Efficacy of prothrombin complex concentrates for the emergency reversal of dabigatran-induced anticoagulation.

Dabigatran is effective in decreasing the risk of ischaemic stroke in patients with atrial fibrillation. However, like all anticoagulants, it is associated with a risk of bleeding. In cases of trauma or emergency surgery, emergency reversal of dabigatran-induced anticoagulation may be required. A specific reversal agent for dabigatran, idarucizumab, has been approved by the US Food and Drug Administration. Alternative reversal agents are available, such as prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs). In this review we evaluate the role of PCCs and aPCCs in the reversal of dabigatran anticoagulation and consider which tests are appropriate for monitoring coagulation in this setting. Pre-clinical studies, small clinical studies and case reports indicate that PCCs and aPCCs may be able to reverse dabigatran-induced anticoagulation in a dose-dependent manner. However, dosing based on coagulation parameters can be difficult because available assays may not provide adequate sensitivity and specificity for measuring anticoagulation induced by dabigatran or the countering effects of PCCs/aPCCs. In addition, PCCs or aPCCs can potentially provoke thromboembolic complications. Despite these limitations and the fact that PCCs and aPCCs are not yet licensed for dabigatran reversal, their use appears to be warranted in patients with life-threatening haemorrhage if idarucizumab is not available.

Imaging of Headache in Pregnancy.

Pregnant women are most likely to have primary headaches, such as migraine and tension-type headaches, which can be diagnosed and treated without brain imaging. Primary headaches may even start de novo during pregnancy, especially in the first few months. However, when the headache occurs late in pregnancy or in the peripartum period, secondary causes of headaches need to be considered and evaluated by brain and/or vascular imaging, generally using magnetic resonance techniques. There is considerable overlap between the cerebrovascular complications of pregnancy, including preeclampsia/eclampsia, posterior reversible encephalopathy syndrome (PRES), reversible cerebral vasoconstriction syndrome (RCVS), and both hemorrhagic and ischemic strokes; although, their imaging may be distinctive. Imaging is necessary to distinguish between arterial and venous pathology causing headache in the peripartum patient, as there can be similar presenting symptoms. Mass lesions, both neoplastic and inflammatory, can enlarge and produce headaches and neurological symptoms late in pregnancy.

Headache and acute stroke.

Disorders associated with prominent headaches, such as migraine with aura and cerebral arterial and venous diseases, increase the risk of ischemic and hemorrhagic stroke. Central nervous system vasculitis, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and cerebral venous thrombosis are all disorders associated with severe or persistent headache in which the risk for ischemic and hemorrhagic stroke is increased. Hemorrhagic strokes, more frequently than ischemic strokes, present with distinct headaches, usually accompanied by focal neurological symptoms. Pregnancy, and especially the postpartum period, is a time of overlap between new-onset headache and stroke risk.

Neuroimaging During Pregnancy and the Postpartum Period.

New onset or exacerbation of preexisting neurologic symptoms during pregnancy often necessitates brain or spinal cord imaging. Magnetic resonance techniques are preferred imaging modalities during pregnancy and the postpartum period. Ionizing radiation with computed tomography and intravenous contrast material with magnetic resonance or computed tomography should be avoided during pregnancy. New onset of headaches in the last trimester or in the postpartum period may indicate cerebrovascular disease or a mass lesion, for which brain imaging is necessary. The continuum of cerebrovascular complications of pregnancy and enlarging lesions may produce neurologic symptoms later in pregnancy and after delivery, necessitating imaging.

Stroke in Women: What is Different?

Stroke, a major cause of morbidity and mortality in the general population, varies in incidence in men and women of different age groups: more boys than girls have strokes; the incidence of stroke is greater in men in their 60s and 70s; and stroke is more common in women after age 80 years. These differences are attributed to hormonal (sex-related) changes and variable risk factors in women, as well as lifestyle and environmental (gender-related) co-morbid conditions. A woman, who is more likely to have a stroke in her lifetime than a myocardial infarction, has a different response to primary and secondary prevention as compared with a man. Although response to thrombolysis is similar, older age and more severe strokes in women lead to poorer outcomes in female stroke survivors.

Imaging of Neurologic Disorders in Pregnancy.

Pregnant women may have exacerbation of preexisting neurologic disorders or new-onset neurologic symptoms for which brain or spinal cord imaging is appropriate. Primary headaches in early pregnancy can be diagnosed and treated without imaging. Headaches later in pregnancy or in the peripartum period may need to be evaluated by brain and/or vascular imaging. Cerebrovascular complications have distinctive imaging but overlapping presentations. Mass lesions can enlarge, producing neurologic symptoms, late in pregnancy. Imaging may be necessary to diagnose neurologic disorders in pregnancy and the peripartum period. MRI is preferred during pregnancy; imaging involving ionizing radiation and/or contrast should be avoided.

Update on antiplatelet agents, including MATCH, CHARISMA, and ESPRIT.

