Final Expanded Disability Status Scale Research Articles

Progression independent of relapse activity in relapsing multiple sclerosis: impact and relationship with secondary progression.

We investigated the occurrence and relative contribution of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) to confirmed disability accrual (CDA) and transition to secondary progression (SP) in relapsing multiple sclerosis (MS). Relapsing-onset MS patients with follow-up > / = 5years (16,130) were extracted from the Italian MS Registry. CDA was a 6-month confirmed increase in Expanded Disability Status Scale (EDSS) score. Sustained disability accumulation (SDA) was a CDA with no EDSS improvement in all subsequent visits. Predictors of PIRA and RAW and the association between final EDSS score and type of CDA were assessed using logistic multivariable regression and multivariable ordinal regression models, respectively. Over 11.8 ± 5.4years, 16,731 CDA events occurred in 8998 (55.8%) patients. PIRA (12,175) accounted for 72.3% of CDA. SDA occurred in 8912 (73.2%) PIRA and 2583 (56.7%) RAW (p < 0.001). 4453 (27.6%) patients transitioned to SPMS, 4010 (73.2%) out of 5476 patients with sustained PIRA and 443 (24.8%) out of 1790 patients with non-sustained PIRA. In the multivariable ordinal regression analysis, higher final EDSS score was associated with PIRA (estimated coefficient 0.349, 95% CI 0.120-0.577, p = 0.003). In this real-world relapsing-onset MS cohort, PIRA was the main driver of disability accumulation and was associated with higher disability in the long term. Sustained PIRA was linked to transition to SP and could represent a more accurate PIRA definition and a criterion to mark the putative onset of the progressive phase.

Comparing Clinical and Radiological Features in Familial and Sporadic Multiple Sclerosis.

Objective To compare the initial presentation, clinical features, disease courses, and radiological parameters between familial multiple sclerosis (fMS) and sporadic multiple sclerosis (sMS) to determine if the two represent distinct clinical entities. Methods This retrospective study was conducted at the Neurology Clinic at Kocaeli University Hospital. Records of 114 fMS and 150 sMS patients, aged 18-65, diagnosed based on either the Poser criteria or the McDonald 2001 criteria were analyzed. Radiological data and Expanded Disability Status Scale (EDSS) evaluations were conducted by a specialist neurologist. Variables included age at MS onset, first symptoms, relapses, EDSS scores at diagnosis and last examination, and MRI findings. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 28, Armonk, NY) was utilized for data analysis. Results Both fMS and sMS groups were comparable in age (43.55±12.50 and 42.35±10.61 years, respectively) and gender distribution (females: fMS 71.9%, sMS 71.3%). No significant difference was noted regarding disease onset age (fMS 29.83±10.77, sMS 30.42±9.7). Age of onset, final EDSS, and relapse rate didn't significantly vary among sMS, fMS with first-degree relatives having MS (fMS(1)), and fMS with second or third-degree relatives having MS (fMS(2)). The fMS group showed a significantly higher incidence of initial spinal cord lesions on MRI compared to the sMS group (38.6% vs. 17.3%; p<0.001). Within the fMS group, the presence of spinal cord lesions on initial MRI correlated with a higher relapse rate and elevated initial and final EDSS scores. Conclusion Despite overarching similarities between fMS and sMS, spinal cord lesions' prevalence and implications in fMS may point to a genetic underpinning warranting in-depth exploration.

