Monica Carletti

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Effect of Anticoagulation and Its Timing: The RAF Study

Background and Purpose— The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. Methods— The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Results— Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30–0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Conclusions— Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Does statin in the acute phase of ischemic stroke improve outcome after intravenous thrombolysis? A retrospective study

BACKGROUNDnIn recent years, the medical literature has shown that statin treatment before and in the acute phase of ischemic stroke has a positive impact on outcome. The possible effect of statins during the acute phase has never been assessed in thrombolysed patients, and the few studies investigating a possible association between prior statin use and outcome after thrombolysis have reported controversial results. The aim of the present study was to assess whether statin treatment started in the acute phase of stroke (within 24h) or before stroke and continued during the acute phase may influence short- and long-term outcome in patients receiving intravenous (IV) thrombolysis.nnnMETHODSnWe conducted a retrospective analysis of 250 patients treated with IV thrombolysis. Outcome measures were 3-month good functional outcome (modified Rankin Scale ≤ 2); neurological improvement (reduction ≥ 4 points on the National Institutes of Health Stroke Scale [NIHSS]) between 24 and 72 h; and symptomatic intracerebral hemorrhage (brain hematoma associated with NIHSS deterioration ≥ 4 points) within 72 h.nnnRESULTSnMultivariate analysis showed that statin treatment started in the acute phase of stroke was associated with both good functional outcome (OR: 6.18; 95% CI: 1.43-26.62; P=0.015) and neurological improvement (OR: 9.47; 95% CI: 1.98-45.37; P=0.005), whereas statin treatment started before stroke and continued in the acute phase was associated with symptomatic intracerebral hemorrhage (OR: 6.65; 95% CI: 1.58-29.12; P=0.010).nnnCONCLUSIONSnOur data suggest that statin treatment started within 24h after IV thrombolysis, but not statin treatment started before stroke and continued in the acute phase, may improve short- and long-term outcome.

Seizure induced ventricular fibrillation: A case of near-SUDEP

Cardiac arrhythmias are a common complication of partial seizures, with ictal sinus tachycardia present in 16 out of 20 patients having undergone prolonged electrocardiographic (ECG) monitoring with implantable loop recorders. Ictal bradyarrhythmia and ictal asystole are more concerning but rare: a prevalence of 0.34–0.4% has been reported in large series. These situations have received a lot of attention recently because they have been postulated as one of the mechanisms underlying sudden unexpected death in epilepsy (SUDEP), although the supporting evidence remains fragmented. The few documented cases of SUDEP (or near-SUDEP) mainly showed apnoea and hypoventilation to be the terminal event, although there are some cases with a primary cardiac mechanism. We report the case of a patient suffering from drug-resistant focal epilepsy who developed ventricular fibrillation at the end of a convulsive seizure, requiring cardiopulmonary resuscitation (CPR).

Mutations in TGFBR2 gene cause spontaneous cervical artery dissection

Mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2) have recently been associated with hereditary connective tissue disorders with widespread vascular involvement, including arterial dissection. To determine whether mutations in these genes cause spontaneous cervical artery dissection (sCAD), all coding exons of TGFBR1 and TGFBR2 were sequenced in 56 consecutive patients with sCAD. Novel TGFBR2 disease causing mutations were found in two patients. The two mutations were the pK327R substitution affecting the kinase domain of TGFBR2 and the pC138R substitution falling in the extracellular domain of the protein, involved in TGFβ binding and signalling. No TGFBR1 mutation was found. The findings indicate that TGFBR2 gene mutations are responsible for sCAD in 3.6% (95% CI 0.0 to 8.4) of cases, have implications in understanding the role of TGFβ signalling in the pathogenesis of sCAD and emphasise the importance of considering molecular characterisation of the TGFBR2 gene in these patients, regardless of the presence of clinical features suggestive of hereditary connective tissue disorders.

Connective tissue anomalies in patients with spontaneous cervical artery dissection

Objective: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD). Methods: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD. Results: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045). Conclusions: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease.

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5xa0h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24xa0h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95xa0% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4xa0%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95xa0% CI 1.61–21.19; pxa0=xa00.024). Off-label thrombolysis may be less effective at 24xa0h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.

