Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.

This study investigated the diagnostic accuracy of plasma biomarkers-specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer's disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E (APOE) ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 (p < 0.001) and TIMP-1 (p < 0.001). Notably, plasma TIMP-1 levels were significantly lower in APOE ε4+ patients than in APOE ε4- patients (p = 0.041). Furthermore, APOE ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD.

Study of monomelic amyotrophy of the lower limbs in the territory of the Western Balkans: Case series.

RATIONALE: Monomelic amyotrophy is a rare form of motor neuron disease in which the neurogenic atrophy is restricted to 1 limb, mostly the distal part of the arm. The disease most often occurs in Asia, especially in Japan and India, while in European countries, this disease is rarely recognized. Registration and publication of new cases of this disease aims to increase the awareness of clinicians about the existence of this disease in European countries, and with the aim of easier recognition and faster diagnosis of this essentially benign disorder. PATIENT CONCERNS: Five patients with signs of atrophy of the muscles of 1 leg were examined at our Institution. DIAGNOSES: The criteria for selecting patients were as follows: clinical evidence of wasting and weakness confined to the 1 lower limb; progressive course, or initial progression followed by stationary course; absence of any definite sensory loss or central nervous system involved; no evidence of compression lesion of the spinal cord. INTERVENTIONS: The clinical characteristics of our patients were similar to those previously described in the literature. The characteristic clinical features were sporadic occurrence, predominance in males with an initially progressive course for 2 to 5 years followed by a stationary state. There was no family history of neuromuscular disease. OUTCOMES: The electromyographic finding was consistent with a chronic neuropathic disorder. Magnetic resonance imaging of the lumbosacral spine excluded intraspinal pathologies and root compression in all cases. LESSONS SUBSECTION: Monomelic amyotrophy of the lower limb is a rare disease that should be considered in cases of slow progressive unilateral amyotrophy of a single leg, especially in younger and middle-aged men, not only in Asia but also in the Western Balkans and Europe.

Values of Nitric Oxide and Superoxide Dismutase in Cerebrospinal Fluid of Patients with Sporadic Amyotrophic Lateral Sclerosis.

Introduction: Neurons are highly energy-dependent and highly specialized cells, showing great sensitivity to oxidative stress (OS). Nitric oxide (NO) and its oxidation products play a central role in neurodegeneration. This study aimed to contribute to the further elucidation of the role of OS in the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods: We assessed NO and superoxide dismutase (SOD) levels in cerebrospinal fluid (CSF) of 24 sporadic ALS (sALS) patients (13 of them presented with spinal form while 11 patients had bulbar form) and 20 controls (CG). Results: The obtained SOD levels in sALS patients were lower than those in CG (p < 0.001), while NO showed higher levels compared to CG (p < 0.001). Observed separately, there were no significant differences in the levels of NO and SOD in CSF between patients about their clinical presentations (p > 0.05). There were significant negative correlations between SOD and NO levels in all sALS patients (r = 0.31, P = 0.025). Significant correlation between SOD and functional rating scale as well as disease progression index was recorded in patients with sALS (r = 0.618. r = 0.425, P < 0.01), while NO levels were significantly associated with disease progression only (r = 0.348, P < 0.01). Conclusion: The data presented clearly support the role of impaired oxidant/antioxidant balance in the pathogenesis of ALS, where NO overproduction and decreased SOD defense activity seem to be particularly involved. The CSF SOD and NO level might serve as useful biomarkers for functional disorder and progression of the disease.

The role of magnetic resonance imaging in the diagnosis and prognosis of dementia.

