Corpus callosum texture analysis: a different perspective approach for diagnosing multiple sclerosis.

Lymphocyte calcium influx characteristics and its modulation by Kv1.3 and IKCa1 potassium channel inhibitors in multiple sclerosis

Objective To observe the quantitative corpus callosum (CC) segmentation MRI topology and brain white matter tractography variations in patients with multiple sclerosis (MS),and to assess the correlation between quantitative indicators and scores of expanded disability status scale (EDSS).Methods Conventional MRI and diffusion tensor imaging (DTI) were applied in 32 MS patients and 32 healthy volunteers,admitted to our hospital from June 2011 to June 2013.The areas,average diffusion coefficent (ADC) values,fractional anisotropy (FA) values and tracked lines of each CC segment (1-5) and total CC were measured.T tests were used to compare the above quantitative indices in MS patients with those in controls.Linear regression model was used to determine the relationship between quantitative indices and scores of EDSS in MS patients.Results Various degrees of damage of white matter tracts in CC of MS patients could be visually identified by tractography.The areas,FA values and tracked lines of each CC segment in MS patients were smaller than those in controls (P＜0.05),and the ADC values of segment 1-3 in MS patients were larger than those in controls (P＜0.05).Moreover,the areas ([549.13±64.07] mm2),FA values (0.55±0.05) and tracked lines (519.78±79.03) of total CC in MS patients were smaller than those in controls ([614.56±39.67] mm2,[0.67±0.02] and [612.34±39.51],P＜0.05),and the ADC values ([0.93±0.09]×10-3 mm2/s) of total CC in MS patients were larger than those in controls ([0.86±0.03]×10-3 mm2/s,P＜0.05).Both areas and tracked lines of each CC segment in MS patients had negative correlations with EDSS scores (P＜0.05).Moreover,both areas and tracked lines of total CC in MS patients were found having negative correlations with EDSS scores (r=-0.686,P=0.000;r=-0.676,P=0.000).Conclusion Both areas and tracked lines of each CC segment and total CC reflect the degrees of clinical disability in MS patients,which can be used for disease and efficacy evaluation of MS patients. Key words: Multiple sclerosis; Corpus callosum; MRI; Diffusion tensor imaging; brain white matter tractography

Objectives:To analyze the correlation between corpus callosum index (CCI), brain volumetry, and disability in multiple sclerosis (MS) patients. The brain volumetry consists of the corpus callosum, cortical gray matter, subcortical gray matter, and white matter volumes.Methods:This was a retrospective cross-sectional study from October 2018 to February 2019 of 30 patients with MS aged 20 to 61 years old. Brain volumetry was performed using FreeSurfer© software. The CCI were measured manually using conventional best mid-sagittal T1W brain MRI. The anterior, posterior, and medium segments were measured and divided to its greatest anteroposterior diameter. Higher CCI values indicated greater corpus callosum volumes. Clinical evaluation was comprised of MS subtype, age of onset, relapse frequency and Expanded Disability Status Scale (EDSS).Results:Thirty MS patients with median of age 22 years were included. Relapsing-remitting (RRMS) subtype were 73.3%. Very significant correlations were shown between the CCI and corpus callosum volume (CCV) (r=0.79; p<0.0001) and cerebral white matter volume (r=0.81; p<0.0001). Significant correlations were shown between the CCI and cortical gray matter volume (r=0.64; p<0.0001) and subcortical gray matter volume (r=0.69; p<0.0001). The CCI was positively correlated with age of onset and inversely with EDSS. The CCV and CCI were smaller in secondary progressive MS (SPMS).Conclusion:The CCI is easy and fast to obtain in conventional MRI and significantly correlated with brain volumetry, age of onset and disability in MS patients.

