Aneurysmal Subarachnoid Hemorrhage
Diagnosis and Treatment
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Background: Aneurysmal subarachnoid hemorrhage (SAH) is associated with a mortality of more than 30%. Only about 30% of patients with SAB recover sufficiently to return to independent living.
Method: This article is based on a selective review of pertinent literature retrieved by a PubMed search.
Results: Acute, severe headache, typically described as the worst headache of the patient’s life, and meningismus are the characteristic manifestations of SAH. Computed tomography (CT) reveals blood in the basal cisterns in the first 12 hours after SAH with approximately 95% sensitivity and specificity. If no blood is seen on CT, a lumbar puncture must be performed to confirm or rule out the diagnosis of SAH. All patients need intensive care so that rebleeding can be avoided and the sequelae of the initial bleed can be minimized. The immediate transfer of patients with acute SAH to a specialized center is crucially important for their outcome. In such centers, cerebral aneurysms can be excluded from the circulation either with an interventional endovascular procedure (coiling) or by microneurosurgery (clipping).
Conclusion: SAH is a life-threatening condition that requires immediate diagnosis, transfer to a neurovascular center, and treatment without delay.
Acute subarachnoid hemorrhage (SAH) is a serious condition that affects not just the brain, but multiple other organ systems as well (1). Despite a steady reduction of mortality from acute SAH in recent years, from over 50% to approximately 35%, this entity is still associated with considerable morbidity and mortality (1, e1–e13). Ten to 25 percent of all patients with acute SAH die immediately after the bleed or before arrival at the hospital (e6). Approximately one-third ultimately remain permanently dependent on nursing care, and only 30% are able to return to independent living (1). The clinical outcome depends on multiple factors, including the severity of the acute bleed, the patient’s initial condition, the presence or absence of early rebleeding, and the presence or absence of delayed cerebral ischemia (DCI). Pulmonary and cardiac complications are also prognostically relevant (2).
Continual refinement of neurosurgical methods—in particular, the introduction of microsurgical operative techniques—has led to steady improvement in surgical outcomes (3). In addition to the operative treatment of aneurysms (clipping), an alternative method of treatment was developed by Guglielmi and others, in which the aneurysm is closed from within by the endovascular application of tiny metal spirals (coiling). This has now become a standard treatment: at present, 50–85% of all saccular intracranial aneurysms can be treated by the endovascular route. Over the period 2002–2008 alone, the rate of endovascular treatment of aneurysms rose from 17% to 58% (4).
Readers of this article should become able to:
- recognize the clinical manifestations of acute SAH and the significance of accompanying manifestations in organs other than the brain,
- know the specific diagnostic evaluation that is needed to confirm the presence of acute SAH, and
- know the specific initial therapeutic measures that must be taken once an acute SAH has been diagnosed.
The incidence and causes of subarachnoid hemorrhage
The incidence of acute SAH has been estimated at 2–22 cases per 100 000 persons per year, and 60% of all acute subarachnoid hemorrhages arise in persons aged 40 to 60 (1, e6). This implies that a general practitioner can typically expect to see a patient with acute SAH perhaps once in every 7 or 8 years (e6).
The most common cause of basal acute SAH is a ruptured cerebral aneurysm. “Basal” means that the blood is most prominently seen in the basal cisterns. In the alternative situation of an acute perimesencephalic SAH, the blood is distributed around the midbrain; cortical acute SAH, on the other hand, is usually due to trauma. Intracranial aneurysms are now held to be acquired rather than congenital lesions (e6−e10). Their prevalence is approximately 2% (range, 1–6%). Their cause is unknown. 90% of all cerebral aneurysms are less than 1 cm in size and have a relatively low risk of bleeding (5). If a patient with acute basal SAH undergoes cerebral angiography and no aneurysm is found, repeated angiography is recommended within 10 days. Acute SAH in which no aneurysm can be demonstrated by angiography is due either to an event belonging to the class of perimesencephalic SAH, or else to a ruptured aneurysm that has subsequently become filled by thrombus and thus temporarily cannot be seen. Rarer causes include pathological vascular changes such as an arteriovenous malformation or fistula, vasculitis, arterial dissection, venous thrombosis, a tumor, or drug abuse (e6).
