Respirometric techniques coupled with laboratory-scale tests for kinetic and stoichiometric characterisation of fungal and bacterial tannin-degrading biofilms.

In environmental biotechnology applications for wastewater treatment, bacterial-based bioprocesses are mostly implemented; on the contrary, the application of fungal-based bioprocesses, is still challenging under non-sterile conditions. In a previous laboratory-scale study, we showed that when specific tannins are used as the sole carbon source, fungi can play a key role in the microbial community, under non-sterile conditions and in the long term. In a previous study, an engineered ecosystem, based on fungal tannin biodegradation, was successfully tested in a laboratory-scale bioreactor under non-sterile conditions. In the present study, a kinetic and stoichiometric characterisation of the biomass developed therein was performed through the application of respirometric techniques applied to the biomass collected from the above-mentioned reactor. To this aim, a respirometric set-up was specifically adapted to obtain valuable information from tannin-degrading fungal biofilms. A mathematical model was also developed and applied to describe both the respirometric profiles and the experimental data collected from the laboratory-scale tests performed in the bioreactor. The microbial growth was described through a Monod-type kinetic equation as a first approach. Substrate inhibition, decay rate and tannin hydrolysis process were included to better describe the behaviour of immobilised biomass selected in the tannin-degrading bioreactor. The model was implemented in AQUASIM using the specific tool Biofilm Compartment to simulate the attached fungal biofilm. Biofilm features and transport parameters were either measured or assumed from the literature. Key kinetic and stoichiometric unknown parameters were successfully estimated, overcoming critical steps for scaling-up a novel fungal-based technology for tannins biodegradation.

Stability of fungal biomass continuously fed with tannic acid in a non-sterile moving-packed bed reactor.

A number of bacteria and fungi are known to degrade tannins. In this study, the efficiency of the white-rot fungus, Bjerkandera adusta MUT 2295, was evaluated for the treatment of a synthetic solution prepared with tannic acid. Tests were performed in continuously fed, bench-scale, packed-bed reactors, operated under non-sterile conditions with biomass immobilized within PolyUrethane Foam cubes (PUFs). The main parameters monitored to evaluate the process efficiency were: soluble Chemical Oxygen Demand (sCOD), Total Organic Carbon (TOC) removal, and activities. of Tannase and Lignin Peroxidase. At the end of the process, additional parameters were evaluated, including the increase of fungal dry weight and the presence of ergosterol. The reactor was operative for 210 days, with maximum sCOD and TOC removal of 81% and 73%, respectively. The reduction of sCOD and TOC were positively correlated with the detection of Tannase and Lignin Peroxidase (LiP) activities. Increases in biomass within the PUF cubes was associated with increases in ergosterol concentrations. This study proved that the fungal-based system tested was efficient for the degradation of tannic acid over a period of time, and under non-sterile conditions.

Evaluation of intralesional injection of hyaluronic acid compared with verapamil in Peyronie's disease: preliminary results from a prospective, double-blinded, randomized study.

Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid (HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil (ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease (PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function (IIEF-5) score. The difference between post- and pre-treatment plaque size was -1.36 mm (SD ± 1.27) for Group A and -1.80 mm (SD ± 2.47) for Group B (p-value = NS). IIEF-5 increased of 1.46 points (SD ± 2.18) in Group A and 1.78 (SD ± 2.48) in Group B (p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° (SD ± 5.63) from the baseline (p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement (PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I.

Effect of cellulose as co-substrate on old landfill leachate treatment using white-rot fungi.

Conventional wastewater treatment technologies are ineffective for remediation of old LandFill Leachate (LFL), and innovative approaches to achieve satisfactory removal of this recalcitrant fraction are needed. This study focused on old LFL treatment with a selected fungal strain, Bjerkandera adusta MUT 2295, through batch and continuous tests, using packed-bed bioreactors under non-sterile conditions. To optimize the process performance, diverse types of co-substrates were used, including milled cellulose from beverage cups waste material. Extracellular enzyme production was assayed, in batch tests, as a function of a) cellulose concentration, b) leachate initial Chemical Oxygen Demand (COD) and Soluble COD (sCOD), and c) co-substrate type. Bioreactors were dosed with an initial start-up of glucose (Rg) or cellulose (Rc). An additional glucose dosage was provided in both reactors, leading to significant performance increases. The highest COD and sCOD removals were i) 63% and 53% in Rg and ii) 54% and 51% in Rc.

