptoms appeared. The age at disease onset was compared across decades. Changes in age were also determined after excluding patients with early-onset disease (50 years of age) to avoid bias. Results: The cohort included 1,622 patients with RRMS, 67.6% of whom were women. Among them, 5.9% and 4% had early-onset and late-onset disease, respectively. The mean age ± standard deviation at onset was 31.11 ± 9.82 years, with no differences between men and women. The mean ages at onset were 23.79 ± 10.19 years between 1970 and 1979, 27.86 ± 9.22 years between 1980 and 1989, 30.07 ± 9.32 years between 1990 and 1999, 32.12 ± 9.47 between 2000 and 2009, and 34.28 ± 9.83 years between 2010 and 2019. The ages at disease onset were progressively higher in the later decades; this trend was statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.264 and R2 of 0.070 (p < 0.001). The results were similar when analysing men and women separately. We conducted an analysis of 1,460 patients (mean age at onset: 31.10 ± 7.99 years), after excluding patients with early-onset and late-onset disease. In this specific subgroup, the mean ages at disease onset were 28.38 ± 8.17 years between 1970 and 1979, 29.22 ± 7.51 years between 1980 and 1989, 30.06 ± 8.02 years between 1990 and 1999, 31.46 ± 7.77 years between 2000 and 2009, and 33.37 ± 7.97 years between 2010 and 2019. The trend was also statistically significant (p < 0.001), with a Pearson linear correlation coefficient R of 0.193 and R2 of 0.037 (p < 0.001).

Introduction Endovascular thrombectomy was recently established as a new standard of care in acute ischemic stroke patients with large artery occlusions. Using small area health statistics, we sought to assess dissemination of endovascular thrombectomy in Catalonia throughout the period 2011–2015. Patients and methods We used registry data to identify all endovascular thrombectomies for acute ischemic stroke performed in Catalonia within the study period. The SONIIA registry is a government-mandated, population-based and externally audited data base that includes all reperfusion therapies for acute ischemic stroke. We linked endovascular thrombectomy cases identified in the registry with the Central Registry of the Catalan Public Health Insurance to obtain the primary care service area of residence for each treated patient, age and sex. We calculated age-sex standardized endovascular thrombectomy rates over time according to different territorial segmentation patterns (metropolitan/provincial rings and primary care service areas). Results Region-wide age-sex standardized endovascular thrombectomy rates increased significantly from 3.9 × 100,000 (95% confidence interval: 3.4–4.4) in 2011 to 6.8 × 100,000 (95% confidence interval: 6.2–7.6) in 2015. Such increase occurred in inner and outer metropolitan rings as well as provinces although highest endovascular thrombectomy rates were persistently seen in the inner metropolitan area. Changes in endovascular thrombectomy access across primary care service areas over time were more subtle, but there was a rather generalized increase of standardized endovascular thrombectomy rates. Discussion This study demonstrates temporal and territorial dissemination of access to endovascular thrombectomy in Catalonia over a 5-year period although variation remains at the completion of the study. Conclusion Mapping of endovascular thrombectomy is essential to assess equity and propose actions for access dissemination.

Background and Purpose— Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. Methods— We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. Results— Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245–435]) and 120 minutes longer in group C (350 minutes [284–408]) compared with group A (230 minutes [160–407]; P Conclusions— Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.

Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein that crosses the blood-brain barrier, binds to myelin, and, hence, has been suggested to be a putative agent for the onset of multiple sclerosis, a demyelinating neuroinflammatory disease. Recently, myelin and lymphocyte (MAL) protein has been identified to be a key protein in the cytotoxic effect of Etx; however, the association of Etx with the immune system remains a central question. Here, we show that Etx selectively recognizes and kills only human cell lines expressing MAL protein through a direct Etx-MAL protein interaction. Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Etx and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes. The overall results open the door to investigation of the role of Etx and Clostridium perfringens on inflammatory and autoimmune diseases like multiple sclerosis.

