Sonographic Phrenic Nerve Changes in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity of the affected patients, limits daily activities, and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. Forty-six participants were included in our study, with 23 patients in the ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as an additional diagnostic tool for ALS.

SARS-CoV-2 Seroprevalence in Healthcare Workers of Kaunas Hospitals during the First Wave of the COVID-19 Pandemic.

Background and objective: Serologic testing is a useful additional method for the diagnosis of COVID-19. It is also used for population-based seroepidemiological studies. The objective of the study was to determine SARS-CoV-2 seroprevalence in healthcare workers of Kaunas hospitals and to compare two methods for specific SARS-CoV-2 antibody testing. Materials and Methods: A total of 432 healthcare workers in Kaunas hospitals were enrolled in this study. Each participant filled a questionnaire including questions about their demographics, contact with suspected or confirmed COVID-19, acute respiratory symptoms, and whether they contacted their general practitioner, could not come to work, or had to be hospitalized. Capillary blood was used to test for SARS-CoV-2 specific immunoglobulin G (IgG) and immunoglobulin M (IgM) a lateral flow immunoassay. Serum samples were used to test for specific IgG and IgA class immunoglobulins using semiquantitative enzyme-linked immunosorbent assay (ELISA) method. Results: 24.77% of study participants had direct contact with a suspected or confirmed case of COVID-19. A total of 64.81% of studied individuals had at least one symptom representing acute respiratory infection, compatible with COVID-19. Lateral flow immunoassay detected SARS-CoV-2 specific IgG class immunoglobulins in 1.16% of the tested group. Fever, cough, dyspnea, nausea, diarrhea, headache, conjunctivitis, muscle pain, and loss of smell and taste predominated in the anti-SARS-CoV-2 IgG-positive group. Using ELISA, specific IgG were detected in 1.32% of the tested samples. Diarrhea, loss of appetite, and loss of smell and taste sensations were the most predominant symptoms in anti-SARS-CoV-2 IgG-positive group. The positive percent agreement of the two testing methods was 50%, and negative percent agreement was 99.66%. Conclusions: 1.16% of tested healthcare workers of Kaunas hospitals were anti-SARS-CoV-2 IgG-positive. The negative percent agreement of the lateral flow immunoassay and ELISA exceeded 99%.

Cerebrospinal fluids from Alzheimer's disease patients exhibit neurotoxic effects on neuronal cell cultures.

A growing number of studies suggest amyloid-ß and tau present in cerebrospinal fluid (CSF) and blood as putative biomarkers for Alzheimer's disease (AD). However, there is a question whether these compounds present in patients' bodily fluids can directly cause neurotoxic effects. We investigated effects of AD and other dementia (OD) patients' blood serum and CSF on viability of cells in primary cerebellar granule cell cultures. Overall, 59 individuals participated in the study from whom 55 samples of biological fluids were taken. Participants were classified into early (E-AD) and middle (M-AD) stages of AD, cognitively healthy control (HC) and OD groups. We found that concentrations of total and phosphorylated tau were higher in CSF from AD patients, while amyloid-ß42 and amyloid-ß40 in the serum was lower compared to HC. The most cytotoxic effects were induced by CSFs from M-AD patients which caused neuronal necrosis and suppressed microglial proliferation, whereas CSFs from the groups of other patients did not kill neurons. Serum and CSF from the E-AD group caused a reduction of neuronal numbers in cultures. There were no significant differences in levels of CSF biomarkers between the AD groups although both tau species in CSFs from M-AD patients were found to be significantly elevated compared to HC. Our data suggest that biological fluids from E-AD induce neuronal loss, whereas effects of CSF on the reduction in neuronal viability can serve as an indicator of M-AD and may be associated with extracellular tau.

Polymorphisms of Proinflammatory Cytokines in Relation to APOE Epsilon 4 and Risk of Alzheimer's Disease in the Lithuanian Population.

