Symbol Digit Modalities Test in progressive multiple sclerosis.

INTRODUCTION: The Symbol Digit Modalities Test (SDMT) is a highly sensitive neuropsychological tool used for the assessment of information processing speed (IPS) in various neurological disorders. STATE OF THE ART: In this review, we have focused on the current knowledge regarding the use of SDMT selectively in the evaluation of progressive multiple sclerosis (PMS) patients. A literature review was performed regarding the application of SDMT in PMS, with a focus on the primary progressive and secondary progressive subtypes. Relationships of diverse disease-associated factors with SDMT have been described, including disease course, imaging findings, molecular biomarkers, treatment and others. CLINICAL IMPLICATIONS: SDMT is a very useful and easily applicable instrument in the diagnostic armamentarium of neurologists and neuropsychologists. It is especially valuable in the evaluation of PMS patients, in whom the prevalence of IPS deficits is higher than in relapsing-remitting multiple sclerosis subjects or in healthy individuals. FUTURE DIRECTIONS: An emphasis should be laid on larger study groups and differentiating between individual PMS subtypes and their separate analysis in the context of cognitive assessment.

Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

Clinical and therapeutic challenges of smouldering multiple sclerosis.

INTRODUCTION: Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process. STATE OF THE ART: Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS. CLINICAL IMPLICATIONS: Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS. FUTURE DIRECTIONS: Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats.

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.

Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats.

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain.

Optical Coherence Tomography in the Differential Diagnosis of Patients with Multiple Sclerosis and Patients with MRI Nonspecific White Matter Lesions.

In the differential diagnosis of nonspecific white matter lesions (NSWMLs) detected on magnetic resonance imaging (MRI), multiple sclerosis (MS) should be taken into consideration. Optical coherence tomography (OCT) is a promising tool applied in the differential diagnostic process of MS. We tested whether OCT may be useful in distinguishing between MS and NSWMLs patients. In patients with MS (n = 41) and NSWMLs (n = 19), the following OCT parameters were measured: thickness of the peripapillary Retinal Nerve Fibre Layer (pRNFL) in superior, inferior, nasal, and temporal segments; thickness of the ganglion cell-inner plexiform layer (GCIPL); thickness of macular RNFL (mRNFL); and macular volume (MV). In MS patients, GCIPL was significantly lower than in NSWMLs patients (p = 0.024). Additionally, in MS patients, mRNFL was significantly lower than in NSWMLs patients (p = 0.030). The average segmental pRNFL and MV did not differ between MS and NSWMLs patients (p > 0.05). GCIPL and macular RNFL thinning significantly influenced the risk of MS (18.6% [95% CI 2.7%, 25.3%]; 27.4% [95% CI 4.5%, 62.3%]), and reduced GCIPL thickness appeared to be the best predictor of MS. We conclude that OCT may be helpful in the differential diagnosis of MS and NSWMLs patients in real-world settings.

Cognitive Dysfunction in the Early Stages of Multiple Sclerosis-How Much and How Important?

PURPOSE OF REVIEW: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that mainly affects young adults and that is one of the leading causes of disability in this age group, with cognitive impairment occurring early in the course of the disease. This article summarizes the current knowledge about cognitive dysfunction in the early phase of MS, including biomarkers, MRI correlates, and its value as a prognostic marker. RECENT FINDINGS: New sets of neuropsychological tests have been established to screen for cognitive dysfunction more easily and accurately. Moreover, structural changes detected by brain MRI and several biomarkers found in cerebrospinal fluid and blood serum have been recently correlated with decreased cognitive performance. Additionally, factors influencing cognition in MS, such as disease-modifying therapy, mood disorders, and lifestyle, are better described. Cognitive impairment early in the course of MS is suggested as a prognostic factor for disease progression. However, clear-cut definitions of the early stage of MS as well as unified criteria for the diagnosis of cognitive impairment are still lacking. New and more reliable tools for evaluating cognition in MS patients should be developed and introduced into everyday practice to facilitate the implementation of effective disease-modifying therapy, cognitive rehabilitation, and lifestyle management.

Differences of the Structure of Immune Regulatory Cell Populations between Cellular Material from Sonographically Detected Focal Thyroid Lesions and Peripheral Blood in Humans.

Focal thyroid lesions are common ultrasound findings with the estimated prevalence up to 67% of the population. They form characteristically enveloped regions with individual encapsulated microenvironment that may involve the specific distribution of immune system compounds-especially antigen presenting cells (APC). We analyzed and compared the most potent APC-plasmacytoid and conventional dendritic cells (DCs) subpopulations and three monocyte subpopulations as well as other immune cells-in peripheral blood and local blood of thyroid gland obtained parallelly in patients with focal thyroid lesions using flow cytometry. The analysis revealed significant differences in the distribution of main subsets of assessed cells between peripheral blood and biopsy material. The results support the existence of local, organ-specific immune reaction control networks within thyroid nodules.

