Anticoagulation in Acute Neurological Disease.

To the Editor: Sir, the study by Canhao and colleagues made the important point that the most frequent cause of death in patients with cerebral venous thrombosis (CVT) is transtentorial herniation and that these patients may potentially have benefited from decompressive hemicraniectomy.1 We would like to corroborate this argument by providing evidence for a rise in intracranial pressure (ICP) preceding brain herniation and death in a patient with CVT. A 29-year-old pregnant woman who presented with confusion and vomiting was admitted to a district general hospital. A right-sided weakness developed within 2 days. A CT brain scan showed a left temporal hemorrhage without mass effect. Her Glasgow Coma Scale score dropped to 8/15; she was intubated and transferred to the neurocritical care …

SUPERIOR SAGITTAL SINUS THROMBOSIS PRESENTING AS DETERIORATING RESIDUAL WEAKNESS

Cerebral venous thrombosis is associated with intracranial hemorrhage. The occurrence of brain bleeding complicates management and is associated with worse outcomes. We aimed to identify clinical and imaging risk factors for intracerebral hemorrhage. We hypothesized that higher clot burden would be associated with a higher risk of intracerebral hemorrhage. Methods: We performed a retrospective analysis of an international, multicenter cohort of patients with cerebral venous thrombosis who underwent CT within 2 weeks of symptom onset and who had a subsequent confirmed diagnosis of CVT on MRV, CTV or DSA. Clinical and imaging features were compared between patients with and without intracranial hemorrhage. Clot burden was assessed by counting the number of thrombosed venous sinuses and veins on confirmatory imaging. Results: We recruited 260 patients with cerebral venous thrombosis from 10 institutions in Europe and Mexico. The mean age was 42 and 74% were female. Intracranial hemorrhage was found in 102 (39%). Intracerebral hemorrhage occurred in 64 (63%), small juxtacortical hemorrhage in 30 (29%), subarachnoid hemorrhage in 24 (24%) and subdural hemorrhage in 11 (11%). Combinations of these types of hemorrhage occurred in 23 (23%). Intraparenchymal hemorrhages in multiple locations occurred in 6 (6%). Older age, presence of hematological disease and superior sagittal thrombosis involvement were significantly associated with presence of hemorrhage. The number of thrombosed venous sinuses was not associated with intracerebral hemorrhage (average number of sinuses/veins involved with hemorrhage 2.1 versus 1.9 without hemorrhage, p=0.4). Conclusion: The high rate of intracranial hemorrhage in cerebral venous thrombosis is not explained by widespread involvement of the venous sinuses. Superior sagittal sinus involvement is associated with the presence of intracranial hemorrhage.

Subarachnoid and intra-cerebral hemorrhage in young adults: Rare and underdiagnosed

Background: Intracerebral hemorrhage (ICH) often carries cardiac implications, and serum troponin has been suggested as a predictive biomarker for patients with ICH and other stroke subtypes. We aimed to determine whether previously described associations between troponin and worse outcomes in ICH patients varied based on the presence of atrial fibrillation (AF). Methods: We performed a single-center cohort study using data from consecutive ICH patients admitted over 12 months. ICH characteristics and 3-month outcomes were prospectively collected, while admission troponin levels were retrospectively abstracted. We performed ordinal and binary logistic regression to determine associations between elevated troponins (>0.05 ng/mL) and 3-month outcomes (using the modified Rankin Scale [mRS]), with multivariable models adjusted for relevant demographics, ICH severity, and comorbidities including AF, anticoagulation use, coronary artery disease (CAD), and chronic kidney disease (CKD). An interaction variable combining elevated troponin and AF was also included in our models. Results: Of 261 ICH patients with troponin measured on admission, 17% (n=44) had elevated troponins. Patients with elevated troponins were not significantly older than patients with normal troponin levels (mean age 74.8±13.6 vs. 70.4±15.4, p=0.08), but were more likely to have AF (36% vs. 21%, p=0.03), CAD (32% vs. 15%, p=0.007), and CKD (16% vs. 5%, p=0.006); ICH size, location, and other predictors were not significantly different between groups. In adjusted models, neither elevated troponin nor AF were independently associated with worse outcomes. However, the interaction between the two was significant (p=0.003), and the presence of elevated admission troponin in the context of AF was significantly associated with worse outcomes (ordinal: common OR 9.8 [95% CI 2.0-47.8]; binary (mRS 4-6): OR 14.4 [95% CI 1.9-106.4]). Conclusions: Troponin may be a useful predictive biomarker in ICH patients with underlying AF, potentially signaling higher levels of cardiac and systemic stress in patients with lower cardiac reserve.

