Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

"Two sides of the same coin": constant motor learning speeds up, whereas variable motor learning stabilizes, speed-accuracy movements.

PURPOSE: The aim of this study was to determine the time course of the trade-off between speed and accuracy, intraindividual variability, and movement transfer and retention (4 weeks after learning) of speed-accuracy tasks. METHODS: The participants in this study were healthy adults randomly divided into three groups (control versus constant versus variable). They were aged 19-24 years, and 30 (15 men and 15 women) were in each group. Participants had to perform various tasks with the right dominant hand: (a) simple reaction test; (b) maximal velocity measurement; and (c) a speed-accuracy task. RESULTS: During constant and variable learning, the trade-off in a speed-accuracy task in specific situations shifted toward improved motor planning and motor execution speed, and to reduced intraindividual variability. However, during variable learning, the maximal velocity and variability of motor planning time did not change. Constant learning effectively transferred into variable tasks in terms of reaction time, average velocity and maximal velocity, and these effects were greater than those associated with variable learning. However, the effects of constant learning did not transfer fully into the performance variability of variable movements. Variable learning effectively transferred into constant tasks for the coefficient of variation of the path of movement, average velocity, maximal velocity and reaction time. The retention effect depended neither on learning nor task specificity (constant versus variable tasks). CONCLUSION: Constant learning speeds up but does not stabilize speed-accuracy movements in variable tasks; whereas, variable learning stabilizes but does not speed up speed-accuracy movements in constant tasks.

One night of sleep deprivation impairs executive function but does not affect psychomotor or motor performance.

The current study assessed the impact of one night of sleep deprivation on cognitive, motor and psychomotor performance. Thirty healthy young adult male subjects completed a 24 h control or 24 h sleep deprived trial. For the control trial, participants (N = 15) were allowed normal night sleep (~8 h). For the sleep deprived trial, participants (N = 15) did not sleep for 24 h. Cognitive performance during go/no-go, Stroop and simple reaction tasks, psychomotor performance during speed-accuracy tasks with fixed and unfixed targets, and motor performance during countermovement jump, hand grip strength, and 30-s maximal voluntary contraction tasks were evaluated on day 1 at 8 am and 7 pm and on day 2 at 8 am. One night of sleep deprivation impaired psychological well-being and executive function but did not affect simple reaction time, the capacity for arm and leg muscle contraction, motor control performance during a speed-accuracy task with both fixed and unfixed targets, and central and peripheral motor fatigue in the 30 s maximal voluntary contraction task. The present study showed that one night of sleep deprivation resulted in executive function deterioration but did not modify motor control or maximal effort requiring performance of motor tasks.

The contribution of low-frequency fatigue to the loss of quadriceps contractile function following repeated drop jumps.

NEW FINDINGS: What is the central question of this study? Why do some subjects recover slowly following a bout of eccentric exercise and why is recovery faster following a repeated bout? What is the main finding and its importance? The results are consistent with two major causes of the reduction of quadriceps torque, the onset of low-frequency fatigue which recovered relatively fast and a second, delayed form of damage. Differences in the delayed damage process largely accounted for the differences in the rate of torque recovery between subjects after a first bout and it was suppression of the delayed damage which accounted for the faster recovery following a repeated bout of eccentric exercise. ABSTRACT: The purpose of this study was to determine the extent to which low-frequency fatigue (LFF) accounts for the loss of quadriceps strength and time course of recovery following a series of drop jumps (DJs). Seventeen female subjects (20.8 ± 1.4 years) undertook 100 DJs, which were repeated 4 weeks later. Maximum isometric torque (MIT) and the ratio of torque generated by 20 and 100 Hz electrical stimulation (20/100), as a measure of LFF, were measured over 7 days following each series of DJs. After the first series the 20/100 ratio fell to a greater extent than MIT (to 35 ± 8.7% and 69 ± 11%, respectively) but recovered over 2-3 days, while MIT showed little recovery over this time. Changes of the 20/100 ratio were similar between subjects with fast or slow MIT recovery. Following the second series of DJs, changes in the 20/100 ratio were similar to those of the first bout and there were no differences between fast and slow recovering subjects. MIT, however, recovered more rapidly than after the first bout; the faster recovery was confined to the subjects who recovered slowly following the first bout. The results are consistent with two major causes of the reduction of quadriceps torque, the onset of low-frequency fatigue which recovered relatively fast and a second, delayed, form of damage. The latter largely accounted for the differences in MIT recovery between subjects after the first bout, while suppression of the delayed damage accounted for the faster recovery following the repeated bout.

