Anoxic Damage Research Articles

Pharmacologic Enhancement of Rotator Cuff Repair: A Narrative Review.

As rotator cuff repairs (RCRs) are among the most common procedures in upper extremity orthopedics, healing augmentation using pharmacologic enhancement of the repaired rotator cuff muscle is of particular interest. The purpose of this study is to review the current understanding of Matrix Metalloproteinases (MMPs), Doxycycline, Testosterone, Estrogen, Growth hormone/ IGF-1, Vitamin D, and Vitamin C as a means to mitigate deleterious effects and propagate factors that support healing following RCR. A review of English language articles in PubMed and Medline was conducted in December of 2020. All articles describing the current understanding of the aforementioned therapies were reviewed. Studies were excluded if they were non-English or reported incomplete results. Matrix metalloproteinases (MMP's) are fundamental to the healing process after rotator cuff tears through a delicate balance of various proteases that can be modulated by doxycycline through inhibition. While testosterone has shown to induce replication and differentiation of the tendon stem-cells, estrogen agonists have been shown to decrease inflammation and muscle atrophy. Though growth hormone being associated with elevated collagen synthesis and decreased anoxic damage when present, clinical studies have shown inconclusive and adverse effects on rotator cuff healing. Patients with Vitamin D deficiency have shown to have increased fatty infiltration in rotator cuff muscle while Vitamin C functions as an antioxidant that increases collagen and fibroblast proliferation. As manipulation of pharmacologic factors shows potential for enhancing healing following RCRs, future studies are needed to establish a viable augmentation strategy to improve patient outcomes.

Quality of models of scales of consciousness level, functional state, and General somatic severity in patients with consequences of brain damage in intensive care and rehabilitation department.

Aims: development and substantiation of a typical scheme for the clinical use of scales of the level of consciousness, general somatic and functional status of patients with of brain damage. Methods: Included 118 patients on 20-50 days after traumatic brain injury, anoxic damage; consequences of acute cerebral circulatory disorders, and neurosurgical operations. In groups of patients who are in a coma, vegetative status, a state of minimal consciousness and a state of clear consciousness, the analysis of the statistical quality of clinical scales was carried out: scales of consciousness: the Glasgow coma Scale (GCS); FOUR (Full Outline of UnResponsiveness); CRS-R-Coma Recovery Scale-Revised; the Glasgow outcome Scale (COS); the extended scale of the Glasgow coma (COSE - Glasgow outcome scale extended); Rancho Los Amigos scale-scale of consciousness and interaction with the environment (the Rancho Los Amigos scale - RLAS); Functional status scales: DRS (the Disability Rating Scale); modified Rankin Scale mRS; Barthel Activities of Daily Living (ADL) Index; functional independence measure-FIM; Karnovsky Index; Rivermead Mobility Index self-assessment of everyday life opportunities in Merton and Sutton (checklist self-maintenance. Merton and Sutton community NHS trust); Scales of General somatic severity: assessment of multi-organ dysfunction on the APACHE II scale (Acute Physiology and Chronic Health Evaluation); APACHE IV scale; SAPS II scale (Simplified Acute Physiology Score); SOFA scale (Sequential Organ Failure Assessment). The functional state of the ANS was recorded using HRV parameters by recording 5-minute RR intervals of the electrocardiogram. Results: There are 4 groups of patients who are in a state of coma, vegetative status, a state of minimal consciousness and a state of clear consciousness. In 67 patients out of 118 examined (56.8%) the parameters of ANS functional activity are in the zone of pathological (sympathetic/parasympathetic hyperactivity) values. Conclusions: Various scales of the level of consciousness, functional and general somatic severity of patients objectively differ in clinical significance in the gradation of coma - vegetative status - minimal consciousness - clear consciousness.

A Randomized Controlled Study of the Effectiveness of Electrophysiological Monitoring of Dexmedetomidine in Patients with Brain Damage of Various Origins

Background.At the same time, the main effect of the use of this drug is the elimination of the autonomic nervous system dysfunction and sympatholysis. It seems important to search for a method of indications and selection of a dose of dexmedetomidine in intensive care.Aims to improve the clinical effectiveness of the electrophysiological navigation of the prolonged use of dexmedetomidine in patients with brain pathology of various origins.Methods.The study included 83 patients 2050 days after the traumatic brain injury, anoxic damage; consequences of acute disorders of cerebral. 37 patients comprised the 1st intervention group with a clinical course of dexmedetomidine (male 28; female 9; average age 49.62.3 years) and 46 patients comprised the 2nd control group without pharmacological correction with dexmedetomidine (male 23; female 23, average age 512.5 years). Criteria for the inclusion of prolonged infusion of the drug dexmedetomidine (Orion Pharma, Finland) are based on heart rate variability (HRV) indicators characteristic of sympathetic hyperactivity, the target task of titration of doses of dexmedetomidine served as the parameters for achieving normal HRV indicators, the appearance of parasympathetic hyperactivity served as the basis for reducing the dosage of the drug or stopping it of application. HRV parameters were recorded before dexmetomedine infusion-initially, on 13; 45; 910; 1520 days of drug administration.Results.The starting dose of dexmedetomidine with sympathetic hyperactivity in patients was 0.12 to 0.24 g.kg1.hr1(average dose 0.160.01; total 200 mg/day). According to digital data from HRV, the effective dose of dexmedetomidine ED50 was 0.260.03 g.kg1.hr1(total daily 353.835.1 g) and was achieved on day 910 using dexmedetomidine.Conclusions.The protective role of dexmedetomidine with correction of sympathetic hyperactivity based on electrophysiological navigation according to the HRV is reliable in the following indicators: The improvement of consciousness; a significant decrease in the incidence of distress lung syndrome; septic shock; mortality.

Prediction of the effectiveness of spontaneous breathing in patients with brain damage of various etiologies

BACKGROUND: Long-term respiratory support is a severe disabling factor and is accompanied by a long stay of patients in intensive care units.
 AIMS: The analysis of the predictors of the success of disconnection from mechanical ventilation on the basis of clinical and diagnostic criteria in patients with brain damage of various etiologies.
 METHODS: The study included 53 patients (husband ― 28, women ― 25; cf. age 53.69 2.34) who are in 2019 with the consequences of traumatic brain injury (TBI) (n = 18; 33.9%); consequences of acute cerebrovascular accident (n = 24; 45.3%); the effects of anoxic brain damage (n = 3; 5.7%); consequences of subarachnoid hemorrhage (n = 8; 15.1%).
 RESULTS: The statistically significant predictor of recovery of spontaneous breathing in the 1st and 2nd groups of patients were preserved chemoreflex sensitivity (IPCS), the sensitivity and specificity of IPCS was 78.57% [95 % DI 49.295.26] and 83.3 % [95 % CI 62.695.26]. The index of peripheral chemoreflex sensitivity (IPCS) was calculated using the formula: IPCS = [RRe / RRi] [Vt(e) / Vt(i)] [VE(e) / VE(i)] [Vt(e) VE(i)], where IPCS is the index of peripheral chemoreflex sensitivity in l/min; RRi and RRe; Vt(i) and Vt(e); VE(e) and VE(i) ― respiratory rate (RR, breaths/min), tidal volume (Vt), minute ventilation (VE), (l/min) of the starting point ― (i) before carrying out a functional stress test and (e) ― during a functional test of normobaric hypoxia with SpO2 in the range of 9080 %.
 CONCLUSIONS: The most significant clinical parameters statistically reliably hampering the process of successful recovery of spontaneous breathing in addition to chemoreflex sensitivity are the presence of severe heart failure, pneumonia, autonomic dysfunction, level of consciousness, age, higher levels of inspiratory and expiratory pressure mounted on a respirator.