Background and objective: Neuroinflammation is one of the pathological pathways of Alzheimer's disease (AD), mediating the progression of neurodegeneration. Polymorphisms of proinflammatory cytokines have been linked to increased AD risk. Identification of certain combinations of polymorphisms could help predict disease in its preclinical stage. The aim of the study was to evaluate differences in the prevalence of TNFα -850T (rs1799724), IL1A -889T (rs1800587), and IL6 -174C (rs1800795, Intron type) polymorphisms between AD patients and healthy controls (HC) and determine the impact of these SNPs in combination with the APOEε4 allele on AD risk. Materials and Methods: The study population is comprised of 107 patients with sporadic AD (AD group) and age- and gender-matched 110 persons without impaired cognitive functions (control group). TNFα -850C > T polymorphism was revealed by a PCR and restriction fragment length polymorphism (RFLP) method. Real time PCR was used for IL1A and IL6 SNP genotyping. APOEε genotyping was done via hybridization method. Results: The frequencies of TNFα -850T, IL1A -889T, IL6 -174C allele and genotype did not differ between the AD and HC groups (p > 0.05). IL6 -174C was not in HWE, and it was not analysed further. APOEε4 allele (p = 0.001) and 3/4 and 4/4 genotypes (p = 0.005) were more prevalent in AD patients. APOEε4 carriage increased the risk of AD (OR 2.65, p = 0.001), while TNFα -850T and IL1A -889T polymorphisms were not found as significant independent risk factors for AD. The presence of at least one IL1A -889T allele in combination with APOEε4+ was associated with a lower risk of AD (OR 2.24, p = 0.047) than the carriage of APOEε4+ alone (OR 2.70, p = 0.015). Conclusions: No significant differences of TNFα -850, IL1A -889, and IL6 -174 polymorphisms frequencies were found between AD and control groups. In APOEε4 carriers IL1A -889T polymorphism was found to reduce the AD risk determined by APOEε4 alone.

Brain MRI morphometric analysis in Parkinson's disease patients with sleep disturbances.

BACKGROUND: Sleep disturbances are common in patients with advanced Parkinson disease (PD). The aim of this study was to evaluate a possible association of cortical thickness, cortical and subcortical volume with sleep disturbances in PD patients. METHODS: Twenty-eight PD patients (14 men and 14 women, median age 58 years) were evaluated for sleep disturbances with PDSS and underwent brain MRI. Control group consisted of 28 healthy volunteers who were matched by age and gender. Automated voxel based image analysis was performed with the FreeSurfer software. RESULTS: PD patients when compared to controls had larger ventricles, smaller volumes of hippocampus and superior cerebellar peduncle, smaller grey matter thickness in the left fusiform, parahipocampal and precentral gyruses, and right caudal anterior cingulate, parahipocampal and precentral hemisphere gyruses, as well as smaller volume of left rostral middle frontal and frontal pole areas, and right entorhinal and transverse temporal areas. According to the Parkinson's disease Sleep Scale (PDSS), 15 (53.58%) patients had severely disturbed sleep. The most frequent complaints were difficulties staying asleep during the night and nocturia. The least frequent sleep disturbances were distressing hallucinations and urine incontinence due to off symptoms. Patients who fidgeted during the night had thicker white matter in the left caudal middle frontal area and lesser global left hemisphere cortical surface, especially in the lateral orbitofrontal and lateral occipital area, and right hemisphere medial orbitofrontal area. Patients with frequent distressful dreams had white matter reduction in cingulate area, and cortical surface reduction in left paracentral area, inferior frontal gyrus and right postcentral and superior frontal areas. Nocturnal hallucinations were associated with volume reduction in the basal ganglia, nucleus accumbens and putamen bilaterally. Patients with disturbing nocturia had reduction of cortical surface on the left pre- and postcentral areas, total white matter volume decrease bilaterally as well in the pons. CONCLUSIONS: PD patients with nocturnal hallucinations had prominent basal ganglia volume reduction. Distressful dreams were associated with limbic system and frontal white matter changes, meanwhile nocturia was mostly associated with global white matter reduction and surface reduction of cortical surface on the left hemisphere pre- and postcentral areas.

