Potential beneficial effect of IFN-ß1a and ocrelizumab in people with MS during the COVID-19 pandemic.

BACKGROUND/AIM: Disease-modifying therapy (DMT) has led to added challenges in the management of people with multiple sclerosis (pwMS) during the COVID-19 era. It can reduce relapse in MS or slow down disease progression, but some DMTs can increased risk of infection. The aim of study was to evaluate risk and severity of COVID-19 in pwMS. METHODS: The examined group of pwMS were divided in group treated with IFN-ß1a, group treated with ocrelizumab and untreated group. The examination included impact of age, gender, duration of MS, type of MS, vaccination status and Expanded Disability Status Scale (EDSS) on the risk and severity of COVID-19 infection. A diagnosis of COVID-19 in pwMS was confirmed by positive polymerase-chain-reaction (PCR) or antigen test. RESULTS: Out of 207 pwMS, 82 patients were treated with ocrelizumab, 63 with IFN-ß1a, while 62 patients were untreated pwMS. The average duration of the MS was longer in the group of patients treated with ocrelizumab than in the group treated with IFN-ß1a (p < 0.05). EDSS was higher in the ocrelizumab group compared to the other two groups (p < 0.001). Untreated (more often unvaccinated) had the same COVID frequency as ocrelizumab-treated (more vaccinated, but higher EDSS). The multivariate logistic regression model indicated that administration of IFN-ß1a reduces the risk of COVID-19 infection (p = 0.001, OR = 0.381, 95% CI 0.602-0.160). The use of both DMTs, driven mainly by the IFN-ß1a effect, reduces the risk of moderate and severe COVID-19 (p < 0.05, OR = 0.105, 95% CI 0.011-0.968). CONCLUSION: This study provides evidence that IFN-ß1a can reduce the frequency of COVID-19 infection and that two DMTs, driven mainly by the IFN-ß1a effect, do not increase the risk of moderate/severe COVID-19.

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.

The first case of combined oxidative phosphorylation deficiency-1 due to a GFM1 mutation in the Serbian population: a case report and literature review.

BACKGROUND: Combined oxidative phosphorylation deficiency-1 (COXPD1) resulting from a mutation in the G elongation factor mitochondrial 1 (GFM1) gene is an autosomal recessive multisystem disorder arising from a defect in the mitochondrial oxidative phosphorylation system. Death usually appears in the first weeks or years of lifespan. CASE: We report a male patient with ventriculomegaly diagnosed in the 8th month of pregnancy. The delivery was done by caesarean section and respiratory failure occurred immediately after birth. Hypoglycemia, lactic acidosis, elevated gamma-glutamyl transferase and hepatomegaly were confirmed. The brain MRI detected hypoplasia of the cerebellar hemispheres, dilated lateral ventricles, and markedly immature brain parenchyma. Epilepsy had been present since the third month. At 5 months of age, neurological follow-up showed his head circumference to be 37 cm, with plagiocephaly, a low hairline, a short neck, axial hypotonia and he did not adopt any developmental milestones. A genetic mutation, a missense variant in the GFM1 gene, was confirmed: c.748C > T (p.Arg250Trp) was homozygous in the GFM1 gene. CONCLUSIONS: To the best of our knowledge, 28 cases of COXPD1 disease caused by mutations in the GFM1 gene have been described in the literature. COXPD1 should be considered due to symptoms and signs which begin during intrauterine life or at birth. Signs of impaired energy metabolism should indicate that the disease is in the group of metabolic encephalopathies.

VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

Potential drug-drug interactions among patients with spontaneous intracerebral hemorrhage treated at the Neurological Intensive Care Unit: a single-center experience

Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.

Risk factors for potential drug-drug interactions in patients with myasthenia gravis.

