Browsing by Author "Ivanovic, Jovana (57196371316)"

Purpose: Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020. Methods: This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved. Conclusion: Our study in a large cohort of MS patients confirmed that PLEX is effective. © The Author(s) under exclusive licence to Belgian Neurological Society 2024.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Background: Reports on outcomes of COVID-19 in patients with neuromyelitis optica spectrum disorder (NMOSD) are scarce, as well as those related to the safety profile of the vaccines in this population. The aim of this survey is to present demographic and clinical characteristics of patients with NMOSD who developed COVID-19 and safety data of the COVID-19 vaccines in these persons. Methods: This study comprise all patients from the Hospital registry of NMOSD, of the Clinic of Neurology in Belgrade, who fulfilled the 2015 NMOSD diagnostic criteria, and who after invitation by phone call, from April 10 to May 10, 2021, accepted to participate and provide information regarding COVID-19 and vaccination against Sars-CoV-2 (n = 53). Results: Sixteen out of 53 enrolled NMOSD patients were diagnosed with COVID-19. In three cases (18.8%), severity of COVID-19 clinical manifestations warranted hospitalization, and one of these patients, died due to COVID-19 (case fatality ratio = 6.25%), after invasive mechanical ventilation. The remaining two patients had grade II COVID -19 severity and were hospitalized because of pneumonia, not requiring supplemental oxygen. Median EDSS in patients requiring hospitalization was 4.5, and in the non-hospitalized group, it was 3.0. Nine out of 53 patients received two doses of vaccine against Sars-Cov-2 (8 Sinopharm and one Pfizer). Pain at the site of application was the only vaccine-related adverse effect. Conclusions: Our survey indicates overall favourable COVID-19 outcome and encouraging safety profile of the vaccines in persons with NMOSD, in our cohort. Prospective studies are warranted to confirm these data. © 2021 Elsevier B.V.

Background: Reports on outcomes of COVID-19 in patients with neuromyelitis optica spectrum disorder (NMOSD) are scarce, as well as those related to the safety profile of the vaccines in this population. The aim of this survey is to present demographic and clinical characteristics of patients with NMOSD who developed COVID-19 and safety data of the COVID-19 vaccines in these persons. Methods: This study comprise all patients from the Hospital registry of NMOSD, of the Clinic of Neurology in Belgrade, who fulfilled the 2015 NMOSD diagnostic criteria, and who after invitation by phone call, from April 10 to May 10, 2021, accepted to participate and provide information regarding COVID-19 and vaccination against Sars-CoV-2 (n = 53). Results: Sixteen out of 53 enrolled NMOSD patients were diagnosed with COVID-19. In three cases (18.8%), severity of COVID-19 clinical manifestations warranted hospitalization, and one of these patients, died due to COVID-19 (case fatality ratio = 6.25%), after invasive mechanical ventilation. The remaining two patients had grade II COVID -19 severity and were hospitalized because of pneumonia, not requiring supplemental oxygen. Median EDSS in patients requiring hospitalization was 4.5, and in the non-hospitalized group, it was 3.0. Nine out of 53 patients received two doses of vaccine against Sars-Cov-2 (8 Sinopharm and one Pfizer). Pain at the site of application was the only vaccine-related adverse effect. Conclusions: Our survey indicates overall favourable COVID-19 outcome and encouraging safety profile of the vaccines in persons with NMOSD, in our cohort. Prospective studies are warranted to confirm these data. © 2021 Elsevier B.V.

[No abstract available]

Aim: The aim of this study was to assess the prevalence of familial MS (fMS) in Belgrade MS population, discern the differences between the persons with fMS and sporadic MS, and to detect the presence of anticipation phenomenon in fMS patients. Methods: The data on the demographic and clinical characteristics of MS patients was obtained from the Belgrade MS population Registry. In cases of vertical transmission of MS, the family members were divided into the younger and older generation, in order to assess the potential presence of anticipation phenomenon. To adjust for follow-up time bias, a secondary analysis including only patients who had the onset of symptoms before 39 years (75.percentile), and those who were 39 + years, was performed. Results: The prevalence of fMS in Belgrade MS population is 6.4%. FMS cases had earlier age at MS symptom onset (30.4 vs. 32.3 years) compared to sporadic MS cohort. When comparing fMS cases across generations, the younger generation had significantly lower age at onset compared with the older one (25.8 vs. 35.7 years, p < 0.001). After adjustment for the different length of the follow-up, the difference in age at symptom onset between the groups was reduced, but it still existed and was statistically significant (30.0 years in younger vs. 36.4 years in older generation, p = 0.040). Conclusion: In our study, the analysis of fMS cases across generations, showed an earlier age of symptom onset in the younger generation, even after adjustment. These results indicate the possibility of existence of anticipation phenomenon. © Fondazione Società Italiana di Neurologia 2024.

