Pilot Study of the Total and Phosphorylated Tau Proteins in Early-Stage Multiple Sclerosis.

Background and Objectives: Recent findings suggest that neurodegeneration starts early in the course of multiple sclerosis (MS) and significantly contributes to the progression of patients' disability. Tau is a microtubule-binding protein that is known to play a role in the pathophysiology of many neurodegenerative disorders. Newly emerging data on tau protein-induced neurodegenerative processes and its possible involvement in MS suggest that it may be involved in the pathology of early-stage MS. Therefore, this study aimed to test this hypothesis in patients with newly diagnosed MS. Materials and Methods: Cerebrospinal fluid (CSF) was collected from 19 patients with newly diagnosed MS and 19 control subjects. All MS patients underwent neurological examination, lumbar punction, and brain magnetic resonance imaging (MRI). CSF concentrations of total and phosphorylated tau (phospho-tau-181) protein were measured using commercial enzyme-linked immunosorbent assay kits. Results: The total tau concentration was significantly higher in the CSF of MS patients compared to controls (141.67 pg/mL, IQR 77.79-189.17 and 68.77 pg/mL, IQR 31.24-109.17, p = 0.025). In MS patients, the total tau protein positively correlated with total CSF protein (r = 0.471, p = 0.048). Significantly higher total tau concentration was measured in MS patients with higher lesion load in brain MRI (≥9 versus <9 lesions; 168.33 pg/mL, IQR 111.67-222.32 and 73.33 pg/mL, IQR -32.13-139.29-, p = 0.021). The CSF concentration of phospho-tau-181 protein was below the detection limit in both MS and control subjects. Conclusions: The concentration of total tau protein level is elevated, whereas phospho-tau-181 is undetectable in the CSF of patients with early-stage MS.

Dynamic Changes of Hemostasis in Patients with Traumatic Brain Injury Undergoing Craniotomy: Association with in-Hospital Mortality.

BACKGROUND: Traumatic brain injury (TBI) induces complex systemic hemostatic alterations associated with secondary brain damage and death. We specifically investigated perioperative changes of hemostasis in patients with isolated TBI undergoing major neurosurgery and searched for their influence on outcome. METHODS: Serial analysis (four time points, T0-T3) of conventional coagulation assay and rotational thromboelastometry data acquired during 72 h from admission of 68 patients who underwent craniotomy to remove hematoma and/or to decompress the brain was performed. The primary outcome was in-hospital mortality. Secondary outcomes were the prevalence of hypocoagulation and increased clotting activity, coagulation parameters between survivors and nonsurvivors, and cutoff values of coagulation parameters predictive of mortality. RESULTS: Overall mortality was 22%. The prevalence of hypocoagulation according to rotational thromboelastometry decreased from 35.8% (T0) to 15.9% (T3). Lower fibrinogen levels, hyperfibrinolysis and fibrinolysis shutdown in the early period (T0-T1) following TBI were associated with higher mortality. Optimal cutoff values were identified: fibrin polymerization thromboelastometry (FIBTEM) clot amplitude at 10 min after clotting time ≤ 13 mm at T0 and FIBTEM clot amplitude at 10 min after clotting time ≤ 16.5 mm at T1 increased the odds of death by 6.0 (95% confidence interval [CI] 1.54-23.13, p = 0.010) and 9.7 (95% CI 2.06-45.36, p = 0.004), respectively. FIBTEM maximum clot firmness ≤ 14.5 mm at T0 and FIBTEM maximum clot firmness ≤ 18.5 mm at T1 increased the odds of death by 6.3 (95% CI 1.56-25.69, p = 0.010) and 9.1 (95% CI 1.88-44.39, p = 0.006). Fibrinogen < 3 g/L on postoperative day 1 (T1) was associated with a 9.5-fold increase of in-hospital mortality (95% CI 1.72-52.98, p = 0.01). Increased clotting activity was not associated with mortality. CONCLUSIONS: Rotational thromboelastometry adds important information for identifying patients with TBI at increased risk of death. Early fibrinogen-related coagulation disorders are associated with mortality of patients with TBI undergoing major neurosurgical procedures. Maintenance of higher fibrinogen levels might be necessary for neurosurgical patients with acute TBI.

The effect of scalp block or local wound infiltration versus systemic analgesia on post-craniotomy pain relief.