OBJECTIVES: Our aim was to determine risk factors for and frequency of potential drug-drug interactions (pDDIs) among hospitalized patients with myasthenia gravis (MG). METHODS: This was a retrospective cross-sectional study of the-first time hospitalized MG patients or patients hospitalized because of the exacerbation of MG at the Neurology Clinic of the Clinical Center of Serbia, Belgrade. Medical records and discharge summaries of hospitalized MG patients over a 10-year period were reviewed. The pDDIs were identified by means of Micromedex, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. RESULTS: The study included 687 patients with MG. In total, 2041 pDDIs were detected in 608 (88.5%) patients. Among the discovered pDDIs, 329 different pDDIs were observed. The most frequent pDDIs were pyridostigmine-prednisone (487patients/70.9%) and aspirin-prednisone (90 patients/13.1%) classified as moderate, and enalapril-potassium chloride (71patients/10.3%) classified as major pDDI. Five drugs (aspirin, insulin, prednisone, cyclosporine, metformin) were responsible for 22.6% of different pDDIs. Dyspnea, generalized form of MG, diabetes mellitus, hypertension, total number of drugs-used, use of antiplatelets were identified as the relevant risk factors for total number of pDDIs (R2 = 0.626,F = 73.797, p < 0.001), while age of patients and history of cancer were inversely correlated with such an outcome. CONCLUSION: The frequency of the pDDIs in hospitalized MG patients is high, and adversely influenced by dyspnea, generalized MG, diabetes mellitus, hypertension, total number of drugs-used and use of antiplatelets.

Prospective analysis of disability and quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

PURPOSE: Even treated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) continues to pose a significant burden in patients' everyday functioning and may continuously affect their quality of life (QoL). The aims of our prospective study were to analyze health-related QoL in CIDP patients during a 1-year follow-up period in real-life settings and to compare QoL changes with changes in disability and with patient impression of change. METHODS: The study comprised 59 patients diagnosed with CIDP. SF-36 questionnaire was applied in order to evaluate patients' QoL. Inflammatory neuropathy cause and treatment (INCAT) disability scale was used to assess patients' functionality. The second question from the SF-36 questionnaire was used as an estimation of the patient impression of change (PIC) after 1 year. RESULTS: SF-36 scores did not change over time in the group as a whole. According to INCAT disability scores, worsening was registered in 24 (40%) patients and improvement in 8 (14%). Fifteen (25%) patients reported worsening and the same number reported improvement, according to PIC. Concordant results on INCAT and PIC were registered in 49% of patients. Pooled SF-36 scores moderately correlated with pooled INCAT disability scores (rho = - 0.27 to - 0.59, p < 0.01). One-year changes of SF-36 scores did not differ when compared to different INCAT outcomes (worsening, stable, improvement). On the other hand, significant changes of SF-36 scores in different outcome groups according to PIC (worsening, stable, improvement) were noted (p < 0.01). CONCLUSION: INCAT, PIC, and SF-36 are complementary outcome measures that provide neurologists with useful items of information. We propose complementary use of these scales in CIDP patients in everyday clinical practice in order to detect worsening of the disease and/or of related symptoms on time.

Depression and Fatigue in Patients With Multiple Sclerosis Have No Influence on the Parameters of Cognitive Evoked Potentials.

PURPOSE: The purpose of this study was to examine if depression and fatigue affect event-related brain potentials (ERPs) in patients with relapsing-remitting multiple sclerosis, and to assess the significance of ERP as an indicator of cognitive impairment. METHODS: A total of 81 relapsing-remitting multiple sclerosis patients and 32 healthy control subjects participated in the study. Cognitive functions were evaluated using a standard PASAT, the symbol digit modality test, and ERP. The degrees of depressive symptomatology and fatigue were assessed with Beck Depression Inventory, the Fatigue Severity Scale, and the Fatigue Impact Scale. RESULTS: Fatigue and depression had a negative effect on the cognitive functions examined by neuropsychological tests. Depression and fatigue did not influence ERP amplitude and latency findings. Depression level was negatively correlated with symbol digit modality test score (r = -0.135, P < 0.05). Fatigue level was negatively correlated with the results for PASAT A (r = -0.225, P < 0.05) and PASAT B (r = -0.342, P < 0.01). Reaction time was positively associated with depression (r = 0.246, P = 0.01) and fatigue (r = 0.281, P = 0.01). CONCLUSIONS: Depression and fatigue have no effect on ERP amplitude and latency, so they cannot participate in risk assessment for the development of cognitive impairment in patients with relapsing-remitting multiple sclerosis.

Recurrent Painful Ophthalmoplegic Neuropathy: Migraine, Neuralgia, or Something Else?

