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Browsing by Author "Dackovic, Jelena (19034069600)"

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    An algorithm for genetic testing of serbian patients with demyelinating charcot-marie-tooth
    (2013)
    Keckarevic Markovic, Milica P. (18434375900)
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    Dackovic, Jelena (19034069600)
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    Mladenovic, Jelena (8310875700)
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    Milic-Rasic, Vedrana (6507653181)
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    Kecmanovic, Miljana (36860979600)
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    Keckarevic, Dusan (6507380019)
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    Romac, Stanka (7003983993)
    Charcot-Marie Tooth (CMT) is a clinically and genetically heterogeneous group of diseases with rough genotype-phenotype correlation, so the final diagnosis requires extensive clinical and electrophysiological examination, family data, and gene mutation analysis. Although there is a common pattern of genetic basis of CMT, there could be some population differences that should be taken into account to facilitate analyses. Here we present the algorithm for genetic testing in Serbian patients with demyelinating CMT, based on their genetic specificities: in cases of no PMP22 duplication, and if -X-linked CMT (CMTX) is not contraindicated by pattern of inheritance (male-to-male transmission), one should test for c.94A>G GJB founder mutation, first. Also, when a patient is of Romani ethnicity, or if there is an autosomal recessive inheritance in a family and unclear ethnicity, c.442C>T mutation in NDRG1 should be tested. © Copyright 2013, Mary Ann Liebert, Inc. 2013.
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    Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats
    (2016)
    Gagic, Milica (58390506600)
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    Markovic, Milica Keckarevic (18434375900)
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    Kecmanovic, Miljana (36860979600)
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    Keckarevic, Dusan (6507380019)
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    Mladenovic, Jelena (8310875700)
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    Dackovic, Jelena (19034069600)
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    Milic-Rasic, Vedrana (6507653181)
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    Romac, Stanka (7003983993)
    Background: Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region. Methods: Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers. Results: In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus. Conclusions: Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing. © 2016 by De Gruyter.
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    Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats
    (2016)
    Gagic, Milica (58390506600)
    ;
    Markovic, Milica Keckarevic (18434375900)
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    Kecmanovic, Miljana (36860979600)
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    Keckarevic, Dusan (6507380019)
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    Mladenovic, Jelena (8310875700)
    ;
    Dackovic, Jelena (19034069600)
    ;
    Milic-Rasic, Vedrana (6507653181)
    ;
    Romac, Stanka (7003983993)
    Background: Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region. Methods: Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers. Results: In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus. Conclusions: Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing. © 2016 by De Gruyter.
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    Clinically isolated syndrome suggestive of multiple sclerosis: Dynamic patterns of gray and white matter changes - A 2-year MR imaging study
    (2016)
    Rocca, Maria A. (34973365100)
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    Preziosa, Paolo (6506754661)
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    Mesaros, Sarlota (7004307592)
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    Pagani, Elisabetta (7005421345)
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    Dackovic, Jelena (19034069600)
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    Stosic-Opincal, Tatjana (55886486600)
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    Drulovic, Jelena (55886929900)
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    Filippi, Massimo (7202268530)
    Purpose: To investigate the patterns of regional gray matter (GM) and white matter (WM) atrophy, WM microstructural tissue damage, and changes in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis at 2 years from clinical onset. Materials and Methods: Institutional review board approval and written informed consent from all patients were obtained. Neurologic assessment and conventional, diffusion-tensor, and volumetric brain MR imaging sequences were performed in 37 patients with CIS within 2 months of clinical onset, and after 3, 12, and 24 months. Fourteen healthy control subjects also were studied. Longitudinal GM and WM volume changes and WM microstructural abnormalities were assessed by using voxel-based morphometry (P <.001, uncorrected) and tract-based spatial statistics (P <.05, corrected). Results: At 24 months, 33 of 37 (89%) patients had developed multiple sclerosis. At month 3, patients with CIS showed a transient volume increase in frontal, parietal, temporal, and cerebellar GM regions. At 12 months, patients with CIS developed atrophy of the thalami, caudate nuclei, cerebellum, and frontal, parietal, and temporal lobes. At 24 months GM volume of the frontal, temporal, and parietal cortical areas further decreased from that at 12 months. WM atrophy involved only a few WM regions at 2 months from clinical onset, with progressive involvement of additional WM tracts with time. A diffuse pattern of WM microstructural abnormalities was detected within 2 months of onset and had worsened at 24 months. Conclusion: After an acute inflammatory event, dynamic modifications of regional GM and WM damage occur in patients with CIS, with a progressive evolution of WM damage from disease onset and a transient, early increase in GM volume, followed by GM atrophy. Neurodegenerative processes start early in patients with multiple sclerosis. © RSNA, 2015.
