A subarachnoid hemorrhage (SAH) is a life-threatening type of hemorrhagic stroke characterized by bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain—often resulting from the rupture of a cerebral aneurysm or trauma, and requiring immediate medical intervention to prevent severe complications or death.[1][2] This condition accounts for approximately 5% of all strokes and has an incidence of 6-10 cases per 100,000 people annually worldwide, with higher rates in women and individuals aged 40-60 years.[3][1][4]The most common cause of nontraumatic SAH is the rupture of an intracranial aneurysm, responsible for about 85% of cases, while other etiologies include arteriovenous malformations, vasculitis, or rare conditions like bleeding disorders or tumors.[1][2] Risk factors encompass both modifiable elements, such as hypertension, smoking, excessive alcohol use, and cocaine abuse, and non-modifiable ones, including family history of aneurysms, connective tissue disorders like Ehlers-Danlos syndrome, and female sex, particularly in postmenopausal women.[4][2] Pathophysiologically, the hemorrhage leads to increased intracranial pressure, potential cerebral ischemia from vasospasm, and inflammation that can exacerbate vessel wall weakening.[1]Clinically, SAH typically presents with a sudden, explosive "thunderclap" headache described as the worst of one's life, often accompanied by nausea, vomiting, neck stiffness, photophobia, seizures, altered consciousness, or focal neurological deficits.[4][2] Diagnosis involves urgent non-contrast CT imaging to detect blood, followed by lumbar puncture if initial scans are negative, and vascular imaging like CT angiography or digital subtraction angiography to identify the source.[1][5]Treatment prioritizes stabilization of vital signs, including blood pressure control and seizure prevention, followed by definitive intervention to secure the aneurysm through surgical clipping or endovascular coiling.[5][2] Medications such as nimodipine are administered to mitigate vasospasm, a common complication occurring in up to 70% of cases, while supportive care addresses hydrocephalus or rebleeding risks.[1][5] Despite advances, outcomes remain guarded, with mortality rates of 40-50% and significant morbidity among survivors, including permanent neurological deficits.[1] Prevention strategies focus on managing hypertension, smoking cessation, and screening for aneurysms in high-risk individuals.[2]
Definition and Classification
Definition
Subarachnoid hemorrhage (SAH) is defined as the accumulation of blood within the subarachnoid space, the compartment located between the arachnoid membrane and the pia mater that envelops the brain and spinal cord. This space contains cerebrospinal fluid (CSF), which circulates to cushion and nourish the central nervous system, and bleeding into it typically results in blood mixing with the CSF, potentially leading to widespread distribution of blood products throughout the ventricular system and spinal canal.[1]SAH most commonly arises from spontaneous (non-traumatic) rupture of a saccular aneurysm in the circle of Willis, though it can also occur due to head trauma or in perimesencephalic patterns without an identifiable vascular lesion. Aneurysmal rupture accounts for the majority of spontaneous cases, while traumatic SAH results from direct injury to cerebral vessels, and perimesencephalic SAH represents a benign variant limited to the basal cisterns around the midbrain.[1]SAH constitutes a neurosurgical emergency characterized by high mortality, approaching 50% in many series, largely attributable to acute neurological deterioration from elevated intracranial pressure, initial hemorrhage volume, and risks of rebleeding. Unlike intracerebral hemorrhage, which involves bleeding directly into brain parenchyma and causes localized mass effect, or subdural hemorrhage, which accumulates between the dura mater and arachnoid layers leading to slower-onset symptoms, SAH's location allows for rapid dissemination via CSF pathways, resulting in global cerebral ischemia and hydrocephalus.[1][4]
Classification Systems
Classification systems for subarachnoid hemorrhage (SAH) provide standardized methods to assess disease severity, guide clinical decision-making, and predict patient outcomes based on clinical presentation and radiographic findings. These scales are essential for stratifying risk, particularly for complications like vasospasm and delayed cerebral ischemia, and are widely used in research and practice.[1]The Hunt and Hess scale, introduced in 1968, is a clinical grading system that evaluates SAH severity based on neurological symptoms and level of consciousness. It ranges from Grade I, characterized by asymptomatic or mild headache with minimal nuchal rigidity, to Grade V, marked by deep coma, decerebrate rigidity, and a moribund appearance. Intermediate grades include Grade II (moderate to severe headache, nuchal rigidity, without neurological deficit except cranial nerve palsy), Grade III (drowsiness or confusion with mild focal deficit), and Grade IV (stupor with moderate to severe hemiparesis and early decerebrate posturing). Higher grades on this scale are associated with poorer prognosis, reflecting increased surgical risk and mortality.[6][7]
Grade
Criteria
