Serum YKL-40 levels in patients with multiple sclerosis / Níveis séricos de YKL-40 em pacientes com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. The YKL-40 protein, which is secreted from various cells that contribute to inflammation and infection, plays a role in immune regulation. Objective: This study investigated the serum YKL-40 levels of patients with clinically isolated syndrome (CIS) and MS. Methods: The participants was divided into three groups: 1) patients with CIS (n = 20); 2) patients with relapsing-remitting MS (RRMS; n = 39); and 3) healthy individuals (n = 35). The YKL-40 levels in serum samples obtained from the participants were measured using enzyme-linked immunoassays. Results: The median serum YKL-40 level was 20.2 ng/mL (range 9.8-75.9 ng/mL) in the patients with CIS, 22.7 ng/mL (range 13.4-57.9 ng/mL) in the patients with RRMS and 11.0 ng/mL (range 10.0-17.3 ng/mL) in the control group (p < 0.001). The serum YKL-40 levels in the patients with RRMS were correlated with the patients' expanded disability status scale scores and ages (p < 0.05). No relationships were determined between the serum YKL-40 levels and the other variables (p > 0.05). The serum YKL-40 levels were higher in the CIS group than in the MS group. These findings show that the serum YKL-40 levels were high even at the beginning of the disease. The serum YKL-40 levels were also not involved in the progression to clinically definite MS. Conclusions: The findings from this study suggested that YKL-40 may be a useful marker for the inflammatory process of MS.

RESUMO Contexto: A Esclerose Múltipla (EM) é uma doença inflamatória crônica que afeta o sistema nervoso central. A proteína UKL-40, secretada de várias células que participam de processos inflamatórios e infecciosos, desempenha um importante papel na regulação imunológica. Objetivo: Este estudo investigou níveis séricos de YKL-40 em pacientes com Síndrome Clinicamente Isolada (SCI) e EM. Métodos: Os participantes foram divididos em três grupos: 1) pacientes com SCI (n = 20); 2) pacientes com EM recorrente-remitente (EMRR; n = 39); e 3) indivíduos saudáveis (n = 35). Os níveis de YKL-40 em amostras séricas obtidas dos participantes foram medidos usando-se imunoensaios ligados a enzimas. Resultados: O nível sérico médio de YKL-40 foi 20.2 ng/mL (range 9.8-75.9 ng/mL) em pacientes com CIS, 22.7 ng/mL (intervalo entre 13.4-57.9 ng/mL) em pacientes com EMRR e 11.0 ng/mL (intervalo entre 10.0-17.3 ng/mL) no grupo controle (p < 0.001). Os níveis séricos de YKL-40 em pacientes com EMRR estavam correlacionados às pontuações e idades dos pacientes na EDSS (p < 0.05). Não foram determinadas relações entre os níveis séricos de YKL-40 e outras variáveis (p > 0.05). Os níveis séricos de YKL-40 no grupo SCI estavam mais elevados do que no grupo EM. Estes resultados demonstram que os níveis séricos de YKL-40 estavam mais elevados até mesmo no início da doença. Os níveis séricos de YKL-40 também não estavam associados à progressão da EM clinicamente definida. Conclusões: A partir deste estudo, os resultados sugeriram que a proteína YKL-40 pode ser um indicador útil no processo inflamatório da EM.

Cerebellar-cerebral resting-state functional connectivity alterations in relapsing-remitting multiple sclerosis / 中华放射学杂志

