Seminars in Cerebrovascular Diseases and Stroke最新文献

Cerebrovascular disease, in particular stroke, is a common complication in cancer patients, secondary in incidence only to brain metastases. Autopsy studies suggest that a substantial proportion of strokes in these patients is overlooked in the clinical setting. In general, the clinical presentation of stroke in cancer patients and in nononcologic patients is similar. Embolic focal cerebral ischemia is the most frequent type of stroke with a reported ratio of approximately 55%, which is substantially lower than the ratio of approximately 80% in the general population. The underlying malignancy influences the proportion of embolic versus hemorrhagic stroke. The most common cause of stroke in cancer patients is nonbacterial thrombotic endocarditis (NBTE), a noninfectious type of endocarditis characterized by sterile fibrin vegetations. Other common causes, in the order of frequency, include tumor-induced coagulopathy, atherosclerosis, modification of blood viscosity, and therapy-induced stroke. There is no general agreement whether cancer is an independent risk factor for stroke such as traditional risk factors like hypertension or smoking. The challenge to the clinician is to elaborate whether the stroke is specifically related to cancer or whether it is due to vascular comorbidity like in the general population. The treatment of stroke in cancer patients is usually similar to the treatment of stroke in the general population, except for the treatment of the underlying malignancy if applicable.

Stroke is a heterogeneous syndrome caused by multiple etiologies. Heritable defects in connective tissue cause a small fraction of ischemic and hemorrhagic stroke. They are the consequence of mutations in genes encoding extracellular matrix constituents such as collagens and proteoglycans. Ehlers–Danlos syndrome, Marfan’s syndrome, osteogenesis imperfecta, and pseudoxantoma elasticum are the most common disorders responsible for cerebrovascular manifestations. Neurofibromatosis and polycystic kidney disease, although not connective tissue disorders, are hereditary diseases with a high prevalence of vascular complications. Ehlers–Danlos syndrome type IV is the most frequent and most life-threatening form due to the presence of intracranial aneurysms, carotid-cavernous fistulas, and arterial dissections. Marfan’s syndrome has a typical phenotype associated with arterial dissections and intracranial aneurysms. Osteogenesis imperfecta, although infrequent, can present with aneurysms, dissections, fistulas, and stenosis of cerebral vessels. Pseudoxanthoma elasticum is commonly associated with occlusive disease of small vessels and other complications such as aneurysms or arteriovenous malformations. Autosomal–dominant polycystic kidney disease is a common cause of multiple intracranial aneurysms. Neurofibromatosis type 1 is characterized by multiple neurofibromas; it is responsible for stenosis or occlusions of intracranial arteries and vascular malformations. These vasculopathies are associated with a relatively high prevalence of cerebrovascular disease; their early recognition should help in the investigation of asymptomatic carriers, and to provide genetic counseling. The growing knowledge of molecular biology could help in the understanding of the underlying mechanism of these complex disorders as well as identify future therapeutic interventions.

Immune mediated systemic disorders may involve the cerebral blood vessels and cause brain ischemia or hemorrhage. Pertinent causes of stroke associated with immune disorders include cardioembolism due to direct involvement of the heart and its valves by the underlying disorder, vasculopathy and a hypercoagulable state related to the primary disorder, frank vasculitis of the cerebral blood vessels, and an increased rate of atherosclerotic changes in the cerebral vasculature secondary to other organ involvement by the primary disease process. It is extremely important to define the exact pathology involved as treatment options vary. Despite the fact that brain involvement is associated with unfavorable prognosis in many of these disorders, prevention of further cerebrovascular events is a feasible goal in most. Furthermore, specific therapy aimed at the cause of the disease (eg, immunosuppressive therapy in giant cell arteritis) results in greatly improved survival rates in certain disorders.

Transcranial Doppler (TCD) is currently used in monitoring subarachnoid hemorrhage, acute stroke, and carotid endarterectomy and in diagnosing intracranial vascular disease. In this article we review other uses of TCD, in systemic conditions related to ischemic stroke. Transcranial Doppler, in fact, can identify right-to-left shunts (RLS), usually due to patent foramen ovale (PFO), a risk factor for cryptogenic stroke in the young. Recently an association between RLS and migraine with aura has been reported; migraine is a risk factor for stroke, for silent brain infarctions, and for silent white matter disease, but there are no data yet on a similar risk for the association of migraine plus PFO. TCD can also be used to stratify the risk of stroke in children with sickle cell disease, to better identify subjects to be transfused to prevent strokes.

Dural arteriovenous shunts comprise 10% to 15% of intracranial vascular malformations. Their pathophysiology is complex and their natural history has only recently been adequately elucidated. High-grade dural arteriovenous shunts (those with cortical venous reflux) are associated with a 6.9% annual incidence of nonhemorrhagic neurologic complications, a 8.1% annual incidence of intracranial hemorrhage, and a 10.1% annual mortality rate. This article provides an overview of the imaging, workup, and indications and latest techniques for endovascular treatment of dural arteriovenous shunts. Treatment efficacy and complication rates are also discussed.

Cerebrovascular disease in AIDS is rare. Ischemic infarcts are more common than intracerebral hemorrhages and are generally due to nonbacterial thrombotic endocarditis or concomitant opportunistic CNS infections.

Recent advances in understanding of angiogenesis and vascular remodeling have been shedding a new light into pathophysiology of vascular malformations in the brain, and new treatment strategies have been emerging. Generally, vascular malformations in the brain include cerebral arteriovenous malformations (AVMs), cavernous malformations, and dural arteriovenous fistulae (DAVF). Although their genesis is not well understood, there is a growing evidence suggesting that some of these lesions undergo active angiogenesis and vascular remodeling in the adult life. This new concept—active angiogenesis and vascular remodeling in intracranial vascular malformations—is opening a new clinical paradigm in which pharmacological interventions are proposed to stabilize these abnormal blood vesels and prevent further growth or hemorrhage.

Dural arteriovenous fistulas (DAVFs) represent important, often misdiagnosed causes of neurological dysfunction. Because these lesions do not always present with “stroke-like” syndromes, the vascular etiology of some DAVF symptoms may not be recognized. In addition, DAVFs cause focal neurological dysfunction remote from the location of the nidus, which also leads to diagnostic confusion. Noninvasive neuroimaging has made diagnosis easier, but neurologists must maintain a high index of suspicion to avoid overlooking these treatable lesions. This article reviews the pathophysiology and clinical presentations of DAVFs affecting the eye, spinal cord, and brain.