Objective To analyze the effectiveness and safety of mechanical thrombectomy in the treatment of cerebral venous sinus thrombosis (CVST). Methods A retrospective review of all CVST cases treated with mechanical thrombectomy between Oct 2007 and Oct 2017 were performed. Clinical and radiological features of the patients, the effectiveness of the surgery, and the relative factors were analyzed. Results A total of 20 patients were included in this study. Main clinical symptoms and signs included headache (20 cases), vomiting (8 cases), epilepsy (6 cases), conscious disturbance (15 cases), limb asthenia (20 cases), and neck rigidity (10 cases). Glasgow coma scale core was (12.8±2.2) points before the surgery. Intracerebral hemorrhage (9 cases), cerebral ischemia (8 cases), subarachnoid hemorrhage (6 cases), cerebral hernia signs (2 cases) were found by the radiological evaluation before the surgery. Preoperative venous examination: 17 patients completed MRV and DSA both, the range of venous sinus occlusion showed by MRV was more than that by DSA in 12 cases, the sigmoid sinus was not demonstrated by MRV in 9 cases, the straight sinus was not demonstrated in 6 cases, unilateral or bilateral transverse sinus was not demonstrated in 3 cases. The range of venous sinus occlusion showed by DSA was more than that by MRV in 6 cases, including 3 cases of transverse sinus occlusion, 1 case of sigmoid sinus occlusion, 1 case of deep venous occlusion, 1 case of cerebral venous occlusion. After mechanical thrombectomy, complete or partial revascularization demonstrated by MRV or DSA was achieved in 15 cases, accounting for 75%. There were no statistically significant differences in age of onset, disease duration, main clinical symptoms, medical history, and the distribution of occluded sinus between patients with poor outcome and patients with good outcome (P>0.05). After the surgery, the whole cerebral circulation time did not significantly change in patients with poor outcome, which was significantly longer than that in patients with good outcome (P<0.05). Conclusion MRV was less sensitive in detecting deep venous and sinus occlusion. Mechanical thrombectomy was very efficient in the treatment of CVST. The high reflowing rate and short cerebral circulation time after surgery were the main determinants of good outcome. Key words: Cerebral venous sinus thrombosis; Mechanical thrombectomy; Digital subtraction angiography

Cerebral Venous Sinus Thromboses in Patients with SARS-CoV-2 Infection: Three Cases and a Review of the Literature

Cerebral venous thrombosis (CVT) is a rare disease. It has numerous and complex etiologies. Inherited or acquired prothrombotic states play a key role in the development of this disease, such as factor V G1691A mutation (FV Leiden). A 15-year-old girl presented to the Department of Neurology with a complaint of severe headache with visual blurring. The diagnosis of CVT was not initially suspected because of the patient's condition on presentation. An MRI showed thrombosis in the superior sagittal sinus, confirming venous stroke. Anticardiolipin and antiphospholipid antibodies were assessed. In addition, inherited prothrombotic defects, such as protein C, protein S, and antithrombin deficiencies, and genetic mutations for FV Leiden, prothrombin gene G20210A (FII G20210A), and methyltetrahydrofolate reductase C677T (MTHFR C677T) were studied. All results were unremarkable except for the unique homozygous FV Leiden mutation, which likely contributed to this prothrombotic situation. This study highlights the fact that FV Leiden may play a significant role in the onset of CVT in young patients.

We aim to provide a pictorial representation of the broad spectrum of intracranial hemorrhages associated with cerebral venous thrombosis (CVT), emphasizing atypical locations and rare intracerebral hemorrhage (ICH) types. We also hypothesize the pathophysiology leading to atypical locations of the ICH in CVT and the outcomes with anticoagulation therapy. ICH complicates about 40% of cases with CVT and is known to cause various types of ICH, including subarachnoid hemorrhage (SAH) and subdural hemorrhage (SDH). A combination of hemorrhages is also reported. Patients with computed tomography and magnetic resonance imaging findings consistent with CVT examined between January 2011 and June 2014 were included in this retrospective review. Demographic and clinical data and imaging findings were reviewed with particular attention to the type and location of ICH and sinus involvement. Treatment details and 3-month outcomes, assessed using the modified Rankin Scale, were analyzed. Eleven patients (9 males), ranging in age from 22 years to 58 years, were included. The most common clinical presentations were headache (n = 8) and seizures (n = 7). Intraparenchymal hemorrhages were most common (n = 7), followed by SDH and SAH (n = 4), intraventricular hemorrhage (IVH; n = 3), and juxtacortical hemorrhage (n = 1). All patients who received anticoagulation therapy (n = 11) experienced complete resolution of their symptoms, and the median modified Rankin Scale was 0. The spectrum of intracranial hemorrhages seen in association with CVT is broad, encompassing atypical locations like basal ganglia, external capsule, and cerebellar hemispheres, and involves multiple intracranial compartments-IVH, SAH, and SDH. While SAH and SDH are seen with superior sagittal sinus thrombosis, ICH is common with lateral sinus thrombosis, and IVH with deep venous thrombosis.

