Stroke without Cerebral Vasculopathy in Sickle Cell Disease Children: Which Causes? Which Treatment?

Sickle cell disease (SCD) is a severe hemoglobinopathy due to abnormal hemoglobin S (HbS). One of the most serious complications of SCD is cerebral vasculopathy (CV) leading to ischemic stroke in 8% of homozygous SS children without prevention strategy. Typical CV in SCD is a stenosis of one or more intracranial or cervical arteries, including internal carotid arteries, anterior cerebral arteries and middle cerebral arteries. However, several studies have reported the occurrence of stroke in SCD children in the absence of typical cerebral vasculopathy. The aim of the study is to investigate the prevalence of stroke without CV in SCD children, and to compare them to "classical" stroke (i.e in a context of typical CV) in terms of suspected etiologies, triggering events, treatment and risk of recurrence. In a large cohort of about 1500 SCD children living in Paris area, France, we recorded all the strokes occurring between 2007 and 2020, excluding venous thrombosis and PRESS Syndrome. These children were followed in a university hospital, and all benefited from early screening for cerebral vasculopathy and an adapted stroke prevention program. We considered as a "typical" stroke any new ischemic lesion of the cerebral parenchyma associated with an acute neurological syndrome occurring in the territory of a pre-existing and/or non-regressive stenosis. 25 strokes occurred during the study period. 12 of them (48%) did not met the definition of a "typical" stroke related to sickle cell CV. The children with "atypical" stroke were older (9 years old +/- 4.6, vs 6.5 years old +/- 4.3 in the typical group, p = 0.0086) and less frequently of SS genotype (33% non-SS vs 8% non-SS in the typical group). They had lower leukocyte count (11.3 G/L +/- 4.6, vs 15.7 G/L +/- 2.3 in the typical group, p=0. 04) and higher hemoglobin level at the time of the stroke (11 g/dl +/- 3 vs 7.4 g/dl +/- 1.3 in the typical group, p= 0.027). 17% of atypical strokes had posterior ischemic lesions, 33% had anterior lesions and 17% had multiple systematized lesions, in counting junctional lesions. We also found 33% of ischemic lesions of the cerebellum. Considering a potential trigger of the stroke, 58% of atypical events were hospitalized in an anesthesia or intensive care unit at the time of the stroke or less than 7 days before, compared to 8% of children with a "classic" stroke (p= 0.011). The etiologies adopted by clinicians and radiologists for the atypical stroke were reversible cerebral vasoconstriction syndrome (RCVS) (Figure 1), cerebral fat embolism, hyperviscosity and vasculitis in systemic inflammatory context. The evolution in the atypical group was more favorable in terms of recurrence (0% within 2 years vs 42 % in the typical group, p= 0.045), although only 33% (3 children) of atypical strokes were still under exchange transfusion program 24 months after the stroke vs 92% in the group of typical stroke. Overall, in a cohort of SCD children with efficient stroke prevention program, atypical strokes account for nearly half of all acute ischemic neurological events, related to hyperviscosity, RVCS or inflammatory vasculitis. Physicians must be aware of the potential triggers and of the context in which such events occur. Nevertheless, stroke without CV may not require long-term transfusion program contrary to stroke with CV, given the very low risk of recurrence we highlighted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Vertebral artery dissection in term pregnancy after cervical spine manipulation: a case report and review the literature

Background Vertebral artery dissection is an uncommon, but potentially fatal, vascular event. This case aimed to describe the pathogenesis and clinical presentation of vertebral artery dissection in a term pregnant patient. Moreover, we focused on the differential diagnosis, reviewing the available evidence. Case presentation A 39-year-old Caucasian woman presented at 38 + 4 weeks of gestation with a short-term history of vertigo, nausea, and vomiting. Symptoms appeared a few days after cervical spine manipulation by an osteopathic specialist. Urgent magnetic resonance imaging of the head was obtained and revealed an ischemic lesion of the right posterolateral portion of the brain bulb. A subsequent computed tomography angiographic scan of the head and neck showed a right vertebral artery dissection. Based on the correlation of the neurological manifestations and imaging findings, a diagnosis of vertebral artery dissection was established. The patient started low-dose acetylsalicylic acid and prophylactic enoxaparin following an urgent cesarean section. Conclusion Vertebral artery dissection is a rare but potential cause of neurologic impairments in pregnancy and during the postpartum period. It should be considered in the differential diagnosis for women who present with headache and/or vertigo. Women with a history of migraines, hypertension, or autoimmune disorders in pregnancy are at higher risk, as well as following cervical spine manipulations. Prompt diagnosis and management of vertebral artery dissection are essential to ensure favorable outcomes.

