Cognitive decline, psychological distress and brain atrophy in recovery and residual periods of aneurysmal subarachnoid hemorrhage

Objective: Recent scientific breakthroughs have allowed for new methods of prognostication for aneurysmal subarachnoid hemorrhage (aSAH) to be developed.We aim to verify whether or not initial indicators of these patients' condition in the acute period can predict cognitive decline in the late phase of the disease. Methods: We examined 114 patients in recovery and residual periods of aneurysmal subarachnoid hemorrhage and divided them into two age groups: Group A, consisting of younger patients from 18 to 44 years (37,72%,), and Group B, with older patients ranging from 45 to 59 years (62,28%).We used MoCA-test (Montreal Cognitive Assessment) to evaluate the cognitive decline, analyzed main parameters of acute period, such as clinical and anatomical type of hemorrhage, Hunt-Hess Grading Scale, Glasgow Coma Scale (GCS). SPSS statistics was applied for the statistical analyses. Results: The linear regression method allowed us to build a mathematical model, which is reflecting the relation of cognitive state in the residual period of aSAH from such parameters of the acute period, as GCS score, Hunt-Hess grade (I-V), type of bleeding (numbered: 1 – for subarachnoid haemorrhage, 2 – subarachnoid accompanied by parenchymal bleeding, 3 – subarachnoid and ventricular, 4 – subarachnoid with parenchymal and ventricular). The previously fixed mathematical constant has to be used during calculations. According to the formula given below, we can predict the remote cognitive decline, while the patient is in the acute period of the disease. MoCA test score = 28,136 + (−2,464 * Patient’s age) + (0,106 * GCS) + (−0,728 * numbered hemorrhage type) + (−1,064 * Hunt-Hess score number 1–4). Conclusion: Thus, the data obtained indicate that patients who have undergone aSAH need an attention and detailed examination similarly to the patients in the acute period. Morphometric indices can be both additional markers of cerebral atrophy and predictors of cognitive decline. Dynamic observation in the recovery and residual periods of aSAH should include the assessment of the quality of life scale, as an additional criterion for assessing the nature and direction of psycho-emotional disorders. Interpretation: Apparently, prediction of cognitive decline will help in improvement of treating methods individually for each patient. The prognostic model may be applied by healthcare professionals, neurologists, neurosurgeons

Ischemic stroke subtypes: some aspects of apoptosis in acute phase of brain infarction

Objectives. The aim of the given research is to analyze the peculiarities of apoptosis and intracellular oxidative protection in acute phase of different ischemic stroke subtypes. Material and methods. The study included 366 patients. We determined the number of white blood cells in the stage of apoptosis and necrosis, with a high content of reactive oxygen spices, with reduced mitochondrial potential, the activity of Cu, Zn-SOD (superoxide dismutase), Mn-SOD and cathepsin D. Outcomes. We noticed mitochondrial dysfunction, intracellular oxidative stress, apoptosis and necrosis of white blood cells at all subtypes of brain infarction on the 1st day. A direct impact of mitochondrial dysfunction on the course of large arteries atherosclerosis (LAAS) in acute phase was established. In acute phase of LAAS we detect activation of both ways of apoptosis: lysosomal one and apoptosis associated with mitochondrial dysfunction. At LACunar stroke (LAC) we observed activation of mainly lysosomal way of apoptosis, due to the apoptosis of endothelial cells, proved by significant correlation between the content of white blood cells in peripheral blood in the stage of apoptosis (ANV+-cells) and total and free activity of cathepsin D. All ischemic stroke subtypes are associated with significantly (p<0,01) decreased activity of intracellular SOD-dependent antioxidant protective system (total SOD, Mn-SOD and Cu, Zn-SOD), that along with the increased number of intracellular reactive oxygen species (ROS) indicates misbalance between ROS formation process and the possibility of its elimination. At cardioembolic infarct (CEI) neutralization of intracellular ROS is due to mitochondrial SOD activity, while at LAC and LAAS – due to the intracellular one. Conclusions. The peculiarities of apoptosis activity and intracellular antioxidant protection in acute phase of brain infarction depend on its subtype

