COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.

OBJECTIVE: Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy. METHODS: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods. RESULTS: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11ß, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05). INTERPRETATION: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.

Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.

Viral cultures for assessing fomite transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: The role of fomites in the transmission of SARS-CoV-2 is unclear. AIM: To assess whether SARS-CoV-2 can be transmitted through fomites, using evidence from viral culture studies. METHODS: Searches were conducted in the World Health Organization COVID-19 Database, PubMed, LitCovid, medRxiv, and Google Scholar to December 31st, 2021. Studies that investigated fomite transmission and performed viral culture to assess the cytopathic effect (CPE) of positive fomite samples and confirmation of SARS-CoV-2 as the cause of the CPE were included. The risk of bias using a checklist modified from the modified Quality Assessment of Diagnostic Accuracy Studies - 2 (QUADAS-2) criteria was assessed. FINDINGS: Twenty-three studies were included. The overall risk of bias was moderate. Five studies demonstrated replication-competent virus from fomite cultures and three used genome sequencing to match fomite samples with human clinical specimens. The mean cycle threshold (CT) of samples with positive viral culture was significantly lower compared with cultured samples that returned negative results (standardized mean difference: -1.45; 95% confidence interval (CI): -2.00 to -0.90; I2 = 0%; P < 0.00001). The likelihood of isolating replication-competent virus was significantly greater when CT was <30 (relative risk: 3.10; 95% CI: 1.32 to 7.31; I2 = 71%; P = 0.01). Infectious specimens were mostly detected within seven days of symptom onset. One study showed possible transmission of SARS-CoV-2 from fomites to humans. CONCLUSION: The evidence from published studies suggests that replication-competent SARS-CoV-2 is present on fomites. Replication-competent SARS-CoV-2 is significantly more likely when the PCR CT for clinical specimens and fomite samples is <30. Further studies should investigate the duration of infectiousness of SARS-CoV-2 and the frequency of transmission from fomites.

Isotopic tracing of the impact of mobility on infectious disease: The origin of people with treponematosis buried in hull, England, in the late medieval period.

Treponematosis has been one of the most studied and debated infectious diseases in paleopathology, particularly from the standpoint of its origin, evolution, and transmission. This study links evidence for treponematosis in skeletons from the 14th-16th century AD cemetery of the Augustinian friary of Hull Magistrates Court, England, with data from stable isotope analysis to test the hypothesis that the people with treponemal disease buried at this site were not locally born and raised. The objective is to explore the potential of using stable isotope data to track the place of origin and extent of mobility of individuals with an infectious disease. Dental enamel samples of 12 skeletons were selected for strontium ((87) Sr/(86) Sr ratio) and oxygen (δ(18) O) stable isotope analysis based on the presence (six - diseased) or absence (six - controls) of bone changes associated with treponemal disease. The oxygen isotope ratios of all but three individuals (1047, 1121, 823) overlapped at two standard deviations with the inferred local precipitation range, and only one individual (1216) had a strontium isotope ratio outside the regional range. Two of the four had probable/possible treponemal bone changes. Those with treponemal bone changes were not demonstrably more likely to be migrants than those without such lesions. However, because of extensive documentary evidence for trade with the Baltic Sea area, and for merchants from towns such as Stralsund, Danzig and Elbing being in Hull, it is very plausible that the four migrants came from the Baltic area or even southern Sweden.

Guideline for Technical Quality Assurance (TQA) of ultrasound devices (B-Mode)--version 1.0 (July 2012): EFSUMB Technical Quality Assurance Group--US-TQA/B.

The Technical Quality Assurance group was initiated by the EFSUMB Board in 2007 and met firstly in 2008 to discuss and evaluate methods and procedures published for performing technical quality assurance for diagnostic ultrasound devices. It is the aim of this group of experts to advise the EFSUMB Board of effective and efficacious methods for routine use and to make recommendations regarding the technical aspects of EFSUMB by-law 9, parts 11.6. & 11.7. The group's work focused on new developments and related European projects to establish a common guideline. There is a great need of a well established protocol and dedicated processing software for the performance testing of medical ultrasound equipment. The measurements should be user independent as much as physically possible. Only if these goals are achieved in an international (firstly European) context, the optimal quality of ultrasound imaging can be offered and maintained to the medical community. This guideline aims to offer and summarize suitable procedures and evaluation processes to lend support for an optimal Technical Quality Assurance (TQA) scheme. The content of this guideline was presented to the EFSUMB Board of Directors (delegates) and approved by the EFSUMB Executive Board (ExB) at the regular meeting during EUROSON 2012 in Madrid April 2012.

