L Sousa

Risk of multiple sclerosis after optic neuritis in patients with normal baseline brain MRI

When assessing and managing a patient with optic neuritis (ON), the risk of future development of multiple sclerosis (MS) is an important issue, as this can be the first presentation of the disease. Although the presence of lesions on baseline brain MRI is the strongest predictor of MS conversion, some patients with normal imaging also develop MS. We aimed to estimate MS risk in patients with ON and a normal baseline MRI and identify individuals with higher risk of conversion. We performed a retrospective study including patients with idiopathic ON and normal baseline brain MRI who presented to our hospital over an 8 year period. Of a total of 42 patients, 10 converted to MS: five during the first follow-up year, seven during the first 2 years and all of the patients within the first 5 years, with a 5 year MS conversion rate of 23.8%. MS conversion rates were significantly higher in patients with history of previous symptoms suggestive of demyelination (p=0.002), cerebrospinal fluid oligoclonal bands unmatched in serum (p=0.004) and incomplete visual acuity recovery (≤6/12) after 1 year (p=0.002). Lower conversion rates were found in patients with optic disc edema (p=0.022). According to these results, a significant proportion of patients with idiopathic ON and a normal baseline brain MRI will develop MS, with a higher risk during the first 5 years. Therefore, in the presence of factors in favor of MS conversion, close follow-up, including semestral medical consultations and yearly brain MRI, can be recommended. Early immunomodulatory treatment may be individually considered as it can delay conversion and reduce new lesion development rate.

Impairment of social cognition in multiple sclerosis: Amygdala atrophy is the main predictor

Background: Patients with multiple sclerosis (MS) frequently reveal social behavior disturbance. Nevertheless, little is known regarding the impact of MS on social cognition, particularly theory of mind (ToM), and its neural basis. Objectives: To explore how ToM is affected in MS and its neural correlates. Methods: Enrolled 60 consecutive MS patients and 60 healthy controls (HC) matched on age, sex, and education. Participants underwent ToM testing (Eyes Test, Videos Test) and 3 T brain magnetic resonance imaging (MRI). Using Freesurfer software, cortical and subcortical gray matter (GM) volumes were calculated. Results: MS patients performed worse on Eyes Test (58.7% ± 13.8% vs 81.9% ± 10.4%, p < 0.001) and Videos Test (75.3% ± 9.3% vs 88.1% ± 7.1%, p < 0.001). Eyes Test performance in MS was positively correlated with the volume of subcortical structures (amygdala, putamen) and cortical regions (entorhinal cortex, fusiform gyrus, superior temporal gyrus, superior parietal gyrus, supramarginal gyrus, medial orbitofrontal cortex, anterior and posterior cingulate gyrus). In regression analysis, amygdala volume was the single predictor of performance (R2 change = 0.064, p = 0.031), and a mediation analysis indicated that it contributes for the differences observed between MS and HC. Conclusion: Patients with MS have impairment on social cognition. Amygdala atrophy was the main predictor probably due to its central position within the “social brain” network.

Disconnection as a mechanism for social cognition impairment in multiple sclerosis

Objective: To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS). Methods: We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM. Results: Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus. Conclusions: These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

The effectiveness of fingolimod in a Portuguese real-world population

INTRODUCTION Fingolimod is an oral treatment for Relapsing-Remitting Multiple Sclerosis (RRMS) with established efficacy in clinical trials. Post-marketing studies are important to assess its effectiveness in real-world populations. OBJECTIVES To report the effectiveness and safety of fingolimod in a real-world population. METHODS A retrospective study of patients with RRMS treated with fingolimod for at least six months. The demographic characteristics, Annualized Relapse Rate (ARR), Expanded Disability Status Score (EDSS), previous treatments and Adverse Events (AE) were analysed. RESULTS 104 patients were included, with a mean treatment duration of 21.06 months. First-line disease modifying therapy failure patients (n=56) had an ARR decrease of 68.53% (1.43 vs. 0.45, p<0.001), 66.07% of them were relapse-free, EDSS significantly decreased (2.5 vs. 2.0, p<0.001) and 91.07% showed no disability progression. In patients previously treated with natalizumab as a second-line drug mainly switched due to safety concerns (n=41), although the differences were not statistically significant, both the ARR and EDSS increased in 41.46% and 19.51% of patients, respectively. In treatment-naive patients (n=7) the ARR decreased 94.90% (1.57 vs. 0.08, p=0.027) and there was no disability progression. 56.7% of all patients experienced AE not considered serious in any of the cases. CONCLUSION In this population, fingolimod was an effective treatment after first-line treatment failure, decreasing both the ARR and EDSS, and may be an effective option after natalizumab.

