STROKE: ruptured intracranial aneurysms by Dr Brown

KNOW THE SIGNS, PREVENT DEATH AND DISABILITY

RUPTURED INTRACRANIAL ANEURYSMS:
MORBIDITY AND MORTALITY

Robert D. Brown, Jr., M.D.
Division of Cerebrovascular Diseases and Department of Neurology
Mayo Clinic and Mayo Foundation
Rochester, Minnesota
Boston, May 20, 1998

Introduction

Subarachnoid hemorrhage (SAH) is a type of intracranial hemorrhage in which bleeding occurs into the subarachnoid space, accounting for about 6 to 8 percent of all strokes. As the twentieth century concludes, SAH continues to be a significant cause of morbidity and mortality, with about 30,000 events in the United States each year (1), predominately affecting young adults of both sexes. While the case-fatality rates from SAH may be decreasing, approximately 30% of persons die within the first two weeks following the acute event (2), and many survivors have persistent long-term deficit. Aneurysmal rupture is the most common identifiable cause of non-traumatic SAH, far surpassing arteriovenous malformation rupture.

Advances in radiologic imaging have improved the non-invasive detection of intracranial aneurysms and arteriovenous malformations enabling delineation of a potential source of hemorrhage prior to its occurrence, yet most aneurysms are detected following rupture. Once the SAH has occurred, medical complications are aggressively treated, but morbidity from factors other than rebleeding is still common. Symptomatic vasospasm continues to be an area of evolving prevention and treatment. Other complications including electrolyte abnormalities, hydrocephalus and cardiac dysfunction and arrhythmias have also undergone intense research, yet the findings and changes in treatment have not been associated with a marked change in mortality.

Subarachnoid Hemorrhage: National History & Incidence

Numerous studies have evaluated the incidence of subarachnoid hemorrhage, short and long term outcome, and frequency of side effects. However, few studies are population-based, have consistent diagnostic criteria for the event, have comprehensive methods of case ascertainment, or adequately define the cause for the event. Many studies restrict the events based on age, or fail to evaluate the entire population.

Still others do not utilize death-certificate diagnoses which would exclude patients presenting with sudden-death or others that failed to receive medical attention following an initial warning hemorrhage with death following a recurrent hemorrhage. Despite these shortcomings, many questions regarding the natural history of SAH may be answered from available data.

Subarachnoid hemorrhage of any cause represents from 4.5 to 13 percent of all strokes. Age-adjusted incidence rates for SAH are available from numerous studies, with reported rates from 7.9 per 100,00 persons per year in Oxfordshire, England, to 15.1 per 100,000 in Helsinki, Finland. Higher incidence rates, at 21 to 25 per 100,000 have been reported in Japan. Long-term trends in SAH incidence is only available from Rochester, Minnesota population-based studies, which indicate there is essentially no change in the incidence rate of subarachnoid hemorrhage through 1989. There may be some gender-related differences, with the female incidence rate being higher than in males in some population-base studies.

The importance of endogenous and exogenous hormonal factors demonstrates a possible reduced occurrence of SAH in pre menopausal women, particularly those without a smoking history. In the same study, hormone replacement reduced the risk in post menopausal women who had never smoked (3). Racial differences have been infrequently studied, although there are data that indicate the incidence rate in the African-American population is twice that of whites (4). Age-related differences are also apparent, with SAH incidence increasing with age.

SAH Morbidity and Mortality

The short-term case-fatality rates following SAH has been determined in numerous population-based studies. In Rochester, Minnesota, 12% of patient died from SAH before reaching medical attention (2,5). Short-tem survival has been reported at 43-58% at 30 days, 43% at seven days, and 40% at 21 days. One-year survival varies from 45 to 57%. It is apparent from the similarity between the short and longer term mortality that most of the SAH deaths occur within the short-term. Long-term trends in SAH mortality indicate that mortality may be decreasing (7). Some have postulated that the decreasing mortality may be caused by falling incidence rates (2), although available data do not support this incidence rate decrease. The change in standard medical practice in the SAH patient is likely contributing significantly to this improvement in mortality rate.

