Cross-Sectional Area and Echogenicity Reference Values for Sonography of Peripheral Nerves in the Lithuanian Population.

OBJECTIVES: We aimed to provide data of nerve sizes and echogenicity reference values of the Lithuanian population. METHODS: High-resolution ultrasound was bilaterally performed according to the Ultrasound Pattern Sum Score and Neuropathy ultrasound protocols for healthy Lithuanian adults. Cross-sectional area (CSA) measurement and echogenicity were used as the main parameters for investigation. Echogenicity was evaluated using ImageJ, and nerves were categorized in classes according to echogenicity. RESULTS: Of 125 subjects enrolled, 63 were males (mean age 47.57 years, range 25-78 years) and 62 were females (mean age 50.50 years, range 25-80 years). Reference values of nerve sizes and values of echogenicity as a fraction of black in percentage of cervical roots, upper and middle trunks of the brachial plexus and the following nerves: vagal, median, ulnar, radial, superficial radial, tibial, fibular, and sural in standard regions were established. Mild to moderate correlations were found between nerves CSA, echogenicity values and anthropometric measurements with the differences according to sex. Inter-rater (ICC 0.93; 95% CI 0.92-0.94) and intra-rater (ICC 0.94; 95% CI 0.93-0.95) reliability was excellent. CONCLUSIONS: Reference values of nerve size and echogenicity of Lithuanians were presented for the first time as a novel such kind of publication from the Baltic countries.

The impact of a comprehensive national policy on improving acute stroke patient care in Lithuania.

Introduction: Reperfusion therapy (RT) is a mainstay treatment for acute ischemic stroke (AIS). We aimed to evaluate the impact of a comprehensive national policy (CNP) to improve access to RT for AIS patients across Lithuania. Patients and methods: Aggregated anonymized data on AIS cases treated in Lithuanian hospitals between 2006 and 2019 were retrospectively obtained from the Institute of Hygiene and the Stroke Integrated Care Management Committee. Through an interrupted time series analysis, we examined the trends in AIS hospital admissions, RT, and in-hospital case fatality rates prior to the enactment of CNP in 2014, changes immediately after the intervention, and differences in trends between the pre- and post-intervention periods. Mean yearly door-to-needle times were calculated post-intervention. Results: 114,436 cases were treated for AIS in Lithuanian hospitals before, and 65,084 after the government intervention. We observed a significant decreasing post-intervention trend change in AIS hospital admission rate per 100,000 population (regression coefficient ± standard error: ß = -16.47 ± 3.95, p = 0.002) and an increasing trend change in the proportion of AIS patients who received reperfusion treatment: intravenous thrombolysis (ß = 1.42 ± 0.96, p < 0.001) and endovascular therapy (ß = 0.85 ± 0.05, p < 0.001). The proportion of patients treated in stroke centers increased immediately after the intervention (ß = 4.95 ± 1.14, p = 0.001), but the long-term post-intervention trend did not change. In addition, there was a significant decreasing trend in all cause in-hospital case fatality rate within primary and comprehensive stroke centers after the intervention (ß = -0.60 ± 0.18, p = 0.008) despite its prompt initial immediate increase (ß = 1.68 ± 0.73, p = 0.043). The mean countrywide door-to-needle time decreased from 68 min in 2014 to 43 min in 2019. Conclusion: The comprehensive national stroke patient care policy could be associated with an immediate increase in stroke center treatment rate, increased access to RT, and improved stroke care performance measures.

Imeglimin Is Neuroprotective Against Ischemic Brain Injury in Rats-a Study Evaluating Neuroinflammation and Mitochondrial Functions.