The oscillatory flow of the cerebrospinal fluid in the Sylvian aqueduct and the prepontine cistern measured with phase contrast MRI in children with hydrocephalus-a preliminary report.

INTRODUCTION: Recognizing patients with ventriculomegaly who are at risk of developing acute hydrocephalus presents a challenge for the clinician. The association between disturbed cerebrospinal fluid flow (CSF) and impaired brain compliance may play a role in the pathogenesis of hydrocephalus. Phase contrast MRI is a noninvasive technique which can be used to assess CSF parameters. The aim of the work is to evaluate the effectiveness of phase contrast MRI in recognizing patients at risk of acute hydrocephalus, based on measuring the pulsatile CSF flow parameters in the Sylvian aqueduct and prepontine cistern in children with ventriculomegaly. AIM: The aim of the work is to characterize the parameters of cerebrospinal fluid (CSF) flow in the Sylvian aqueduct and prepontine cistern in children with ventriculomegaly with regard to patient age and symptoms. We hypothesize that the relationship between CSF flow parameters in these two regions will vary according to analyzed factors and it will allow to recognize children at risk of hydrocephalus. MATERIALS AND METHODS: A group of 26 children with ventriculomegaly (five girls and 21 boys) underwent phase contrast MRI examinations (Philips 3T Achieva with Q-flow integral application). Amplitudes of average and peak velocities of the CSF flow through the Sylvian aqueduct and prepontine cistern were used to calculate ratios of oscillation and peak velocities, respectively. The relationship between the oscillation coefficient, the peak velocity coefficient, and stroke volume was then assessed in accordance with age and clinical symptoms. RESULTS: The peak velocity coefficient was significantly higher in patients with hyper-oscillating flow through the Sylvian aqueduct (3.04 ± 3.37 vs. 0.54 ± 0.28; p = 0.0094). Moreover, these patients tended to develop symptoms more often (p = 0.0612). No significant age-related changes were observed in CSF flow parameters. CONCLUSION: Phase contrast MRI is a useful tool for noninvasive assessment of CSF flow parameters. The application of coefficients instead of direct values seems to better represent hemodynamic conditions in the ventricular system. However, further studies are required to evaluate their clinical significance and normal limits.

The Molecular Effect of Diagnostic Absorbed Doses from 131I on Papillary Thyroid Cancer Cells In Vitro.

Diagnostic whole-body scan is a standard procedure in patients with thyroid cancer prior to the application of a therapeutic dose of 131I. Unfortunately, administration of the radioisotope in a diagnostic dose may decrease further radioiodine uptake-the phenomenon called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in the sodium iodide symporter (NIS) gene promoter, and the NIS protein level in a K1 cell line derived from the metastasis of a human papillary thyroid carcinoma exposed to 131I in culture. The different activities applied were calculated to result in absorbed doses of 5, 10 and 20 Gy. Radioiodine did not affect the expression of the NIS gene at the mRNA level, however, we observed significant changes in the NIS protein level in K1 cells. The decrease of the NIS protein level observed in the cells subjected to the lowest absorbed dose was paralleled by a significant increase in 8-oxo-dG concentrations (p < 0.01) and followed by late activation of the DNA repair pathways. Our findings suggest that the impact of 131I radiation on thyroid cells, in the range compared to doses absorbed during diagnostic procedures, is not linear and depends on various factors including the cellular components of thyroid pathology.

Metallothioneins in Normal and Cancer Cells.

Metallothioneins (MTs) are low molecular weight proteins, which are present in almost all types of organisms. In mammals, four main MT isoforms designated from MT-1 to MT-4 were identified. Their biological role, according to their characteristic structure, was shown to be mostly associated with cellular metabolism of metal ions, especially zinc. Moreover, the available evidence suggests broad regulatory properties of MTs in the control of cell senescence and various pathological processes including neurodegeneration, cardiovascular pathology, metabolic disorders, and various malignancies. This extensive review provides general in formation on the structure of MT family members and the cellular functions of MT-1, MT-2, and MT-4 isoforms as well as insights into divergent biological roles of MT-3. Due to the involvement of MT molecules in various processes related to carcinogenesis, an organ-specific presentation of current data concerning their potential impact on the progression of various tumors is given. The regulatory role of MT family members in the function of the immune system is also discussed in depth.

Association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.

