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Background Memory impairment (MI) is a common symptom of MS. Previous studies were conflicting in respect to the possible existence of early MI and the role of hippocampal atrophy. The objective of this study was to investigate MI and structural MRI correlates in homogenous groups of early and late MS, controlling for a potential information-processing speed (IPS) deficit, and utilizing multiple memory test paradigms. Methods 152 individually matched subjects were recruited: early MS (EMS, N = 25, disease duration 1.0 ± 0.8 years), late MS (LMS, N = 52, 16.5 ± 5.2 years), and corresponding controls. Five memory tests were utilized to account for differences in learning material (verbal, visual), encoding (incidental, intentional), and retrieval (free recall, recognition, recurring recognition). Performance was related to IPS, memory-specific (hippocampal volumes), and unspecific MRI measures (T1/T2LL, brain volume, cortical thickness). Results Memory was impaired across all tests in LMS, but not in EMS. LMS-patients were also significantly impaired in IPS which was correlated with several memory scores. Regression analyses revealed IPS and cortical thickness as predictors for visual MI, and IPS, sex, and left hippocampal volume as predictors for verbal MI. Conclusion Additionally to direct destructions in memory specific tracts such as the hippocampus, memory decline in MS may also be related to a general factor comprising slowed information-processing and global tissue loss.

Multiple sclerosis is the most common cause of non-traumatic disability in young adults. The following article addresses special features of multiple sclerosis in the context of neurological rehabilitation. The rehabilitative and symptomatic therapy of frequent symptoms and functional deficits are presented independently of the course of the disease. Rehabilitation in MS focuses on functional deficits in mobility, paresis, spasticity, ataxia, bladder dysfunction, fatigue, cognitive symptoms, depression and pain. The multimodal inpatient rehabilitation comprises aerobic training in MS-specific groups and interventions targeting individual deficits. Neuropsychological training, individual and group session on coping and adherence to therapy as well as advice on social issues and the evaluation of the work place situation complement the therapy options. The early age of onset of the disease often causes an early restriction of participation in working life. The restoration and maintenance of work ability is therefore an essential goal of neurological rehabilitation, as well as the organization of aftercare and the introduction of vocational rehabilitation services.Bei multipler Sklerose (MS) sind aufgrund einer frühzeitigen Einschränkung der Teilhabe am Arbeitsleben die Wiederherstellung und der Erhalt der Erwerbsfähigkeit wesentliche Ziele der neurologischen Rehabilitation. Neben den Besonderheiten der MS in der neurologischen Rehabilitation wird in diesem Beitrag unabhängig von der Verlaufsform die rehabilitative und symptomatische Therapie häufiger Symptome dargestellt und in einem Fallbeispiel vertieft.

Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance.

Objective: The objective of this study was to assess the effect of treatment with interferon (IFN) β-1a, 44 µg subcutaneously (sc) three times weekly (tiw), on clinical and magnetic resonance imaging (MRI) outcomes in patients with relapsing multiple sclerosis (MS) following mitoxantrone therapy. Methods: This was an open-label, randomized, multicentre, rater-blinded, 96-week observational study conducted in Germany. Clinically stable patients with relapsing forms of MS, who had discontinued mitoxantrone treatment 1–6 months before study entry, were randomized to IFN β-1a sc 44 µg tiw, or no treatment. The primary endpoint was time to first relapse. Secondary endpoints included the number of relapse-free patients, disease activity assessed by MRI and time to 3-month confirmed Expanded Disability Status Scale (EDSS) progression, all at week 96. Results: A total of 30 patients were randomized (intent-to-treat population: 14 IFN β-1a, 15 untreated; one patient from the safety population discontinued the study after 25 days owing to an adverse event and without providing any postbaseline efficacy data, and was thus excluded from the intent-to-treat population). Overall, 71.4% (10/14) of patients in the IFN β-1a group remained relapse free over 96 weeks, versus 46.7% (7/15) in the untreated group ( p = 0.26). IFN β-1a delayed the time to first relapse versus no treatment ( p = 0.14); time to first relapse (25th percentile) was 95.4 (IFN β-1a) versus 46.0 weeks (no treatment). Confirmed EDSS progression was observed in five patients in each treatment group. Mean change in EDSS score was 0.3 in both groups ( p = 0.79). Changes in the number or volume of T1 and T2 lesions at week 96 were not significantly different between treatment groups ( p > 0.05). There were no new or unexpected adverse events related to IFN β-1a treatment. Conclusions: Several endpoints appeared to show a benefit of IFN β-1a treatment, but no significant differences could be detected owing to the small sample. Therefore, these data only permit, at best, tentative conclusions about the disease course in patients with MS after de-escalation from mitoxantrone and continuation with or without IFN β-1a. Larger confirmatory studies are required.

Background: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. Objectives: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. Methods: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20–60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. Results: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently ( p Conclusions: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Multiple sclerosis (MS) is an inflammatory disease the central nervous system. Its first manifestation and clinical course of the disease is highly heterogeneous. The diagnosis is based on the verification of neurological deficits, the development of the clinical course and the magnetic resonance imaging (MRI) of the head and spine. The therapy comprises disease modifying drugs (DMD), therapy for acute relapses and escalation therapy according the German MS-Therapy-Consensus-Group (MSTKG). An early therapy initiation and a systematic therapy of acute relapses and symptoms determine the modern MS-management.

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS ( n = 34) and SPMS ( n = 197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group ( P = 0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks ( P = 0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group ( P = 0.028). The difference was significant in PPMS ( P = 0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance ( P = 0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS. Multiple Sclerosis 2007; 13: 1107—1117. http://msj.sagepub.com

To assess whether TGF-beta isoforms are significantly increased after intravenous immunoglobulin (i.v.IG) infusion in the plasma of patients with multiple sclerosis (MS), 19 patients with clinically definite MS were enrolled in a double blind placebo controlled i.v.IG study. TGF-beta1, TGF-beta2, TGF-beta3 plasma concentrations were measured prior and directly after i.v.IG infusions by specific ELISA. Compared to the placebo group, we found a significant increase in the plasma levels of all three TGF-beta isoforms in patients treated with i.v.IG. The significantly increased TGF-beta plasma concentrations in treated patients suggest an additional, immediate mechanism of action that may accompany the molecular effects of i.v.IG therapy in MS. The variable amount of the potent anti-inflammatory TGF-beta isoforms within the i.v.IG preparations may exert a differentiated view regarding the manifold indications of i.v.IG therapy.

Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo , the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper‐intense and T1 hypo‐intense lesion volumes. High‐resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age‐matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject’s entire brain and computed cross‐subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t ‐tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression. Received October 24, 2002. Revised February 24, 2003. Second revision March 27, 2003. Accepted March 28, 2003

Neurocognitive involvement in multiple sclerosis (MS) is heterogeneous with some authors suggesting a frontal pattern in patients with predominantly frontal lesions. To assess the relationship between the distribution of lesions and two cognitive components (visual N2, auditory P3a) of the event-related brain potential (ERP) receiving contributions from frontal lobe structures, we performed a combined ERP and magnetic resonance imaging (MRI) study. Thirty-four MS patients were assigned to “low lesion volume, (LLV)”(n = 12), “high lesion volume, (HLV)” (n = 12) and “frontal lesion volume, (FLV)” (n = 10) groups according to lesion volume and distribution on T2-weighted MRI-scans of the brain. ERPs in visual and auditory classification tasks as well as neuropsychological tests were carried out in patients and control subjects (n = 15). The index for automatic feature registration, the N2 component with its mainly frontal contribution in the visual task, was significantly reduced in amplitude in the FLV and HLV groups (both p < 0.01 vs. controls). Moreover its amplitude correlated with lesion volume (r=0.64, p < 0.001). In contrast neither P3a nor P3b subcomponents with a multiple generator nature in the auditory task varied systematically with lesion volume or distribution. Total lesion volume rather than predominant lesion arrangement appears to be the most important factor in neurocognitive changes in MS. This is most consistent with the view that MS lesions lead to partial disconnections within widespread cortical networks which in turn produce a pattern of neuropsychological deficits that reflect total lesion load more than lesion distribution.

OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study. METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ). RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis. CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point: (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

Neurodegeneration following inflammatory injury is considered to be a pathological correlate of irreversible disability in patients with multiple sclerosis. The availability of neurotrophins could influence the probability or rate of disease progression and the time of onset. The BDNF-Val66Met-polymorphism leads to altered intracellular transport and secretion of BDNF, and is thus a logical candidate for a gene that influences susceptibility and, more specifically, the clinical course of multiple sclerosis. In order to test this hypothesis we genotyped the polymorphism in 951 UK multiple sclerosis trio families, but found no evidence for association before (p=0.63) or after stratification for clinical course (p=0.73).

