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Cerebral Vascular Disease in Neurosurgery

Stroke is the third leading cause of death and the leading cause of disability in the United States. Stroke is currently an area of dynamic clinical and investigational interest, and our contemporary understanding of the area is rapidly evolving. The establishment of Stroke Centers for the comprehensive care of patients afflicted with cerebral vascular disease represents an exciting and relatively new advancement. The Comprehensive Stroke Center at the University of Virginia encompasses specialists in the areas of neurosurgery, neurology, radiology, anesthesiology, critical care medicine, physical medicine and rehabilitation, physical and occupational therapy, nursing, social work and neuropsychology. This team of experts is able to effectively treat patients suffering from the entire spectrum of disease of the cerebral vascular system through the orchestration of the efforts of multiple health care providers. The following discussion will review the majority of diseases commonly treated by neurosurgeons at the University of Virginia's Comprehensive Stroke Center. These diseases also represent areas of active clinical and laboratory research.

HEMORRHAGIC STROKE

Aneurysms, Vascular Malformations and Spontaneous Intracerebral Hemorrhage

I. Intracranial Aneurysms

Intracranial aneurysms represent a pathological state characterized by focal arterial dilations of the cerebral vasculature. They are most commonly situated at major branching points of the intracranial vessels as they navigate through the subarachnoid space.

Intracranial aneurysms have a propensity to spontaneously rupture, thereby giving rise to subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage (ICH). Typically, aneurysms are described by location according to the portion of the cerebral circulation from which it arises (e.g., anterior [carotid] circulation [88%-92%) vs. posterior [vertebrobasilar] circulation [8%-12%] ) and by size (small (<12 mm), large (12-25 mm) and giant (>25mm). Common locations of origin include the anterior communicating artery, posterior communicating artery, middle cerebral artery, carotid bifurcation (anterior circulation) and the basilar bifurcation (basilar tip) and posterior inferior cerebellar artery (posterior circulation). Multiple aneurysms are seen in 20% to 30% of patients. It is estimated that between 1 and 12 million Americans have intracranial aneurysms (0.5-4%), and that approximately 30,000 persons per year suffer SAH. The balance of data indicates that the risk of rupture of the asymptomatic unruptured aneurysm is approximately 1% per year. Once ruptured, aneurysms have a very high risk of early and late rebleeding. Rebleeding is often fatal and is associated with a 70% mortality rate. The risk of rebleeding is highest in the first 24 hours (4%), and then diminishes to 1-2% per day for the next two weeks. This highlights the need for prompt referral and/or treatment to allow definitive early management to prevent a devastating rebleed and to facilitate the prevention and management of cerebral vasospasm.

Aneurysms most commonly present following rupture, which produces SAH and possibly intracerebral hemmorhage (ICH). SAH is heralded by the sudden onset of headache (often described as explosive and the worst headache of my life) and signs of meningeal irritation (meningismus, photophobia, nausea/vomiting). The Hunt-Hess Scale (Table I) is used to clinically grade patients sustaining SAH. The patient's condition at presentation is the most important predictor of outcome after SAH. Aneurysms may also present secondary to mass effect and compression of adjacent structures as the aneurysm enlarges and encroaches upon neighboring regions. Additionally, aneurysms may be picked up incidentally during work-up for other reasons, such as headache or seizures, or they may rarely manifest as cerebral ischemic symptoms from embolization of intra-aneurysmal thrombus.

TABLE I - Hunt-Hess Clinical Grading Scale for Subarachnoid Hemorrhage

Patients suspected of sustaining a SAH must undergo an emergent computed tomographic (CT) study without contrast. If positive, patients should then be referred for specialized neurovascular attention, including cerebral angiography and treatment (critical care, surgery and/or coiling). If the CT scan is negative and the suspicion of SAH is still high, then a lumbar puncture should be performed. Other adjunctive tests such as CT or magnetic resonance (MR) angiography may also be performed.

Definitive treatment of intracranial aneurysms is aimed at excluding the aneurysm from the cerebral circulation with preservation of the parent artery. Exclusion of the aneurysm from the cerebral circulation by means of clip placement across the aneurysm neck surgically or with the placement of coils endovascularly, theoretically eliminates the risk of future rupture and its associated disability. Small intracranial aneurysms, in locations such as the cavernous sinus, may be managed conservatively with caution. Treatment of complications associated with aneurysmal SAH, such as seizures, cerebral vasospasm and hydrocephalus is also executed concomitantly.

Treatment at the University of Virginia is currently undertaken in cooperative fashion between neurovascular surgeons, diagnostic and interventional neuroradiologists, neuroanesthetists, neurointensivists and other specialists to allow for comprehensive and individualized treatment for each patient.