Freshwater fish gill ion transport: August Krogh to morpholinos and microprobes.

August Krogh proposed that freshwater fishes (and other freshwater animals) maintain body NaCl homoeostasis by extracting these ions from the environment via separate Na(+) /NH(4)(+) and Cl(-) /HCO(3)(-) exchangers in the gill epithelium. Subsequent data from other laboratories suggested that Na(+) uptake was more probably coupled to H(+) secretion via a vesicular proton pump (V-ATPase) electrically coupled to a Na(+) channel. However, despite uncertainty about electrochemical gradients, evidence has accrued that epithelial Na(+) /H(+) exchange indeed may be an alternative pathway for Na(+) uptake. The specific pathways for Na(+) uptake may be species and environment specific. An apical Cl(-) /HCO(3)(-) exchanger is generally accepted for most species (some species do not extract Cl(-) from freshwater), but the relative roles of anion exchanger-like (SLC4A1) vs. pendrin-like (SLC26Z4) exchangers are unknown, and also may be species specific. Most recently, data have supported the presence of an apical Na(+) + Cl(-) cotransporter (NCC-type), despite thermodynamic uncertainty. Ammonia extrusion may be via NH(3) diffusing through the paracellular junctions or NH(4) (+) substitution on both basolateral and apical ionic exchangers (Na(+) + K(+) -ATPase; Na(+) + K(+) + Cl(-) - cotransporter; and Na(+) /H(+) exchanger), but recent evidence suggests that Rhesus-glycoproteins mediate both basolateral and apical movement of ammonia.

Colour flow and motion imaging.

Colour flow imaging (CFI) is an ultrasound imaging technique whereby colour-coded maps of tissue velocity are superimposed on grey-scale pulse-echo images of tissue anatomy. The most widespread use of the method is to image the movement of blood through arteries and veins, but it may also be used to image the motion of solid tissue. The production of velocity information is technically more demanding than the production of the anatomical information, partly because the target of interest is often blood, which backscatters significantly less power than solid tissues, and partly because several transmit-receive cycles are necessary for each velocity estimate. This review first describes the various components of basic CFI systems necessary to generate the velocity information and to combine it with anatomical information. It then describes a number of variations on the basic autocorrelation technique, including cross-correlation-based techniques, power Doppler, Doppler tissue imaging, and three-dimensional (3D) Doppler imaging. Finally, a number of limitations of current techniques and some potential solutions are reviewed.

Vaccinia virus particles mix inefficiently, and in a way that would restrict viral recombination, in coinfected cells.

It is well established that poxviruses are subjected to genetic recombination, but attempts to map vaccinia virus genes using classical genetic crosses were historically confounded by high levels of experimental noise and a poor correlation between physical and genetic map distances. These virus-by-virus crosses also never produced the 50% recombinant progeny that should be seen in experiments involving distant markers. Poxviruses replicate in membrane-wrapped cytoplasmic structures called virosomes (or factories) and we have developed a method for tracking the development of these structures using live cell imaging and cells expressing phage lambda Cro protein fused to enhanced green fluorescent protein (EGFP). The EGFP-cro protein binds nonspecifically to DNA and permits live cell imaging of developing vaccinia virus factories. Using this method, we see virosomes first appearing about 4 to 5 h postinfection. The early virosomes exhibit a compact appearance and then, after a period of exponential growth lasting several hours, blur and start to dissipate in a process presumably linked to viral packaging. During the growth period, the virosomes migrate toward the nuclear periphery while colliding and fusing at a rate dependent upon the numbers of infecting particles. However, even at high multiplicities of infection (10 PFU/cell), we estimate approximately 20% of the virosomes never fuse. We have also used fluorescence in situ hybridization (FISH) methods to study virosomes formed by the fusion of viruses carrying different gene markers. FISH showed that DNA mixes rather poorly within fused virosomes and the amount of mixing is inversely dependent on the time between virosome appearance and fusion. Our studies suggest that the intracellular movement and mixing of virosomes create constraints that reduce opportunities for forming recombinants and that these phenomena create outcomes reflected in classical poxvirus genetics.

Immunolocalization of Na+/K+-ATPase and Na+/K+/2Cl- cotransporter in the tubular epithelia of sea snake salt glands.