Predictors of disability in a cohort with neuromyelitis optica spectrum

Disability in neuromyelitis optica spectrum disorder (NMOSD) is common and can be severe. To determine factors associated with increased disability in NMOSD. Observational, analytical, ambispective study in a cohort of patients with NMOSD between January 2015 and July 2021, using a secondary source to review variables and the expanded disability status scale (EDSS) after onset and a primary source, with a telephone survey for the final EDSS and missing data. Major disability was defined as occurring when the EDSS score was = 6. The analysis was performed by means of logistic regression with SPSS 25®. A total of 125 patients were analysed. The average age at onset was 41 (standard deviation: 14) years, with a female-to-male ratio of 8:1. Of the total sample, 87% (109) were positive for anti-aquaporin antibodies. Optic neuritis (44.8%) and transverse myelitis (39.2%) were the most frequent clinical manifestations at onset. Altogether 71.2% of patients received acute treatment at their first relapse. Mean chronic treatment initiation was 12 months (interquartile range: 3-60) and 44% had difficulties with immunosuppression compliance. Of the total number of patients, 80.8% had relapses and 44% had a final EDSS score = 6. The median baseline-to-final EDSS score was 1 (interquartile range: 0-3), often towards disability accumulation. An association was found between a relapsing course (odds ratio = 3.73; p = 0.011) and a high baseline EDSS (odds ratio = 1.54; p = 0.0001) with increased disability. In the multivariate analysis, with a higher baseline EDSS and a relapsing course disability was 1.6 and 5.3 times more likely to occur, respectively. Disease relapses and high EDSS after the first episode are predictors of disability in NMOSD.

Response to treatment in NMOSD: the Australasian experience

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is associated with significant morbidity and mortality. Several therapies have been recommended for NMOSD and more recently clinical trials have demonstrated efficacy for three monoclonal antibody therapies. We present a retrospective observational study of treatment response in NMOSD. MethodsThis was a retrospective, unblinded, observational study of treatment efficacy for rituximab and traditional immunosuppressive therapy in patients with AQP4 antibody positive NMOSD. Treatment efficacy was assessed using annualised relapse rates (ARR), time to first relapse and expanded disability status scale (EDSS) scores. ResultsComplete relapse and treatment data were available for 43/68 (63%) of AQP4 antibody positive NMOSD cases covering 74 episodes of treatment. In a time to first relapse analysis rituximab showed a risk ratio of 0.23 (95% CI 0.08 – 0.65) when compared with no treatment and there was a non-significant reduction in ARR of 35% compared to pre-treatment. β-interferon (p = 0.0002) and cyclophosphamide (p = 0.0034) were associated with an increased ARR compared to pre-treatment. Rituximab (median 4.0 [range 0.0 – 7.0]; p = 0.042) and traditional immunosuppressive therapy (median 4.0 [range 0.0 – 8.0]; p = 0.016) were associated with a lower final EDSS compared to β-interferon (median 6.0 [range 4.0 – 7.5]). ConclusionsThese data provide additional support for the use of rituximab in preference to traditional immunosuppressive agents and MS disease modifying therapies as first line treatment of NMOSD.

Serum Immunoglobulin G Level and Neutrophils to Lymphocytes Ratio Associated with the Prognosis of Neuromyelitis Optica Spectrum Disorder.

To investigate the factors related to the prognosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) in cerebrospinal fluid and peripheral blood examination. In this study, we enrolled 111 patients who were admitted to the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2018 and diagnosed with NMOSD. The patients were divided into the relapse group (n = 48) and remission group (n = 67). Before treatment, all the patients underwent a routine Cerebrospinal Fluid (CSF) and peripheral blood test on the second morning of admission. The association between laboratory data and disease prognosis was evaluated. The immunoglobulin G (IgG) level in the serum showed a strong correlation with the relapse of patients, especially in the aquaporin-4-Antibody (AQP4-Ab) positive group (p < 0.01). A high level of serum IgG concentration was associated with the relapse of NMOSD, especially in the anti-AQP4 positive group. The area under the Receiver Operating Characteristic (ROC) curve of serum IgG level was 0.888 (p<0.001, 95%CI: 0.808-0.968). The ratio of Neutrophils to Lymphocytes (NLR) was associated with the disability degree of NMOSD patients in 3 years. The NLR value was a linear correlation with final Expanded Disability Status Scale (EDSS) scores; patients with a high level of NLR value presented an increased degree of disability in the following three years (R2 = 0.053, p= 0.015). The serum IgG level and NLR of first-attack patients were correlated with the prognosis of NMOSD.

