Plasma exchange in neurology patients-experience from single center in Montenegro.

INTRODUCTION: Plasma exchange (PE) is widely used in many immune-based neurological diseases. Our aim is to analyze characteristics of PE in neurological patients at the Clinical Center of Montenegro. METHODS: Our study involved neurological patients treated with PE between January 2020 and April 2022. RESULTS: In total, 246 PEs were performed in 43 patients. We divided patients into 4 groups according to indications. In 8/9 multiple sclerosis (MS) patients a decrease of Expanded Dysability Status Scale at least 0.5 was verified. In 14/20 Guillain Barre syndrome patients reduction of Hughes was observed. Four patients with myasthenia gravis (MG) were treated with PE. The most heterogeneous group (4) consisted of patients in whom the mechanism of disease development is assumed to be immune system dysregulation. Fourteen patients had any adverse event. CONCLUSION: Our results show that PE is widely used and safe in the treatment of neurological diseases.

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.

Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers.

BACKGROUND: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). OBJECTIVES: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). METHODS: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. RESULTS: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. CONCLUSION: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.

Retinal microvascular complexity as a putative biomarker of biological age: a pilot study.

Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older "biological age" compared to their "chronological age". Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer's dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl's, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl's analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.

Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers.

Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4 years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1-2 new lesions) or moderate (1 relapse, 3-4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine.

Inflammation-Related microRNAs-146a and -155 Are Upregulated in Mild Cognitive Impairment Subjects Among Older Age Population in Montenegro.

BACKGROUND: Pathological and clinical features of Alzheimer's disease (AD) are in temporal discrepancy and currently accepted clinical tests provide the diagnosis decades after the initial pathophysiological events. In order to enable a more timely detection of AD, research efforts are directed to identification of biomarkers of the early symptomatic stage. Neuroinflammatory signaling pathways and inflammation-related microRNAs (miRNAs) could possibly have a crucial role in AD, making them promising potential biomarkers. OBJECTIVE: We examined the expression of circulatory miRNAs with a documented role in AD pathophysiology: miR-29a/b, miR-101, miR-125b, miR-146a, and miR-155 in the plasma of AD patients (AD, n = 12), people with mild cognitive impairment (MCI, n = 9), and normocognitive group (CTRL, n = 18). We hypothesized that these miRNA expression levels could correlate with the level of participants' cognitive decline. METHODS: The study participants completed the standardized interview, neurological examination, neuropsychological assessment, and biochemical analyses. miRNA expression levels were assessed by RT-PCR. RESULTS: Neurological and laboratory findings could not account for MCI, but miR-146a and -155 were upregulated in the MCI group compared to the control. miR-146a, known to mediate early neuroinflammatory AD events, was also upregulated in the MCI compared to AD group. ROC curve analysis for miRNA-146a showed 77.8% sensitivity and 94.4% specificity and 66.7% sensitivity and 88.9% specificity for miR-155. CONCLUSION: Determination of circulatory inflamma-miRs-146a and -155 expression, together with neuropsychological screening, could become a non-invasive tool for detecting individuals with an increased risk for AD, but research on a larger cohort is warranted.

Screening of dysphagia in relapsing-remitting multiple sclerosis patients in Montenegro.

OBJECTIVES: To perform screening of dysphagia in Montenegrin multiple sclerosis (MS) patients. Dysphagia is often neglected problem in patients with MS. METHODS: We included 104 patients with relapsing-remitting MS who completed 3 questionnaires: dysphagia in multiple sclerosis (DYMUS), eating assessment tool-10 (EAT-10) and swallowing disturbance questionnaire (SDQ). Our study was performed in the clinic for neurology of the Clinical Center of Montenegro (Podgorica, Montenegro) and Polyclinic Neuron (Bijelo Polje, Montenegro) between November 2020 and December 2020. RESULTS: Self-reported prevalence of this symptom in our group was simmilar to previously reported results. We did not find correlation between DYMUS and expanded disability status scale (EDSS), as it was reported before. Time spent from disease onset to diagnosis is strongly correlated with reported SDQ results. The population of dysphagia-patients is statistically significantly older compared to the non-dysphagia patients, and statistically higher mean values in this population of our subjects were proven on all 3 questionnaires used. CONCLUSION: The importance of this issue is not just because it warns of potientially malnutrion in MS patients, but also important factor in therapy choosing algorithm in the era of orally used immunomodulatory drugs.

Reorganization of multiple sclerosis health care system in Clinical Centre of Montenegro during the COVID-19 pandemic.

The COVID-19 epidemic has brought a number of changes to health systems, including the provision of health services to patients with multiple sclerosis (MS). Work in the Clinic for Neurology of the Clinical Center of Montenegro (CN-CCM) with MS patients continued as much as possible during the epidemic. The administration of the already started disease-modifying therapy (DMT) continued, and the introduction of the new one was postponed until the moment when the epidemic started to slow down. During the epidemic period, plasmapheresis treatment was performed in CN-CCM without any complications. New ways of communications (special e-mail address and phone line) with MS patients during epidemic were realized. During epidemic, smaller number of relapses were reported compared to same period in 2019. There were not MS patients in Montenegro suffering from SARS-Cov2 virus infection.