80–90% of all cerebral aneurysms are located in the anterior circulation of the brain (the internal carotid artery, the anterior and middle cerebral arteries, and their branches) and only 10–20% in the posterior circulation (the vertebral, basilar, and posterior cerebral arteries and their branches). Unruptured aneurysms are usually asymptomatic, yet in 5% of cases they can give rise to epileptic seizures or, if large, to a thromboembolic event or a neurologic deficit due to mass effect (e.g., an oculomotor nerve palsy).
The mechanisms leading to aneurysm rupture are only partly known. Numerous intrinsic and extrinsic factors have been identified, including the size, location, configuration, surface characteristics, and hemodynamic features of the aneurysm (6–13, e11–e23). Moreover, the known cardiovascular risk factors, such as arterial hypertension and cigarette smoking, and alcohol abuse have been found to promote the progressive increase of aneurysm size, finally leading to rupture (14, e13–e15).
Neurologic manifestations and classification
The main clinical feature of acute SAH is a very severe headache of sudden onset (often described as the worst headache of the patient’s life). Both the severity and acute onset of the headache are highly characteristic of SAH (e6). Patients who already suffered from chronic headache before having their SAH often state that the pain is of an entirely different nature and intensity. This is important, as such patients are in danger of having their headache misdiagnosed as, for example, a migraine attack. Acute SAH is also often associated with signs of meningeal irritation (meningismus, photophobia), signs of intracranial hypertension (nausea and vomiting, decline of consciousness ranging to coma), epileptic seizures, and focal neurologic deficits (1). The latter usually reflect cranial nerve dysfunction, intraparenchymal bleeding, or focal ischemia (e6).
Two different clinical schemes for the severity of acute SAH are now in use in Germany, namely, the Hunt and Hess classification (Table 1) and the World Federation of Neurosurgical Societies (WFNS) classification (9, 10).
Acute SAH impairs not only the perfusion and the function of the central nervous system, but also multiple other organ systems as well.
Approximately 10% of patients with acute SAH have intraocular hemorrhages. In most cases, these are small, linear, preretinal subhyaloid hemorrhages near the optic disc. Severe preretinal hemorrhages can extend into the vitreous body (Terson syndrome [e6]).
Cardiac complications are also very commonly seen after acute SAH. Cardiac manifestations reflect a disturbance of the physiological link between the nervous system and the heart: elevated catecholamine secretion after acute SAH can lead to myocardial necrosis and myocardial dysfunction. More than 90% of all patients with acute SAH have ECG abnormalities, and these can be very hard to distinguish from those of an acute myocardial infarction. Ischemic signs (ST elevation) are seen, as well as arrhythmias and prolongation of the QT segment.
These ECG changes may be attributed to a primary cardiac problem rather than an underlying acute SAH when the patient is initially seen in the emergency room, and there is thus a danger that the diagnosis of SAH will be overlooked (15, 16, e24). Excessively elevated catecholamine secretion after acute SAH can also cause pulmonary hypertension and pulmonary edema, leading to increased mortality (14–16).
Electrolyte disturbances are another common finding after acute SAH, arising in approximately 30% of patients. The cause can be either cerebral salt-wasting syndrome or the syndrome of inappropriate ADH secretion (SIADH, also called Schwartz–Bartter syndrome) (15, 16, e24). Salt-wasting syndrome is characterized by hyponatremia with excessive loss of fluid and sodium in the urine, with resulting hypovolemia and an elevated risk of vasospasm. SIADH, on the other hand, is characterized by euvolemic hyponatremia.