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders.

Background: Many patients with neuromyelitis optica spectrum disorders (NMOSD) experience the adverse consequences of relapse and disability aggravation. Thus, it is necessary to identify sensitive and reliable biomarkers for early prognosis. This study investigated whether serum homocysteine (Hcy) level was associated with the risk of relapse or poor prognosis in first-attack NMOSD patients.Methods: We enrolled 161 first-attack NMOSD patients in this retrospective study. We reviewed their medical records and evaluated their initial Expanded Disability Status Scale (EDSS). Clinical outcomes were measured by the final EDSS and the relapse rate. The association between Hcy levels and EDSS score at last follow-up was analyzed by binary logistic regression. The association between Hcy levels and relapse rate was assessed by Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was used to predict the target value of Hcy reduction.Results: Compared with the high Hcy group, the final EDSS score in the low Hcy group was significantly lower (median: 0.5 vs. 2.5, P < 0.001). The relapse rate differed significantly between these groups (30.6 vs. 50.0%, P = 0.023). Multivariate analysis showed that the initial EDSS score (odds ratio [OR] 3.03, 95% confidence interval [CI] 2.07–4.45, P < 0.001) and serum Hcy level (OR 1.13, 95%CI 1.04–1.22, P = 0.002) were significantly associated with poor prognosis in NMOSD patients. Additionally, multivariate analysis showed that serum Hcy level (hazard ratio 1.06, 95%CI 1.04–1.09, P < 0.001) was an independent predictor of the risk for relapse in NMOSD. The 12-month relapse rate of the high Hcy group was 34.8%, and 50% of high Hcy patients relapsed within 35 months after the first onset. A serum Hcy level exceeding 14.525 μmol/L indicated a high risk of relapse, with a sensitivity of 43.7%, specificity of 90.0%, and area under the ROC curve of 0.674 (95%CI 0.59–0.76, P < 0.001).Conclusion: Serum Hcy level is an independent predictor of relapse and poor prognosis in first-attack NMOSD patients. Early monitoring and reduction of serum Hcy levels may be of great significance in the prevention of disease relapse and severe disability.

Safety and efficacy of fingolimod in Iranian patients with relapsing-remitting multiple sclerosis: An open-label study.

Background:Fingolimod was the first oral therapy approved for treating relapsing-remitting multiple sclerosis (RRMS) in 2010. This open-label study evaluated the safety and efficacy of fingolideR, 0.5 mg in Iranian MS patients during one-year follow-up.Methods:A multicenter, open-label, longitudinal was designed to evaluate the safety and efficacy of fingolideR, 0.5 mg over a one-year follow-up period across 11 centers. The patients were visited by their neurologists every two months to evaluate possible adverse events and clinical disease activity considered by recording Kurtzke’s Expanded Disability Status Scale (EDSS).Results:A total of 252 patients with the mean treatment duration of 343±45.70 days were. 20 patients experienced adverse events (AEs) and serious adverse events (SAEs) such as resistant urinary tract infection (UTI), premature atrial contraction (PAC), skin allergic reaction, macular edema, chicken pox, zona, panic attacks, and exacerbations associated with steroids treatment, all of which led to FingolideR discontinuation. The mean EDSS decreased from (2.15±1.29, 95%CI: 1.99to2.32) at baseline to (1.85±1.22, 95%CI: 1.68to2.02) at 12th month (final visit) while a p-value revealed significant differences comparing baseline and final EDSS (p<0.001). Mean annualized relapse rate (ARR) of the patients in one year prior to the study was (0.006±0.016, 95%CI: 0.004to0.008) which changed to (0.005±0.016, 95%CI: 0.003to0.007) at the end of the study period. Patients with a 12-month period of fingolideR treatment experienced sustained ARR and disease progression (p<0.001).Conclusion:The obtained findings suggest that the administration of FingolideR, 0.5 mg (Fingolimod, Osvahpharma, Tehran, Iran) is safe and efficient for Iranian MS patients.

