Understanding brain dysfunction in sepsis Sonneville, Romain; Verdonk, Franck; Rauturier, Camille ...
Annals of intensive care,
05/2013, Volume:
3, Issue:
1
Journal Article
Peer reviewed
Open access
Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and ...noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors.
Risk factors for intracerebral hemorrhage (ICH) include hypertension and cerebral amyloid angiopathy (CAA). The objective of this study was to determine the autopsy prevalence of CAA and the ...potential overlap with other risk factors among patients who died from ICH and also the correlation of CAA with cerebral microbleeds.
We analyzed 81 consecutive autopsy brains from patients with ICH. Staining for CAA detection was performed. We used an age- and sex-matched control group of routine brain autopsies of nonneurological patients to determine the frequencies of CAA and hypertension. Postmortem 3D T2-weighted gradient-echo magnetic resonance imaging (MRI) with a 1.5-T magnet was performed in 11 brains with ICH (5 with CAA and 6 without) and histological correlation was performed when microbleeds were detected.
Hypertension and CAA were found in 69.1 and 24.7% of cases respectively. Among patients with CAA, 65.0% also had hypertension. The prevalence of CAA was similar among non-hypertensive cases and controls (33.3 and 23.1%; p = 0.54), whereas a significant difference was found between hypertensive cases vs. controls (28.9% vs. 0; p = 0.01). MRI documented 48 microbleeds and all 5 brains with CAA had ≥1 microbleed, compared to 3/6 brains without CAA. Among 48 microbleeds on MRI, 45 corresponded histologically to microbleeds surrounding microvessels (23 <200 µm in diameter, 19 between 200 µm and 2 mm, 3 were hemosiderin granules).
Both hypertension and CAA frequently coexist in patients with ICH. MRI-detected microbleeds, proven by histological analysis, were twice as common in patients with CAA as in those with hypertensive ICH.
Summary Background Diagnosis and treatment of cerebral and retinal transient ischaemic attacks (TIAs) are often delayed by the lack of immediate access to a dedicated TIA clinic. We evaluated the ...effects of rapid assessment of patients with TIA on clinical decision making, length of hospital stay, and subsequent stroke rates. Methods We set up SOS-TIA, a hospital clinic with 24-h access. Patients were admitted if they had sudden retinal or cerebral focal symptoms judged to relate to ischaemia and if they made a total recovery. Assessment, which included neurological, arterial, and cardiac imaging, was within 4 h of admission. A leaflet about TIA with a toll-free telephone number for SOS-TIA was sent to 15 000 family doctors, cardiologists, neurologists, and ophthalmologists in Paris and its administrative region. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death within 1 year. Findings Between January, 2003, and December, 2005, we admitted 1085 patients with suspected TIA; 574 (53%) were seen within 24 h of symptom onset. 701 (65%) patients had confirmed TIA or minor stroke, and 144 (13%) had possible TIA. 108 (17%) of the 643 patients with confirmed TIA had brain tissue damage. Median duration of symptoms was 15 min (IQR 5–75 min). Of the patients with confirmed or possible TIA, all started a stroke prevention programme, 43 (5%) had urgent carotid revascularisation, and 44 (5%) were treated for atrial fibrillation with anticoagulants. 808 (74%) of all patients seen were sent home on the same day. The 90-day stroke rate was 1·24% (95% CI 0·72–2·12), whereas the rate predicted from ABCD2 scores was 5·96%. Interpretation Use of TIA clinics with 24-h access and immediate initiation of preventive treatment might greatly reduce length of hospital stay and risk of stroke compared with expected risk.
Dans cet article je souhaiterai poser les bases d’une approche de l’antiféminisme qui puisse prendre en compte d’une part et utiliser d’autre part l’identité sexuelle de genre qui est la mienne : ...celle d’une femme. Cette approche s’oppose à l’idée que la production de connaissances est détachée clairement des affects et de tout intérêt personnel. J’appellerai cette approche « conception traditionnelle de la science ». Mais elle se détache également d’une approche militante développée dans les années 70 qui aurait pour but de mettre au jour son intérêt dans la production de savoir en tant que chercheur. Pour l’étude de l’antiféminisme, il s’agit de déconstruire la rhétorique de l’antiféminisme afin de donner des outils aux féministes pour se défendre contre des discours fallacieux.
Objective
Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. ...Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE.
Methods
The study was conducted in the framework of a single‐center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol‐, formalin‐, and methanol‐fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme‐linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi‐square or Fisher's exact tests.
Results
Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3‐ANCAs or MPO‐ANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3‐ANCAs or MPO‐ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti‐PR3/anti‐MPO–positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P = 0.022), more frequent occurrence of echocardiographic vegetations (P = 0.043), and above‐normal serum IgG levels (P = 0.017).
Conclusion
ANCAs, including PR3‐ and MPO‐ANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.