Neurogenic bladder and disc disease: a brief review.

OBJECTIVE: Neurogenic bladder refers to morphofunctional alterations of the bladder-sphincter complex secondary to central or peripheral neurological lesions. Discal etiology can be suggested by clinical observation in patients complaining of classical lower back pain, but not excluded even without musculoskeletal pain. This review provides a brief overview of associations between neurogenic bladder and disc disease, analyzing neuroanatomy, pathophysiology, clinical and urodynamic findings. Therapy is reviewed focusing on etiological treatments. METHODS: The literature search was performed on PubMed, Medline and Google scholar using the following keywords: 'neurogenic bladder', 'disc herniation', 'disc prolapse', 'disc protrusion', 'cauda equina syndrome', 'treatment', 'surgery', 'urodynamic', either alone or in combination using 'AND' or 'OR'. The reference lists of articles retrieved were examined to capture other potentially relevant articles. The search was restricted to articles published between 1970 and 2012. Seventy-nine papers were found, but only 42 were reviewed and summarized. FINDINGS: The literature reviewed confirmed correlations between neurogenic bladder and disc disease. Approximately 40% of patients with lumbar disc disease have abnormal urodynamic testing, and an even larger proportion complain of voiding symptoms. The most common urodynamic finding is detrusor areflexia, but underactive or overactive detrusor can also be observed. Electromyography can show perineal floor muscle innervation abnormalities. Chronic nervous damage induces reduction of bladder sensitivity and detrusor atrophy. An overdistension of the bladder follows, with global and circumferential thinning of the bladder wall. Overactive detrusor is related to early nerve roots stretching causing an irritative state responsible for overstimulation and neurogenic overactivity. Detrusor hypertrophy is the anatomical deformation correlated. CONCLUSIONS: Benefits for neurogenic bladder obtained through disc disease treatment should be studied in more detail, especially conservative therapies, not yet discussed in literature. Spine surgery effectiveness on voiding function should be valued in the light of the latest surgical techniques, considering the controversial results reported after laminectomy.

ApolipoproteinE epsilon 4 allele is not associated with disease course and severity in multiple sclerosis.

BACKGROUND: No study has assessed the association between apolipoproteinE (APOE) and multiple sclerosis (MS) forms grouped by also taking into account cognitive performance. AIMS OF THE STUDY: To assess the relationship between APOE and disease course, particularly focusing on benign MS (BMS), defined as also including cognitive preservation. METHODS: In 173 consecutive patients, we assessed the association between APOE and MS course and severity. RESULTS: Twenty-nine APOE-epsilon4 carriers were identified. The epsilon4 allele was not associated with BMS. Moreover, it was associated neither with other disease courses nor with the time to reach disability milestones and secondary progression. CONCLUSION: Although plausible, the association between APOE and MS course (particularly with BMS defined by including cognitive preservation) and disease severity remains controversial.

Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis.