What are the best isometric exercises of muscle potentiation?

PURPOSE: The aim of this study was to follow post-activation potentiation (PAP), low-frequency fatigue (LFF), metabolic-induced fatigue and post-contractile depression (PCD) in response to different isometric muscle contraction modalities. METHODS: Young healthy men (N = 120) were randomly assigned to one of ten exercise modality groups which differed in contraction duration (5-60 s), activation pattern (intermittent or continuous contractions), activation mode (voluntary or stimulated), and intensity [maximal or submaximal (50%)]. Isometric maximal voluntary contraction (MVC), and electrically induced knee extension torque were measured at baseline and at regular intervals for 60 min after exercise. RESULTS: Muscle contraction modalities involving 5 s MVC were the most effective for PAP, whereas the lowest PAP effectiveness was found after the 12 × 5-MVC modality. After all of the 5-15 s MVC and 6 × 5-MVC protocols, the potentiation of the twitch rate was significantly higher than that recorded after continuous 30-60 s protocols (P < 0.001). Tetanic maximal torque (100 Hz) potentiation occurred 5 min after 15-30 s repetitive MVC modalities and after modality involving 15 electrical stimuli (P < 0.05). CONCLUSIONS: The findings demonstrate that post-activation potentiation was most effective after brief duration continuous and repetitive MVC protocols. To understand the resultant warm-up of motor performance, it is necessary to recognize the coexistence of muscle PAP, tetanic maximal force potentiation, rapid recovery of metabolic muscle, and central muscle activation processes, as well as prolonged LFF and prolonged PCD.

Children, Young Adults, and Older Adults Choose Different Fast Learning Strategies.

The aim of the study was to establish whether there were differences in speed-accuracy movement learning strategies between children, young adults, and older adults. A total of 30 boys, 30 young adult men, and 30 older men were seated in a special chair at a table with a Dynamic Parameter Analyzer 1. Participants had to perform a speed-accuracy task with the right-dominant hand. It may be assumed that the motor variables of children are more prone to change during the fast learning process than those of young adults and older adults and that the development of internal models is more changeable in children than in young adults and the older adults during the fast adaptation-based learning process.

Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species.

Increased production of reactive oxygen/nitrogen species (ROS) and impaired cellular Ca2+ handling are implicated in the prolonged low-frequency force depression (PLFFD) observed in skeletal muscle after both metabolically and mechanically demanding exercise. Metabolically demanding high-intensity exercise can induce PLFFD accompanied by ROS-dependent fragmentation of the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptor 1s (RyR1s). We tested whether similar changes occur after mechanically demanding eccentric contractions. Human subjects performed 100 repeated drop jumps, which require eccentric knee extensor contractions upon landing. This exercise caused a major PLFFD, such that maximum voluntary and electrically evoked forces did not recover within 24 h. Drop jumps induced only minor signs of increased ROS, and RyR1 fragmentation was observed in only 3 of 7 elderly subjects. Also, isolated mouse muscle preparations exposed to drop-jump-mimicking eccentric contractions showed neither signs of increased ROS nor RyR1 fragmentation. Still, the free cytosolic [Ca2+] during tetanic contractions was decreased by ∼15% 1 h after contractions, which can explain the exaggerated force decrease at low-stimulation frequencies but not the major frequency-independent force depression. In conclusion, PLFFD caused by mechanically demanding eccentric contractions does not involve any major increase in ROS or RyR1 fragmentation.-Kamandulis, S., de Souza Leite, F., Hernandez, A., Katz, A., Brazaitis, M., Bruton, J. D., Venckunas, T., Masiulis, N., Mickeviciene, D., Eimantas, N., Subocius, A., Rassier, D. E., Skurvydas, A., Ivarsson, N., Westerblad, H. Prolonged force depression after mechanically demanding contractions is largely independent of Ca2+ and reactive oxygen species.

Task-relevant cognitive and motor functions are prioritized during prolonged speed-accuracy motor task performance.