Summary Background The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a ...combined IV–endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion. Methods We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV–endovascular approach. Analysis was by intention to treat. Findings 46 (87%) of 53 patients treated with the IV–endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk RR 1·49, 95% CI 1·21–1·84; p=0·0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV–endovascular group and 42 (39%) patients in the IV group (adjusted RR 1·36, 0·97–1·91; p=0·07). Favourable outcome (mRS of 0–2 at 90 days) occurred in 30 (57%) patients in the IV–endovascular group and 47 (44%) patients in the IV group (adjusted RR 1·16, 0·85–1·58; p=0·35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV–endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV–endovascular group. Interpretation An IV–endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV–endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes. Funding SOS-ATTAQUE CEREBRALE.
Pontine infarction is most often related to basilar artery atherosclerosis when the lesion abuts on the basal surface (paramedian pontine infarction), whereas small medial pontine lesion is usually ...attributed to small vessel lipohyalinosis. A previous study has found that high-resolution MRI can detect basilar atherosclerotic plaques in up to 70% of patient with paramedian pontine infarction, even in patients with normal angiograms, but none has evaluated the presence of basilar artery plaque by high-resolution MRI in patients with small medial pontine lesion in the medial part of the pons.
Consecutive patients with pontine infarction underwent basilar angiography using time-of-flight and contrast-enhanced 3-dimensional MR angiography to assess the presence of basilar artery stenosis and high-resolution MRI to assess the presence of atherosclerotic plaque. Basilar artery angiogram was scored as "normal," "irregular," or "stenosed" >or=30%" and basilar artery by high-resolution MRI was scored as "normal" or "presence of plaque." Medial pontine infarcts were divided into paramedian pontine infarction and small medial pontine lesion groups.
Forty-one patients with pontine infarction were included, 26 with paramedian pontine infarction and 15 with small medial pontine lesion. High-resolution MRI detected basilar artery atherosclerosis in 42% of patients with a pontine infarction and normal basilar angiograms. Among patients with paramedian pontine infarction, 65% had normal basilar angiograms but 77% had basilar artery atherosclerosis detected on high-resolution MRI. Among patients with small medial pontine lesion, 46% had normal basilar angiograms but 73% had basilar artery plaques detected on by high-resolution MRI.
This study suggests that medial pontine lacunes may be due to a penetrating artery disease secondary to basilar artery atherosclerosis. High-resolution MRI could help precise stroke subtyping.
Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to ...assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization.
We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days.
A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005).
Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.
there is an overlap between stroke and coronary heart disease, but the exact prevalence of coronary artery disease in patients with nonfatal cerebral infarction is unclear, particularly when there is ...no known history of coronary heart disease.
we consecutively enrolled 405 patients presenting with acute cerebral infarction documented by neuroimaging who underwent carotid and femoral artery, thoracic, and abdominal aorta ultrasound examinations. Of the 342 patients with no known coronary heart disease, 315 underwent coronary angiography a median of 8 days (interquartile range, 6-11) after stroke onset.
coronary plaques on angiography, regardless of stenosis severity, were present in 61.9% of patients (95% confidence interval CI, 56.5-67.3) and coronary stenoses ≥ 50% were found in 25.7% (95% CI, 20.9-30.5). The overall prevalence of coronary plaque increased with the number of arterial territories (carotid or femoral arteries) involved, with an adjusted odds ratio of coronary artery disease of 1.25 (95% CI, 0.58-2.71) for presence of plaque in 1 territory, and 4.31 (95% CI, 1.92-9.68) for presence of plaque in both territories, compared with no plaque in either territory. The presence of plaque in both femoral and carotid arteries had an age- and sex-adjusted positive predictive value of 84% for presence of coronary plaque and a negative predictive value of 44%.
there is a high burden of silent coronary artery disease in patients with nonfatal cerebral infarction and no known coronary heart disease, even in the absence of systemic atherosclerosis. The prevalence is even higher in patients with evidence of carotid and/or femoral plaque.
Contrary to typical transient symptoms (TS), atypical TS, such as partial sensory deficit, dysarthria, vertigo/unsteadiness, unusual cortical visual deficit, and diplopia, are not usually classified ...as symptoms of transient ischemic attack when they occur in isolation, and their clinical relevance is frequently denied.
Consecutive patients with recent TS admitted in our transient ischemic attack clinic (2003-2008) had systematic brain, arterial, and cardiac investigations. We compared the prevalence of recent infarction on brain imaging, major investigational findings (symptomatic intracranial or extracranial atherosclerotic stenosis ≥50%, cervical arterial dissection, and major source of cardiac embolism), and 1-year risk of major vascular events in patients with isolated typical or atypical TS and nonisolated TS, after exclusion of the main differential diagnoses.
Among 1850 patients with possible or definite ischemic diagnoses, 798 (43.1%) had isolated TS: 621 (33.6%) typical and 177 (9.6%) atypical. Acute infarction on brain imaging was similar in patients with isolated atypical and typical TS but less frequent than in patients with nonisolated TS, observed in 10.0%, 11.5%, and 15.3%, respectively (
<0.0001). Major investigational findings were found in 18.1%, 26.4%, and 26.3%, respectively (
=0.06). One-year risk of a major vascular events was not significantly different in the 3 groups.
Transient ischemic attack diagnosis should be considered and investigated in patients with isolated atypical TS.
PDF