Aims The aims of this study were to assess the sensitivity of the International Behavioural Variant FTD Criteria Consortium (FTDC) revised criteria of behavioural variant frontotemporal dementia (bvFTD) in a pathological cohort and to determine their predictive values in a clinical context suggestive of bvFTD. In addition, the study aimed to assess the influence of the age at onset and underlying pathology in the clinicopathological correlations. Methods Retrospective, blinded review of the clinical and neuropathological data from the Neurological Tissue Bank of the Biobank Hospital Clinic–IDIBAPS, Barcelona (Spain) was conducted, assessing the fulfilment of the diagnostic criteria on a case-by-case basis. Two separate nonexclusive cohorts were selected: Cohort 1 (n = 58) subjects with pathological diagnosis of frontotemporal lobar degeneration (FTLD) and Cohort 2 (n = 66) subjects with the premortem diagnosis of bvFTD. Results The FTDC criteria reached a sensitivity of 93% for possible and 80% for probable bvFTD. Early-onset cases displayed significantly more disinhibition, loss of empathy and compulsive behaviour with respect to late-onset bvFTD, leading to a slightly higher sensitivity of the diagnostic criteria (97% vs. 91%). There were no differences in the diagnostic performance between tau-positive and tau-negative cases. In subjects clinically diagnosed as bvFTD, a ‘possible bvFTD’ diagnosis reached a positive predictive value for FTLD pathology of 90%, irrespective of underlying proteinopathy. False-positive clinical diagnoses were mainly Alzheimer's disease. These cases were significantly older, had less family history of dementia and had a predominantly apathetic clinical picture. Conclusions The revised bvFTD criteria present good sensitivity and positive predictive value in both early- and late-onset cases and regardless of the underlying FTLD pathology.

Introduction Bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SEP) is a reliable predictor of poor neurological outcome in postanoxic coma after cardiopulmonary resuscitation. However the preservation of N20 does not prognosticate awakening, in fact is an uncertain pattern. The prognostic value of N20 amplitude has still not been sufficiently documented. In our knowledge only one study has analyzed N20 amplitude. The aim of this study was to review the relationship between N20 amplitude and neurological outcome in our postanoxic patients. Methods We retrospectively review the data of all our patients who remained comatose after cardiopulmonary resuscitation between 2013 and 2017. The following variables were collected: N20 amplitude, clinical examination, EEG data, neuron-specific enolase and outcome determined upon hospital discharge by means of Cerebral performance category (CPC). The patients with CPC 1–3 were defined as good outcome, and those with CPC 4–5 as poor outcome. Results We identified 76 postanoxic patients with N20 present. Fifty-three (69.7%) had poor outcome (CPC 4–5). The mean N20 amplitude in these patients was 1.90 μV (SD 2.01 range 0.16–7.9). Twenty-three patients (30.2%) had good outcome (CPC 1–3) and the mean N20 amplitude in these patients was 3.43 μV (SD 2.73 range 0.93–11.3). The ROC curve shows 0.86 μV as the cut-value for a better specificity with higher sensitivity. Any patient with amplitude lowest than 0.86 μV had good outcome (specificity 100%, sensitivity 50.9%, positive predictive value 100%, negative predictive value 46.9%). Conclusion In our postanoxic patients very low N20 amplitudes appear to be highly predictive of poor outcome. Our results corroborate published data.