5226The majority of 30-day survivors of in-hospital cardiac arrest are alive one-year post-arrest without anoxic brain damage, admission to nursing home or need of in-home care

Abstract Background Survivors of in-hospital cardiac arrest are at risk of anoxic brain damage that can lead to admission to nursing home or need of in-home care. However, studies on long-term outcomes after in-hospital cardiac arrest are scarce with previous research focusing on short term measures such as survival-to-discharge. Purpose This study aimed to investigate the composite endpoint of nursing home admission or anoxic brain damage among 30-day survivors of in-hospital cardiac arrest within the first-year post-arrest. As a sub analysis, we also investigated the additional need of in-home care. Methods All in-hospital cardiac arrests in 13 Danish hospitals during 2013–2015 were identified from the DANARREST register. Inclusion criteria were indication for a resuscitation attempt and survival to day 30. Patients who, prior to arrest, already lived in a nursing home, and/or had anoxic brain damage were excluded. In the sub analysis patients who received in-home care prior to arrest were also excluded. The DANARREST data was linked to nationwide registries including the National Patient Register and administrative nursing home and home care registries using the Danish Civil Registration Number, a unique personal identification number that is given to every citizen in Denmark. Results The primary study population comprised of 454 (26.3%) 30 day-survivors out of 1723 eligible patients. Median age was 67 (Q1-Q3 57–75); 301 (66.9%) were men. In this group, the 1-year risk of anoxic brain damage or nursing home admission was 4.6% (95% CI 2.7%- 6.6%) with a competing risk of death of 15.6% (95% CI 12.3%-19.0%), leaving 79.8% alive without anoxic brain damage or nursing home admission at one-year follow-up (see Figure 1A). The sub study population comprised of 343 30-day survivors with a 1-year risk of anoxic brain damage, nursing home admission or need of in-home care of 23.6% (95% CI 19.1%-28.1%). The competing risk of death was 7.6% (95% CI 4.8%-10.4%), leaving 68.8% alive without anoxic brain damage, nursing home admission or need of in-home care at one-year follow-up (see Figure 1B). Figure 1 Conclusion The majority of 30-day survivors of in-hospital cardiac arrest were alive at one-year follow-up without being diagnosed with anoxic brain damage, admitted to nursing home or without need of in-home care.

P1728Cardiogenic shock patients: those with and those without out-of-hospital cardiac arrest are different clinical entities

Abstract Introduction Cardiogenic shock (CS) due to myocardial infarction (MI) carries 30-day mortality rates as high as 50%. The vast majority of study cohorts assessing mortality in CS comprise both patients presenting with and without out-of-hospital cardiac arrest (OHCA). Patients with and without OHCA are likely to represent two distinctive entities, which may be problematic to combine in an intervention trial. Purpose The aim of the study was to compare CS due to MI patients presenting with and without OHCA in terms of patient characteristics and outcome. Methods In the period from 2010–2017 all patients admitted at two tertiary heart centres in Denmark with CS following MI were individually identified and validated through patient records. The two centres have a catchment area of 3.9 million citizens corresponding to two-thirds of the Danish population. Results A total of 1716 CS patients were identified, of which 42% presented with OHCA. OHCA patients were younger (mean 63 vs 67 years), more frequently male (85 vs 67%), had higher lactate concentration (median 6.2 vs 5.0 mmol/L) on admission and higher left ventricular ejection fraction (median 30 vs 25%) compared to patients without OHCA (p<0.0001 for all). Patients presenting with OHCA had lower 30-day mortality compared to patients without OHCA (49% vs. 57%, respectively, plogrank<0.0001, Figure). Cause of in hospital death differed markedly between the two groups. Not surprisingly, anoxic brain damage was the leading cause of in hospital death in the OHCA group (56%) and only seen in 4% of patients without OHCA. In contrast, cardiac failure was the main cause of death in hospital death among patients without OHCA (60%), compared to 27% in patients with OHCA (p<0.0001). Figure 1 Conclusion Among patients with CS due to MI, overall 30-day mortality was significantly lower in patients presenting with OHCA. Anoxic brain damage was the main cause of in hospital death among OHCA patients, whereas fatal heart failure prevailed in patients without OHCA. Combining these two groups in a single trial with one specific intervention seems inappropriate and likely to cause an imbalance in the signal-to-noise ratio. Acknowledgement/Funding The Danish Heart Foundation and a research grant from Abiomed