Initial diagnostic imaging studies
Severe headache of sudden onset combined with meningismus is the clinical hallmark of acute SAH. The diagnostic method of choice for demonstrating the presence of blood in the subarachnoid space is computed tomography (CT) of the head without intravenous contrast medium: this reveals blood as a hyperdense signal in the basal cisterns (and, if present, in the ventricular system and brain parenchyma). Within the first few hours after an acute SAH, CT has nearly 100% sensitivity and specificity for the detection of blood in the subarachnoid space; if the CT is negative, an acute SAH is practically ruled out in most cases (eFigure 1a) (17, e25–e27). Rarely, however, an acute SAH can involve only a “minor leak,” i.e., the entrance of such a small quantity of blood in the subarachnoid space that it cannot be detected by CT; if clinical suspicion warrants, a lumbar puncture should be performed (e6). Because CT becomes less sensitive for acute SAH over time, patients who present at longer latencies after the bleed also need a lumbar puncture to establish the diagnosis (17, e6). The so-called three-glass test has often been described as a method of distinguishing an acute SAH from bleeding caused by the puncture itself (a “traumatic tap”), but its reliability is debated. CSF spectrometry for the detection of bilirubin and CSF cytology for the detection of siderophages can be used to detect SAH even weeks after the event. A lumbar puncture is also useful in some cases to help rule out major differential diagnoses that may themselves be life-threatening, e.g., meningitis (18). Magnetic resonance imaging (MRI) with multiple sequences in combination seems to be more sensitive than CT (19). If the CT is negative, it may be reasonable to perform an MRI as the next test. Nonetheless, MRI is not used routinely in the diagnostic evaluation of acute SAH (in contrast to acute cerebral ischemia), because it tends to be both logistically cumbersome and hard to interpret (20).
The gold standard for the detection of cerebral aneurysms as the source of bleeding in a basal acute SAH is digital subtraction angiography (DSA) (e25) (eFigure 1c–e), which enables good visualization of the site and configuration of the aneurysm, its ingoing and outgoing vessels, and its relation to the nearby vasculature. The important information that it provides serves as the basis for the planning of definitive treatment to secure the aneurysm. DSA carries a small risk of aneurysmal rebleeding (ca. 1–2%) as well as of new neurologic deficits (1.8% [e6]). CT angiography may be a reliable and sensitive alternative to DSA in some situations (e25) (eFigure 1b). Particularly when surgical intervention is urgently needed, as in patients with massive bleeding and signs of cerebral herniation, DSA should be dispensed with in favor of CT angiography. As long as the patient’s situation is not immediately life-threatening, however, DSA remains the imaging modality of choice, and CT angiography should not be substituted for it.
Early pathophysiological changes and complications
The early pathophysiological changes and complications after acute SAH are distinct from those that arise in the patient’s later course (i.e., from the third day onward). These early changes are designated by the term “early brain injury.” Immediately after an aneurysm ruptures and blood extravasates into the subarachnoid space, the intracranial pressure rises precipitously—sometimes to values above the diastolic blood pressure, up to 100 mmHg, blocking further extravasation (21–23, e29–e49; for further information, see also e50, e52–e55, e57). As a rule, the intracranial pressure falls again within a few minutes, though usually not all the way back to the level that prevailed before the bleed.
Acute hydrocephalus, an intracerebral or (less commonly) subdural hematoma, and generalized cerebral edema are treatable further sequelae that can cause acute—and, often, potentially reversible—neurologic impairment in patients with acute SAH. A second acute SAH due to rebleeding of a ruptured aneurysm that has not yet been secured by clipping or coiling is a further clinically significant early complication (15% in the first 24 hours) (1, 15, e6). Aneurysmal re-rupture and second bleeds are associated with a mortality of 70–90%.