Characteristics of cerebral hemodynamics in patients with chronic brain ischemia

Background. Literature sources report conflicting results regarding the severity of clinical symptoms of hydrocephalus (HC) and their association with cerebral arterial blood flow (CABF); most studies do not show a direct relationship, while some suggest a link between clinical severity and progressive decrease in CABF. The study of hemodynamic changes in the brain of patients with chronic brain ischemia (CBI), elucidation of their relationship with cognitive impairments helps to improve diagnostic approaches and optimize the prognosis of the disease. The purpose of this study is to investigate the state of cerebral hemodynamics and to establish its relationship with changes in cognitive functions in patients with CBI and HC. Materials and Methods. A comprehensive examination of 110 patients with CBI and HC was performed. The localization of the HC and results of Montreal Cognitive Test (MoCA scale) were taken into account. Computed tomography of the brain was performed with subsequent determination of morphometric parameters and indices. The state of cerebral blood flow and structural changes of blood vessels were studied using transcranial color-coded duplex ultrasonography (TCCS) of intracranial vessels and extracranial divisions. Microsoft Excel 2011 and Statistica were used for statistical processing of the results. Results. It was found that there was a significantly larger diameter of both common carotid arteries (CCA), thickness of complex intima\media (CIM), maximum systolic velocity (Vs), velocity at the end of the diastolic cycle (Vd), as well as peripheral resistance (IR) in left CCA (p &lt;0,05) in patients with CBI and HC compared with patients with CBI without HC. Significantly larger diameter of left internal carotid artery (ICA), Vs, Vd and IR was revealed; Vs and Vd in the right ICA; Vd in the extracranial devision of vertebral artery (VA) in patients with HC. A significant relationship was found between the following blood flow parameters and the values of the MoCA scale: Vs MCA/MoCA (r = 0,45, p &lt;0,05), Vs ACA/MoCA (r = 0,38, p &lt;0.05), ICA diameter/MoCA (r = -0,51, p &lt;0,05). It was found that the diameter of CCA and the thickness of CIM were significantly larger in patients with CBI with internal HC in comparison with patients with CBI with external HC (p &lt;0,01). Vs and Vd in patients with internal hydrocephalus were significantly lower, and IR was significantly higher compared with patients with external hydrocephalus (p &lt;0,01). The diameter of ICA and IR in patients with CBI with internal HC was significantly higher, and Vs was significantly lower compared with patients with CBI and external HC (p &lt;0,01). Significantly different values were found in Vs and IR meanings in middle cerebral artery (MCA) and Vs in anterior cerebral artery (ACA) in patients with CBI with internal HC compared with patients with CBI with external HC.Conclusions. Functional parameters of blood flow and structural changes of cerebral arteries in patients with CBI with concomitant hydrocephalus differed significantly from those in patients without hydrocephalus and depended on the type and severity of hydrocephalus. ICA occlusion, ICA stenosis &gt;50%, and intracranial venous stasis were significantly more common in patients with severe and moderate HC compared with those with mild HC. A weak relationship was found between the structure of carotid arteries and blood flow in intracranial arteries in patients with CBI and HC. There was a significant relationship between blood flow indices and the values of the MoCA scale, which indicated the effect of changes in the vessels of the anterior circular basin on the cognitive functions and the lack of such connection with blood flow indices in vertebrobasilar basin.</p

Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial

BackgroundSatralizumab, a humanised monoclonal antibody targeting the interleukin-6 receptor, reduced the risk of relapse in patients with neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant therapy. This study assessed the safety and efficacy of satralizumab monotherapy in patients with the disorder.MethodsIn this phase 3, double-blind, placebo-controlled, parallel-group trial, we enrolled adults aged 18-74 years with aquaporin-4 antibody seropositive or seronegative NMOSD at 44 investigational sites in 13 countries. Eligible participants had experienced at least one documented NMOSD attack or relapse in the past 12 months and had a score of 6·5 or less on the Expanded Disability Status Scale. Exclusion criteria included clinical relapse 30 days or fewer before baseline. Participants were randomly assigned (2:1) to receive satralizumab 120 mg or visually matched placebo subcutaneously at weeks 0, 2, 4, and every 4 weeks thereafter. Taking immunosuppressants concomitantly was prohibited. The primary endpoint was time to the first protocol-defined relapse, based on the intention-to-treat population and analysed with stratification for two randomisation factors (previous therapy for prevention of attacks and nature of the most recent attack). Safety was assessed in all participants who received at least one dose of satralizumab or placebo. The double-blind phase was due to last until 44 protocol-defined relapses occurred or 1·5 years after random assignment of the last patient enrolled, whichever occurred first; participants could enter an open-label phase after the occurrence of a protocol-defined relapse or at the end of the double-blind phase. The study is registered with ClinicalTrials.gov, NCT02073279.Findings95 (57%) of 168 screened participants were randomly assigned to treatment (63 to satralizumab; 32 to placebo) between Aug 5, 2014, and April 2, 2017. Protocol-defined relapses occurred in 19 (30%) patients receiving satralizumab and 16 (50%) receiving placebo (hazard ratio 0·45, 95% CI 0·23-0·89; p=0·018). 473·9 adverse events per 100 patient-years occurred in the satralizumab group, as did 495·2 per 100 patient-years in the placebo group; the incidence of serious adverse events and adverse events leading to withdrawal was similar between groups.InterpretationSatralizumab monotherapy reduced the rate of NMOSD relapse compared with placebo in the overall trial population, with a favourable safety profile. The patient population included a ratio of aquaporin-4 antibody seropositive and seronegative patients that was reflective of clinical practice. Satralizumab has the potential to become a valuable treatment option for patients with NMOSD.FundingChugai Pharmaceutical (Roche)

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study

Objective: To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment. Methods: An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs). Results: Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL. Significance: ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged