Stability, survival, patient satisfaction, and cost-minimization of CAD/CAM versus conventional multistranded fixed retainers in orthodontic patients: a 2-year follow-up of a two-centre randomized controlled trial.

BACKGROUND: CAD/CAM (computer-aided design/computer-aided manufacturing) fixed retainers (FRs) as an alternative to multistranded FRs to maintain orthodontic treatment outcome. OBJECTIVES: The primary aim was to compare CAD/CAM versus conventional multistranded FRs in terms of stability until 2 years. Secondary outcomes were failure rates, patient satisfaction, and cost-minimization. TRIAL DESIGN: 2-arm parallel, two-centre randomized controlled trial. METHODS: Patients were randomized to CAD/CAM or conventional FRs in both arches, in a 1:1 ratio and blocks of four. Allocation concealment was secured by using sequentially numbered envelopes. Patients were blinded. FRs were bonded at the end of treatment, and patients were recalled after 12 and 24 months. First-time retainer failures were recorded and digital impressions were taken. Arch widths and lengths, as well as Little's Irregularity Index (LII), were measured. Additionally, patients answered satisfaction questionnaires. Linear mixed models were applied for measurements and patient satisfaction. Survival analyses were estimated with Kaplan-Meier curves, along with Cox-regression modelling. Cost-minimization analysis was undertaken. RESULTS: One hundred and eighty-one patients were randomized (98 in Centre 1, and 83 in Centre 2): 90 in CAD/CAM and 91 in conventional group. One hundred and fifty three patients attended T24 follow-up. There were no significant differences in LII and arch dimensions between groups for failure-free patients. Within 24 months, 34% maxillary CAD/CAM FRs and 38% maxillary conventional FRs failed, along with 42% mandibular CAD/CAM FRs and 40% mandibular conventional FRs, with no significant difference in survival between groups (hazard ratios conventional to CAD/CAM: maxillary arch: 1.20 [P = 0.46], mandibular arch: 0.98 [P = 0.94]). There were no significant differences in patient satisfaction between groups. No harms were observed. Cost-minimization analysis showed that CAD/CAM FRs were slightly cheaper than conventional FRs. CONCLUSIONS: There were no clinically significant differences in LII, arch widths, and lengths between CAD/CAM and conventional FRs after 24 months. There were no differences in failures and patient satisfaction between groups. CAD/CAM FRs were slightly cheaper than conventional FRs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04389879.

Availability of Third Molars as Donor Teeth for Autotransplantation to Replace Congenitally Absent Second Premolars in Children and Young Adults.

The aim of the study was to assess the presence and distribution of third molars (M3) regarding their autotransplantation in patients with congenital absence of second premolars (PM2). Additionally, M3 development in relation to patients' age and gender was investigated. Panoramic radiographs of non-syndromic patients with at least one congenitally absent PM2 were used to assess the localization and number of missing PM2 and the presence or absence of M3 (minimum age 10 years). The alternate logistic regression model was applied to analyze associations between the presence of PM2 and M3. A total of 131 patients with PM2 agenesis were identified (82 females, 49 males). At least one M3 was present in 75.6% and all M3 were present in 42.7% of patients. A statistically significant association between the number of PM2 and M3 agenesis was found; the effects of age and gender were not significant. More than half of M3 in patients between 14-17 years old had completed » of their root development. The congenital absence of maxillary PM2 was associated with the absence of maxillary PM2, M3, and no correlation was found in the mandible. In patients with PM2 agenesis, at least one M3 is often present and can be considered as a donor tooth for autotransplantation.

Ceramide is implicated in humoral peripheral and intrathecal autoimmune response in MS patients.

