Earlier age of symptom onset in younger generation of familial cases of multiple sclerosis.

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.

Transcranial Sonography Characteristics of Cerebellar Neurodegenerative Ataxias.

Cerebellar neurodegenerative ataxias are a group of disorders affecting the cerebellum and its pathways with different neurological structures. Transcranial sonography (TCS) has been used for the evaluation of brain parenchymal structures in various diseases because of its fast and safe utilization, especially in neuropsychiatric and neurodegenerative diseases. The aim of our study was to investigate TCS characteristics of patients with neurodegenerative cerebellar ataxias. In our study, we included 74 patients with cerebellar degenerative ataxia; 36.5% had autosomal dominant onset, while 33.8% had sporadic onset. Standardized ultrasonographic planes were used for the identification of brain structures of interest. The SARA, INAS, neuropsychological and psychiatric scales were used for the further clinical evaluation of our study participants. The brainstem raphe was discontinued in 33.8% of the patients. The substantia nigra (SN) hyperechogenicity was identified in 79.7%. The third and fourth ventricle enlargement had 79.7% and 45.9% of patients, respectively. A positive and statistically significant correlation was found between SN hyperechogenicity with dystonia (p < 0.01), rigidity and dyskinesia (p < 0.05). The higher SARA total score is statistically significantly correlated with the larger diameter of the III (r = 0.373; p = 0.001) and IV ventricles (r = 0.324; p = 0.005). In such patients, the echogenicity of substantia nigra has been linked to extrapyramidal signs, and raphe discontinuity to depression. Furthermore, ataxia and its clinical subtypes have positively correlated with the IV ventricle diameter, indicating brain atrophy and brain mass reduction.

ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.

BACKGROUND: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). METHODS: Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. RESULTS: Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. CONCLUSIONS: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Exclusive breastfeeding may be a protective factor in individuals with familial multiple sclerosis. A population registry-based case-control study.

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.

The impact of the comorbid seizure/epilepsy on the health related quality of life in people with multiple sclerosis: an international multicentric study.

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.

Impact of the autonomic dysfunction on the quality of life in people with NMOSD and MS: An international cross-sectional study.

BACKGROUND: A substantial autonomic nervous system (ANS) dysfunction has been described in multiple sclerosis (MS) and recently, also in neuromyelitis optica spectrum disorder (NMOSD). The prevalence of ANS symptoms contributes to the chronic symptom burden in both diseases. The aim of our study was to assess ANS dysfunction in people with (pw) NMOSD and MS, using the Composite Autonomic Symptom Score-31 (COMPASS-31), and additionally, to evaluate if ANS dysfunction have impact on the quality of life of these patients. METHODS: We conducted cross-sectional study at three national referral neurological clinics in Serbia, Croatia, and Montenegro. A total of 180 consecutive subjects, 80 pwNMOSD and 100 pwMS, followed-up at these clinics, were enrolled in the study. Subjects included in the study completed: the validated versions of the COMPASS-31 and the Multiple Sclerosis Quality of Life-54 (MSQoL-54), and the Beck Depression Inventory (BDI). RESULTS: This study demonstrated that the total COMPASS-31 score > 0.0, implicating the presence of ANS dysfunction, was detected in almost all NMOSD and MS study participants tested (80/80, and 97/100, respectively). Our findings showed that autonomic symptom burden was statistically significantly correlated with decreased quality of life, in both NMOSD and MS cohorts. The independent predictors of the better quality of life in pwNMOSD were lower autonomic burden, particularly the absence of the orthostatic intolerance (p = 0.005), along with lower EDSS and BDI score (p ≤ 0.001). Similarly, in pwMS, independent predictors were EDSS, BDI, orthostatic intolerance, and the total COMPASS-31 (p ≤ 0.001). CONCLUSION: Our study demonstrated that a significant proportion of persons with both NMOSD and MS have considerable dysautonomic symptom burden which is correlated with the decreased quality of life. Further investigations are warranted in order to optimize treatment interventions in MS and NMOSD.

The Impact of Demographic and Clinical Factors on the Quality of Life in Patients with Neurodegenerative Cerebellar Ataxias.