This study aimed to explore the effect of prolonged speed-accuracy motor task on the indicators of psychological, cognitive, psychomotor and motor function. Ten young men aged 21.1 ± 1.0 years performed a fast- and accurate-reaching movement task and a control task. Both tasks were performed for 2 h. Despite decreased motivation, and increased perception of effort as well as subjective feeling of fatigue, speed-accuracy motor task performance improved during the whole period of task execution. After the motor task, the increased working memory function and prefrontal cortex oxygenation at rest and during conflict detection, and the decreased efficiency of incorrect response inhibition and visuomotor tracking were observed. The speed-accuracy motor task increased the amplitude of motor-evoked potentials, while grip strength was not affected. These findings demonstrate that to sustain the performance of 2-h speed-accuracy task under conditions of self-reported fatigue, task-relevant functions are maintained or even improved, whereas less critical functions are impaired.

Effect of constant, predictable, and unpredictable motor tasks on motor performance and blood markers of stress.

An unfamiliar or novel physical stimulus induces activation of dopaminergic neurons within the brain and greater activity in areas involved in emotion; considering this, we aimed to establish whether unpredictable prolonged (fatiguing) motor task (vs. constant vs. predictable) evokes greater dopaminergic activity, enhances neuromuscular performance, motor accuracy, and perception of effort, and delays overall central fatigue. Fifteen healthy male volunteers (aged 22 ± 4 years) were required to perform 1 of 3 exercise trials (at least 1 week apart) of 100 intermittent isometric contraction (IIC) tasks involving knee extensions at 60° flexion. Trials were structured differently by simulated contraction intensity. A fatigue task involved 5-s contractions and 20-s rest. Variables measured before, during, and after IIC were electrically induced force, maximal voluntary contraction, central activation ratio, intramuscular temperature, and blood levels of dopamine, cortisol, and prolactin, and intraindividual motor variability and accuracy (constant and absolute error). We found that IIC increased central and peripheral fatigue, force sensation, and T mu, and decreased absolute and constant error without visual feedback, but did not affect motor variability. There were no significant differences between the three IIC tasks. However, only unpredictable tasks increased dopaminergic activity, which was insufficient to affect central motivation to perform isometric exercise and alter centrally mediated components of fatigue.

The effects of 4 weeks stretching training to the point of pain on flexibility and muscle tendon unit properties.

PURPOSE: The purpose of this study was to compare the benefits and possible problems of 4 weeks stretching when taken to the point of pain (POP) and to the point of discomfort (POD). METHODS: Twenty-six physically active women (20 ± 1.1 years) took part in group-based stretching classes of the hamstring muscles, 4 times per week for 4 weeks, one group one stretching to POD, the other to POP. Passive stiffness, joint range of motion (ROM), maximal isometric torque and concentric knee flexion torque, were measured before training and 2 days after the last training session. RESULTS: Hip flexion ROM increased by 14.1° (10.1°-18.1°) and 19.8° (15.1°-24.5°) and sit-and-reach by 7.6 (5.2-10.0) cm and 7.5 (5.0-10.0) cm for POD and POP, respectively (Mean and 95% CI; p < 0.001 within group; NS between groups), with no evidence of damage in either group. Despite the large increases in flexibility there were no changes in either compliance or viscoelastic properties of the muscle tendon unit (MTU). CONCLUSION: Hamstrings stretching to POP increased flexibility and had no detrimental effects on muscle function but the benefits were no better than when stretching to POD so there is no justification for recommending painful stretching. The improvements in flexibility over 4 weeks of stretching training appear to be largely due to changes in the perception of pain rather than physical properties of the MTU although less flexible individuals benefited more from the training and increased hamstring muscle length.

Prevalence and burden of headache disorders in Lithuania and their public-health and policy implications: a population-based study within the Eurolight Project.