BACKGROUND: The disturbed metabolism of ceramide (Cer) is supposed to evoke the autoimmune response, contributing to MS pathology. OBJECTIVES: To determine levels of anti-Cer immunoglobulins G (IgGs) in the CSF and serum of subjects with various phenotypes of MS, and to investigate relationships between levels of anti-Cer antibodies and MS-related variables. METHODS: IgGs isolated from serum and the CSF of 68 MS patients and appropriate controls were examined for their reactivity to Cer subspecies. Their levels were compared between the studied groups and compartments, and analyzed with regard to clinical variables. RESULTS: Increased levels of anti-C16:0-, C18:0-, C18:1-, C24:0- and C24:1-Cer IgGs were detected in the CSF and serum of MS patients in comparison with controls. For IgGs against particular Cer subspecies, correlations were found between their CSF and serum level, as well as with the Link index. Serum and the CSF anti-Cer IgGs differed between patients with clinically isolated syndrome (CIS) and relapsing-remitting MS from those with progressive MS. No correlations were found between anti-Cer IgGs and other MS-related clinical variables. CONCLUSION: Patients with MS have shown altered panels of anti-Cer IgGs in the CSF and serum, which might suggest a relevant, though limited role of Cer as a target for autoimmune humoral response. Utility of antibodies against Cer subspecies as potential markers for MS activity and progression deserves further investigations.

Cantilevers: Multi-Tool in Orthodontic Treatment.

This review aims to discuss and illustrate various uses of cantilevers to solve multiple clinical issues and prove their versatility. Cantilevers are commonly used in the segmented arch technique, and they can be designed to solve various clinical problems with highly predictable results. Its design and shape can modify the various combinations of vertical and horizontal forces. The novel trend is to combine cantilevers with skeletal anchorage. Cantilevers offer a very simple and statically determined force system. The advantage is the control over side effects, which normally occur on the anchor teeth and the occlusion. The disadvantages include possible side effects on the anchorage unit, when the anchorage is poorly controlled. The review highlights the clear benefits of cantilever use in complex corrections of single teeth, segments, and entire arch with a diminished effect on the dentition, also with the use of skeletal anchorage. With their simple and easily tailored design, these springs can be called an orthodontic multi-tool.

Force Systems Produced by Different Cantilever Configurations during Deactivation.

Intrusion with a three-piece arch is routinely achieved during orthodontic treatment. This study aimed to experimentally determine how the cantilever design influences the generated force system. Both straight and arch-formed cantilever designs: tip-back (TB), flat curve (FC) deep curve (DC), and 3 mm and 6 mm high utility arch (UA3; UA6) were activated for 5 mm and 10 mm. Force systems were determined by a hexapod. Typodonts simulating a three piece-intrusion arch were scanned using an intraoral scanner (3Shape, TRIOS, Denmark) before (T0) and after (T1) the experiment and superimposed with Mimics software (Materialise, Leuven, Belgium). Data were analyzed. All straight designs displayed an extrusive force in the vertical plane, and all arch-formed an intrusive force. DC and TB showed a retrusive force in the sagittal plane and UA6 a protrusive. For the medial/lateral forces, DC and TB displayed a medial, and UA6 a lateral force. Configurations can be distinctively ranked from DC, FC, TB to UA3, and UA6 according to the increasing protrusive nature of the generated sagittal forces. A DC or TB configuration should be used for intrusion and retraction, while for an intrusion and a protrusion, a UA6 configuration. All straight configurations showed a higher force level than the arch-formed configurations.

The Effect of Symmetric and Asymmetric Loading of Frontal Segment with Two Curved Cantilevers: An In Vitro Study.

Cantilevers generate statically determined force systems. The frontal segment loading with symmetric and asymmetric cantilevers in a three-piece intrusion base arch can be used to correct midline asymmetry. Three types of 0.017″ × 0.025″ beta-titanium cantilevers: tip-back (TB), deep curve (DC), utility arch (UA) were tested on typodonts simulating intrusion of the maxillary anterior segment. Typodonts with symmetric and asymmetric cantilevers were scanned with intraoral scanner (3Shape, TRIOS, Copenhagen, Denmark) before (T0) and after (T1) the experiment, scans were superimposed using Mimics software (Materialise, Leuven, Belgium). Data were analysed with qualitative analysis. All cantilevers generated vertical and horizontal forces. For symmetric design, the DC and TB displayed intrusive force with retrusive component, UA intrusion and protrusion. The asymmetric cantilevers produced transverse displacement of anterior segment. DC created lateral, UA medial force, the anterior segment displacement was consistent with the used configuration. The movement of an anterior segment with TB is smaller compared to DC and UA. Symmetric cantilevers configurations can achieve simultaneous intrusion and retrusion or protrusion of the anterior segment. The asymmetric design with transversal force can clinically aid the correction of midline discrepancies. The effect of the cantilever configuration on delivered force direction was confirmed.