Clinical predictors of an optimal response to natalizumab in multiple sclerosis

Despite the high level of effectiveness of natalizumab (NTZ) in the treatment of patients with multiple sclerosis (MS), concerns about its high direct cost and its safety have restricted its use. Our aim was to identify and quantify the clinical factors that predict an optimal response to NTZ. Patients with MS undergoing treatment with NTZ for at least 12 months were classified as optimal responders if, during treatment, they sustained a reduction in their Kurtzke Expanded Disability Status Scale (EDSS) score of 1 point or more or experienced a reduction in annualised relapse rate (ARR) of more than 1. The remaining patients were classified as suboptimal responders and non-responders. Our subject pool included 48 patients. The variables associated with optimal response included: ARR in the previous year of at least 2, an age at first administration of 37.5 years or less, a baseline EDSS score of 4.5 points or less, a disease duration of 9.5 years or less and, in patients with secondary-progressive MS, a progressive-phase duration of 4.5 years or less. The characteristics of the disease at its onset did not affect responsiveness, indicating that patients with highly active disease and low disability are the ideal candidates for NTZ treatment, regardless of previous clinical characteristics.

Anti-JCV antibody serostatus and longitudinal evaluation in a Portuguese Multiple Sclerosis population

Multiple Sclerosis (MS) treatment with natalizumab is associated with Progressive Multifocal Leukoencephalopathy (PML). The risk of PML being related to the anti-JCV antibody index is well established, but there is less known about seroconversion rates in natalizumab-treated patients and longitudinal variation in the anti-JCV antibody index. Our objective was to assess anti-JCV antibody prevalence in an MS population and to evaluate the evolution of the anti-JCV antibody index in natalizumab-treated patients. To assess anti-JCV antibody prevalence, we included all patients who had the anti-JCV antibody test in our consultation, regardless of the treatment. To evaluate the evolution of the anti-JCV antibody index and seroconversion, only natalizumab-treated patients with at least two samples were selected. Demographic characteristics were evaluated. From a total of 371 patients included, 68.19% (n=253) were seropositive for anti-JCV antibodies (JCV+). There was a significant difference in anti-JCV antibody seropositivity concerning gender (male 76.27% vs. female 64.43%, p=0.023), but not age. To evaluate seroconversion, 85 patients who were initially seronegative (JCV-) were selected. The annual rate of seroconversion in the first two years was stable, but after that there was a significant increase with treatment duration (ρ=0.90, p=0.037): in the first year it was 5.88% (n=5/85); in the second, 5.71% (n=4/70); in the third, 6.82% (n=3/44); in the fourth, 10.34% (n=3/29); and in the fifth, 15.0% (n=3/20). The mean index variability was higher in patients who experienced seroconversion (1.16±0.97), followed by JCV+ patients (0.44±0.48), compared to JCV- patients (0.08±0.05). In conclusion, anti-JCV antibody prevalence in our population is comparable to other reported cohorts. The seroconversion rate increased with treatment duration. We found a high fluctuation in the antibody index in JCV+ patients.

The Montreal Cognitive Assessment (MoCA) as a screening test for cognitive dysfunction in multiple sclerosis

ABSTRACT This study investigates the utility of the Portuguese version of Montreal Cognitive Assessment (MoCA) as a screening-method for identifying cognitive dysfunction (CD) in multiple sclerosis (MS). The 118 participants with comprehensive neuropsychological assessment were divided into two subgroups: (I) MS group (n = 59) and (II) control group (n = 59). The MS patients were classified as cognitively intact (n = 26) or impaired (n = 33, 56%). The results indicated that the MoCA is a psychometrically valid instrument in assessment of MS patients. The Multiple Linear Regression analyses highlighted the significant influence of Modified Fatigue Impact Scale and Irregular Word Reading Test on MoCA performance. The MoCA total score showed a good discriminative capacity between cognitively impaired and cognitively intact subjects. In addition, there were significant differences in MoCA cognitive domain scores between groups. The MoCA total score cut-off point for identifying CD in MS patients was a score below 26 points (AUC = 0.837, CI = 0.736–0.937). A proposed EM-MoCA-Subscore for identifying the MS-related cognitive impairment (max. score = 19 points, cut-off <17 points, AUC = 0.871, CI = 0.784–0.958), can reduce administration time for cognitive screening in clinical settings. The MoCA is a useful and sensitive instrument to identify the MS-related cognitive impairment.