Background: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system, which most likely results from the interplay between environmental and genetic factors. The aim of our study was to assess the effect of breastfeeding on the risk of developing familial multiple sclerosis (fMS) in persons with positive MS history, being the first such investigation performed in fMS cohort. Methods: A case-control study based on the Belgrade population MS Registry was conducted. Cases for the sporadic MS (sMS) control group were randomly selected from the Registry, and matched with individuals with fMS at a ratio of 1:1. Spouses of the persons with fMS were included as a healthy control (HC) group. A specific questionnaire that was previously validated was used to obtain the data. To evaluate risk factors associated with breastfeeding for fMS occurrence compared with sMS and HC, multinomial regression analysis was performed to compute the relative risk ratios (RRR) along with 95% confidence intervals (95% CI). The analysis was afterwards repeated, stratified by sex. Both models were adjusted for potential confounding factors. Results: A total of 393 participants were included in our case-control study, 131 per group. There were more individuals who were exclusively breastfed longer than six months in the sMS group compared to fMS group (RRR 2.01, 95% CI 1.22–3.32). After stratification by sex, exclusive breastfeeding was shown to be a protective factor for fMS only in male population, for individuals breastfed ≥4 months. The results of both the main and stratified analysis remained robust after adjustment. Conclusion: Our study findings indicate that breastfeeding reduces the risk of MS in infants with family history of the disease, although this protective effect may be limited to the male population. Further investigation into the differences in risk factors between fMS and sMS is warranted to gain a more comprehensive understanding of the disease. © 2023

Background: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system, which most likely results from the interplay between environmental and genetic factors. The aim of our study was to assess the effect of breastfeeding on the risk of developing familial multiple sclerosis (fMS) in persons with positive MS history, being the first such investigation performed in fMS cohort. Methods: A case-control study based on the Belgrade population MS Registry was conducted. Cases for the sporadic MS (sMS) control group were randomly selected from the Registry, and matched with individuals with fMS at a ratio of 1:1. Spouses of the persons with fMS were included as a healthy control (HC) group. A specific questionnaire that was previously validated was used to obtain the data. To evaluate risk factors associated with breastfeeding for fMS occurrence compared with sMS and HC, multinomial regression analysis was performed to compute the relative risk ratios (RRR) along with 95% confidence intervals (95% CI). The analysis was afterwards repeated, stratified by sex. Both models were adjusted for potential confounding factors. Results: A total of 393 participants were included in our case-control study, 131 per group. There were more individuals who were exclusively breastfed longer than six months in the sMS group compared to fMS group (RRR 2.01, 95% CI 1.22–3.32). After stratification by sex, exclusive breastfeeding was shown to be a protective factor for fMS only in male population, for individuals breastfed ≥4 months. The results of both the main and stratified analysis remained robust after adjustment. Conclusion: Our study findings indicate that breastfeeding reduces the risk of MS in infants with family history of the disease, although this protective effect may be limited to the male population. Further investigation into the differences in risk factors between fMS and sMS is warranted to gain a more comprehensive understanding of the disease. © 2023

[No abstract available]

Background: It has been generally accepted that people with MS (PwMS) should be vaccinated against COVID-19. The aim of our investigation was to evaluate the humoral response to natural SARS-CoV-2 infection and to two COVID-19 vaccines (BNT162b2 Pfizer-BioNTech and Beijing/Sinopharm BBIBP-CorV) in our cohort of PwMS under high efficacy disease modifying therapies (DMTs), cladribine and alemtuzumab. Methods: Twenty two PwMS treated at the Clinic of Neurology, in Belgrade, who developed COVID-19 and/or were vaccinated against SARS-CoV-2, during treatment with cladribine and alemtuzumab, were included. Out of 18 patients treated with cladribine, 11 developed COVID-19, and 11 were vaccinated against SARS-CoV-2 (four with mRNA vaccine, 7 with Sinopharm). Four MS patients under alemtuzumab were vaccinated against SARS-CoV-2; three with mRNA, and one with Sinopharm vaccine. SARS-Cov-2 IgG response was measured using ELISA anti-spike protein-based serology (INEP, Belgrade, Serbia). Results: All 7 patients under cladribine treatment who suffered from COVID-19, developed IgG antibodies, 2.0-5.5 months after last symptoms. All four (100%) patients under cladribine who were vaccinated with Pfizer-BioNTech vaccine, and three out of seven (42.9%) vaccinated with Sinopharm, developed antibodies. All 4 patients under alemtuzumab developed antibodies after vaccination. In all cases, seroprotection occurred, irrespective of timing of vaccination and absolute lymphocyte count. Conclusion: Our findings in a small number of highly active PwMS in whom, lymphodepleting, immune reconstitution therapies, were applied in order to successfully manage MS, indicate that in a number of these patients it was possible to develop at the same time seroprotection in these patients after COVID-19 vaccination in these complex circumstances. © 2021 The Author(s)

