Peter Turcani

Impaired baroreflex sensitivity predicts outcome of acute intracerebral hemorrhage

Objective:Impaired blood pressure regulation in the acute phase of stroke has been associated with less favorable outcome. Mechanisms and effects of blood pressure dysregulation in stroke are not well understood; however, central autonomic impairment with sympathetic overactivity and baroreflex involvement are discussed. Baroreflex sensitivity (BRS) in spontaneous intracerebral hemorrhage has not been investigated. We sought to examine BRS in patients with intracerebral hemorrhage and evaluate the relationship between BRS and short-term outcome measures. Design:An open, prospective study. Setting:Neurocritical care unit and stroke unit in a university hospital. Patients and Measurements:We studied 45 patients with acute intracerebral hemorrhage within 72 hrs from onset of symptoms and 38 control subjects. BRS was measured noninvasively using a hemodynamic monitoring device. Beat-to-beat blood pressure variability was derived. The effects of the BRS, hemorrhage volume, intraventricular blood, and admission scores on outcome at 10 days were studied using a multivariate regression model. Main Results:Compared with the control group, patients with intracerebral hemorrhage had significantly decreased BRS (p = 0.002) and significantly increased systolic, diastolic, and mean beat-to-beat blood pressure variability (p < 0.0001, p = 0.007, p = 0.015). After adjusting for age, National Institute of Heath Stroke Scale at admission, volume of intracerebral hemorrhage and presence of intraventricular blood in a multivariate regression model, BRS gain was an independent predictor of outcome at 10 days. Conclusions:We found that BRS was decreased in patients with acute intracerebral hemorrhage and correlated with increased beat-to-beat blood pressure variability. BRS independently predicted outcome at 10 days. Modulation of baroreceptor reflex sensitivity may represent a new therapeutic target in acute stroke and warrants future studies.

Baroreflex: A New Therapeutic Target in Human Stroke?

Background and Purpose— Autonomic dysfunction, including increased sympathetic drive and blunted baroreflex, has repeatedly been observed in acute stroke. Of clinical importance is that the stroke-related autonomic imbalance seems to be linked to worse outcome after stroke. Here, we discuss the role of baroreflex impairment in acute stroke and its possible pathophysiological and therapeutic relevance. Summary of Review— Possible mechanisms linking baroreflex impairment with unfavorable outcome in stroke may include increased cardiovascular morbidity and mortality, promotion of secondary brain injury due to local inflammation, hyperglycemia, or altered cerebral perfusion. Conclusions— We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke.

Impaired Baroreceptor Reflex Sensitivity in Acute Stroke Is Associated With Insular Involvement, But Not With Carotid Atherosclerosis

Background and Purpose— Impaired baroreflex sensitivity (BRS) has been previously shown to be of prognostic value in patients with cardiovascular disease and stroke. Because baroreflex seems to be blunted by both carotid atherosclerosis and by lesions affecting central processing, controversy exists regarding the etiology of stroke-related baroreflex changes. The insula may play a central role in baroreflex modulation. The aim of the study was therefore to examine BRS in patients with acute stroke with regard to carotid atherosclerosis and insular involvement. Methods— We evaluated spontaneous BRS in 96 patients with acute stroke within 72 hours of ictus and 41 control subjects using a sequential crosscorrelation method. Results— Fifty-two patients with ischemic stroke and 44 patients with intracerebral hemorrhage, mean age 58.4 years, were included. With comparable carotid atherosclerosis profiles, patients with stroke had significantly lower BRS than control subjects (3.3 versus 5.3, P<0.001). Carotid atherosclerosis had no influence on variance of the BRS values in the acute stroke group. Patients with insular involvement had significantly lower BRS than patients with no insular involvement (2.55 versus 4.35, P=0.001) or control subjects (2.55 versus 5.3, P<0.001). Furthermore, patients with left insular involvement had significantly lower BRS than patients with right insular involvement (2.3 versus 3.5, P=0.049). There was no significant difference between patients with no insular lesions and control subjects (P=0.263). Conclusions— We demonstrated that baroreflex impairment in acute stroke is not associated with carotid atherosclerosis but with insular involvement. Both insulae seem to participate in processing the baroreceptor information with the left insula being more dominant.