Dementia is a syndrome characterized by multidomain acquired chronic cognitive impairment that has a profound impact on daily life. Neurogenerative diseases such as Alzheimer's disease or nondegenerative diseases such as vascular dementia are considered to cause dementia. The need for further diagnostic improvement originates from the prevalence of these conditions, especially in developed countries with a predominance of the elderly population. Today, the diagnosis and follow-up of all neurodegenerative diseases cannot be performed without radiological imaging, primarily magnetic resonance imaging (MRI). The introduction of 3T MRI and its modern techniques, such as arterial spin labeling, has enabled better visualization of morphologic changes in dementia. For better diagnosis and follow-up in patients with dementia, various semiquantitative scales have been designed to improve the accuracy of assessment and decrease interobserver variability. Moreover, there is a growing need for MRI in the assessment of novel therapies and their side effects. To better apply MRI findings in the diagnosis of both already developed dementia and its early stages, the aim of this paper is to review the available literature and summarize the specific MRI changes.

Impact of Sensorineural Hearing Loss during the Pandemic of COVID-19 on the Appearance of Depressive Symptoms, Anxiety and Stress.

BACKGROUND: The incidence of hearing loss is constantly increasing and according to the World Health Organization, by 2050, 900 million people will suffer from hearing loss. The main Objective of the study was to determine the differences between the severity of the symptoms of stress, anxiety and depression in participants with varying degrees of sensorineural hearing loss during the COVID-19 pandemic. An additional aim was to examine the extent and manner in which protective face masks impact the communication of people with hearing loss. Matrials and Methods: A cross-sectional study was conducted, which included 160 patients (81 men and 79 women) with bilateral sensorineural hearing loss. The patients' age range was 50 to 80 years. Depending on the degree of hearing loss or pure-tone threshold, the participants were divided into four groups: mild hearing loss, moderate hearing loss, severe hearing loss and profound hearing loss. The research used the Depression, Anxiety and Stress Scale (DASS-21) and a questionnaire in which the participants reported whether surgical face masks (medical three-layer masks) worn by speakers makes communication difficult, to what extent and in what way. RESULTS: The average age of the patients was 67.97 ± 8.16. A significant correlation was found between the degree of hearing loss and communication difficulties caused by the use of protective face masks (p < 0.001). For patients with severe and profound hearing loss, communication is significantly more difficult (50.0% and 45.0% respectively) when the interlocutor wears a face mask. There is a significant correlation between the degree of hearing loss and the way in which communication is made more difficult when the interlocutor wears a face mask (p < 0.001). A statistically significant difference was determined between the degrees of hearing loss in all measured subscales: stress (p = 0.024), anxiety (p = 0.026) and depression (p = 0.016). CONCLUSIONS: We have determined that face masks used during the COVID-19 pandemic significantly hamper communication among the study groups (p = 0.007) and there is a significant correlation between the degree of sensorineural hearing loss and the presence of symptoms in all three DASS-21 subscales, meaning that the symptoms of stress, anxiety and depression were more intense in severe and profound hearing loss.

Importance of a functional measure in the evaluation of patients in a memory clinic: Validation of the Serbian version of the Amsterdam instrumental activities of daily living questionnaire.

