Transapical Approach to Septal Myectomy for Hypertrophic Cardiomyopathy.

A 63-year-old symptomatic female with apical hypertrophic cardiomyopathy and diastolic disfunction was admitted to the hospital. What is the best way to manage this patient? This study is a literature review that was performed to answer this question. The following PubMed search strategy was used: 'Hypertrophic obstructive cardiomyopathy' [All Fields] OR 'apical myectomy' [All Fields], NOT 'animal [mh]' NOT 'human [mh]' NOT 'comment [All Fields]' OR 'editorial [All Fields]' OR 'meta-analysis [All Fields]' OR 'practice-guideline [All Fields]' OR 'review [All Fields]' OR 'pediatrics [mh]'. The natural history of the disease has a benign prognosis; however, a watchful strategy was associated with the risk of adverse cardiovacular events. Contrastingly, transapical myectomy was associated with low surgical risk and acceptable outcomes. In our case, the patient underwent transapical myectomy with an unconventional post-operative period. Control echocardiography showed marked left ventricular (LV) cavity enlargement: LV end-diastolic volume, 74 mL; LV ejection fraction, 65%; and LV stroke volume index increased to 27 mL/m2. The patient was discharged 7 days after myectomy. At 6 months post-operation, the patient was NYHA Class I, with a 6 min walk test score of 420 m. Therefore, transapical myectomy may be considered as a feasible procedure in patients with apical hypertrophic cardiomyopathy and progressive heart failure.

Spectroscopy of Laser-Induced Dielectric Breakdown Plasma in Mixtures of Air with Inert Gases Ar, He, Kr, and Xe.

The generation of ozone and nitrogen oxides by laser-induced dielectric breakdown (LIDB) in mixtures of air with noble gases Ar, He, Kr, and Xe is investigated using OES and IR spectroscopy, mass spectrometry, and absorption spectrophotometry. It is shown that the formation of NO and NO2 noticeably depends on the type of inert gas; the more complex electronic configuration and the lower ionization potential of the inert gas led to increased production of NO and NO2. The formation of ozone occurs mainly due to the photolytic reaction outside the gas discharge zone. Equilibrium thermodynamic analysis showed that the formation of NO in mixtures of air with inert gases does not depend on the choice of an inert gas, while the equilibrium concentration of the NO+ ion decreases with increasing complexity of the electronic configuration of an inert gas.

Some Beneficial Effects of Inert Gases on Blood Oxidative Metabolism: In Vivo Study.

The aim of the study was to assess the effect of external use of inert gases (helium and argon) on the state of free radical processes in vivo. The experiment was performed on 30 male Wistar stock rats (age-3 months, weight-200-220 g.), randomly distributed into 3 equal groups. The first group of animals was intact (n = 10). The animals of the second and third groups were treated with argon and helium streams, respectively. Our research has allowed us to establish that the studied inert gases have a modulating effect on the state of oxidative metabolism of rat blood, and the nature of this effect is directly determined by the type of gas. The results of this study allowed us to establish the potential antioxidant effect of the helium stream, mainly realized due to the activation of the catalytic properties of the enzymatic link of the antioxidant system of rat blood plasma. At the same time, the revealed features of shifts in oxidative metabolism during treatment with argon flow include not only stimulation of the antioxidant system but also the pronounced induction of free radical oxidation. Thus, the conducted studies made it possible to verify the specificity of the response of the oxidative metabolism of blood plasma to the use of inert gases, depending on their type.

High-frequency limit of spectroscopy.

We consider an arbitrary quantum mechanical system, initially in its ground-state, exposed to a time-dependent electromagnetic pulse with a carrier frequency ω0 and a slowly varying envelope of finite duration. By working out a solution to the time-dependent Schrödinger equation in the high-ω0 limit, we find that, to the leading order in ω0 -1, a perfect self-cancellation of the system's linear response occurs as the pulse switches off. Surprisingly, the system's observables are, nonetheless, describable in terms of a combination of its linear density response function and nonlinear functions of the electric field. An analysis of a jellium slab and jellium sphere models reveals a very high surface sensitivity of the considered setup, producing a richer excitation spectrum than accessible within the conventional linear response regime. On this basis, we propose a new spectroscopic technique, which we provisionally name the Nonlinear High-Frequency Pulsed Spectroscopy (NLHFPS). Combining the advantages of the extraordinary surface sensitivity, the absence of constraints by the traditional dipole selection rules, and the clarity of theoretical interpretation utilizing the linear response time-dependent density functional theory, NLHFPS has a potential to evolve into a powerful characterization method for nanoscience and nanotechnology.