BACKGROUND: The Eurolight project assessed the impact of headache disorders in ten EU countries, using the same structured questionnaire but varying sampling methods. In Lithuania, sample selection employed methods in line with consensus recommendations for population-based burden-of-headache studies. METHODS: The survey was cross-sectional. We identified, from the Residents' Register Service, a sample of inhabitants of Kaunas city and surrounding Kaunas region reflecting age (in the range 18-65 years), gender and rural/urban distributions of Lithuania. Medical students called unannounced at their homes and conducted face-to-face interviews employing a structured questionnaire. RESULTS: Of 1137 people in the pre-identified sample, 573 (male 237 [41.4%], female 336 [58.6%]; mean age 40.9 ± 13.8 years) completed interviews (participation proportion: 50.4%). Gender-adjusted 1-year prevalences were: any headache 74.7%; migraine 18.8%; tension-type headache (TTH) 42.2%; all headache on ≥15 days/month 8.6%; probable medication-overuse headache (pMOH) 3.2%. Migraine (OR: 3.6) and pMOH (OR: 2.9) were associated with female gender. All headache types except TTH were associated with significantly diminished quality of life. Migraine caused a mean 4.5% loss in paid worktime per affected male and 3.5% per affected female. Lost per-person times due to TTH were much less, but to pMOH and other headache on ≥15 days/month much higher. Among the entire workforce, lost productivity to migraine was estimated at 0.7%, to TTH 0.3% and to pMOH or other headache on ≥15 days/month 0.5%. The total of 1.5% may translate directly into lost GDP. Alternative calculations based on headache yesterday (with little recall error) produced, for all headache, a corroborating 1.7%. Similar losses from household work would also drain the nation's economy. Our findings were comparable to those from earlier studies using similar methods in Russia and Georgia. CONCLUSIONS: The multiple burdens from headache in Lithuania indicate substantial ill-health and unmet need for health care. The heavy burdens on individuals are matched by heavy economic burden. Of particular concern is the high prevalence of headache on ≥15 days/month, seen also in Russia and Georgia. Health policy in Lithuania must heed WHO's advice that effective treatment of headache, clearly desirable for its health benefits, is also expected to be cost-saving.

Crucial role of carotid ultrasound for the rapid diagnosis of hyperacute aortic dissection complicated by cerebral infarction: A case report and literature review.

Aortic dissection is a life-threatening rare condition that may virtually present by any organ system dysfunction, the nervous system included. Acute cerebral infarction among multiple other neurological and non-neurological presentations is part of this acute aortic syndrome. Rapid and correct diagnosis is of extreme importance keeping in mind the possibility of thrombolytic treatment if a patient with a suspected ischemic stroke arrives to the Emergency Department within a 4.5-h window after symptom onset. Systemic intravenous thrombolysis in the case of an acute brain infarction due to aortic dissection may lead to fatal outcomes. In this neurological emergency it is important to rule out underlying aortic dissection by choosing appropriately quick and accurate diagnostic tool. We aimed to present a prospective follow-up case, where carotid ultrasound examination was the primary key method that led to a correct diagnosis in hyperacute (<24h) Stanford type A aortic dissection presenting as an acute ischemic stroke, and thereafter with a repeated contrast-enhanced computed tomography and transthoracic echocardiography, helped to monitor topography of intravascular processes and hemodynamic properties during the clinical course of a disease, which influenced treatment decisions. Thus, we reviewed the literature mainly focusing on the various neurological aspects associated with aortic dissection.

Test-Retest Cross-Reliability of Tests to Assess Neuromuscular Function as a Multidimensional Concept.

The purpose of this investigation was to estimate the test-retest cross-reliability of peripheral and central changes with respect to nonlinear and linear measures of a surface electromyography (EMG) signal measured during isometric maximal voluntary contraction (MVC) combined with superimposed electrical stimulation during a brief and fatiguing task involving the ankle plantar flexors over 2 follicular phases of menstrual cycle. Ten healthy female adults underwent 1 familiarization session and 5 identical test-retest sessions. The results showed that the decrease in plantar flexor EMG components (root mean square [RMS], mean frequency [MnF], wavelet packet entropy [WPE]) for soleus and gastrocnemius muscles, central activation ratio (CAR) and MVC, and contractile properties (P20, P100, PTT-100, and half-relaxation time) of the plantar flexor muscles at the end of 2-minute MVC were similar (time effect; p < 0.001, η(p)² > 0.7, statistical power [SP] > 99%) and exhibited high stability over 5 trials (trial effect; p > 0.05; η(p)² < 0.2, SP < 30%). High reliability between trials was found for 5-second MVC (intraclass correlation coefficient [ICC] > 0.82, p < 0.001) and meaningful reliability for 2-minute MVC (ICC > 0.66, p < 0.01). In conclusion, in young healthy women, measurements of neuromuscular function, such as RMS, MnF, and WPE of a surface EMG signal, MVC, and CAR from a brief and sustained MVC of the ankle plantar flexors, are reliable, and multidimensional stability was found with respect to both high and low correlation outcomes across the 5 identical test-retest trials of any 2 properties measured during brief and sustained MVC.