Some microstructure parameters, such as permeability, remain elusive because mathematical models that express their relationship to the MR signal accurately are intractable. Here, we propose to use computational models learned from simulations to estimate these parameters. We demonstrate the approach in an example which estimates water residence time in brain white matter. The residence time τi of water inside axons is a potentially important biomarker for white matter pathologies of the human central nervous system, as myelin damage is hypothesised to affect axonal permeability, and thus τi. We construct a computational model using Monte Carlo simulations and machine learning (specifically here a random forest regressor) in order to learn a mapping between features derived from diffusion weighted MR signals and ground truth microstructure parameters, including τi. We test our numerical model using simulated and in vivo human brain data. Simulation results show that estimated parameters have strong correlations with the ground truth parameters (R2={0.88,0.95,0.82,0.99}) for volume fraction, residence time, axon radius and diffusivity respectively), and provide a marked improvement over the most widely used Kärger model (R2={0.75,0.60,0.11,0.99}). The trained model also estimates sensible microstructure parameters from in vivo human brain data acquired from healthy controls, matching values found in literature, and provides better reproducibility than the Kärger model on both the voxel and ROI level. Finally, we acquire data from two Multiple Sclerosis (MS) patients and compare to the values in healthy subjects. We find that in the splenium of corpus callosum (CC-S) the estimate of the residence time is 0.57±0.05s for the healthy subjects, while in the MS patient with a lesion in CC-S it is 0.33±0.12s in the normal appearing white matter (NAWM) and 0.19±0.11s in the lesion. In the corticospinal tracts (CST) the estimate of the residence time is 0.52±0.09s for the healthy subjects, while in the MS patient with a lesion in CST it is 0.56±0.05s in the NAWM and 0.13±0.09s in the lesion. These results agree with our expectations that the residence time in lesions would be lower than in NAWM because the loss of myelin should increase permeability. Overall, we find parameter estimates in the two MS patients consistent with expectations from the pathology of MS lesions demonstrating the clinical potential of this new technique.

Characteristics of COVID-19 disease in multiple sclerosis patients

Mental Disorders in Mexican Patients With Multiple Sclerosis

On the role of the amygdala for experiencing fatigue in patients with multiple sclerosis

Background: The prevalence of trigeminal neuralgia (TN) is higher in multiple sclerosis (MS) as compared in the general population. Clinical and treatment responses of MS patients compared with non-MS patients are in debate. Objective: To evaluate clinical differences in trigeminal pain presentation and pharmacological treatment response in patients with and without underlying MS. Material and methods: A retrospective study of 10 MS patients that had TN as a first symptom or in the MS course (from the total 545 MS patients). Data regarding MS (sex, age at MS onset, type, symptomatology, number and site of lesions on brain MRI, treatment) and TN (clinical characteristics of facial pain, treatment), period from TN as a clinically isolated syndrome to defined MS or period from MS onset to TN beginning were analyzed. Clinical, demographical and treatment response were compared with corresponding data of 10 consecutive patients hospitalized for idiopathic TN. Results: The only difference between MS and non-MS patients was the age of onset of TN (41.8 ±6.12 in MS vs 52.7±16.5 in non –MS patients, p=0.07, unpaired Student’s t-test). There are no differences in trigeminal pain characteristics between MS and non-MS patients. Conclusions: TN among MS patients has an onset at younger age but share the same pain characteristics and treatment responds with TN in the general population. TN in MS has multiple mechanisms of aetiopathogenesis and surgical treatment must be held in mind in selected cases.