The long-term outcome of MOGAD: An observational national cohort study of 61 patients.

The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a matter of debate. Our aim was to assess the long-term outcomes of patients with MOGAD. We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG-IgG) and who had clinical follow-up of at least 8years from their first episode. Sixty-one patients (median [range] age at onset 27 [3-69] years), with a median (mean; range) follow-up of 177(212.8; 98-657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0-7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long-term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found. Overall long-term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon.

Effect of Vitamin D Supplements on Relapse Rate and Expanded Disability Status Scale (EDSS) in Multiple Sclerosis (MS): A Systematic Review and Meta-Analysis.

Background:Multiple sclerosis (MS) is an inflammatory disease while there are controversies regarding the role of vitamin D supplements in controlling relapse and disability improvement during treatment.Objective:The goal of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplements on MS-related relapse and the Expanded Disability Status Scale (EDSS).Methods:We searched databases to include randomized clinical trials (RCTs) which were published up to October 2018. We included RCTs, being single-blinded or double-blinded or open-label trials in which one of the main outcomes was EDSS and/or relapse after vitamin D supplementation. All statistical analyses were performed using RevMan 5.3. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for relapse between treatment arms. The mean difference was calculated for EDSS comparisons.Results:Nine articles were included for analysis. Of these nine studies, five compared vitamin D supplement groups with placebo (group 1 studies), and four compared high- and low-dose vitamin D groups. A total of 561 patients were analyzed. Being treated with vitamin D instead of placebo showed no effect on relapse rate (OR = 0.66, 95% CI = 0.28–1.54) as well as EDSS (mean difference = 0.06, 95%CI [-0.31, 0.42]). The results of studies comparing high- vs. low-dose vitamin D interventions showed no significant effect on relapse rate (OR = 1.08, 95%CI [0.29–4.08] as well as final EDSS (mean difference = 0.17, 95% CI = -0.73, 1.07).Conclusions:Our findings show that vitamin D supplements (high or low dose) have no significant effect on relapse rate and disability during treatment in MS patients.

Free thyroxine level is associated with both relapse rate and poor neurofunction in first-attack Neuromyelitis Optica Spectrum Disorder (NMOSD) patients

BackgroundTo investigate whether the serum free thyroxine (FT4) level is a prognostic factor for the first-attack neuromyelitis optica spectrum disorders (NMOSD).MethodsThis retrospective study enrolled 109 patients with first-attack NMOSD. The Expanded Disability Status Scale (EDSS) and the relapse rate were used to evaluate the outcomes. The logistic regression model was used to analyze the independent effects of FT4 on relapse and final EDSS. Kaplan-Meier analysis, scatter plot smoothing method, and two-phase piecewise linear regression model were used to investigate the relationship between the FT4 level and the relapse rate.ResultsMultivariate analysis revealed that serum FT4 level might be a risk factor for both final EDSS (β = 0.17; 95% confidence interval: 0.03–0.32) and the relapse rate (HR = 1.18; 95% confidence interval: 1.05–1.32). Furthermore, 1400 days after the onset, nearly 100% of patients in the high-FT4 group relapsed, while only 40% of the patients in the low-FT4 group relapsed. Finally, we found that the relationship between the FT4 level and the NMOSD relapse rate was nonlinear. The risk of NMOSD relapse increased with the FT4 level up to the inflection point of 12.01 pmol/L (HR = 1.45; 95% confidence interval: 1.06–1.98). When the FT4 level was > 12.01 pmol/L, there was no correlation between the FT4 level and the risk of NMOSD relapse (HR = 1.05; 95% confidence interval: 0.78–1.41).ConclusionSerum FT4 level may be a prognostic indicator for the first-attack in patients with NMOSD. High FT4 levels are associated with poor neurofunctions and a high relapse rate in patients with the first-attack in patients with NMOSD.