INTRODUCTION AND AIM: The Amsterdam instrumental activities of daily living questionnaire (A-IADL-Q) was developed as a sensitive tool in detecting a functional decline in early dementia. The aim of our study was to analyze the validity and reliability of the Serbian translation of the short version of A-IADL-Q in a population of memory clinic patients. MATERIAL AND METHODS: We have included 160 subjects with Alzhemier's disease (AD) dementia, mild cognitive impairment (MCI), or normal cognition (NC). All patients were examined by a neurologist, screened for cognitive impairment (MMSE) and depression, and referred to laboratory testing, neuroimaging examination, and neuropsychological assessment. Informants (close friends or relatives) completed Serbian language versions of the A-IADL-Q -Short version and the Lawton-Brody Instrumental Activities of Daily Living (LB-IADL) scale. Reliability analysis was performed by assessing internal consistency and reproducibility (test-retest reliability). Construct validity was assessed as the impact of gender, аgе, education, diagnosis, cognitive and functional measures on A-IADL-Q scores. RESULTS: The internal consistency of the Serbian version of A-IADL-Q was acceptable (Cronbach's alpha 0.82), Test-retest reliability of the A-IADL-Q was excellent (ICC=0.92, 95% CI 0.84-0.98, p < 0.001). There was no statistically significant difference in A-IADL-Q scores between male and female subjects (t = 1.183; p = 0.241), while the difference was registered between subjects with different education levels (F=12.955; p < 0.001) and diagnosis (F=209.433; p < 0.001). There was a strong and statistically significant correlation between A-IADL-Q and MMSE scores (tau-b= 0.638; p < 0.001) and IADL-Q and LB-ADL scores (tau-b=0.714; p < 0.001). A significant multiple regression model was found (F(4, 155) = 103.692;p < 0.001), which explained 72.1% of the A-IADL-Q score variance with MMSE score and age as significant predictors. CONCLUSION: The Serbian adaptation of the A-IADL-Q-short version is a reliable and valid measure of instrumental activities of daily living in patients with dementia and mild cognitive impairment. This easy-to-administer instrument is useful for the early diagnostics of dementia syndrome in a memory clinic population.

Quality of sleep and fatigue in patients with the relapsing-remitting multiple sclerosis during the coronavirus disease-2019 pandemic.

ОBJECTIVE: Sleep disturbances and fatigue are frequent symptoms in multiple sclerosis patients. The aim was to assess the quality of sleep (QoS) and fatigue in patients with the relapsing-remitting multiple sclerosis (RRMS), during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: The study included 67 patients with RRMS and 85 healthy control subjects. RRMS patients, who were tested in first half of 2019, were retested in April and May 2020, during the COVID-19 pandemic. We collected sociodemographic and clinical data, and also used the following questionnaires: Pittsburgh sleep quality index (PSQI), Fatigue Severity Scale (FSS), and Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54). RESULTS: The FSS score and PSQI global score were significantly higher in patients with RRMS than in the control group (p < 0.01). We noticed a statistically significant difference between the results obtained a year ago and the results during the COVID-19 pandemic in PSQI global score (p < 0.01) and all subscores. Higher disability status was an independent predictor of the worse PSQI scores. CONCLUSION: During the COVID-19 outbreak worse QoS were noticed in RRMS patients than in healthy individuals. Also, QoS of RRMS patients is more affected during the COVID-19 pandemic than in regular circumstances. High levels of sleep disturbance and fatigue in RRMS patients correlates with worse life quality, female gender, lower educational level and partner status. The results of the present study provide evidence in support of regular screening and monitoring of fatigue and QoS in this patient population, especially during the pandemic states.

Quality of sleep and health-related quality of life among health care professionals treating patients with coronavirus disease-19.

BACKGROUND: Health care professionals exposed to coronavirus disease 2019 (COVID-19) are facing high levels of stress. AIM: The aim was to evaluate the quality of sleep (QoS) and health-related quality of life (HRQoL), among health care professionals treating patients with COVID-19, as well as quantifying the magnitude of symptoms of depression and levels of anxiety. METHODS: We included 201 health care professionals in a cross-sectional, web-based study by applying 7-item Generalized Anxiety Disorder (GAD-7) Scale, Zung Self-rating Depression Scale, 36-item Health Survey of the Medical Outcomes Study Short Form (SF36), Pittsburgh Sleep Quality Index (PSQI) and additional survey constructed for the purpose of the study. RESULTS: Health care workers who treated COVID-19 patients were more afraid of becoming infected or of transmitting the infection to a family member with a significantly low self-assessment of their mental status. Poor QoS and HRQoL correlated with high health anxiety and severe depressive symptoms and several demographic characteristics. Multiple linear regression analysis showed that higher scores on GAD-7 (beta = .71, p < .01) and lower scores on mental health (MH) subscale on SF36 questionnaire (beta = -.69; p < .01) were independent predictors of the higher PSQI score (adjusted R2 = .61, p < .01 for overall model). Higher scores on GAD-7 (beta = .68, p < .01) and worse self-perceived mental status (beta = .25; p < .05) were independent predictors of the lower SF36 scores (adjusted R2 = .73, p < .01 for overall model). CONCLUSION: The major MH burden of health care professionals treating infected patients during the COVID-19 pandemic indicates that they need psychological support.