Is intraindividual variability different between unimanual and bimanual speed-accuracy movements?

Dominant (right) and nondominant (left) hand differences in motor performance variables were investigated during targeted rapid aiming unimanual and bimanual (to two separate targets) speed-accuracy tasks. The performance of the dominant and nondominant hands were compared during rapid targeted unimanual and bimanual reaching tasks (50 repetitions) in adult, neurologically intact, right-handed men (n = 20). As task difficulty increased from unimanual to bimanual tasks, reaction time increased and velocity (average and maximal) of performance decreased significantly. The effect of hand was significant only on average movement velocity and on intraindividual variability of accuracy (in both cases performance in the left hand was worse). Variability of movement path (accuracy) was less in the right hand during both unimanual and bimanual tasks.

Intermittent whole-body cold immersion induces similar thermal stress but different motor and cognitive responses between males and females.

The main aim of this study was to compare the thermal responses and the responses of cognitive and motor functions to intermittent cold stress between males and females. The intermittent cold stress continued until rectal temperature (TRE) reached 35.5°C or for a maximum of 170 min. Thermal response and motor and cognitive performance were monitored. During intermittent cold stress, body temperature variables decreased in all subjects (P < 0.001) and did not differ between sexes. The presence of fast and slow cooling types for participants with similar effect on physiological variables were observed; thus the different rate coolers were grouped together and were attributed only sex specific responses. Overall, TRE cooling rate and cold strain index did not differ between sexes. Maximal voluntary contraction (MVC) decreased after intermittent cold exposure only in males (P < 0.001), whereas changes in muscle electromyography (EMG) activity did not differ between sexes. The effects of intermittent cold stress on electrically evoked muscle properties, spinal (H-reflex), and supraspinal (V-waves) reflexes did not differ between sexes. Intermittent cold-induced cognitive perturbation of attention and memory task performance was greater in males (P < 0.05). Contrary to our expectations, the results of the present study indicated that males and females experience similar thermal stress induced by intermittent whole-body cold immersion. Although no sex-specific differences were observed in muscle EMG activity, involuntary muscle properties, spinal and supraspinal reflexes, some of the sex differences observed (e.g., lower isometric MVC and greater cognitive perturbation in males) support the view of sex-specific physiological responses to core temperature decrease.

The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania.

BACKGROUND: The association of HLA DRB1 alleles with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical features and disability is still unclear probably due to diversity in ethnicity and geographic location of the studied populations. The aim of the present study was to investigate the influence of HLA DRB1 alleles on the clinical features and disability of the patients with MS in Lithuania. METHODS: This was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction. RESULTS: The first symptoms of MS in patients with HLA DRB1*15 allele manifested at younger age than in those without this allele (28.32 +/- 5.49 yrs vs. 30.94 +/- 8.43 yrs, respectively, p = 0.043). HLA DRB1*08 allele was more prevalent among relapsing-remitting (RR) MS patients than among patients with progressive course of MS (25.0% vs. 8.3%, respectively, chi^2 = 6.000, p = 0.05). MS patients with this allele had lower relapse rate than those without this allele (1.00 +/- 0.97 and 1.44 +/- 0.85, respectively, p = 0.043). Degree of disability during the last visit was lower among the patients with HLA DRB1*08 allele (EDSS score 3.15 +/- 1.95 vs. 4.49 +/- 1.96, p = 0.006), and higher among those with HLA DRB1*15 allele (EDSS score 4.60 +/- 2.10 vs.4.05 +/- 1.94, p = 0.047) compared to patients without these alleles but there were no significant associations between these alleles and the duration of the disease to disability. HLA DRB1*08 allele (OR = 0.18, 95% CI 0,039-0,8, p = 0.029) was demonstradet to be independent factor to take a longer time to reach an EDSS of 6, while HLA DRB1*01 allele (OR = 5.92, 95% CI 1,30-26,8, p = 0.021) was related in a shorter time to reach and EDSS of 6. Patients with HLA DRB1*08 allele had lower IgG index compared to patients without this allele (0.58 +/- 0.17 and 0.73 +/- 0.31, respectively, p = 0.04), and HLA DRB1*15 allele was more often found among MS patients with oligoclonal bands (OCBs) in cerebrospinal fluid than among those without OCBs (OR 2.3, CI 95% 1.017-5.301; p = 0.043). CONCLUSIONS: HLA DRB1*15 allele was related with an earlier manifestation of the first MS symptoms, progressive course of the disease and higher degree of disability. HLA DRB1*08 allele was more prevalent among the RR MS patients and was associated with the lower rate of relapse, degree of disability and IgG index.