Introduction Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can change the excitability of the central nervous system and contribute to motor recovery of patients with stroke. The functional benefit may increase with the combination of tDCS with manoeuvres facilitating motor output. Most previous studies included patients in the chronic phase. We have evaluated the effects of tDCS coupled with radial nerve stimulation in the acute phase after stroke, as an add-on treatment to neurorehabilitation therapy that could potentially enhance motor recovery. Methods Twenty patients with a history of first acute cortical and/or subcortical stroke (11 ischemic and 9 hemorrhagic) were included in a prospective, double-blind, randomized study. Patients presented a moderate to severe motor deficit at onset (NIHSS: 14 ± 4.4 range 6–21 and upper limb Fugl-Meyer score: 17.4 ± 15.3, range 4–60). We studied the effects of combined peripheral radial nerve stimulation (PNS) to the paretic hand and anodal tDCS to the affected hemisphere (cathodal in the contralateral hemisphere). tDCS together with PNS were applied to 11 patients: 20 min during 5 consecutive days starting 7–15 days after the stroke. The results were compared with those of 9 patients receiving PNS with sham tDCS. All patients were under routine neurorehabilitation therapy. In sessions before, immediately after and 3, 6 months and one year after tDCS, we assessed Fugl-Meyer (FM) and modified Ashworth scales (MAS), resting motor threshold (RMT), MEPs and SEPs amplitudes, contralateral and ipsilateral silent period (cSP and iSP) duration and Hmax/Mmax ratio. Results There were significant time-related changes in clinical and neurophysiological scores, suggesting improvement in the clinically affected side in both groups (sham and real tDCS). However, there were no significant differences between real and sham tDCS in RMT, MEP amplitude, Hmax/Max ratio, cSP to TMS to the affected hemisphere, iSP to TMS to the unaffected hemisphere and FM and MAS scores (p Conclusion Five-daily sessions bihemispheric tDCS combined with radial nerve stimulation in the acute stroke patients of our study, showed a significant improvement in some clinical and neurophysiological scores, but these changes were similar to those observed in patients that received sham tDCS and PNS.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by a hypercoagulable state. Ischaemic stroke represents the most common neurological manifestation (1). Several other ...

La cefalea por abuso de medicacion es una cefalea cronica que aparece en pacientes con migrana o cefalea tensional por un consumo excesivo de la medicacion utilizada para su tratamiento. Los profesionales sanitarios jugamos un importante papel en su prevencion, y en su identificacion de cara a revertir una situacion que, de otra forma, se cronificara.

Background:Prospective studies on the clinical progression of Alzheimer's disease (AD) and its relationship to caregiver burden are needed to improve illness management and use of resources.Methods:This national, multicenter, observational study evaluated 1235 moderate to severe AD patients under routine care in Spain. Baseline cross-sectional sociodemographic and clinical data, and changes from baseline to month 12 of various neuropsychological tests and clinical ratings, including Blessed Dementia Scale, Mini-mental State Examination (MMSE), Hughes Clinical Dementia Rating sum-of-boxes (CDR-SB), Clinical Global Impression of Change (CGIC) and Zarit Caregiver Burden scales, were recorded and comprehensively analyzed.Results:Baseline data were in accordance with characteristics consistently reported to influence AD risk regarding anthropometrics, sociocultural features and comorbidities. Significant progressive functional impairments (i.e. in routine activities and essential daily tasks) and cognitive (i.e. MMSE and CDR-SB) impairments were found at month 12. However, patients' behavior and caregivers' burden improved slightly, but significantly, corroborating the major influence of behavioral symptoms on caregivers' distress. Caregivers showed significantly lower burden with patients with higher levels of education and, to a lesser extent, when patients received AD-specific medication. Physicians accurately detected AD clinical evolution as their CGIC ratings significantly correlated with all tests.Conclusions:These findings reinforce previous AD knowledge and add data on the clinical course of advanced stages of AD. Caregiver burden depended more on patients' behavioral alterations than on their functional or cognitive declines; and it was diminished by their patients having higher levels of education and being treated with AD-specific medications. Research into unexplored factors that might reduce caregiver burden, ultimately benefiting both patients and caregivers, is encouraged.

There is limited long-term data on the effect of interferon-β1b (IFN-β1b) on disability progression in patients with multiple sclerosis (MS). There is also no reliable way of predicting individual responses to IFN-β1b treatment. This prospective study investigated early clinical prognostic markers of disease activity and progression in 115 patients with relapsing-remitting MS (RRMS) treated with IFN-β1b for almost 5 years. The study also compared progression of disability in IFN-β1b-treated patients with a historic untreated cohort of MS patients (n = 44). The number of relapses in the first 2 years of MS and in the 2 years before treatment predicted an early relapse after IFN-β1b treatment. The IFN-β1b-treated group experienced a slower progression of disability than the untreated cohort, suggesting that IFN-β1b treatment delays progression of disability in RRMS.