I
Asymptomatic or mild headache and slight nuchal rigidity
II
Moderate to severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy
III
Drowsiness, confusion, or mild focal deficit
IV
Stupor, moderate to severe hemiparesis, possible early decerebrate rigidity, vegetative disturbances
V
Deep coma, decerebrate rigidity, moribund appearance
The World Federation of Neurosurgical Societies (WFNS) scale, established in 1988, offers a more objective clinical assessment by incorporating the Glasgow Coma Scale (GCS) score and presence of motor deficits. It is graded from 1 to 5, with Grade 1 indicating GCS 15 without motor deficit, Grade 2 as GCS 13-14 without motor deficit, Grade 3 as GCS 13-14 with motor deficit, Grade 4 as GCS 7-12 with any motor deficit, and Grade 5 as GCS 3-6 with any motor deficit. This scale improves reproducibility over purely descriptive systems and correlates with adverse outcomes in higher grades.[8][1]
Grade
GCS Score
Motor Deficit
1
15
Absent
2
13-14
Absent
3
13-14
Present
4
7-12
Present
5
3-6
Present
The Fisher scale, developed in 1980, is a radiographic grading system based on the amount and distribution of blood visible on non-contrast computed tomography (CT) scans, which helps predict the risk of cerebral vasospasm. It categorizes SAH into four groups: Grade 1 (no subarachnoid blood detected), Grade 2 (diffuse or vertical layers of subarachnoid blood less than 1 mm thick, no clots), Grade 3 (localized clots or vertical layers greater than 1 mm thick), and Grade 4 (diffuse or minimal subarachnoid blood with intracerebral or intraventricular clots). Higher grades indicate greater blood volume and are linked to increased vasospasm incidence.[9]
Grade
CT Findings
1
No subarachnoid blood
2
Diffuse subarachnoid blood <1 mm thick, no clots
3
Thick subarachnoid blood ≥1 mm or localized clots
4
Intracerebral or intraventricular clot, with diffuse or no subarachnoid blood
The modified Fisher scale, proposed in 2006, refines the original by explicitly accounting for intraventricular hemorrhage (IVH) alongside subarachnoid blood thickness to enhance prediction of delayed cerebral ischemia. It assigns Grade 0 (no SAH or IVH), Grade 1 (thin SAH without IVH), Grade 2 (thin SAH with IVH), Grade 3 (thick SAH without IVH), and Grade 4 (thick SAH with IVH), where thin SAH is defined as less than 1 mm thick and thick as 1 mm or greater. This modification improves prognostic accuracy for ischemia compared to the original scale.[10]
Grade
CT Findings
0
No SAH or IVH
1
Thin SAH, no IVH
2
Thin SAH, with IVH
3
Thick SAH, no IVH
4
Thick SAH, with IVH
Despite their utility, these classification systems have limitations, including inter-observer variability due to subjective interpretations in the Hunt and Hess and WFNS scales, and challenges in CT-based assessment for the Fisher scales influenced by scan timing and image quality. Modern high-resolution imaging has prompted ongoing refinements to address these issues and improve reliability.[7][11]
Epidemiology
Incidence and Prevalence
Subarachnoid hemorrhage (SAH) has a global age-standardized incidence rate of approximately 8.3 cases per 100,000 person-years, with estimates ranging from 6 to 10 cases per 100,000 person-years across populations.[12][13] This places SAH as a relatively rare subtype of stroke, accounting for about 5% of all strokes worldwide, though it contributes disproportionately to stroke-related morbidity and mortality due to its severity.[14] Incidence rates vary regionally, with notably higher figures in Japan (up to 23 per 100,000) and Finland (around 20 per 100,000), potentially linked to genetic and environmental factors.[13][15]The incidence of SAH increases with age, peaking between 40 and 60 years, though some populations exhibit a bimodal distribution, particularly among males with secondary peaks in younger adulthood.[16][17] It is higher among postmenopausal women compared to age-matched men, suggesting a role for hormonal changes in vulnerability.[18] From 1990 to 2021, while the absolute number of incident cases rose by 51.7% globally due to population aging and growth, age-standardized incidence rates declined by about 1% annually, reflecting overall improvements in preventive care.[19] In high-income countries, this decline is attributed to enhanced hypertension screening and control, a key modifiable risk factor alongside smoking.[20]Geographic and seasonal variations further influence SAH occurrence, with slightly higher rates in rural areas potentially due to limited access to screening and vascular health management.[21] A modest winter peak in incidence has been observed in multiple studies, possibly related to environmental factors like cold weather exacerbating vascular stress.[22] In low- and middle-income settings, age-standardized rates have remained stable or shown slower declines compared to high-income regions, highlighting persistent disparities in healthcare resources.[23]
Risk Factors and Demographics