Sirs: Recent studies have reported an association of low serum levels of the natural antioxidant urate and multiple sclerosis (MS). First, it was shown that MS patients have lower serum levels of urate than controls [3, 6–8] (though there were no significant differences in other studies [1, 4]); second, hyperuricemia (gout) and MS were found to be mutually exclusive [3]; third, serum urate levels correlated negatively with the duration of MS and its severity [1, 8] (but there were no such correlations in another study [6]). Furthermore, a therapeutic effect of urate was observed in the rodent model of MS, experimental allergic encephalomyelitis (EAE) [2, 3]. To date, the interpretation of decreased urate blood levels in MS patients is not clear. Two current explanations are that lower urate blood concentrations predispose to MS or that they are secondary to oxidative degradation of urate [3]. However, its oxidation product allantoin has not so far been measured in MS patients. Accordingly, we determined the concentrations of urate and allantoin in the CSF and serum of MS and control patients. The samples were obtained for diagnostic purposes after obtaining informed consent. All MS patients (n = 70) met the current “McDonald” diagnostic criteria. Forty-four patients had a relapsing-remitting disease course (RRMS). Thirty-six of them had an acute exacerbation and 8 were in remission when the samples were obtained. In 25 of the RRMS patients, cranial MRI was performed at the time of sample collection, gadolinium-enhancing lesions being detected in 18 cases. Twelve patients had a secondary (SPMS) and 14 a primary progressive (PPMS) disease course. Control patients (n = 24) were diagnosed, after extensive diagnostic study, with migraine (12), tension-type headache (7), transient ischemic attack (2), cyclosporine intoxication (1), cervical disc herniation (1), and normal pressure hydrocephalus (1). None of the MS patients or controls had received any immunomodulatory therapy during 6 months prior to the collection of the samples. Urate and allantoin were measured by high pressure liquid chromatography (HPLC) as previously described [5]. Continuous variables were compared by t-test or one-way ANOVA for multiple comparisons. Gender distribution was compared by Fisher’s exact test. Only two-sided tests were used and p < 0.05 was considered significant. When controls and all MS patients were compared, CSF and serum levels of urate or allantoin and allantoin/urate ratios in CSF or serum did not differ significantly (data not shown). When controls, RRMS, SPMS, and PPMS patients were compared with each other (Table) and when RRMS patients with an acute exacerbation and in remission or with and without enhancing lesions on MRI were compared (data not shown), the before-mentioned parameters did not differ either. Our finding of similar serum urate levels in MS patients and controls is in agreement with some previous reports [1, 4], but stands in contrast to others [3, 6–8]. Differences in the MS patient (e. g., course or severity of disease) or control groups (heterogeneous cohorts of patients with other neurological diseases) may perhaps account for the discrepant results. More importantly, in our sample of MS patients we did not detect raised allantoin levels in the CSF or serum. Thus, we could not find any evidence supporting an increased oxidative degradation of urate during MS. LETTER TO THE EDITORS

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM

BackgroundWith the recent pandemic of the novel coronavirus disease (COVID-19), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients for their compromised immune system have been in significant concern. Awareness and attitude about this virus have an important impact on infection prevention and coping with stress and anxiety. So we conducted this study to assess knowledge, attitude, and mental health status in MS and NMOSD patients within the COVID-19 pandemic.MethodIn this cross-sectional study, the link of Depression Anxiety Stress Scales-21 (DASS-21) and a self-administered structured questionnaire were sent through social media to MS and NMOSD patients and two control groups consisting of healthy and migraine individuals.ResultsA total of 223 MS patients, 41 NMOSD, 29 migraine, and 245 healthy subjects participated in this study. MS patients had higher total DASS scores compared to healthy participants (p = 0.012). There were no significant differences among the study groups regarding knowledge and attitude. In MS patients, physical comorbidity was associated with a total score of attitude (OR 1.59, 95% CI 0.53, 2.66, p = 0.004). We did not find association between other demographic and clinical variables with DASS scores, attitude, and knowledge in MS patients.ConclusionThe current data highlight the necessity of attitude, knowledge, and mental health assessment among MS and NMOSD patients. Further studies in other countries need to be carried to assess these points among MS and NMOSD patients.