There is also a significant referral bias in subarachnoid hemorrhage survival, with a 20% difference between 49 community based patients and 328 referral patients determined in one study. The Hunt and Hess grade was also different between the two groups with grade IV and V constituting 20% of referral cases and 40% of population-based cases (7).

In a study of subarachnoid hemorrhage in a United States Metropolitan area in 1988, the thirty day mortality was 45%, with 61% of cases dying within 2 days of symptom onset. The initial hemorrhage caused 21 of 22 deaths occurring with 2 days, with the other death caused by rebleeding. Nine of 14 deaths occurred after day 2, 2 caused by initial hemorrhage and 7 by rebleeding. Volume of SAH was a useful predictor of 30-day mortality (8).
In addition to age, gender, and race, numerous potentially reversible risk factors for subarachnoid hemorrhage have been evaluated. Cigarette smoking appears to be a risk factor (9).

Subarachnoid hemorrhage: Clinical Aspects

Acute onset of a generalized, severe headache is the classical presentation for subarachnoid hemorrhage, and must be recognized by all medical personnel that may be called upon to evaluate patients in an inpatient or outpatient setting. The headache usually reaches maximal severity quite quickly, may be localized to the occipital region, and usually lasts for at least 48 hours. The severe headache may also be accompanied by nausea, vomiting or a brief loss of consciousness. Nuchal rigidity of meningismus is noted in about 70% of patients. Saccular aneurysms may present with warning leak or sentinel hemorrhage, causing this sudden, severe headache, which lasts at least 48 hours. A high index of suspicion must be maintained. In one study, 41 of 182 consecutive patients with SAH presenting to a single medical centre had a delay in diagnosis, including 3 patients with repeat hemorrhage before SAH diagnosis (10). Even the classic headache history may be misdiagnosed as a cause other than SAH such as muscular-tension type headache, viral syndrome, migraine headache, malingering, influenza, and aseptic meningitis (10).

The character of presenting symptoms and frequency of warning hemorrhages have been evaluated in numerous studies. In one study of 364 patients with SAH, information about warning symptoms that may be useful in predicting clinical symptoms as a SAH before a recurrent, potentially devastating SAH was obtained. Over 20% of those patients had retrospectively collected evidence of a probable sentinel bleed, with 98% of these having headache, and others had symptoms such as nausea and vomiting, dizziness, and transient loss of consciousness.

The headache was unassociated with other symptoms in one-third of patients. Others evaluated incidence of warning headache, consequence of misdiagnosis following the warning headache and headache mechanism. The lack of clearly differentiating characteristics for the sentinel bleed related headache makes consistent recognition and correct diagnosis an ongoing challenge.

Accompanying symptoms

Transient alteration in level of consciousness occurs in nearly 50% of patients with SAH. At the time of SAH, particularly those due to saccular aneurysm, the intracranial pressure abruptly increases, approaching mean arterial pressure, leading to a reduction in cerebral perfusion pressure. The loss of consciousness typically is not followed by a headache; instead, the first complaint of headache occurs after awakening, a period of time from several minutes to days. Patients with SAH may also die before reaching medical attention. In a population based study, 13 of 113 patients with SAH died without reaching medical attention. Posterior circulation aneurysms were more frequent among those with this sudden death phenomena. The frequency of this presentation did not change during 1960-1984 (11).

Ruptured Aneurysms

Natural History

Numerous studies have evaluated the natural history of aneurysmal subarachnoid hemorrhage. It is apparent that patients may die a sudden death and never reach medical care. However, among patients that do reach medical care (12,13) it appears that the rebleeding risk is highest in the first day following subarachnoid hemorrhage (4%) and then is about 1-2% per day during the next month (13). The mortality risk for recurrent hemorrhage is about 42% (14), and a ruptured aneurysm that remains untreated and does not hemorrhage within the first six months following initial hemorrhage has a long-term hemorrhage risk of about 3%. Long-term risk of rebleeding after the first month is likely related to aneurysm size and location.

In one population based study, the probability of rebleeding among patients with Hunt and Hess grades I, II and III who survived the initial SAH to obtain medical attention, seen between 1945-1974 was 2% per day over the first 10 days and at 30 days, the total rebleed rate was slightly less than 30% (14). In the Cooperative Study, the rebleeding rate was 23% over 2 weeks, and 35% over the first month, including definite and probable rebleeds. For definite rebleeds, the rate was 15% over the first 2 weeks and 20% over the first month.