Early imaging predictors of longer term multiple sclerosis risk and severity in acute optic neuritis.

BackgroundBiomarkers are urgently required for predicting the likely progression of multiple sclerosis (MS) at the earliest stages of the disease to aid in personalised therapy.ObjectiveWe aimed to examine early brain volumetric and microstructural changes and retinal nerve fibre layer thinning as predictors of longer term MS severity in patients with clinically isolated syndromes (CIS).MethodsLesion metrics, brain and regional atrophy, diffusion fractional anisotropy and retinal nerve fibre layer thickness were prospectively assessed in 36 patients with CIS over the first 12 months after presentation and compared with clinical outcomes at longer term follow-up [median (IQR) = 8.5 (7.8–8.9) years].ResultsIn total, 25 (69%) patients converted to MS and had greater baseline lesion volume (p = 0.008) and number (p = 0.03)than CIS patients. Over the initial 12 months, new lesions (p = 0.0001), retinal nerve fibre layer thinning (p = 0.04) and ventricular enlargement (p = 0.03) were greater in MS than CIS patients. In MS patients, final Expanded Disability Status Scale score correlated with retinal nerve fibre layer thinning over the first 12 months (ρ = −0.67, p = 0.001).ConclusionsAdditional to lesion metrics, early measurements of fractional anisotropy and retinal nerve fibre layer thinning are informative about longer term clinical outcomes in CIS.

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination

ObjectiveWe characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.MethodsWe evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy...

Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP).

Endotherapia (GEMSP) is a novel therapeutic approach for multiple sclerosis (MS). The aim of the present study was to demonstrate the efficiency of Endotherapia in the follow-up of 193 patients with MS. The efficiency coefficient that was evaluated was the Expanded Disability Status Scale (EDSS) score, which is a functional scale of MS progression. The evaluated score of each patient during follow-up visits was compared with the theoretical score of the disease progression without GEMSP. The evolution of the EDSS score was evaluated according to the inclusion score. The quantitative global study of the EDSS score highlighted a statistically significant difference between the final average scores of the treatment with GEMSP (M) and worldwide reference (R) groups. The improvement of the M group compared with the R group was 24.5%. According to the final EDSS scores, the study highlighted a difference in favor of the M group with 62.0% for scores ≤3, 7.8% for scores between 3 and 6 and 19.6% for scores ≥6. According to the qualitative evolution of the EDSS scores, the improvements in favor of group M were 49.3% for scores ≤3, 79.1% for scores between 3 and 6 and 19.5% for scores ≥6. The qualitative study of the EDSS score showed a statistically significant success percentage; the success percentages were between 59.1 and 90.0%. In a larger population of MS patients, the data confirm the beneficial effects of GEMSP that were previously reported in pre-clinical and clinical studies. In addition, 78% of patients showed an improvement or deceleration of the disease.

Presence of anti-Ro/SSA antibody may be associated with anti-aquaporin-4 antibody positivity in neuromyelitis optica spectrum disorder

BackgroundNeuromyelitis optica (NMO) is often associated with systemic autoimmune diseases or serological markers of non-organ-specific autoimmunity, and has been most frequently associated with Sjögren's syndrome and anti-Ro/SSA antibody (SSA-Ab) positivity in Asian populations. ObjectiveWe evaluated the clinical significance of anti-Ro/SSA antibody positivity in patients with NMO spectrum disorder (NMOSD). MethodsWe retrospectively collected data from 106 consecutive patients with NMOSD and reviewed clinical features and laboratory findings. All patients underwent tests for SSA-Ab and anti-aquaporin-4 antibody (AQP4-Ab) using cell-based indirect immunofluorescence assays. ResultsAmong 106 patients, 20 (18.9%) were positive for SSA-Ab. Of 48 AQP4-Ab-positive patients, 18 (37.5%) had SSA-Ab. AQP4-Ab seropositivity was 90.0% in patients positive for SSA-Ab, and 32.6% in patients without SSA-Ab (p<0.001). Presence of SSA-Ab was associated with systemic autoimmune diseases, including Sjögren's syndrome (p<0.001) and systemic lupus erythematosus (p=0.003), and with the presence of non-organ-specific autoantibodies such as anti-nuclear antibody and anti-dsDNA antibody in patients with NMOSD, but was not associated with annualized relapse rate or final Expanded Disability Status Scale score independent of AQP4-Ab positivity. ConclusionWe found that the presence of SSA-Ab was highly associated with seropositivity for AQP4-Ab in patients with NMOSD.