The sublingual salt gland is the primary site of salt excretion in sea snakes; however, little is known about the mechanisms mediating ion excretion. Na(+)/K(+)-ATPase (NKA) and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) are two proteins known to regulate membrane potential and drive salt secretion in most vertebrate secretory cells. We hypothesized that NKA and NKCC would localize to the basolateral membranes of the principal cells comprising the tubular epithelia of sea snake salt glands. Although there is evidence of NKA activity in salt glands from several species of sea snake, the localization of NKA and NKCC and other potential ion transporters remains unstudied. Using histology and immunohistochemistry, we localized NKA and NKCC in salt glands from three species of laticaudine sea snake: Laticauda semifasciata, L. laticaudata, and L. colubrina. Antibody specificity was confirmed using Western blots. The compound tubular glands of all three species were found to be composed of serous secretory epithelia, and NKA and NKCC were abundant in the basolateral membranes. These results are consistent with the morphology of secretory epithelia found in the rectal salt glands of marine elasmobranchs, the nasal glands of marine birds and the gills of teleost fishes, suggesting a similar function in regulating ion secretion.

Phototherapy promotes cell migration in the presence of hydroxyurea.

Phototherapy has been shown to cause an increase in cell proliferation and migration. This study focused on viability (trypan blue), proliferation [sodium 3'-(1-(phenylaminocarbonyl)-3,4-tetrazolium)-bis(4-methoxy-6-nitro)-benzene sulphonic acid hydrate (XTT) and adenosine triphosphate (ATP)] and migration of WS1 cells following irradiation in the presence of hydroxyurea (HU), which is an inhibitor of proliferation. Wounded cells were irradiated on days 1 and 4 with a fluence of 5 J/cm(2) with a helium-neon (He-Ne) laser at 632.8 nm. After a repair time of 24 h, cellular responses were assessed. Wounded irradiated cells without HU showed an increase in cell viability and proliferation, which was confirmed by complete wound closure by day 4. Although wounded irradiated cells treated with 5 mM HU showed incomplete wound closure, these cells showed increased migration compared with that of control cells. This study showed that laser irradiation using an He-Ne laser with a fluence of 5 J/cm(2) stimulates cell viability. The HU results confirmed that laser irradiation promotes cell migration and proliferation.

Identifying the high-risk patient with clinically relevant embolisation after carotid endarterectomy.

OBJECTIVES: Sustained embolisation after carotid endarterectomy (CEA) predicts an increased risk of stroke due to post-operative carotid thrombosis (POCT). Progression towards stroke can be prevented by transcranial Doppler (TCD) directed intravenous Dextran therapy. However, TCD monitoring is extremely labour intensive. The aim of this study was to see whether a small cohort of high-risk patients could be identified following a 30-min period of monitoring in the Recovery Area of the operating theatre so as to reduce the overall burden of monitoring for the majority of patients. METHODS: Retrospective audit of prospectively acquired data in 821 patients with an accessible temporal window who had undergone 3h of TCD monitoring after CEA. Patients with >25 emboli in any 10 min period or large emboli distorting the waveform received Dextran. RESULTS: Group 1: 694 patients (85%) with

The Leicester Cough Monitor: preliminary validation of an automated cough detection system in chronic cough.

Chronic cough is a common condition that presents to both primary and secondary care. Assessment and management are hampered by the absence of well-validated outcome measures. The present study comprises the validation of the Leicester Cough Monitor (LCM), an automated sound-based ambulatory cough monitor. Cough frequency was measured with the LCM and compared with coughs and other sounds counted manually over 2 h of a 6-h recording by two observers in nine patients with chronic cough in order to determine the sensitivity and specificity of the LCM. Automated cough frequency was also compared with manual counts from one observer in 15 patients with chronic cough and eight healthy subjects. All subjects underwent 6-h recordings. A subgroup consisting of six control and five patients with stable chronic cough underwent repeat automated measurements > or = 3 months apart. A further 50 patients with chronic cough underwent 24-h automated cough monitoring. The LCM had a sensitivity and specificity of 91 and 99%, respectively, for detecting cough and a false-positive rate of 2.5 events x h(-1). Mean+/-SEM automated cough counts x patient x h(-1) was 48+/-9 in patients with chronic cough and 2+/-1 in the control group (mean difference 46 counts x patient x h(-1); 95% confidence interval (CI) 20-71). The automated cough counts were repeatable (intra-subject SD 11.4 coughs x patient x h(-1); intra-class correlation coefficient 0.9). The cough frequency in patients undergoing 24-h automated monitoring was 19 coughs x patient x h(-1); daytime (08:00-22:00 h) cough frequency was significantly greater than overnight cough frequency (25 versus 10 coughs x patient x h(-1); mean difference 15 coughs x patient x h(-1), 95% CI 8-22). The Leicester Cough Monitor is a valid and reliable tool that can be used to assess 24-h cough frequency in patients with cough. It should be a useful tool to assess patients with cough in clinical trials and longitudinal studies.

Cerebral critical closing pressure estimation from Finapres and arterial blood pressure measurements in the aorta.