Background: It has been generally accepted that people with MS (PwMS) should be vaccinated against COVID-19. The aim of our investigation was to evaluate the humoral response to natural SARS-CoV-2 infection and to two COVID-19 vaccines (BNT162b2 Pfizer-BioNTech and Beijing/Sinopharm BBIBP-CorV) in our cohort of PwMS under high efficacy disease modifying therapies (DMTs), cladribine and alemtuzumab. Methods: Twenty two PwMS treated at the Clinic of Neurology, in Belgrade, who developed COVID-19 and/or were vaccinated against SARS-CoV-2, during treatment with cladribine and alemtuzumab, were included. Out of 18 patients treated with cladribine, 11 developed COVID-19, and 11 were vaccinated against SARS-CoV-2 (four with mRNA vaccine, 7 with Sinopharm). Four MS patients under alemtuzumab were vaccinated against SARS-CoV-2; three with mRNA, and one with Sinopharm vaccine. SARS-Cov-2 IgG response was measured using ELISA anti-spike protein-based serology (INEP, Belgrade, Serbia). Results: All 7 patients under cladribine treatment who suffered from COVID-19, developed IgG antibodies, 2.0-5.5 months after last symptoms. All four (100%) patients under cladribine who were vaccinated with Pfizer-BioNTech vaccine, and three out of seven (42.9%) vaccinated with Sinopharm, developed antibodies. All 4 patients under alemtuzumab developed antibodies after vaccination. In all cases, seroprotection occurred, irrespective of timing of vaccination and absolute lymphocyte count. Conclusion: Our findings in a small number of highly active PwMS in whom, lymphodepleting, immune reconstitution therapies, were applied in order to successfully manage MS, indicate that in a number of these patients it was possible to develop at the same time seroprotection in these patients after COVID-19 vaccination in these complex circumstances. © 2021 The Author(s)

The aim of this study was to evaluate the humoral response to the SARS-CoV-2 infection and vaccination in the NMOSD patients, treated with various immunosuppresants (ISs). Serum IgG against the complete sequence of the receptor binding domain of the spike protein was measured using ELISA SARS-CoV-2 IgG, INEP, Belgrade. Seroconversion occurred in 8/10 patients with COVID-19, and in 5/9 after vaccination. One out of four patients treated with inebilizumab seroconverted (after COVID-19); antibodies were not detected in any of the remaining 3 patients who were vaccinated. Antibodies developed after COVID-19 in 4/5 patients treated with azathioprine and all treated with mycophenolate-mofetil, and after vaccination, in 5/6 patients treated with these ISs. Post-vaccination humoral response was impaired in our NMOSD patients treated with B-cell depleting therapies; seroconversion occurred in almost all patients treated with conventional synthetic disease modifying ISs. © 2022

The aim of this study was to evaluate the humoral response to the SARS-CoV-2 infection and vaccination in the NMOSD patients, treated with various immunosuppresants (ISs). Serum IgG against the complete sequence of the receptor binding domain of the spike protein was measured using ELISA SARS-CoV-2 IgG, INEP, Belgrade. Seroconversion occurred in 8/10 patients with COVID-19, and in 5/9 after vaccination. One out of four patients treated with inebilizumab seroconverted (after COVID-19); antibodies were not detected in any of the remaining 3 patients who were vaccinated. Antibodies developed after COVID-19 in 4/5 patients treated with azathioprine and all treated with mycophenolate-mofetil, and after vaccination, in 5/6 patients treated with these ISs. Post-vaccination humoral response was impaired in our NMOSD patients treated with B-cell depleting therapies; seroconversion occurred in almost all patients treated with conventional synthetic disease modifying ISs. © 2022