Acute SAH is a life-threatening condition that is often incorrectly diagnosed at first, despite its characteristic clinical presentation; precise figures on misdiagnosed SAH are unavailable (23). Attention must be paid to meningismus, a common accompaniment of SAH. While patients who sustain a severe SAH and present with impaired consciousness generally undergo the appropriate diagnostic studies immediately, those with less severe hemorrhages can present diagnostic difficulties. In particular, in patients who already have a history of frequent headaches of a specific type (such as migraine, cluster headache, or cervicogenic headache), acute SAH may be mistakenly omitted from the differential diagnosis. The management of patients with acute SAH in the period before the source of the bleeding has been secured is aimed at preventing life-threatening complications and second bleeds, and thereby minimizing further damage to the brain (Figure 1, Table 2). Second bleeds in the first 24 hours often arise in association with transport and medical interventions; it is nonetheless clear that patients whose consciousness is impaired should be transferred to a neurovascular center as soon as possible, because any delay worsens the prognosis (23). All patients with acute SAH should immediately be taken to such a center (i.e., a hospital where specialized units for neurosurgery, neurology, and neuroradiology are present and have experience treating patients with aneurysmal SAH). Lieshout et al. showed in 2016 that delayed transport to a neurosurgical center, with prolongation of the interval from the onset of SAH to arrival in the center, significantly worsens mortality (23). Delayed transport is often accounted for by initial presentation to a hospital without a neurosurgical service, or else by an initial misdiagnosis (23). Patients with acute SAH initially misdiagnosed as suffering from coronary heart disease (CHD) suffered up to 75% mortality because of the time wasted in ruling out CHD (23). Until the aneurysm has been secured by clipping or coiling, the patient’s vital signs must be continuously monitored (with continuous recording of blood pressure and, in some cases, ECG), and the neurological status must be documented at close intervals as well (state of consciousness, Glasgow Coma Scale, pupillary responses, and any focal neurologic deficits). Rapid neurological, and possibly systemic, deterioration can occur at any time.
Because aneurysmal re-rupture carries a 70–90% mortality, all risk factors that can promote re-rupture need to be thoroughly addressed (7). Blood pressure control is particularly important: high blood pressure and rapid increases of blood pressure must be avoided. Keeping the systolic blood pressure below 140 mmHg is recommended (20). Absolute blood pressure may, however, be less important than relative increases in comparison to the patient’s usual premorbid blood pressure level. Suitable drugs for blood pressure control after acute SAH include urapidil, clonidine, and calcium antagonists. Sodium nitroprusside is not recommended, as it may raise the intracranial pressure (20). In addition to balanced blood pressure management, potential stress factors must be removed or treated, i.e., pain, agitation, and anxiety must be dealt with effectively. For this reason, the indication for any potentially painful procedure, such as arterial and central venous line placement, in an unsedated patient should be carefully considered. In a neurosurgical center, progressively worsening hydrocephalus and the accompanying rise in intracranial pressure can be effectively treated by the insertion of an external ventricular or lumbar drainage system. Life-threatening intraparenchymal or subdural hematomas require immediate neurosurgical evacuation; because of the risk of intraoperative aneurysm rupture, such procedures should only be performed by a neurosurgeon with adequate expertise in vascular neurosurgery.
Securing the aneurysm—clipping or coiling?
The most effective way to prevent a second acute subarachnoid hemorrhage is to exclude the source of bleeding from the circulation. Securing ruptured cerebral aneurysms as early as possible has been shown to lessen mortality (24–26). In particular, securing the aneurysm by the second day after the SAH seems to yield better outcomes than doing so at later times (15, 24, 27).
The surgical treatment of cerebral aneurysms originated with Walter E. Dandy in 1937 and has been steadily refined ever since (28). The aneurysm is closed off from its parent vessel by the placement of a metal clip to occlude its neck (eFigure 2). As an alternative to open surgery, a method of endovascular interventional treatment has been developed in which the aneurysm is occluded from within by the placement of platinum spirals (coils) inside it (29, 30). Figure 2 shows the endovascular treatment of an aneurysm of the posterior cerebral artery by stent implantation and coiling.
The choice of the optimal method for securing intracranial aneurysms is a topic on which there has been much discussion. Interdisciplinary consideration of each individual case by experts in both procedures, i.e., neurosurgeons and endovascular neuro-interventionalists, is essential and constitutes the current standard.
