Stroke-induced immunodepression and dysphagia independently predict stroke-associated pneumonia - The PREDICT study.

Stroke-associated pneumonia is a frequent complication after stroke associated with poor outcome. Dysphagia is a known risk factor for stroke-associated pneumonia but accumulating evidence suggests that stroke induces an immunodepressive state increasing susceptibility for stroke-associated pneumonia. We aimed to confirm that stroke-induced immunodepression syndrome is associated with stroke-associated pneumonia independently from dysphagia by investigating the predictive properties of monocytic HLA-DR expression as a marker of immunodepression as well as biomarkers for inflammation (interleukin-6) and infection (lipopolysaccharide-binding protein). This was a prospective, multicenter study with 11 study sites in Germany and Spain, including 486 patients with acute ischemic stroke. Daily screening for stroke-associated pneumonia, dysphagia and biomarkers was performed. Frequency of stroke-associated pneumonia was 5.2%. Dysphagia and decreased monocytic HLA-DR were independent predictors for stroke-associated pneumonia in multivariable regression analysis. Proportion of pneumonia ranged between 0.9% in the higher monocytic HLA-DR quartile (≥21,876 mAb/cell) and 8.5% in the lower quartile (≤12,369 mAb/cell). In the presence of dysphagia, proportion of pneumonia increased to 5.9% and 18.8%, respectively. Patients without dysphagia and normal monocytic HLA-DR expression had no stroke-associated pneumonia risk. We demonstrate that dysphagia and stroke-induced immunodepression syndrome are independent risk factors for stroke-associated pneumonia. Screening for immunodepression and dysphagia might be useful for identifying patients at high risk for stroke-associated pneumonia.

Standardized prehospital treatment of stroke.

BACKGROUND: The lack of standardized pre-hospital treatment is a weak link in the care of acute stroke patients. METHODS: Selective review of the literature on acute stroke, with consideration of current guidelines in Germany and other countries (DGN, ESO, AHA/ASA). RESULTS: The mandatory, immediate transfer of acute stroke patients to a specialized stroke unit is supported by high-level evidence. Simple, sensitive screening tests for the diagnosis of stroke are available that can be performed in the field by trained non-physician emergency medical personnel. With regard to pre-hospital treatment, adequate scientific evidence supports cardiopulmonary stabilization, as well as oxygen supplementation if there are signs of hypoxemia. The patient's neurological findings, time of onset of symptoms, current medications, and past medical and surgical history must all be precisely and thoroughly documented. The receiving hospital must be informed of the patient's impending arrival as early as possible, particularly in cases where recanalizing procedures are still a therapeutic option. Treatment with aspirin or heparin must not be started in situ, i.e. without prior cerebral imaging. CONCLUSION: In the pre-hospital phase of stroke care delivery, the goal of a high capture rate can best be achieved through the use of appropriate diagnostic tests with maximal sensitivity. Patients with suspected acute stroke should be given the highest priority for transfer to a specialized stroke unit. Optimal pre-hospital care requires the smoothly functioning cooperation of all professionals involved, from the triaging and nursing personnel to the paramedics, dispatchers, emergency physicians in the field, and admitting physicians in the hospital.

Fiberoptic endoscopic Dysphagia severity scale predicts outcome after acute stroke.

BACKGROUND AND PURPOSE: Fiberoptic endoscopic evaluation of swallowing (FEES) is a suitable method for dysphagia assessment after acute stroke. Recently, we developed the fiberoptic endoscopic dysphagia severity scale (FEDSS) for acute stroke patients, grading dysphagia into 6 severity codes (1 to 6; 1 being best). The purpose of this study was to investigate the impact of the FEDSS as a predictor of outcomes at 3 months and intermediate complications during acute treatment. METHODS: A total of 153 consecutive first-ever acute stroke patients were enrolled. Dysphagia was classified according to the FEDSS, assessed within 24 h after admission. Intermediate outcomes were pneumonia and endotracheal intubation. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months. Multivariate regression analysis was used to identify whether the FEDSS was an independent predictor of outcome and intercurrent complications. Analyses were adjusted for sex, age and National Institutes of Health Stroke Scale (NIH-SS) on admission. RESULTS: The FEDSS was found to predict the mRS at 3 months as well as but independent from the NIH-SS. For each additional point on the FEDSS, the likelihood of dependency at 3 months (mRS > or = 3) raised by approximately 50%. Each increase of 1 point on the FEDSS conferred a more than 2-fold increased chance of developing pneumonia. The odds for the necessity of endotracheal intubation raised by a factor of nearly 2.5 with each additional point on the FEDSS. CONCLUSIONS: The FEDSS strongly and independently predicts outcome and intercurrent complications after acute stroke. Thus, a baseline FEES examination provides valuable prognostic information for the treatment of acute stroke patients.