Objective: The aim of this study is to assess the impact of interferon (IFN) beta treatment on the development of worsening disability in relapsing-remitting (RR) multiple sclerosis (MS) patients in the single-center observation cohort. Method: This is a prospective study of 236 IFN-beta-treated and 183 untreated RRMS patients recruited consecutively at the Clinic of Neurology in Belgrade (Serbia). Out of this original cohort, 10-year follow-up data were available for 233 IFN-beta-treated and 131 untreated subjects. The median time since recruitment was 9.7 years. Results: IFN-beta treatment significantly delayed (p < 0.001) the time to reach each of the clinical outcomes (secondary progression-SP, EDSS scores 4 and 6) since recruitment. Time from the first visit to SP was reached after 9.7 years for IFN-beta-treated vs. 7.8 years for untreated patients. The delay for the development of EDSS score ≥ 4 from the first visit was 1.6 years (8.7 years for IFN-beta-treated vs. 7.1 years for untreated patients). Time from the first visit to EDSS score of 6 was reached after 9.8 years for IFN-beta-treated vs. 8.8 years for untreated patients. The IFN-beta-treated group showed significant reduction (p < 0.001) in the risk of conversion to SP when compared with untreated patients (HR = 0.22). There was also a significant difference in reaching EDSS scores 4 and 6 (p < 0.001), in favor of the IFN-beta-treated group (HR = 0.40 and HR = 0.27, respectively). Conclusion: Comparison of outcomes in our IFN-beta-treated vs. untreated RRMS patients suggests that this treatment may delay development of long-term disability in MS. © 2019, Fondazione Società Italiana di Neurologia.

Objective Since astrocytes at the blood-brain barrier are targeted by neuromyelitis optica spectrum disorder (NMOSD), this study aims to assess whether patients with NMOSD have a subclinical accumulation of brain water and if it differs according to disease activity. Methods Seventy-seven aquaporin-4-positive patients with NMOSD and 105 healthy controls were enrolled at two European centres. Brain dual-echo turbo spin-echo MR images were evaluated and maps of T2 relaxation time (T2rt) in the normal-appearing white matter (NAWM), grey matter and basal ganglia were obtained. Patients with a clinical relapse within 1 month before or after MRI acquisition were defined 'active'. Differences between patients and controls were assessed using z-scores of T2rt obtained with age-adjusted and sex-adjusted linear models from each site. A stepwise binary logistic regression was run on clinical and MRI variables to identify independent predictors of disease activity. Results Patients had increased T2rt in both white and grey matter structures (p range: 0.014 to <0.0001). Twenty patients with NMOSD were defined active. Despite similar clinical and MRI features, active patients had a significantly increased T2rt in the NAWM and grey matter compared with those clinically stable (p range: 0.010-0.002). The stepwise binary logistic regression selected the NAWM as independently associated with disease activity (beta=2.06, SE=0.58, Nagelkerke R 2 =0.46, p<0.001). Conclusions In line with the research hypothesis, patients with NMOSD have increased brain T2rt. The magnitude of this alteration might be useful for identifying those patients with active disease. © 2022 BMJ Publishing Group. All rights reserved.

[No abstract available]

Longitudinally extensive transverse myelitis (LETM) is defined as a spinal cord lesion that extends over three or more vertebrae. LETM very rarely occurs in patients with the systemic malignancy. We report a 38-year old woman with adenocarcinoma of the cervix and LETM. Cervical and thoracic spine MRI showed hyperintense signal on T2W involving predominantly central spinal cord from the C4 level distally, including conus medullaris. In this patient corticosteroid therapy and therapeutic plasma exchange (TPE) courses were performed. On discharge, five weeks after TPE initiation, patient could walk with bilateral assistance. After a 16-month follow-up, her neurological finding was almost normal and MRI lesions disappeared. Thus, we present our patient as one of the rare cases of paraneoplastic LETM with excellent treatment response. © 2018

Longitudinally extensive transverse myelitis (LETM) is defined as a spinal cord lesion that extends over three or more vertebrae. LETM very rarely occurs in patients with the systemic malignancy. We report a 38-year old woman with adenocarcinoma of the cervix and LETM. Cervical and thoracic spine MRI showed hyperintense signal on T2W involving predominantly central spinal cord from the C4 level distally, including conus medullaris. In this patient corticosteroid therapy and therapeutic plasma exchange (TPE) courses were performed. On discharge, five weeks after TPE initiation, patient could walk with bilateral assistance. After a 16-month follow-up, her neurological finding was almost normal and MRI lesions disappeared. Thus, we present our patient as one of the rare cases of paraneoplastic LETM with excellent treatment response. © 2018

Introduction: The health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS. Methods: We conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients. Results: The study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy. Discussion: Our results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy. Copyright © 2023 Drulovic, Pekmezovic, Tamas, Adamec, Aleksic, Andabaka, Basic Kes, Butkovic Soldo, Cukic, Despinic, Dincic, Djelilovic Vranic, Grgic, Habek, Hristova, Ivanovic, Jovanovic, Jovicevic, Krbot Skoric, Kuzmanovski, Maric, Mesaros, Milanov, Miletic Drakulic, Sinanovic, Skarpa Prpic, Sremec, Tadic, Toncev and Sokic.