•We report two UK cases of cerebral venous sinus thrombosis and thrombocytopenia following first dose of the Vaxzevria vaccine (previously named COVID-19 Vaccine AstraZeneca).•The proposed ...pathophysiology is a vaccine-induced immune mechanism, supported by the detection of antibodies to platelet factor-4.•Neuroimaging revealed high clot burden with large amount of parenchymal and subarachnoid haemorrhage, leading to fatal outcomes.•Management of this condition differs from usual treatment of cerebral venous sinus thrombosis,in particular avoiding heparin and platelet transfusions.
Recent reports have highlighted rare, and sometimes fatal, cases of cerebral venous sinus thrombosis (CVST) and thrombocytopenia following the Vaxzevria vaccine. An underlying immunological mechanism similar to that of spontaneous heparin-induced thrombocytopenia (HIT) is suspected, with the identification of antibodies to platelet factor-4 (PF4), but without previous heparin exposure. This unusual mechanism has significant implications for the management approach used, which differs from usual treatment of CVST. We describe the cases of two young males, who developed severe thrombocytopenia and fatal CVST following the first dose of Vaxzevria. Both presented with a headache,with subsequent rapid neurological deterioration. One patient underwent PF4 antibody testing, which was positive. Arapid vaccinationprogramme is essential in helping to control the COVID-19 pandemic. Hence, it is vital that such COVID-19 vaccine-associated events, which at this stage appear to be very rare, are viewed through this lens.However, some cases have proved fatal. Itis critical that clinicians arealerted to the emergence of such eventstofacilitate appropriate management.Patients presenting with CVST features and thrombocytopenia post-vaccination should undergoPF4 antibody testing and be managed in a similar fashion to HIT,in particular avoiding heparin and platelet transfusions.
The development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive ...value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT).
We performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH.
We identified 187 patients with a median age of 74 years (interquartile range IQR 60-81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13-22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00-1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89.
NLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.
Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV).
To analyze clinical, imaging, and ...laboratory findings and outcomes of cerebrovascular manifestations of HSV infection.
Systematic literature review from January 2000 to July 2018.
We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations.
We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.
Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in ...which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication.
Amyloid-β-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy, characterized by amyloid-β deposition in the leptomeningeal and cortical vessels with associated ...angiodestructive granulomatous inflammation. The clinical presentation is variable, including subacute cognitive decline, behavioural changes, headaches, seizures and focal neurological deficits, which may mimic other conditions. Here, we present a case with fatal thrombolysis-related haemorrhage associated with ABRA in a middle-aged patient.
A 55-year-old man was admitted to hospital with sudden onset left-sided cheek, arm and hand sensory loss, blurred vision, and worsening headache, with a National Institutes of Health Stroke Scale (NIHSS) score of 3. An acute CT head scan showed no contraindications, and therefore the decision was made to give intravenous thrombolysis. Post-thrombolysis, he showed rapid deterioration with visual disturbances, headache and confusion, and a repeat CT head scan confirmed several areas of intracerebral haemorrhage. No benefit from surgical intervention was expected, and the patient died four days after the first presentation. Neuropathological examination found acute ischemic infarcts of three to five days duration in the basal ganglia, insular cortex and occipital lobe, correlating with the initial clinical symptoms. There were also extensive recent intracerebral haemorrhages most likely secondary to thrombolysis. Furthermore, the histological examination revealed severe cerebral amyloid angiopathy associated with granulomatous inflammatory reaction, consistent with ABRA.
Presentation of ABRA in a middle-aged patient highlighted the difficulties in recognition and management of this rare condition. There is emerging evidence that patients with CAA may have increased risk of fatal intracerebral haemorrhages following thrombolysis. This may be further increased by a coexisting CAA-related inflammatory vasculopathy which is potentially treatable with steroid therapy if early diagnosis is made.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose
Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral ...anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke.
Methods
We performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase.