Monitoring of the Effectiveness of Intensive Care and Rehabilitation by Evaluating the Functional Activity of the Autonomic Nervous System in Patients with Brain Damage

Purpose: evaluation of the clinical significance of parametric monitoring of the effectiveness of intensive care and rehabilitation based on the analysis of the functional state of the autonomous nervous system in patients with brain damage of different genesis.Materials and methods. The study included 66 patients on day 20—50 after the traumatic brain injury; anoxic damage; and stroke consequences. The isolation of clinical groups and subsequent analysis of clinical status is based on the analysis of the functional state of the autonomic nervous system based on the dynamics of the heart rate variability (HRV) parameters. Findings obtained in studies of 500 patients in the postoperative period with a 5-minute HRV were tested as normal and abnormal ANS parameters [1]. Parasympathetic hyperactivity was measured within the limits for SDNN (standard deviation of all normal-to-normal R-R intervals) > 41.5 ms; for rMSSD (root-meansquare of the successive normal sinus R-R interval difference) > 42.4 ms; for pNN50% (the percentage of interval differences in successive NN intervals greater than 50 ms (NN50) / total number of NN intervals) > 8.1%; for SI (Baevsky stress index, in normalized units) < 80 n. u.; for TP (total power of variance of all NN intervals) > 2000 ms2. Sympathetic hyperactivity was determined within the limits for following parameters: SDNN, < 4.54 ms; rMSSD, < 2.25 ms; pNN50%, < 0.109%; SI, > 900 n. u.; TP < 200 ms2. Normal HRV parameters were selected within the limits of the values for: SDNN [13.31-41.4ms]; rMSSD [5.78—42.3 ms]; pNN50% [0.110—8.1%]; SI [80—900 nu]; for TP [200—2000 ms2]. To verify the parasympathetic or sympathetic hyperactivity within these limits, 3 of 5 parameters were chosen [1].Results. Based on the dynamics of the HRV parameters before the intensive care and on days 30—60 of the intensive therapy and rehabilitation of patients with traumatic and non-traumatic brain injuries, 5 main clinical groups of patients were identified. Group 1 (n=27) consisted of patients with normal parameters of the ANS functional activity (both at the time of admission to the hospital and on the 30—60th day of the intensive therapy and rehabilitation). Group 2 (n=9) included patients with the baseline sympathetic hyperactivity of the ANS at admission to the intensive care unit and normal functional activity of the ANS on the 30—60th day of the intensive care and rehabilitation. Group 3 (n=8) included patients with baseline normal functional state of the ANS and the signs of sympathetic hyperactivity of the ANS on the 30—60th day of the intensive care and rehabilitation. Group 4 (n=15) consisted of patients with signs of sympathetic hyperactivity of the ANS both initially and on the 30—60th day of the intensive care and rehabilitation. Group 5 (n=7) included patients with signs of parasympathetic hyperactivity of the ANS (according to the parameters of HRV) both at baseline, at admission to the intensive care unit, and on the 30—60th day of the intensive care and rehabilitation.Conclusion: The normalization of HRV parameters is accompanied by patients’ recovery from the vegetative state and coma to minimal consciousness or normal consciousness; the index of disability rate decreases, the social reintegration grows, according to the DRS scale (M. Rappaport, 1982); dependence on mechanical ventilation reduces, and the muscle tone normalizes.

Organ Donation in Pediatric Patients with Severe Anoxic Brain Injury.

