Arteriovenous malformations and aneurysms in young women

CARDIOVASCULAR UPDATE

ARTERIOVENOUS MALFORMATIONS AND ANEURYSMS IN YOUNG WOMEN Joseph G. D’Alton,

MD

ELSEVIER

Aneurysms and arteriovenous malformations commonly present in young women after they have ruptured and caused a subarachnoid hemorrhage. Early diagnosis and treatmentis cruciaJ to achieve optimaf reduction of the high mortality and morbidity associated with this type of stroke. Patients are generally best managed in hospitaJs with appropriate neurosurgical and intensive care facilities. It is important for primary care physicians to be aware that many patients present initially with a severe headache of sudden onset and immediate maximal intensity. Misdiagnosis of this sentinel headache is not rare, but can result in an adverse patient outcome. A high index of suspicion should lead to a CT scan and, if negative, an appropriately timed Jumbarpuncture. The earlyrecognition of a “warning leak” can allow neurosurgical and other treatment modalities to prevent a catastrophic rebleed. (Prim Care Update OblGyns 1998;5:74-78. 0 1998 Elsevier Science Inc. AIJ rights reserved.)

Arteriovenous malformations (AVMs) are congenital coiled masses of arteries and veins in the brain without an intevening capillary bed. They displace rather than invade normal brain tissue and are believed to form at the third embryFrom the Division of Neurology. Metro ical Center, Framingham, Massachusetts.

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ologic week, owing to arrest of the vascular network. They account for about 1% of all strokes. Large autopsy series suggest a prevalence of between 0.04% and O.52%, and many are asymptomatic in life. Berry aneurysms occur at the bifurcation of the large arteries at the base of the brain and may rupture into the subarachnoid space of the basal cisterns. The incidence of aneurysmal rupture increases with age, with a mean age of approximately 50 years, and is more common in women. In children and adolescents aneurysms are rare, and subarachnoid hemorrhage is usually from an AVM. It is more likely caused by aneurysm rupture in patients older than age 20. Although autopsy studies suggest an aneurysm incidence of 5%, (at least 10 times more common than AVM), the frequency of aneurysm rupture is about 11 per 100,000 in the United States, with approximately 30,000 cases per year. Aneurysms are named according to the vessel of origin; in decreasing order of frequency, these are the internal carotid artery, anterior cerebral artery, middle cerebral artery, and vertebral or basilar artery.

Clinical

Features

Arteriovenous malformations may remain asymptomatic throughout life. The most common clinical presentation is hemorrhage, either parenchymal or subarachnoid.’ The former is more common and causes Inc..

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sudden onset of a focal neurologic deficit, which at onset needs differentiation from other causes of acute stroke. This initially involves making a diagnosis of hemorrhage rather than brain infarction and may be difficult on clinical grounds. Computed tomography (CT) scanning is now routinely performed in the emergency room and is 100% accurate in detecting any significant parenchymal hemorrhage. Differentiation from other causes of intracerebral hemorrhage is mandatory, particularly hypertension, trauma, bleeding diatheses, or brain tumors. At least 30% of patients with AVMs present with seizures. These may be partial, complex-partial, or generalized tonic clonic seizures. A seizure is a more common presentation between ages 11 and 20 years, and hemorrhage a more common presentation between ages 21 and 30 years. Less well documented is the association between AVMs and headaches. AIthough headache often is said to be a presenting symptom and scintillating scotomas do occur in patients with AVMs, the incidence may be no more than in the general population. Occasionally, large AVMS present with a slowly progressive neurologic deficit, such as a hemiparesis. This is a “steal syndrome,” asthe shunting of blood through the high pressure fistula results in underperfusion of the adjacent brain, leading to focal symptoms and signs. Some patients have a bruit

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Figure I. Computed tomography space (courtesy of G. Shoukimas).

scan demonstrating

detectable by auscultation over the orbit or cranium. Most aneurysms are asymptomatic prior to rupture. Occasionally, an unruptured expanding aneurysm may compress an adjacent cranial nerve or other neural structure. The most common clinical presentation is painful onset of a third cranial neuropathy, usually with pupillary involvement. This is often a prodromal syndrome prior to rupture. This contrasts with the other common cause of a painful third cranial neuropathy, diabetes mellitus, whose hallmark is pupillary sparing.