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    Dynamic volumetric changes of hippocampal subfields in clinically isolated syndrome patients: A 2-year MRI study
    (2019)
    Cacciaguerra, Laura (57185733400)
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    Pagani, Elisabetta (7005421345)
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    Mesaros, Sharlota (7004307592)
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    Dackovic, Jelena (19034069600)
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    Dujmovic-Basuroski, Irena (6701590899)
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    Drulovic, Jelena (55886929900)
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    Valsasina, Paola (6506051299)
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    Filippi, Massimo (7202268530)
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    Rocca, Maria Assunta (34973365100)
    Background: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. Objective: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. Methods: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. Results: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. Conclusion: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions. © The Author(s), 2018.
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    Dynamic volumetric changes of hippocampal subfields in clinically isolated syndrome patients: A 2-year MRI study
    (2019)
    Cacciaguerra, Laura (57185733400)
    ;
    Pagani, Elisabetta (7005421345)
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    Mesaros, Sharlota (7004307592)
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    Dackovic, Jelena (19034069600)
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    Dujmovic-Basuroski, Irena (6701590899)
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    Drulovic, Jelena (55886929900)
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    Valsasina, Paola (6506051299)
    ;
    Filippi, Massimo (7202268530)
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    Rocca, Maria Assunta (34973365100)
    Background: Different subregional patterns of hippocampal involvement have been observed in diverse multiple sclerosis (MS) phenotypes. Objective: To evaluate the occurrence of regional hippocampal variations in clinically isolated syndrome (CIS) patients, their relationships with focal white matter (WM) lesions, and their prognostic implications. Methods: Brain dual-echo and three-dimensional (3D) T1-weighted scans were acquired from 14 healthy controls and 36 CIS patients within 2 months from clinical onset and after 3, 12, and 24 months. Radial distance distribution was assessed using 3D parametric surface mesh models. A cognitive screening was also performed. Results: Patients showed clusters of reduced radial distance in the Cornu Ammonis 1 from month 3, progressively extending to the subiculum, negatively correlated with ipsilateral T2 and T1 lesion volume. Increased radial distance appeared in the right dentate gyrus after 3 (p < 0.05), 12, and 24 (p < 0.001) months, and in the left one after 3 and 24 months (p < 0.001), positively correlated with lesional measures. Hippocampal volume variations were more pronounced in patients converting to MS after 24 months and did not correlate with cognitive performance. Conclusion: Regional hippocampal changes occur in CIS, are more pronounced in patients converting to MS, and are modulated by focal WM lesions. © The Author(s), 2018.