Background and Purpose— Recent trials have shown the superiority of endovascular thrombectomy (EVT) over medical therapy alone in certain stroke patients with proximal arterial occlusion. Using data from the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke due to Anterior Circulation Large Vessel Occlusion Presenting Within 8-Hours of Symptom Onset (REVASCAT) and a parallel reperfusion treatment registry, we sought to assess the utilization of EVT in a defined patient population, comparing the outcomes of patients treated in and outside the REVASCAT trial. Methods— SONIIA [Sistema Online d’Informació de l’Ictus Agut], a population-based, government-mandated, prospective registry of reperfusion therapies for stroke encompassing the entire population of Catalonia, was used as data source. The registry documents 5 key inclusion criteria of the REVASCAT trial: age, stroke severity, time to treatment, baseline functional status, and occlusion site. We compared procedural, safety, and functional outcomes in patients treated inside and outside the trial. Results— From November 2012 to December 2014, out of 17596 ischemic stroke patients in Catalonia (population 7.5 million), 2576 patients received reperfusion therapies (17/100000 inhabitants-year), mainly intravenous thrombolysis only (2036). From the remaining 540 treated with EVT, 103 patients (out of 206 randomized) were treated within REVASCAT and 437 outside the trial. Of these, 399 did not fulfill some of the study criteria, and 38 were trial candidates (8 treated at REVASCAT centers and 30 at 2 non-REVASCAT centers). The majority of procedural, safety, and functional outcomes were similar in patients treated with EVT within and outside REVASCAT. Conclusions— REVASCAT enrolled nearly all eligible patients representing one third of all patients treated with EVT. Patients treated with EVT within and outside REVASCAT had similar outcomes, reinforcing the therapeutic value of EVT. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01692379.

OBJECTIVE To evaluate the efficacy and safety of IFNbeta-1a (Avonex, Biogen, Inc., Cambridge, MA, USA) in patients with relapsing-remitting multiple sclerosis (MS). METHODS In this multicenter, open-label, prospective clinical trial, 96 patients with relapsing-remitting MS received IFNbeta-1a 30 mcg intramuscularly once weekly for 2 years. Outcome variables included: change from baseline in mean number of exacerbations, proportion of exacerbation-free patients, and mean Expanded Disability Status Scale (EDSS) scores at Years 1 and 2. RESULTS IFNbeta-1a significantly (P < 0.0001) reduced exacerbation rate at Years 1 and 2 of treatment. The percentage of exacerbation-free patients was 53% during Year 1 and 33% during Year 2. Mean EDSS scores were 2.96 +/- 1.26 at baseline, 2.89 +/- 1.42 at Year 1, and 3.00 +/- 1.62 at Year 2 (P = 0.116). EDSS scores improved in 35.4%, remained stable in 28.1%, and worsened in 36.5% of patients. IFNbeta-1a treatment was well tolerated. CONCLUSION This study confirms and extends the beneficial clinical profile for IFNbeta-1a in relapsing MS.

Background: Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. Methods: We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. Results: The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score matched: 1.45; 95% CI: 0.91-2.32). Conclusion: This comparative effectiveness study shows that in ischemic stroke patients with contraindications for IV thrombolysis, primary endovascular treatment might be an alternative therapy at least as effective as IV thrombolysis alone. Randomized controlled trials are urgently needed.