Imeglimin is a novel oral antidiabetic drug modulating mitochondrial functions. However, neuroprotective effects of this drug have not been investigated. The aim of this study was to investigate effects of imeglimin against ischemia-induced brain damage and neurological deficits and whether it acted via inhibition of mitochondrial permeability transition pore (mPTP) and suppression of microglial activation. Ischemia in rats was induced by permanent middle cerebral artery occlusion (pMCAO) for 48 h. Imeglimin (135 µg/kg/day) was injected intraperitoneally immediately after pMCAO and repeated after 24 h. Immunohistochemical staining was used to evaluate total numbers of neurons, astrocytes, and microglia as well as interleukin-10 (IL-10) producing cells in brain slices. Respiration of isolated brain mitochondria was assessed using high-resolution respirometry. Assessment of ionomycin-induced mPTP opening in intact cultured primary rat neuronal, astrocytic, and microglial cells was performed using fluorescence microscopy. Treatment with imeglimin significantly decreased infarct size, brain edema, and neurological deficits after pMCAO. Moreover, imeglimin protected against pMCAO-induced neuronal loss as well as microglial proliferation and activation, and increased the number of astrocytes and the number of cells producing anti-inflammatory cytokine IL-10 in the ischemic hemisphere. Imeglimin in vitro acutely prevented mPTP opening in cultured neurons and astrocytes but not in microglial cells; however, treatment with imeglimin did not prevent ischemia-induced mitochondrial respiratory dysfunction after pMCAO. This study demonstrates that post-stroke treatment with imeglimin exerts neuroprotective effects by reducing infarct size and neuronal loss possibly via the resolution of neuroinflammation and partly via inhibition of mPTP opening in neurons and astrocytes.

Brain dysfunction in tubular and tubulointerstitial kidney diseases.

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research.

Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system.

Odor Identification and Regional Gray Matter Atrophy in Patients with Alzheimer's Disease, Parkinson's Disease, and the Healthy Elderly: A Cross-Sectional Structural MRI Study.

Multiple associations between impaired olfactory performance and regional cortical and deep gray matter atrophy have been reported in separate studies of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and of the healthy elderly. We aimed to evaluate such possible associations among these populations in a unified manner. Twenty AD, twenty PD patients' and twenty healthy age- and sex-matched controls' odor identification performance was assessed with the Lithuanian adaptation of the Sniffin' Sticks 12 odor identification test, followed by morphometric gray matter analysis by MRI using FreeSurfer. AD patients had significantly lower cognitive performance than both PD patients and the healthy elderly, as evaluated with the Mini-Mental State Examination (MMSE). Odor identification performance was significantly worse in AD and PD patients compared with the healthy elderly; AD patients performed slightly worse than PD patients, but the difference was not statistically significant. Among patients with AD, worse odor identification performance was initially correlated with atrophy of multiple cortical and deep gray matter regions known to be involved in olfactory processing, however, only two measures-decreased thicknesses of the right medial and left lateral orbitofrontal cortices-remained significant after adjustment for possible confounders (age, MMSE score, and global cortical thickness). Among patients with PD and the healthy elderly we found no similar statistically significant correlations. Our findings support the key role of the orbitofrontal cortex in odor identification among patients with AD, and suggest that correlations between impaired odor identification performance and regional gray matter atrophy may be relatively more pronounced in AD rather than in PD.

Creutzfeldt-Jakob disease with neuroleptic malignant syndrome.

Creutzfeldt­Jakob disease (CJD) is a rare rapidly progressive fatal neurodegenerative disease. Neuroleptic malignant syndrome (NMS) is a complication of antipsychotic medications which may be used to treat neuropsychiatric symptoms of CJD. We present a case of a 51­year­ old woman with CJD who developed NMS after being prescribed quetiapine.

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.

Evaluation of the Effectiveness of Post-Stroke Metformin Treatment Using Permanent Middle Cerebral Artery Occlusion in Rats.