The Impact of the Coronavirus Disease-2019 Pandemic on the Psychological Status and Quality of Life of Myasthenia Gravis Patients.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) is the largest pandemic of our times. We wanted to investigate the impact of COVID-19 pandemic on the psychological status, quality of life (QoL) and quality of sleep (QoS) of myasthenia gravis (MG) patients. METHODS: Data on the epidemiological and clinical characteristics of MG were collected. We used a self-designed questionnaire (consisting of 12 questions), a revised 15-item Myasthenia Gravis Quality of Life Questionnaire (MGQOL15r), a 36-item health survey of the Medical Outcomes Study Short Form (SF36), Pittsburgh sleep quality index (PSQI), Hamilton scales for the assessment of anxiety (HAM-A), and depression (HAMD) were used. We reassessed patients who were tested three years ago using the same questionnaires. RESULTS: The study included 64 MG patients. We noticed a statistically significant difference between the results obtained three years ago and the results from April 2020 in PSQI scores (P < 0.01). MGQOL15r, SF36, and PSQI scores correlate with severe clinical manifestation, high scores on HAM-A and HAM-D (P < 0.01). Higher scores on HAM-D and fear that MG symptoms will be worse if the patient gets an upper respiratory infection were independent predictors of the lower SF36 scores. Regarding MGQOL15r-independent predictors of the higher score were higher scores on HAM-D. CONCLUSIONS: There is a significant impact of the COVID-19 epidemic on the psychological status and especially on the quality of sleep of MG patients. Healthcare organizations need to provide professional therapeutic advice and psychosocial support for this population of patients during the pandemic.

Psychological status of patients with relapsing-remitting multiple sclerosis during coronavirus disease-2019 outbreak.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a global health emergency. The aim was to investigate the impact of COVID-19 pandemic on the psychological status of patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Data on the socio-demographic and clinical characteristics of 95 RRMS patients were collected. We used a self-designed questionnaire, the Multiple Sclerosis Quality of Life-54 Instrument (MSQOL-54), Hamilton scales for the assessment of anxiety (HAM-A), and depression (HAM-D). Patients who were tested one year ago were reassessed using the same questionnaires during the COVID-19 outbreak. Group of 99 healthy individuals (HC) were tested, using the same questionnaires. RESULTS: The main concerns in RRMS patients were that someone that they know could be infected with COVID-19 (78.5%), or could die due to the infection (33.8%), and the lack of specific treatment options (25.8%). The main concerns about the RRMS status were that their disease would be worse if they get infected with COVID-19 (36.4%), that they would experience some difficulties in drug availability (43.6%), that they could not go to the hospital as usual (72.4%). Results on all questionnaires were worse in RRMS patients than in HC (p<0.01). We noticed a statistically significant difference between the results obtained a year ago and the results from April 2020 in HAM-A (p<0.05). CONCLUSIONS: There is an impact of the COVID-19 pandemic on the psychological status of RRMS patients. Healthcare organizations need to provide professional therapeutic advice and psychosocial support for this population of patients during the pandemic.

The influence of diversity on the measurement of functional impairment: An international validation of the Amsterdam IADL Questionnaire in eight countries.

INTRODUCTION: To understand the potential influence of diversity on the measurement of functional impairment in dementia, we aimed to investigate possible bias caused by age, gender, education, and cultural differences. METHODS: A total of 3571 individuals (67.1 ± 9.5 years old, 44.7% female) from The Netherlands, Spain, France, United States, United Kingdom, Greece, Serbia, and Finland were included. Functional impairment was measured using the Amsterdam Instrumental Activities of Daily Living (IADL) Questionnaire. Item bias was assessed using differential item functioning (DIF) analysis. RESULTS: There were some differences in activity endorsement. A few items showed statistically significant DIF. However, there was no evidence of meaningful item bias: Effect sizes were low (ΔR 2 range 0-0.03). Impact on total scores was minimal. DISCUSSION: The results imply a limited bias for age, gender, education, and culture in the measurement of functional impairment. This study provides an important step in recognizing the potential influence of diversity on primary outcomes in dementia research.

Quality of Life of Myasthenia Gravis Patients in Regard to Epidemiological and Clinical Characteristics of the Disease.

BACKGROUND: Myasthenia gravis (MG) affects overall quality of life (QoL). The aim of the research was to evaluate QoL in patients suffering from MG in regard to epidemiological and clinical factors of the disease. METHODS: The study included 70 patients. The severity of clinical manifestation was estimated using quantitative MG score and MG composite score. Patients were classified by using Myasthenia Gravis Foundation of America Classification. The Questionnaire of Life Quality Specific for Myasthenia Gravis-15 items (MGQOL15) is developed for QoL assessment in patients suffering from MG. In addition to the MGQOL15 revised version (MGQOL15r), a 36-item health survey of the Medical Outcomes Study Short Form (SF36) questionnaire, the Hamilton scales for the assessment of anxiety (HAM-A), and depression (HAM-D) were also used. RESULTS: MGQOL15r scores are negatively correlated with SF36 scores and positively correlated with scores on HAM-A and HAM-D scales (P<0.001). Patients with longer disease duration and severe clinical manifestation often manifest anxiety, depression, and have poorer QoL (P<0.05). In relation to the presence of the anti-nAchR antibody, statistically significant differences were found in relation to the summed scores on scales for assessing QoL, as well as on a HAM-A scale (P<0.05). Physical workers and unemployed patients had worse scores in relation to retired and administrators/intellectual workers on all scales (P<0.001). CONCLUSION: MGQOL15r is a life quality assessment questionnaire that could be used in routine practice in patients with MG. It is much simpler for use in these patients than SF36 and provides relevant data.

The association of CAT-262C/T polymorphism with catalase activity and treatment response in juvenile idiopathic arthritis.

Oxidative stress is believed to be of great importance for both the etiology and the persistence of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the association of -262C/T polymorphism of the catalase (CAT) gene with JIA, as well as to evaluate whether this polymorphism can influence plasma CAT activity and outcome in JIA patients treated with etanercept. A total of 154 subjects (60 JIA patients and 94 healthy volunteers) were screened for CAT-262C/T gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma CAT activity was determined using the spectrophotometric method according to Goth, prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA ACR (American College of Rheumatology) response criteria. The genotype and allele frequency distributions of CAT-262C/T polymorphism in the patients were significantly different from those of the controls (p = 0.014, p = 0.006). The TT genotype (polymorphic homozygous) was associated with a 4.36-fold higher likelihood of having JIA (95% CI 1.545-12.323, p = 0.005) as compared to the CC genotype (wild-type). At month 12 of treatment, JIA patients, carriers of the CC genotype, showed significantly higher plasma CAT activity (p = 0.004) and achieved the JIA ACR 70 response more often (p = 0.003) than the patients, carriers of the CT/TT genotype. This is the first study implying the possible association of CAT-262C/T polymorphism with JIA. The results suggest the potential protective effect of the CC genotype, with regard to CAT activity and treatment outcome.

Vitamin D receptor gene polymorphism influences lipid profile in patients with juvenile idiopathic arthritis.