Subarachnoid hemorrhage (SAH) is influenced by a combination of modifiable and non-modifiable risk factors, with demographic variations contributing to disparities in incidence. Modifiable risks, particularly those amenable to lifestyle and medical interventions, play a significant role in primary prevention. Non-modifiable factors, including genetic predispositions, highlight the importance of targeted screening in high-risk groups.Among modifiable risk factors, hypertension stands out as the strongest, with meta-analyses indicating an odds ratio (OR) of approximately 2 to 4 for SAH in affected individuals compared to those with normal blood pressure. Smoking is another major contributor, showing a dose-dependent association; current smokers face roughly double the risk (OR ~2.5 for women and 4.5 for men), escalating with pack-years of exposure, and accounting for about one-third of attributable cases. Excessive alcohol consumption, defined as more than 30 grams per day, also elevates risk, with heavy drinkers experiencing up to a twofold increase. Cocaine and amphetamine abuse independently heighten the likelihood of SAH, with cocaine use linked to an OR of about 6 for cerebral vasospasm and hemorrhage complications post-event.Non-modifiable risks include female sex, which confers a 1.5- to 2-fold higher incidence, particularly after menopause (relative risk ~1.6 overall). A positive family history of SAH or aneurysms increases risk 3- to 7-fold among first-degree relatives, with 5% to 10% of cases involving hereditary components. Connective tissue disorders, such as vascular Ehlers-Danlos syndrome, predispose individuals to aneurysm formation and rupture due to vascular fragility.Demographically, SAH incidence is higher among Black and Hispanic populations in the US; for instance, age- and sex-adjusted rates are twice as high in African Americans (12 per 100,000) compared to Whites (6 per 100,000), and 67% higher in Mexican Americans versus non-Hispanic Whites. Socioeconomic disparities exacerbate these patterns, with lower socioeconomic status associated with increased odds of SAH presentation, often linked to limited access to preventive care.Protective factors include statin use, which is associated with a reduced SAH risk (hazard ratio ~0.7-0.8, especially in those with hypertension), and effective blood pressure control, which mitigates the hypertensive risk by up to 50% through sustained management.Risk interactions amplify vulnerability; for example, smoking synergizes with hypertension, producing a combined OR exceeding the sum of individual effects (up to 7-10 in some cohorts), underscoring the need for multifaceted interventions.
Causes
Aneurysmal Causes
Subarachnoid hemorrhage (SAH) resulting from the rupture of intracranial aneurysms accounts for approximately 85% of non-traumatic cases, with saccular (berry) aneurysms being the predominant type. These aneurysms typically form at arterial bifurcations within the circle of Willis, where hemodynamic stress is highest. The anterior communicating artery is the most common site, involved in 30-35% of ruptured cases, followed closely by the posterior communicating artery at around 30%. Other frequent locations include the middle cerebral artery bifurcation and the internal carotid artery terminus.[24][25]Aneurysm characteristics significantly influence rupture risk. Size is a key determinant, with aneurysms larger than 7 mm exhibiting markedly higher annual rupture rates compared to smaller ones; the International Study of Unruptured Intracranial Aneurysms (ISUIA) reported an annual rupture rate of approximately 0.05% for aneurysms under 7 mm in the anterior circulation in patients without prior subarachnoid hemorrhage, escalating to over 50% cumulative risk for giant aneurysms exceeding 25 mm. Irregular or multilobulated shapes further elevate risk by creating focal areas of wall stress, independent of size or location. Aneurysms in the posterior circulation, such as those on the basilar artery, also carry a higher rupture probability due to greater hemodynamic forces.[26][27][28]Genetic predispositions play a role in aneurysmal formation and rupture. Autosomal dominant polycystic kidney disease (ADPKD) is notably associated, with intracranial aneurysm prevalence reaching 10-20% in affected individuals—substantially higher than the 2-3% in the general population—due to underlying vascular connective tissue defects. Rupture often occurs spontaneously without identifiable precipitants, though acute hypertensive surges and therapeutic anticoagulation can exacerbate bleeding extent upon rupture. Multiple aneurysms are identified in 20-30% of SAH patients, posing challenges in pinpointing the culprit lesion and necessitating comprehensive vascular imaging.[29][30][31]
Non-Aneurysmal Causes
Subarachnoid hemorrhage (SAH) can arise from non-aneurysmal sources, broadly categorized into traumatic and spontaneous variants, accounting for a significant portion of cases beyond ruptured saccular aneurysms. Traumatic SAH occurs in approximately 33-60% of patients with moderate to severe traumatic brain injury (TBI), often resulting from direct mechanical disruption of subarachnoid vessels due to head trauma.[32] These cases are frequently associated with cerebral contusions, skull fractures (particularly at the skull base), and other intracranial injuries such as subdural or epidural hematomas, with the pattern of bleeding typically multifocal and distributed along the convexity or basal cisterns. Prognosis is closely linked to the overall severity of the trauma, as measured by scales like the Glasgow Coma Scale, rather than the SAH itself, and outcomes range from favorable in isolated cases to poor in severe polytrauma.