Objective:To investigate the alterations of cerebellar and cerebral functional connectivity (FC) in patients with relapsing-remitting multiple sclerosis (RRMS) and associations with clinical parameters.Methods:Eighteen acute RRMS patients, 25 remitting RRMS patients and 20 healthy controls (HC) who underwent 3.0 T brain MRI using resting-state functional protocols were collected retrospectively from September 2012 to June 2019 at the First Hospital of Nanchang University. After data preprocessing, the functional connectivity coefficients were calculated between each seed of the cerebellum and every other voxel in the cerebrum for comparison of the inter-groups difference and correlation analysis with clinical variables.Results:Compared with HC, the acute RRMS patients showed significant decreased FC of left cerebellar lobule Ⅵ, the right cerebellar lobule Ⅵ and the left vermis ( P<0.001, Gaussian Random Field theory correction at cluster level P<0.05), the remitting RRMS patients showed the decreased FC of the right cerebellar Crus I, the left cerebellar Crus Ⅰ, the left cerebellar lobule Ⅴ and right cerebellar lobule Ⅴ ( P<0.001, Gaussian Random Field theory correction at cluster level P<0.05). In the acute RRMS patients, FC between the left cerebellar lobule Ⅵ and the right precentral/postcentral gyrus was negatively correlated with illness duration ( r=-0.492, P=0.038). FC between the right cerebellar lobule Ⅵ and the right postcentral gyrus/right superior parietal gyrus was negatively correlated with the expanded disability status scale scores ( r=-0.611, P=0.007). FC between the left vermis and the left calcarine gyrus was negatively correlated with illness duration ( r=-0.534, P=0.02). In the remitting RRMS patients, FC between the right Crus Ⅰ and the left anterior insula was negatively correlated with normalized total white matter lesion load ( r=-0.453, P=0.023). FC between the right Crus Ⅰ and the right anterior insula was negatively correlated with modified fatigue impact scale ( r=-0.450, P=0.024). Conclusions:The cerebello-cerebral connection of cognitive related networks is decreased in both acute attack and remission stages of RRMS patients. In addition, the cerebello-cerebral connection in sensorimotor network can also be significantly impacted in acute attack stage, while the cerebello-cerebral connection of emotional network may be decreased in remission stage.

Differentiation of relapsing-remitting and secondary progressive multiple sclerosis: a magnetic resonance spectroscopy study based on machine learning / Diferenciação de esclerose múltipla recorrente-remitente e progressiva secundária: um estudo de ressonância magnética com espectroscopia baseado em aprendizado de máquina

ABSTRACT Introduction: Magnetic resonance imaging (MRI) is the most important tool for diagnosis and follow-up in multiple sclerosis (MS). The discrimination of relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS) is clinically difficult, and developing the proposal presented in this study would contribute to the process. Objective: This study aimed to ensure the automatic classification of healthy controls, RRMS, and SPMS by using MR spectroscopy and machine learning methods. Methods: MR spectroscopy (MRS) was performed on a total of 91 participants, distributed into healthy controls (n=30), RRMS (n=36), and SPMS (n=25). Firstly, MRS metabolites were identified using signal processing techniques. Secondly, feature extraction was performed based on MRS Spectra. N-acetylaspartate (NAA) was the most significant metabolite in differentiating MS types. Lastly, binary classifications (healthy controls-RRMS and RRMS-SPMS) were carried out according to features obtained by the Support Vector Machine algorithm. Results: RRMS cases were differentiated from healthy controls with 85% accuracy, 90.91% sensitivity, and 77.78% specificity. RRMS and SPMS were classified with 83.33% accuracy, 81.81% sensitivity, and 85.71% specificity. Conclusions: A combined analysis of MRS and computer-aided diagnosis may be useful as a complementary imaging technique to determine MS types.

RESUMO Introdução: A ressonância magnética é a ferramenta mais importante para o diagnóstico e acompanhamento na EM. A transição da EM recorrente-remitente (EMRR) para a EM progressiva secundária (EMPS) é clinicamente difícil e seria importante desenvolver a proposta apresentada neste estudo a fim de contribuir com o processo. Objetivo: o objetivo deste estudo foi garantir a classificação automática de grupo controle saudável, EMRR e EMPS usando a RM com espectroscopia e métodos de aprendizado de máquina. Métodos: Os exames de RM com espectroscopia foram realizados em um total de 91 amostras com grupo controle saudável (n=30), EMRR (n=36) e EMPS (n=25). Em primeiro lugar, os metabólitos da RM com espectroscopia foram identificados usando técnicas de processamento de sinal. Em segundo lugar, a extração de recursos foi realizada a partir do MRS Spectra. O NAA foi determinado como o metabólito mais significativo na diferenciação dos tipos de MS. Por fim, as classificações binárias (Healthy Control Group-RRMS e RRMS-SPMS) foram realizadas de acordo com as características obtidas por meio do algoritmo Support Vector Machine. Resultados: Os casos de EMRR e do grupo de controle saudável foram diferenciados entre si com 85% de acerto, 90,91% de sensibilidade e 77,78% de especificidade, respectivamente. A EMRR e a EMPS foram classificadas com 83,33% de acurácia, 81,81% de sensibilidade e 85,71% de especificidade, respectivamente. Conclusões: Uma análise combinada de RM com espectroscopia e abordagem de diagnóstico auxiliado por computador pode ser útil como uma técnica de imagem complementar na determinação dos tipos de EM.