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    Gait pattern in patients with different multiple sclerosis phenotypes
    (2017)
    Dujmovic, Irena (6701590899)
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    Radovanovic, Sasa (6604015284)
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    Martinovic, Vanja (56925159700)
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    Dackovic, Jelena (19034069600)
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    Maric, Gorica (56433592800)
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    Mesaros, Sarlota (7004307592)
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    Pekmezovic, Tatjana (7003989932)
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    Kostic, Vladimir (57189017751)
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    Drulovic, Jelena (55886929900)
    Background Gait pattern is frequently impaired in multiple sclerosis (MS), however gait characteristics in patients with different MS phenotypes have not been fully elucidated. Methods We analyzed spatio-temporal gait pattern characteristics in patients with relapsing-remitting (RR, n=52) and primary-progressive (PP, n=18) MS in comparison with age-matched healthy controls (HC, n=40). All subjects performed a standardized simple walking task, a dual motor- motor task, a dual motor-mental task, and a triple combined motor-mental task at a GAITRite electronic walkway of 5.5 m active area. We measured: cycle time (CT), stride length (SL), swing time (ST), double support time (DST), gait velocity (GV) and calculated symmetry index (SI) for CT, SL and ST. Results With each task performed, CT and DST in the total MS group were significantly longer while SL was significantly shorter and GV significantly lower than in HC. ST was similar in the total MS patient group and HC. In both MS patients and HC, CT and DST increased and SL and GV decreased over repeated assessments. Dual and triple tasks while walking influenced walking performance in both MS patients and HC. Although patients with PPMS differed significantly from those with RRMS in the majority of gait parameters, the subgroup analysis in patients matched for age and disability (Expanded Disability Status Scale Score -EDSS, 3.0–5.0) showed similar gait performance in RRMS and PPMS patients having the same level of disability, except for CT and ST- symmetry parameters that were more impaired in the PPMS group. The EDSS score correlated significantly with CT, DST, SL and GV, but no significant correlation was found with ST except at the triple combined motor-mental task. Conclusion A disturbed gait pattern in MS patients with different MS phenotypes depends on disability and reflects a cognitive-motor interference. © 2017 Elsevier B.V.
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    Gait pattern in patients with different multiple sclerosis phenotypes
    (2017)
    Dujmovic, Irena (6701590899)
    ;
    Radovanovic, Sasa (6604015284)
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    Martinovic, Vanja (56925159700)
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    Dackovic, Jelena (19034069600)
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    Maric, Gorica (56433592800)
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    Mesaros, Sarlota (7004307592)
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    Pekmezovic, Tatjana (7003989932)
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    Kostic, Vladimir (57189017751)
    ;
    Drulovic, Jelena (55886929900)
    Background Gait pattern is frequently impaired in multiple sclerosis (MS), however gait characteristics in patients with different MS phenotypes have not been fully elucidated. Methods We analyzed spatio-temporal gait pattern characteristics in patients with relapsing-remitting (RR, n=52) and primary-progressive (PP, n=18) MS in comparison with age-matched healthy controls (HC, n=40). All subjects performed a standardized simple walking task, a dual motor- motor task, a dual motor-mental task, and a triple combined motor-mental task at a GAITRite electronic walkway of 5.5 m active area. We measured: cycle time (CT), stride length (SL), swing time (ST), double support time (DST), gait velocity (GV) and calculated symmetry index (SI) for CT, SL and ST. Results With each task performed, CT and DST in the total MS group were significantly longer while SL was significantly shorter and GV significantly lower than in HC. ST was similar in the total MS patient group and HC. In both MS patients and HC, CT and DST increased and SL and GV decreased over repeated assessments. Dual and triple tasks while walking influenced walking performance in both MS patients and HC. Although patients with PPMS differed significantly from those with RRMS in the majority of gait parameters, the subgroup analysis in patients matched for age and disability (Expanded Disability Status Scale Score -EDSS, 3.0–5.0) showed similar gait performance in RRMS and PPMS patients having the same level of disability, except for CT and ST- symmetry parameters that were more impaired in the PPMS group. The EDSS score correlated significantly with CT, DST, SL and GV, but no significant correlation was found with ST except at the triple combined motor-mental task. Conclusion A disturbed gait pattern in MS patients with different MS phenotypes depends on disability and reflects a cognitive-motor interference. © 2017 Elsevier B.V.