Cold Argon Athmospheric Plasma for Biomedicine: Biological Effects, Applications and Possibilities.

Currently, plasma medicine is a synthetic direction that unites the efforts of specialists of various profiles. For the successful formation of plasma medicine, it is necessary to solve a large complex of problems, including creating equipment for generating cold plasma, revealing the biological effects of this effect, as well as identifying and justifying the most promising areas of its application. It is known that these biological effects include antibacterial and antiviral activity, the ability to stimulate hemocoagulation, pro-regenerative properties, etc. The possibility of using the factor in tissue engineering and implantology is also shown. Based on this, the purpose of this review was to form a unified understanding of the biological effects and biomedical applications of argon cold plasma. The review shows that cold plasma, like any other physical and chemical factors, has dose dependence, and the variable parameter in this case is the exposure of its application. One of the significant characteristics determining the specificity of the cold plasma effect is the carrier gas selection. This gas carrier is not just an ionized medium but modulates the response of biosystems to it. Finally, the perception of cold plasma by cellular structures can be carried out by activating a special molecular biosensor, the functioning of which significantly depends on the parameters of the medium (in the field of plasma generation and the cell itself). Further research in this area can open up new prospects for the effective use of cold plasma.

APOBEC mutagenesis is low in most types of non-B DNA structures.

While somatic mutations are known to be enriched in genome regions with non-canonical DNA secondary structure, the impact of particular mutagens still needs to be elucidated. Here, we demonstrate that in human cancers, the APOBEC mutagenesis is not enriched in direct repeats, mirror repeats, short tandem repeats, and G-quadruplexes, and even decreased below its level in B-DNA for cancer samples with very high APOBEC activity. In contrast, we observe that the APOBEC-induced mutational density is positively associated with APOBEC activity in inverted repeats (cruciform structures), where the impact of cytosine at the 3'-end of the hairpin loop is substantial. Surprisingly, the APOBEC-signature mutation density per TC motif in the single-stranded DNA of a G-quadruplex (G4) is lower than in the four-stranded part of G4 and in B-DNA. The APOBEC mutagenesis, as well as the UV-mutagenesis in melanoma samples, are absent in Z-DNA regions, owing to the depletion of their mutational signature motifs.

A retrospective analysis of colchicine in combination with NSAIDs therapy in patients with systemic form of adult-onset Still's disease with serositis.

OBJECTIVES: Adult-onset Still's disease (AOSD) is increasingly viewed as autoinflammatory disease associated with the so-called inflammasomopathy. Proinflammatory cytokines, such as IL-18 and IL-1ß, processed through the inflammasome machinery, play an important role in the pathogenesis of AOSD. AOSD is heterogenous, therefore there are two subtypes of the disease, systemic and articular, which probably imply different approaches for the treatment. Over 20% of patients with systemic AOSD have serositis. Recently, colchicine in combination with non-steroidal anti-inflammatory drugs (NSAIDs) has become the "gold standard" for recurrent pericarditis treatment. However, data on this combination therapy in AOSD are scarce. METHODS: In this retrospective case series study, we assessed the medical history of 20 patients with a systemic form of AOSD. All patients had pericarditis and received а combination of NSAIDs (in most cases ibuprofen 600-800 mg x3 daily) and colchicine (1 mg daily) for treatment. RESULTS: 13/20 (65%) of patients responded to this combination of anti-inflammatory drugs. Of note, not only pericarditis, but also other manifestations were improved such as arthritis, rash, hepatomegaly, acute phase reactants, and abnormal liver tests. CONCLUSIONS: The low cost, safety and wide availability of such therapy make this option relevant and determine the need for further study.

Early post-septal myectomy outcomes for hypertrophic obstructive cardiomyopathy.