The effect of temperature on amount and structure of motor variability during 2-minute maximum voluntary contraction.

INTRODUCTION: In this study, we questioned whether local cooling of muscle or heating involving core and muscle temperatures are the main indicators for force variability. METHODS: Ten volunteers performed a 2-min maximum voluntary contraction (MVC) of the knee extensors under control (CON) conditions after passive heating (HT) and cooling (CL) of the lower body. RESULTS: HT increased muscle and rectal temperatures, whereas CL lowered muscle temperature but did not affect rectal temperature. During 2-min MVC, peak force decreased to a lower level in HT compared with CON and CL experiments. Greater central fatigue was found in the HT experiment, and there was less in the CL experiment than in the CON experiment. CONCLUSIONS: Increased core and muscle temperature increased physiological tremor and the amount and structural complexity of force variability of the exercising muscles, whereas local muscle cooling decreased all force variability variables measured.

Frequency of HLA-DRB1 gene alleles in patients with multiple sclerosis in a Lithuanian population.

The aim of the present study was to investigate the influence of HLA-DRB1 alleles on the genetic susceptibility to multiple sclerosis in the Lithuanian population. MATERIAL AND METHODS. A total of 120 patients with multiple sclerosis and 120 unrelated healthy controls were enrolled in this case-control study. Allelic frequencies were compared between the groups. HLA-DRB1 alleles were genotyped using the polymerase chain reaction. RESULTS. HLA-DRB1*15 was present in 55.8% of the patients with multiple sclerosis and 10.0% of the controls (OR, 5.58; 95% CI, 3.19-9.77; P<0.0001). The protective alleles that were found to be more prevalent among the controls compared with the patients with multiple sclerosis were HLA-DRB1*01 (26.7% vs. 7.5%, P<0.0001), *03 (17.5% vs. 8.3%, P=0.034), and *16 (11.7% vs. 3.3%, P=0.014). HLA-DRB1*15 was more common among the female patients with multiple sclerosis than among the male patients (68.4% vs. 34.1%; OR, 4.18; 95%, CI 1.90-9.22; P=0.001). The heterozygous inheritance of HLA-DRB1*15 allele was more common in the patients with a history of maternal multiple sclerosis than in those with a history of paternal multiple sclerosis (29.4% vs. 9.8%; P=0.045). CONCLUSIONS. HLA-DRB1*15 was found to be associated with multiple sclerosis in the Lithuanian population. This allele was more prevalent among the female patients with multiple sclerosis. Maternal multiple sclerosis was more common than paternal multiple sclerosis, but the relationship with HLA-DRB1*15 allele was not established. HLA-DRB1*01, *03, and *16 appeared to be the protective alleles in this series.

Reliability and validity of DPA-1 testing after anterior cruciate ligament reconstruction.