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    Multidisciplinary rehabilitation and steroids in the management of multiple sclerosis relapses: A randomized controlled trial
    (2016)
    Nedeljkovic, Una (35107650700)
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    Dackovic, Jelena (19034069600)
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    Tepavcevic, Darija Kisic (57218390033)
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    Basuroski, Irena Dujmovic (6701590899)
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    Mesaros, Sarlota (7004307592)
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    Pekmezovic, Tatjana (7003989932)
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    Drulovic, Jelena (55886929900)
    Introduction: Periodic relapses are one of the main characteristics of multiple sclerosis (MS), from which recovery is often incomplete despite highdose methylprednisolone (HDMP) treatment. The aim of our study was to evaluate the potential benefits of short-term HDMP combined with multidisciplinary rehabilitation (MDR) in persons with MS in relapse in order to assess whether combination of steroid therapy with MDR is more beneficial than steroid therapy alone. Material and methods: This investigation was conducted as a randomized controlled trial. The MS patients were eligible if they had an established diagnosis and relapse requiring application of HDMP. Forty-nine patients were included in the study and randomized to control and treatment groups, and 37 completed the study. High-dose methylprednisolone was administered to all patients. The treatment group additionally underwent an MDR program over a 3-week period. All outcome measures were completed at baseline and 1 and 3 months later. Results: The Expanded Disability Status Scale (EDSS) and Functional Independence Measure (FIM) motor scores improved statistically significantly 1 month after HDMP, in both treatment and control groups. During the study period, in the treatment group, a sustained large effect size (ES) was found for both physical and mental composite scores of Multiple Sclerosis Quality of Life-54 (MSQoL-54), while in the controls, a sustained moderate ES was demonstrated only for physical composite score. Conclusions: Our findings suggest that MDR improves MS relapse outcome. © 2016 Termedia & Banach.
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    Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5-year study
    (2017)
    Preziosa, Paolo (6506754661)
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    Pagani, Elisabetta (7005421345)
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    Mesaros, Sarlota (7004307592)
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    Riccitelli, Gianna C. (57193017272)
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    Dackovic, Jelena (19034069600)
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    Drulovic, Jelena (55886929900)
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    Filippi, Massimo (7202268530)
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    Rocca, Maria A. (34973365100)
    In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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    Progression of regional atrophy in the left hemisphere contributes to clinical and cognitive deterioration in multiple sclerosis: A 5-year study
    (2017)
    Preziosa, Paolo (6506754661)
    ;
    Pagani, Elisabetta (7005421345)
    ;
    Mesaros, Sarlota (7004307592)
    ;
    Riccitelli, Gianna C. (57193017272)
    ;
    Dackovic, Jelena (19034069600)
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    Drulovic, Jelena (55886929900)
    ;
    Filippi, Massimo (7202268530)
    ;
    Rocca, Maria A. (34973365100)
    In this longitudinal study, we investigated the regional patterns of focal lesions accumulation, and gray (GM) and white matter (WM) atrophy progression over a five-year follow-up (FU) in multiple sclerosis (MS) patients and their association with clinical and cognitive deterioration. Neurological, neuropsychological and brain MRI (dual-echo and 3D T1-weighted sequences) assessments were prospectively performed at baseline (T0) and after a median FU of 4.9 years from 66 MS patients (including relapse-onset and primary progressive MS) and 16 matched controls. Lesion probability maps were obtained. Longitudinal changes of GM and WM volumes and their association with clinical and cognitive deterioration were assessed using tensor-based morphometry and SPM12. At FU, 36/66 (54.5%) MS patients showed a significant disability worsening, 14/66 (21.2%) evolved to a worse clinical phenotype, and 18/63 (28.6%) developed cognitive deterioration. At T0, compared to controls, MS patients showed a widespread pattern of GM atrophy, involving cortex, deep GM and cerebellum, and atrophy of the majority