Complications after rupture of intracranial aneurysms are frequent. SAH may be complicated by cerebral vasospasm and ischemic stroke resulting from the delayed narrowing of intracranial vessels. Cerebral vasospasm typically develops three to five days post-hemorrhage, peaks after seven to 10 days and diminishes over two to three weeks. The incidence of clinical vasospasm following SAH is approximately 25% - 30%, although angiographic evidence is seen in approximately 60% - 70% of cases. The most significant predictor of the development of cerebral vasospasm following aneurysmal SAH is the amount and location of subarachnoid blood visualized by CT imaging as popularized by Fischer (Table II). Nearly 50% of patients with symptomatic vasospasm develop infarction despite therapy. Fifteen to 20% of patients with symptomatic vasospasm will develop a disabling stroke or die of progressive ischemia. Cerebral vasospasm remains the leading treatable cause of death and disability ascribed to aneurysmal SAH.

TABLE II - Fishcher Grade - Computed Tomographic Scan Classification of Subarachnoid Hemorrhage

Other complications include seizures, hydrocephalus, electrolyte abnormalities (most commonly hyponatremia) in addition to medical complications commonly encountered by critically ill patients.

II. Vascular Malformations

Contemporary understanding and treatment of intracranial vascular malformations has evolved considerably over the past three decades as significant advancements in neuroimaging, endovascular therapy, microsurgical technique and stereotactic radiosurgery have occurred.

Vascular malformations may be divided into four distinct categories each with distinctive anatomical, pathological, radiological and clinical features. The four traditional subtypes include: arteriovenous malformations (AVMs), cavernous malformations, venous malformations and capillary telangiectasias. The two most common and clinically significant are the arteriovenous and cavernous malformation and will be discussed below. Patients typically present between the second and fourth decades with these lesions (and thus are generally younger at presentation than those suffering from ruptured intracranial aneurysms).

A. Arteriovenous Malformations

AVMs are approximately one seventh to one tenth as common as cerebral aneurysms with between 2,500 to 3,000 new cases presenting each year. An estimated 280,000 patients are afflicted with AVMs in the United States.

The natural history of AVMs is incompletely understood. The annual risk of hemorrhage is noted to be 4% and 2% for symptomatic and asymptomatic AVMs, respectively. Each hemorrhagic episode appears to be associated with a 20% risk of major neurologic morbidity and a 10% mortality. There is an increased risk of rupture with smaller malformations, AVMs with associated aneurysms, a single draining vein, deep venous drainage or venous stenosis.

AVMs most frequently present as a consequence of hemorrhage in patients in their third and fourth decades. Unlike with rupture of cerebral aneurysms, early rebleeding (within two weeks) and cerebral vasospasm is rare in association with rupture of AVMs because hemorrhage secondary to AVMs is predominantly located intraparenchymally, rather than within the subarachnoid space. Seizures are the second most common presentation of patients with AVMs being noted in 11% - 33% of cases. Additionally, patients may present with the new onset of headache (from stretching of the dura, elevated venous pressure or from hydrocephalus) or progressive neurological deficit or cognitive decline (from arterial steal or venous hypertension). Cerebral angiography remains the gold standard for diagnostic evaluation of putative AVMs. It provides detailed information regarding the configuration and vascular dynamic properties (such as flow rate, arterial steal/venous hypertension and collateral flow). Magnetic resonance (MR) imaging and computed tomographic (CT) imaging are also useful adjuncts.

Comprehensive management of patients harboring AVMs involves three main therapeutic modalities: endovascular therapy, microsurgery and stereotactic radiosurgery. Endovascular therapy, applying catheter administered materials for embolization, is a useful adjunct to microsurgery and stereotactic radiosurgery to diminish the degree of arterial shunt. Embolization is rarely curative alone, however. In younger patients possessing superficial lesion in noneloquent areas, microsurgery is clearly the treatment of choice. Microsurgery is also more effective than radiosurgery in ameliorating symptoms of patients with intractable epilepsy and headaches. Stereotactic radiosurgery is reserved for patients with small (< 3 cm), unruptured AVMs in eloquent brain substance with deep venous drainage.

Stereotactic radiosurgery invokes vascular injury and produces delayed thrombosis after months to years. Thus, protection from hemorrhage imparted from radiosurgery is delayed unlike with surgery. Benefits of radiosurgery diminish and adverse effects (damage to adjacent parenchyma) increase as the size of the lesion increases. Radiosurgery may be a viable option for the treatment of deep, residual AVMs after attempted microsurgical resection. At the University of Virgnia, the treatment of AVMs is individualized on the clinical and radiologic characteristics of the single case and incorporates all of these treatment modalities alone or in various combinations.