Vitamin D receptor (VDR) gene FokI (rs2228570) polymorphism was postulated to influence outcome of several inflammatory diseases. The aim of this study was to evaluate the influence of rs2228570 polymorphism on lipid profile and on outcome in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. A total of 153 subjects (62 JIA patients and 91 controls) were screened for the rs2228570 using the PCR-RFLP method. Lipid profile (cholesterol, triacylglycerol, HDL-C, and LDL-C) was determined using standard biochemical analysis in controls, while in JIA patients, it was determined prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA-American College of Rheumatology (ACR) response criteria. There were significant differences in the distribution of genotypes (p = 0.024) and alleles (p = 0.006; OR = 2.222, 95% CI 1.136-4.348) of the rs2228570 between patients and controls. Etanercept treatment significantly increased HDL-C levels (p = 0.006) in JIA patients with FF genotype in comparison to baseline values. No significant differences were seen in JIA-ACR 30/50/70 responses at month 12 between FF and Ff/ff genotype carriers. This is the first study to demonstrate the protective effect of the VDR FokI FF genotype on lipid profile in JIA patients treated with etanercept. However, this has to be confirmed in a larger cohort of patients.

Slower EEG alpha generation, synchronization and "flow"-possible biomarkers of cognitive impairment and neuropathology of minor stroke.

BACKGROUND: We investigated EEG rhythms, particularly alpha activity, and their relationship to post-stroke neuropathology and cognitive functions in the subacute and chronic stages of minor strokes. METHODS: We included 10 patients with right middle cerebral artery (MCA) ischemic strokes and 11 healthy controls. All the assessments of stroke patients were done both in the subacute and chronic stages. Neurological impairment was measured using the National Institute of Health Stroke Scale (NIHSS), whereas cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) and MoCA memory index (MoCA-MIS). The EEG was recorded using a 19 channel EEG system with standard EEG electrode placement. In particular, we analyzed the EEGs derived from the four lateral frontal (F3, F7, F4, F8), and corresponding lateral posterior (P3, P4, T5, T6) electrodes. Quantitative EEG analysis included: the group FFT spectra, the weighted average of alpha frequency (αAVG), the group probability density distributions of all conventional EEG frequency band relative amplitudes (EEG microstructure), the inter- and intra-hemispheric coherences, and the topographic distribution of alpha carrier frequency phase potentials (PPs). Statistical analysis was done using a Kruskal-Wallis ANOVA with a post-hoc Mann-Whitney U two-tailed test, and Spearman's correlation. RESULTS: We demonstrated transient cognitive impairment alongside a slower alpha frequency (αAVG) in the subacute right MCA stroke patients vs. the controls. This slower alpha frequency showed no amplitude change, but was highly synchronized intra-hemispherically, overlying the ipsi-lesional hemisphere, and inter-hemispherically, overlying the frontal cortex. In addition, the disturbances in EEG alpha activity in subacute stroke patients were expressed as a decrease in alpha PPs over the frontal cortex and an altered "alpha flow", indicating the sustained augmentation of inter-hemispheric interactions. Although the stroke induced slower alpha was a transient phenomenon, the increased alpha intra-hemispheric synchronization, overlying the ipsi-lesional hemisphere, the increased alpha F3-F4 inter-hemispheric synchronization, the delayed alpha waves, and the newly established inter-hemispheric "alpha flow" within the frontal cortex, remained as a permanent consequence of the minor stroke. This newly established frontal inter-hemispheric "alpha flow" represented a permanent consequence of the "hidden" stroke neuropathology, despite the fact that cognitive impairment has been returned to the control values. All the detected permanent changes at the EEG level with no cognitive impairment after a minor stroke could be a way for the brain to compensate for the lesion and restore the lost function. DISCUSSION: Our study indicates slower EEG alpha generation, synchronization and "flow" as potential biomarkers of cognitive impairment onset and/or compensatory post-stroke re-organizational processes.

Identification of clinical and paraclinical findings predictive for headache occurrence during spontaneous subarachnoid hemorrhage.