Relapsing-remitting multiple sclerosis at remission stage treated with acupuncture:a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the differences in the therapeutic effects on relapsing-remitting multiple sclerosis (RRMS) at remission stage between acupuncture at acupoints and shallow needling therapy at the nearby points.</p><p><b>METHODS</b>Forty-two patients of RRMS were randomized into an observation group and a control group, 21 cases in each one. In the observation group, besides the basic treatment, acupuncture was applied according to's empirical prescriptions as "the empirical ten needles" "thirteen needles of the governor vessel" "twelve needles of hand and foot" as well as the symptomatic points. In the control group, the basic treatment was given. Additionally, the shallow needling therapy was given at the sites 0.2 to 0.3lateral to the acupoints, and the arrival ofwas not required. In the two groups, acupuncture was given once a day for 5 days a week, continuously for 2 weeks. At the intervals of 2 weeks, totally the treatment of 3 months was required. The follow-up visit was conducted for 2 years. Separately, the scores of the expanded disability status scale (EDSS) before and in follow-up after treatment, the annual recurrent rate before and after treatment and recurrent interval after treatment were observed in the patients of the two groups.</p><p><b>RESULTS</b>In the observation group, EDSS scores in 3-month and 6-month follow-up were reduced as compared with those before treatment (both<0.05) and those in the 12-month and 24-month follow-up were increased (both<0.05). In the control group, EDSS scores were increased in tendency continuously in 3-month, 6-month, 12-month and 24-month follow-up (all<0.05). In each time point of follow-up, the different value of EDSS scores in the observation group was lower than that in the control group (<0.05,<0.01). The annual recurrent rates after treatment were reduced as compared with those before treatment in the two groups (both<0.01) and the value in the observation group was lower than that in the control group (<0.01). The recurrent interval in the observation group was longer than that in the control group[(441.56±65.37) d vs (382.78±59.33) d,<0.01].</p><p><b>CONCLUSIONS</b>Acupuncture achieves the significant therapeutic effects on RRMS at the remission stage. This therapy relieves the symptoms of neural functional deficits, delays the time of occurrence and reduces the annual recurrent rate.</p>

Studies of the perfusion and permeability characteristic in the brain lesions of patients with relapsing-remitting multiple sclerosis using dynamic contrast-enhanced MRI / 中华放射学杂志

Objective To evaluate dynamic contrast-enhanced MRI (DCE-MRI) with Patlak model for depicting the perfusion and permeability characteristics of lesions and normal-appearing white matter (NAWM) regions in patients with relapsing-remitting multiple sclerosis (RRMS). Methods Twenty-three patients with clinical confirmed RRMS were retrospectively analyzed, who had underwent conventional MRI and DCE-MRI using a 3.0 T MR scanner . The clinical characteristics and imaging data were collected. Post-processing was performed using the Patlak model. Volume transfer constant (Ktrans), fractional plasma volume (Vp) and perfusion parameters including cerebral blood flow (CBF) and cerebral blood volume (CBV) were represented as median and interquartile range(IQR). The four parameters of non-enhanced(NE) lesions, NAWM regions located close to NE lesions(NAWM close) and NAWM regions located far from NE lesions (NAWM far) were compared using the Kruskal-Wallis H rank sum test. Artificial color mappings were also proceeded. Results MR imaging biomarkers Ktrans was 0.132(0.064, 0.233) min-1 for NE lesions, 0.111 (0.060, 0.233) min-1 for NAWM close and 0.077(0.044, 0.185) min-1 for NAWM far, respectively. CBV was 10.660(5.555, 22.193) ml · 100 g-1 for NE lesions, 9.359(4.883, 16.290) ml · 100 g-1 for NAWM close, 6.814 (4.699, 13.623) ml·100 g-1 for NAWM far, respectively. Ktrans and CBV of NE lesions was significantly higher than that of NAWM far(χ2=7.582,P0.05). Conclusion DCE-MRI with Patlak model can measure perfusion and permeability characteristics and hemodynamic abnormalities of NE lesions and NAWM regions in patients with multiple sclerosis.