In neurodegenerative cerebellar ataxias, not only ataxia but also extra-cerebellar signs have a significant impact on patients' health related to quality of life (HRQoL). The aim of this study was to evaluate the various aspects of HRQoL and predictors of QoL in patients with neurodegenerative cerebellar ataxias. We included a total of 107 patients with cerebellar degenerative ataxia. Patients filled out the validated Serbian version of the SF-36 used for the assessment of HRQoL. All patients were clinically evaluated using SARA, INAS, and neuropsychological tests to assess their global cognitive status and different psychiatric scales. The most frequent types of neurodegenerative cerebellar ataxias were autosomal dominant ataxias (38.3%) and sporadic ataxias (32.7%). Mean age at diagnosis was 35.3 ± 16.23 years, and disease duration was on average 12.1 ± 9.91 years. Mean total SF-36 score was 50.63 ± 20.50. Hierarchical regression analysis showed that in the case of the PHC score, the most significant predictors are the patient's actual age, severity of ataxia, and ACE total score. For MHC, the Hamilton depression score was the most important predictor. Our study has shown that HRQoL measured by SF-36 in patients with neurodegenerative cerebellar disorders is strongly influenced by impaired mobility and depression.

Transverse myelitis following COVID-19: Insights from a multi-center study and systematic literature review.

INTRODUCTION: We aimed to provide insights into transverse myelitis (TM) following COVID-19 by analyzing cases treated at tertiary care neurology centers and a systemic review of the literature. METHODS: The retrospective observational multi-center study was conducted at the four university neurology departments in Croatia, Slovenia, Serbia, and Austria. We searched for acute myelitis cases that occurred during or after COVID-19. A systemic review of the literature on COVID-19 and transverse myelitis was performed. RESULTS: We identified 76 persons with TM associated with COVID-19, 13 from the multi-center study and 63 from the literature review. Most of the participants (55.6%) had an intermediate latency, 25.4% had short and 19% long latency from COVID-19 symptoms to TM. The clinical presentation consisted of the typical TM signs. More than half of the participants had inflammatory changes in the CSF, with rare patients having intrathecal OCB synthesis and positive serology for anti-MOG or anti-AQP4 antibodies. Persons with autonomic symptoms and CSF pleocytosis were significantly more common to have an intermediate latency of 8 to 21 days from COVID-19 to TM (p = 0.005 and p = 0.003; respectively). According to logistic regression analysis, only participants with lesions evident on spinal cord MRI compared to normal spinal cord MRI had reduced risks for poor recovery. >80% of participants were treated with a combination of corticosteroids and intravenous immunoglobulins or plasma exchange with 73% having incomplete recovery. CONCLUSION: Our study further characterizes clinical, laboratory, and MRI features, as well as treatment of TM associated with COVID-19.

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia.

Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region.

Occurrence of malignant diseases in patients with multiple sclerosis: population-based MS Registry data.

INTRODUCTION: Among different comorbidities occurring in multiple sclerosis (MS), the presence of malignant diseases in these patients is of the particular importance. The aim of this study was to determine the malignant diseases burden in a whole cohort of patients with MS in the Belgrade region, based on the Belgrade population registry data. MATERIAL AND METHODS: This study comprises 2725 MS patients from the MS Registry, which represents a source for all necessary demographic and clinical data. Firstly, the Registry was searched for all persons with MS who had cancer comorbidity, during the period 1996-2019. Diagnosis of cancer was validated by the patients' medical documentation. In order to investigate factors associated with the occurrence of any type of the cancer and/ or breast cancer only, in persons with MS, different logistic regression analyses were performed. RESULTS: A total of 64 persons with 69 malignant diseases were observed (prevalence 2.53%). The most frequent malignancies in males were skin cancer (50.0%) and in females, breast cancer (23.2%). The cumulative incidence of cancer comorbidity in persons with MS was 324.9 new cases per 100,000 person-years for the total population (137.6/100,000 in males and 403.6 per 100,000 in females). Comparison of cancer incidence rate between MS and general Belgrade population revealed lower risk for malignancy occurrence in the MS population in total (standardized incidence ratio, SIR = 0.58, 95% CI 0.16-1.49). CONCLUSIONS: Our findings demonstrate that MS patients in the Belgrade region have lower risk for the development of malignancy than age- and sex-matched general population.

Cognitive assessment in patients with myotonic dystrophy type 2.