[33]Spontaneous non-aneurysmal SAH, comprising about 15-20% of all spontaneous SAH cases, includes several etiologies distinct from aneurysmal rupture. Vascular malformations, such as arteriovenous malformations (AVMs) and dural arteriovenous fistulas, contribute to roughly 5% of all spontaneous SAH, where abnormal vascular connections lead to hemorrhage into the subarachnoid space; these are often identified via angiography and may present with focal or diffuse bleeding patterns.[34]Perimesencephalic SAH (pSAH), representing approximately 5-10% of all spontaneous SAH (and about 30-70% of non-aneurysmal spontaneous SAH), features a characteristic benign pattern of blood localized to the cisterns around the midbrain and pons, with minimal extension; it is frequently idiopathic, carries a low risk of rebleeding (less than 1%), and is associated with excellent outcomes in over 90% of cases due to the absence of underlying structural lesions.[35]Other spontaneous causes include anticoagulation-related bleeding, such as from warfarin overdose or therapeutic anticoagulation, which can precipitate SAH by impairing hemostasis, though it is rarely the sole etiology and often exacerbates underlying vessel fragility. Illicit drug use, particularly cocaine, induces vasculopathy through acute hypertension and endothelial damage, leading to non-aneurysmal SAH in susceptible individuals. Pituitary apoplexy, involving hemorrhage into a pituitary adenoma, can extend into the subarachnoid space and mimic classic SAH presentations. Rare causes encompass conditions like sickle cell disease (via vaso-occlusive crises), primary brain tumors eroding into the subarachnoid space, and coagulopathies such as hemophilia, each presenting with variable bleeding patterns but generally low incidence.[1][36]Differentiating non-aneurysmal from aneurysmal SAH relies on imaging characteristics and clinical context: traumatic cases often show multifocal, trauma-associated bleeds with extracranial injuries, while spontaneous non-aneurysmal variants like pSAH exhibit localized patterns and confer a better overall prognosis compared to aneurysmal rupture, with lower rates of vasospasm and rebleeding.[34]
Pathophysiology
Mechanisms of Hemorrhage
Subarachnoid hemorrhage (SAH) typically results from the sudden rupture of a cerebral aneurysm or other vascular abnormality, leading to a high-pressure jet of arterial blood entering the subarachnoid space. This rupture causes an abrupt failure in the vessel wall, often due to hemodynamic stress or structural weakness, releasing blood directly into the cerebrospinal fluid (CSF)-filled subarachnoid compartment.[37] The influx of blood occurs rapidly, with pressures capable of exceeding 100 mmHg, which temporarily halts further bleeding by equalizing intracranial and vascular pressures.[38]The distribution of blood in the subarachnoid space follows gravitational and anatomical patterns, commonly visualized on computed tomography (CT) scans. Blood often accumulates in the basal cisterns, such as the suprasellar and perimesencephalic cisterns, and may extend into the Sylvian fissure or interhemispheric fissure, depending on the rupture site.[33] These patterns influence the risk of complications; for instance, dense blood in the basal cisterns correlates with higher rates of early hydrocephalus and ischemia due to CSF pathway obstruction and local mass effect.[33]Immediately following the bleed, acute physiological disruptions ensue, including a sharp rise in intracranial pressure (ICP) from the added blood volume in the confined cranial space. This ICP elevation, often reaching levels that impair cerebral perfusion, can lead to early hydrocephalus in 30% of cases through obstruction of CSF flow at the basal cisterns or foramina.[38] Additionally, blood breakdown products, such as oxyhemoglobin released from lysed erythrocytes within hours, irritate the meninges, initiating an inflammatory cascade with neutrophil infiltration and cytokine release in the subarachnoid space.[39]The transient ICP surge also precipitates global cerebral ischemia by reducing cerebral perfusion pressure and suspending cerebral blood flow for 2-3 minutes post-rupture. This early ischemic event, distinct from later focal deficits, arises from the mechanical compression of cerebral vessels and can cause widespread neuronal excitotoxicity and metabolic derangements, such as elevated glutamate levels.[40] Recovery of perfusion typically occurs within minutes, but residual hypoperfusion may persist, exacerbating initial brain injury.[40]
Secondary Brain Injury