Stroke is the second leading cause of death worldwide. Treatment options for ischemic stroke are limited, and the development of new therapeutic agents or combined therapies is imperative. Growing evidence suggests that metformin treatment, due to its anti-inflammatory action, exerts a neuroprotective effect against ischemia/reperfusion-induced brain damage. Experimental assessment has typically been performed in models of cerebral transient ischemia followed by long-term reperfusion. The aim of this study was to evaluate the neuroprotective effect of metformin treatment after permanent middle cerebral artery occlusion (pMCAO) without reperfusion in rats. Neurological deficits were assessed using the Longa scale, which offers a graded scale on body movement following pMCAO. Both infarct size and brain oedema area were measured by staining with 2,3,5-triphenyltetrazolium chloride. The number of neurons and total and activated microglia, as well as interleukin 10 (IL-10) production, in brain sections were evaluated by immunohistochemical staining. Our results show that metformin treatment improves the neurological state and reduces infarct size after 120 h of pMCAO. Metformin also prevents neuronal loss in the ischemic cortex but not in the striatum after 48 h of pMCAO. Moreover, post-stroke treatment with metformin significantly decreases the number of total and activated microglia at 48 h. The anti-inflammatory effect of metformin is associated with increased IL-10 production at 48 h after pMCAO. The results of the present study suggest that post-stroke treatment with metformin exerts anti-inflammatory and neuroprotective effects in a pMCAO model.

Association between stroke occurrence and changes in atmospheric circulation.

BACKGROUND: The impact of weather on morbidity from stroke has been analysed in previous studies. As the risk of stroke was mostly associated with changing weather, the changes in the daily stroke occurrence may be associated with changes in atmospheric circulation. The aim of our study was to detect and evaluate the association between daily numbers of ischaemic strokes (ISs) and haemorrhagic strokes (HSs) and the teleconnection pattern. METHODS: The study was performed in Kaunas, Lithuania, from 2000 to 2010. The daily numbers of ISs, subarachnoid haemorrhages (SAHs), and intracerebral haemorrhages (ICHs) were obtained from the Kaunas Stroke Register. We evaluated the association between these types of stroke and the teleconnection pattern by applying Poisson regression and adjusting for the linear trend, month, and other weather variables. RESULTS: During the study period, we analysed 4038 cases (2226 men and 1812 women) of stroke. Of these, 3245 (80.4%) cases were ISs, 533 (13.2%) cases were ICHs, and 260 (6.4%) cases were SAHs. An increased risk of SAH was associated with a change in mean daily atmospheric pressure over 3.9 hPa (RR = 1.49, 95% CI 1.14-1.96), and a stronger El Niño event had a protective effect against SAHs (RR = 0.34, 95% CI 0.16-0.69). The risk of HS was positively associated with East Atlantic/West Russia indices (RR = 1.13, 95% CI 1.04-1.23). The risk of IS was negatively associated with the Arctic Oscillation index on the same day and on the previous day (RR = 0.97, p < 0.033). During November-March, the risk of HS was associated with a positive North Atlantic Oscillation (NAO) (RR = 1.29, 95% CI 1.03-1.62), and the risk of IS was negatively associated with the NAO index (RR = 0.92, 95% CI 0.85-0.99). CONCLUSIONS: The results of our study provide new evidence that the North Atlantic Oscillation, Arctic Oscillation, East Atlantic/West Russia, and El Niño-Southern Oscillation pattern may affect the risk of stroke. The impact of these teleconnections is not identical for various types of stroke. Emergency services should be aware that specific weather conditions are more likely to prompt calls for more severe strokes.

Diagnostic Ability of Radiofrequency Ultrasound in Parkinson's Disease Compared to Conventional Transcranial Sonography and Magnetic Resonance Imaging.