OBJECTIVE: To assess whether neuropsychological tests and MRI measures could be used as predictors of short-term disease evolution in a population of patients with benign multiple sclerosis (B-MS). BACKGROUND: The definition of B-MS is controversial. Recent data suggest that neuropsychological tests and MRI measures can provide valuable information for a more correct definition and interpretation of B-MS. METHODS: Sixty-three patients with B-MS (Expanded Disability Status Scale [EDSS] < or =3.0 and disease duration > or =15 years) underwent neuropsychological assessment using the Rao's Brief Repeatable Neuropsychological Battery and the Stroop Test. At that time, conventional brain MRI and magnetization transfer (MT) imaging was performed. White matter lesion load, global and regional brain volumes, and MT ratio in lesions and normal-appearing brain were measured. After a mean follow-up of 5 years, patients still having an EDSS score < or =3.5 were classified as still benign, whereas patients who had developed a secondary progressive course or who had an EDSS score > or =4.0 were defined as no longer benign (NLB). RESULTS: At end of follow-up, 29% of patients were classified as NLB. Male gender (hazard ratio [HR] = 2.9; 95% confidence interval [CI] 1.2-7.5; p = 0.02), number of neuropsychological tests failed (HR = 1.4; 95% CI 1.1-1.7; p = 0.003), and T1-weighted lesions (HR = 1.3; 95% CI 1.1-1.5; p = 0.002) were related to NLB status. In a model including these 3 variables, the NLB status was predicted with an accuracy of 82%. CONCLUSIONS: Cognitive assessment and MRI metrics can predict short-term disease evolution in benign multiple sclerosis (B-MS). This information can be useful to correctly identify patients with B-MS.

Switching to second-line therapies in interferon-beta-treated relapsing-remitting multiple sclerosis patients.

BACKGROUND: Interferon-beta (IFNB) therapies are the most widely used as first-line intervention in the treatment of relapsing-remitting (RR) multiple sclerosis (MS). Despite long-term experience, however, the definition and prediction of response remain controversial. AIM: The objective of this study was to assess the long-term validity of the main clinical definitions of response applied after 1 and 2 years of IFNB therapy in a cohort of RRMS patients followed up for at least 5 years. METHODS: We tested these different definitions against a 'hard' parameter of treatment failure, represented by the need to suspend IFNB and switch to an intravenous immunosuppressive (IVIS) treatment, using Kaplan-Meier and Cox survival analyses. RESULTS: Out of 147 RRMS patients treated with IFNB therapy and followed up for 7.8 +/- 2.1 years, 26 (18%) were switched to an IVIS therapy. On the whole, disability progression as indicated using the Expanded Disability Status Scale (EDSS) and a higher number of relapses in the first 2 years of therapy were related to long-term treatment failure. CONCLUSION: Our study highlights the role of disability and high relapse rate in the first 2 years of treatment in predicting long-term response and the switching to second-line therapies.

The contribution of cerebrospinal fluid oligoclonal bands to the early diagnosis of multiple sclerosis.

BACKGROUND: McDonald Criteria (MDC) have been validated in selected patients at high risk for multiple sclerosis (MS). However, possible overdiagnosis of MS can represent critical issues in less controlled clinical settings. OBJECTIVE: To assess the contribution of oligoclonal bands (OB) to MS diagnosis in current clinical practice. METHODS: We included all the patients admitted to our Department since 2001 who had undergone diagnostic workup for a possible MS diagnosis, followed up for at least 1 year. We assessed the accuracy of MDC, OB, and two MDC definitions of dissemination in space (DIS-MRI: fulfillment of MRI criteria, DIS-OB: two MRI lesions+OB). RESULTS: We included 118 patients (median follow-up 4.0 years). Twenty-eight cases received an alternative diagnosis, whereas none of these presented OB, 43% fulfilled the DIS-MRI criteria. OB were present in 70% of the remaining 90 patients. By the end of the follow-up, 56% of the diagnoses had converted to clinically definite MS and OB showed higher accuracy than DIS-MRI fulfillment (70% vs 58%). Moreover, after 1 year and at the end of the follow-up, DIS-OB yielded a higher Specificity level in comparison with DIS-MRI. CONCLUSION: OB can improve overall diagnostic Accuracy by increasing Specificity and negative predictive value.

A short version of Rao's Brief Repeatable Battery as a screening tool for cognitive impairment in multiple sclerosis.

Rao's Brief Repeatable Battery (BRB) is the most widely used instrument for cognitive evaluation in multiple sclerosis (MS). We assessed a short version of the BRB in 116 relapsing-remitting participants. We found that the administration of three tests, the Selective Reminding Test, the Paced Auditory Serial Addition Test-3 seconds and the Symbol Digit Modalities Test, was able to detect cognitive impairment with a sensitivity of 94%, a specificity of 84%, and an accuracy of 89%. On the basis of these results we developed a screening algorithm requiring 5 to 15 minutes, which may represent a highly sensitive and rapid tool to detect MS-associated cognitive impairment.