Impact of the World Health Organization Pain Treatment Guidelines and the European Medicines Agency Safety Recommendations on Nonsteroidal Anti-Inflammatory Drug Use in Lithuania: An Observational Study.

Background and objective: Irrational use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the main cause of adverse effects-associated hospitalizations among all medication groups leading to extremely increased costs for health care. Pharmacoepidemiological studies can partly reveal such issues and encourage further decisions. Therefore, the aim of our study was to evaluate the utilization of non-opioid analgesics (ATC classification N02B and M01A) in Lithuania, and to compare it with that of other Baltic and Scandinavian countries in terms of compliance to the WHO pain treatment guidelines and the EMA safety recommendations on NSAID use. Materials and methods: The dispensing data were obtained from the sales analysis software provider in the Baltic countries (SoftDent, Ltd., Kaunas, Lithuania); State Medicine Control Agencies of Lithuania, Latvia, and Estonia; Norwegian Prescription Database; Swedish Database for Medicines; and Danish Prescription Database. Data included the utilization of both prescription and over-the-counter drugs. Utilization was expressed in defined daily doses (DDD)/1000 inhabitants/day. Results: During the 11-year period, the utilization of drugs belonging to the N02B and M01A groups increased by 22.8%, from 58.37 in 2005 to 71.68 DDD/1000 inhabitants/day in 2016 in Lithuania. Contrary to the WHO guidelines on pain management, all Baltic countries were more likely to use NSAIDs than other analgesics and antipyretics: in 2015, the drugs of the M01A group were used 6.04, 5.79, and 6.11 times more than those of N02B in Lithuania, Estonia, and Latvia, respectively, whereas the Scandinavian countries preferred the N02B to the M01A group: in Denmark and Sweden, the utilization of other analgesics and antipyretics was 2.33 and 1.24, respectively, times higher than that of NSAIDs. In Norway, the use of both groups was similar. In the Scandinavian countries, paracetamol was the analgesic of first choice, whereas, in Lithuania, it took only the third place. The most popular drug in Lithuania was diclofenac, and its utilization accounted for 30.04% of all non-opioid analgesics in 2016. Although the European Medicines Agency (EMA) restricted the use of certain NSAIDs, i.e., cyclooxygenase-2 (COX-2) inhibitors, nimesulide, and diclofenac, their use consistently increased by 15.91, 2.83, and 1.41 times, respectively, showing incompliance with the international guidelines. Conclusions: Neither the EMA safety policy on NSAID use nor the WHO pain treatment guidelines had a sufficient impact on the rational use of NSAIDs in Lithuania. The use of NSAIDs restricted by the EMA (diclofenac, COX-2 inhibitors, nimesulide, and piroxicam) remains high or even increases, while the utilization of safer alternatives (paracetamol and naproxen) remains relatively low as compared with the Scandinavian countries. Incompliance with international guidelines may result in increased morbidity, mortality and higher costs for health care.

Response inhibition, set shifting, and complex executive function in patients with chronic lower back pain.

OBJECTIVE: The aim of our study was to evaluate how response inhibition, set shifting, and complex executive function (represented by risky decision-making) are altered in chronic lower back pain patients. MATERIALS AND METHODS: A total of 29 patients with chronic lower back pain (CLBP >6 months) aged 49-69 years and 30 healthy volunteers matched for age, gender, and education were enrolled in a case-control study. The study was conducted in the Departments of Neurology and Neurosurgery of Panevezys Regional Hospital, Lithuania. Pain was evaluated by the visual analog scale, Pakula Pain Questionnaire (Lithuanian analog of McGill Pain Questionnaire), and Fibromyalgia Tender Points Examination. A battery of neuropsychological tests used included Stroop Test Victoria version, Trail Making Test parts A and B, and Game of Dice Task (GDT). RESULTS: CLBP patients did not score significantly worse in any examined neuropsychological tests. Response Inhibition correlated inversely with number of tender points in CLBP patients. GDT performance showed no significant difference in net score (number of safe minus risky decisions). Unexpectedly, both groups favored risky decisions. CONCLUSIONS: We found no statistically significant difference in response inhibition, set shifting, or complex executive function between CLBP patients and healthy older adults. Moreover, a risky decision-making pattern found in the Lithuanian population may underscore the importance of cultural context when examining complex executive function. However, further studies are needed to prove this point.