Paradoxical brain embolism in a young man with isolated pulmonary arteriovenous fistula

We herein report a case of ischemic stroke due to paradoxical brain embolism in a young man, a trumpet player. Extensive diagnostic investigations revealed the presence of an isolated pulmonary arteriovenous fistula as the only risk factor for stroke. The peculiarity of this case is the early onset of neurological symptoms in the absence of Hereditary Hemorrhagic Teleangiectasia. The Authors suppose the repeated Valsalva maneuvers as a possible factor promoting fistula enlargement and symptoms development.

Prognostic value of trans-thoracic echocardiography in patients with acute stroke and atrial fibrillation: findings from the RAF study

AbstractAnticoagulant therapy is recommended for the secondary prevention of stroke in patients with atrial fibrillation (AF). Tnhe identification of patients at high risk for early recurrence, which are potential candidates to prompt anticoagulation, is crucial to justify the risk of bleeding associated with early anticoagulant treatment. The aim of this study was to evaluate in patients with acute ischemic stroke and AF the association between findings at trans-thoracic echocardiography (TTE) and 90xa0days recurrence. In consecutive patients with acute ischemic stroke and AF, TTE was performed within 7xa0days from hospital admission. Study outcomes were recurrent ischemic cerebrovascular events (stroke or TIA) and systemic embolism. 854 patients (mean age 76.3xa0±xa09.5xa0years) underwent a TTE evaluation; 63 patients (7.4xa0%) had at least a study outcome event. Left atrial thrombosis was present in 11 patients (1.3xa0%) among whom 1 had recurrent ischemic event. Left atrial enlargement was present in 548 patients (64.2xa0%) among whom 51 (9.3xa0%) had recurrent ischemic events. The recurrence rate in the 197 patients with severe left atrial enlargement was 11.7xa0%. On multivariate analysis, the presence of atrial enlargement (OR 2.13; 95xa0% CI 1.06–4.29, pxa0=xa00.033) and CHA2DS2-VASc score (OR 1.22; 95xa0% CI 1.04–1.45, pxa0=xa00.018, for each point increase) were correlated with ischemic recurrences. In patients with AF-associated acute stroke, left atrial enlargement is an independent marker of recurrent stroke and systemic embolism. The risk of recurrence is accounted for by severe atrial enlargement. TTE-detected left atrial thrombosis is relatively uncommon.

A model of multi-disciplinary approach to the diagnosis and treatment of young patients with cryptogenic stroke and patent foramen ovale.

BACKGROUNDnTreatment of patent foramen ovale in young patients with stroke is not supported by robust scientific evidence. In clinical practice, a pragmatic approach is needed to guide such therapeutic decisions. This study aims at standardising the diagnostic pathway for stroke patients younger than 55 years of age with a patent foramen ovale; elaborating a therapeutic algorithm; discussing every case in regular interdisciplinary counselling meeting; and setting up a follow-up schedule to assess clinical outcomes.nnnMETHODSnThis is a cohort study on the effect of a standardised treatment of stroke patients with a patent foramen ovale. The primary endpoints include occurrence of recurrent ischaemic events, major bleeding, and device-related complications. The secondary endpoints include drug- or procedure-related side effects, persistence of right-to-left shunt, and persistent cardiac arrhythmia of new onset.nnnRESULTSnA total of 103 patients have been enrolled. In all, 51 patients underwent percutaneous atrial septal repair; of these, one had minor post-procedural bleeding. At 12 months, 25% of this group of patients showed a latent I grade shunt, one patient a latent II degree shunt, and none had a persistent shunt. The remaining 52 patients were addressed to medical therapy; one of them experienced stroke recurrences while on medical therapy.nnnCONCLUSIONSnThis model of implementation of available evidence to clinical practice via a group-based, multi-disciplinary counselling provides a shared and coherent decision pathway and yielded a very low rate of recurrent events and therapy-related complications. This approach could be replicated in specific protocols for other complex or neglected clinical problems.

Intravenous thrombolysis on early recurrent cardioembolic stroke: “Dr. Jekyll” or “Mr. Hyde”?

Early recurrent cardioembolic stroke on the previously unaffected side has very rarely been reported during or after intravenous recombinant tissue plasminogen activator for acute ischemic stroke. For these cases, thrombolysis guidelines lack any clear recommendation. We report two cases of thrombolysed stroke patients, with paroxysmal atrial fibrillation but normal sinus rhythm on admission, who respectively developed recurrent ischemic stroke within few hours after complete improvement and during intravenous recombinant tissue plasminogen activator infusion. Intravenous thrombolysis was successfully repeated after echocardiographic evidence of left appendage thrombus in the first case and discontinued before complete administration in the second.