Despite recent advances in the acute treatment of stroke, prevention and risk factor modification remain the mainstays of management for patients with ischemic stroke and transient ischemic attack. The majority of noncardioembolic ischemic strokes are atherothrombotic, presumed to be associated with the activation and aggregation of platelets. Antiplatelet medications have been shown to be effective in the secondary prevention of stroke of presumed arterial origin, both as monotherapy and in combination. Among combination of antiplatelet agents, aspirin plus extended-release dipyridamole has demonstrated statistically significant additive benefit over monotherapy with each agent. Clopidogrel plus aspirin does not prevent recurrent ischemic stroke over each component individually, and the combination increases the risk of hemorrhagic side effects. This article reviews the most recent studies on antiplatelet medications, including the combination of aspirin and clopidogrel or extended-release dipyridamole, and discusses some of the controversies that still exist with the use of antiplatelet agents.

Secondary prevention of ischemic stroke: evolution from a stepwise to a risk stratification approach to care.

Survivors of ischemic stroke are at significant risk for recurrent stroke. Appropriate therapy for stroke prevention is needed given the significant morbidity and mortality associated with stroke, the high financial costs, and the neurologic disability associated with treatment failure. A treatment strategy based on assessed risk represents an appropriate use of medical resources and results in improved outcomes. This approach requires evaluation of major risk factors, the most serious of which is a history of ischemic stroke or transient ischemic attack. The annual risk for recurrent stroke is 6% during the first 5 years after an initial stroke. Non-modifiable risk factors include age, race, ethnicity, gender, family history, and geography. The most important modifiable risk factor is hypertension. Diabetes mellitus, hyperlipidemia, left ventricular hypertrophy, atrial fibrillation, and lifestyle factors such as smoking, alcohol abuse, and obesity contribute to stroke risk. Antihypertensive, lipid-lowering, and antiplatelet therapies have been successful in reducing the incidence of secondary stroke. Clinical trials validate the benefits of statin therapy in reducing the risk for secondary stroke. Studies of antiplatelet agents, including aspirin, clopidogrel, and aspirin combined with extended-release dipyridamole, have evaluated the risk reduction in recurrent stroke and have been concerned particularly with the risk for hemorrhage. Therapy for stroke prevention based on risk stratification can identify patients who are appropriate targets for aggressive intervention.

An Acute Disseminated Encephalomyelitis-Like Illness in the Elderly: Neuroimaging and Neuropathology Findings.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system (CNS) that classically occurs in children and adolescents. It characteristically presents with acute inflammation, resulting in demyelination, often following an infectious disease. ADEM has been described in adult patients, but the incidence in the adult and especially elderly population is low. CASES: We describe five older adults (age 57 to 85) who presented with acute neurological symptoms. Three patients presented with an infectious illness preceding the event, 4 patients were encephalopathic, and oligoclonal bands (OCBs) were negative in all tested cases. The clinical scenario and imaging studies suggested alternative diagnoses, such as metastasis, primary CNS tumor, or stroke. Two patients had contrast enhancing lesions, two other patients had lesions with restricted diffusion on diffusion-weighted imaging. Neuropathologic diagnostic from biopsy or autopsy was eventually conclusive, showing perivascular zones of myelin loss with relative axonal sparing in all five cases. CONCLUSION: Each of these patients was found to have pathological findings of acute demyelination on tissue diagnosis, suggesting ADEM or ADEM-like disease. The initial presentation and imaging was pointing toward other diagnoses. Broad differential diagnosis is important, especially for older patients, and pathological proof might be warranted for a conclusive diagnosis.

Review of antiplatelet therapy in secondary prevention of cerebrovascular events: a need for direct comparisons between antiplatelet agents.

Patients experiencing stroke or transient ischemic attack (TIA) are at high risk for recurrent (secondary) strokes, which comprise 29% of all strokes in the United States. Current recommendations for prevention of secondary stroke from the American College of Chest Physicians (ACCP) call for the broad use of platelet antiaggregation (antiplatelet) agents for patients with a history of noncardioembolic stroke or TIA. Five agents--aspirin, ticlopidine, clopidogrel, extended-release dipyridamole (ER-DP), and triflusal--have demonstrated efficacy in large-scale clinical studies in the prevention of recurrent vascular events and/or stroke in patients with a history of stroke. The results of the following studies are reviewed and compared: the Swedish Aspirin Low-Dose Trial (SALT), the United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial, Dutch Transient Ischemic Attack (Dutch TIA) study (aspirin), the Canadian American Ticlopidine Study (CATS), the Ticlopidine Aspirin Stroke Study (TASS), the African American Antiplatelet Stroke Prevention Study (AAASPS) (ticlopidine), the Clopidogrel versus Aspirin in Patients at Risk of Recurrent Ischemic Events (CAPRIE) trial, the Management of Atherothrombosis With Clopidogrel in High-Risk Patients study (MATCH) (clopidogrel), the second European Stroke Prevention Study (ESPS2) (aspirin plus ER-DP), and the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP) study. In comparative monotherapy studies of patients with previous stroke, ticlopidine demonstrates statistically significant improved efficacy over aspirin, and clopidogrel demonstrates nonsignificant slight improvement over aspirin for the prevention of ischemic cardiac and cerebrovascular events; however, the adverse event profile of ticlopidine (including rash, diarrhea, and neutropenia) will probably limit its long-term use. Among combination approaches, only aspirin plus ER-DP has demonstrated statistically significant, clinically meaningful additive benefit over monotherapy with each agent. Clopidogrel plus aspirin did not significantly improve preventive efficacy and increased the risk of serious side effects, including life-threatening bleeding episodes. The 15,500-patient PRoFESS (the Prevention Regimen for Effectively Avoiding Second Strokes) study, with results expected in 2008, will directly compare aspirin plus ER-DP with clopidogrel monotherapy for the prevention of recurrent stroke and should provide statistically robust estimates of comparative efficacy for the development of improved recommendations.