Diffuse prothrombotic syndrome after ChAdOx1 nCoV-19 vaccine administration: a case report

Background Vaccine-induced immune thrombotic thrombocytopenia is emerging as one of the most relevant side effects of adenoviral-based vaccines against coronavirus disease 2019. Given the novelty of this disease, the medical community is seeking new evidence and clinical experiences on the management of these patients. Case presentation In this article, we describe the case of a 73-year-old Caucasian woman who presented with diffuse prothrombotic syndrome, both in the arterial and venous districts, following the first dose administration of ChAdOx1 CoV-19 vaccine. The main thrombotic sites included the brain, with both a cortical ischemic lesion and thromboses of the left transverse and sigmoid sinuses and the lower limbs, with deep venous thrombosis accompanied by subsegmental pulmonary thromboembolism. The deep venous thrombosis progressively evolved into acute limb ischemia, requiring surgical intervention with thromboendoarterectomy. Anticoagulation was maintained throughout the whole hospitalization period and continued in the outpatient setting using vitamin K antagonists for a recommended period of 6 months. Conclusions This case describes the management of vaccine-induced immune thrombotic thrombocytopenia in a complicated clinical scenario, including multisite arterial and venous thromboses. Given the complexity of the patient presentation, this case may implement the comprehension of the mechanisms and clinical features of this disease; it also provides a picture of the challenges related to the management, often requiring a multidisciplinary approach.

Reclassifications of ischemic stroke patterns due to variants of the Circle of Willis

Background Variants of the Circle of Willis (vCoW) may impede correct identification of ischemic lesion patterns and stroke etiology. We assessed reclassifications of ischemic lesion patterns due to vCoW. Methods We analyzed vCoW in patients with acute ischemic stroke from the 1000+ study using time-of-flight magnetic resonance angiography (TOF MRA) of intracranial arteries. We assessed A1 segment agenesis or hypoplasia in the anterior circulation and fetal posterior cerebral artery in the posterior circulation. Stroke patterns were classified as one or more-than-one territory stroke pattern. We examined associations between vCoW and stroke patterns and the frequency of reclassifications of stroke patterns due to vCoW. Results Of 1000 patients, 991 had evaluable magnetic resonance angiography. At least one vCoW was present in 37.1%. VCoW were more common in the posterior than in the anterior circulation (33.3% vs. 6.7%). Of 238 patients initially thought to have a more-than-one territory stroke pattern, 20 (8.4%) had to be reclassified to a one territory stroke pattern after considering vCoW. All these patients had fetal posterior cerebral artery and six (30%) additionally had carotid artery disease. Of 753 patients initially presumed to have a one-territory stroke pattern, four (0.5%) were reclassified as having more-than-one territory pattern. Conclusions VCoW are present in about one in three stroke patients and more common in the posterior circulation. Reclassifications of stroke lesion patterns due to vCoW occurred predominantly in the posterior circulation with fetal posterior cerebral artery mimicking multiple territory stroke pattern. Considering vCoW in these cases may uncover symptomatic carotid disease.

Quantitative Lesion Water Uptake as Stroke Imaging Biomarker: A Tool for Treatment Selection in the Extended Time Window?

Background and Purpose: Patients presenting in the extended time window may benefit from mechanical thrombectomy. However, selection for mechanical thrombectomy in this patient group has only been performed using specialized image processing platforms, which are not widely available. We hypothesized that quantitative lesion water uptake calculated in acute stroke computed tomography (CT) may serve as imaging biomarker to estimate ischemic lesion progression and predict clinical outcome in patients undergoing mechanical thrombectomy in the extended time window. Methods: All patients with ischemic anterior circulation stroke presenting within 4.5 to 24 hours after symptom onset who received initial multimodal CT between August 2014 and March 2020 and underwent mechanical thrombectomy were analyzed. Quantitative lesion net water uptake was calculated from the admission CT. Prediction of clinical outcome was assessed using univariable receiver operating characteristic curve analysis and logistic regression analyses. Results: One hundred two patients met the inclusion criteria. In the multivariable logistic regression analysis, net water uptake (odds ratio, 0.78 [95% CI, 0.64–0.95], P =0.01), age (odds ratio, 0.94 [95% CI, 0.88–0.99]; P =0.02), and National Institutes of Health Stroke Scale (odds ratio, 0.88 [95% CI, 0.79–0.99], P =0.03) were significantly and independently associated with favorable outcome (modified Rankin Scale score ≤1), adjusted for degree of recanalization and Alberta Stroke Program Early CT Score. A multivariable predictive model including the above parameters yielded the highest diagnostic ability in the classification of functional outcome, with an area under the curve of 0.88 (sensitivity 92.3%, specificity 82.9%). Conclusions: The implementation of quantitative lesion water uptake as imaging biomarker in the diagnosis of patients with ischemic stroke presenting in the extended time window might improve clinical prognosis. Future studies could test this biomarker as complementary or even alternative tool to CT perfusion.