Recurrent painful ophthalmoplegic neuropathy (RPON) is a very rare disease characterized by recurrent attacks (at least two) of unilateral headache associated with ipsilateral ophthalmoplegia due to paresis of one or more cranial motor nerves, not due to any orbital, parasellar, or posterior fossa lesions. The differential diagnoses for this condition are broad. In addition to disability during an acute attack, this disease could also cause a permanent neurologic deficit. The understanding of RPON pathogenesis has changed over time, leading to a change in the classification of this disorder between editions of the International Classification of Headache Disorders, in which the condition was moved from the chapter on migraine to the chapter on cranial neuralgias and central causes of facial pain. There is no consensus on the pathogenesis of RPON. It is possible that multiple pathogenic mechanisms underlie various clinical forms of the disease. A depiction of pathologic analyses of patients with radiologically confirmed changes in the affected nerves during and outside of attacks would significantly contribute to knowledge of its pathogenesis. Brain imaging should be performed in each patient during an acute RPON attack and at a regular schedule between attacks. Further case reports and case series are required before further conclusions can be made regarding RPON pathogenesis and proposals for treatment options.

Potential Drug-drug Interactions in Acute Ischemic Stroke Patients at the Neurological Intensive Care Unit.

BACKGROUND: Clinically relevant potential drug-drug interactions are considered preventable adverse drug reactions. OBJECTIVE: The aim of this study was to ascertain the frequency of potential drug-drug interactions in acute ischemic stroke patients and to explore factors associated with occurrence of potentially contraindicated drug-drug interactions. METHODS: This observational retrospective cohort and nested case-control study was carried out among patients treated for acute ischemic stroke at the Neurological Intensive Care Unit in the Clinical Centre Kragujevac, Serbia. The potentially drug-drug interactions for each day of hospitalization were identifi ed using Micromedex® soft ware. Based on the existence or absence of potentially contraindicated drug-drug interactions, the participants were divided into a group of cases (n=111) and the control group (n=444). RESULTS: A total of 696 patients were analysed. All patients had a minimum of one potential drug-drug interaction during hospitalization. The most common drugs involved in potential drug-drug interactions were aspirin (8.02%), diclofenac (7.49%) and warfarin (7.14%). The number of medications prescribed for simultaneous use during hospitalisation and the use of antipsychotics in therapy signifi cantly increased the likelihood of potentially contraindicated drug-drug interactions aft er adjustment by means of logistic regression for 1.2 and 3 times, respectively. CONCLUSIONS: This study suggests that patients with acute ischemic stroke are frequently exposed to potential drug-drug interactions. It is essential to identify potentially drug-drug interactions in these patients as early as possible in order to prevent adverse drug reactions and ensure safe recovery. Besides, full attention should be paid when adding each new medication in therapy, particularly when a neurologist decides to prescribe antipsychotics, such as risperidone.

Suffering from Cerebral Small Vessel Disease with and without Metabolic Syndrome.

BACKGROUND: Cerebral small vessel disease (CSVD) and metabolic syndrome were separately associated with cognitive impairment and depression. However, whether metabolic syndrome adds to cognitive impairment and depression in patients who already have CSVD remained unanswered. OBJECTIVE: The aim of our study was to investigate the association of metabolic syndrome with cognitive impairment and depression in patients with CSVD who have lacunar lesions or white matter hyperintensities. METHODS: This prospective cohort study was conducted at Neurology Clinic, Clinical Center, Kragujevac, Serbia. Main outcomes of the study were cognitive assessment, and assessment of depression among hospitalized patients with or without CSVD. RESULTS: The study included 74 inpatients, 25 of them having lacunary infarctions, 24 with the white matter hyperintensities, and 25 control patients without CSVD. The CSVD was accompanied by impairment of cognition and depression, the patients with lacunary lesions being more cognitively impaired and more depressive than the patients with the white matter hyperintensities. The patients with CSVD who also had metabolic syndrome were more cognitively impaired and depressed than the patients with CSVD alone. CONCLUSIONS: In conclusion, our study showed that metabolic syndrome is associated with further worsening of already impaired cognition and existing depression in patients with CSVD.

Checking the potential shift to perceived usefulness-The analysis of users' response to the updated electronic health record core features.