Validation of the EFFECT questionnaire for competence-based clinical teaching in residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into a competency-based medical education curriculum. To assess the quality of clinical teaching in residency training, we chose the EFFECT (evaluation and feedback for effective clinical teaching) questionnaire designed and validated at the Radboud University Medical Centre in the Netherlands. The aim of this study was to validate the EFFECT questionnaire for quality assessment of clinical teaching in residency training. MATERIALS AND METHODS: The research was conducted as an online survey using the questionnaire containing 58 items in 7 domains. The questionnaire was double-translated into Lithuanian. It was sent to 182 residents of 7 residency programs (anesthesiology reanimathology, cardiology, dermatovenerology, emergency medicine, neurology, obstetrics and gynecology, physical medicine and rehabilitation). Overall, 333 questionnaires about 146 clinical teachers were filled in. To determine the item characteristics and internal consistency (Cronbach's α), the item and reliability analyses were performed. Furthermore, confirmatory factor analysis (CFI) was performed using a model for maximum-likelihood estimation. RESULTS: Cronbach's α within different domains ranged between 0.91 and 0.97 and was comparable with the original version of the questionnaire. Confirmatory factor analysis demonstrated satisfactory model-fit with CFI of 0.841 and absolute model-fit RMSEA of 0.098. CONCLUSIONS: The results suggest that the Lithuanian version of the EFFECT maintains its original validity and may serve as a valid instrument for quality assessment of clinical teaching in competency-based residency training in Lithuania.

Evaluation of clinical teaching quality in competency-based residency training in Lithuania.

BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University of Health Sciences were renewed into the competency-based medical education curriculum (CBME). In 2015, we implemented the validated EFFECT questionnaire together with the EFFECT-System for quality assessment of clinical teaching in residency training. The aim of this study was to investigate the influence of characteristics of the resident (year of training) and clinical teacher (gender, age, and type of academic position) on teaching quality, as well as to assess areas for teaching quality improvement. MATERIALS AND METHODS: Residents from 7 different residency study programs filled out 333 EFFECT questionnaires evaluating 146 clinical teachers. We received 143 self-evaluations of clinical teachers using the same questionnaire. Items were scored on a 6-point Likert scale. Main outcome measures were residents' mean overall (MOS), mean subdomain (MSS) and clinical teachers' self-evaluation scores. The overall comparisons of MOS and MSS across study groups and subgroups were done using Student's t test and ANOVA for trend. The intraclass correlation coefficient (ICC) was calculated in order to see how residents' evaluations match with self-evaluations for every particular teacher. To indicate areas for quality improvement items were analyzed subtracting their mean score from the respective (sub)domain score. RESULTS: MOS for domains of "role modeling", "task allocation", "feedback", "teaching methodology" and "assessment" valued by residents were significantly higher than those valued by teachers (P<0.01). Teachers who filled out self-evaluation questionnaires were rated significantly higher by residents in role modeling subdomains (P<0.05). Male teachers in (sub)domains "role modeling: CanMEDS roles and reflection", "task allocation", "planning" and "personal support" were rated significantly higher than the female teachers (P<0.05). Teachers aged 40 years or younger were rated higher (P<0.01). Residents ratings by type of teachers' academic position almost in all (sub)domains differed significantly (P<0.05). No correlation observed between MOS of a particular teacher and MOS as rated by residents (ICC=0.055, P=0.399). The main areas for improvement were "feedback" and "assessment". CONCLUSIONS: Resident evaluations of clinical teachers are influenced by teachers' age, gender, year of residency training, type of teachers' academic position and whether or not a clinical teacher performed self-evaluation. Development of CBME should be focused on the continuous evaluation of quality, clinical teachers educational support and the implementation of e-portfolio.

Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

BACKGROUND: Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. CASE PRESENTATION: We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. CONCLUSIONS: In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

Accuracy, Precision, Sensitivity, and Specificity of Noninvasive ICP Absolute Value Measurements.

An innovative absolute intracranial pressure (ICP) value measurement method has been validated by multicenter comparative clinical studies. The method is based on two-depth transcranial Doppler (TCD) technology and uses intracranial and extracranial segments of the ophthalmic artery as pressure sensors. The ophthalmic artery is used as a natural pair of "scales" that compares ICP with controlled pressure Pe, which is externally applied to the orbit. To balance the scales, ICP = Pe a special two-depth TCD device was used as a pressure balance indicator. The proposed method is the only noninvasive ICP measurement method that does not need patient-specific calibration.

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.

Navigating the Neurobiology of Parkinson's: The Impact and Potential of α-Synuclein.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide; therefore, since its initial description, significant progress has been made, yet a mystery remains regarding its pathogenesis and elusive root cause. The widespread distribution of pathological α-synuclein (αSyn) aggregates throughout the body raises inquiries regarding the etiology, which has prompted several hypotheses, with the most prominent one being αSyn-associated proteinopathy. The identification of αSyn protein within Lewy bodies, coupled with genetic evidence linking αSyn locus duplication, triplication, as well as point mutations to familial Parkinson's disease, has underscored the significance of αSyn in initiating and propagating Lewy body pathology throughout the brain. In monogenic and sporadic PD, the presence of early inflammation and synaptic dysfunction leads to αSyn aggregation and neuronal death through mitochondrial, lysosomal, and endosomal functional impairment. However, much remains to be understood about αSyn pathogenesis, which is heavily grounded in biomarkers and treatment strategies. In this review, we provide emerging new evidence on the current knowledge about αSyn's pathophysiological impact on PD, and its presumable role as a specific disease biomarker or main target of disease-modifying therapies, highlighting that this understanding today offers the best potential of disease-modifying therapy in the near future.

The Antinociceptive Role of Nrf2 in Neuropathic Pain: From Mechanisms to Clinical Perspectives.

Neuropathic pain, a chronic condition resulting from nerve injury or dysfunction, presents significant therapeutic challenges and is closely associated with oxidative stress and inflammation, both of which can lead to mitochondrial dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a critical cellular defense mechanism against oxidative stress, has emerged as a promising target for neuropathic pain management. Nrf2 modulators enhance the expression of antioxidant and cytoprotective genes, thereby reducing oxidative damage, inflammation, and mitochondrial impairment. This review explores the antinociceptive effects of Nrf2, highlighting how pharmacological agents and natural compounds may be used as potential therapeutic strategies against neuropathic pain. Although preclinical studies demonstrate significant pain reduction and improved nerve function through Nrf2 activation, several clinical challenges need to be addressed. However, emerging clinical evidence suggests potential benefits of Nrf2 modulators in several conditions, such as diabetic neuropathy and multiple sclerosis. Future research should focus on further elucidating the molecular role of Nrf2 in neuropathic pain to optimize its modulation efficacy and maximize clinical utility.

Cognitive failure evaluation and therapy based on pharmacy practice - utilization of anti-dementia drugs and food supplements in Lithuania.