"The ""small-world"" property of default mode network in relapsing-remitting multiple sclerosis:a graph theory resting-state functional network analysis" / 中华行为医学与脑科学杂志

Objective To investigate the small-world property of default mode network in relapsingremitting multiple sclerosis (RRMS) compared with the (matched) healthy control subjects,using a graph theory for resting-state functional network analysis.Methods Twenty four patients with RRMS and 24 age-,and sexmatched healthy controls were exanined with resting-state functional MRI (R-fMRI) and 3D-T1WI on Trio 3.0 Tesla.The R-fMRI data were preprocessed,then 20 regions of interest (ROIs) was defined and extracted from the default mode network.The functional connectivity between a pair of regions was defined as the Pearson's correlation coefficient in the time courses.Graph theoretical analysis was implemented and compared with the property of binary functional network.Further,the relationships were examined between the topological property of functional networks and the clinical parameters.Results In this study,functional network in the default mode network was conducted,and the small-world characteristics were observed in both RRMS and healthy control group.In the range of densities (Dmin:0.01∶0.48 ;Dmin =0.42),compared with healthy control group,RRMS groups had a slightly smaller normalized clustering coefficient (P＞0.05),a slightly larger normalized path length (P＞0.05),and a slightly decrease small-world index (P＞0.05).The left posterior cingulated cortex showed a significantly larger clustering coefficient in RRMS group (P=0.031) on the network threshold at Dmin.The area under a curve (AUC) for clustering coefficient measure curves of the left posterior cingulated cortex (density range of 0.42:0.01:0.48) between two groups were compared.The AUC result was similar to the Dmin result (P=0.031).Negative correlation was observed between the clustering coefficient of left posterior cingulated cortex and the Paced Auditory Serial Addition Test (PASAT) in both the Dmin(P=0.023) and the AUC (P=0.020).Conclusion The default mode network has small-world property in RRMS group.The significantly increased clustering coefficience is observed in the left posterior cingulated cortex,which may be a side effect.

Effect of methylprednisolone on T helper 17 cell related cytokines in patients with relapsing remitting multiple sclerosis / 中华神经科杂志

Objective To investigate the effect of methylprednisolone on T helper 17 cell (Th17 cells) related cytokines (interleukin (IL)-23,17A,21,22,6,and tansforming growth factor (TGF)-β) in serum and cerebrospinal fluid from patients with relapsing remitting multiple sclerosis and their effects on the pathogenesis.Methods We recruited relapsing remitting multiple sclerosis group (38 patients)and noninflammatory neurological disease group (20 controls),and detected the levels of IL-23,IL-17A,IL-21,IL-22,TGF-β and IL-6 in serum and cerebrospinal fluid (CSF) with ELISA kit in both controls and patients before and after treatment by methylprednisolone.Results After treatment in relapsing remitting multiple sclerosis patients,IL-17A,IL-23,IL-21,and IL-22 levels in cerebrospinal fluid and serum were significantly decreased,however,they were still higher than that in the non-inflammatory neurological disease patients.TGF-β levels was significantly increased (serum:(17.2 ± 5.9) pg/ml vs (34.1 ± 6.5) pg/ml,t =14.351,P =0.000 ; CSF:(26.4 ± 4.7) pg/ml vs (73.2 ± 19.7) pg/ml,t =16.352,P =0.000).The levels of TGF-β in serum and CSF in patients before treatment were lower than those of in non-inflammatory neurological disease patients (serum:(30.2 ± 8.9) pg/ml,t =6.769,P =0.012 ; CSF:(3 1.4 ± 7.5) pg/ml,t =9.368,P =0.017).However,the levels of TGF-β in CSF in patients after treatment were significantly higher than those in non-inflammatory neurological disease patients (t =9.138,P =0.000).Correlation analysis showed that IL-23 and IL-17A were positive correlation in the serum of relapsing remitting multiple sclerosis patients before treatment.Moreover,positive correlations among IL-23,IL-17A and IL-21 were detected in the CSF of relapsing remitting multiple sclerosis patients before treatment.Conclusions Decreased levels of IL-23,IL-17A,IL-21 and IL-22,and elevated levels of TGF-β were detected in serum and CSF of patients with relapsing remitting multiple sclerosis after methylprednisolone treatment.IL-23,IL-17A,IL-21,IL-22 and TGF-β might involve in the pathogenesis of relapsing remitting multiple sclerosis.