Cognitive assessment and quantitative magnetic resonance metrics can help to identify benign multiple sclerosis.

BACKGROUND: The definition of benign multiple sclerosis (B-MS) is still controversial. This mainly takes into account the subject's motor ability, with little or no relevance to other important features such as cognition. Moreover, no paraclinical markers are currently available to reliably identify patients who will remain benign in the long term. OBJECTIVES: To assess, by using quantitative magnetic resonance (MR) metrics, differences in tissue damage between B-MS patients after dividing them into two groups on the basis of their cognitive performance. METHODS: Forty-seven B-MS patients (Expanded Disability Status Scale score /=15 years) underwent neuropsychological assessment through the Rao Brief Repeatable Battery and the Stroop Test. At that time, B-MS patients underwent conventional brain MR and magnetization transfer (MT) imaging. White matter lesion load, global and regional brain volumes, and MT ratio (MTr) in lesions and normal-appearing brain were measured. Quantitative MR measures were compared in cognitively impaired (CI-MS) and cognitively preserved (CP-MS) patients and in 24 demographically matched healthy controls. Test performance was correlated with MR changes in specific cortical regions. RESULTS: Eleven patients were classified as CI-MS, and 36 were classified as CP-MS. Both T2-weighted and T1-weighted lesion loads were higher (p = 0.05 and 0.001) in CI-MS than in CP-MS patients. Furthermore, CI-MS patients were characterized by more pronounced decrease in neocortical volume (p = 0.005) and cortical MTr (p = 0.02) values than CP-MS patients. Finally, test performance correlated significantly with MR changes in relevant cortical regions. CONCLUSIONS: Cognitive assessment and quantitative magnetic resonance can help to reliably identify benign multiple sclerosis patients.

Long-term adherence to interferon beta therapy in relapsing-remitting multiple sclerosis.

BACKGROUND/AIMS: To assess the proportion and the reasons of drop-outs in relapsing-remitting multiple sclerosis patients treated with interferon-beta (IFNB) and the outcome of switching subjects. METHODS: Patients stopping IFNB were classified according to the reason of drop-out: perceived lack of efficacy (PLE) side effects (SE) and other reasons. Long-term adherence was described using the Kaplan-Meier curves. RESULTS: We evaluated 225 subjects (158 women; age = 36.6 +/- 9.2 years, disease duration = 8.0 +/- 6.1 years, Expanded Disability Status Scale score = 1.9 +/- 1.2) who received Betaferon (46), Avonex (88) and Rebif (91) therapy. The mean follow-up duration was 4.2 +/- 2.7 years. Forty-six percent of patients suspended therapy, 29% because of PLE, 15% because of SE and the remaining 2% due to other reasons. Twenty-five out of 33 subjects who suspended IFNB because of SE and 62 out of 65 patients who suspended the therapy due to PLE were switched to another disease-modifying drug. At the end of the follow-up, the majority of these patients could continue the treatment. CONCLUSIONS: When starting IFNB therapy in relapsing-remitting multiple sclerosis, a relatively high proportion of discontinuation is to be expected over time. Switching from a treatment to another taking into account the reasons of drop-out and the disease activity is a suitable option.

Influence of impaired T- and B-cell compartments on efficacy of IVIg in dysimmune neuropathies.