Anoxic brain injury in children is a rare and devastating occurrence. Families are shocked by the unexpected nature of their child's neurologic injury, which may be the result of a sudden and prolonged cardiac arrest. Organ donation in these children is subject to much discussion and controversy. Recently, we encountered three pediatric patients with anoxic brain damage who progressed to brain death within a few days of admission. Pediatric palliative care was involved from the time of arrival to the hospital in all the patients. The team served as a critical conduit to support families and helped in managing end-of-life decisions including organ donation. All three families consented to organ donation. We discuss here the patients, the palliative care involvement, and the factors responsible for successful donation.

A rare neurological complication of Waldenstrom’s Macroglobulinemia

Bilateral and simultaneous facial nerve palsy (FNP) is a rare clinical condition occurring in 0.3–2.0% of facial palsy cases and is typically a manifestation of an underlying systemic disease. We here describe a case of a 67-year-old Hispanic man with a known history of Waldenstrom’s Macroglobulinemia (WM) who presented to the clinic with a sub-acute onset of bilateral facial weakness. No alternate etiology for the facial weakness was identified after a thorough diagnostic approach. WM is a rare hematological condition due to low-grade B cell lymphoma, where lymphoplasmacytoid cells infiltrate different tissues and secrete monoclonal IgM. Peripheral neuropathy develops in 15–30% of the cases, being usually a chronic, progressive, symmetric, predominantly distal polyneuropathy. Facial nerve impairment is unusual; however, it could be caused by anoxic damage as a result of an increased blood viscosity from IgM monoclonal gammopathy, direct nerve infiltration of tumorous cells and an antibody (anti-MAG) mediated demyelinating process. Treatment is directed to the established mechanism for neural injury. This report highlights a rare condition (WM) with a rare complication (bilateral facial nerve palsy) and illustrates the broad differential comprised by this presenting complaint.

Multiple factors related to better outcome in out-of-hospital cardiac arrest—is mediation analysis the solution?

We thank Dr. Goto for his editorial in the Journal of Emergency and Critical Care Medicine entitled “Bystander Interventions for Out-of-Hospital Cardiac Arrests: Substantiated Critical Components of the Chain of Survival” (1), commenting on the recent New England Journal of Medicine manuscript “Bystander Efforts and 1-Year Outcomes in Out-of-Hospital Cardiac Arrest” conducted by our research group (2). Dr. Goto’s outline of the nationwide initiatives taken in Denmark during the last ten to fifteen years to increase rates of early resuscitative efforts by bystanders is extensively and accurately described. These initiatives include widespread voluntary and mandatory courses in basic life support, introduction and implementation of dispatch-assisted CPR, widespread automated external defibrillator (AED) dissemination and formation of an AED registry and linkage to emergency dispatch centers, enabling healthcare professionals to guide bystanders to the nearest AED (1-4). Bystander CPR and 30-day survival rates have more than tripled since the beginning of the past decade, where the Danish Cardiac Arrest Registry was established (5). In addition to the increased survival rates, Dr. Goto also highlighted from our recent New England Journal of Medicine manuscript that 30-day survivors were significantly less likely to be diagnosed with anoxic brain damage or admitted to a nursing home during the first year after out-of-hospital cardiac arrest (OHCA) had they received bystander CPR or bystander defibrillation relative to no bystander resuscitation (1,2).

DL-3-n-butylphthalide protects endothelial cells against advanced glycation end product-induced injury by attenuating oxidative stress and inflammation responses.

Endothelial dysfunction, regarded as a key step in the pathophysiological course of diabetic vascular complications, is initiated and deteriorated by advanced glycation end products (AGEs). DL-3-n-butylphthalide (DL-NBP) has been proven to have protective effects on neurons and vascular endothelial cells against ischemic and anoxic damage. The aim of the present study was to investigate whether NBP is able to attenuate AGE-induced endothelial dysfunction in vitro, and also elucidate the possible underlying mechanism. An injury model of human umbilical vein endothelial cells (HUVECs) induced by AGEs (200 µg/ml) was established. The results demonstrated that pretreatment with NBP (1-100 µM) significantly increased HUVEC viability and inhibited the apoptosis induced by AGEs. In addition, AGEs stimulated the expression levels of the receptor for AGEs protein and the downstream protein nuclear factor-κB in HUVECs, which were inhibited by pretreatment with NBP. Furthermore, it significantly reduced reactive oxygen species generation and the level of the inflammatory cytokines, intercellular cell adhesion molecule-1 and monocyte chemotactic protein-1, in HUVECs mediated by AGEs. The current findings indicated that NBP attenuated AGE-induced endothelial dysfunction by ameliorating inflammation and oxidative stress responses.