OBJECTIVE: To evaluate cognitive failures of patients visiting pharmacies and to study utilization of drugs for dementia therapy in Lithuania. METHODS: 153 patients completed a Cognitive Failure Questionnaire (CFQ) at pharmacy. The ATC/DDD method was used to evaluate utilization of drugs licensed for dementia treatment, including C04AE (peripheral vasodilators), N04BD (MAO inhibitors), N06D (anti-dementia drugs), N06BX (nootropics), N07C (anti-vertigo), and A11HA (plain vitamin E) preparations. RESULTS: 53 of 153 study participants (34.6%) scored over 45 CFQ points and reported cognitive failure, assessed by three factors: F1 - forgetfulness, F2 - distractibility and F3 - false triggering. All three factors correlate with age and the most significant extent has memory performance (Spearman's rank correlation coefficient (rs) F1 - rs = 0.85, p < 0.01; F3 - rs = 0.79, p < 0.01, and F2 - rs = 0.4, p < 0.01) and do not depend on gender or educational background. Total use of anti-dementia drugs and food supplements decreased from 27.08 DDD/1,000 inhabitants/day in 2006 to 26.46 DDD/1,000 inhabitants/day in 2011. Nicergoline 6.26 DDD/1,000 inhabitants/day and cinnarizine 6.16 DDD/1,000 inhabitants/ day - were the most prescribed medications in 2011. Total costs for anti-dementia drugs increased from EUR 8.91 million to EUR 11.63 million during the same period. The largest amount of EUR 3.166 million was spent on nicergoline. Older people were more likely than younger people to report using prescription drugs (rs = 0.468; p < 0.01), while younger population used more supplements (rs = -0.227; p = 0.005). CONCLUSIONS: Trend of anti-dementia drugs use in Lithuania is similar to other EU countries; however, there are some deviations from dementia treatment guidelines, particularly in terms of nicergoline and cinnarizine recommendations.

Novel Drug Targets and Emerging Pharmacotherapies in Neuropathic Pain.

Neuropathic pain is a debilitating condition characterized by abnormal signaling within the nervous system, resulting in persistent and often intense sensations of pain. It can arise from various causes, including traumatic nerve injury, neuropathy, and certain diseases. We present an overview of current and emerging pharmacotherapies for neuropathic pain, focusing on novel drug targets and potential therapeutic agents. Current pharmacotherapies, including tricyclic antidepressants, gabapentinoids, and serotonin norepinephrine re-uptake inhibitors, are discussed, as are emerging treatments, such as ambroxol, cannabidiol, and N-acetyl-L-cysteine. Additionally, the article highlights the need for further research in this field to identify new targets and develop more effective and targeted therapies for neuropathic pain management.

Diurnal variation of clock genes expression and other sleep-wake rhythm biomarkers among acute ischemic stroke patients.

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/ß), PER1, and PER3) showed significant time-of-day variation in both patients' and controls' groups, except expression of NR1D1 (Rev-erbα/ß) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/ß) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

Interactive Training of the Emergency Medical Services Improved Prehospital Stroke Recognition and Transport Time.

Background and Purpose: Acute stroke treatment outcomes are predicated on reperfusion timeliness which can be improved by better prehospital stroke identification. We aimed to assess the effect of interactive emergency medical services (EMS) training on stroke recognition and prehospital care performance in a very high-risk cardiovascular risk population in Lithuania. Methods: We conducted a single-center interrupted time-series study between March 1, 2019 and March 15, 2020. Two-hour small-group interactive stroke training sessions were organized for 166 paramedics serving our stroke network. We evaluated positive predictive value (PPV) and sensitivity for stroke including transient ischemic attack identification, onset-to-door time, and hospital-based outcomes during 6-months prior and 3.5 months after the training. The study outcomes were compared between EMS providers in urban and suburban areas. Results: In total, 677 suspected stroke cases and 239 stroke chameleons (median age 75 years, 54.8% women) were transported by EMS. After the training, we observed improved PPV for stroke recognition (79.8% vs. 71.8%, p = 0.017) and a trend of decreased in-hospital mortality (7.8% vs. 12.3, p = 0.070). Multivariable logistic regression models adjusted for age, gender, EMS location, and stroke subtype showed an association between EMS stroke training and improved odds of stroke identification (adjusted odds ratio [aOR] 1.6 [1.1-2.3]) and onset-to-door ≤ 90 min (aOR 1.6 [1.1-2.5]). The improvement of PPV was observed in urban EMS (84.9% vs. 71.2%, p = 0.003), but not in the suburban group (75.0% vs. 72.6%, p = 0.621). Conclusions: The interactive EMS training was associated with a robust improvement of stroke recognition, onset to hospital transport time, and a trend of decreased in-hospital mortality. Adapted training strategies may be needed for EMS providers in suburban areas. Future studies should evaluate the long-term effects of the EMS training and identify optimal retraining intervals.