OBJECTIVE: The primary objective of this paper is to identify the main factors which have an impact on the users' attitude towards the functionalities representing the perceived ease of use and to those representing the perceived usefulness. Another objective is to examine whether there occurred a shift towards the perceived usefulness of users' behavior over a period of time. To support these objectives, two different cases are examined - the case in which users are simultaneously offered basic and updated functionalities, and the one in which users are offered a completely new set of features. The results of this study are expected to exert a significant impact on a further development of new software components, as well as the updates of the existing ones. MATERIAL AND METHODS: As the starting point, there were employed the user behavior indicators defined in similar researches and conducted in the countries with a similar cultural background or with a comparatively similar national healthcare system. What ensued was an updated set of functionalities offered within the electronic health record based medical information system. Instead of the survey being posted, the effects of implanted updates were measured through the analysis of the collected data. The data collected in the Nis Primary and Ambulatory Care Center during a four-year period represented the material used in the research. The obtained records indicating the usage of the initial and updated visit registration form, as well as the usage of the new types of visits, were examined in relation to the technology acceptance model and integrated behavior model. RESULTS: The response to the initial functionalities, perceived as easy to use, was high as expected since they kept the users in their "comfort zone". As regards the updated features, the ones corresponding to the perceived usefulness, the initial overall acceptance rate was 60%, while the overall increase of their acceptance was around 20%. The overall usage of the newly introduced features was doubled in some cases throughout the four-year period, while some of them were not accepted as expected. DISCUSSION: Carefully designed additional functionalities, aimed to improve the most common daily activities, have a significant potential to be accepted by the medical professionals. The shift from the perceived ease of use to the perceived usefulness is not uniform, nor is its use in different departments or by the users of the same department. A higher acceptance rate was observed in the departments with more complex administrative procedures, as well as among the users having contacts with more patients and using the system for a longer period. CONCLUSION: When accepting new features, medical professionals will initially choose the simpler ones with obvious benefits. If the usage of a feature triggers indirect benefits, the number of examined patients is of a crucial importance for the acceptance of that feature. In the event of the advanced functionality with an extended set of options competing with the simple functionality covering basic requirements, the latter will be used. A feature design, together with a proper training, system stability and ensuring utilization, represent a key point for increasing the positive impact that the information system can have in many application areas, including the healthcare.

Data summarization method for chronic disease tracking.

OBJECTIVES: Bearing in mind the rising prevalence of chronic medical conditions, the chronic disease management is one of the key features required by medical information systems used in primary healthcare. Our research group paid a particular attention to this specific area by offering a set of custom data collection forms and reports in order to improve medical professionals' daily routine. The main idea was to provide an overview of history for chronic diseases, which, as it seems, had not been properly supported in previous administrative workflows. After five years of active use of medical information systems in more than 25 primary healthcare institutions, we were able to identify several scenarios that were often end-user-action dependent and could result in the data related to chronic diagnoses being loosely connected. An additional benefit would be a more effective identification of potentially new patients suffering from chronic diseases. METHODS: For this particular reason, we introduced an extension of the existing data structures and a summarizing method along with a specific tool that should help in connecting all the data related to a patient and a diagnosis. The summarization method was based on the principle of connecting all of the records pertaining to a specific diagnosis for the selected patient, and it was envisaged to work in both automatic and on-demand mode. The expected results were a more effective identification of new potential patients and a completion of the existing histories of diseases associated with chronic diagnoses. RESULTS: The current system usage analysis shows that a small number of doctors used functionalities specially designed for chronic diseases affecting less than 6% of the total population (around 11,500 out of more than 200,000 patients). In initial tests, the on-demand data summarization mode was applied in general practice and 89 out of 155 users identified more than 3000 new patients with a chronic disease over a three-month test period. During the tests, more than 100,000 medical documents were paired up with the existing histories of diseases. Furthermore, a significant number of physicians that accepted the standard history of disease helped with the identification of the additional 22% of the population. Applying the automatic summarization would help identify all patients with at least one record related to the diagnosis usually marked as chronic, but ultimately, this data had to be filtered and medical professionals should have the final say. Depending on the data filter definition, the total percentage of newly discovered patients with a chronic disease is between 35% and 53%, as expected. CONCLUSIONS: Although the medical practitioner should have the final say about any medical record changes, new, innovative methods which can help in the data summarization are welcome. In addition to being focused on the summarization in relation to the patient, or to the diagnosis, this proposed method and tool can be effectively used when the patient-diagnosis relation is not one-to-one but many-to-many. The proposed summarization principles were tested on a single type of the medical information system, but can easily be applied to other medical software packages, too. Depending on the existing data structure of the target system, as well as identified use cases, it is possible to extend the data and customize the proposed summarization method.