of WM tracts, which further progressed at FU (P < 0.001, uncorrected). Compared to stable patients, those with clinical and cognitive worsening showed a left-lateralized pattern of GM and WM atrophy, involving deep GM, fronto-temporo-parieto-occipital regions, cerebellum, and several WM tracts (P < 0.001, uncorrected).GM and WM atrophy of relevant brain regions occur in MS after 5 years. A different vulnerability of the two brain hemispheres to irreversible structural damage may be among the factors contributing to clinical and cognitive worsening in these patients. Hum Brain Mapp 38:5648–5665, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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    Relationship between damage to the cerebellar peduncles and clinical disability in multiple sclerosis
    (2014)
    Preziosa, Paolo (6506754661)
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    Rocca, Maria A. (34973365100)
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    Mesaros, Sarlota (7004307592)
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    Pagani, Elisabetta (7005421345)
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    Drulovic, Jelena (55886929900)
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    Stosic-Opincal, Tatjana (55886486600)
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    Dackovic, Jelena (19034069600)
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    Copetti, Massimiliano (24474249000)
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    Caputo, Domenico (7103299939)
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    Filippi, Massimo (7202268530)
    Purpose: To assess whether a structural disconnection between the cerebellum and the cerebral hemispheres contributes to cerebellar and brainstem symptoms in multiple sclerosis (MS). Materials and Methods: This study was approved by the local ethics committee, and written informed consent was obtained from each participant. Brain T2 lesion load, cerebellar white matter and gray matter volumes, and tract-specific measures of the middle and superior cerebellar peduncles were derived from 172 patients with MS and 46 control subjects. Predictors of clinical impairment, which was determined at ambulation and with cerebellar and brainstem functional system scores, were identified by using random forest analysis. Results: Of the 172 patients, 112 (65%) had middle cerebellar peduncle T2 lesions and 74 (43%) had superior cerebellar peduncle T2 lesions. T2 lesions in the middle and superior cerebellar peduncles were more common in clinically impaired patients than in unimpaired patients (P =.05 to <.0001). Most conventional magnetic resonance imaging metrics were more abnormal in impaired patients than in unimpaired patients (P =.03 to <.0001). Except for axial diffusivity, diffusivity abnormalities of the middle and superior cerebellar peduncles were more severe in clinically impaired patients than in unimpaired patients (P =.04 to <.0001). A minimal overlap was found between diffusivity abnormalities and T2 lesions. Compared with volumetric measures of T2 lesions or cerebellar atrophy, diffusivity measures of middle or superior cerebellar peduncle damage enabled better differentiation between clinically impaired and unimpaired patients (C statistics: 61%-70%). Conclusion: The assessment of middle and superior cerebellar peduncle damage contributes to the explanation of cerebellar and/or brainstem symptoms and ambulatory impairment in MS. © 2014 RSNA.
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    The impact of betaplus program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicentric cross-sectional survey in the western Balkan countries
    (2017)
    Drulovic, Jelena (55886929900)
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    Cukic, Mirjana (55891936800)
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    Grgic, Sanja (56698137700)
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    Dincic, Evica (6602112999)
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    Raicevic, Ranko (7007036037)
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    Nadj, Congor (6507608134)
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    Toncev, Gordana (6506651230)
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    Vojinovic, Slobodan (25623848900)
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    Mesaros, Sarlota (7004307592)
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    Kisic Tepavcevic, Darija (57218390033)
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    Dujmovic, Irena (6701590899)
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    Tadic, Daliborka (55596493000)
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    Miletic-Drakulic, Svetlana (36623676800)
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    Dackovic, Jelena (19034069600)