Autoimmune mechanisms are postulated to play a role in the development and progression of dysimmune neuropathies (DN). We investigated the relation between lymphocyte number and marker expression, and disease activity in 20 patients with DN under intravenous immunoglobulins (IVIg) treatment. B- and T-lymphocyte markers were studied by flow cytometry of the expression of CD5, CD25, CD23 and CD38 markers on B cells and of CD3, CD4 and CD8 markers, respectively. These parameters were compared with those obtained from matched healthy volunteers. The proportions of CD38+ B cells were higher in patients compared with those of controls. Proportions of activated CD4+ and CD8+ T cells were comparable in peripheral blood mononuclear cells of patients and controls, but a significant reduction of the absolute numbers of CD3+, CD4+ and CD8+ cells were observed in DN patients. The percentages of CD25+ memory T cells were instead significantly increased in DN patients. Lastly, T-cell reduction and the CD19/CD38 ratio over total B (CD19+) cells directly correlated with a poor response to IVIg therapy. In DN, whereas T-cell number is reduced, activated T and B cells are increased, thus suggesting an intrinsic defect of the immune response.

Autologous hematopoietic stem cell transplantation for very active relapsing-remitting multiple sclerosis: report of two cases.

Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a rescue treatment in multiple sclerosis (MS) patients not responding to first- or second-line therapies. To date, most of the treated cases had a secondary progressive disease course. However, patients with high inflammatory activity, but no secondary progression of the disease, could be candidates to take greater advantage of AHSCT. In this paper, we report two cases with very active, relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic resolution to disease activity.

Response to interferon-beta therapy in relapsing-remitting multiple sclerosis: a comparison of different clinical criteria.

We assessed the proportion and potential predictors of response to interferon-beta (IFNbeta) therapy in relapsing remitting (RR) multiple sclerosis (MS) patients, comparing different definitions of response: a) lower relapse rate during therapy compared to the year and the two years before therapy, b) reduction of relapse rate during therapy of at least 30% compared to the two years before therapy, c) no relapse during treatment, d) no progression on the Expanded Disability Status Scale (EDSS). Among 147 RR patients treated for at least one year, 33 received IFNbeta-1b subcutaneously (SC) (Betaferon), 59 IFNbeta-1a intramuscularly (Avonex) and 55 IFNbeta-1a SC (Rebif). Using definitions a), b) and d), 72%, 73% and 73% patients, respectively, were considered responders. Forty-four per cent of our patients were completely relapse free. In the logistic regression model, using definitions a) and b), a higher relapse rate in the two years preceding the therapy turned out to be a significant predictor of response. Considering definition c), lower baseline relapse rate was associated with a more favourable response.

A new methodology to calculate the environmental protection index (Ep). A case study applied to a company producing composite materials.

Environmental indicators can be used as a first stage in progress towards comprehensive environmental impact measures [J. Environ. Manage 65/3 (2002) 285]. In this article, we develop a 'pollutant interaction matrix method' that allows calculation of a global environmental protection index (Ep) in order to verify the eco-compatibility of an industrial activity. Two methods are proposed for the Ep index evaluation (which represents the numerical measure of the environmental sustainability): the Direct Method (Epd) and the Weighted Method (Epw). Both methods need to define, in the whole industrial process, homogeneous sectors (defined as construction sites where activities of the same type are carried out). Furthermore, for each activity a set of parameters (t, duration of pollution effect, P, quantity of pollutant produced,G, hazard of the pollutant) are required to evaluate the relative pollution index Y. All indices calculations were carried out using a set of matrices. The correct use of Ep evaluation provides an improvement in the total environmental performance of companies because it points out possible critical operations in each homogeneous sector which require solutions. The methodology is applied to evaluate the environmental pollution risk of a company that produces polymer materials and to improve their environmental performance. The results obtained show that the whole productive process has a low environmental impact factor. Nevertheless the applied methodology puts in evidence some processes that generate local pollution in specific areas of the factory and which could be dangerous for the workers' health.

Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment.