Attitudes of patients with relapsing-remitting form of multiple sclerosis using disease-modifying drugs in Montenegro regarding COVID-19 pandemic.

BACKGROUND: In the days of the reorganization of healthcare systems due to SARS-Cov2 pandemic, patients suffering from chronic diseases are being often neglected. The aim of our study was to examine the attitudes and behaviors of patient suffering from relapsing-remitting form of multiple sclerosis using disease-modifying drugs in Montenegro in relation to the current pandemic. METHODS: The research was conducted through an online-generated questionnaire during the peak of the pandemic. RESULTS: There is a high level of concern about COVID-19 (3.22±1.23), especially about safety behavior intensification (3.80±1.29). Possibility of relapse during pandemic was considered as moderate (2.06±1.42), but relapse symptoms would be reported by the majority of subjects (1.55±1.23). Our unemployed patients statistically more often reported that they had more frequent mood changes, but also that they felt more energy loss. Surprisingly, there was no difference among the subjects according to smoking status. According therapy groups there was significant difference between the groups regarding some variables: patients using ocrelizumab are most concerned about COVID-19; patients using interferon beta 1a i.m. statistically more often have frequent changes in their mood, memory problems, poor appetite, feeling of nausea or upset stomach and patients on fingolimod have bigger afraid of coming to regular visits. CONCLUSION: Our patients showed concern about their disease future status in the current epidemic era, but also showed a high degree of trust in physicians and the overall health system.

Health-related quality of life in adolescents with epilepsy in Montenegro.

OBJECTIVE: The objective of this study was to establish potential risk factors for poor health-related quality of life among adolescents with epilepsy in Montenegro. MATERIAL AND METHODS: A sample of 104 adolescents with epilepsy (age: 11-19years) at a tertiary referral center in Podgorica, Montenegro, completed the validated Serbian version of the QOLIE-AD-48 questionnaire. They were divided into two groups: a group with active epilepsy (60 adolescents) and a group with inactive epilepsy (44 adolescents). Demographic and clinical data were collected. RESULTS: Adolescents with active epilepsy had low quality of life and felt the negative impact of the disease. They also had more cognitive impairments, felt more stigmatized, and had considerably more distorted perception of their health than adolescents with inactive epilepsy (p<0.05). Females reported better social support than males (p<0.05). Older males had lower grades at school (p<0.05) than the younger ones. As expected, adolescents with the highest number of seizures in the past two years had the lowest quality of life (p<0.05). CONCLUSION: In our study, the quality of life in adolescents with epilepsy was determined by severity of the disease, age, and gender.

Psychiatric comorbidities among patients with epilepsy in Montenegro.

The aim of this study was to evaluate the prevalence of psychiatric comorbidities, depression and anxiety, among patients with epilepsy in the outpatient Clinic for Epilepsy, Clinical Centre of Montenegro. Patients aged 18 and above with a diagnosis of epilepsy for at least one year were consecutively enrolled during a six-month period. Patients anonymously filled out a questionnaire which included data on the gender, age, education, marital status and degree of seizure control. The Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Rating Scale (HAM-A) were used to evaluate the presence or absence of anxiety and depression. Total number of study patients was 70, including 52 patients with partial seizures and 18 patients with generalized tonic-clonic seizures. The mean patient age was 37 ± 7.92 years. The prevalence of depression in our sample was 32.8%, whereas the prevalence of anxiety was 21.4%. Patients with partial seizures were more depressed, while those with idiopathic generalized seizures were more anxious (p < 0.01). Depression was associated with a lower educational level, unemployment and poor seizure control (p < 0.05). The number of antiepileptic drugs showed a trend towards negative association with depression (p = 0.005). Anxiety was associated with the level of education and uncontrolled seizures (p < 0.01). Neither depression nor anxiety was associated with age, gender, marital status, age at onset and duration of epilepsy. Psychiatric disorders among patients with epilepsy are quite common but yet under-recognized. Therefore, appropriate recognition and efficient treatment of these disorders in patients with epilepsy might improve their quality of life and could consequently lead to better treatment success.

[Disulfiram-induced polyneurophaty].

INTRODUCTION: Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms produced after ethanol intake. Although it is well tolerated in most patients, one in 15,000 patients will develop peripheral neuropathy every year, which is frequently misdiagnosed as alcoholic neuropathy. CASE REPORT: We report clinical, laboratory, electrophysiological and histopathological features in a 19-year-old patient who developed an acute distal sensorymotor neuropathy during the treatment of alcoholism. At the end of 4-month treatment with disulfiram 250 mg/day, the patient complained of weakness in distal segments of the lower limbs associated with burning dysesthesias, numbness and pain in the soles of the feet and the legs below the knees; reduction in foot strength, the absence of ankle jerk tendon reflexes, and tactile stocking pin-pick and vibratory sensory impairment in the lower limbs below the knee. Recovery was successful after treatment cessation. CONCLUSION: The significance of toxic neuropathy is shown by the fact that the recognition of clinical picture, identifying etiological factors and its elimination may prevent the evolution of polyneuropathy. This allows for more effective treatment of these neuropathies as apposite to idiopathic ones which can be treated only symptomatically. Our case report indicates the possibilities during a period with no serious damage to the axons manifested.