Table 1. Hunt and Hess Scale Grade 1

2 3 4 5

blood in the subarachnoid

Subarachnoid hemorrhage invariably causes sudden onset of a severe headache, qualitatively different than ever experienced by the patient previously. Intensity is maximal within a few minutes, and the pain often is described as excruciating or like a sledgehammer. About 50% of patients lose consciousness. This usually is transient, although more severe cases remain comatose.’ The headache, even when a manifestation of a small “warning leak,” always lasts for many hours or days. Difficulty in diagnosis may arise in patients with preexisting migraine. A careful history should

Neurologic

Status

Asymptomatic Severe headache or meningismus; no neurologic deficit (except cranial nerve palsy) Drowsy; minimal neurogic deficit Stuporous: moderate to severe hemiparesis Deep coma; decerebrate posturing

raise suspicion, particularly when sudden onset of a severe headache, different than a usual migraine, occurs. This is often the most severe headache ever experienced. Nuchal rigidity is usually not present for several hours and may never develop in small leaks. Subhyaloid hemorrhages are seen, with fundoscopy, only in large bleeds, often in patients with persistent impairment of consciousness. Concurrent parenchymal brain hemorrhage, with a resulting focal neurogic deficit, occurs if the high-pressure leak points into the brain substance. This usually is associated with anterior or middle cerebral aneurysms. In general, a ruptured aneurysm causes a higher pressure bleed and more serious clinical deficit than an AVM. At presentation, patients often are categorized using the grading scale of Hunt and Hess (Table 1). Patients who are grade 1 or 2 have a good prognosis, whereas the reverse is true for grades 4 and 5. About 15% of patients with a subarachnoid hemorrhage have no aneurysm or AVM detected on the initial angiogram. About two thirds have a perimesencephalic pattern of bleeding on CT scanning, and this group has an excellent prognosis. A cause has not been established, but a ruptured vein is suspected.3

laboratory

Investigations

COMPUTED TOMOGRAPHY SCANNING AND LUMBAR PUNCTURE More than 90% of patients with a subarachnoid hemorrhage will have blood evident in the basal cisterns on a CT scan done within 48 hours of onset. The scan should be done as soon as possible; it is invaluable to assess the amount and location of subarachnoid blood. A strong clinical suspicion should lead to a lumbar puncture if the CT scan is negative. The demonstration of blood,

D’ALTON clearly documented with angiography. Recently, many centers are using the less accurate but noninvasive technique of transcrania) Doppler to diagnose and follow this complication.

Prognosis and Natural History

2. Cerebralangiogramwith a large internal carotid aneurysm at the junction with the posterior communicating artery [courtesy of G. Shoukimas). Figure

which fails to clear in successive tubes, favors subarachnoid bleeding over a traumatic tap. The fluid should be immediately centrifuged, if bloody, and examined for xanthochromia, which, if present, indicates the presence of blood breakdown products and is diagnostic of recent subarachnoid hemorrhage, in the absence of jaundice or vitamin A toxicity. The timing of the lumbar puncture (LP) should be based on the fact xanthochromia often takes up to 12 hours to develop. There is nothing to be gained by doing an LP if the CT scan is positive.

MAGNETIC

RESONANCE IMAGING

Magnetic resonance imaging scanning has no advantage over CT in the evaluation of the acute patient, is often logistically difficult, and may in fact be less accurate in detecting acute bleeding. Magnetic resonance imaging or magnetic resonance angiography (MRA) may be used to electively diagnose and re-

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view the anatomy of AVMs and larger berry aneurysms, either as part of a preoperative assessment or in following patients with known lesions.

CEREBRAL ANGIOGRAPHY Selective four vessel cerebral angiography is mandatory in all young patients with a recent subarachnoid hemorrhage or in other patients with a known or suspected AVM or Berry aneurysm in whom surgery is planned. About 15% of patients have multiple aneurysms at the time of presentation, and about the same percentage have aneurysms affecting the posterior circulation. About 15% of cerebral angiograms done for subarachnoid hemorrhage will not indicate a source of bleeding. Repeat angiography in approximately 1 week will document an aneurysm in l-2% of cases. After several days, a significant number of patients with subarachnoid hemorrhage develop vasospasm with clinical deterioration, and this can be