We aimed to estimate tissue displacements' parameters in midbrain using ultrasound radiofrequency (RF) signals and to compare diagnostic ability of this RF transcranial sonography (TCS)-based dynamic features of disease affected tissues with conventional TCS (cTCS) and magnetic resonance imaging (MRI) while differentiating patients with Parkinson's disease (PD) from healthy controls (HC). US tissue displacement waveform parametrization by RF TCS for endogenous brain tissue motion, standard neurological examination, cTCS and MRI data collection were performed for 20 PD patients and for 20 age- and sex-matched HC in a prospective manner. Three logistic regression models were constructed, and receiver operating characteristic (ROC) curve analyses were applied. The model constructed of RF TCS-based brain tissue displacement parameters-frequency of high-end spectra peak and root mean square-revealed presumably increased anisotropy in the midbrain and demonstrated rather good diagnostic ability in the PD evaluation, although it was not superior to that of the cTCS or MRI. Future studies are needed in order to establish the true place of RF TCS detected tissue displacement parameters for the evaluation of pathologically affected brain tissue.

Deiodinases, organic anion transporter polypeptide polymorphisms and symptoms of anxiety and depression after ischemic stroke.

BACKGROUND: Emotional disturbances, such as anxiety and depression are common after acute ischemic stroke (AIS). Individual variation in emotional outcome is strongly influenced by genetic factors. One of pituitary axis, is the hypothalamic-pituitary-thyroid axis, a critical regulator of post-stroke recovery, suggesting that allelic variants in thyroid hormone (TH) signaling regulation can influence stroke outcome. AIM: To determine associations between AIS emotional outcome and allelic variants of the TH metabolizing enzymes 1-3 type deiodinase (DIO1-3) and the membrane transporting organic anion polypeptide 1C1 (OATP1C1). METHODS: Eligible AIS patients from Lithuania (n=168) were genotyped for ten DIO1-3 and OATP1C1 single nucleotide polymorphisms (SNP): DIO1 rs12095080-A/G, rs11206244-C/T, and rs2235544-A/C; DIO2 rs225014-T/C and rs225015-G/A; DIO3 rs945006-T/G; OATP1C1 rs974453-G/A, rs10444412-T/C, rs10770704-C/T, and rs1515777-A/G. Emotional outcome was evaluated using the Hospital Anxiety and Depression Scale at discharge from the neurology department after experienced index AIS. RESULTS: After adjustment for potential confounders, the major allelic (wild-type) DIO1-rs12095080 genotype (AA) was associated with higher odds ratio of anxiety symptoms (OR = 5.16; 95% CI: 1.04-25.58; p = 0.045), conversely, DIO1-rs11206244 wild-type genotype (CC) and wild-type OATP1C1-rs1515777 allele containing the genotypes (AA + AG) were associated with lower odds ratio of symptoms of anxiety (OR = 0.37; 95% CI: 0.14-0.96; p = 0.041 and OR = 0.30; 95% CI: 0.12-0.76; p = 0.011, respectively). Wild-type OATP1C1-rs974453 genotype (GG) was associated with higher odds ratio of symptoms of depression (OR = 2.73; 95% CI: 1.04-7.12; p = 0.041). CONCLUSION: Allelic variants in thyroid axis genes may predict emotional outcomes of AIS.

Diagnostic Ability of Structural Transcranial Sonography in Patients with Alzheimer's Disease.

The aim of this study was to assess the diagnostic ability of transcranial sonography (TCS) for the evaluation of the medial temporal lobe (MTL) in Alzheimer's disease (AD). Standard neuropsychological evaluation, TCS and 1.5 T MRI were performed for 20 patients with AD and for 20 age- and sex-matched healthy controls in a prospective manner. Measurements of the size of the third ventricle and heights of the MTL (A) and the choroidal fissure (B) were performed twice on each side by two independent neurosonologists for all participants. On MRI, both conventional and volumetric analyses of the third ventricle and hippocampus were performed. Receiver operating characteristic (ROC) curves analyses were applied. Height of the MTL on TCS had sensitivities of 73.7% (right)/63.2%(left) and specificities of 65% (right)/65-70% (left) Area under a curve (AUC) 75.4-77.2% (right), 60.4-67.8% (left)) for AD. A/B ratio on TCS had sensitivities of 73.7% (right)/57.9% (left) and specificities of 70.0% (right)/55.0% (left) (AUC 73.3% (right), 60.4% (left)) by the experienced neurosonologist, and sensitivities of 78.9% (right and left) and specificities of 60.0% (right)/65.0% (left) (AUC 77.8-80.0%) by the inexperienced neurosonologist for AD. On MRI, linear measurement of the hippocampus and parahippocampal gyrus height had sensitivities of 84.2% (right)/89.5% (left) and specificities of 80.0% (right)/85% (left) (AUC 86.1-92.9%) for AD. Hippocampal volume had sensitivities of 70% (right and left) and specificities of 75% (right)/80% (left) (AUC 77.5-78%) for AD. Atrophy of the right MTL in AD could be detected on TCS with a good diagnostic ability, however MRI performed better on the left.