Estimates of cerebral critical closing pressure (CrCP) and resistance-area product (RAP) are often derived using noninvasive measurements of arterial blood pressure (ABP) in the finger, but the errors introduced by this approach, in relation to intra-vascular measurements of ABP, are not known. Continuous recordings of ABP (Finapres and solid-state catheter-tip transducer in the ascending aorta), cerebral blood flow velocity (CBFV, bilateral Doppler), ECG and transcutaneous CO(2) were performed following coronary catheterization. CrCP and RAP were calculated for each of 12,784 cardiac cycles from 27 subjects using the classical linear regression (LR) of the instantaneous CBFV-ABP relationship and also the first harmonic (H(1)) of the Fourier transform. There was a better agreement between LR and H(1) for the aortic measurements than for the Finapres (p < 0.000,01). For LR there were no significant differences for either CrCP or RAP due to the source of ABP measurement, but for H(1) the differences were highly significant (p < 0.000,03). The coherence functions between either CrCP or RAP values calculated with aortic pressure (input) or the Finapres (output) were significantly higher for H(1) than for LR for most harmonics below 0.2 Hz. When using the Finapres to estimate CrCP and RAP values, the LR method produces similar results to intra-arterial measurements of ABP for time-averaged values, but H(1) should be preferred in applications analysing beat-to-beat changes in these parameters.

Objective selection of signals for assessment of cerebral blood flow autoregulation in neonates.

A number of different system identification techniques have been proposed to assess dynamic cerebral autoregulation in critically ill patients. From these methods, the response to a standard stepwise change in blood pressure can be estimated. Responses lacking physiological consistency are a common occurrence and could be the consequence of particular system identification procedures or, alternatively, caused by measurements with a poor signal-to-noise ratio. A multi-observer approach was adopted in this paper to classify cerebral blood flow velocity (CBFV) step responses to spontaneous changes in arterial blood pressure in a group of 43 neonates with a mean gestational age of 33.7 weeks (range 24-42 weeks) and a mean birthweight of 1,980 g (range 570-3,910 g). Three experienced observers independently analysed the estimated step responses in 191 recordings each lasting 100 s; for an autoregressive (ARX) model, 124 (65%) of the step responses were accepted by at least two of the three observers. Two other system identification methods, transfer function analysis and the moving average Wiener-Laguerre model, gave 90 (45%) and 98 (51%) acceptable responses, respectively. Only 54 epochs (28%) were accepted with all three methods. With 88 (46%) responses rejected by at least two methods, it can be concluded that signal quality was the main reason for nonphysiological step responses. To avoid the need for subjective visual selection, an automatic procedure for classifying step responses was implemented leading to sensitivities and specificities in the range 85-90%, with respect to the agreement with subjective evaluations. Objective selection of CBFV step responses is thus feasible and could also be adapted for other physiological measurement techniques relying on system identification methods.

Real-time identification and archiving of micro-embolic Doppler signals using a knowledge-based DSP system.

Identification of micro-emboli in the cerebral circulation using transcranial Doppler ultrasound provides valuable clinical information, but, currently, embolic signal detection and analysis are significantly limited because they mainly rely on costly off-line analysis by human experts. In this study, a reliable, high-resolution, real-time automated system for the detection and archiving of embolic signals was designed and implemented using expert system theory and modern DSP technology. Preliminary tests were conducted to evaluate the functions and the performance of the system using data from ten carotid endarterectomy patients and two normal volunteers. Using the widely accepted 7 dB threshold for human reliability and a human expert, majority-decision gold standard, the real-time system reached sensitivity and specificity of 93.6% and 99.3%, respectively, which were close to the results obtained by three human experts under ideal laboratory conditions (90.1% and 99.8%, 98.4% and 99.9%, 98.9 and 99.9%). The new system has the potential to be used either as a bedside monitoring and signal acquisition device, or as a laboratory investigation tool.

Neural network modelling of dynamic cerebral autoregulation: assessment and comparison with established methods.

A time lagged recurrent neural network (TLRN) was implemented to model the dynamic relationship between arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) and its performance was compared to classical linear model such as transfer function analysis, Aaslid's dynamic autoregulation model, and the Wiener-Laguerre moving average filter. A simple linear regression was also tested as a naive estimator. In 16 normal subjects, CBFV was continuously recorded with Doppler ultrasound and ABP with the Finapres device during six repeated thigh cuff manoeuvres. Using mean beat-to-beat values of ABP as input and CBFV as output, the performance of each method was assessed by the model's predicted velocity correlation coefficient and normalized mean square error (MSE). Cross-validation was performed using three thigh cuff manoeuvres for the training data set and the other three for the validation set. The four methods studied performed significantly better than the zero-order naive estimator. The TLRN performed better than transfer function analysis, but was not significantly different from the time-domain techniques, despite showing the minimum predictive MSE. CBFV step responses could be extracted from the TLRN showing the presence of non-linear behaviour both in terms of amplitude and directionality.