B. Cavernous Malformations

Cavernous malformations are benign tumors of blood vessels and represent a lobulated collection of dilated endothelial-lined sinusoidal spaces. A familial tendency has been noted in certain instances. Clinically significant hemorrhage is thought to have an annual incidence of 1% to 4.5% in asymptomatic and symptomatic lesions, respectively. Seizures are the most common manifestation of supratentorial cavernous malformations. Surrounding hemosiderin and gliosis is thought to account for the epileptogenicity. Symptomatic hemorrhage is the next most common presenting scenario followed by headaches. Additionally, cavernous malformations are frequent incidental findings on radiographic studies for other indications. Cavernous malformations are angiographically occult lesions and are best seen with MR imaging. With MR imaging, cavernous malformations appear as a central focus of mixed signal intensity representing hemorrhage of various stages (popcorn-like) surrounded by a hypointense rim of hemosiderin from multiple micro-hemorrhages. Cavernous malformations that are asymptomatic are not generally treated because of their low risk of hemorrhage (~ 1 % / year). Microsurgical resection is indicated for supratentorial lesions that present with hemorrhage or that are associated with medically intractable epilepsy or headaches. Brainstem cavernous malformations are considered for surgical resection when there is repeat hemorrhage, progressive neurological deficit and superficial location. Surprisingly and inexplicably, these do not appear to be amenable to radiosurgery and such treatment is frequently complicated by a high incidence of radionecrosis.

III. SPONTANEOUS INTRACEREBRAL HEMORRHAGE

Spontaneous intracerebral hemorrhage (ICH) is defined as hemorrhage occurring in the absence of trauma. It is relatively common and may result from a myriad of causes. The majority of ICH is related to hypertension and is typically seen in specific regions, such as the basal ganglia, thalami, pons and cerebellum. Other more common causes include cerebral amyloid angiopathy, hemorrhagic transformation of infarction, tumors, anticoagulation, drugs such as cocaine, aneurysms and AVMs. Clinical suspicion coupled with confirmatory imaging studies makes the diagnosis.

Neurosurgeons at the University of Virginia are involved in the care of all patients admitted with ICH. Acute treatment in the intensive care unit is aimed at stabilization, and subsequent subacute and chronic treatment is undertaken for rehabilitation and treatment of underlying disorders. Patients are managed by aggressive medical treatment and with surgery in selected instances in which patients become refractory to medical management. Surgery may entail a hemicraniectomy to allow expansion of the swelling brain and to prevent dangerous herniation, ischemia, and potentially death) with or without evacuation of the underlying hematoma. Other specialists are also involved in the provision of care.

ISCHEMIC STROKE

Ischemic stroke is much more common than hemorrhagic stroke (85% vs. 15%, respectively). Neurosurgeons are frequently involved in the prevention and treatment of this most common and potentially devastating condition.

Unequivocal data have accrued to indicate that carotid endarterectomy (CEA) is beneficial in patients with high-grade, symptomatic carotid stenosis. Furthermore, CEA may be beneficial in asymptomatic patients with high-grade carotid stensosis as well. Neurosurgeons at the University of Virginia have a large experience in the care of patients with carotid artery disease. Patients referred for neurosurgical treatment receive maximal medical therapy and management of cardiovascular risk factors, in addition to receiving surgical treatment as indicated. Such treatment is undertaken as a team with stroke neurologists.

Neurosurgeons may also become involved in the care of patients with recurrent cerebral ischemia and evolving or completed infarction. A specific subset of patients with cerebral ischemia refractory to medical therapy may benefit from surgical revascularization. Such procedures may include extracranial to intracranial (EC-IC) bypass or intracranial bypass. In patients with limited cerebral vascular reserve capacity, the augmentation of cerebral blood flow may be efficacious in ameliorating symptoms of ischemia.

Neurosurgeons may also become involved with cerebral infarction when aggressive measures to treat and monitor intracranial pressure (ICP) are necessary. Neurosurgeons commonly place ICP monitors (extraventricular drains or intraparenchymal monitors) for observation and/or treatment of raised ICP. Additionally, neurosurgeons may perform hemicraniectomies to relieve pressure acutely. The bone may be replaced at a later time as the infarction evolves and edema abates.

CONCLUSION

Disease of the cerebral circulation is both rampant and of formidable significance in contemporary society. The care of patients afflicted withcerebral vascular disease is evolving towards a multidisciplinary effort incorporating the special skills and interests of multiple healthcare providers. Comprehensive Stroke Centers are now capable of treating patients suffering from the full gamut of cerebral vascular disease in a comprehensive and coherent fashion. The University of Virginia's Comprehensive Stroke Center is one such example of a dynamic program dedicated to patient care, research and education.

Aaron S. Dumont, M.D., asd2f@virginia.edu

Giuseppe Lanzino, M.D., gl3h@virginia.edu

Neal F. Kassell, M.D., nfk8g@virginia.edu