BACKGROUND: We aimed to evaluate early outcomes of septal myectomy in patients with hypertrophic cardiomyopathy. METHODS: We retrospectively analyzed data collected over a 9-year period from 583 patients who underwent septal myectomy for hypertrophic cardiomyopathy at our institution. RESULTS: The mean age was 55.7 ± 13.1 years, and 338 (58%) patients were in New York Heart Association class III or IV. There were 11 (1.9%) early deaths, including 3 (0.5%) intraoperative deaths. Early mortality was lowest after isolated septal myectomy (0.8%) and highest after concomitant mitral valve replacement (6.1%). There were 4 (0.7%) and 9 (1.5%) patients with left ventricular wall rupture and ventricular septal defect, respectively, after myectomy. New pacemaker implantation caused by atrioventricular disturbances was required in 29 (5.0%) patients, and was associated with previous alcohol septal ablation (odds ratio 3.34, 95% confidence interval 1.02-11.0, P = 0.047). Left ventricular wall rupture, intraoperative residual (15.5% moderate, 0.3% severe) mitral regurgitation, and pre-discharge residual outflow tract gradient >30 mm Hg (4.6%) occurrences were surgeon-dependent. CONCLUSIONS: The early results are consistent with example targets reported in the 2020 American College of Cardiology/American Heart Association guidelines for septal reduction therapy outcomes. Septal myectomy safety and efficacy are surgeon-dependent. Previous alcohol septal ablation increases the risk of permanent pacemaker implantation due to postoperative complete atrioventricular block. Therefore, continuous education, mentoring, and learning by doing may play an important role in achieving reasonable septal myectomy safety and efficacy.

Near-Field Microwave Tomography of Biological Tissues: Future Perspectives.

This overview shows the mapping of specific visualization techniques, depth assessment of the structure of the underlying tissues and used wavelengths of radiation. Medical imaging is currently one of the most dynamically developing areas of medical science. The main aim of the review is a systematization of information on the current status of the microwave imaging of biological objects, primarily of body tissues. The main options of microwave sensing of biological objects are analyzed. Two basic techniques for sensing differing evaluation parameters are characterized. They are microwave thermometry (passive) and near-field resonance imaging. The physical principles of microwave sensing application are discussed. It is shown that the resonant near-field microwave tomography allows visualization of the structure of biological tissues on the basis of the spatial distribution of their electrodynamic characteristics - permittivity and conductivity. Potential areas for this method in dermatology, including dermatooncology, are shown. The known results of applying the method to patients with dermatoses are given. The informativeness of the technology in the early diagnosis of melanoma is shown. The prospects of microwave diagnostics in combustiology, reconstructive and plastic surgery are demonstrated. Thus, microwave sensing is a modern, dynamically developing method of biophysical assessment of body tissues. There is a strong indication of the feasibility of application of microwave sensing in combustiology (in different periods of burn disease), as well as in reconstructive surgery. Further research in this and other areas of biomedicine will significantly expand the range of possibilities of modern technologies of visualization.

Breakdown of the ionization potential theorem of density functional theory in mesoscopic systems.

The ionization potential (IP)-theorem of Kohn-Sham (KS) density functional theory (DFT) states that the energy of the highest occupied molecular orbital (HOMO) ϵHOMO equals the negative of the first IP, thus ascribing a physical meaning to one of the eigenvalues of the KS Hamiltonian. We scrutinize the fact that the validity of the IP-theorem relies critically on the electron density n(r), far from the system, to be determined by HOMO only, behaving as n(r)∼r→∞e-2-2ϵHOMOr. While this behavior always holds for finite systems, it does not hold for mesoscopic ones, such as quasi-two-dimensional (Q2D) electron gas or Q2D crystals. We show that this leads to the violation of the IP-theorem for the latter class of systems. This finding has a strong bearing on the role of the KS valence band with respect to the work-function problem in the mesoscopic case. Based on our results, we introduce a concept of the IP band structure as an observable alternative to its unphysical KS counterpart. A practical method of the determination of the IP band structure in terms of DFT quantities is provided.

Peroral endoscopic myotomy in a pregnant woman diagnosed with mitochondrial disease: A case report.

BACKGROUND: Achalasia is a primary esophageal motility disease characterized by impairment of normal esophageal peristalsis and absence of relaxation of the lower esophageal sphincter. Sometimes is can be a part of some genetic disorders. One of the causes of gastrointestinal motility disorders, including achalasia, is mitochondrial defects. CASE SUMMARY: We report about a pregnant woman with a history of symptoms associated with inherited mitochondrial disease, which was confirmed by genetic tests, and who was treated via peroral endoscopic myotomy. CONCLUSION: Peroral endoscopic myotomy is possible treatment option for a pregnant woman with achalasia caused by mitochondrial disease.

Many-Body Quantum Dynamics by the Reduced Density Matrix Based on Time-Dependent Density-Functional Theory.

