Case report: Meningitis: a cause of reversible cerebral vasoconstriction syndrome?

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache and reversible cerebral arteries vasoconstriction. The pathophysiology remains unclear, but many triggers were reported. Case reports: We reported two cases of patients with meningitis who developed RCVS confirmed by brain imaging. They presented clinical and CSF features of meningitis that are suspected to be infectious, but no agent was identified. Headache and artery irregularities were resolved with the improvement of CSF. Conclusion: These cases suggest that in the context of meningitis, modification or atypical headaches should lead to brain imaging to rule out RCVS. We hypothesized that CSF inflammation may trigger cerebral arteries vasoconstriction.

Is carotid web an arterial wall dysplasia? A histological series.

INTRODUCTION: Described for 60 years under various names, the carotid web is a suspected cause of cryptogenic stroke, especially in young patients. The web creates an intraluminal protrusion that may contribute to turbulent flow and thrombus embolization into cerebral arteries. Although the carotid web has frequently been related to arterial fibrodysplasia, its natural history and pathological description remain unclear. PATIENTS: Among all consecutive patients admitted to the stroke unit of Sainte-Anne Hospital and referred to the vascular surgery department from January 2015 to December 2022, we retrospectively identified 9 patients with a carotid web. The surgical specimens of the 9 patients were submitted to systematic pathological analysis. RESULTS: The patients with a histologically confirmed carotid web were young (median age was 42 years), prominently women (7/9), and presenting with low cardiovascular risk. Eight patients had a stroke proven by a magnetic resonance imaging, and 1 had transient monocular amaurosis. The typical pathological lesion supporting the imaging pattern of the carotid web was a focal eccentric intimal hyperplasia forming a protruding lesion characterized by a population of vascular smooth muscle cells intermingled in an abundant, most often loose extracellular matrix. Pathologically proven thrombus was observed in 4 cases. Importantly atherosclerosis was absent. CONCLUSION: Histological features in our 9 cases strengthen carotid web characterization as a homogeneous pattern of localized intimal hyperplasia. It is a unique entity consistent with intimal fibroplasia, distinct from medial fibromuscular dysplasia and early atherosclerosis.

Initiation and development of a percutaneous left atrial appendage closure programme: A French centre's experience and literature review.

BACKGROUND: Percutaneous left atrial appendage closure may be considered in selected patients with atrial fibrillation at significant risk of both thromboembolism and haemorrhage. AIMS: To report the experience of a tertiary French centre in percutaneous left atrial appendage closure and to discuss the outcomes compared with previously published series. METHODS: This was a retrospective observational cohort study of all patients referred for percutaneous left atrial appendage closure between 2014 and 2020. Patient characteristics, procedural management and outcomes were reported, and the incidence of thromboembolic and bleeding events during follow-up were compared with historical incidence rates. RESULTS: Overall, 207 patients had left atrial appendage closure (mean age 75.3±8.6 years; 68% men; CHA2DS2-VASc score 4.8±1.5 ; HAS-BLED score 3.3±1.1), with a 97.6% (n=202) success rate. Twenty (9.7%) patients had at least one significant periprocedural complication, including six (2.9%) tamponades and three (1.4%) thromboembolisms. Periprocedural complication rates decreased from earlier to more recent periods (from 13% before 2018 to 5.9% after; P=0.07). During a mean follow-up of 23.1±20.2 months, 11 thromboembolic events were observed (2.8% per patient-year), a 72% risk reduction compared with the estimated theoretical annual risk. Conversely, 21 (10%) patients experienced bleeding during follow-up, with almost half of the events occurring during the first 3 months. After the first 3 months, the risk of major bleeding was 4.0% per patient-year, a 31% risk reduction compared with the expected estimated risk. CONCLUSION: This real-world evaluation emphasizes the feasibility and benefit of left atrial appendage closure, but also illustrates the need for multidisciplinary expertise to initiate and develop this activity.

Patent foramen ovale closure in stroke patients with migraine in the CLOSE trial. The CLOSE-MIG study.