Detection of posterior cingulate cortex functional connectivity characteristics in resting-state functional magnetic resonance imaging in relapsing-remitting multiple sclerosis / 中华神经科杂志

Objective To examine brain regions with a functional connection to posterior cingulate cortex (PCC) in a relapsing-remitting multiple sclerosis (RRMS) group compared with matched control subjects,and to employ resting-state functional MRI (rs-fMRI) to PCC connectivity gathered by investigating synchronic low frequency fMRI signal fluctuations of default mode network with seed-based correlation analysis (SCA).Methods Twenty-seven patients with RRMS (RRMS group) and 27 age-,and sexmatched healthy controls (HC group) were examined by resting-state fMRI,DTI and 3D-T1 on Siemens Trio Tim 3.0T.The fMRI data preprocessing and processing was performed using Data Processing Assistant for Resting-State fMRI Advanced Edition (DPARSFA) based on Matlab 2012a,and PCC (-5,-49,40)was selected as seed.An SCA approach was used to analyze the rs-fMRI data.We examined the differences in SCA-derived connectivity metrics in patients with RRMS and healthy controls,and analyzed correlations between connectivity correlation coefficient of the differences regions and MRI-derived metrics (brain parenchymal fraction,T2 lesion load),as well as clinical metrics (expanded disability status scale,paced auditory serial addition test,and disease duration) of the disease.Results The SCA via functional connectivity of PCC showed that the temporal correlation between the blood-oxygen-level-dependent signals of the default mode network was reliable spatial patterns of activation in patients with RRMS.The lower connectivity in right superior frontal gyrus within default mode network,and higher connectivity in right posterior lobe of cerebellum,right crus of cerebellum,right medial frontal gyrus,right medial occipital gyrus,left precuneus/cingulate gyrus,right angular gyrus and right cingulate gyrus were found in our study.Significant negative-related was observed between the paced auditory serial addition test and functional connectivity in right middle temporal gyrus (0.387 ± 0.216) of RRMS patients (r =-0.59,P =0.001).Significant negative correlation also was observed between the course of disease and functional connectivity in right superior frontal gyrus (0.039 ± 0.293) in patients (r =-0.39,P =0.041).There was no significant correlations between other regions with different functional connectivity and expanded disability status scale,disease duration,or brain atrophy.The connectivity in right superior frontal gyrus,left medial occipital gyrus,left precentral gyrus was decreased; and connectivity in right cerebellum anterior lobe (dentate),right frontal lobe white matter was significantly increased.Significant positive correlation was observed between the course of disease and functional connectivity in left precentral gyrus (-0.924 ± 0.253),right cerebellum anterior lobe (dentate ;0.217 ± 0.208) of RRMS patients (r =0.650,P =0.000;r =0.436,P =0.023),respectively.Conclusion These findings reveal the compensatory mechanism of the brain in response to structural damage,by means of increased activation or synchronization of default mode network,which seems to be finite.

Functional and structural connectivity abnormalities of default mode network in relapsing-remitting multiple sclerosis: a study combining functional MRI and diffusion tensor imaging / 中华放射学杂志

Objective To investigate the functional and structural changes of connectivity of default mode network (DMN) in relapsing-remitting multiple sclerosis (RRMS) by functional MRI (fMRI) and diffusion tensor imaging (DTI) and to study the relationship between them.Methods Twenty-seven RRMS patients(clinically diagnosed as RRMS)and 27 healthy volunteers (matched to the patients in age and gender) were selected to participate in this study.All the subjects underwent 3.0 T MR scanning.Softwares such as DPARSF,MICA,TrackVis were used for data post-processing.Medial prefrontal cortex (mPFC) and posterior cingulate cortex(PCC) of DMN were chosen as ROIs,and functional and structural changes of DMN and the relationship between them were analyzed.Values of r reflecting the functional connectivity and fractional anisotropy(FA) of two groups were obtained.Then statistical analysis was performed by using student t test and Pearson correlation analysis.Results The DMN space pattern of the RRMS patients was mostly identical to that of controls,but with specific difference in the connectivity strength with respect to that of controls.Particularly,the patient group showed increased DMN connectivity in the mPFC,but decreased connectivity in the inferior parietal lobule (IPL) and PCC.Compared with controls,the r value (0.695 ±0.151 vs.0.796±0.085),FA value(0.261 ±0.012 vs.0.285 ±0.017) between mPFC and PCC in RRMS patients were decreased (t =-3.020,-6.206,P ＜ 0.05).In addition,functional connectivity (r value) was found to correlate with structural connectivity(FA value) between the PCC and mPFC (r =0.704,0.735,P ＜ 0.01).The number of MS lesion,had no correlation with r value or FA value (P ＞ 0.05).Conclusions The functional connectivity and structural connectivity of DMN change in RRMS patients.The functional connectivity and structural connectivity between mPFC and PCC are both decreased in RRMS patients compared with the controls.The injury of structural connectivity may be the structural basis of the decrease of functional connectivity.