Secondary brain injury following subarachnoid hemorrhage (SAH) encompasses a series of delayed pathophysiological cascades that amplify neuronal damage beyond the initial bleed, primarily through ischemia, inflammation, and mechanical complications. These processes unfold over hours to weeks and contribute significantly to morbidity and mortality, with mechanisms involving vascular, inflammatory, and systemic disruptions.[41]Vasospasm represents a hallmark of secondary injury, characterized by arterial narrowing that typically begins around day 3 post-SAH, peaks between days 4 and 14, and resolves within 2-3 weeks. This narrowing arises from oxyhemoglobin released by erythrocyte lysis in the subarachnoid space, which induces oxidative stress and contraction of vascular smooth muscle cells, leading to reduced cerebral blood flow. Consequently, delayed cerebral ischemia (DCI) develops in approximately 30% of patients with angiographic vasospasm, manifesting as neurological deficits due to hypoperfusion.[42]Inflammation exacerbates secondary injury through the release of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which are elevated in cerebrospinal fluid shortly after SAH and correlate with poor outcomes. These cytokines promote blood-brain barrier disruption by downregulating tight junction proteins like occludin and claudin-5, allowing influx of inflammatory cells and edema formation. Additionally, inflammatory cascades facilitate microthrombosis in cerebral microvessels via neutrophil-endothelial interactions, further impairing perfusion and contributing to tissue damage.[39]Hydrocephalus emerges as another key mechanism, occurring acutely from blood clot obstruction of cerebrospinal fluid pathways, such as the ventricular system or aqueduct, or chronically from fibrosis of arachnoid villi due to exposure to blood breakdown products and transforming growth factor. This impaired cerebrospinal fluid dynamics elevates intracranial pressure and requires ventriculoperitoneal shunting in about 20% of SAH cases.[43]Rebleeding poses an immediate risk of recurrent hemorrhage, with the highest incidence—estimated at 15%—occurring within the first 24 hours from unsecured ruptured aneurysms, often before definitive treatment. This event substantially worsens prognosis by expanding the initial hematoma and intensifying secondary cascades.[1]Seizures in SAH arise from cortical irritation by subarachnoid blood products and associated infarcts, which generate epileptogenic foci through free radical production and neuronal hyperexcitability. Electrolyte disturbances, particularly hyponatremia from cerebral salt wasting or syndrome of inappropriate antidiuretic hormone secretion, further lower the seizure threshold by altering neuronal membrane potentials.[44][45]Systemic effects include neurogenic cardiac stunning, a reversible left ventricular dysfunction triggered by massive catecholamine release from sympathetic overactivation post-SAH, leading to troponin elevation and wall motion abnormalities. Concurrently, neurogenic pulmonary edema develops from increased vascular permeability and endothelial injury due to the same catecholamine surge, resulting in acute respiratory compromise in up to 20-40% of severe cases.[46]
Clinical Presentation
Acute Signs and Symptoms
The acute presentation of subarachnoid hemorrhage (SAH) is often dramatic and life-threatening, with the classic triad consisting of a sudden-onset severe headache, nausea and vomiting, and neck stiffness. The headache, frequently described as a "thunderclap" or the worst of the patient's life, occurs in over 95% of cases and results from the rapid increase in intracranial pressure (ICP) and meningeal irritation caused by blood in the subarachnoid space.[47][48] Nausea and vomiting, reported in approximately 75% of patients, are triggered by elevated ICP and irritation of the meninges or brainstem.[47] Neck stiffness, a sign of meningeal irritation from blood spreading into the basal cisterns and spinal subarachnoid space, typically develops 6-24 hours after onset and affects about 61% of individuals. Photophobia is also common, occurring in around 50-70% of cases.[47][1]Neurological deficits are common and reflect the severity of the bleed and secondary effects like mass effect or ischemia. Loss of consciousness at onset occurs in roughly 50% of cases, often transient but potentially leading to coma in severe instances due to acute ICP elevation.[47] Focal neurological signs, such as hemiparesis from hematoma mass effect or cranial nerve palsies, may accompany the presentation in up to 30% of patients.[38] Seizures manifest at the time of rupture in about 10% of cases, likely due to cortical irritation from blood products or associated intraparenchymal extension.[49]Systemic vital sign abnormalities often signal underlying physiological derangements. Hypertension is frequent, driven by a catecholamine surge in response to the hemorrhage, while bradycardia may occur as part of the Cushing reflex—a compensatory response to elevated ICP that aims to maintain cerebral perfusion.[50] Fever can develop early from chemical meningeal irritation by subarachnoid blood, mimicking infectious processes.[51] Ocular findings include subhyaloid preretinal hemorrhage as part of Terson syndrome, seen in approximately 10-20% of cases due to elevated ICP transmitting pressure to the optic nerve sheath, and papilledema from sustained ICP rise.[38][52]Atypical presentations, particularly in the elderly or comatose patients, may lack the classic thunderclap headache, instead featuring subtle symptoms like mild headache, dizziness, or isolated vomiting, which can delay recognition and worsen outcomes.[53] In comatose individuals, symptoms may be entirely absent or masked by the altered mental status, emphasizing the need for high clinical suspicion in at-risk groups.