BACKGROUND AND PURPOSE: The efficacy of patent foramen ovale (PFO) closure to reduce the frequency of migraine attacks remains controversial. METHODS: This was a planned sub-study in migraine patients enrolled in a randomized, clinical trial designed to assess the superiority of PFO closure plus antiplatelet therapy over antiplatelet therapy alone to prevent stroke recurrence in patients younger than 60 years with a PFO-associated cryptogenic ischaemic stroke. The main outcome was the mean annual number of migraine attacks in migraine patients with aura and in those without aura, as recorded at each follow-up visit by study neurologists. RESULTS: Of 473 patients randomized to PFO closure or antiplatelet therapy, 145 (mean age 41.9 years; women 58.6%) had migraine (75 with aura and 70 without aura). Sixty-seven patients were randomized to PFO closure and 78 to antiplatelet therapy. During a mean follow-up of about 5 years, there were no differences between antiplatelet-only and PFO closure groups in the mean annual number of migraine attacks, both in migraine patients with aura (9.2 [11.9] vs. 12.0 [19.1], p = 0.81) and in those without aura (12.1 [16.1] vs. 11.8 [18.4], p > 0.999). There were no differences between treatment groups regarding cessation of migraine attacks, migraine-related disability at 2 years and use of migraine-preventive drugs during follow-up. CONCLUSIONS: In young and middle-aged adults with PFO-associated cryptogenic stroke and migraine, PFO closure plus antiplatelet therapy did not reduce the mean annual number of migraine attacks compared to antiplatelet therapy alone, in migraine patients both with and without aura.

Cathodal Transcranial Direct Current Stimulation in Acute Ischemic Stroke: Pilot Randomized Controlled Trial.

Background and Purpose: In acute stroke, preventing infarct growth until complete recanalization occurs is a promising approach as an adjunct to reperfusion therapies to reduce infarct size and improve outcome. In rodent models, cathodal transcranial direct current stimulation (C-tDCS) decreases peri-infarct depolarizations and reduces infarct volume. We hypothesized that C-tDCS would nonpharmacologically reduce infarct growth in hyperacute middle cerebral artery territory stroke patients receiving reperfusion therapy. Methods: STICA (Cathodal Transcranial Direct Stimulation in Acute Middle Cerebral Artery Stroke) was a pilot single-center, double-blind, 2-arms 1:1 randomized trial evaluating the safety, feasibility, and efficacy of C-tDCS versus sham stimulation in patients eligible for recanalization therapies. Magnetic resonance imaging was obtained both on admission and 24 hours later. The primary end point was 24-hour infarct growth. Secondary outcomes were (1) National Institutes of Health Stroke Scale score difference between day 7 and admission and (2) 3-month modified Rankin Scale score. Results: Forty-five patients were randomized. Median magnetic resonance imaging-to-C-tDCS start time was 45 minutes; C-tDCS was started before completion of recanalization procedure in all patients. The intervention proved feasible in all patients. No major adverse effects occurred in either group. There was no significant difference between active and sham groups for any end point. However, an apparent trend towards smaller infarct growth in the C-tDCS arm was observed in the whole group (unadjusted median difference [IC95%]: −2.2 mL [−12.2 to 1.5]) and in the prespecified subsamples with moderate-to-severe stroke and large vessel occlusion (−5.7 mL [−21.6 to 2.6] and −7.7 mL [−24.2 to 2.6], respectively). Conclusions: C-tDCS was feasible and well tolerated. No significant difference was found between the active and sham groups. However, the data suggest potential benefits of C-tDCS in patients with National Institutes of Health Stroke Scale score of >10 or large vessel occlusion. Using the observed effect size and standard α=5% and ß=20%, samples of 102 and 86, respectively, can be estimated for future trials in patients with these characteristics. Randomized trials particularly targeting these populations may be warranted.

Spontaneous Cervical Artery Dissection in Vascular Ehlers-Danlos Syndrome: A Cohort Study.

BACKGROUND AND PURPOSE: Vascular Ehlers-Danlos syndrome is a rare inherited connective tissue disorder because of pathogenic variants in the COL3A1 gene. Arterial complications can affect all anatomic areas and about 25% involve supra-aortic trunks (SATs) but no systematic assessment of cervical artery lesions has been made. The primary objective was to determine an accurate prevalence of spontaneous SAT lesions in a large series of patients with vascular Ehlers-Danlos syndrome at diagnosis and during follow-up. Secondary objectives were to study their neurological consequences (transient ischemic attack or stroke) and the possible relationships with sex, genotype, ascertainment status. METHODS: A retrospective review of a monocentric cohort of patients with molecularly proven vascular Ehlers-Danlos syndrome followed in a tertiary referral center from 2000 to 2017. RESULTS: One hundred forty-four patients were analyzed, 56.9% (n=82) had SAT lesions: 64.6% females, 74.4% index-case patients. Most lesions were identified in early arterial assessment (48% at first work-up, mean age of 35.7±13.0 years). Cumulative incidence of a first identification of a SAT lesion was 41.7% at 40 years old. On the complete period of survey, 183 SAT lesions (with 132 dissections and 33 aneurysms) were identified, mainly in internal carotid arteries (56.3%) and vertebral arteries (28.9%), more rarely in patients with COL3A1 null mutations (P=0.008). Transient ischemic attack or stroke were reported in n=16 (19.5%) of the 82 patients with SAT lesions without relation with age, sex, treatment, or hypertension. CONCLUSIONS: Cervical artery lesions are frequent and mostly asymptomatic in patients with vascular Ehlers-Danlos syndrome. Local dissections and aneurysms are the most frequent type of lesions, but transient ischemic attack or stroke seem rare.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Pathophysiology of carotid-cavernous fistulas in vascular Ehlers-Danlos syndrome: a retrospective cohort and comprehensive review.