Background/Aims: The factors related to cerebrovascular complications in cerebral venous sinus thrombosis (CVST) are controversial. We focused on venous stasis and investigated its relationship with cerebrovascular complications in CVST. Methods: CVST patients between June 2013 and October 2016 were enrolled. Relationships between cerebrovascular complications, defined as cerebral venous infarction, intracerebral hemorrhage, or subarachnoid hemorrhage, and cerebrum venous stasis and other clinical information were retrospectively analyzed. Venous stasis was evaluated by the prominence of the veins on susceptibility-weighted imaging (SWI). The cerebrum was divided into 10 regions according to the venous drainage territories, and venous stasis was quantified by adding one point for venous prominence on SWI for each region (CVST SWI score). Results: All 5 cases in the noncomplicated group had a CVST SWI score of 0. The 3 patients with CVST SWI scores higher than 0 had cerebrovascular complications. The CVST SWI scores were higher in the complicated group than in the noncomplicated group (3.0 vs. 0, p = 0.010). Seizures were seen in all patients with complications and in none of the patients without complications (3 vs. 0, p = 0.018). Conclusion: Venous stasis evaluated by SWI can help predict cerebrovascular complications in CVST. A seizure is an important initial symptom that suggests cerebrovascular complications in CVST.

Cerebral venous sinus thrombosis (CVST) combined with intracerebral hemorrhage(ICH) is a special subgroup, and whether intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) therapy should be carried out is controversial because of previous hemorrhage and possible delayed hemorrhage.The aim of this study was to analyze the safety and effectiveness of endovascular treatment of CVST with ICH and further discuss the treatment strategy. This is a retrospective study of 56 cases admitted from January 2010 to June 2019 diagnosed with CVST combined with ICH, and all were treated with endovascular treatment including IST with or without MT. We reviewed the clinical, radiological, and outcome data of all patients. The percentage of cases that showed complete and partial recanalization were 67.8% and 26.9% after endovascular treatment. ICH exacerbation occurred in 5 cases during thrombolysis. The percentage of cases with good outcome was 87.5% at discharge. 51 cases were followed up at sixth month. 49 cases had a mRS score of 0–2,and 2 cases had a mRS score of 3–4 at sixth month.Our data suggest that endovascular treatment may improve clinical and radiological outcome in most patients of CVST with ICH, but confirmation in prospective, controlled studies is warranted.

IntroductionHemorrhagic stroke and cerebral venous sinus thrombosis (CVST) are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. We aimed to investigate changes in the incidence of hemorrhagic stroke and CVST in South Korea before and during the coronavirus disease 2019 pandemic and the factors associated with these changes.Materials and methodsWe conducted a nationwide time-series study using population-based databases between 2007 and 2022. The real-world and forecasted incidences of acute non-traumatic subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and CVST during the pandemic period (2020–2022) were estimated and compared with the pre-pandemic period (2007–2019). The prevalence of conventional risk factors was measured using time-series data. Finally, a time-series correlation analysis was performed to examine the temporal association between conventional risk factors, SARS-CoV-2 infection, and SARS-CoV-2 vaccination.ResultsThe incidence of hemorrhagic stroke (SAH and ICH) was lower during the pandemic than during the pre-pandemic period. This observed decrease was associated with a reduction in the prevalence of conventional risk factors but not with SARS-CoV-2 infection or vaccination. The incidence of CVST was higher during the pandemic than during the pre-pandemic period, which may be temporally related to SARS-CoV-2 vaccination (Pearson correlation coefficient [r] = 0.349, P = 0.031).ConclusionWe report reassuring evidence of hemorrhagic stroke associated with SARS-CoV-2 infection and vaccination. However, awareness of CVST may be required for future vaccine rollouts and SARS-CoV-2 outbreaks.