Synaptic damage underlies EEG abnormalities in postanoxic encephalopathy: A computational study.

In postanoxic coma, EEG patterns indicate the severity of encephalopathy and typically evolve in time. We aim to improve the understanding of pathophysiological mechanisms underlying these EEG abnormalities. We used a mean field model comprising excitatory and inhibitory neurons, local synaptic connections, and input from thalamic afferents. Anoxic damage is modeled as aggravated short-term synaptic depression, with gradual recovery over many hours. Additionally, excitatory neurotransmission is potentiated, scaling with the severity of anoxic encephalopathy. Simulations were compared with continuous EEG recordings of 155 comatose patients after cardiac arrest. The simulations agree well with six common categories of EEG rhythms in postanoxic encephalopathy, including typical transitions in time. Plausible results were only obtained if excitatory synapses were more severely affected by short-term synaptic depression than inhibitory synapses. In postanoxic encephalopathy, the evolution of EEG patterns presumably results from gradual improvement of complete synaptic failure, where excitatory synapses are more severely affected than inhibitory synapses. The range of EEG patterns depends on the excitation-inhibition imbalance, probably resulting from long-term potentiation of excitatory neurotransmission. Our study is the first to relate microscopic synaptic dynamics in anoxic brain injury to both typical EEG observations and their evolution in time.

Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model.

Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidation and Lectin-like oxidized LDL receptor-1 (LOX-1) induction, leading to a pathological hippocampal response, namely, ischemic long-term potentiation (i-LTP). These events may correlate with the progressive neural loss observed in NPCD. To test these hypotheses, hippocampal slices from Wild Type (WT) and NPC1−/− mice were prepared, and field potential in the CA1 region was analyzed during transient oxygen/glucose deprivation (OGD). Moreover, LOX-1 expression was evaluated by RT-qPCR, immunocytochemical, and Western blot analyses before and after an anoxic episode. Our results demonstrate the development of a precocious i-LTP in NPC1−/− mice during OGD application. We also observed a higher expression of LOX-1 transcript and protein in NPC1−/− mice with respect to WT mice; after anoxic damage to LOX-1 expression, a further increase in both NPC1−/− and WT mice was observed, although the protein expression seems to be delayed, suggesting a different kinetic of induction. These data clearly suggest an elevated susceptibility to neurodegeneration in NPC1−/− mice due to oxidative stress. The observed up-regulation of LOX-1 in the hippocampus of NPC1−/− mice may also open a new scenario in which new biomarkers can be identified.

Effects of multi-environmental factors on physiological and biochemical responses of large yellow croaker, Larimichthys crocea

Land-based recirculating aquaculture systems (RAS) and cage culture are important methods of Larimichthys crocea production. The effects of environmental factors on physiological and biochemical aspects of L. crocea require clarification. Temperature and salinity are controlled in RAS and directly affect L. crocea growth and survival. To explore optimal parameters, the oxygen consumption rate (RO), ammonium excretion rate (RN), and O/N ratio at different temperatures (8, 14, 20, 26, and 32 °C) and salinities (5, 15, 25, and 35‰) were determined. RO, RN, and O/N first increased and then decreased with elevated temperature and salinity, peaking at 26 °C and 25‰, respectively. This suggests that the metabolism of L. crocea was maximal at 26 °C and 25‰ salinity, which promote its growth and survival. Additionally, hypoxia affects cage culture, and has significant effects on enzymatic activities and stress-inducible gene expression. To accelerate the selective breeding of hypoxia-tolerant L. crocea in cage culture, we measured adenosine triphosphatase (ATPase), lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH) activities, and hypoxia-inducing factor 1 (HIF-1) mRNA expression in the myocardium under hypoxia (2.5, 3.5, and 4.5 mg L−1). ATPase and SDH activities first decreased and then increased under hypoxia, whereas LDH activity and HIF-1α expression first increased and then decreased. Thus, under hypoxia, the myocardial mitochondria switched from being susceptible to being resistant to injury induced by energy metabolism, and respiration in L. crocea likely converted from aerobic to anaerobic during adaptation. Furthermore, the upregulation of HIF-1α mRNA suggests it has an active role in protection against anoxic damage.