Predictors of first-line treatment persistence in a Portuguese cohort of relapsing-remitting multiple sclerosis

Treatment persistence in first-line injectable disease-modifying therapies (DMT) for relapsing-remitting multiple sclerosis (RRMS) is an important indicator of effectiveness. Identifying predictors of treatment discontinuation is important as there are other therapies currently available and a growing range of emerging drugs. We report a retrospective study of RRMS and clinically isolated syndrome patients followed in a University Hospital during a 13-year period with the objective of identifying predictors of treatment persistence. An evaluation of persistence on the first DMT, rates of DMT discontinuation, and reasons and predictors of discontinuation was performed. A total of 410 patients were included, 69% female, with mean disease duration of 37.8months, mean age of 34.2years and mean follow-up time of 6.1years. The first DMT was glatiramer acetate (GA) in 27.56% of patients, interferon (IFN) β-1a intramuscular in 26.34%, IFNβ-1b in 26.10%, IFNβ-1a22 in 13.66% and IFNβ-1a44 in 6.34%. Treatment was discontinued in 16.34% of patients after 1year of treatment and in 50.24% of patients in the total follow-up time, with a mean time for discontinuation of 39.80months. Higher baseline Expanded Disability Status Scale score was an independent predictor of treatment discontinuation (hazard ratio 1.35, p=0.002). After the first year, treatment persistence was 90.74% for IFNβ-1a-IM, 88.46% for IFNβ-1a44, 83.18% for IFNβ-1b, 83.19% for GA and 69.64% for IFNβ-1a22 (p=0.014). Lower frequency of administration was associated with higher persistence rates. The most common reason for treatment discontinuation was lack of efficacy in all DMT subgroups.

Encephalopathy Associated with Autoimmune Thyroid Disease: A Potentially Reversible Condition

Autoimmune thyroid disease may occasionally associate with unspecific neurological symptoms, which are more commonly insidious, include cognitive or behavioural symptoms, and may associate with tremor, myoclonus, or ataxia. We report a 61-year-old female patient who presented with chronic headache, insidious mood, and cognitive disturbance which evolved in a few months to dementia associated with exuberant limb myoclonus. Diagnostic workup revealed high anti-thyroid peroxidase antibody titers and an inflammatory CSF profile, and it was negative for other possible etiologies. Treatment with steroids induced significant improvement. The diagnosis of encephalopathy associated with autoimmune thyroid disease is still controversial given the fact that the clinical presentation and diagnostic workup are unspecific, the pathophysiology is still undetermined, and the diagnosis is mostly of exclusion. No direct correlation is found between anti-thyroid antibody titers and clinical presentation, and it is currently speculated that other still unrecognized antibodies may be responsible for this clinical entity. It is extremely important to recognize this entity because it is potentially treatable with immunotherapies. It is also increasingly recognized that clinical improvement with first-line treatment with steroids may be absent or incomplete, and other immunotherapies as immunosuppressants, intravenous immunoglobulin, or plasma exchange must be attempted in the clinical suspicion of EEAT.

Apathy in multiple sclerosis: gender matters

Apathy has been recognized as a frequent symptom in multiple sclerosis (MS) but uncertainty remains about its prevalence and clinical correlates. Therefore, the objective of this work was to assess the prevalence of apathy in patients with MS and to identify clinical and demographic correlates. A case-control study with 30 patients and 30 healthy controls matched for age, gender and education was performed. Apathy diagnosis was established using Robert et al.s criteria. Additionally, apathy was assessed using the 10-item short version of the clinical-rated Apathy Evaluation Scale (AES-C-10). The Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS), and Montreal Cognitive Assessment (MoCA) were used to evaluate depression, fatigue and cognitive impairment, respectively. Apathy prevalence in MS patients was 43.3%. Patients with MS had higher AES-C-10 scores than controls (13.9 vs. 12.0, p=0.015). Patients with apathy presented a higher proportion of males (53.8% vs. 11.8%, p=0.02), lower educational level (53.8% vs. 11.8% of patients with up to 9years of education), higher scores on cognitive dimension of MFIS (18.0 vs. 8.0, p=0.048) and BDI (13.0 vs. 7.0, p=0.035) and worse performance on MoCA (24.0 vs. 26.0, p=0.028). Gender was the only independent predictor of apathy, with men presenting a higher risk compared to women (OR: 9.62; 95%CI: 1.02-90.61; p=0.048). In conclusion, apathy is a common neuropsychiatric disorder in MS and it is probably underdiagnosed. Male patients seem to have an increased risk of apathy, and this finding may be related to the generally more unfavorable course of MS in men.