There is a lack of equipment and methods for the reliable and valid measurements of human neuromuscular control. To overcome this limitation, an analyzer of dynamic parameters (DPA-1) of human hand and leg movements was constructed by Kaunas University of Technology and "Katra" engineers in collaboration with the Lithuanian Academy of Physical Education. The aim of the study was to determine the reliability and validity of the tests performed on the DPA-1 in healthy and injured subjects after the anterior cruciate ligament (ACL) reconstruction surgery. MATERIAL AND METHODS. The men who had undergone a unilateral ACL reconstruction (n=17, on the average 3.8 months [SD, 2.1] after the surgery) and healthy untrained men (n=17) performed the research protocol twice within 24 hours in between. Average reaction time, mean and maximal movement speed, time to reach maximal speed, and movement distance of the right and left feet for the patients and of the dominant foot for the healthy subjects using the DPA-1 as well as the scores of isokinetic muscle strength and self-assessment tests were registered. RESULTS. There was a significantly reduced concentric peak torque on the injured knee compared with the uninjured knee during knee extension, and the mean score of the Lysholm scale for the injured knee was 69.1 (SD, 13.7) (P<0.05, compared between legs). The test-retest reliability for all the DPA-1 tests varied from 0.68 to 0.94 (P<0.05). However, there were no significant differences in most variables measured by the DPA-1 between injured knee, uninjured knee, and control knee. CONCLUSIONS. The results revealed low validity of the DPA-1 tests for the evaluation of patients following ACL surgery, despite the reliability of these tests varied from moderate to very high.

Comorbidity in multiple sclerosis: Emphasis on patient-reported outcomes.

BACKGROUND: Aim of our study was to estimate the prevalence of comorbid conditions and adverse health behaviors in relapsing-remitting multiple sclerosis (RRMS) patients and evaluate association between comorbidity and MS outcomes (relapse rate, fatigue and quality of life) in Lithuanian setting. METHODS: A prospective cohort study was carried out in the MS center of Lithuanian University of Health Sciences Hospital Kaunas clinics from November 2016 to March 2021. People with MS filled a self-report comorbidity and adverse health behavior questionnaire, visual analogue fatigue scale (VAFS), a Short Form 36 (SF-36) v2 health related quality of life questionnaire (QoL). Information about disability and relapses was acquired from medical documentation and Lithuanian MS registry at baseline and after 24-month observational period. Chi square, t-test, ANOVA, Mann-Whitney U were used for basic statistical evaluation. Multivariable logistic regression models were used to prognose MS outcomes in association to comorbidity and adverse health behaviors, adjusting for age and baseline disability. RESULTS: Of 230 RRMS patients, 167 (72.6%) were women, average age was 42 years. 207 persons were followed through the observational period and included into relapse analysis. 112 (48.7%) of participants reported having at least one comorbidity, the most prevalent were arterial hypertension (19.1%) depression (16.5%) and anxiety (14.8%). People with comorbidities had higher fatigue (6.6 vs. 5.3, p < 0.001) and lower quality of life (overall SF-36 46.3 vs 59.1, p < 0.001). People consuming alcohol had fewer relapses per 24 months (0.56 vs. 0.82, p = 0.01), lower fatigue (5.7 vs. 6.4, p = 0.03), better quality of life (overall SF-36: 56.8 vs. 45.6, p < 0.001), compared to abstinents. In regression models, comorbidities were associated with severe (>7 VAFS) fatigue (Exp(B)=1.98, 95% CI [1.02, 3.86], p = 0.043), diminished (<50 SF-36) QoL (Exp(B)=3.50, 95% CI [1.72, 7.09], p = 0.001). Depression was independently associated with lower QoL (Exp(B)= 2.86, 95% CI [1.04, 7.88], p = 0.042) and severe fatigue (Exp(B)=4.65, 95% CI [2.39, 9.01], p < 0.001); anxiety with diminished QoL (Exp(B)= 4.99, 95%CI [1.67, 14.92], p = 0.002). Light alcohol consumption (compared to abstinents) was associated with decreased risk for: relapse during 24 months (Exp(B)=0.44, 95% CI[0.24, 0.77], p = 0.005), severe fatigue (Exp(B)=0.48, 95% CI [0.24, 0.98], p = 0.042) and lower QoL (Exp(B)= 0.32, 95% CI [0.16, 0.65], p = 0.002). CONCLUSION: Comorbidity is a relevant issue in multiple sclerosis as half of people with MS report concomitant conditions. Hypertension, depression, and anxiety are especially prevalent in MS. In our study, comorbidity is associated with quality of life and fatigue, but not relapse rate. Depression and anxiety are independently associated with lower quality of life and higher fatigue. Light alcohol consumption is associated with reduced relapse risk, less fatigue and better quality of life. Overweight and tobacco smoking do not seem to have negative impact on MS outcomes in our sample.