BACKGROUND: Vascular Ehlers-Danlos syndrome (vEDS) is a rare condition characterized by connective tissue fragility. Direct spontaneous carotid-cavernous fistula (sCCF) is reportedly pathognomonic of vEDS. We conducted this study to understand the possible mechanisms of occurrence of sCCF in this subset of patients. METHODS: We conducted a retrospective analysis of a monocentric vEDS cohort along with a literature review regarding sCCF in this condition. RESULTS: Of 133 patients regularly followed in our centre between 2000 and 2017, 13 (9.8%) had a diagnosis of direct sCCF (92.3% female, median age 33.0 years, interquartile range (IQR) [26.0-39.5]). There were 7 Glycine missense and 6 splice-site variants but no variant leading to haploinsufficiency. The literature search identified 97 vEDS patients with direct sCCF (79.4% female, 7.2% sex not reported, median age 31.0 years, IQR [24.0-39.0]). Increased carotid circumferential wall stress, higher carotid distensibility and lower carotid intima-media thickness could contribute to a higher risk for direct sCCF in vEDS. There is no predictive factor for the occurrence of sCCF apart from female sex in vEDS. CONCLUSIONS: In vEDS, anatomical and pathophysiological features of the intra-cavernous internal carotid artery make it prone to shunting in the cavernous sinus, due either to a spontaneous rupture or to a spontaneous dissection with pseudoaneurysm formation. Direct sCCF in seemingly healthy young individuals should be highly suggestive of vEDS and prompt further investigation.

Cyclosporine in acute ischemic stroke.

OBJECTIVES: We examined whether IV administration of cyclosporine in combination with thrombolysis might reduce cerebral infarct size. METHODS: Patients aged 18 to 85 years, presenting with an anterior-circulation stroke and eligible for thrombolytic therapy, were enrolled in this multicenter, single-blinded, controlled trial. Fifteen minutes after randomization, patients received either an IV bolus injection of 2.0 mg/kg cyclosporine (Sandimmune, Novartis) or placebo. The primary endpoint was infarct volume on MRI at 30 days. Secondary endpoints included infarct volume according to the site (proximal/distal) of arterial occlusion and recanalization after thrombolysis. RESULTS: From October 2009 to July 2013, 127 patients were enrolled. The primary endpoint was assessed in 110 of 127 patients. The reduction of infarct volume in the cyclosporine compared with the control group was overall not significant (21.8 mL [interquartile range, IQR 5.1, 69.2 mL] vs 28.8 mL [IQR 7.7, 95.0 mL], respectively; p = 0.18). However, in patients with proximal occlusion and effective recanalization, infarct volume was significantly reduced in the cyclosporine compared with the control group (14.9 mL [IQR 1.3, 23.2 mL] vs 48.3 mL [IQR 34.5, 118.2 mL], respectively; p = 0.009). CONCLUSIONS: Cyclosporine was generally not effective in reducing infarct size. However, a smaller infarct size was observed in patients with proximal cerebral artery occlusion and efficient recanalization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with an acute anterior-circulation stroke, thrombolysis plus IV cyclosporine does not significantly decrease 30-day MRI infarct volume compared with thrombolysis alone.

Clinical and magnetic resonance imaging predictors of very early neurological response to intravenous thrombolysis in patients with middle cerebral artery occlusion.