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    Kostic, Smiljana (47961079200)
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    Erakovic, Jevto (57192306386)
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    Sakalas, Lorand (56156559400)
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    Savic, Dejan (26023774800)
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    Suknjaja, Vesna (35727065400)
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    Martinovic, Vanja (56925159700)
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    Maric, Gorica (56433592800)
    ;
    Pekmezovic, Tatjana (7003989932)
    Background Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on clinical outcomes in multiple sclerosis (MS). It has been recently emphasized that low treatment satisfaction (TS) may be an important factor for achieving high rates of treatment adherence. Interferon (IFN) beta-1b was the first DMD approved for the treatment of MS. The aims of our study were to assess TS in subjects with relapsing-remitting (RR) MS treated with IFN beta-1b in Serbia, Montenegro and the Republika Srpska, Bosnia and Herzegovina (B&H), and additionally, to evaluate the impact of patient support program on TS and adherence. Methods This is a cross-sectional survey performed in order to examine TS and adherence with IFN beta-1b in seven MS centers across three countries (Serbia, Montenegro and B&H). Included in the study were 296 adult patients with RRMS treated with IFN beta-1b for at least 6 months. They were invited to complete the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional two treatment adherence questions were also asked. Patient support program (Betaplus®) was available exclusively for patients in Serbia and not for those in Montenegro and the Republika Srpska, B&H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&H and compared their results with those from patients in Serbia. Statistical analysis includes multivariable linear regression analysis in order to assess the differences between three MS patients groups in terms of the TSQM scores, adjusted for potential confounders. For the evaluation of the effects of Betaplus® program, multivariable logistic regression was used, controlling for the same confounding factors. Results Each of the TSQM summary scores in all three countries implicated high level of patients' satisfaction. There was statistically significant group difference on the Effectiveness summary score (p=0.001) and the Side effects summary score (p=0.006) between the group of subjects from Serbia and the combined group of subjects from Montenegro and B&H, in favor of the former cohort. There was statistically significant group difference neither on the Convenience summary score nor on the Overall satisfaction summary score. Results of adjusted logistic regression analysis based on the availability of patient support program (dependent variable) implicate that it had the most significant impact on the Effectiveness summary score (p=0.008). According to the correlation coefficients in the total patient cohort, all TSMQ summary scores except Effectiveness significantly correlated with the decreased adherence (Side effects: p=0.037; Convenience: p=0.016; Overall satisfaction: p=0.046). Conclusion TS with IFN beta-1b was high in our MS patients. Additionally, these results have demonstrated that patient support program have significant impact on TS with IFN beta-1b in the Balkan cohort of RRMS patients. © 2016
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    The impact of betaplus program on patient treatment satisfaction with interferon beta-1b in multiple sclerosis: Multicentric cross-sectional survey in the western Balkan countries
    (2017)
    Drulovic, Jelena (55886929900)
    ;
    Cukic, Mirjana (55891936800)
    ;
    Grgic, Sanja (56698137700)
    ;
    Dincic, Evica (6602112999)
    ;
    Raicevic, Ranko (7007036037)
    ;
    Nadj, Congor (6507608134)
    ;
    Toncev, Gordana (6506651230)
    ;
    Vojinovic, Slobodan (25623848900)
    ;
    Mesaros, Sarlota (7004307592)
    ;
    Kisic Tepavcevic, Darija (57218390033)
    ;
    Dujmovic, Irena (6701590899)
    ;
    Tadic, Daliborka (55596493000)
    ;
    Miletic-Drakulic, Svetlana (36623676800)
    ;
    Dackovic, Jelena (19034069600)
    ;
    Kostic, Smiljana (47961079200)
    ;
    Erakovic, Jevto (57192306386)
    ;
    Sakalas, Lorand (56156559400)
    ;
    Savic, Dejan (26023774800)
    ;
    Suknjaja, Vesna (35727065400)
    ;
    Martinovic, Vanja (56925159700)
    ;
    Maric, Gorica (56433592800)
    ;
    Pekmezovic, Tatjana (7003989932)