Análisis de impacto presupuestal de la introducción de fingolimod en el tratamiento de esclerosis múltiple en Colombia: a budget impact analysis / Introduction of fingolimod for the treatment of multiple sclerosis in Colombia

La esclerosis múltiple está asociada con discapacidad a largo plazo y un significativo impacto social. La introducción de fingolimod, un medicamento eficaz en la reducción de recaídas, en comparación con interferon beta 1a, justifica un análisis de impacto presupuestal desde la perspectiva del sistema de salud colombiano. OBJETIVO: desarrollar un análisis de impacto presupuestal, para los años 2012 a 2016 de la introducción de fingolimod en el sistema de salud de Colombia. MATERIALES Y MÉTODOS: usando la perspectiva del sistema de salud, se diseñó un modelo de impacto presupuestal para determinar el efecto que la introducción del fingolimod para el tratamiento de pacientes con esclerosis múltiple remitente recurrente tendría sobre los recursos del sistema de salud. La información clínica y de prevalencia fue obtenidas de la literatura, los costos fueron tomados de registros hospitalarios. Se realizó una simulación de Monte Carlo como parte del análisis de sensibilidad. RESULTADOS: el costo neto anual (2012-2016) para el escenario sin fingolimod fue, en miles de millones de pesos, $20,96, $22,29, $23,37, $24,68, y $25,98. En el escenario con fingolimod el costo neto fue: $21,01, $22,42, $23,50, $24,91 y $26,39. Por otro lado, fingolimod se asoció con 91 recaídas evitadas en este periodo de cinco años. La simulación de Monte Carlo no mostró diferencias significativas de los costos entre los dos escenarios. CONCLUSIÓN: considerando estos supuestos, la introducción de fingolimod en el sistema de salud colombiano no implica un impacto presupuestal significativo, y representa una importante reducción en el número de recaídas prevenidas.

INTRODUCTION: multiple sclerosis (MS) is associated with long-term disability and significant social impact. First-line disease modifying treatments for MS (interferons and glatiramer acetate) have moderate efficacy and must be administered in daily or weekly injections. The introduction of fingolimod, a molecule with superior efficacy in reducing MS relapses compared to interferon-beta 1a justifies a budget impact analysis from a Colombian health system perspective. OBJETIVES: to develop a budget impact analysis, for years 2012 to 2016, of the introduction of fingolimod in the Colombian health system. MATERIALS AND METHODS: using the perspective of the Colombian health system, we designed a budget impact model to determine the effect that the introduction of fingolimod for patients with relapsing-remitting MS would have on the resources of the health system. Clinical data and prevalence were obtained from published literature, costs were collected from local sources. A Monte Carlo simulation was done as part of the sensitivity analysis. Exchange rate used was 2,565 pesos per euro (July 2011). RESULTS: total annual net costs (2012-2016) for the scenario without fingolimod were, in million euros, €8.17, €€8.69, €9.11, €9.62, and €10.13. In the fingolimod scenario net costs were: €8.19, €8.74, €9.16, €9.71 and €10.29. On the other hand, fingolimod was associated with 91 relapses averted in this five-year period. Monte Carlo simulation does not show relevant differences in costs between both scenarios. CONCLUSION: under these assumptions, the introduction of fingolimod in Colombian health care system does not imply a significant budget impact but represents an important reduction in the number MS relapses.