PURPOSE: Epilepsy is a disease of neurological character. Approximately one third of epileptic patients demonstrate a drug-resistant phenotype, which is associated with the development of drug-resistant epilepsy. The multidrug resistance protein 1 and glycoprotein P, encoded by MDR1, play a significant role in the transmembrane transport of anti-epileptic agents. Single nucleotide polymorphism C3435T (rs1045642) within MDR1 gene may be associated with an increased expression of P-gp which affects the levels of antiepileptic drugs in plasma. The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children. METHODS: C3435T polymorphism of MDR1 gene was analysed by the high resolution melting technique in a group of patients with drug-resistant (n = 106) and drug-responsive epilepsy (n = 67), as well as in non-epileptic children (n = 98) hospitalised at the Department of Neurology, Polish Mother's Memorial Hospital in Lodz. Genotype and allele distributions were evaluated and their compatibility with the Hardy-Weinberg distribution was assessed by means of the χ(2) test. Genotype and allele evaluation, regarding their relationship with a given feature, was supported by an analysis of odds ratio and 95 % confidence interval, calculated according to the logistic regression model. RESULTS: An association was observed between the incidence rate of DRE and the presence of C allele in C3435T polymorphism of MDR1 gene, which may enhance the risk of the disease. The T allele may then play a protective role. No differences were found in the studied groups, regarding either genotype or allele distribution in reference to patient's gender or concomitant diseases. CONCLUSION: Following the obtained results, C3435T polymorphism of MDR1 gene may be connected with the incidence of drug-resistant epilepsy in the population of Polish children. ISRCTN ISRCTN73824458. Registered 28th September 2014.

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro.

BACKGROUND: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). MATERIALS AND METHODS: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. RESULTS: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. CONCLUSIONS: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis.

Portal blood - a new source of dendritic cells for pancreatic cancer vaccine.

INTRODUCTION: Cohort study evaluated dendritic cells (DCs) subsets in portal and peripheral blood of patients with pancreatic cancer (PC) and chronic pancreatitis (CHP). MATERIAL AND METHODS: Myeloid type 1 (mDCs1) and 2 (mDCs2), plasmocytoid (pDCs) and SLAN + DCs were assessed in PC (n = 20) and CHP (n = 6) patients. RESULTS: Percentage of mDCs1 was significantly lower in PC patients when compared to CHP (0.48 ± 0.26 vs 0.76 ± 0.3; p = 0.038) only in portal, but not peripheral blood. DISCUSSION: Further studies to assess the functional properties of portal blood DCs and their applicability in anticancer vaccination are needed.

Intracellular Accumulation and Secretion of YKL-40 (CHI3L1) in the Course of DMSO-Induced HL-60 Cell Differentiation.

YKL-40 (CHI3L1) is a matrix glycoprotein stored in human neutrophil-specific granules and released upon activation. While it is implicated in inflammation, cancer progression, and cell differentiation, its exact physiological role remains unclear. This study investigated the intracellular expression and secretion of YKL-40 by untreated and DMSO-treated HL-60 cells in association with surface expression of CD11b and CD66b throughout the differentiation process (up to 120 h). Secreted YKL-40 protein and mRNA levels of YKL-40, CD66b, and CD11b were measured by ELISA and quantitative RT-PCR, respectively. The intracellular YKL-40 and surface CD11b and CD66b expression were assessed by flow cytometry. A significant increase in CD11b expression confirmed DMSO-induced differentiation of HL-60 cells. Upon DMSO stimulation, YKL-40 mRNA expression increased in a time-dependent manner, unlike CD66b. The lack of CD66b (a granulocyte maturation and activation marker) on the surface of HL-60 cells might suggest that DMSO treatment did not induce full maturation or activation. The intracellular YKL-40 protein expression was increasing up to 96 h of DMSO treatment and then declined. YKL-40 secretion into the culture medium was detectable only at later time points (96 and 120 h), which was correlated with a decreased proliferation of DMSO-treated HL-60 cells. These findings suggest sequential changes in YKL-40 production and secretion during DMSO-induced differentiation of HL-60 cells and might contribute to a better understanding of YKL-40's involvement in both physiological processes and disease development, including multiple sclerosis.

Differences in Brain Atrophy Pattern between People with Multiple Sclerosis and Systemic Diseases with Central Nervous System Involvement Based on Two-Dimensional Linear Measures.