The long term risk of rebleeding has also been evaluated both in community-based studies and by the Cooperative Aneurysm Study Group. In Rochester, Minnesota, most recurrent hemorrhages occurred within 30 days, while the rebleed rate was 1.5% per year after 30 days (2,14). In the Cooperative Study, the rate was 2.2% per year between 6 months and 10 years following SAH, and 0.86% per year for the second decade. In another evaluation of 387 patients treated for aneurysmal subarachnoid hemorrhage, 44 in-hospital rebleeds occurred, including 2% on the day after admission to the hospital, 0.6% on day 2, and 0.8% on day 3. Rerupture rate then increased somewhat during the next 10 days, and another peak was noted at 4 weeks. The actuarial risk of rebleed was 23% at 2 weeks and 42% at four weeks (15).

Survival free of focal neurological deficit in patients with grade I, II, or III SAH surviving to reach medical attention, excluding isolated cranial neuropathy or altered level of consciousness alone in the first 30 days was 50%. In 21%, patients had focal deficit occurring simultaneously with SAH onset (2). Utilizing a linear discriminate analysis of SAH prognosis, three variables were found to be useful, including prior hypertension, clinical grade at first medical attention, and presence of intracerebral hematoma. Difference in prognosis based upon whether hematoma was present or absent occurred independent of history of hypertension, and hypertension predicted a higher probability of death regardless of presence of hematoma. Hunt and Hess grade at time of first medical attention also made a major impact at survival to 30 days. Clinical grade was less important among patients with hematoma because prognosis was poor compared to those without hematoma (2).

Cognition may also be affected long-term following subarachnoid hemorrhage. The occurrence of abnormalities on neuropsychological studies is dependent on the type of studies performed. Normal tests of memory and cognition have been noted, although visuospatial construction and memory, mental flexibility and psychomotor speed were decreased one year following SAH (16).

SAH Complications
Vasospasm: Introduction

A leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage is cerebral vasospasm (17). In this disorder, narrowing of the arteries at the base of the brain causes reduced blood flow distally and may lead to delayed ischemic deficit and cerebral infarction.

Arteriographic or transcranial Doppler evidence of vasospasm typically occurs about three to five days following aneurysmal subarachnoid hemorrhage, although the onset may be delayed up to 21 days. It is typically maximum from 3 - 14 days (18).
The clinical manifestations of vasospasm are quite variable. At least 50% of patients will remain asymptomatic, while 20 - 30% have some delayed neurologic ischemic deficit. These deficits may be focal, but one may also see confusion, delayed level of consciousness, and coma. Others may only manifest an increase in headache or blood pressure. Cerebral infarction occurs in about 50% of those manifesting some clinical symptoms (19).

Vasospasm Predictors

The occurrence of cerebral vasospasm following subarachnoid hemorrhage is dependent on the extent and location of subarachnoid hemorrhage as detected on computed tomography (20). It has been demonstrated that in patients with subarachnoid clots larger than 3 x 5 mm in the basilar cistern or blood more than 1 mm thick predict an increased occurrence of vasospasm. Following a retrospective study demonstrating the relationship (20), a prospective study revealed that patients could be subcategorized into four groups depending on the computed tomographic location and amount of hemorrhage. These include the Group 1 patients with no detectable blood, Group 2 patients with diffuse blood that was not dense or indicative of a large, thick clot, Group 3 with clot greater than 1 mm thick in the vertical plane (in the interhemispheric fissure, insular cistern, or ambient cistern), or greater than 5 x 3 mm in the basilar cisterns, and Group 4, intracerebral or intraventricular clots with only diffuse blood or no blood in the basilar cisterns (21). In a prospective evaluation of the patients, none of the patients with the Group 1 findings had vasospasm. However, five of 14 with diffuse subarachnoid blood (Group 2) had severe vasospasm with two manifesting clinical findings. Patients with Group 3 computed tomographic findings typically demonstrated severe vasospasm in the vessels distal to the clot or thick layer of blood. Vasospasm was predicted in 20 of 22 cases, with one of the two false positives due to a misinterpretation of clot type. In Group 4 patients, no severe vasospasm was seen. The utility of these findings applies only to computed tomography performed within 24 hours of the hemorrhage, because subarachnoid blood may dissipated following 24 hours (22).