Autonomic Shift and Increased Susceptibility to Infections After Acute Intracerebral Hemorrhage

Background and Purpose— High infection rate after severe stroke may partly relate to brain-induced immunodepression syndrome. However, the underlying pathophysiology remains unclear. The aim of the current study was to investigate the role of autonomic shift in increased susceptibility to infection after acute intracerebral hemorrhage (ICH). Methods— We retrospectively analyzed 62 selected patients with acute ICH from our prospective database. Autonomic shift was assessed using the cross-correlational baroreflex sensitivity (BRS). The occurrence and cause of in-hospital infections were assessed based on the clinical and laboratory courses. Demographic and clinical data including initial stroke severity, hemorrhage volume, intraventricular blood extension, history of aspiration, and invasive procedures such as mechanical ventilation, surgical hematoma evacuation, external ventricular drainage, central venous and urinary catheters, and nasogastric feeding were recorded and included in the analysis. Results— We identified 36 (58%) patients with infection during the first 5 days of hospital stay. Patients with infections had significantly lower BRS, higher initial NIHSS scores, larger hemorrhages, and more frequently had intraventricular blood extension and underwent invasive procedures. In the multivariate regression model, decreased BRS (OR, 0.54; 95% CI, 0.32–0.91; P=0.02) and invasive procedures (OR, 2.32; 95% CI, 1.5–3.6; P<0.001) remained independent predictors for an infection after ICH. Conclusions— Decreased BRS was independently associated with infections after ICH. Autonomic shift may play an important role in increased susceptibility to infections after acute brain injury including ICH. The possible therapeutic relevance of autonomic modulation warrants further studies.

Subacute perihematomal edema in intracerebral hemorrhage is associated with impaired blood pressure regulation.

BACKGROUND Perihematomal edema and secondary brain injury may influence the clinical course after intracerebral hemorrhage (ICH). The role of blood pressure (BP) in edema formation in ICH has not been studied sufficiently. We hypothesize that impaired blood pressure regulation (as measured by baroreflex sensitivity) leading to excessive BP fluctuations may enhance perilesional edema. The aims of our study were therefore to explore the effects of impaired baroreflex on edema in acute ICH and to evaluate the effects of perihematomal edema on early neurologic deterioration. METHODS In 38 patients with acute intracerebral hemorrhage we assessed baroreflex sensitivity (BRS) within the first 72 h using a time-domain cross-correlation method. Blood pressure was continuously monitored for 72 h after admission. Relative perihematomal edema was calculated from the follow-up scans at 48-72 h from ictus. Possible confounders such as body temperature, inflammation parameters, or glycemia were recorded. Early neurologic deterioration was defined as increase of 4 points at NIHSS within the first 72 h. RESULTS Decreased BRS correlated significantly with increased 72-hour MAP variability (r=-0.46, p=0.004). In a stepwise multivariate linear regression model, decreased BRS was an independent predictor for relative edema (p=0.005). Relative edema (p=0.009, OR 22.6, CI 2.2-232.5) and body temperature at admission (p=0.031, OR 0.17, CI 0.04-0.85) independently predicted early neurologic deterioration. CONCLUSIONS We found an independent association between decreased baroreflex sensitivity with increased blood pressure fluctuations and relative perihematomal edema in ICH. Moreover, independent effects of relative edema on early neurologic deterioration have been observed.

Baroreflex Sensitivity to Predict Malignant Middle Cerebral Artery Infarction

Background and Purpose— Hemicraniectomy has been shown to be an effective treatment of life-threatening edema (LTE) in malignant middle cerebral artery infarction when performed early. Identifying patients who will develop LTE is therefore imperative. We hypothesize that autonomic shift toward sympathetic dominance may relate to LTE formation. We aimed to investigate the predictive potential of baroreflex sensitivity (BRS) as a marker of autonomic balance for calculating the course of large middle cerebral artery infarction. Methods— Patients with middle cerebral artery infarction >2/3 of the territory and BRS measurement at admission were analyzed. BRS was estimated using the cross-correlational method. Demographic, clinical, and radiological data including stroke severity, infarct size, and basal ganglia involvement were recorded. Malignant course with LTE was defined as clinical deterioration and midline shift ≥5 mm in the first 48 hours. Results— Eighteen (62.8%) patients developed LTE. Patients with LTE had lower BRS (2.3 versus 4.4 mm Hg/ms, P=0.007), larger infarcts (214 versus 144 mL, P=0.03), more frequent involvement of the basal ganglia (14 versus 4, P=0.03), and more often underwent thrombolysis combined with endovascular intervention (6 versus 0, P=0.04). In a multivariate model, BRS (OR, 0.36; CI, 0.14–0.93; P=0.03) and basal ganglia involvement (OR, 11.53; CI, 1.15–115.9; P=0.04) were independent predictors for LTE. This model correctly classified 86.2% of the malignant cases. Conclusions— Decreased BRS, mirroring sympathetic activation, and basal ganglia involvement were associated with development of malignant course with LTE in large middle cerebral artery infarction. The predictive relevance of our findings needs to be confirmed in further studies.

