Downstream microvascular thrombosis (DMT) is known to be a contributing factor to incomplete reperfusion in acute ischemic stroke. The aim of this study was to determine the timing of DMT with ...intravital imaging and to test the hypothesis that intravenous alteplase infusion could reduce DMT in a transient middle cerebral artery occlusion (MCAO) rat stroke model.
Rats were subjected to 60-minute transient MCAO. Alteplase (10 mg/kg) was administered 30 minutes after the beginning of MCAO. Real-time intravital fluorescence microscopy through a dura-sparing craniotomy was used to visualize circulating blood cells and fibrinogen. Cerebral microvessel patency was quantitatively evaluated by fluorescein isothiocyanate-dextran perfusion.
Immediately after MCAO, platelet and leukocyte accumulation were observed mostly in the venous compartment. Within 30 minutes after MCAO, microthrombi and parietal fibrin deposits were detected in postcapillary microvessels. Alteplase treatment significantly (P=0.006) reduced infarct volume and increased the percentage of perfused vessels during MCAO (P=0.02) compared with saline. Plasma levels of fibrinogen from alteplase-treated rats showed a rapid and profound hypofibrinogenemia. In vitro platelet aggregation demonstrated that alteplase reduced platelet aggregation (P=0.0001) and facilitated platelet disaggregation (P=0.001). These effects were reversible in the presence of exogenous fibrinogen.
Our data demonstrate that DMT is an early phenomenon initiated before recanalization. We further show that alteplase-dependent maintenance of downstream perfusion during MCAO improves acute ischemic stroke outcome through a fibrinogen-dependent platelet aggregation reduction. Our results indicate that early targeting of DMT represents a therapeutic strategy to improve the benefit of large artery recanalization in acute ischemic stroke.
To report the occurrence of non-ischemic cerebral enhancing (NICE) lesions following mechanical thrombectomy (MT) through the retrospective French nationwide registry of NICE lesions. All ...thrombectomy capable stroke centers (TSC) in France were invited to fill out a questionnaire disseminated through a trainee-led research network (JENI-RC:
Jeunes en Neuroradiologie Interventionnelle-Research Collaborative
). NICE lesions were defined according to previous literature as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema and vascular distribution in the territory of the MT with no other confounding disease. All 43 TSC French centers responded. Three patients were reported by 3 different centers over a total of 34,824 MT (2015–2020). Patient no. 1 developed symptomatic NICE lesions 8 weeks after MT with combination of aspiration and stentriever for a right middle cerebral artery occlusion. Patient no. 2 developed asymptomatic NICE lesions 5 weeks after MT with direct thromboaspiration for a right middle cerebral artery occlusion. Patient no. 3 developed symptomatic NICE lesions 6 weeks after MT with direct thromboaspiration, and combination of aspiration and stentriever for a basilar artery occlusion. This study provides evidence that NICE lesions following MT are a possible rare complication with a similar presentation as previously described following endovascular aneurysm treatment. Both radiologists and neurologists should be aware of this adverse event and make use of MRI contrast agents in case of unexplained symptoms/images during follow-up after MT.
Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in ...nonendemic areas are not known.
We conducted a retrospective multicenter cohort study (2004-2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3-6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling.
We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ≤ 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0-1.07), cerebrospinal fluid protein level ≥ 2 g/L (aOR 5.31, 95% CI 1.67-16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57-115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03-0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%-59%) was 0.23 (95% CI 0.11-0.44). Among survivors at 1 year, functional independence (mRS of 0-2) was observed in 27/37 (73%, 95% CI 59%-87%) cases.
A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors.
Convexity spontaneous subacute subdural hematoma (CSSSH) frequently relapse after one or more surgical drainages. This may be due to spontaneous intracranial hypotension (SIH), for which the gold ...standard treatment is the epidural blood patch. In this study, we report 4 cases of refractory CSSSH treated with rescue epidural saline patch, although history and imaging studies showed no evidence of SIH.
All 4 patients received a lumbar saline epidural rescue patch for consciousness impairment associated with refractory CSSSH, and one is particularly detailed. No patient had typical radiologic signs of SIH or, on the contrary, uncal herniation that could have indicated intracranial hypertension.
The Glasgow Coma Scale score improved significantly in the days after application of the epidural patch in 3 patients. All patients showed an improvement of the CT scan. Two patients underwent lumbar pressure measurement to confirm low values before the epidural injection, and for one, the intrathecal pressure profile during epidural patching is presented.
An epidural patch may be considered in managing CSSSH with no uncal herniation, even in the absence of signs of SIH on brain and spinal imaging. Whether it should be combined with surgical evacuation or used as first-line therapy remains to be determined.
To investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes ...(LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC).
We retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent brain angiography. The main outcome was 3-month functional independence (modified Rankin Scale score ≤2). Recanalization (revised Treatment in Cerebral Ischemia score 2b-3) was evaluated before (pre-MT) and after MT (final).
We included 588 patients (median age 75 years interquartile range (IQR) 61-84; 315 women 54%; median NIH Stroke Scale score 16 IQR 10-20), of whom 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95% confidence interval CI 43.0-51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95% CI 17.2-23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 20.6%; secondary transfer, n = 106/520 20.4%;
> 0.99) despite a shorter median IVT to puncture time in directly admitted patients (38 IQR 23-55 vs 86 IQR 70-110 minutes;
< 0.001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4-86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95% CI 1.4-4.1).