    Background Long-term treatment adherence to disease-modifying drugs (DMDs) may have significant impact on clinical outcomes in multiple sclerosis (MS). It has been recently emphasized that low treatment satisfaction (TS) may be an important factor for achieving high rates of treatment adherence. Interferon (IFN) beta-1b was the first DMD approved for the treatment of MS. The aims of our study were to assess TS in subjects with relapsing-remitting (RR) MS treated with IFN beta-1b in Serbia, Montenegro and the Republika Srpska, Bosnia and Herzegovina (B&H), and additionally, to evaluate the impact of patient support program on TS and adherence. Methods This is a cross-sectional survey performed in order to examine TS and adherence with IFN beta-1b in seven MS centers across three countries (Serbia, Montenegro and B&H). Included in the study were 296 adult patients with RRMS treated with IFN beta-1b for at least 6 months. They were invited to complete the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional two treatment adherence questions were also asked. Patient support program (Betaplus®) was available exclusively for patients in Serbia and not for those in Montenegro and the Republika Srpska, B&H. In order to assess the potential impact of this program on TSQM, we combined two groups of patients from Montenegro and B&H and compared their results with those from patients in Serbia. Statistical analysis includes multivariable linear regression analysis in order to assess the differences between three MS patients groups in terms of the TSQM scores, adjusted for potential confounders. For the evaluation of the effects of Betaplus® program, multivariable logistic regression was used, controlling for the same confounding factors. Results Each of the TSQM summary scores in all three countries implicated high level of patients' satisfaction. There was statistically significant group difference on the Effectiveness summary score (p=0.001) and the Side effects summary score (p=0.006) between the group of subjects from Serbia and the combined group of subjects from Montenegro and B&H, in favor of the former cohort. There was statistically significant group difference neither on the Convenience summary score nor on the Overall satisfaction summary score. Results of adjusted logistic regression analysis based on the availability of patient support program (dependent variable) implicate that it had the most significant impact on the Effectiveness summary score (p=0.008). According to the correlation coefficients in the total patient cohort, all TSMQ summary scores except Effectiveness significantly correlated with the decreased adherence (Side effects: p=0.037; Convenience: p=0.016; Overall satisfaction: p=0.046). Conclusion TS with IFN beta-1b was high in our MS patients. Additionally, these results have demonstrated that patient support program have significant impact on TS with IFN beta-1b in the Balkan cohort of RRMS patients. © 2016
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    The Rao’s Brief Repeatable Battery in the study of cognition in different multiple sclerosis phenotypes: application of normative data in a Serbian population
    (2016)
    Dackovic, Jelena (19034069600)
    ;
    Pekmezovic, Tatjana (7003989932)
    ;
    Mesaros, Sarlota (7004307592)
    ;
    Dujmovic, Irena (6701590899)
    ;
    Stojsavljevic, Nebojsa (6603086728)
    ;
    Martinovic, Vanja (56925159700)
    ;
    Drulovic, Jelena (55886929900)
    Cognitive impairment is prevalent in multiple sclerosis (MS) occurring in 43–72 % of patients with all MS phenotypes. The aim of our study was to assess cognitive performance in different MS subtypes in Serbian population. Rao’s Brief Repeatable Battery of neuropsychological tests (BRB-N) was administered to 168 MS patients [37 patients with clinically isolated syndrome (CIS) suggestive of MS, 65 with relapsing-remitting MS (RRMS), 31 with secondary progressive MS (SPMS) and 35 patients with primary progressive MS (PPMS)]. The percentage of cognitively impaired patients in our total MS cohort was 58.9 %. Prevalence of cognitive dysfunction was 40.5 % in CIS group, 36.9 % in RRMS, 96.8 % in SPMS, and 85.7 % in PPMS group. Patients in CIS and RRMS groups performed consistently better all tests of the Rao’s battery than patients in SPMS and PPMS cohort. CIS and RRMS groups performed consistently better in all tests of the Rao’s battery than SPMS and PPMS cohort. Additionally, difference in the performance of any of the BRB-N tests was not found between CIS and RRMS. However, there was a significant difference between SPMS and PPMS patients in the performance on five tests of Rao’s battery. Statistical significance (p < 0.05) in favor of PPMS patients was demonstrated for the following tasks: SRT_lts, SRT_cltr, SDMT, SRT_D, SPART_D. Our study demonstrates that cognitive impairment is frequent in all MS phenotypes. Furthermore, we have found that cognitive deficit is most severe and most frequent in SPMS patients, followed by PPMS subjects and then CIS and RRMS patients. © 2016, Springer-Verlag Italia.