High level of cerebral microembolization in patients supported with the DeBakey left ventricular assist device.

OBJECTIVE: Microembolic signals detected by transcranial Doppler ultrasonography have been demonstrated to be clinically relevant in patients supported with pulsatile left ventricular assist devices. We prospectively investigated the quantity of microembolic signals in patients supported with the continuous-flow DeBakey left ventricular assist device (MicroMed DeBakey VAD; MicroMed Technology, Inc, Houston, Tex) including the refined Carmeda BioActive Surface system (Carmeda AB, Stockholm, Sweden). METHODS: Twenty-three patients (20 male) aged 14 to 62 years supported with DeBakey left ventricular assist devices (n = 6 with Carmeda) were enrolled in this study. Microembolic signal monitorings were performed twice weekly by insonating the middle cerebral artery for 20 minutes without and 20 minutes with oronasal application of oxygen (6 L/min). Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: Despite a low incidence of thromboembolic complications (0.24 per 100 left ventricular assist device days), 20 patients (87%) showed circulating microemboli. Overall, microembolic signals were found in 175 of 499 transcranial Doppler ultrasonographic examinations (35.1%), with mean counts of 81.2 +/- 443 (range 0-5042 signals/h). Both microembolic signal prevalence (25% vs 34%, P = .01) and absolute signal counts (46.5 vs 104, P < .01) significantly declined with oxygen delivery. There was no significant correlation between the individual microembolic signal activity and the incidence of clinical thromboembolism or the intensity of antihemostatic treatment. Patients supported with the Carmeda device did not show reduced rates of clinical thromboembolization or cerebral microemboli. CONCLUSION: In patients with DeBakey left ventricular assist devices, a high load of clinically silent microemboli can be detected within the cerebral arteries despite a low incidence of embolic complications. It needs to be investigated whether such continuous, presumably gaseous microembolization causes cognitive or neuropsychologic deficits.

Capnography screening for sleep apnea in patients with acute stroke.

Sleep apnea syndrome (SAS) is a prominent clinical feature in acute stroke patients. Diagnosis is usually established by polysomnography or cardio-respiratory polygraphy (CRP). Both diagnostic procedures produce high costs, are dependent on the access to a specialized sleep laboratory, and are poorly tolerated by patients with acute stroke. In this study we therefore investigated whether capnography may work as a simple screening tool in this context. In addition to conventional CRP, 27 patients with acute stroke were studied with capnography provided by our standard monitoring system. The trend graphs of the end-tidal CO(2) values (EtCO(2)) were used to determine the capnography-based estimate of the apnea-hypopnea index (AHI(CO2)). Index events were scored when the EtCO(2) value dropped for > 50% of the previous baseline value. We found that the AHI(CO2) correlated significantly with the apnea-hypopnea index measured with conventional CRP (AHI(CRP)) (r = 0.94; p < 0.001). An AHI(CO2) > 5 turned out to be highly predictive of an AHI(CRP) > 10. According to our findings, routinely acquired capnography may provide a reliable estimate of the AHI(CRP). The equipment needed for this screening procedure is provided by the monitoring systems of most intensive care units and stroke units where stroke patients are regularly treated during the first days of their illness. Therefore, early diagnosis of SAS in these patients is made substantially easier.

Cerebral small vessel diseases: cerebral microangiopathies.