Hydrocephalus

Acute hydrocephalus occurs in up to 20 - 67% within three days following subarachnoid hemorrhage (23).

Hydrocephalus is typically caused by alteration in cerebrospinal fluid flow due to intraventricular and subarachnoid blood with alteration of flow through the aqueduct of Sylvius, in the basal cisterns, or altered cerebrospinal fluid reabsorption at the arachnoid granulations. The diagnosis is based on decreased level of consciousness, increasing headache, and confusion. Non-contrast computed tomography then displays the ventriculomegaly.
Factors predictive of hydrocephalus were studied in the Cooperative Study which included 3521 patients, with hydrocephalus detected in 15 % of patients; 13.2% were clinically symptomatic. Factors noted to be related to hydrocephalus included increasing age (23), a history of hypertension, hypertension at admission, admission computed tomography demonstrating intraventricular hemorrhage, thick focal collection of subarachnoid blood or diffuse blood, posterior circulation aneurysm, focal ischemic status at presentation, use of antifibrinolytic druges, decreased level of consciousness at admission and hyponatremia. In another study of 660 patients following SAH, deterioration in neurologic status due to hydrocephalus was predicted by factors including presence of cisternal blood on the initial CT, hydrocephalus on initial CT, presence of intraventricular blood on initial CT, and long-term treatment with tranexamic acid (24).

Cardiac Complications

Early and late complications may occur following subarachnoid hemorrhage. At admission, the EKG may reveal altered patterns including peaked P waves, prolonged Q-T interval, heightened T waves, deep inverted T waves and S-T segment elevation or depression. The pattern may also mimic that seen in myocardial infarction, making it imperative to monitor the cardiac rhythm and rule out infarction with appropriate enzyme studies and repeat electrocardiogram. Resolution of such abnormalities following aneurysmal clipping have been reported, and pathology studies of similar patients have failed to reveal evidence of myocardial necrosis in selected cases, making it likely that coronary vasospasm lead to the syndrome of "stunned myocardium" and abnormal EKG. Other patients have demonstrated similar EKG findings and been accompanied by elevation in cardiac enzymes, typically in patients with severe subarachnoid hemorrhages. The overall frequency of EKG abnormalities is unknown, with some reporting a 100% occurrence of at least transient alterations, although usually without any associated symptoms, while others have detected an overall frequency of EKG abnormalities in those without a previous cardiac history at 44%.

Neurogenic pulmonary edema (NPE) is a rare complications of subarachnoid hemorrhage, likely also caused by an excessive sympathetic discharge. In one study of NPE, the left ventricular function was reduced on echocardiogram, but was a reversible phenomena.

 

Electrolyte alterations

Hyponatremia is the most common electrolyte abnormality following SAH, detected in 10 to 25% of cases (25), while mild hyperkalemia occurs less frequently. The degree of hyponatremia is typically relatively mild, occurring within 2 to 4 days of SAH, reaching a peak occurrence at about 7 days and then becoming less frequent. Clinical manifestations may include a decrease in level of consciousness and seizures, with delayed ischemic deficit and vasospasm reported as outcomes of previously utilized treatment with fluid restriction. The overall clinical outcome is worse in patients with hyponatremia. There are few studies available that predict which patients will develop hyponatremia, although poor clinical grade and ventriculomegaly were associated in one study.

Seizures

The frequency of seizures following subarachnoid hemorrhage is not known with certainty (26). In the early period, seizures occur between 16% and 90%. Risk factors for seizures in the early period following subarachnoid hemorrhage include previous history of hypertension, computed tomography presence of a focal intraparenchymal hemorrhage, occurrence of a cerebral infarction, middle cerebral artery aneurysm location, and duration of coma after subarachnoid hemorrhage. In one study evaluating risk factors for seizure occurring after 12 hours following the initial subarachnoid hemorrhage, risk factors for seizure in a multivariate analysis included a significant amount of cisternal blood and an aneurysmal rebleed.

Nonaneurysmal SAH

Outcome