Prodromal Features
Prodromal features of subarachnoid hemorrhage (SAH) refer to warning signs that may occur days to weeks before the major aneurysmal rupture, often indicating minor leaks or aneurysm enlargement. These symptoms are particularly relevant in aneurysmal SAH, where they can provide a critical window for intervention if recognized promptly.[54]Sentinel headaches represent the most common prodromal symptom, occurring in 15% to 60% of aneurysmal SAH cases and typically manifesting as a mild to moderate thunderclap-like headache 1 to 2 weeks prior to the full rupture. These headaches are attributed to microleaks from the aneurysm or transient distension of the aneurysmal wall, and they often resolve spontaneously but recur with increasing severity.[55][56]Ocular symptoms, such as third nerve (oculomotor) palsy, can also serve as a prodromal indicator, especially with aneurysms of the posterior communicating artery, where the enlarging sac compresses the nerve before rupture occurs. This presents as ptosis, diplopia, or pupil dilation, highlighting the need for urgent neuroimaging in patients with new-onset oculomotor deficits and risk factors for aneurysm.[57][58]Other warning signs include transient visual disturbances like blurred vision or amaurosis fugax, epistaxis potentially linked to vascular instability in certain aneurysm locations, and localized neck pain from meningeal irritation due to minor subarachnoid blood. These symptoms occur in up to 50% of cases preceding rupture and are often nonspecific, complicating early detection.[59][60]Recognition of these prodromal features is frequently challenged by misdiagnosis as benign conditions such as migraine, tension headache, or sinusitis, leading to delayed evaluation and treatment. In one study, up to 51% of SAH cases were initially misdiagnosed, often due to failure to perform head imaging in patients presenting with sudden severe headache.[61][56]Evidence underscores the urgency of addressing these warnings, as unrecognized sentinel headaches are associated with a 20% to 30% risk of major rebleeding if the aneurysm remains unsecured, with some analyses showing a 10-fold higher rebleeding rate compared to those without prior symptoms; this emphasizes prompt CT angiography or lumbar puncture in high-risk patients to prevent catastrophic outcomes.[54][62]
Diagnosis
Clinical Assessment
The clinical assessment of suspected subarachnoid hemorrhage (SAH) begins with a detailed history to identify key features suggestive of this life-threatening condition. Patients often describe a sudden-onset thunderclap headache, characterized as the "worst headache of their life," reaching maximal intensity within seconds to minutes.[63] Associated symptoms frequently include nausea, vomiting, photophobia, and neck stiffness, which arise from meningeal irritation by blood in the subarachnoid space.[1] Risk factors elicited during history-taking include hypertension, smoking, family history of aneurysms, and connective tissue disorders such as Ehlers-Danlos syndrome.[4] Inquiry should also probe for prodromal or sentinel headaches—milder episodes in the preceding weeks that may precede major hemorrhage by up to 43% of cases.[63]Physical examination focuses on evaluating neurological status and signs of meningeal irritation. The Glasgow Coma Scale (GCS) is routinely used to assess level of consciousness, with scores ranging from 3 to 15; lower scores indicate poorer prognosis and higher-grade SAH.[1] Focal neurological deficits, such as cranial nerve palsies (e.g., third or sixth nerve involvement), motor or sensory impairments, and altered pupillary responses, should be documented to gauge severity.[63] Meningeal signs are common, including nuchal rigidity, positive Kernig's sign (pain on knee extension with hip flexed), and Brudzinski's sign (involuntary hip flexion on neck flexion), reflecting irritation from subarachnoid blood.[1] Fundoscopic examination may reveal papilledema, indicating elevated intracranial pressure, or intraretinal hemorrhages associated with Terson's syndrome in up to 20% of cases.[64]Red flags that heighten suspicion for SAH include sudden headache onset, age greater than 50 years, history of hypertension, and altered mental status, as these features align with validated screening tools like the Ottawa SAH Rule, which demonstrates high sensitivity for identifying low-risk patients.[65] These elements warrant immediate evaluation to differentiate SAH from mimics.Differential diagnosis considerations encompass conditions presenting with acute headache, such as migraine (typically recurrent without thunderclap features), bacterial meningitis (often with fever and rash), and sentinel bleeds (warning hemorrhages that mimic but precede full SAH).[63] Clinical judgment integrates these to prioritize SAH in high-risk presentations.Triage emphasizes urgent stabilization following airway, breathing, and circulation (ABCs) protocols to address potential hemodynamic instability or coma.[65] Lumbar puncture should be deferred if signs of elevated intracranial pressure (e.g., papilledema or coma) are present, to avoid herniation risk.[66] Prompt transfer to a neurocritical care center is recommended for comprehensive management.[65]