Conventional brain magnetic resonance imaging (MRI) in systemic diseases with central nervous system involvement (SDCNS) may imitate MRI findings of multiple sclerosis (MS). In order to better describe the MRI characteristics of these conditions, in our study we assessed brain volume parameters in MS (n = 58) and SDCNS (n = 41) patients using two-dimensional linear measurements (2DLMs): bicaudate ratio (BCR), corpus callosum index (CCI) and width of third ventricle (W3V). In SDCNS patients, all 2DLMs were affected by age (CCI p = 0.005, BCR p < 0.001, W3V p < 0.001, respectively), whereas in MS patients only BCR and W3V were (p = 0.001 and p = 0.015, respectively). Contrary to SDCNS, in the MS cohort BCR and W3V were associated with T1 lesion volume (T1LV) (p = 0.020, p = 0.009, respectively) and T2 lesion volume (T2LV) (p = 0.015, p = 0.009, respectively). CCI was associated with T1LV in the MS cohort only (p = 0.015). Moreover, BCR was significantly higher in the SDCNS group (p = 0.01) and CCI was significantly lower in MS patients (p = 0.01). The best predictive model to distinguish MS and SDCNS encompassed gender, BCR and T2LV as the explanatory variables (sensitivity 0.91; specificity 0.68; AUC 0.86). Implementation of 2DLMs in the brain MRI analysis of MS and SDCNS patients allowed for the identification of diverse patterns of local brain atrophy in these clinical conditions.

Can Selected Parameters of Brain Injury Reflect Neuronal Damage in Smoldering Multiple Sclerosis?

BACKGROUND: Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. METHODS: A single-center prospective observational study was performed. The median age of the patients was 40 (31-52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. RESULTS: The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. CONCLUSIONS: The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.

Predictive value of brain atrophy, serum biomarkers and information processing speed for early disease progression in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance. Methods: This prospective study included patients with MS diagnosed up to 1 year before recruitment. We analyzed serum biomarkers such as CXCL13, CHI3L1, OPN, IL-6, and GFAP and neurofilament light chains (NfLs); brain MRI parameters of linear atrophy such as bicaudate ratio (BCR), third ventricle width (TVW); and information processing speed were measured using the Symbol Digit Modalities Test (SDMT) during the 2 years follow-up. Results: The study included a total of 50 patients recruited shortly after the diagnosis of MS diagnosis (median 0 months; range 0-11 months), and the mean time of observation was 28 months (SD = 4.75). We observed a statistically significant increase in the EDSS score (Wilcoxon test: Z = 3.06, p = 0.002), BCR (Wilcoxon test: Z = 4.66, p < 0.001), and TVW (Wilcoxon test: Z = 2.84, p = 0.005) after 2 years of disease. Patients who had a significantly higher baseline level of NfL suffered from a more severe disease course as per the EDSS score (Mann-Whitney U-test: U = 107, Z = -2,74, p = 0.006) and presence of relapse (Mann-Whitney U-test: U = 188, Z = -2.01, p = 0.044). In the logistic regression model, none of the parameters was a significant predictor for the achieving of no evidence of disease activity status (NEDA). In the model considering all assessed parameters, only the level of NfL had a significant impact on disease progression, measured as the increase in EDSS (logistic regression: ß = 0.002, p = 0.017). Conclusion: We confirmed that NfL levels in serum are associated with more active disease. Moreover, we found that TVW at the time of diagnosis was associated with an impairment in cognitive function measured by information processing speed at the end of the 2-year observation. The inclusion of serum NfL and TVW assessment early in the disease may be a good predictor of disease progression independent of NEDA.

Cerebrospinal Fluid Biomarkers in Differential Diagnosis of Multiple Sclerosis and Systemic Inflammatory Diseases with Central Nervous System Involvement.

BACKGROUND: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). METHODS: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. RESULTS: The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. CONCLUSIONS: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

Clinical Characteristics of Patients with Vertebral Artery Hypoplasia.

Vertebral artery hypoplasia (VAH) belongs to the relatively frequent Doppler ultrasonography (US) findings. However, its clinical significance remains controversial. This was a retrospective study analyzing clinical data of patients undergoing US because of cerebrovascular disease in a single academic neurology center. In the dataset of 2500 US examinations, 80 individuals with VAH (VA diameter < 2.0 mm) were identified (3.2% of all patients). Patients with significant vertebral artery asymmetry (SVAA, difference in VA diameters > 1.0 mm) (n = 80) and patients with normal VA diameter (n = 80) were also recruited. Clinical parameters including clinical signs and symptoms, concomitant diseases, imaging findings and the hospitalization outcome were compared between groups. The frequency of vertigo was highest in VAH group. Ischemic lesions of the cerebellum were found in 10% of VAH patients, 16% of SVAA patients and 5% of control subjects. Neurological deficits improved in over 60% of patients in each group, whereas ca. 30% of patients remained in a stable neurological status. The percentage of patients who deteriorated did not exceed 5% in any of the groups. The results of our study support a relatively high frequency of VAH. Our observations suggest coexistence of VAH with a higher frequency of neurological presentations associated with posterior arterial circulation of the central nervous system.