PURPOSE OF REVIEW: Small vessel diseases of the brain are still clinically underrecognized whereas their burden is increasing steeply. The most frequent is acquired degenerative small vessel disease. Many hereditary or idiopathic small vessel diseases have also been identified, of which cerebral autosomal-dominant arteriopathy with stroke and ischaemic leukoencephalopathy (CADASIL) is the most prominent. In this review, we will highlight current evidence on pathophysiology and genetics, new imaging tools, and treatment options. RECENT FINDINGS: Recent imaging studies have stressed the disruption of white matter connections in the pathogenesis of cognitive impairment in acquired small vessel disease. Clinical trials suggest a therapeutic benefit of acetylcholinesterase inhibitors. CADASIL is caused by mutations in the Notch3 gene. Current basic research has identified Notch genes to be important for endothelial and smooth muscle cells to form arteries and veins. Diagnosis can now be made reliably by magnetic resonance brain imaging, skin biopsy, or genetic testing. The so-called retinocerebral vasculopathies share the involvement of both retinal, cerebral and cochlear arterioles (e.g. Susac's syndrome). Cerebral amyloid angiopathy, occurring either sporadically or as a cause of various gene mutations, predisposes to lobar haemorrhages caused by rupture of affected small cortical vessels. Other rare cerebral microangiopathies, such as mitochondrial cytopathies, Fabry's disease and toxemic vasculopathy, offer established or new therapeutic options. SUMMARY: Cerebral small vessel diseases are highly variable in their aetiopathogenesis and clinical course. Current pathophysiological insights will help develop better treatment modalities; new imaging tools will provide surrogate markers for monitoring disease progression and treatment effects.

Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections.

Mild hyperhomocysteinemia is a probable risk factor for atherosclerotic diseases and stroke. Recently, associations of elevated plasma homocysteine concentrations in the acute phase and of MTHFR 677 TT genotype with spontaneous cervical artery dissections (sCAD) have been reported. The purpose of this study was to test this hypothesis in the currently largest sample of patients with sCAD, taking into account known factors influencing plasma homocysteine levels. Ninety-five patients with past sCAD were compared with 95 age- and sex-matched healthy individuals. Homocysteine, vitamin B6, B12, folate, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), cystathionine beta-synthase (CBS 844ins68bp) and methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1 G1958A) were assessed and any associations were analysed using multivariate statistics. The occurrence of sCAD was associated with elevated homocysteine levels with an odds ratio of 1.327 per 20 % percentile. Homocysteine levels were influenced by gender, smoking status, occurrence of hypertension, vitamin B12 and folate levels, and by the MTHFR TT genotype. MTHFR, CBS 844ins68bp, and MTHFD1 G1958A genotype were not independently associated with the occurrence of sCAD. These data suggest that elevated homocysteine is associated with the occurrence of sCAD. The MTHFR C677T polymorphism is associated with the homocysteine level.

Doppler microembolic load predicts risk of thromboembolic complications in Novacor patients.

OBJECTIVE: Left ventricular assist devices have become an established method to bridge patients with end-stage cardiac failure to heart transplantation. Besides infection and bleeding, thromboembolism represents one of the most serious complications. We evaluated the value of microembolic signals in predicting thromboembolic events for individual patients and distinctive left ventricular assist device periods. METHODS: Twenty patients (14 male) aged 23-57 years supported with the Novacor N100 left ventricular assist device were enrolled in this study. All patients were on effective anticoagulation, 12 patients additionally received antiplatelet therapy. Unilateral detection of microembolic signals was performed once weekly by insonation of the middle cerebral artery using transcranial Doppler sonography for 30 minutes duration. Evidence of clinically manifest thromboembolic events was based on regular questionnaires, clinical examinations, and results of diagnostic procedures. RESULTS: During a cumulative follow-up of 3876 left ventricular assist device days, 44 thromboembolic complications occurred (incidence, 1.1%) in 15 out of 20 patients. A total of 360 transcranial Doppler sonography monitorings (range, 5-34 per patient) were performed with an overall microembolic signals prevalence of 35.3% and a microembolic signal mean of 2.3 +/- 9.2 per examination. There was a highly significant correlation between the individual microembolic signal activity and the respective incidence of clinical thromboembolism (r = 0.61-0.9; P <.01). Patients with additional antiplatelet treatment had significantly less thromboembolic complications (0.7%) and lower microembolic signal prevalence (18.3%) than those without (2.8% and 65.4%, respectively). Individual patients and left ventricular assist device months with clinical thromboembolization could be identified using the microembolic signal activity with moderate positive (0.37-0.7) and high negative predictive values (0.82-1.0). CONCLUSIONS: The amount of microembolic signals, serially detected in patients with the Novacor left ventricular assist device, is significantly associated with their incidence of embolic complications. The high negative predictive value of microembolic signals enables to identify those patients and left ventricular assist device periods with particularly low risk of clinical thromboembolization.