Multiple sclerosis (MS) is a chronic demyelinating disease, which represents a great economic burden to society. Cost-of-illness studies of MS tend to underestimate the intangible costs related to pain, anxiety and helplessness. The purpose of this study was to estimate the intangible costs of MS, and determine whether these costs increase as disability progresses. We studied 211 consecutive patients with MS who attended our MS unit. Patients mean age was 41.6 (SD: 10.7) years, 69% were female, and their mean Expanded Disability Status Scale (EDSS) score was 2.47 (SD: 2.05). Quality-of-life was measured with the EuroQoL visual analogue scale. Quality-adjusted life year (QALY) was calculated for each patient. Patients were grouped into five disability stages according to their EDSS, and QALY was compared between patients and a group of healthy controls matched by age and sex. A benchmark value was ascribed to each QALY lost, and the intangible costs per patient-year were calculated as 0 (EDSS =0), 1100 (EDSS =1-3), 8250 (EDSS =3.5-5.5), 9900 (EDSS =6-7) and 11 000 (EDSS >7.5). Sensitivity analysis showed a similar progression of costs. We conclude that intangible costs are relevant in MS, especially when disability increases. Although the method to calculate the costs remains controversial, we consider that they should be included in cost analysis of MS. Multiple Sclerosis 2007; 13: 800-804. http://msj.sagepub.com

There is limited long-term data on the effect of interferon-beta1b (IFN-beta1b) on disability progression in patients with multiple sclerosis (MS). There is also no reliable way of predicting individual responses to IFN-beta1b treatment. This prospective study investigated early clinical prognostic markers of disease activity and progression in 115 patients with relapsing-remitting MS (RRMS) treated with IFN-beta1b for almost 5 years. The study also compared progression of disability in IFN-beta1b-treated patients with a historic untreated cohort of MS patients (n = 44). The number of relapses in the first 2 years of MS and in the 2 years before treatment predicted an early relapse after IFN-beta1b treatment. The IFN-beta1b-treated group experienced a slower progression of disability than the untreated cohort, suggesting that IFN-beta1b treatment delays progression of disability in RRMS.

In order to ensure sufficient disease activity, patients with relapsing remitting (RR) multiple sclerosis (MS) are often included in randomized placebo-controlled trials, only if they have a high baseline activity. These patients, whose evolution is unusual in the pre-study period, will tend to show a more usual behavior when followed up over a period of time. This phenomenon is known as regression to the mean. Regression to the mean should be taken into account in correctly interpreting long-term studies of cohorts treated without a placebo control group, which use the baseline period as control. The aim of this study was to evaluate the relevance of this phenomenon in a non-treated cohort of RRMS patients, selected with similar criteria to those used in randomized placebo-controlled clinical trials. Forty-four patients with definite RRMS, with two or more relapses in the previous two years, and a baseline EDSS ≤ 5.5 were prospectively followed. The mean number of relapses spontaneously decreased from 1.72 (SD: 1.4) in the year prior to enrolment, to 1.0 (SD: 1.3) during the first year of follow-up (PB < 0.05). Regression to the mean may explain as much as 40% of the reduction in the relapse rate from the baseline period to the period on-study.

Background Multiple sclerosis (MS) is an incurable chronic disease that predominantly affects young adults. It has a high socio-economic impact which increases as disability progresses. An assessment of the real costs of MS may contribute to our knowledge of the disease and to treat it more efficiently. Our objective is to assess the direct and indirect costs of MS from a societal perspective, in patients monitored in our MS Unit (Baix Llobregat, Catalonia) and grouped according to their disability (EDSS). Methods We analysed data from 200 MS patients, who answered a questionnaire on resource consumption, employment and economical status. Mean age was 41.6 years, mean EDSS 2.7, 65.5% of patients were female, 79.5% had a relapsing-remitting course, and 67.5% of them were receiving immunomodulatory treatment (IT). Patients were grouped into five EDSS stages. Data from the questionnaires, hospital charts, Catalan Health Service tariffs, and figures from Catalan Institute of Statistics were used to calculate the direct and indirect costs. The cost-of-illness method, and the human capital approach for indirect costs, were applied. Sensitivity analyses were performed to strengthen results. Results The mean total annual cost of MS per patient results 24272 euros. This cost varied according to EDSS: 14327 euros (EDSS = 0), 18837 euros (EDSS = 1–3), 27870 euros (EDSS = 3.5–5.5), 41198 euros (EDSS = 6–7) and 52841 euros (EDSS>7.5). When the mean total annual costs was adjusted by the mean % of patients on IT in our Unit (31%) the result was 19589 euros. The key-drivers for direct costs were IT in low EDSS stages, and caregiver costs in high stages. Indirect costs were assessed in terms of the loss of productivity when patients stop working. Direct costs accounted for around 60% of total costs in all EDSS groups. IT accounts from 78% to 11% of direct costs, and decreased as disability progressed. Conclusion The total mean social costs of MS in a cohort from Baix Llobregat (Catalonia) were estimated at 24272 euros per patient/year, and ranged between 14327 euros (EDSS = 0) and 52841 euros (EDSS = 7.5–9.5). Total costs, and particularly informal and direct costs, increased as the disability progressed. IT should be able to delay the progression of disability to be efficient and not only effective.