Ultrasonic Assessment of the Medial Temporal Lobe Tissue Displacements in Alzheimer's Disease.

We aim to estimate brain tissue displacements in the medial temporal lobe (MTL) using backscattered ultrasound radiofrequency (US RF) signals, and to assess the diagnostic ability of brain tissue displacement parameters for the differentiation of patients with Alzheimer's disease (AD) from healthy controls (HC). Standard neuropsychological evaluation and transcranial sonography (TCS) for endogenous brain tissue motion data collection are performed for 20 patients with AD and for 20 age- and sex-matched HC in a prospective manner. Essential modifications of our previous method in US waveform parametrization, raising the confidence of micrometer-range displacement signals in the presence of noise, are done. Four logistic regression models are constructed, and receiver operating characteristic (ROC) curve analyses are applied. All models have cut-offs from 61.0 to 68.5% and separate AD patients from HC with a sensitivity of 89.5% and a specificity of 100%. The area under a ROC curve of predicted probability in all models is excellent (from 95.2 to 95.7%). According to our models, AD patients can be differentiated from HC by a sharper morphology of some individual MTL spatial point displacements (i.e., by spreading the spectrum of displacements to the high-end frequencies with higher variability across spatial points within a region), by lower displacement amplitude differences between adjacent spatial points (i.e., lower strain), and by a higher interaction of these attributes.

Evaluating the functional and structural changes in the vagus nerve: Should the vagus nerve be tested in patients with atrial fibrillation?

One of the multiple factors believed to contribute to the initiation and maintenance of atrial fibrillation (AF) is altered activity of the autonomic nervous system. Debate continues about the role of the vagus nerve (CNX) in AF since its effect depends on the level of its activation as well as on simultaneous sympathetic activation. Surplus either vagal or sympathetic activity may rarely induce the development of AF; however, typically loss of balance between the both systems mediates the induction and maintenance of AF. Vagal stimulation has been proposed as a novel treatment approach for AF because the anti-arrhythmic effects of low-level vagus nerve stimulation have been shown both in patients and animal models. We hypothesize that in typical cases of AF without any clear trigger by either autonomic nervous system, significant changes in vagus somatosensory evoked potentials and a smaller cross-sectional area of CNX could be detected, representing functional and structural changes in CNX, respectively.

Quantification of Endogenous Brain Tissue Displacement Imaging by Radiofrequency Ultrasound.

The purpose of this paper is a quantification of displacement parameters used in the imaging of brain tissue endogenous motion using ultrasonic radiofrequency (RF) signals. In a preclinical study, an ultrasonic diagnostic system with RF output was equipped with dedicated signal processing software and subject head-ultrasonic transducer stabilization. This allowed the use of RF scanning frames for the calculation of micrometer-range displacements, excluding sonographer-induced motions. Analysis of quantitative displacement estimates in dynamical phantom experiments showed that displacements of 55 µm down to 2 µm were quantified as confident according to Pearson correlation between signal fragments (minimum p ≤ 0.001). The same algorithm and scanning hardware were used in experiments and clinical imaging which allows translating phantom results to Alzheimer's disease patients and healthy elderly subjects as examples. The confident quantitative displacement waveforms of six in vivo heart-cycle episodes ranged from 8 µm up to 263 µm (Pearson correlation p ≤ 0.01). Displacement time sequences showed promising possibilities to evaluate the morphology of endogenous displacement signals at each point of the scanning plane, while displacement maps-regional distribution of displacement parameters-were essential for tissue characterization.