A study of the internal construct and predictive validity of the SMART assessment for emergence from vegetative state

ABSTRACTObjective: The Sensory Modality Assessment and Rehabilitation Technique (SMART) was developed to assess the levels of awareness, functional, sensory and communicative abilities of adults in vegetative (VS) or minimally-conscious states following severe brain injury. The current study seeks to ascertain if a total score can be derived from the individual assessments contained within SMART and to test the internal construct and predictive validity of that total score.Subjects: Persons in VS were recruited over a 3-year period and current status was determined after a 17-year follow-up.Design: Data were evaluated by fit to the Rasch model. Predictive validity for emergence from VS was ascertained through an Area-Under-the-Curve [AUC] analysis.Results: Sixty people in VS were assessed on several occasions. Average age on admission was 38.8 years; 30 had anoxic brain damage; 21 traumatic injury. The Rasch analysis indicated the raw score was a sufficient statistic for awareness. Over half [55%] failed to emerge from VS. For those with anoxic brain injury, a SMART cut point of 85 gave an AUC of 0.966 (95% CI = 0.910–1.00) for emergence, as did a cut point of 68 for those with traumatic brain injury.Discussion: The current analysis suggests that SMART may have important predictive attributes for emergence (or lack thereof). No change in status of those discharged in VS has been reported to this present day.

Orthostatic hypotension and cognitive impairment in Parkinson's disease: Causation or association?

Orthostatic hypotension and cognitive impairment are common in Parkinson's disease (PD) and significantly impair quality of life. Orthostatic hypotension and cognitive impairment appear to be interrelated. Whether the relationship is causative or associative remains unclear. The vascular hypothesis proposes that recurrent episodic hypotension results in cerebral hypoperfusion, in turn causing anoxic damage to vulnerable areas of the brain and impaired cognitive function. Support for this hypothesis has come from brain MRI studies showing an association between white matter hyperintensities and a postural drop in blood pressure among PD patients. Alternatively, the association between orthostatic hypotension and cognitive decline in PD may reflect shared underlying synuclein-related pathology affecting common neuroanatomical and neurochemical substrates. Cardiac imaging studies demonstrate noradrenergic denervation early in PD, and cardiac denervation has been associated with poorer cognition. Neurogenic orthostatic hypotension occurs as a result of defective norepinephrine release from sympathetic terminals upon standing. Neuropathological studies have also demonstrated Lewy body pathology in the locus coeruleus; the main source of noradrenaline in the brain. Locus coeruleus norepinephrine levels are reduced in PD patients with dementia when compared with PD patients without. In this review, we examine the evidence for an association between orthostatic hypotension and cognitive impairment in PD. We evaluate the literature supporting the hypothesis that progressive noradrenergic denervation underlies both orthostatic hypotension and cognitive impairment, and we examine studies suggesting that recurrent cerebral hypoperfusion results in cognitive decline in PD. Finally, we explore how modulation of blood pressure and the noradrenergic nervous system may improve cognition in PD. © 2016 International Parkinson and Movement Disorder Society.