Objective The Transverse Myelitis Consortium Working Group has proposed new diagnostic criteria for idiopathic acute transverse myelitis (ATM). We reviewed patients admitted to our center diagnosed with myelitis with two objectives: (i) to evaluate the usefulness of these criteria in distinguishing between myelitis as the first episode of multiple sclerosis (MS) and idiopathic ATM; and (ii) to analyse the clinical and laboratory variables that may be used as functional prognostic markers. Methods We selected patients who met the criteria. We recorded clinical epidemiological data, patients treated with methylprednisolone, maximal disability reached and disability at final follow-up. We also recorded cerebrospinal fluid (CSF) data and the number of levels affected in the spinal magnetic resonance imaging (MRI). Results Twenty-four patients fulfilled the criteria for definite ATM and 21 for possible ATM. Five patients converted to MS. Mean follow-up time was 3.5 years. There was an association between younger patients and female patients with conversion to MS. The highest Rankin score reached and increased CSF glucose levels were associated with a poor outcome. In multivariate analysis, only the admission Rankin score was associated with outcome. Conclusions (i) About 10% of patients who met the criteria may convert to MS; and (ii) admission Rankin score was the only independent prognostic factor found.

We analyzed the prognostic value of Tau protein, a marker of axonal damage, detected in the cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RRMS). We sampled the CSF from 32 patients with probable or definite RRMS, having had the disease for less than 5 years. We studied the relationship between Tau protein concentration in the CSF (CSF-TAU) and disability, time to next relapse and time to experience a one point increase on the Expanded Disability Status Scale (EDSS). CSF-TAU was correlated with the Progression Index at the end of follow-up. Patients with higher CSF-TAU experienced a more rapid one point increase in the EDSS. CSF-TAU was the only independent variable to predict the time to next relapse. CSF-TAU, as a marker of axonal loss, may help us to predict short-term outcome in patients with early RRMS.

Axonal damage probably occurs early in the evolution of MS. Five of 38 (13%) patients had a positive assay for the neuronal 14-3-3 protein in the CSF obtained at the first clinically isolated syndrome suggestive of MS. A positive 14-3-3 assay was the only independent predictor for a shorter time to conversion to clinical definite MS (risk ratio 4.1; 95% CI 1.1 to 15) and to reach an Expanded Disability Status Scale (EDSS) > or =2 at the end of follow-up (odds ratio 14.8; 95% CI 2.86 to 76.8). The detection of the 14-3-3 protein in the CSF at the first neurologic event suggestive of MS may be a useful predictor of short-term evolution.

Behçet disease is a systemic form of vasculitis which presents with neurological symptoms with a frequency varying between 16 and 40%. Involvement of the parenchyma has been found to worsen the prognosis in patients with neuroBehçet (NB).To review the clinical features and course of patients with NB involving the parenchyma of the central nervous system (CNS).Seven patients with Behçet disease and neurological localizing signs were seen in our hospital between 1989 and 1996. The initial diagnosis was of ischemic ictus in five of the seven patients. Both neuroimaging studies and investigation of the cerebrospinal fluid were always pathological in all cases. Vascular studies (arteriography and echo-Doppler of the supra-aortic trunks) were normal. One patient died. Four patients had serious sequelae following treatment.NB should be included in the different diagnosis of ictus. Involvement of the parenchyma of the CNS was accompanied by lymphocytic meningitis, perhaps also leading to a worse functional prognosis.