We evaluate the density matrix of an arbitrary quantum mechanical system in terms of the quantities pertinent to the solution of the time-dependent density functional theory (TDDFT) problem. Our theory utilizes the adiabatic connection perturbation method of Görling and Levy, from which the expansion of the many-body density matrix in powers of the coupling constant λ naturally arises. We then find the reduced density matrix ρ_{λ}(r,r^{'},t), which, by construction, has the λ independent diagonal elements ρ_{λ}(r,r,t)=n(r,t), n(r,t) being the particle density. The off-diagonal elements of ρ_{λ}(r,r^{'},t) contribute importantly to the processes unaccessible via the density, directly or by the use of the known TDDFT functionals. Of those, we consider the momentum-resolved photoemission, doing this to the first order in λ, i.e., on the level of the exact exchange theory. In illustrative calculations of photoemission from the quasi-2D electron gas and isolated atoms, we find quantitatively strong and conceptually far-reaching differences with the independent-particle Fermi's golden rule formula.

Vimentin as antigenic target in autoimmunity: A comprehensive review.

Vimentin is a protein of intermediate filament family, which is expressed in all mesenchymal cells. Vimentin plays a key role in the physiology of the cell, cellular interactions and the functioning of the immune system. Post-translationally modified and native forms of vimentin are involved in the pathogenesis of inflammation and many autoimmune diseases: rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, antiphospholipid syndrome, Crohn's disease, ankylosing spondyloarthritis and idiopathic pulmonary fibrosis. Modifications of the protein lead to the formation of antigenic epitopes and, as a result, to the synthesis of antibodies. Citrullinated, carbamylated and acetylated forms of vimentin participate in the pathogenesis of RA, and antibodies against them serve as diagnostic and prognostic markers of the disease. Epitopes of native vimentin are antigenic in the group of HLA-DRB1*0301 positive patients with sarcoidosis. In addition, vimentin takes part in pathogenesis of tubulointerstitial inflammation and glomerulonephritis in lupus. In antiphospholipid syndrome interactions of vimentin and cardiolipin on the surface of apoptotic cells lead to the formation of an immunogenic complex. Antibodies against vimentin/cardiolipin complex are involved in the mechanism of thrombogenesis and serve to identify patients seronegative for antibodies to cardiolipin and ß2glycoprotein-I with the clinical features. Post-translationally modified form of the protein is citrullinated and MMP-degraded vimentin, which was found in serum of patients with Crohn's disease and ankylosing spondyloarthritis.

Theoretical approach to embed nanocrystallites into a bulk crystalline matrix and the embedding influence on the electronic band structure and optical properties of the resulting heterostructures.

We develop an approach and present results of the combined molecular dynamics and density functional theory calculations of the structural and optical properties of the nanometer-sized crystallites embedded in a bulk crystalline matrix. The method is designed and implemented for both compatible and incompatible lattices of the nanocrystallite (NC) and the host matrix, when determining the NC optimal orientation relative to the matrix constitutes a challenging problem. We suggest and substantiate an expression for the cost function of the search algorithm, which is the energy per supercell generalized for varying number of atoms in the latter. The epitaxial relationships at the Si/NC interfaces and the optical properties are obtained and found to be in a reasonable agreement with experimental data. Dielectric functions show significant sensitivity to the NC's orientation relative to the matrix at energies below 0.5 eV.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis.

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included. Kappa and lambda FLC concentrations in serum and cerebrospinal fluid (CSF) samples of MS patients were measured using ELISA assay. FLC quotients (Q-k and Q-λ, respectively) were calculated. In a cross-sectional group (n = 92), the MRI data were acquired within 6 months from the date of the lumbar puncture. Twenty patients from this cohort performed a follow-up MRI after 1 year of observation. Brain volumes were calculated with SIENAX and the brain atrophy (percentage brain volume change (PBVC)) was assessed with SIENA. Spearman's test was performed to assess correlations. We have shown statistically significant correlation of Expanded Disability Status Scale (EDSS) level with normalized brain volume (NBV, r = - 0.2721, p = 0.0062), white matter volume (WMV, r = - 0.2425, p = 0.015), and gray matter volume (GMV, r = - 0.216, p = 0.0309). Multiple Sclerosis Severity Score (MSSS) score correlated with NBV (r = - 0.2521, p = 0.0352) and WMV (r = - 0.315, p = 0.0079). Neither EDSS, nor MSSS scores correlated with the age of patients and relapse rate during the first year and 5 years. In our study, we found statistically significant correlations of k-FLC in the CSF with NBV (r = - 0.311, p = 0.003) and with GMV (r = - 0.213, p = 0.0423). Q-k correlated only with NBV (r = - 0.340, p = 0.006) and Q-λ were negatively correlated with WMV (r = - 0.366, p = 0.003). We did not find correlations of k-FLC in CSF, λ-FLC in CSF, Q-k, and Q-λ with duration of MS course, EDSS, MSSS, number of relapses during the first year, and during the first 5 years of disease. Additionally, we subdivided the study population in accordance with level of k-FLC CSF, Q-k, and Q-λ on the 25th and 75th percentile subgroups (25-k-FLCCSF/75-k-FLCCSF; 25-λ-FLCCSF/75-λ-FLCCSF; 25-Q-k/75-Q-k; 25-Q-λ/75-Q-λ). We found statistically significant difference of NBV and GMV between 25-k-FLCCSF and 75-k-FLCCSF subgroups (p = 0.0047, p = 0.0297 respectively), NBV between 25-Q-k and 75-Q-k subgroups (p = 0.038), and NBV and WMV between 25-Q-λ and 75-Q-λ subgroups (p = 0.0446, p = 0.0026 respectively). PBVC in the prospective group showed negative correlation with kappa FLC in the CSF (r = - 0.4853, p = 0.0301) and Q-k (r = - 0.6132, p = 0.0224), but not with other clinical, epidemiological data. In this study, we showed a strong negative correlation of k-FLC, Q-k, and Q-λ with brain atrophy in MS patients. Additionally, patients with high concentration of FLC had lower brain volumes. We did not find correlations of FLC with the relapse rate, age of patients, and MS time course. In the prospective group, the rate of atrophy was correlated with k-FLC and Q-k. We suggest that level of intrathecal production of FLC can be a good prognostic biomarker for MS.