ID 163 – Prefrontal transcranial direct current stimulation in patients with disorders of consciousness – A case series study

Disorders of consciousness (DOC) as a result of global anoxic damage affect the level of awareness and expression of goal-directed behaviors. However, recent experience suggests that noninvasive brain stimulation, in some individuals can lead to improving the level of consciousness impairment. The aim of this prospective case series study was to analyze the clinical and electrophysiologic markers of outcome after treatment with transcranial direct current stimulation (tDCS). Two patients (19 and 20 yrs) with minimally conscious state (MCS), duration longer than 12 months, and one in subacute coma (76 yrs), were treated with pre-frontal tDCS for three weeks, and followed up for two months. The rate of functional recovery on the JFK Coma Recovery Scale Revised, was estimated as well as quantitative EEG parameters. In two MCS patients during the follow-up period sustainable tDCS-related gain of 4 and 3 points on JFK CRS-R, respectively were recorded. The older patient who was initially comatose (GCS = 3) after treatment showed marked improvement (GCS = 13, JFK CRS-R = 26). Adverse effects of procedure were not observed. Consistent improvement of various magnitudes, which was recorded in the patients and the absence of adverse effects encourage further application of the pre-frontal tDCS in patients with disorders of consciousness.

Lenticulostriate arterial distribution pathology may underlie pediatric anoxic brain injury in drowning.

Drowning is a leading cause of neurological morbidity and mortality in young children. Anoxic brain injury (ABI) can result from nonfatal drowning and typically entails substantial neurological impairment. The neuropathology of drowning-induced pediatric ABI is not well established. Specifically, quantitative characterization of the spatial extent and tissue distribution of anoxic damage in pediatric nonfatal drowning has not previously been reported but could clarify the underlying pathophysiological processes and inform clinical management. To this end, we used voxel-based morphometric (VBM) analyses to quantify the extent and spatial distribution of consistent, between-subject alterations in gray and white matter volume. Whole-brain, high-resolution T1-weighted MRI datasets were acquired in 11 children with chronic ABI and 11 age- and gender-matched neurotypical controls (4–12 years). Group-wise VBM analyses demonstrated predominantly central subcortical pathology in the ABI group in both gray matter (bilateral basal ganglia nuclei) and white matter (bilateral external and posterior internal capsules) (P < 0.001); minimal damage was found outside of these deep subcortical regions. These highly spatially convergent gray and white matter findings reflect the vascular distribution of perforating lenticulostriate arteries, an end-arterial watershed zone, and suggest that vascular distribution may be a more important determinant of tissue loss than oxygen metabolic rate in pediatric ABI. Further, these results inform future directions for diagnostic and therapeutic modalities.

Low risk of nursing home admission and anoxic brain damage in 30-day survivors of out-of-hospital cardiac arrest irrespective of age

Low risk of nursing home admission and anoxic brain damage in 30-day survivors of out-of-hospital cardiac arrest irrespective of age

Neuroprotective effects of hypothermia.

The neuroprotective effects of hypothermia have been shown in case reports and animal studies. Therapeutic hypothermia is used to provide neuroprotection during certain types of surgery and after serious events that pose a threat to the brain. The aim of this review is to describe the efficacy of such treatment in adults. All articles retrieved from five searches in PubMed were examined. Studies were included if they had a hypothermia protocol and a measurement of neuroprotection. The list of randomised studies was completed using studies identified from five international review articles. In all, 103 of 678 studies fulfilled the inclusion criteria, of which 48 were clinical trials. Ten of the clinical trials were randomised, using a normothermic control group. Several randomised clinical trials have suggested that avoidance of hyperthermia provides the same neuroprotection as therapeutic hypothermia after cardiac arrest and traumatic brain injury, but prognostic factors and inclusion criteria vary markedly between the patient populations, including time to target temperature. Two studies found that cognitive function after prolonged aortic surgery under deep hypothermia was equivalent to that after brief normothermic interventions. Animal studies show a neuroprotective effect of hypothermia, but this is dependent on the extent of anoxic damage as well as the rate of cooling. It remains uncertain how best to implement therapeutic hypothermia to achieve neuroprotection after acute events that pose a threat to the brain. Hypothermia during aortic surgery seems to provide adequate neuroprotection for prolonged interventions.