Background Prevalence rates of cognitive impairment (CI) in multiple sclerosis (MS) vary between 40% and 80%. Differences in classification criteria for CI may explain this variance. Objective This study reviewed and compared classification criteria for CI in patients with early and late MS. Methods The paper consists of two parts: a systematic review of published classification criteria and the presentation of new data. Criteria were reviewed in respect to percentage of abnormal parameters and cut-offs concerning standard deviations. Thereafter, criteria were applied to cognitive data of 25 patients with early MS (duration ≤ 2 y), 52 matched patients with late MS (≥ 12 y), and 75 matched controls. The test battery assessed alertness, divided attention, mental flexibility, verbal and visual learning, memory, and visuospatial abilities. Results Seventy classification criteria were revealed and grouped into 20 distinct approaches that can be subdivided into three basic classification strategies. Most commonly, CI was defined as performing 1.5 SD or 2 SD below the normative mean in 18–30% of test parameters (n = 42). Other criteria utilized cognitive domains (n = 6), composite indices (n = 8), or combinations of cut-offs and strategies. The stringency of the criteria was correlated with the prevalence rate of CI (r = − .43) and disease duration (r = .48). In the new data, a substantial effect of classification criteria was found with a prevalence rate ranging from 0 to 68% in early and 4 to 81% in late MS. Increased rates of CI in patients vs. controls were found following 18 out of 20 criteria in the sample of late MS. In early MS, an increased rate of CI was only found following a liberal 1.5 SD cut-off criterion. Inter-rater reliability between all criteria was moderate. However, between criteria of comparable stringency the inter-rater reliability was found to be strong. Conclusion Classification based on different published criteria is not fully comparable and criteria need to be better homogenized.

Background: In multiple sclerosis inflammation is primarily injurious to the central nervous system, but its therapeutic suppression might inhibit repair-promoting factors. Objectives: We aimed at better describing the complexity of biological effects during an acute relapse and analysed the effects of intervention with high-dose i.v. glucocorticoids and immunomodulatory treatment with interferon-beta (IFNβ). Methods: We studied the intracellular expression levels of the pro-inflammatory mediators tumour necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) together with the neurotrophins ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in freshly isolated peripheral blood mononuclear cells of multiple sclerosis patients during an acute relapse, after intervention with i.v. methylprednisolone and at baseline, using a highly quantitative flow-cytometric approach. Results: We demonstrated the expression of CNTF in human leucocytes. We showed that CNTF levels differed in acutely relapsing multiple sclerosis patients compared with controls and increased after corticosteroid treatment. CNTF can counteract the toxicity of TNFα towards oligodendrocytes and we found TNFα increased during acute relapses. Following corticosteroids, neither TNFα nor iNOS expression was reduced. Levels of BDNF were not affected by glucocorticoids, but increased during IFNβ therapy. However, IFNβ also increased the expression of iNOS and major histocompatibility complex class I (MHC-I), underlining its immunomodulatory potential. Conclusions: Multiple sclerosis patients might benefit from reparative, and not solely from anti-inflammatory, effects of glucocorticoids. Interactive effects of glucocorticoid- and IFNβ-treatment need to be considered to improve neuroprotection and remyelination resulting from immunomodulatory treatment.

Multiple sclerosis (MS) is an inflammatory disease the central nervous system. Its first manifestation and clinical course of the disease is highly heterogeneous. The diagnosis is based on the verification of neurological deficits, the development of the clinical course and the magnetic resonance imaging (MRI) of the head and spine. The therapy comprises disease modifying drugs (DMD), therapy for acute relapses and escalation therapy according the German MS-Therapy-Consensus-Group (MSTKG). An early therapy initiation and a systematic therapy of acute relapses and symptoms determine the modern MS-management.

1477-0970 (Electronic) 1352-4585 (Linking) Journal Article; This study was performed to assess the temporal evolution of damage within lesions and the normal-appearing white matter, measured using frequent magnetization transfer (MT) MRI, in relapsing-remitting multiple sclerosis (RRMS). The relationship of MT ratio (MTR) changes with measures of lesion burden, and the sample sizes needed to demonstrate a treatment effect on MTR metrics in placebo-controlled MS trials were also investigated. Bimonthly brain conventional and MT MRI scans were acquired from 42 patients with RRMS enrolled in the placebo arm of a 14-month, double-blind trial. Longitudinal MRI changes were evaluated using a random effect linear model accounting for repeated measures, and adjusted for centre effects. The Expanded Disability Status Scale (EDSS) score remained stable over the study period. A weak, but not statistically significant, decrease over time was detected for normal-appearing brain tissue (NABT) average MTR (-0.02% per visit; p = 0.14), and MTR peak height (-0.15 per visit; p = 0.17), while average lesion MTR showed a significant decrease over the study period (-0.07% per visit; p = 0.03). At each visit, all MTR variables were significantly correlated with T2 lesion volume (LV) (average coefficients of correlation ranging from -0.54 to -0.28, and p-values from