Pseudotumoral Forms of Multiple Sclerosis: Report of 14 Cases and Review of the Literature

Background: The pseudotumoral form of multiple sclerosis (MS) is a rare condition with few descriptions in the literature. It supposes a diagnostic challenge especially when appearing at the onset of disease. Methods: We retrospectively describe a case series of pseudotumoral MS patients that attended our hospital from 2004, analyzing demographic, clinical and radiological variables. We classified the lesions according to the recently proposed morphologic classification (infiltrative, megacystic, Baló or ring-like) and according to the contrast enhancement pattern (nodular, complete ring, incomplete ring and diffuse). Results: Fourteen patients (11 female, 3 male), with a mean age of 35 years, were identified. All of them suffered from a relapsing-remitting form of MS. Eleven patients (78.57%) had symptomatic pseudotumoral lesions (PL), being the form of clinical presentation in the majority of those patients that were symptomatic (81.81%). Several patients presented atypical clinical manifestations such as cognitive impairment (21.42%) and epileptic seizures (14.28%). Full recovery was found in 53.84% of all symptomatic episodes. After a mean follow-up of 43 months, recurrent PL episodes were seldom observed (21.42%), the annualized relapse rate was 0.95 and the mean final Expanded Disability Status Scale score was 1.5. The majority of PLs were supratentorial, coexisted with typical demyelinating plaques and showed the ring-like morphology and the ring pattern of contrast enhancement. Three patients had more than one PL on the same scan, all of the lesions with similar morphology. Conclusions: Our findings contribute to a better characterization of pseudotumoral forms of MS. However, larger studies are required to define this atypical entity more exactly.

Long-term Outcomes of CLIPPERS (Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids) in a Consecutive Series of 12 Patients

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. To describe the disease course of CLIPPERS. A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. Academic research. Twelve patients with CLIPPERS. The therapeutic management of CLIPPERS was evaluated. Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

Influence of treatment in multiple sclerosis dysability: an open, retrospective, non-randomized long-term analysis

The efficacies of immunosuppressive (IMS) and immunomodulatory (IMM) drugs for multiple sclerosis (MS) have been reported in several studies. These agents can reduce relapse rates and lesions observed by magnetic resonance imaging studies. However, the effect of these medications in disability progression over 4 years is rarely examined. To study the disabilities associated with MS patients after a long time period and to analyze the therapeutic influence of different types of treatments in patient disease progression. This is an open, uncontrolled, non-randomized, retrospective study of the disease progression using the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) in 155 cases of MS, which were 76% female with a mean age of onset of 30.21+/-9.70. The follow-up period was 115.39+/-88.08 months (median 92, 3 to 447 months). These cases were submitted to the following 277 different therapeutic procedures: 62 without IMS or IMM therapy (SYT) (just corticosteroids), 53 with azathioprine (AZA), 53 interferon-beta (IFNbeta)-1b 250 microg (BET), 55 IFNbeta-1a 22 microg (R22), 19 IFNbeta-1a 30 microg (AVO), 15 IFNbeta-1a 44 microg (R44), 15 glatiramer acetate (COP) 20 mg, and 5 cases with mitoxantrone (MIT). The median EDSS group was 2.00 (0 to 5.5, mean 1.89+/-1.52) at the onset of each treatment and 2.50 (0 to 9, mean 3.06+/-2.18) at the end. The median initial MSSS was 3.34 (0.25 to 9.50, mean 3.94+/-2.91) and the final medial was 3.90 (0.05 to 9.88, mean 4.02+/-2.78). The EDSS between initial and final score for the whole group had statistically significant progression, as well as for the sub-groups SYT, AZA, BET and R22. No statistically significance difference was found in the MSSS between initial and final scores in the whole group or treatment sub-groups. The variation between the initial and final EDSS and MSSS among the types of treatments found no statistical significance for any group. In this study series, no statistical difference was found in the long-term progression of disability among the IMS and IMM treated cases, nor in the cases treated only with corticosteroids.

Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis

To assess the relationship between the spectroscopically measured axonal damage in the normal-appearing white matter of the brainstem, the total brain T2-hyperintense lesion volume (T2LV), and disability in patients with early relapsing-remitting multiple sclerosis (RRMS). Forty-three RRMS patients and 10 sex- and age-matched healthy controls were prospectively studied for 2 years. T2-weighted magnetic resonance (MR) images and proton MR spectroscopy were acquired at the time of recruitment and at year 2. Brainstem was considered, where large tracts join together, as a suitable region to detect early axonal damage. The T2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) resonances areas were integrated with the jMRUI program, and the ratios were calculated for the sum of the volume elements represented at brainstem. The basal NAA/Cho ratio was significantly decreased in patients compared with controls. After 2-year follow-up, there was a decrease in the NAA/Cho (-9%; p = 0.002) and NAA/Cr (-13%; p = 0.001) ratios, and an increase in the T2LV (19%; p = 0.043) in multiple sclerosis patients, whereas control subjects had no significant metabolic changes. Significant NAA/Cr ratio decreases were observed in both patients, with and without relapses, whereas T2LV only increased in patients with relapses. The final Expanded Disability Status Scale (EDSS) score correlated with T2LV at baseline, but no significant correlations were found between metabolic values, T2LV change, or EDSS score over the study period. Our data reveal an early and progressive axonal damage in relapsing-remitting multiple sclerosis. Axonal loss and T2 lesion volume seem to be at least partly dissociated processes in early stages of the disease.

Treatment of early-onset multiple sclerosis with intramuscular interferonβ-1a: long-term results

The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFNbeta-1a; Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or adolescence. Patients with a diagnosis of definite MS according to McDonald's criteria, relapsing course according to Lublin's criteria, onset of symptoms of MS before 16 years of age, and who had received IM IFNbeta-1a therapy before 16 years of age were eligible for the study if they had a pretreatment and treatment duration of at least 6 months. Clinical and laboratory evaluations were performed every 3 months. A total of 52 patients were identified as receiving treatment with IM IFNbeta-1a 30 mg once a week before 16 years of age. Mean age at onset of symptoms of MS was 11.7+/-2.7 years, mean disease duration was 25.9+/-30.3 months, mean annualised relapse rate was 1.9+/-1.1 and mean Expanded Disability Status Scale (EDSS) score was 1.5+/-1.1. After a mean (+/-SD) treatment duration of 42.9+/-19.9 months, annualised relapse rate decreased to 0.4+/-0.5. Final EDSS score was 1.3+/-1.1. Adverse events were recorded for 35 (67%) patients (flulike syndrome, 33%; headache, 29%; myalgia, 21%; fever, 11%; fatigue, 6%; nausea and vomiting, 6%; and skin reaction, 4%); most were transient. IM IFNbeta-1a was effective and well tolerated in these paediatric patients with MS.

Therapeutic penetrating keratoplasty in keratomalacia.

<h3>Objective</h3> We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. <h3>Methods</h3> We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. <h3>Results</h3> The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses &lt;10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). <h3>Conclusion</h3> Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.