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder. Previous studies conducted on small cohorts of DM2 patients indicated presence of a cognitive dysfunction. We aimed to assess cognitive functions in a larger cohort of Serbian DM2 patients using an extensive battery of neuropsychological tests. The study included 76 patients with a genetically confirmed DM2, 68 of whom had all tests for different cognitive domains performed. Patients underwent clinical and neuropsychological testing, including cognitive screening and assessment of general intellectual level, attention, executive and visuospatial abilities, memory, and language functions. Only 6% of patients achieved a below-average score on the general intellectual level test. Cognitive screening tests indicated presence of cognitive deficits in 5.5% of patients according to the Mini Mental State Examination test and 25.8% according to the Addenbrooke's Cognitive Examination Revised test. Twenty-four (35.3%) patients had a cognitive impairment (being two standard deviations out of norm in at least two cognitive domains). Around one quarter of DM2 patients had a significant cognitive impairment that interfered with their everyday functioning. Patients with significant cognitive impairment were older at testing and at disease onset, less educated, and had more severe muscle weakness.

Humoral response to SARS-CoV-2 infection and vaccines against COVID-19 in patients with neuromyelitis optica spectrum disorders: Impact of immunosuppressive treatment.

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.

COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders.

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.

Impact of comorbidities on the disability progression in multiple sclerosis.

OBJECTIVES: Investigation of the comorbidity burden in persons with multiple sclerosis (PwMS) has become increasingly important. The aim of this study was to investigate the relationships of cardiovascular disease (CVD) comorbidities and type 2 diabetes with the disability progression. MATERIALS & METHODS: The retrospective cohort study was conducted at the Clinic of Neurology, Belgrade. The Belgrade MS population Registry, which comprises 2725 active MS cases, was used as the source of data. The mean duration of the disease was 21.6 ± 12.5 years. Expanded Disability Status Scale (EDSS) was followed in all PwMS in the Registry. In the statistical analysis, the Cox proportional hazard regression analysis and Kaplan-Meier curve were performed. RESULTS: Hypertension statistically significantly contributed to more rapid reaching investigated levels of irreversible disability (EDSS 4.0, 6.0, and 7.0), while the presence of any of the investigated CVD comorbidities and type 2 diabetes significantly contributed to faster reaching EDSS 4.0 and EDSS 6.0. In a multivariable model, progression index (PI) was singled out (HR = 3.171, p < .001), indicating that higher progression index (PI) was an independent predictor of CVD occurrence in MS patients. In the case of type 2 diabetes, PI (p < .001) and MS phenotype (p = .015) were statistically significant in multivariable Cox regression analysis. CONCLUSIONS: Our study confirms the impact of CVD comorbidities and type 2 diabetes in MS on the progression of disability as measured by EDSS in the large cohort of PwMS from the population Registry.

Responsiveness of 2 Different Ability Outcome Measures in Guillain-Barré Syndrome.

BACKGROUND: The most frequently used ability outcome measure in Guillain-Barré syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months. METHODS: Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014). RESULTS: Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS. CONCLUSION: Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.

Social Cognition in Patients With Cerebellar Neurodegenerative Disorders.

OBJECTIVE: Cerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs. MATERIALS AND METHODS: Social cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood. RESULTS: CD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) - recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients' achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT - Delayed free recall predicted their performance on the Faux Pas Recognition Test. CONCLUSION: Patients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language.

Humoral response to SARS-CoV-2 COVID-19 vaccines in patients with multiple sclerosis treated with immune reconstitution therapies.

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.

The prevalence of comorbidities in patients with multiple sclerosis: population-based registry data.

BACKGROUND: Comorbidities occur frequently in persons with multiple sclerosis (MS). The aim of the present study was to determine the prevalence of the most common comorbidities in the population of MS patients in Belgrade, Serbia. MATERIAL AND METHODS: Data on diagnosed and fully documented comorbidities were taken from the Belgrade MS population registry. The list of explored comorbidities included cardiovascular, malignant, and autoimmune diseases; psychiatric disorders; epilepsy; and type 2 diabetes. In the data analysis, crude, age- and gender-specific, and age-adjusted prevalence was calculated. Additionally, comorbidities were analyzed in patients with various MS phenotypes. RESULTS: The most prevalent group of comorbidities were psychiatric (prevalence (Prev) = 20.59%, 95% CI 19.10-22.17) and cardiovascular comorbidities (Prev = 15.23%, 95% CI 13.93-16.63). The most prevalent single comorbidities were depression (Prev = 11.82%, 95% CI 10.64-13.11) and hypertension (Prev = 11.41%, 95% CI 10.25-12.68). Type 2 diabetes was significantly more prevalent in patients with primary progressive MS compared with the patients with relapsing-remitting and secondary progressive MS (p < 0.001). We found statistically significant positive correlation between number of comorbidities and progression index (p < 0.001). Patients treated with disease-modifying therapies (DMTs) had significantly higher risk of developing comorbidity, after treatment initiation, compared with those who were untreated (p = 0.001). CONCLUSIONS: Our study demonstrated high prevalence of comorbidities in persons with MS, with psychiatric and cardiovascular diseases being the most common. Furthermore, our findings confirmed the association of comorbidities with progression of disability and emphasized their role in treatment decision-making in MS.