Blood Pressure Course in Acute Stroke Relates to Baroreflex Dysfunction

Background: Acute hypertension frequently occurs in acute stroke and is associated with unfavorable outcome. However, despite the high prevalence, the pathophysiology remains unclear. Baroreflex dysfunction has repeatedly been reported in stroke patients. We hypothesize that blood pressure (BP) derangements in the acute phase relate to the impairment of baroreflex. Methods: We assessed baroreflex sensitivity (BRS) in 109 acute stroke patients with both ischemic and hemorrhagic stroke using the sequential cross-correlation method. Admission BP and BP values derived from continuous 72-hour monitoring were recorded. Demographic and clinical data including stroke volumes and admission NIHSS scores were included into the analysis. Results: The BRS significantly correlated with admission BP (r = –0.24, p = 0.01), with the occurrence of acute hypertension (≧220mm Hg/≧ 110 mm Hg) on admission (r = –0.37, p < 0.001) and with the number of episodes with ≧220 mm Hg/≧110 mm Hg in the first 72 h after admission (r = –0.44, p < 0.001). Admission NIHSS or lesion volume did not correlate with acute hypertension on admission or hypertensive episodes within the first 72 h. In a multivariable model, BRS remained a significant, independent predictor for both the occurrence of acute hypertension on admission and hypertensive episodes within the first 72 h. Conclusions: In acute stroke, decreased BRS was independently associated with the occurrence of acute hypertension on admission. In addition, BRS seemed to be a valid predictor of the BP course in the first 72 h. As some antihypertensives may ameliorate BRS, therapeutic relevance of this finding warrants further attention.

Are blood platelets involved in the pathogenesis of ischemic brain edema in gerbils

Edema formation following severe permanent or temporary cerebral ischemia in gerbils with an artificially reduced platelet count was investigated. Acute focal cerebral ischemia was produced by extracranial carotid ligation, and the local cerebral blood flow was estimated using the hydrogen clearance method. Brain tissue water and sodium and potassium contents were taken as indexes of brain edema. The platelet count was reduced in some gerbils by intravenous injection of neuraminidase. After 60 minutes of ischemia, a marked increase in tissue water and sodium contents accompanied by a decrease in potassium content was observed in untreated gerbils. However, gerbils with a reduced platelet count revealed similar but significantly smaller changes in all the measured parameters. Restoration of blood flow after 60 minutes of ischemia resulted in further accumulation of water and sodium and in depletion of potassium in both groups. These changes were significantly smaller in the gerbils with a reduced platelet count. It is concluded that platelets, activated by cerebral ischemia, may be involved in the development of ischemic brain edema in gerbils.

How Does Fingolimod (Gilenya®) Fit in the Treatment Algorithm for Highly Active Relapsing-Remitting Multiple Sclerosis?

Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, disease-modifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.

Sleep disorders in patients with multiple sclerosis.

OBJECTIVE Poor sleep is a frequent symptom in patients with multiple sclerosis (MS). The objective of the study was to assess the relationship between nocturnal polysomnographic (PSG) findings and quality of sleep, fatigue, and increased daytime sleepiness among patients with MS. METHODS Clinical characteristics were collected. Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and International Restless Legs Syndrome Rating Scale were used to assess quality of sleep, fatigue, excessive daytime sleepiness, and the presence of restless legs syndrome (RLS). All patients underwent nocturnal diagnostic PSG examination. RESULTS Fifty patients with MS were enrolled into the study. Age was the only independent variable significantly determining apnea-hypopnea index and desaturation index (DI) (beta = 0.369, p = 0.010, beta 0.301, p = 0.040). PSQI and ESS score were significantly higher in a population with RLS (p = 0.004, p = 0.011). FSS significantly correlated with DI (r = 0.400, p = 0.048). Presence of RLS was the only independent variable significantly determining PSQI and ESS (p = 0.005, p = 0.025). DI and presence of RLS were independent variables determining FSS (p = 0.015, p = 0.024). CONCLUSION Presence of RLS seems to be the main factor determining poor sleep, fatigue, and daytime somnolence. Sleep disordered breathing and its severity influences only fatigue in patients with MS.