Association between dynamic cerebral autoregulation and mortality in severe head injury.

The objective of the study was to test the hypothesis that dynamic cerebral pressure-autoregulation is associated with the outcome of patients with severe head injury and to derive optimal criteria for future studies on the predictive value of autoregulation indices. Repeated measurements were performed on 32 patients with severe head injury. Arterial blood pressure (ABP) was measured continuously with an intravascular catheter, intracranial pressure (ICP) was recorded with a subdural semiconductor transducer and cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery. Transfer function analysis was performed on mean beat-to-beat values, using ABP or CBFV as input variables and CBFV or ICP as the output variables. A dynamic index of autoregulation (ARI) ranging between 0 and 9 was extracted from the CBFV step response for a change in ABP. No significant differences between survivors and non-survivors were found due to mean values of ICP, ABP, CPP, CBFV, pCO2, GCS, age or heart rate. The transfer functions between ABP-ICP and CBFV-ICP did not show any significant differences either. The median [lower, upper quartiles] ARI was significantly lower for non-survivors compared with survivors [4.8 (0.0, 5.9) v. 6.9 (5.9, 7.4), p= 0.004]. The correlation between ARI and GOS was also significant (r=0.464, p=0.011). Cohen's coefficient was optimal for a threshold of ARI= 5.86 (kappa 0.51, p=0.0036), leading to a sensitivity for death of 75%, specificity=76.5%, odds ratio =9.75 and overall precision = 75.8%. The difference in ARI values between survivors and non-survivors persisted when results were adjusted for GCS (p = 0.028). A similar analysis for the Marshall CT scale did not reach significance (p = 0.072). A logistic regression analysis confirmed that apart from the ARI, no other variables had a significant contribution to predict outcome. In this group of patients, death following severe head injury could not be explained by traditional indices of risk, but was strongly correlated to indices of dynamic cerebral pressure-autoregulation extracted by means of transfer function analysis. Future studies using a prospective design are needed to validate the predictive value of the ARI index, as estimated by transfer function analysis, in relation to death and other unfavourable outcomes.

An automatic selections method for cerebral blood flow autoregulation signals from neonates

Interpretation and quantification of cerebral blood flow autoregulation can be carreid out from step responses to arterial blood pressure changes estimated with various identification methods. However estimates usually need to be visually inspected to rejected some that are not physiologically acceptable...

Cerebral autoregulation under moderate hypothermia in patients with acute stroke.

BACKGROUND AND PURPOSE: We undertook this study to examine the integrity of cerebral autoregulation in patients with acute ischemic stroke treated with moderate hypothermia (33 degrees C). METHODS: Fourteen patients, aged 58+/-11 years, with an acute anterior circulation infarction and National Institutes of Health Stroke Scale score >15 were evaluated. Patients received catecholamines (norepinephrine) via continuous intravenous infusion and were mechanically ventilated. Alpha-stat was used for pH maintenance. Arterial pressure (AP) and intracranial pressure (ICP) were invasively monitored. Flow velocity in the middle cerebral artery (MCA) supplying the unaffected hemisphere was continuously monitored. Instantaneous maximum flow velocity (V(max) MCA), ICP, and AP were simultaneously recorded in real time. Mean values of V(max) MCA (V(mean) MCA) and AP (MAP) were calculated over 1 minute. Static cerebral autoregulation (sCA) was calculated as sCA=(%DeltaCVR/%DeltaMAP)x100% (where %DeltaCVR is an estimate of percent change in cerebrovascular resistance). An sCA value of 0% indicates absent autoregulation, and a value of 100% indicates perfect autoregulation. Autoregulation is considered impaired when sCA values are <40%. MAP changes were produced by increasing the rate of the norepinephrine infusion. Six patients were examined under both normothermic and hypothermic conditions, while 8 were examined only under hypothermia. RESULTS: The induced MAP increase was 22+/-7 mm Hg (minimum 13, maximum 40 mm Hg). Mean sCA was 64+/-16% (minimum 40%, maximum 100%). No effect of moderate hypothermia on sCA or V(mean) MCA was evident in any of the 6 serially examined patients. Normocapnia was observed in all cases. CONCLUSIONS: sCA appears intact under moderate hypothermia with the use of alpha-stat for pH maintenance.