Effect of aging on vagus somatosensory evoked potentials and ultrasonographic parameters of the vagus nerve.

Vagus somatosensory evoked potentials (VSEP) and ultrasonography can be used to detect functional and structural changes of the vagus nerve (VN) that are hypothesized to be associated with neurodegenerative diseases. However, it has not yet been established whether age-related changes in the VN occur in the healthy population. In this pilot study we included healthy volunteers in the 26-30 and 51-55 age range who comprised the younger (n = 20) and older (n = 20) groups, respectively. VSEP were recorded separately for stimulation of the auricular branch of the left and right VN. The VN CSA was measured in the transverse plane proximal to the carotid bifurcation, at the level of the distal end of the common carotid artery. No differences were found between the younger and older groups when comparing the average VN CSA (2.01 ± 0.20 vs 2.05 ± 0.20, mm2; p = 0.570) or the CSA of the right (2.08 ± 0.19 vs 2.17 ± 0.24, mm2; p = 0.233) or left VN (1.94 ± 0.26 vs 1.93 ± 0.24, mm2; p = 0.911). The right VN was larger than the left in 95% (n = 19) of older participants and in 65% (n = 13) of younger participants (p = 0.055). In comparison with the younger group, older participants showed significantly longer VSEP latencies of all wave components for electrodes C4-F4 and Fz-F3, of P1 for electrodes C3-F3 and of N1 and P2 for electrodes Fz-F4. The results of this study indicate that older age is associated with longer VSEP latencies but not with changes in VN CSA.

SARS-CoV-2 Seroprevalence in Lithuania: Results of National Population Survey.

SUMMARY BACKGROUND: Betacoronavirus SARS-CoV-2 has spread in early 2020 worldwide just in several months. The official statistics are consistently collected, but this is mainly based on symptomatic reports. This study was aimed to estimate the seroprevalence of SARS-CoV-2 infection in Lithuanian population. MATERIALS AND METHODS: Study was conducted during August-September 2020 in 6 municipalities of Lithuania. The sample comprised 3087 adult participants from the general population (mean age 53.7 years, 64% female). SARS-CoV-2 antibodies were assessed using AMP IgM/IgG Rapid Test, other data were based on self-report. Seroprevalence was assessed as a crude estimate and as adjusted by sensitivity-specificity of the test. RESULTS: The crude seroprevalence in the total sample was 1.9%, the adjusted - 1.4%, ranging from 0.8% to 2.4% across municipalities. Among seroprevalent cases, 67.2% had IgG, 29.3% had IgM, and 3.5% had both IgG and IgM. An increased risk for seropositive test was observed among people who reported having had close contacts with SARS-CoV-2 positives (OR=5.49, p<0.001). At the borderline significance were female gender (OR=1.75, p=0.082) and non-smoking status (OR=2.95, p=0.072). Among the seropositive participants, 69.0% reported having had no COVID-19 symptoms since 1 March 2020, while 31.0% reported having had at least one of the symptoms. CONCLUSIONS: The SARS-CoV-2 seroprevalence in Lithuanian sample in August-September 2020 was 1.4%, ranging from 0.8% to 2.4% across municipalities. Given the overall official data, by the end of study (11 September 2020) the total COVID-19 rate in Lithuania was 117.5 per 100,000 population or 0.12%. This suggests more than 10 times higher prevalence of virus across the population than the official estimates.