BACKGROUND: The early identification of patients who are unlikely to respond to intravenous recombinant tissue plasminogen activator (IV-tPA) could help select candidates for additional intra-arterial therapy or add-on antithrombotic drugs during the acute stage of stroke. Given that very early neurological improvement (VENI) is a reliable surrogate of early recanalization, we assessed the clinical and magnetic resonance imaging predictors of lack of VENI. METHODS AND RESULTS: We reviewed consecutive ischemic stroke patients with middle cerebral artery occlusion and treated within 4.5 hours by IV-tPA between 2003 and 2012 in our center, where magnetic resonance imaging is systematically implemented as first-line diagnostic workup. Lack of VENI was defined as a <40% decrease in baseline National Institutes of Health Stroke Scale (NIHSS) score 1 hour after start of IV-tPA. Poor outcome was defined as a 3-month modified Rankin scale ≥2. Associations between lack of VENI and potential determinants were assessed in logistic regression models. In all, 186 patients were included (median baseline NIHSS score, 16; median onset to treatment time, 155 minutes). One hundred forty-three patients (77%) had no VENI. The variables significantly associated with lack of VENI in multivariable analysis were baseline NIHSS (OR, 1.08; 95% CI, 1.01 to 1.16 per 1-point increase; P=0.03), onset to treatment time >120 minutes (OR, 2.94; 95% CI, 1.31 to 6.63; P=0.009) and diffusion weighted imaging--Alberta Stroke Programme Early CT Score ≤5 (OR, 3.60; 95% CI, 1.14 to 11.35; P=0.03). Patients without VENI were more likely to have a modified Rankin Scale ≥2 than those without VENI (68% versus 24%; OR, 5.01; 95% CI, 2.12 to 11.82) and less likely to have recanalization after 24 hours (OR, 0.41; 95% CI, 0.19 to 0.88). CONCLUSIONS: Lack of VENI provides an early estimate of 3-month outcome and recanalization after IV-tPA. Baseline NIHSS, onset to treatment time, and diffusion weighted imaging--Alberta Stroke Programme Early CT Score could help to predict lack of VENI and, in turn, might help early selection of candidates for complementary reperfusion strategies.

Reversible cerebral angiopathy: efficacy of nimodipine.

Reversible cerebral angiopathy (RCA) is responsible for disabling headache and potential stroke complications. Most patients respond poorly to analgesics. We describe four patients with typical RCA whose headache rapidly disappeared after IV nimodipine treatment was initiated.

Subarachnoid hemorrhage as the initial presentation of dural sinus thrombosis.

Cerebral venous thrombosis (CVT) can be difficult to diagnose because of its wide spectrum of clinical manifestations. Its diagnosis may be further complicated when patients initially present with acute subarachnoid hemorrhage (SAH). We report on four patients with SAH revealing a CVT and discuss the role of imaging for diagnostic and pretherapeutic workup. In three women and one man presenting with severe headaches, images initially suggested SAH with no associated parenchymal bleeding. In all patients, SAH involved the sulci of the convexity and spared the basal cisterns. Digital subtracted angiography showed occlusion of intracranial venous sinuses but did not reveal any other cause of SAH. All patients improved with anticoagulant therapy. Risk factors for CVT and SAH, namely, head trauma and oral contraception, were identified in two patients. These cases highlight the fact SAH may reveal a CVT, which should be considered in the diagnostic workup of SAH, especially when the basal cisterns are not involved.

Spontaneous intracerebral hematoma on diffusion-weighted images: influence of T2-shine-through and T2-blackout effects.

BACKGROUND AND PURPOSE: On diffusion-weighted (DW) images, primary hematomas are initially mainly hyperintense, and then hypointense during the first few days after stroke onset. As in other brain disorders, variations in the T2 relaxation time of the hematoma influence the DW imaging signal intensity. Our aim was to evaluate the contribution of the T2 signal intensity and apparent diffusion coefficient (ADC) changes to signal intensity displayed by DW imaging through the course of hematoma. METHODS: The MR images of 33 patients with primary intracranial hemorrhage were retrospectively reviewed. Variations in T2-weighted echo planar images, DW imaging signal intensity, and apparent diffusion coefficient (ADC) ratios (core of hematoma/contralateral hemisphere) were analyzed according to the putative stages of hematoma, as seen on T1- and T2-weighted images. RESULTS: On both T2-weighted echo planar and DW images, the core of the hematomas was hyperintense at the hyperacute (oxyhemoglobin, n = 11) and late subacute stages (extracellular methemoglobin, n = 4), while being hypointense at the acute (deoxyhemoglobin, n = 11) and early subacute stages (extracellular methemoglobin, n = 7). There was a positive correlation between the signal intensity ratio on T2-weighted echo planar and DW images (r = 0.93, P < .05). ADC ratios were significantly decreased in the whole population and in each of the first three stages of hematoma, without any correlation between DW imaging findings and ADC changes (r = 0.09, P = .6). CONCLUSION: Our results confirm that the core of hematomas is hyperintense on DW images with decreased ADC values at the earliest time point, and may thus mimic arterial stroke on DW images. T2 shine-through and T2 blackout effects contribute to the DW imaging findings of hyperintense and hypointense hematomas, respectively, while ADC values are moderately but consistently decreased during the first three stages of hematoma.