Results
We identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70–84). The median National Institute of Health Stroke Scale score at baseline was 10 (
n
= 20, interquartile range 5–11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (
n
= 18, interquartile range 122–214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported.
Conclusion
Experience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.
The contribution of lipids, including low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and triglycerides (TG), to stroke outcomes is still debated. We sought to determine ...the impact of LDL-C concentrations on the outcome of patients with ischemic stroke in the anterior circulation who received treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of consecutive patients with acute ischemic stroke treated at a tertiary center between 2012 and 2016. Patients treated with EVT for large artery occlusion in the anterior circulation were selected. The primary endpoint was functional outcome at 3 months as measured with the modified Rankin Scale (mRS). Secondary outcome measures included hospital death and final infarct volume (FIV). Blood lipid levels were determined in a fasting state, 1 day after admission. We studied a total of 174 patients (44.8% men) with a median age of 74 years (interquartile range IQR 61–82) and median National Institutes of Health Stroke Scale at admission of 18 (14–22). Bridging therapy with intravenous tissue-plasminogen activator (t-PA) was administered in 122 (70.5%). The median LDL-C was 90 mg/dl (72–115). LDL-C demonstrated a U-type relationship with FIV (
p
= 0.036). Eighty-three (50.0%) patients had an mRS of 0–2 at 3 months. This favorable outcome was independently associated with younger age (OR 0.944, 95% CI 0.90–0.99,
p
= 0.012), thrombolysis in cerebral infarction 2b-3 reperfusion (OR 5.12, 95% CI 1.01–25.80,
p
= 0.015), smaller FIV (0.97 per cm
3
, 95% CI 0.97–0.99,
p
< 0.001), good leptomeningeal collaterals (OR 5.29, 95% CI 1.48–18.9,
p
= 0.011), and LDL-C more than 77 mg/dl (OR 0.179, 95% CI 0.04–0.74,
p
= 0.018). A higher LDL-C concentration early in the course of a stroke caused by large artery occlusion in the anterior circulation is independently associated with a favorable clinical outcome at 3 months. Further studies into the pathophysiological mechanisms underlying this observation are warranted.
Carotid stenosis and the cognitive function Sztriha, Laszlo K; Nemeth, Dezso; Sefcsik, Tamas ...
Journal of the neurological sciences,
08/2009, Letnik:
283, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Abstract While stroke is a known cause of a cognitive impairment, the relationship between a carotid artery stenosis and the cognitive function in individuals without a history of stroke is less ...clear. A number of risk factors for vascular disease are related to a cognitive impairment. Hypertension, diabetes mellitus, cigarette smoking, and dyslipidemia are also associated with an increased risk of carotid artery disease. Some studies have suggested that a stenosis of the internal carotid artery may be an independent risk factor for a cognitive impairment. A high-grade stenosis of the internal carotid artery may be associated with a cognitive impairment even without evidence of infarction on magnetic resonance imaging. On the other hand, it is fairly common that patients display a normal cognition despite severe carotid artery disease, highlighting the important role of an efficient collateral blood supply. The possible pathomechanisms of a cognitive impairment include silent embolization and hypoperfusion. Carotid endarterectomy or stenting may lead to a decline in the cognitive function in consequence of microembolic ischemia or intraprocedural hypoperfusion. Conversely, perfusion restoration could improve a cognitive dysfunction that might have occurred from a state of chronic hypoperfusion. It is unclear whether these complex interactions ultimately result in a net improvement or a deterioration of the cognitive function. The evidence available at present does not seem strong enough to include consideration of a loss of cognition as a factor in determining the balance of the risks and benefits of therapy for a carotid stenosis.
Highlights • Stroke survivors demonstrated sequence specific learning, irrespective of transcranial direct current stimulation (tDCS) condition. • Improvement in the Jebsen Taylor Test was seen after ...unilateral motor cortex tDCS but not after bihemispheric motor cortex tDCS. • Changes in performance with tDCS were independent of changes in transcallosal inhibition.
A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously ...identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes' availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.
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