OBJECTIVE: To assess neocortical changes and their relevance to cognitive impairment in early relapsing-remitting (RR) multiple sclerosis (MS). METHODS: Conventional MR was acquired in 41 patients with RR MS and 16 demographically matched normal control subjects (NCs). An automated analysis tool was used with conventional T1-weighted MRI to obtain measures of cortical brain volumes normalized for head size. Neuropsychological performance of MS patients was assessed using the Rao Brief Repeatable Battery. Relationship between volumetric MR measures and neuropsychological scores was assessed. RESULTS: Neuropsychological assessment allowed for the identification of 18 cognitively preserved (MS-cp) and 23 cognitively impaired (MS-ci) MS patients. The whole MS sample showed lower values of normalized cortical volumes (NCVs) than did the NC group (p = 0.01). Upon grouping of MS patients according to cognitive performance, NCV values were lower (p = 0.02) in MS-ci patients than in both MS-cp patients and NCs. Moreover, there were positive correlations between NCV values and measures of verbal memory (r = 0.51, p = 0.02), verbal fluency (r = 0.51, p = 0.01), and attention/concentration (r = 0.65, p < 0.001) in MS-ci patients. Furthermore, NCV values were decreased in patients who scored lower on a greater number of tests (r = -0.58, p < 0.01) in the MS-ci group. None of the neuropsychological measures correlated to NCV values in the MS-cp patient group. CONCLUSIONS: Cortical atrophy was found only in cognitively impaired patients and was significantly correlated with a poorer performance on tests of verbal memory, attention/concentration, and verbal fluency. Gray matter pathology may contribute to the development of cognitive impairment in MS from the earliest stages of the disease.

Mouse blastocysts release a lipid which activates anandamide hydrolase in intact uterus.

Anandamide (N-arachidonoylethanolamine, AEA) is a major endocannabinoid, known to impair mouse pregnancy and embryo development and to induce apoptosis in blastocysts. Here we show that mouse blastocysts rapidly (within 30 min of culture) release a soluble compound, that increases by approximately 2.5-fold the activity of AEA hydrolase (fatty acid amide hydrolase, FAAH) present in the mouse uterus, without affecting FAAH gene expression at the translational level. This "FAAH activator" was produced by both trophoblast and inner cell mass cells, and its initial biochemical characterization showed that it was fully neutralized by adding lipase to the blastocyst-conditioned medium (BCM), and was potentiated by adding trypsin to BCM. Other proteases, phospholipases A(2), C or D, DNAse I or RNAse A were ineffective. BCM did not affect the AEA-synthesizing phospholipase D, the AEA-binding cannabinoid receptors, or the selective AEA membrane transporter in mouse uterus. The FAAH activator was absent in uterine fluid from pregnant mice and could not be identified with any factor known to be released by blastocysts. In fact, platelet-activating factor inhibited non-competitively FAAH in mouse uterus extracts, but not in intact uterine horns, whereas leukotriene B(4) or prostaglandins E(2) and F(2)alpha had no effect. Overall, it can be suggested that blastocysts may protect themselves against the noxious effects of uterine endocannabinoids by locally releasing a lipid able to cross the cell membranes and to activate FAAH. The precise molecular identity of this activator, the first ever reported for FAAH, remains to be elucidated.

Safety and tolerability of cyclophosphamide 'pulses' in multiple sclerosis: a prospective study in a clinical cohort.

To assess the safety and tolerability of cyclophosphamide (CTX) 'pulse' therapy in progressive or very active multiple sclerosis (MS), we reviewed our experience in a cohort of MS patients who have been treated and prospectively followed-up in our Department since 1997. One hundred and twelve patients received intravenous CTX in monthly 'pulses' for 12 months at the dosage of 700 mg/m2 of body surface, then bimonthly for another 12 months. We evaluated the frequency and the severity of side-effects, as well as overall tolerability by the patient perspective using a visual analogue scale (VAS). Side-effects resulted in the discontinuation of therapy in 20 (18%) cases. Serious side-effects were observed in 24 patients (21.4%), most commonly definitive amenorrhea (33.3% of fertile women), hypogammaglobulinemia (5.4%), and hemorrhagic cystitis (4.5%). Malignancies were diagnosed in four (3.6%) subjects, three of whom were previously treated with azathioprine (AZA). Finally, 81.8% of the patients judged the treatment regimen as very or relatively acceptable and tolerable. Our data point to a reasonable safety and tolerability of CTX 'pulse' therapy. Further trials are needed to definitively assess the efficacy of CTX as an alternative therapeutic option for progressive or very active MS.

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.