Defining tools in magnetic resonance imaging (MRI) representing specific pathological processes is needed to understand the complex relationship between inflammation, myelin breakdown, axonal injury and clinical symptoms in multiple sclerosis (MS) and its variants. Here, we describe a case of histologically-defined MS, in which the radiological appearance of the lesion and clinical course support the diagnosis of Balo's concentric sclerosis. Serial magnetization transfer, diffusion tensor imaging and 1H-magnetic resonance spectroscopy, from 14 days to 13 months after biopsy, allow the contextual interpretation of specific pathological changes. In our case, acute inflammation was sensitively traced by fractional anisotropy and increased lactate in spectroscopy. In contrast, magnetization transfer ratio and the apparent diffusion coefficient monitor the sequential loss of tissue in selected rings of the lesion. The delay from the peak of symptoms in a dramatic clinical course to the maximum tissue destruction indicated through MRI suggests that compromise of axonal function may be decisive for the acute clinical situation. This is the first report comparing 1Hmagnetic resonance spectroscopy, magnetization transfer and diffusion tensor imaging with histopathology in a patient with Balo's concentric sclerosis. Multiple Sclerosis 2007; 13: 471-482. http://msj.sagepub.com

Recently, several in vitro studies have demonstrated production of the potent immunosuppressive cytokine transforming growth factor beta (TGF-beta)2 in glioblastoma cell lines. Systematic studies of the concentration of TGF-beta isoforms in the plasma of patients harboring intracerebral tumors do not exist. In the present study, the concentrations of TGF-beta1 and TGF-beta2 in platelet-poor plasma of 21 patients with glioblastoma before and after extensive resection were measured by specific ELISA systems and related to survival. The plasma concentrations of latent TGF-beta1 of patients with glioblastoma prior to surgery were significantly higher in comparison to healthy control probands, but not to patients with multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to be significantly increased in the plasma of patients with glioblastoma in comparison to healthy control probands and patients with MS. After extensive resection of the tumor, the value of latent TGF-beta2 evidently decreased. Interestingly, the concentration of latent TGF-beta2 prior to surgery was correlated with survival and a strong relationship was found between the survival and the difference of latent TGF-beta2 levels prior to surgery minus the TGF-beta2 concentrations 7 days after surgery. A higher difference in these plasma concentrations >6 ng/ml vs.

The aim of this study was to use neuropsychological data to characterize two subtypes of multiple sclerosis (MS) patients in a large patient sample. We studied patients with primary-progressive MS (PPMS) and secondary-progressive MS (SPMS). A group of 121 MS patients (36 PPS, 85 SPMS) and 40 healthy controls were administered a brief battery of cognitive tests. Executive functioning, memory and attention were studied. Results demonstrate that PPMS patients exhibited slightly more impairment than patients with SPMS, although this difference is not significant (50% vs 37%). However, PPMS patients revealed a significantly poorer performance in verbal learning (p0.05) and in verbal fluency (p0.05). Whereas PPMS patients had significantly shorter disease durations (p0.05), there was no statistical difference in disability between both groups. We conclude from our study that cognitive deficits in progressive MS are frequent. Patients with PPMS tend to be more frequently and severely affected than SPMS patients. Our findings of high prevalence of cognitive involvement in PPMS have not been reported previously

In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability.Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke's Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability).Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61).In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment.

We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis (MS) and fatigue with objective electrophysiological measures. Behavioral methods (Reaction Time, RT) and two different Event Related Potential (ERP) components measuring i) stimulus selection (Selection Negativity, SN) and ii) response selection (Lateralized Readiness Potential, LRP) were employed. Twenty-four patients with clinical definite MS (10 relapsing remitting and 14 secondary progressive) and confirmed fatigue in the past three months (Fatigue Severity Scale (FSS) > 4) were included. Patients were randomized in a double-blind, placebo-controlled cross-over design. We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms. This negativity had a higher amplitude during amantadine treatment regardless of treatment order. The RT did not differ significantly between the treated and untreated groups. Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position (practice effect), but no treatment effect, while patients with a longer MS duration showed no practice effect, but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine. The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS, but appears to be limited to subjects with a longer duration of the disease.