Analysis of tympanic sinus shape for purposes of intraoperative hearing monitoring: a microCT study.

PURPOSE: Sinus tympani is the space in the retrotympanum, with variable morphology. Computed tomography is a common tool to investigate sinus tympani anatomy. During cochlear implantation or tympanoplasty, electrocochleography can be used for hearing monitoring. In such a surgical strategy the electrode is placed in the round window's region throughout posterior tympanotomy. Common accessible needle-shaped electrodes using is difficult in achieving intraoperative stabilization. The aim of the study is to assess the dimensions and shape of sinus tympani, basing on the micro computed tomography scans for purposes of establishing the possible new electrocochleography electrode shape. MATERIALS AND METHODS: Sixteen fresh frozen cadaveric temporal bones were dissected. MicroCT measurements included the depth and the width of sinus tympani, width of facial canal with stapedius muscle chamber. Obtained data were analyzed statistically with the use of RStudio 1.3.959 software. RESULTS: The highest average width of sinus tympani amounted for 2.68 mm, depth measured at the round window plane for 3.19 mm. Width of facial canal with stapedius muscle chamber highest average values at the round window plane- 3.32 mm. The lowest average minimum and maximum values were calculated at the 1 mm above the round window plane. The highest average posterior tympanotomy width was 2.91 mm. CONCLUSIONS: The shape of the tympanic sinus is like a trough with the narrowest and deepest dimensions in the middle part. The ST shape and dimensions should be taken into account in constructing the ECochG electrode, designed for optimal placement through posterior tympanotomy approach.

Craniofacial shape from pre- to post-adolescence.

AIM: Craniofacial growth demonstrates significant variation and is difficult to predict. The aim of the present investigation was twofold: (1) to assess the association (covariation) between craniofacial shape at pre- and post-adolescence and (2) to evaluate if pre-adolescent craniofacial shape is related (covaries) with growth magnitude and direction. SUBJECTS AND METHODS: One hundred fifty subjects (86 males and 64 females) untreated orthodontically were selected from AAOF Craniofacial Growth Legacy Collection. Each subject had cephalograms taken before 9 (pre-adolescent stage) and after 15 years of age (post-adolescent). Fourteen curves comprising 123 points (10 fixed and 113 sliding semilandmarks) comprehensively covering the craniofacial skeleton were digitally traced on each cephalogram. Procrustes alignment, principal component analysis, 2-block partial least squares (2B-PLS) analysis, and regression analysis were done after sliding the semilandmarks to minimize bending energy. RESULTS: The first 16 principal components (PCs) were non-trivial and explained 85.2% of total shape variability in the sample. PC1 depicted mainly variability in the vertical direction, PC2 represented mostly variability in the saddle angle and in the antero-posterior position of the mandible, and PC3 depicted primarily variability of the mandibular shape (steep versus flat mandibular plane). The covariation between pre- and post-adolescent facial shape was statistically significant, both in the pooled sample (RV coefficient = 0.604) and in boys (RV = 0.639) and girls (RV = 0.629). The pre-adolescent shape was weakly associated with the magnitude of facial change-2-block PLS analysis demonstrated that blocks 1 and 2 were independent (P = 0.118, RV = 0.035). CONCLUSIONS: The pre-adolescent shape of the craniofacial complex explained approximately 60% of the post-adolescent shape of the craniofacial complex; however, the relationship between pre-adolescent shape of the craniofacial complex and magnitude of its change was weak.

Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis. METHODS: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403). FINDINGS: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21-11·53, p<0·0001). 65 (77%) of 84 patients in the efgartigimod group and 70 (84%) of 83 in the placebo group had treatment-emergent adverse events, with the most frequent being headache (efgartigimod 24 [29%] vs placebo 23 [28%]) and nasopharyngitis (efgartigimod ten [12%] vs placebo 15 [18%]). Four (5%) efgartigimod-treated patients and seven (8%) patients in the placebo group had a serious adverse event. Three patients in each treatment group (4%) discontinued treatment during the study. There were no deaths. INTERPRETATION: Efgartigimod was well tolerated and efficacious in patients with generalised myasthenia gravis. The individualised dosing based on clinical response was a unique feature of ADAPT, and translation to clinical practice with longer term safety and efficacy data will be further informed by the ongoing open-label extension. FUNDING: argenx.

The Relationship between Occupationally Exposed Arsenic, Cadmium and Lead and Brain Bioelectrical Activity-A Visual and Brainstem Auditory Evoked Potentials Study.

The aim of this study was to evaluate the parameters of visual and brainstem auditory evoked potentials in patients occupationally exposed to arsenic, cadmium and lead. The study group comprised 41 copper smelter and refinery workers (average age: 51.27) with occupational exposure to arsenic, cadmium and lead. The control group consisted of 36 healthy volunteers (35 men and 1 woman, aged 27-66, average age: 51.08). Neurological examination, brain imaging, and visual and brainstem auditory evoked potentials were performed, and the relationship between blood Cd, Pb concentration (Cd-B, Pb-B), blood zinc protoporphyrin (ZnPP), and urine As concentration (As-U) were assessed. In the workers, exceedances of allowable biological concentrations were observed, with the urinary concentration of arsenic being 5.2%, the cadmium and lead in blood being 1.3%, while the case of ZnPP was 2.6%. The mean P100, relative P100, and N145 visual evoked potential (VEP) latencies were significantly longer in exposed workers than in the controls. The mean wave III and V brainstem auditory evoked potential (BAEP) latency and the mean wave III-V and I-V interpeak latencies were longer, and the I and V amplitude was lower in the workers than the controls. In summary, occupational exposure to As, Cd, and Pb is associated with prolonged latency and reduced evoked potential amplitude, but As-U, Pb-B, Cd-B, and ZnPP concentrations are not linearly related to potential components. The analysis of evoked potentials may be a useful method of assessment of the central nervous system in patients with occupational exposure to heavy metals.

Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.

Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis.

OBJECTIVE: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. METHODS: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity. RESULTS: Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement. CONCLUSIONS: Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

BACKGROUND: The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. OBJECTIVES: Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. MATERIAL AND METHODS: In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. RESULTS: There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. CONCLUSIONS: Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.

Preliminary Study on the Role of TMEM39A Gene in Multiple Sclerosis.

Genome-wide association studies (GWAS) have identified hundreds of new potential genetic risk loci associated with numerous complex diseases such as multiple sclerosis (MS). Genes which have been discovered by GWAS are now the focus of numerous ongoing studies. The goal of this study was to confirm and understand the potential role of one of such genes-transmembrane protein 39A gene (TMEM39A)-in multiple sclerosis.We showed the difference in TMEM39A messenger RNA (mRNA) expression between MS patients and controls (T 22;74 = 5.429; p = 0.0063). In our study, the lower mRNA expression of TMEM39A gene in patients did not correlate with a higher methylation level of the TMEM39A promoter. Moreover, a decreased level of TMEM39A mRNA was associated neither with rs1132200 nor with rs17281647. Additionally, we did not find an association between these two TMEM39A polymorphisms and the risk and progression of multiple sclerosis.Our investigation is the first which indicates that TMEM39A mRNA expression may be associated with the development and/or course of multiple sclerosis.

PD-1 gene polymorphic variation is linked with first symptom of disease and severity of relapsing-remitting form of MS.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor.

Profile of autonomic dysfunctions in patients with primary brain tumor and possible autoimmunity.