Observation on the effect of methylprednisolone combined with interferon in the treatment of patients with relapse remitting multiple sclerosis / 中国基层医药

Objective To explore the effect of methylprednisolone combined with interferon in the treatment patients with relapse remitting multiple sclerosis.Methods 90 patients with relapse remitting multiple sclerosis were randomly divided into experimental group and treatment group.The experimental group during the acute stage with methylprednisolone pulse therapy,remission with interferon β (IFN-β) treatment; the control group only in the acute phase with methylprednisolone pulse therapy.Results The total effective rate of methylprednisolone pulse therapy in the acute stage was 98.9％.Experimental group during the treatment with IFN-β1α,relapse rate was 30.2％ ;patients in the control group were followed up for two years,the recurrence rate was 53.3％.Experimental group and control group was significantly different ( P ＜ 0.05 ),the experimental group was significantly lower than the control group.Conclusion For relapsing-remitting MS,using MPPT could relieve acute symptom in the acute stage,and in remission using of IFN-β1α relapse prevention was a good choice for clinicians.

Feature of grey matter atrophy in relapsing-remitting multiple sclerosis:a voxel-based morphometry Study / 中华神经科杂志

Objective To investigate the feature of regional grey matter volume changes in relapsing-remitting multiple sclerosis (RRMS) patients by voxel-based morphometry ( VBM) and presume the possible pathophysiological basis.Methods Conventional magnetic resonance imaging (MRI) and T1-weighted three-dimensional MRI were obtained from 32 RRMS and 32 sex- and age-matched normal controls.The comparison of grey matter volume between the two groups was analyzed by statistical analysis software SPM5 and VBM.A Pearson correlational analysis was used to assess correlation between gre matter loss and disease duration,expanded disability status scale (EDSS) and visible brain lesion volume.Results Compared with normal controls,RRMS patients had extensive bilateral grey matter atrophy in thalami (left 2031 and right 1711),caudate (left 815 and right 1031) and parahippocampal gyrus (left 313 and right 467),as well as several cortical regions in frontal,temporal,parietal,and occipital lobes (t value were between 8.853 and 11.163,all P ＜ 0.01).Regional grey matter loss in bilateral thalami ( r value were - 0.596 on left and were - 0.694 on right) and right caudate ( r = - 0.409 ) were strongly negatively correlated with visible brain lesion volume in RRMS (all P ＜ 0.05 ).Conclusions By means of VBM,extensive grey matter atrophy are found in RRMS patients,especially in deep grey matter.Axonal degeneration secondary to visible brain lesions may be a key pathogenesis of grey matter atrophy in RRMS.

Quantitative diffusion tensor imaging of normal-appearing white matter fiber tracts of the brainstem in patients with relapsing-remitting multiple sclerosis / 中国医学影像技术

Objective To assess the changes in normal-appearing white matter fiber tracts of the brainstem in patients with relapsing-remitting multiple sclerosis (RRMS) quantitatively with diffusion tensor imaging (DTI). Methods Fifty patients with RRMS were recruited, and twenty five healthy volunteers with the same gender and age were selected as controls. Conventional magnetic resonance imaging and DTI was performed. Quantitative indexes as fractional anisotropy (FA) and mean diffusivity (MD) values in the brainstem fiber tracts, including corticopontine tract/corticospinal tract (cpt/cst), superior cerebellar peduncle (scp), middle cerebellar peduncle (mcp), inferior cerebellar peduncle (icp), and medial lemniscus (ml) were measured and analyzed. Results In comparison with controls, decreasing FA values in cpt/cst (L:P=0.030; R:P=0.020), icp (L:P=0.030; R:P=0.037), scp (L:P=0.036; R:P=0.041) and ml (L:P=0.014; R:P=0.035), as well as increasing MD values in cpt/cst (L:P=0.004; R:P=0.046), icp (L:P=0.047; R:P=0.011), scp (L:P=0.021; R:P=0.011) and ml (L:P=0.002; R:P=0.044) were found in patients with RRMS. No significant difference of FA and MD values was found in mcp between patients with RRMS and controls (P＞0.05). None of the MD or FA values in fiber tracts of the brainstem in patients with RRMS was correlated with brain parenchymal fraction (BPF) or T2 lesion volume. Conclusion The relevant abnormalities which were found in normal-appearing white matter fiber tracts of the brainstem in RRMS patients by DTI scanning suggested pathological changes. It is presumed that the changes may be due to demyelination caused by hiding lesions.