Endovascular interventional treatment is now considered the standard approach for aneurysms of the posterior circulation (particularly basilar tip aneurysms) because of the relatively high risk of surgical complications in these patients (31).
The surgical and endovascular interventional methods of securing aneurysms after acute SAH have now been compared in four prospective randomized and controlled trials and in numerous prospective and retrospective cohort studies. Two trials play a particularly important role, the International Subarachnoid Aneurysm Trial (ISAT) and the Barrow Ruptured Aneurysm Trial (BRAT) (3, 31, 32). The findings of these two trials, as well as of meta-analyses, suggest that interventional treatment yields a significantly better clinical outcome 1 year later. This advantage seems to lessen on longer follow-up, however, as the reperfusion and rebleed rates of coiled aneurysms are apparently higher than those of surgically clipped aneurysms.
In conclusion, both surgical clipping and interventional coiling are now well-established methods for the treatment of cerebral aneurysms.
Late pathophysiological changes and complications
Beyond the time frame for so-called early brain injury, further important pathophysiological changes can arise from the third day after SAH onward. Cerebral vasospasm was at one time held to be responsible for late cerebral hypoperfusion and for ensuing neurological decompensation and poor clinical outcomes. The concept of cerebral vasospasm as the main factor leading to poor outcomes in patients with acute SAH has been called into question, however, now that multiple clinical trials (e.g., the CONSCIOUS-1 trial) have shown that a decrease in the incidence of cerebral vasospasm is not necessarily accompanied by a corresponding improvement in outcome. The complex syndrome of delayed cerebral hypoperfusion and neurological decompensation is now called delayed cerebral ischemia (DCI) (33–35, e51, e57–e80).
DCI can manifest itself clinically as gradual neurological deterioration over the course of several hours, as a decline in the state of consciousness (a drop of more than 2 points on the Glasgow Coma scale), or as a focal neurologic deficit of acute onset (e.g., hemiparesis, aphasia, apraxia, or neglect).
Specific pharmacotherapy for DCI consists mainly of the administration of dihydropyridine L-type calcium channel blockers (e77–e84). These are the only drugs in routine clinical use with demonstrated efficacy in the prevention and treatment of DCI (e77–e84). DCI that arises or persists despite the administration of calcium channel blockers can be treated by induced hypertension with sustained elevation of the systolic blood pressure. Additionally induced hypovolemia, or what has been called triple-H therapy (hypervolemia, hypertension, and hemodilution), yields no further clinical advantage (20, e80).
Long-term complications and clinical outcomes
Approximately 30% of all patients with aneurysmal SAH develop hydrocephalus, reflecting disturbed circulation of the cerebrospinal fluid (CSF), at some time in the course of their disease and go on to require a permanent CSF diversion procedure. The long-term incidence of a second SAH within 10 years of the first one is 2–3%. One-half of these rebleeds are due to reperfusion and rupture of the treated aneurysm, and the other half to rupture of a new aneurysm (36, 37, e6). Thus, patients should routinely undergo regular follow-up examinations and imaging studies, as there is otherwise no way to assess the risk of rebleeding.
Not all patients return to normal everyday living in the aftermath of an acute SAH. Permanent deficits are common (e6). Approximately 30% develop permanent anosmia (e6). Most patients suffer from markedly impaired quality of life over the short term. 60% report personality changes, more than a third complain of increased irritability, and one-quarter complain of emotional lability (e6). One in 14–20 patients develops epilepsy. Overall, only 25% of the patients who are able to resume their previous everyday routine are psychologically and neurologically asymptomatic (e6).
Conflict of interest statement
The authors state that no conflict of interest exists.
Translated from the original German by Ethan Taub, M.D.
Manuscript received on 29 August 2016; revised version accepted on 28 November 2016.
PD Dr. med. Athanasios K. Petridis
40225 Düsseldorf, Germany
For eReferences pleaser refer to:
Department of Diagnostic and Interventional Radiology, Düsseldorf University Hospital: Prof. Dr. med. Turowski
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