Acute brain injuries, including ischemic and hemorrhagic stroke, as well as traumatic brain injury (TBI), are major worldwide health concerns with very limited options for effective diagnosis and treatment. Stroke and TBI pose an increased risk for the development of chronic neurodegenerative diseases, notably chronic traumatic encephalopathy, Alzheimer's disease, and Parkinson's disease. The existence of premorbid neurodegenerative diseases can exacerbate the severity and prognosis of acute brain injuries. Apoptosis involving caspase-3 is one of the most common mechanisms involved in the etiopathology of both acute and chronic neurological and neurodegenerative diseases, suggesting a relationship between these disorders. Over the past two decades, several clinical biomarkers of apoptosis have been identified in cerebrospinal fluid and peripheral blood following ischemic stroke, intracerebral and subarachnoid hemorrhage, and TBI. These biomarkers include selected caspases, notably caspase-3 and its specific cleavage products such as caspase-cleaved cytokeratin-18, caspase-cleaved tau, and a caspase-specific 120 kDa αII-spectrin breakdown product. The levels of these biomarkers might be a valuable tool for the identification of pathological pathways such as apoptosis and inflammation involved in injury progression, assessment of injury severity, and prediction of clinical outcomes. This review focuses on clinical studies involving biomarkers of caspase-3-mediated pathways, following stroke and TBI. The review further examines their prospective diagnostic utility, as well as clinical utility for improved personalized treatment of stroke and TBI patients and the development of prophylactic treatment chronic neurodegenerative disease.

Cerebral venous thrombosis (CVT), thrombosis of the dural sinus, cerebral veins, or both, is a rare cerebrovascular disease. Although mortality rates after CVT have declined over time, this condition can result in devastating neurologic outcomes. This article reviews the latest literature regarding CVT epidemiology, details new factors associated with the development of CVT, and describes advances in CVT treatment. It also contains a discussion of future directions in the field, including novel diagnostic imaging modalities, and potential strategies to reduce the risks associated with CVT. The incidence of CVT may be as high as 2 per 100,000 adults per year. It remains a difficult condition to diagnose given its variable clinical manifestations and the necessity of neuroimaging for confirmation. The COVID-19 pandemic has revealed a novel CVT trigger, vaccine-induced immune thrombotic thrombocytopenia (VITT), as well as an association between COVID-19 infection and CVT. Although VITT is a very rare event, timely diagnosis and treatment of CVT due to VITT likely improves patient outcomes. Direct oral anticoagulants are currently being used to treat CVT and emerging data suggest that these agents are as safe and effective as vitamin K antagonists. The role of endovascular therapy to treat CVT, despite a recent clinical trial, remains unproven. The incidence of CVT has increased, outcomes have improved, and the use of direct oral anticoagulants to treat CVT represents an important advance in the clinical care of these patients. Rates of CVT as a complication of COVID-19 vaccines using adenoviral vectors are very low (<5 per million vaccine doses administered), with the benefits of COVID-19 vaccination far outweighing the risks.

Posttraumatic craniocervical vascular injuries in pediatric traumatic brain injury (TBI) are rare, and children-specific, evidence-based standards on screening and therapy of posttraumatic carotid-cavernous fistula (CCF), craniocervical artery dissections (CCAD), traumatic aneurysms (TA), and posttraumatic sinus venous thrombosis (SVT) is lacking. The aim of this review is to summarize the data on epidemiology, clinical presentation, and treatment of these traumatic lesions in a systematic manner. We performed a systematic PubMed search for records of CCF, CCAD, TA, and SVT related to pediatric TBI published until June 2019. After screening 2439 records, 42 were included in the quantitative analysis. Incidences for CCAD in blunt TBI were 0.21% (range 0.02-6.82%). 11.7% (range 1.69-15.58%) of pediatric aneurysms were found to be traumatic of origin, whereas 38.2% (range 36.84-40%) of all pediatric SVT were due to blunt TBI. For all of the posttraumatic cerebrovascular pathologies, we found a clear male predominance with 68.75% in CCF, 63.4% in CCAD, 60% in TA, and 58.33% in SVT. Clinical presentation did not differ from the adult population with exception of young child. While there is only recommendation for the therapy of CCAD and SVT in the pediatric population, no such recommendation exists for the treatment of CCF's and TA's, and data from randomized controlled trials is lacking. While these results show that posttraumatic CCF, CCAD, TA, and SVT are rarely encountered in children, misdiagnosis may have potentially drastic consequences due to a longer lifetime burden in the pediatric population. Awareness, early recognition, and prompt initiation of the appropriate therapy are essential to avoid morbidity and mortality. Further studies should focus on the development of clinical and radiological screening criteria of posttraumatic vascular lesions in children.