Mid-term results of mitral valve repair using flexible bands versus complete rings in patients with degenerative mitral valve disease: a prospective, randomized study.

BACKGROUND: We aimed to compare the outcomes of mitral valve repair with flexible band (FB) versus complete semirigid ring (SR) in degenerative mitral valve disease patients. METHODS: From September 2011 to 2014, 171 patients were randomized and underwent successful mitral valve repair using a SR (n = 85) or FB (n = 86). There were no significant between-group differences at baseline. RESULTS: There were no early mortalities. The mean follow up was 24.7 months. The 2-year survival was 96.0 ± 2.3% (95% confidence interval [CI], 88.6-98.7%) and 94.3 ± 2.8% (95% CI, 85.5-97.9%) in the SR and FB groups, respectively (p = 0.899). The left ventricle remodeling was similar between the groups. Higher transmitral peak (8.5 [3.9-17] vs. 6 [2.1-18] mmHg, p < 0.001), mean pressure gradients (3.7 [1.3-8] vs. 2.8 [0.6-6.8] mmHg, p = 0.001), and systolic pulmonary artery pressure (34.5 [20-68] vs. 29.5 [8-48] mmHg, p < 0.001) was observed in the SR group. The 2-year freedom from recurrence of significant mitral regurgitation was significantly higher in the FB group than the SR group (p = 0.002). Residual mitral regurgitation was an independent prognostic factor of recurrence of mitral regurgitation. The 3-year freedom from reoperation was significantly higher in the FB group than the SR group (p = 0.044). CONCLUSION: Patients with degenerative mitral valve disease may benefit from valve repair with FBs. Residual mitral regurgitation before discharge is an independent risk factor of late insufficiency recurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT03278574 , retrospectively registered on 06.09.2017.

Quasi-Low-Dimensional Electron Gas with One Populated Band as a Testing Ground for Time-Dependent Density-Functional Theory of Mesoscopic Systems.

We find an exact analytical solution to the exchange-only time-dependent density-functional theory (TDDFT) problem for a significant class of quasi-low-dimensional (QLD) materials: QLD electron gas with only one band filled in the direction perpendicular to the layer or wire. The theory yields the TD exchange potential as an explicit nonlocal operator of the TD spin density. The dressed interband (image states) excitation spectra of quasi-two-dimensional electron gas are obtained, while the comparison with the Kohn-Sham transitions provides insights into the qualitative and quantitative role of the many-body interactions. Important cancellations between the Hartree f_{H} and the exchange f_{x} kernels of TDDFT are found in the low-density regime, elucidating the interrelations between the Kohn-Sham and the many-body dynamics in mesoscopic systems.

Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis.

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR) sequence. Expanded Disability Status Scale (EDSS) score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54) of patients. LMCE-positive patients had longer disease duration (p = 0,0098) and higher EDSS score (p = 0,039), but not a higher relapse rate (p = 0,091). No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p = 0,3842). Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p = 0.043, F = 2.529), the total grey matter volume (p = 0.043, F = 2.54), and total ventricular volume (p = 0.039, F = 2.605). Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis.

BACKGROUND AND OBJECTIVE: In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS). METHODS: We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients. RESULTS: The levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056). CONCLUSION: The concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.