Neuroimaging
Non-contrast computed tomography (CT) of the head is the initial imaging modality of choice for suspected subarachnoid hemorrhage (SAH), offering high sensitivity for detecting acute blood in the subarachnoid space, particularly when performed within the first 24 hours of symptom onset.[67] It typically reveals hyperdense (bright) blood within the basal cisterns, Sylvian fissures, interhemispheric fissure, or sulci, with patterns such as the hyperdense crescent sign indicating aneurysmal rupture.[68] Sensitivity exceeds 95% within 6 hours and remains above 90% up to 24 hours, but declines progressively to approximately 50% after one week due to blood resorption and degradation.[69][70] Beam-hardening artifacts from adjacent bone can obscure blood in posterior fossa or perimesencephalic regions, potentially leading to false negatives.[71]CT angiography (CTA), performed immediately following non-contrast CT, is recommended as the preferred noninvasive method for identifying the vascular source of SAH, such as aneurysms greater than 3 mm in diameter.[65] It demonstrates high sensitivity of 92-100% and specificity of 83-100% for detecting intracranial aneurysms, allowing rapid assessment of aneurysm location, size, and morphology to guide treatment decisions.[72][73] CTA is particularly valuable in hemodynamically stable patients, as it can visualize vascular abnormalities without the invasiveness of catheter-based techniques, though it may miss small aneurysms (<3 mm) or non-aneurysmal causes in up to 5-30% of cases.[73]Magnetic resonance imaging (MRI), while not routinely used in the acute phase due to longer acquisition times and limited availability in emergencies, provides complementary visualization of subacute SAH through fluid-attenuated inversion recovery (FLAIR) sequences, which detect blood as hyperintense signals in the subarachnoid space as early as 12 hours post-ictus.[68][74] Magnetic resonance angiography (MRA) can evaluate vessel patency and aneurysms noninvasively but is less sensitive than CTA or DSA for fine vascular details and is generally reserved for subacute or follow-up imaging in stable patients.[74] Contraindications include patient instability, metallic implants, or claustrophobia, limiting its acute utility.[75]Digital subtraction angiography (DSA) serves as the gold standard for definitive characterization of aneurysm morphology, neck width, and branch vessel involvement in SAH, with sensitivity exceeding 95% for identifying culprit lesions.[76][77] As an invasive procedure, DSA not only confirms diagnosis but also enables therapeutic interventions like endovascular coiling or balloon-assisted techniques during the same session, making it essential when CTA is inconclusive or for complex cases.[78] However, it carries risks of complications such as vessel dissection or contrast-induced nephropathy, particularly in unstable patients, and is typically deferred until after initial stabilization.[78]
Cerebrospinal Fluid Analysis
Cerebrospinal fluid analysis via lumbar puncture serves as a critical diagnostic tool for confirming subarachnoid hemorrhage (SAH) in cases of high clinical suspicion when noncontrast head computed tomography (CT) is negative or nondiagnostic.[65] It is particularly indicated for patients presenting with thunderclap headache or other suggestive features, as these symptoms warrant further evaluation despite initial imaging results.[79] The procedure is optimally performed 6 to 12 hours after symptom onset to maximize sensitivity for key pathological markers, though it can be conducted earlier if clinical urgency demands.[65]During the lumbar puncture, opening pressure is measured first, with elevations above 20 cm H₂O indicating possible increased intracranial pressure, which occurs in up to 60% of SAH cases.[80] Cerebrospinal fluid (CSF) is then collected in serial tubes for analysis, including red blood cell (RBC) count, visual or spectrophotometric assessment for xanthochromia, and evaluation of protein and glucose levels. Spectrophotometry for xanthochromia, which detects bilirubin from RBC breakdown resulting in a yellow tint, offers 100% sensitivity and 95.2% specificity for SAH when performed more than 12 hours post-onset.[65]Diagnostic findings in SAH include an RBC count exceeding 1,000 to 2,000 cells/mm³ in the final tube that does not decrease significantly across serial samples, distinguishing true hemorrhage from a traumatic tap.