Tenecteplase before MT is safe, effective, and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy.
This study provides Class IV evidence that tenecteplase within 270 minutes of LVO-AIS increases the probability of functional independence.
Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including ...vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model.
Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls.
Research laboratory of a university hospital.
Male Wistar rats.
Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions.
In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02).
This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.
Purpose
Acute respiratory failure (ARF) is common and potentially fatal in patients with primary malignant brain tumors (PMBT). However, few data are available regarding its precipitating factors and ...prognosis. We sought to: (1) compare the causes of ARF and the outcome between patients with PMBT and patients with other peripheral solid tumors (PST), (2) identify the factors influencing ICU survival in PMBT patients.
Methods
Two-center retrospective case-control study from March 1996 to May 2014. Primary central nervous system lymphomas were also included.
Results
Eighty-four patients with PMBT and 133 patients with PST were included. Acute infectious pneumonia was more frequent in PMBT than PST patients (77 vs. 36%, p < 0.001). Pulmonary embolism was also more frequent in PMBT patients (13% vs. 5%, p = 0.042), while cardiogenic pulmonary edema and acute-on-chronic respiratory failure were more frequent in PST patients (37 vs. 10%, p < 0.001). Among acute infectious pneumonia,
Pneumocystis
pneumonia and aspiration pneumonia were more frequent in PMBT patients (19 vs. 2%, p < 0.001 and 19 vs. 8%, p < 0.001, respectively). ICU mortality was similar between PMBT and PST patients (24% vs. 24%, p = 0.966). In multivariate analysis, cancer progression (OR 7.25 95% CI 1.13–46.45, p = 0.034), need for intubation (OR 7.01 95% CI 1.29–38.54, p = 0.022), were independently associated with ICU mortality in PMBT patients.
Conclusions
The cause of ARF in patients with PMBT differs significantly than those with PST and up to 50% may have been prevented. Mortality did not differ between the two groups. These results suggest that PMBT alone is not a relevant criterion for ICU recusal.
Purpose of Review
The purpose of this paper is to provide recent insights in management of neurologic complications of left-sided infective endocarditis (IE).
Recent Findings
Cerebral lesions ...observed in IE patients are thought to involve synergistic pathophysiological mechanisms including thromboembolism, sepsis, meningitis, and small-vessel cerebral vasculitis. Brain MRI represents a major tool for the detection of asymptomatic events occurring in the majority of patients. The latter can impact therapeutic decisions and prognosis, especially when cardiac surgery is indicated. In patients presenting with neurologic complications, surgery could be safely performed earlier than previously thought.
Summary
Symptomatic cerebral ischemic or hemorrhagic events occur in 20–55% of IE patients, whereas asymptomatic events are detected in 60–80% of patients undergoing systematic brain MRI. Management of such patients requires an experienced multidisciplinary team. Recent studies suggest that early cardiac surgery, when indicated, can be performed safely in patients with cerebral ischemic events. Other important issues include the appropriate use of anti-infective and anti-thrombotic agents, and endovascular treatment for mycotic aneurysms. Altered mental status at IE onset, which is associated with brain injury, is a major determinant of short-term outcome.
Status epilepticus (SE) is a common complication of acute encephalitis, but its determinants and prognostic value in this setting are not known.Risk factors for early-onset SE (within 48 hours of ...intensive care unit ICU admission) in consecutive adult patients with all-cause encephalitis admitted to the medical ICU of a university hospital (1991-2013) were evaluated by multivariate logistic regression analysis. To examine the prognostic value of SE, patients were classified into 3 groups: no SE, nonrefractory SE (NRSE), and refractory SE (RSE). Poor neurologic outcome was defined by a modified Rankin score of 4 to 6.Among the 290 patients, 58 (20%, 95% CI: 15%-25%) developed early-onset SE, comprising 44 patients with NRSE and 14 patients with RSE. Coma (adjusted odds ratio OR: 3.1, 95% CI: 1.5-6.3), cortical lesions on neuroimaging (adjusted OR: 3.7, 95% CI: 1.8-7.8), and nonneurologic organ failure(s) (adjusted OR: 13.6, 95% CI: 4.9-37.7) were found to be independent risk factors for SE. By contrast, a bacterial etiology had a protective effect (adjusted OR: 0.3, 95% CI: 0.1-0.7). Age, body temperature, and blood sodium levels were not independently associated with SE. Poor neurologic outcomes were observed at day 90 in respectively 23% (95% CI: 17%-28%), 23% (95% CI: 10%-35%), and 71% (95% CI: 48%-95%) of no SE, NRSE, and RSE patients (P < 0.01). After adjusting for confounders, RSE, but not NRSE, remained independently associated with 90-day mortality (adjusted OR: 6.0, 95% CI: 1.5-23.3).Coma, cortical involvement on neuroimaging, and nonneurologic organ failure(s) are independent risk factors for SE in patients with acute encephalitis. Conversely, a bacterial etiology is associated with a lower risk of SE.These findings may help identify patients who may benefit from prophylactic antiepileptic drugs.
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