The safety of triptans in the treatment of patients with migraine.

The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in the past decade has brought migraine-specific pain relief to those suffering from migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on cerebral vessels. Concerns about their safety, particularly in patients with vascular risk factors, have been raised because triptans also activate the 5-HT(1B) receptors on coronary arteries. Although triptans are contraindicated in patients with cardiac or cerebrovascular disease, they are safer than many other medications used to treat patients with migraine, including the nonspecific serotonin-agonist ergot preparations.

The role of neuroimaging in headache.

Headaches are a universal experience and one of the most common causes for physician consultation. The physician must determine whether a neuroimaging study is warranted to aid in the diagnosis of primary or secondary headaches. Guidelines on neuroimaging of headache patients have been developed based on review of the literature; however, their applicability must be adapted to specific clinical situations. In general, neuroimaging is most likely to be useful if the history is not typical of a primary headache type (e.g., tension type, migraine, cluster headaches) or the neurological examination is abnormal. Neuroimaging has been crucial in the investigation of the pathogenesis of migraine and cluster headaches. Secondary headaches, which may be diagnosed by neuroimaging studies, include subarachnoid hemorrhage, cerebral venous thrombosis, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, aqueductal stenosis, and arterial dissection.

What the nonneurologist can do to treat headache.

Nonneurologists who treat patients with headaches should be able recognize common headache types and to initiate therapy for tension-type headaches and migraines. Patients with complicated headache scenarios should be referred to a neurologist for consultation.

Developing practice recommendations for endovascular revascularization for acute ischemic stroke.

Guidelines have been established for the management of acute ischemic stroke; however, specific recommendations for endovascular revascularization therapy are lacking. Burgeoning investigation of endovascular revascularization therapies for acute ischemic stroke, rapid device development, and a diverse training background of the providers performing the procedures underscore the need for practice recommendations. This review provides a concise summary of the Society of Vascular and Interventional Neurology endovascular acute ischemic stroke roundtable meeting. This document was developed to review current clinical efficacy of pharmacologic and mechanical revascularization therapy, selection criteria, periprocedure management, and endovascular time metrics and to highlight current practice patterns. It therefore provides an outline for the future development of multisociety guidelines and recommendations to improve patient selection, procedural management, and organizational strategies for revascularization therapies in acute ischemic stroke.

Diagnosis of ischemic stroke.

Early stroke management, and early initiation of secondary stroke prevention, may improve outcomes in patients with acute ischemic stroke. However, <10% of patients with acute ischemic stroke arrive at the receiving hospital within 3 hours of symptom onset. Factors such as poor public awareness of symptoms, lack of rapid detection by emergency medical services (EMS), poor coordination between EMS and the hospital emergency department, or delay of diagnosis on arrival at the emergency department are all contributing factors in the failure to provide prompt diagnosis and treatment of acute ischemic stroke. This article focuses on the critical steps in diagnosing ischemic stroke, starting at the initial patient evaluation by emergency personnel. Stroke mimics and different imaging techniques that may be used in the differential diagnosis and evaluation of acute ischemic stroke are also discussed.

Gender considerations in stroke management.

BACKGROUND: Stroke is a major cause of morbidity and mortality in the general population and especially in older women. REVIEW SUMMARY: The incidence of stroke differs between men and women of a range of ages, with a higher lifetime risk for women than men. Pregnancy and the postpartum period are times of increased risk of stroke. Use of exogenous estrogen, especially in vulnerable populations, increases stroke risk. Women and men have different responses to primary and secondary stroke prevention. Women may not be offered acute ischemic stroke treatment as frequently as men; and female stroke survivors have worse outcomes. CONCLUSIONS: Gender-related differences in stroke are attributed to the hormonal changes that women experience through their lifetime, diverse risk factors for stroke in men and women, and specific lifestyles, and comorbid conditions. Neurologists need to be aware of aspects of stroke that are particularly relevant to women.