Objective to investigate whether optical coherence tomography (OCT) could demonstrate axonal loss through thinning of the retinal nerve fiber layer (RNFL) in multiple sclerosis (MS) patients. Furthermore, the degree of RNFL loss was compared in the different MS subgroups (with or without optic neuritis, affected or fellow eye, single episode or recurrent optic neuritis, relapsing remitting or progressive MS). RNFL thinning was also determined in MS patients who had serial OCT without any intervening clinical optic neuritis. Design: Retrospective chart review. Setting: Academic tertiary care MS centers. Participants: 177 patients (334 eyes) with multiple sclerosis, with or without optic neuritis, and 159 healthy controls that underwent OCT RNFL measurements. Main Outcome: Retinal nerve fiber layer measurements by OCT. Results: Average RNFL measurements were thinner in MS patients (90 μm) compared to controls (105 μm), p <0.0001. RNFL was significantly reduced in MS patients with optic neuritis (87 μm) versus those without optic neuritis (94 μm), p <0.0001. Among the different quadrants, the degree of RNFL loss was greatest in the temporal quadrant of MS patients (22%). Progressive (primary and secondary progressive) MS patients had thinner RNFL (82 μm) compared to all relapsing remitting MS patients (90 μm), p <0.0001. Greater RNFL loss was seen in SPMS patients (77 μm) versus PPMS (88 μm), p = 0.004. In the 45 MS patients without any intervening clinical optic neuritis, serial OCT (mean of 2 OCT scans per patients, averaging 11 months apart) showed that RNFL decreased by 3.7 μm per year. Conclusion: Retinal nerve fiber layer is significantly reduced in patients with multiple sclerosis. Progressive MS subtypes showed more marked RNFL thinning than relapsing remitting MS. This study reflects the role of OCT in MS patient monitoring and its potential as a surrogate marker in MS therapeutic trials.

SummaryBackroundThe aim of the study was to assess the impairment of the selected white matter tracts within normal appearing white matter (NAWM) in multiple sclerosis (MS) patients using diffusion tensor imaging (DTI).Material/MethodsThirty-six patients (mean age 33.4 yrs) with clinically definite, relapsing-remitting MS and mild disability (EDSS – Expanded Disability Status Scale 1–3.5) and 16 control subjects (mean age 34.4 yrs) were enrolled in the study. DTI examinations were performed on a 1.5T MR scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained with a small ROI method in several white matter tracts within NAWM including: the middle cerebellar peduncles (MCP), the inferior longitudinal fasciculi (ILF), inferior frontooccipital fasciculi (IFOF), genu (GCC) and splenium of the corpus callosum (SCC), posterior limbs of the internal capsules (PLIC), superior longitudinal fasciculi (SLF) and posterior cingula (CG). There were no demyelinative lesions within the ROIs in any of the patients.ResultsA significant decrease in FA was found in MS patients in both the ILFs and IFOFs (p<0.001) and in the left MCP and right SLF (p<0.05), compared to the normal subjects. There were no significant differences in FA values in the remaining evaluated ROIs, between MS patients and the control group. A significant increase in ADC (p<0.05) was found only in the right PLIC and the right SLF in MS subjects, compared to the control group.ConclusionsThe FA values could be a noninvasive neuroimaging biomarker for assessing the microstructural changes within NAWM tracts in MS patients.

Electrophysiological correlates of cognitive symptoms in multiple sclerosis through neuromagnetic resting-state functional connectivity

Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are auto immune demyelinating disorders. Both MS and NMO patients suffer from urinary dysfunction. Objectives: Investigation of frequency and severity of urinary symptoms in two groups of MS and NMO patients. Materials &amp; Methods: 56 MS patients and 20 NMO patients were enrolled in this cross sectional study conducted in Isfahan Kashani hospital from March 2018 to September 2018. Frequency and severity of urinary symptoms were assessed using the urogenital distress inventory (UDI-6) and international prostate symptom score (IPSS) questionnaire. Data were analyzed using independent t-test, Mann Whitney U test and Pearson correlation coefficient with the SPSS V. 18. Results: The Mean±SD of age was 40.2±11.45 and 34.1±9.09 in NMO and MS group respectively. There was a significant difference between MS and NMO patients regarding their overall IPSS score (9.8±7.9 and 14.6±11.3 respectively). The frequency of mild, moderate and severe urinary symptoms was 25%, 50 % and 25% among NMO patients and 48.2%, 35.7% and 16.1% among MS patients respectively. Based on UDI-6 questionnaire the most frequent symptoms in MS and NMO patients were frequency and urgency respectively and they are more frequent among NMO patients rather than MS patients. Conclusion: Our results showed a significant difference in frequency and severity of urinary symptoms between NMO and MS patients and NMO patients tend to experience more severe urinary symptoms.