Nonthyroidal Illness Syndrome in Ischaemic Stroke Patients is Associated with Increased Mortality.

BACKGROUND: Results of studies on associations between triiodothyronine serum levels and mortality after acute ischemic stroke (AIS) are inconsistent. Therefore, the aim of this prospective study was to evaluate links between serum levels of thyroid axis associated hormones and all-cause mortality during 1 year after AIS. METHODS AND RESULTS: This study involved 255 patients with AIS. Patients were divided into two groups: those who survived 1 year after their index stroke and those who not, and by quartiles of free triiodothyronine (FT3) and ΔFT3 (difference between basal FT3 and repeated FT3 on discharge) hormone serum concentrations. To assess serum levels of thyroid stimulating hormone (TSH), FT3 and free tetraiodothyronine (FT4), venous blood was taken from all included patients on admission to hospital. On discharge, blood tests were repeated for 178 (69.8%) patients. Study endpoints were overall mortality within 30, 90 and 365 days after AIS. RESULTS: Compared with the survivals, those who died had significantly lower mean FT3, FT3/FT4 ratio in all periods and lower median TSH within 30 days. Higher FT3 serum levels versus lower, even after adjustment for included important variables, remained significant for lower odds of death within 365 days after AIS (OR=0.57; 95% CI: 0.33-0.97, p=0.04), but added insignificant additional predictive value to the NIHSS score or age. Kaplan-Meier survival curves demonstrated that the first FT3 quartile was significantly associated with increased mortality compared with all other quartiles within 365 days after AIS. With ΔFT3 quartiles no such association was found. CONCLUSIONS: Higher FT3 levels on admission versus lower are significantly associated with lower mortality within 365 days after AIS. FT3 serum levels changes over time didn't show any association with mortality within first year.

Optimal Cerebral Perfusion Pressure: Targeted Treatment for Severe Traumatic Brain Injury.

Identification of individual therapy targets is critical for traumatic brain injury (TBI) patients. Clinical outcomes depend on cerebrovascular autoregulation (CA) impairment. Here, we compare the effectiveness of optimal cerebral perfusion pressure (CPPopt)-targeted therapy in younger (<45 years of age) and elderly (≥45 years of age) TBI patients. Single-center multi-modal invasive arterial blood pressure(t), intracranial pressure (ICP)(t), cerebral perfusion pressure CPP(t), and CPPopt(t) monitoring (n = 81) was performed. ICM+ software was used for continuous CPPopt(t) status assessment by identification of pressure reactivity index (PRx). The most significant prognostic factors were age, Glasgow Coma Scale, serum glucose, and duration of longest CA ompairment event (LCAI) when PRx(t) >0.5 within 24 h after admission. The modeled accuracies for favorable and unfavorable outcome prediction were 86.5% and 90.9%, respectively. Age above 45 years and averaged ICP during all monitoring time above 21.3 mm Hg was associated with unfavorable outcome of an individual patient. Averaged CPP values close to CPPopt were associated with a better outcome in younger patients. Averaged ΔCPPopt <-5.0 mm Hg, averaged PRx >0.36, and LCAI >100 min were significantly associated with mortality for the younger patients. The critical values of averaged PRx >0.26 and LCAI >61 min were significantly associated with mortality for the elderly group. Autoregulation-guided treatment was important for individual TBI management, especially in younger patients. Further randomized multi-center studies are needed to prove final benefit.

Subjective and objective features of sleep disorders in patients with acute ischemic or haemorrhagic stroke: It is not only sleep apnoea which is important.