OBJECTIVES: Headache is recognized as the main but unwarranted symptom of subarachnoid hemorrhage (SAH). There are no enough findings identified as predictive for headache occurrence in SAH. We evaluated the clinical and paraclinical factors predictive for headache occurrence in SAH. PATIENTS AND METHODS: We retrospectively analyzed medical records of 431 consecutive non traumatic SAH patients (264 females and 167 males), ages from 19 to 91 years, presenting with headache (70.3%) and without headache (29.7%) during period of 11years. RESULTS: Among all tested parameters, as negative predictors for headache occurrence were recognized: patients' ages (OR 0.97 [95%CI: 0.96-0.99], p=0.025), persistence of coagulation abnormality (OR 0.23 [95%CI: 0.08-0.67], p=0.006), atrial fibrilation (OR 0.23 [95%CI: 0.09-0.59], p=0.002), chronic renal failure (OR 0.26 [95%CI: 0.09-0.76], p=0.014) and more diseases (OR 0.11 [95%CI: 0.04-0.32], p<0.0001), as higher clinical score (OR 0.94 [95%CI: 0.90-0.99], p=0.018) including positive neurological findings (OR 0.34 [95%CI: 0.21-0.55], p<0.001) and loss of consciousness (OR 0.22 [95%CI: 0.12-0.39], p<0.001) at the SAH onset, while the complaint of neck stiffness was identified as its positive predictor (OR 1.93 [95%CI: 1.19-3.10], p=0.007). CONCLUSIONS: Although diagnosis based solely on clinical presentation is not reliable and speculative, our findings could provide physicians with evidence to consider SAH not only in conditions of its headache occurrence but also in those with headache absence.

Post-stroke dementia - a comprehensive review.

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.

Clinical and epidemiological features of Guillain-Barré syndrome in the Western Balkans.

The aim of this study was to define features of Guillain-Barré syndrome in a large cohort of patients from three Western Balkans countries. Data from adult Guillain-Barré syndrome (GBS) cases from 2009 to 2013 were retrospectively obtained from all tertiary health care centers. During the 5-year period, 327 new cases of GBS were identified with a male to female ratio of 1.7 : 1. The most common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of patients were chair-bound, confined to bed, or required assisted ventilation, while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per 100,000 population, and age-adjusted incidence according to the world standard population was 0.86 per 100,000. Incidence was particularly high in 50- to 80-year-old men. Statistically significant seasonal variations of GBS were not observed. This study of patients with GBS in the Western Balkans allows us to prepare the health system better and to improve the management of patients. This study also opens opportunities for international collaboration and for taking part in the multinational studies on GBS.

Hospitalizations due to spontaneous intracerebral hemorrhage in the region of Nis (Serbia): 11-year time-series analysis.

BACKGROUND: The study of seasonal variability of intracerebral hemorrhage (ICH) occurrence may contribute to a better understanding of the nature of this disease and open up new perspectives in its prevention. The aim of this study was to test seasonal patterns in the number of admissions of ICH patients and determine which months have maximal and minimal number of admissions. METHODS: The main data source for this study was a hospital-based registry at the Clinic of Neurology in Nis, Serbia. During the studied period (1997-2007) a total of 1569 ICH patients were registered. Time series, consisting of the monthly number of hospitalized patients, for the 128 months of the study duration, has been successfully modeled using the multiplicative Auto Regressive Integrated Moving Average (ARIMA) model. RESULTS: Using the maximum likelihood method, utilizing Melrad's algorithm, the parameters of this ARIMA model have been calculated: constant (estimate 12.068, p<0.001), auto regressive-AR(1) (estimate 0.866, p<0.001), moving average-MA(1) (estimate 0.775, p<0.001), seasonal moving average-SMA(12) (estimate -0.198, p=0.036). ARIMA modeling has been successful and showed that there is a clear seasonal pattern in the data analyzed. CONCLUSION: Based on the seasonal multiplicative ARIMA model and the seasonal time series decomposition, we showed that, in the period covered by the study, the peak of admissions occurred in March, and the trough of admissions was found in August.