Arteriovenous malformations have an overall Z-4% annual risk of hemorrhage, with a combined annual morbidity and mortality of approximately 3%. Risk factors for bleeding include a history of a prior bleed, ditf’use AVM morphology, and one draining vein. The cumulative lifetime bleeding risk for young patients is substantial. Between 6% and 19% of AVM patients have an associated aneurysm. The pathogenesis is believed to be either a shared congenital abnormality or an effect of high pressure flow. They do not in this situation necessarily indicate an increased risk of hemorrhage. The prevalence of unruptured intracranial aneurysms in the general population is probably between 0.5% and l%, or 2 million individuals in the United States. The annual risk of rupture is estimated at between 1% and 2%. Size appears to be the major determinant of subsequent rupture, with aneurysms of 3 mm or less at little risk, and aneurysms greater than 10 mm at greatest risk. The critical size appears to be between 5 and 7 mrns4 Once an aneurysm ruptures, the morbidity and mortality are significant. Rupture is rare in women younger than age 25, and a subarachnoid hemorrhage in this age group should raise suspicion of another cause. Many patients die before they reach the hospital, perhaps as many as 10%. For patients surviving the acute bleed the mortality in the first week is about 2 7%. Many of these patients have a combined subarachnoid and intraparenPrim

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chymal bleed. Rebleeding is a major problem in the untreated patient, affecting approximately 33% in the first month, and killing more than 40% of these individuals. The greatest risk is in the first 2 weeks. In addition to rebleeding, late deterioration may be caused by vasospasm or hydrocephalus. Vasospasm, with resultant narrowing of brain arteries, is one of the most ominous complications and causes cerebral ischemia and infarction. A high incidence occurs in patients with large blood clots in the basal cisterns on the initial CT scan. The mechanism somehow appears related to the effect of blood products on arterial smooth muscle, and it seems to develop between day 4 and day 14 after hemorrhage. Angiographic vasospasm occurs in more than 50% of patients and is symptomatic in about half. It starts between days 3 and 5 after hemorrhage, peaks between days 5 to 14, and gradually resolves over 2-4 weeks. Between 15% and 20% of symptomatic patients suffer a stroke or die from vasospasm despite optimal treatment. Acute obstructive hydrocephalus due to intraventricular blood occurs in up to 20% of patients. Communicating hydrocephalus can develop any time after subarachnoid hemorrhage, but it generally develops between days 4 and 20. It cannot be predicted and may cause no clinical change or profound stupor or coma. It is due to blockage of CSF flow by subarachnoid blood.

Effect of Pregnancy Subarachnoid hemorrhage is now the third leading cause of nonobstetric maternal mortality in the United States. The physiologic changes that occur in pregnancy, particularly the increased cardiac output, may predispose to AVM or aneurysm rupture, and both account for about equal numbers of

intracranial hemorrhage. The stresses of labor may cause elevated intracranial pressure. The peak time for aneurysm rupture is in the third trimester, whereas AVMs are more likely to bleed in the second trimester or in labor. Aneurysms rarely rupture in labor, though rebleeding is common. Hemorrhage from an AVM in pregnancy is likely to be larger, have a worse prognosis, and to recur.

Treatment Subarachnoid hemorrhage is a medical emergency, and once stabilized, patients should be transferred to a specialized unit. MEDICAL MANAGEMENT OF SUBARACHNOID HEMORRHAGE In the comatose or stuporous patient, airway protection, adequate ventilation, maintenance of the circulation, and control of accelerated hypertension take priority. An intracerebral hematoma may need emergency neurosurgical evacuation, or acute hydrocephalus aventriculostomy, if either causes acute intracranial hypertension and threatens life. Clotting disorders should be ruled out and intravenous fluids carefully managed. Hyponatremia, owing to natriuresis and volume contraction can develop, and the physician should monitor the patient for this. It is more common in people with poor clinical grades, is often seen in patients with vasospasm, and may be an independent marker of poor outcome. Treatment involves administration of isotonic fluids, avoidance of volume contraction, and hemodynamic monitoring if necessary. All patients are put on strict bedrest in a quiet, dark room, administered stool softeners, and if necessary, gentle sedation, in an effort to reduce the risk of rebleeding. Analgesics such as acetominophen or meperidine are given for headache. Heavy sedation may