BACKGROUND: More than half of stroke patients present with a sleep-related breathing disorder including both central and obstructive forms of sleep apnoea. A cerebral infarction in different brain areas can disrupt sleep regulating pathways and cause insomnia, hypersomnia, circadian rhythm disturbances and other sleep disorders. Therefore, there is a need of objective data about various sleep disorders arising after ischemic or haemorrhagic stroke in order to implement practical recommendations how to suspect, diagnose and treat these conditions. Our medical hypothesis is that non-breathing sleep disorders are common among patients with acute ischemic or haemorrhagic stroke. OBJECTIVE: To investigate the subjective and objective sleep parameters in the patients with an acute ischemic or haemorrhagic stroke. METHODS: In the acute period (from 3 to 10 days after the first symptoms) of stroke all the patients completed questionnaires about sleep complaints and symptoms experienced before and after stroke, Epworth Sleepiness Scale (ESS), National Institute of Health Stroke Scale, Hospital Anxiety and Depression Scale and Modified Rankin Scale. Patients were included for further polysomnography (PSG) and sleep electroencephalography according to these criteria: (1) patients expressing severe sleep related complaints and/or symptoms that are new or have exacerbated after the stroke; and/or (2) patients having the ESS score equal or >10. RESULTS: 66 patients were examined in the acute period of stroke. 33 (50%) patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mostly related to obstructive sleep apnoea (OSA) and insomnia. Finally, 13 (19.7% of the whole sample) patients were selected for performing PSG. 12 of 13 patients were diagnosed with sleep disorder: 1 patient got the diagnosis of mild OSA, 1 - central sleep apnoea (CSA), 2 - combination of OSA and CSA, 1 - combination of mild OSA, periodic limb movement disorder (PLMD) and REM sleep behaviour disorder (RBD), 1 - combination of mild OSA and PLMD, 3 - combination of PLMD and insomnia, 3 - insomnia. There were no significant relations between type, location or treatment of stroke and various PSG measures, as well as type of a diagnosed sleep disorder. CONCLUSIONS: Half of our acute stroke patients had at least one or more new or exacerbated sleep complaints and/or symptoms, mainly related to OSA or insomnia. In the selected PSG group almost all patients were diagnosed with a sleep disorder, half of them having non-breathing sleep disorder, such as PLMD, RBD and insomnia.

Deiodinases, organic anion transporter polypeptide polymorphisms and ischemic stroke outcomes.

BACKGROUND: Ischemic stroke is a major cause of premature death and chronic disability worldwide, and individual variation in functional outcome is strongly influenced by genetic factors. Neuroendocrine signaling by the hypothalamic-hypophyseal-thyroid axis is a critical regulator of post-stroke pathogenesis, suggesting that allelic variants in thyroid hormone (TH) signaling can influence stroke outcome. AIM: To examine associations between acute ischemic stroke (AIS) outcome and allelic variants of the TH metabolizing enzymes deiodinase type 1-3 (DIO1-3) and membrane transporting organic anion polypeptide C1 (OATP1C1). METHODS: Eligible AIS patients from Lithuania (n = 248) were genotyped for ten DIO1-3 and OATP1C1 single nucleotide polymorphisms (SNPs): DIO1 rs12095080-A/G, rs11206244-C/T, and rs2235544-A/C; DIO2 rs225014-T/C and rs225015-G/A; DIO3 rs945006-T/G; OATP1C1 rs974453-G/A, rs10444412-T/C, rs10770704-C/T, and rs1515777-A/G. Functional outcome was evaluated one year after index AIS using the modified Rankin Scale. Analyses were adjusted for important confounders, including serum free triiodothyronine. RESULTS: After adjustment for potential confounders, the major allelic (wild-type) DIO3 genotype rs945006-TT was associated with better 1-year AIS functional outcome (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.08-0.74; p = .013), while the wild-type OATP1C1 genotype rs10770704-CC was associated with poorer outcome (OR = 2.00, 95%CI: 1.04-3.86; p = .038). CONCLUSION: Allelic variants in thyroid axis genes may prove useful for prognosis and treatment guidance.