Self-reported autonomic dysfunction in a recovery phase of Guillain-Barré syndrome.

OBJECTIVE: Autonomic dysfunction occurs in approximately two-thirds of Guillain-Barré syndrome (GBS) patients in the acute phase of the disease. Although improving over time, subclinical autonomic involvement may be present for 3-8 years after the GBS episode. The aim of this study was to determine the frequency of self-reported autonomic disorders in GBS patients three and six months after disease onset compared to healthy controls (HCs). METHODS: Our study included adult patients diagnosed with GBS from May 2017 until May 2018 in seven healthcare centers (67.6 % with demyelinating and 13.6 % with axonal syubtype). Functional disability was assessed by the Guillain-Barré syndrome disability scale (GDS). Each subject filled in the Serbian version of the SCOPA-Aut questionnaire. Using GDS and SCOPA-Aut, patients were tested at month 3 (M3) (n = 71) and month 6 (M6) (n = 70) from symptom onset. RESULTS: Dysautonomia was more common in patients with GBS compared to HCs at M3 (p < 0.01), while there was no difference at M6 (p > 0.05). Among autonomic disorders, constipation, complications to pass stool, and orthostatic hypotension were the most frequently reported. Patients with axonal variants had worse total SCOPA-Aut scores at M3 in comparison to AIDP patients (11.7 ± 10.1 vs. 6.1 ± 5.1, p < 0.05). GDS score correlated with the total SCOPA-Aut score. CONCLUSION: Autonomic symptoms are common in GBS patients during the recovery phase. They are more pronounced in patients with axonal forms of GBS and those with a higher degree of functional disability.

Could the performance of oral glucose tolerance test contribute to the brain health-focused care in multiple sclerosis?

BACKGROUND: It has not been clarified yet if persons with multiple sclerosis (MS) are at increased risk to develop glucose metabolism dysregulation. The aims of the present study were to evaluate glucose metabolism characteristics in persons with MS and to compare it to the healthy individuals; to examine the association of glucose metabolism with the level of disability and its progression. METHODS: The study enrolled 78 patients with MS and 26, comparable for age, gender and body mass index (BMI), healthy controls (HC). Disability and its progression were evaluated by the Expanded Disability Status Scale (EDSS) score, progression index (PI) and multiple sclerosis severity score (MSSS). All participants performed an oral glucose tolerance test (OGTT). Insulin and lipid parameters were analyzed. RESULTS: Fasting glucose concentrations (5.3±0.7 in MS patients vs. 4.5±0.9 mmol/L in HC, p=0.001) and 2 hour post-load glucose concentrations were statistically significantly higher in MS patients compared with controls. Glucose levels at all different time points during OGTT, baseline insulin, Homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol and LDL were statistically significantly (p<0.05) associated with MS, in univariable logistic regression analysis. Glucose level at 120' was independently associated with MS (OR=3.937, 95% CI 1.178-13.159, p=0.026), in the multivariable model. The prevalence of IR was 64.1% in the MS group compared to 30.8% in the control group (p=0.008), based on HOMA-IR. EDSS and Multiple sclerosis severity score (MSSS) were associated with glucose levels at different time points (p<0.05). According to the ROC analysis, best cut-off value for HOMA-IR is 2.3, providing both sensitivity and specificity of 66.7% in discriminating persons with MS and HC. CONCLUSION: Our results demonstrate the presence of higher prevalence of IR in MS patients compared to healthy individuals, and strong association between impaired glucose metabolism and disability. Finally, it has to be emphasized that further studies are warranted to confirm our findings implicating that MS patients have significantly higher risk of impaired glucose metabolism, which could suggest the potential importance of the performance of OGTT in patients with this disorder.