MALFORMATIONS

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interfere with neurologic assessment and is avoided. Prophylactic phenytoin usually is given because although of low incidence, a generalized tonic clonic seizure might raise intracranial pressure and cause a devastating rerupture. Dexamethasone is often empirically given, although clear proof of benefit is lacking. Early cerebral angiography is preferable, as early aneurysm clipping has been shown to reduce the risk of early rebleeding and allows more aggressive management of vasospasm, if necessary. Most patients are managed in an intensive care unit initially. MANAGEMENT OF ARTERIOVENOUS MALFORMATIONS The current management4 of AVMs involves the use of microsurgery, endovascular procedures, and radiosurgery, alone or in combination, and is best done in tertiary centers where all three techniques are available. When selecting treatment in a younger patient, the location and size of the lesion determine the potential risk of major perioperative complications. In general, smaller and more superficial AVMs are surgically excised, often after preoperative embolization of feeding arteries, in an effort to reduce the size and thus make surgical excision safer and technically easier. Deep hemisphere or brainstem AVMs often are treated with focused external irradiation and the most favored technique currently is gamma knife surgery. Radionecrosis results in obliteration of the AVM in successful cases. There is often a latent interval of up to 2 years, and the risk of bleeding during this time should be considered when selecting a treatment modality. In one series, 57 brainstem AVMs were treated with gamma knife irradiation. A 2-year follow-up was obtained in 28 cases: 20 (71.4%) were completely obliter-

ated and 5 (17.9%) were subtotally obliterated.” If an AVM is diagnosed during pregnancy after bleeding has occurred, definitive surgical treatment should be considered because of the high risk of rebleeding and the overall poor prognosis. If this is not possible, elective cesarean section prior to term often is recommended because of the potential for rebleeding during labor.

SURGERY FOR RUPTURED ANEURYSM Early referral to a specialized center after aneurysm rupture is recommended. Surgical clipping of the aneurysm is the definitive treatment, and whenever possible, complete surgical obliteration is carried out. Early surgery is recommended for the good-grade patients with an uncomplicated aneurysm. For others, early or delayed surgery may be appropriate depending on the specific clinical situation. In pregnant patients, the aneurysm should be treated in the usual way. If aneurysm clipping is not possible, elective cesarean section is favored by many in the hope of reducing the risk of rebleeding. Surgical morbidity is determined by numerous factors, including the size, location, and morphology of the aneurysm, as well as the medical and neurologic status of the patient and coexistence of other complications of subarachnoid hemorrhage.

TREATMENT

OF VASOSPASM

Oral nimodipine has been shown to reduce poor outcome due to vaso-

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spasm in all grades of patients, and it is now routinely prescribed for all patients presenting with a subarachnoid hemorrhage. The improved clinical outcome occurs despite no impact on the incidence of vasospasm or vessel caliber by angiography. Drug side effects are minimal. If ischemic complications of vasospasm occur, the deficits may resolve, following elevation of blood pressure, volume expansion, and hemodilution. Only a proportion of patients respond to hypertension/ hypervolemialhemodilution, with stroke and death rates approaching 15% in the series with the best outcome.7 This therapy is associated with significant risk, including volume overload and rupture of an unsecured aneurysm; it is best administered in an intensive care unit, with appropriate hemodynamic monitoring following aneurysm clipping. Transluminal angioplasty has been successfully used to treat vasospasm refractory to other therapies. In selected patients, dramatic neurologic recovery has been associated with restoration of normal arterial caliber in about 80% of patients, and a complication rate of vessel or aneurysm rupture in only

5%.

Conclusion Modern medicine has had a major impact in the diagnosis and treatment of AVMs and aneurysms, in-

cluding those in young women. Nevertheless, the morbidity and mortality rates remain large, and ongoing vigilance and timely referral of affected individuals to a specialized unit is of the utmost importance.

References 1. Pollack B, Flickinger J, Dade L, et al. Factors that predict the bleeding risk of cerebral arteriovenous malformations. Stroke 1996;27:1-6. 2. Longstreth W, Nelson L, Koepsell T, et al. Clinical course of spontaneous subarachnoid hemorrhage. Neurology 1993;43:712-18. E. 3. Rinkel G, van Gijn J, Wijdicks Subarachnoid hemorrhage without detectable aneurysm: a review of the causes. Stroke 1992;24:1403-10. 4. Seppo J, Porras M, Heiskanen 0. Natural history of unruptured intracranial aneurysms: a long term follow-up study. J Neurosurg 1993;79: 174-82. 5. Mayberg M, Hunt B, Dacey R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. Stroke 1994;25:2315-28. 6. Steiner L, Lindquist C, Cail W, et al. Microsurgery and radiosurgery in brain arteriovenous malformations. J Neurosurg 1993;79:647-52. 7. Awad IA, Carter LP, Spetzler RF, et al. Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 1987;18: 365-72.

Address correspondenceand reprint reguests to JosephD’Alton, MD, Division of Neurology, Metro West Medical Center, 463 Worcester Road, Suite 101 1Framingham, MA 01701.

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