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    Validity and reliability of the Serbian version of Patient-Reported Impact of Spasticity Measure in multiple sclerosis
    (2015)
    Knezevic, Tatjana (25121459700)
    ;
    Konstantinovic, Ljubica (16207335300)
    ;
    Rodic, Sindi (56241921400)
    ;
    Foti, Calogero (7006569923)
    ;
    Drulovic, Jelena (55886929900)
    ;
    Dackovic, Jelena (19034069600)
    ;
    Nikolic, Dejan (26023650800)
    ;
    Petronic, Ivana (25121756800)
    ;
    Stokic, Dobrivoje S. (7005398132)
    The Patient-Reported Impact of Spasticity Measure (PRISM) has been developed recently to assess the impact of spasticity on quality of life after spinal cord injury. Although PRISM may also be useful in patients with multiple sclerosis (MS), its psychometric properties in MS have not been established and PRISM is currently available only in English. The aims of this cross-sectional study were to translate PRISM into the Serbian language (PRISM SR) and examine its validity (construct, convergent, divergent) and reliability (internal consistency, test-retest reliability) in 48 patients with spasticity because of MS diagnosed at least 1 year earlier and in remission at least 3 months. PRISM SR was administered twice 3 days apart. The validity of seven PRISM SR subscales was examined against the Modified Ashworth Scale (MAS), the Numerical Rating Scale (NRS) for spasticity, sex, and education. Internal consistency was assessed with Cronbach α and test-retest reliability with intraclass correlation coefficient for agreement (ICC 2,1). During the forward-backward translation, only one PRISM item required minor cultural adaption. Almost all PRISM SR scores correlated significantly with MAS and NRS scores (r=0.29-0.51, 0.001≤P≤0.043). They were all significantly higher for MAS≥2 group versus the MAS<2 group (0.003≤P≤0.035) and for the NRS≥7 group versus the NRS<7 group (0.001≤P≤0.042), except for the Social Embarrassment subscale (P=0.083). The PRISM SR scores were not significantly different between sexes (P≥0.104) or those with high school versus college degree (P≥0.139). Both Cronbach α (0.78-0.93) and test-retest ICC 2,1 (0.82-0.90) were high. The original PRISM may be translated successfully into other languages. PRISM SR shows adequate validity and reliability for assessing the impact of spasticity on quality of life in patients with MS. © 2015 Wolters Kluwer Health, Inc.
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    Validity and reliability of the Serbian version of Patient-Reported Impact of Spasticity Measure in multiple sclerosis
    (2015)
    Knezevic, Tatjana (25121459700)
    ;
    Konstantinovic, Ljubica (16207335300)
    ;
    Rodic, Sindi (56241921400)
    ;
    Foti, Calogero (7006569923)
    ;
    Drulovic, Jelena (55886929900)
    ;
    Dackovic, Jelena (19034069600)
    ;
    Nikolic, Dejan (26023650800)
    ;
    Petronic, Ivana (25121756800)
    ;
    Stokic, Dobrivoje S. (7005398132)
    The Patient-Reported Impact of Spasticity Measure (PRISM) has been developed recently to assess the impact of spasticity on quality of life after spinal cord injury. Although PRISM may also be useful in patients with multiple sclerosis (MS), its psychometric properties in MS have not been established and PRISM is currently available only in English. The aims of this cross-sectional study were to translate PRISM into the Serbian language (PRISM SR) and examine its validity (construct, convergent, divergent) and reliability (internal consistency, test-retest reliability) in 48 patients with spasticity because of MS diagnosed at least 1 year earlier and in remission at least 3 months. PRISM SR was administered twice 3 days apart. The validity of seven PRISM SR subscales was examined against the Modified Ashworth Scale (MAS), the Numerical Rating Scale (NRS) for spasticity, sex, and education. Internal consistency was assessed with Cronbach α and test-retest reliability with intraclass correlation coefficient for agreement (ICC 2,1). During the forward-backward translation, only one PRISM item required minor cultural adaption. Almost all PRISM SR scores correlated significantly with MAS and NRS scores (r=0.29-0.51, 0.001≤P≤0.043). They were all significantly higher for MAS≥2 group versus the MAS<2 group (0.003≤P≤0.035) and for the NRS≥7 group versus the NRS<7 group (0.001≤P≤0.042), except for the Social Embarrassment subscale (P=0.083). The PRISM SR scores were not significantly different between sexes (P≥0.104) or those with high school versus college degree (P≥0.139). Both Cronbach α (0.78-0.93) and test-retest ICC 2,1 (0.82-0.90) were high. The original PRISM may be translated successfully into other languages. PRISM SR shows adequate validity and reliability for assessing the impact of spasticity on quality of life in patients with MS. © 2015 Wolters Kluwer Health, Inc.

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