OBJECTIVE: Cerebral lesion due to different neurological conditions could be complicated by autonomic dysfunction, reported in the literature as a sympathetic hyperactivity. The mechanisms of dysautonomia still remains partial. The aim of the study was to assess the profile of autonomic dysfunction in patient with primary brain tumors, with attempt to estimate the additional factors in pathogenesis of dysautonomia. MATERIAL AND METHODS: Neurological examinations, the Low's autonomic disorder questionnaire, electrophysiological autonomic tests (Heart Rate Variability test at rest and during deep breathing, spectral analysis of R-R intervals, sympathetic skin response test), studies of peripheral nerves, blood sampling collection for antibodies were done in 33 patients with recognized primary brain tumors. RESULTS: The averaged Low's Questionnaire score in the patients group was significantly higher than in the controls, systolic blood pressure was increased, heart rate tended to be higher without significance, but heart rate variability was severe low, LF/HF ratio also tended to be higher in the patients group. In SSR test the amplitude of responses from hand and foot was significantly lower without changes in their latencies. We found changes in the electrophysiological tests of peripheral nerves, and positive anti-neural antibodies in 5 patients. CONCLUSIONS: The results of the study indicated to the sympathetic nervous system hyperactivity in patients with primary brain tumors. Local brain lesion with high intracranial pressure, additional peripheral nerve damage probably in the course of autoimmunity, and direct influence of autoimmunity to the central part of autonomic nervous system are possible in the pathogenesis of dysautonomia.

Cognitive performance, fatigue and event-related potentials in patients with clinically isolated syndrome.

OBJECTIVES: Cognitive impairment and fatigue are regarded as important aspects of multiple sclerosis. The aim of this study was to evaluate cognitive performance, the level of fatigue and parameters of event-related potentials (ERP) in patients diagnosed with clinically isolated syndrome (CIS). PATIENTS AND METHODS: The study comprised 44 patients with CIS and 45 healthy controls. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBNT), fatigue - using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Auditory ERP were performed and the parameters of N200 and P300 components were analyzed. Neuropsychological and electrophysiological measures were referred to clinical and radiological features of the disease activity. RESULTS: Forty five% of patients failed in at least one test from BRBNT, mainly within the domains of memory and attention. In 18% of patients FSS corresponded with moderate or severe fatigue. The mean latency of N200 and P300 was significantly longer and amplitude of P300 was lower in those patients with CIS than in the controls. Significant correlations were found between the results of MFIS and tests evaluating verbal memory and attention, as well as between N200 latency and results of tests for verbal memory. CONCLUSIONS: Cognitive performance and fatigue deserve attention from the earliest clinical stage of MS. Abnormalities of event-related potentials in CIS suggest early impact of the disease on functional neural networks.

Event-related potentials and cognitive performance in multiple sclerosis patients with fatigue.

The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue.

Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors?

INTRODUCTION: Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors. MATERIALS AND METHODS: Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2-4 days after their admission to our department. RESULTS: We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti-neuroendothelium, anti-GFAP, anti-MAG, anti-PCNA, and anti-Ro52 antibodies. CONCLUSIONS: In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.

Polymorphisms in CD28, CTLA-4, CD80 and CD86 genes may influence the risk of multiple sclerosis and its age of onset.

CD28/CTLA-4­CD80/CD86 molecules play an important role in the regulation of T cells activation. Defects in proteins involved in this pathway may lead to the development of autoimmune diseases in which T cells are involved. In this case­control study (336 multiple sclerosis (MS) patients and 322 controls) we investigated the possible association of eleven polymorphisms in CD28, CTLA-4, CD80 and CD86 genes with susceptibility to MS and/or its progression. We also took into account HLA-DRB1*15:01 status. Moreover, this study aimed to determine the possible gene-gene interactions between examined SNPs associated with the susceptibility to MS and its outcome. Our investigation revealed that in HLA-DRB1*15:01 negative individuals, G allele in rs231775A NGof CTLA-4 gene was associatedwith higher risk ofmultiple sclerosis. Additionally, the association of rs2715267T NGof CD86 gene withMS susceptibilitywas detected. In details, carriers of G allele at this polymorphic site possessed higher risk of MS in comparison to TT homozygotes. On the other hand, the lower risk of MS was observed in individuals carrying A allele at the rs1599795T N A polymorphic site of CD80. Furthermore, the analysis revealed an interaction between three polymorphisms: rs3116496T N C (CD28), rs6641T N G (CD80) and rs17281995G N C (CD86), associated with the age of MS onset.