The aim of this study was to compare the efficacy of IgIV versus plasmapheresis in the treatment of Guillain-Barré syndrome. Twenty-four Guillain-Barré patients were treated either with IgIV (n = 17), or plasmapheresis (n = 7). Evolution during the first year after onset were assessed using the motor functional scale of Hughes and nerve conduction studies. IgIV treated patients had better functional recovery than the plasmapheresis group (p0.05) and shorter hospital stays (p0.05). These differences were significant from day 30 after treatment. Complications occurred in 14 patients: 9 (58%) in the IgIV group, and 5 (71%) in the patients treated with plasmapheresis. IgIV treated patients had better functional recovery scores and shorter hospital stays. There were no differences in the complication rates. Therefore we believe that IgIV is the treatment of choice for Guillain-Barré syndrome in our clinical setting.

Introducción: la enfermedad de Behçet es una vasculitis sistémica que presenta clínica neurológica con una frecuencia que varía entre el 16 y el 40%. Se ha relacionado la afectación parenquimatosa con un peor pronóstico en los pacientes con neurobehçet (NB). Objetivo: revisar la clínica y evolución de los pacientes con NB y afectación parenquimatosa del sistema nervioso central (SNC). Casos clínicos. Siete pacientes con enfermedad de Behçet y focalidad neurológica fueron atendidos en nuestro centro entre 1989 y 1996. El diagnóstico inicial fue de ictus isquémico en cinco de los siete pacientes. Tanto los estudios de neuroimagen como los del líquido cefalorraquídeo resultaron siempre patológicos. Los estudios vasculares (arteriografía y eco-Doppler de troncos supraórticos) fueron normales. Un enfermo fue éxitus letalis. Cuatro pacientes presentaron secuelas tras el tratamiento. Conclusión: el NB ha de formar parte del diagnóstico diferencial del ictus. La afectación parenquimatosa del SNC se acompaña de meningitis linfocitaria y puede, además, condicionar un peor pronóstico funcional.

In recent years the need to create scales for measuring the dysfunction or impairment suffered by patients with multiple sclerosis has increased. The aim of the scales that measure neurological impairment is two fold: to homogenise the data from different series so that studies into the prognosis and natural history of the disease can be compared, and to measure the changes in the progress of the disease when a therapy has been established. Over the past few years a large number of scales have appeared that attempt to redress the shortcomings of the EDSS (Expanded Disability Status Scale). The latest of these, the MSF Composite, manages to overcome the statistical problems of the EDSS and enables significant differences between two groups to be detected when studying the effect of a treatment.In the coming years we will possibly witness a joint use of several of the scales described, and both the EDSS and the Composite will be employed together in the evaluation of patients in therapeutic protocols, perhaps together with a quality of life scale.

The presence of axonal lesions in plaques of demyelination in patients with multiple sclerosis (MS) has been known for many years. Traditionally it was believed that axonal loss occurred in chronic lesions. However, demonstration of pathological degeneration in active plaques, use of new resonance techniques such as spectroscopy or the transfer of magnetization, showing axonal damage in white matter of apparently normal aspect, and the presence of axonal neurofilaments in the cerebrospinal fluid during the episode has made it necessary to reconsider the contribution made by axonal damage to the pathogenesis of MS. Besides, recent studies have shown that a factor present in the cerebrospinal fluid of patients with MS may contribute to the induction of neuronal apoptosis. These facts, apart from their pathogenic implications and consequent clinical repercussions, will affect investigation of alternative treatments for this disorder, and by means of clinico-immunoradiological correlation will help to define the prognosis of the course of the disorder in these patients.