BACKGROUND: This is a prospective, double-blind observational study in which different types of analgesia and its effect on postoperative pain reduction in patients undergoing craniotomy for brain tumor removal were compared. METHODS: The study included 141 adult craniotomy patients that were randomly separated into three equal groups. A group with scalp nerve blockade (B) and wound infiltration (I) received 0.25% bupivacaine combined with 1% lidocaine and 1:200,000 epinephrine. One gram of paracetamol and 2 mg/kg ketoprofen were administered intravenously (IV) after skin closure in a group with systemic analgesia (S). Pain intensity was evaluated after 1, 3, 6, and 24 h postoperatively using a visual analogue scale (VAS). The amount of rescue analgesia (ketorolac, paracetamol, and pethidine) and the duration for its first requirement were recorded. RESULTS: One hundred and forty-one patients were included in the study. The main pain scores were significantly lower in the groups with regional anesthesia compared to group S in the first hours post-surgery (p < 0.05). Significantly lower pain scores were observed in the group with a scalp nerve blockade compared to the group with systemic analgesia or wound infiltration after 24 h (p < 0.05). Regional anesthesia ensured a stable analgesic effect for all 24 h. Patients in groups B and I required significantly fewer rescue analgesics compared to patients in group S. The duration for the requirement of the first rescue analgesia was significantly longer in groups B and I compared to group S (p = 0.000). CONCLUSIONS: The results of our study show that most patients experience pain in the early postsurgical hours. Regional analgesia could help reduce the incidence and severity of pain after a craniotomy and the amount of rescue analgesia used in this group of patients.

Implementation of Thromboelastometry for Coagulation Management in Isolated Traumatic Brain Injury Patients Undergoing Craniotomy.

BACKGROUND Coagulopathy (CP) is a modifiable factor linked with secondary brain damage and poor outcome of traumatic brain injury (TBI). A shift towards goal-directed coagulation management has been observed recently. We investigated whether rotational thromboelastometry (ROTEM) based management could be successfully implemented in TBI patients and improve outcomes. MATERIAL AND METHODS A prospective, case-control study was performed. Adult patients with isolated TBI requiring craniotomy were included in this study. All patients underwent standard coagulation tests (SCT). Patients were identified as either in control group or in case group. Patients in the case group were additionally tested with ROTEM to specify their coagulation status. Management of the patients in the control group was based on SCT, whereas management of patients in the case group was guided by ROTEM. Outcome measures were as follows: CP rate, protocol adhesion, blood loss, transfusions, progressive hemorrhagic injury (PHI), re-intervention, Glasgow coma score (GCS) and Glasgow outcome score (GOS) at discharge, and in-hospital mortality. RESULTS There were 134 patients enrolled (65 patients in the control group and 69 patients in the case group). Twenty-six patients in the control group (40%) were found to be coagulopathic (control-CP subgroup) and 34 patients in the case group (49.3%) were found to be coagulopathic (case-CP subgroup). Twenty-five case-CP patients had ROTEM abnormalities triggering protocolized intervention, and 24 of them were treated. Overall ROTEM-based protocol adhesion rate was 85.3%. Postoperative ROTEM parameters of case-CP patients significantly improved, and the number of coagulopathic patients decreased. The incidence of PHI (control versus case group) and neurosurgical re-intervention (control-CP versus case-CP subgroup) was in favor of ROTEM guidance (P<0.05). Mortality and GCS and GOS at discharge did not differ significantly between groups. CONCLUSIONS ROTEM led to consistent coagulation management, improved clot quality, and decreased incidence of PHI and neurosurgical re-intervention. Further studies are needed to confirm benefits of ROTEM in cases of TBI.

Role of Multimodal Analgesia in the Evolving Enhanced Recovery after Surgery Pathways.

Enhanced recovery after surgery (ERAS) are specially designed multimodal perioperative care pathways which are intended to attain and improve rapid recovery after surgical interventions by supporting preoperative organ function and attenuating the stress response caused by surgical trauma, allowing patients to get back to normal activities as soon as possible. Evidence-based protocols are prepared and published to implement the conception of ERAS. Although they vary amongst health care institutions, the main three elements (preoperative, perioperative, and postoperative components) remain the cornerstones. Postoperative pain influences the quality and length of the postoperative recovery period, and later, the quality of life. Therefore, the optimal postoperative pain management (PPM) applying multimodal analgesia (MA) is one of the most important components of ERAS. The main purpose of this article is to discuss the concept of MA in PPM, particularly reviewing the use of opioid-sparing measures such as paracetamol, nonsteroid anti-inflammatory drugs (NSAIDs), other adjuvants, and regional techniques.

Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Bleeding in Neurosurgical Patients: A Single-Center Experience.

Objective: The number of patients presenting with warfarin-associated intracranial bleeding and needing neurosurgical intervention is growing. Prothrombin complex concentrate (PCC) is commonly used for anti-coagulation reversal before emergent surgery. We present our experience with PCC use in patients presenting with coagulopathy and needing urgent craniotomy. Methods: We retrospectively identified all patients presenting with intracranial bleeding and coagulopathy due to warfarin use, requiring urgent neurosurgical procedures, from January, 2014 (implementation of 4-PCC therapy) until December, 2016. For coagulation reversal, all patients received 4-PCC (Octaplex) and vitamin K. Results: Thirty-five consecutive patients (17 men; median age 72 years) were administered 4-PCC before emergent neurosurgical procedures. The majority of patients presented with traumatic subdural hematoma (62%) and spontaneous intracerebral hemorrhage (32%). All patients were taking warfarin. Median international normalized ratio (INR) on admission was 2.94 (range: 1.20 to 8.60). Median 4-PCC dose was 2000 I.U. (range: 500 I.U. to 3000 I.U.). There was a statically significant decrease in INR (p < 0.01), PT (p < 0.01), and PTT (p = 0.02) after 4-PCC administration. Postoperative INR values were ≤3.00 in all patients, and seven (20%) patients had normal INR values. There were no 4-PCC related complications. Four (11%) patients developed subdural/epidural hematoma and 20 (57%) patients died. Mortality was associated with lower Glasgow coma scale (GCS) score. Conclusions: The 4-PCC facilitates INR reversal and surgery in patients presenting with warfarin-associated coagulopathy and intracranial bleeding requiring urgent neurosurgical intervention.

Hemodynamic response during aneurysm clipping surgery among experienced neurosurgeons.

BACKGROUND: Neurosurgery is a challenging field associated with high levels of mental stress. The goal of this study was to investigate the hemodynamic response of experienced neurosurgeons during aneurysm clipping surgery and to evaluate whether neurosurgeons' hemodynamic responses are associated with patients' clinical statuses. METHODS: Four vascular neurosurgeons (all male; mean age 51 ± 10 years; post-residency experience ≥7 years) were studied during 42 aneurysm clipping procedures. Blood pressure (BP) and heart rate (HR) were assessed at rest and during seven phases of surgery: before the skin incision, after craniotomy, after dural opening, after aneurysm neck dissection, after aneurysm clipping, after dural closure and after skin closure. RESULTS: HR and BP were significantly greater during surgery relative to the rest situation (p ≤ 0.03). There was a statistically significant increase in neurosurgeons' HR (F [6, 41] = 10.88, p < 0.001), systolic BP (F [6, 41] = 2.97, p = 0.01), diastolic BP (F [6, 41] = 2.49, p = 0.02) and mean BP (F [6, 41] = 3.36, p = 0.003) during surgery. The greatest mean HR was after aneurysm clipping, and the greatest BP was after aneurysm neck dissection. Systolic, diastolic and mean BPs were significantly greater during surgical clipping for unruptured aneurysms compared to ruptured aneurysms across all stages of surgery (p ≤ 0.002); however, after adjusting for neurosurgeon experience, the difference in BP as a function of aneurysm rupture was not significant (p > 0.08). Aneurysm location, intraoperative aneurysm rupture, admission WFNS score, admission Glasgow Coma Scale scores and Fisher grade were not associated with neurosurgeons' intraoperative HR and BP (all p > 0.07). CONCLUSIONS: Aneurysm clipping surgery is associated with significant hemodynamic system activation among experienced neurosurgeons. The greatest HR and BP were after aneurysm neck dissection and clipping. Aneurysm location and patient clinical status were not associated with intraoperative changes of neurosurgeons' HR and BP.

Predictive value of early near-infrared spectroscopy monitoring of patients with traumatic brain injury.

BACKGROUND AND OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of death and disability in young adults. Study aimed to define the predictive value of early near-infrared spectroscopy (NIRS) monitoring of TBI patients in a Lithuanian clinical setting. MATERIALS AND METHODS: Data of 61 patients was analyzed. Predictive value of early NIRS monitoring, computed tomography data and regular intensive care unit (ICU) parameters was investigated. RESULTS: Twenty-six patients expressed clinically severe TBI; 14 patients deceased. Patients who survived expressed higher NIRS values at the periods of admission to operative room (75.4%±9.8% vs. 71.0%±20.5%; P=0.013) and 1h after admission to ICU (74.7%±1.5% vs. 61.9%±19.4%; P=0.029). The NIRS values discriminated hospital mortality groups more accurately than admission GCS score, blood sugar or hemoglobin levels. Admission INR value and NIRS value at 1h after admission to ICU were selected by discriminant analysis into the optimal set of features when classifying hospital mortality groups. Average efficiency of classification using this method was 88.9%. When rsO2 values at 1h after admission to ICU did not exceed 68.0% in the left hemisphere and 68.3% in the right hemisphere, the hazard ratio for death increased by 17.7 times (P<0.01) and 5.1 times (P<0.05), respectively. CONCLUSIONS: NIRS plays an important role in the clinical care of TBI patients. Regional brain saturation monitoring provides accurate predictive data, which can improve the allocation of scarce medical resources, set the treatment goals and alleviate the early communication with patients' relatives.

Brugada-like electrocardiographic patterns induced by hyperkalemia.

Brugada syndrome was described in 1992 as a new clinical and electrocardiographic syndrome involving susceptibility to ventricular arrhythmias and sudden cardiac death in patients with no obvious structural heart disease. Brugada syndrome is characterized by a hereditary anomaly in the sodium ion channel (mutation of the SCN5A gene) identified by a wide QRS associated with the ST-segment elevation and the T­wave inversion in the right precordial leads. The Brugada-like electrocardiographic pattern can be caused by sodium channel-blocking drugs and electrolyte disorders. Hyperkalemia may produce multiple ECG abnormalities, including the ST-segment elevation and pseudomyocardial infarction with a resolution of these abnormalities after the correction of hyperkalemia. This article describes 8 cases of pseudoanteroseptal myocardial infarction in acute renal insufficiency with hyperkalemia. The ST-segment elevation related to hyperkalemia is resolved by the reduced serum potassium level. Clinicians should recognize that hyperkalemia is one of the etiologies of the Brugada-like electrocardiographic pattern.

[The assessment of clinical evaluation and treatment results of high-energy blunt polytrauma patients]. / Dideles energijos buka trauma patyrusiu pacientu klinikinio tyrimo duomenu ir gydymo rezultatu ivertinimas.

UNLABELLED: The aim of this study was to evaluate the mechanism of high-energy blunt trauma, age and gender of patients, severity of regional and multiple injury, ventilation time, length of stay in intensive care unit and in-hospital stay, in-hospital complications, and treatment outcome. MATERIALS AND METHODS: Data on 159 patients with severe multiple injuries, meeting inclusion criteria, were collected prospectively and evaluated retrospectively. RESULTS: The mean age of multiple trauma patients was 43.9+/-1.4 years; males were injured 2.5 times more often than females (P<0.001). More than half (66.7%) of patients were 17-64-year-old males. Majority (83%) of all patients were injured in motor vehicle crashes, and 52.2% of these patients were pedestrians. The mean Injury Severity Score was 29.5+/-0.8, and severe (Abbreviated Injury Scale score of 3 and more) injuries of extremities, head, and chest made up 69.1% of all injuries. The mean ventilation time, mean length of stay in intensive care unit, and mean in-hospital stay were 5.5+/-0.7, 7.0+/-0.8, and 23.6+/-1.6 days, respectively. Acute lung complications were the most common (25.2%). Systemic inflammatory response syndrome developed in 7.5% of patients, and sepsis in 3.8% of patients. More than one-fifth (20.8%) of polytrauma patients died. CONCLUSIONS: Working-age male pedestrians (17-64 years old) made up two-thirds of all polytrauma patients. Severe injuries of extremities, head, and chest were present in 69.1% of all cases. Lung complications were the most common.