[81] Protein levels are typically elevated due to blood breakdown products, while glucose remains normal or only mildly reduced.[82] RBCs from SAH persist in the CSF for weeks, and xanthochromia remains detectable for up to two weeks, allowing for delayed diagnosis if symptoms evolve.[79]Complications of lumbar puncture in this context are infrequent but include a 1% to 2% risk of cerebral herniation if an undiagnosed mass lesion causes elevated intracranial pressure; this risk is substantially mitigated by performing a pre-procedure CT scan to exclude such lesions.[83] Other potential issues encompass post-procedural headache and traumatic tap, which can confound interpretation but are managed through careful technique and serial sampling.[79]
Ancillary Tests
Electrocardiographic (ECG) changes are frequently observed in patients with subarachnoid hemorrhage (SAH) due to neurogenic stress cardiomyopathy, often mimicking acute coronary ischemia. Common abnormalities include T-wave inversions, which occur in up to 50% of cases, ST-segment depression, and QT interval prolongation, resulting from heightened sympathetic activity and catecholamine release.[84][85] These findings necessitate cardiac evaluation to differentiate from primary myocardial events, as they are associated with increased neurological severity but not independently predictive of mortality.[86]Laboratory tests play a supportive role in SAH evaluation by assessing for complications and guiding management. Complete blood count (CBC) may reveal anemia or thrombocytopenia due to blood loss or consumptive coagulopathy, while coagulation panels, including prothrombin time (PT) and international normalized ratio (INR), help evaluate bleeding risk prior to interventions.[87] Elevated troponin levels, indicative of myocardial injury from neurogenic stress, are seen in 20-34% of patients and correlate with worse outcomes, including higher in-hospital mortality.[88][89]Biomarkers such as S100B and glial fibrillary acidic protein (GFAP) provide prognostic insights in SAH by reflecting astroglial injury, with elevated serum levels predicting poor neurological outcomes and increased mortality risk.[90][91] However, these are not routinely used in clinical practice due to variability in thresholds and lack of standardized integration into decision-making.[92]Electroencephalography (EEG), particularly continuous EEG monitoring, is employed in patients with altered mental status to detect nonconvulsive seizures, which occur in approximately 19% of SAH cases and may contribute to secondary brain injury if undetected.[93]Intracranial pressure (ICP) monitoring via intraventricular catheter is indicated in severe SAH cases, such as those with Glasgow Coma Scale ≤8, neurological deterioration, or hydrocephalus, primarily to guide therapeutic interventions like cerebrospinal fluid drainage rather than solely for diagnosis.[94]
Management
Acute Stabilization
Upon presentation with subarachnoid hemorrhage (SAH), immediate acute stabilization focuses on securing the airway, optimizing hemodynamics, managing intracranial pressure (ICP), preventing seizures, and establishing comprehensive monitoring to mitigate secondary brain injury prior to definitive aneurysm treatment.[65] The 2023 American Heart Association/American Stroke Association (AHA/ASA) guidelines emphasize activation of a multidisciplinary team, including neurosurgery, neurocritical care, neurology, and interventional neuroradiology, to coordinate care in a high-volume center with dedicated neurocritical care units, as this approach is associated with improved outcomes and reduced length of stay.[65]Airway management is prioritized in patients with depressed level of consciousness, defined by a Glasgow Coma Scale (GCS) score less than 8 or signs of respiratory failure, to prevent aspiration and hypoxia. Endotracheal intubation is recommended using rapid-sequence techniques while avoiding hypotension, as even brief episodes of low blood pressure can exacerbate cerebral ischemia in SAH.[95] Standard intensive care unit (ICU) ventilator bundles, including lung-protective ventilation strategies, are applied to mechanically ventilated patients to minimize ventilator-associated complications.[65]Blood pressure control is critical to balance the risk of rebleeding from uncontrolled hypertension against the need to maintain cerebral perfusion. Prior to aneurysm securing, systolic blood pressure (SBP) should be targeted below 160 mmHg using short-acting intravenous agents such as labetalol or nicardipine to reduce rebleeding risk without inducing hypotension (mean arterial pressure <65 mmHg).[65] After aneurysm securing, a strategy of permissive hypertension may be employed, allowing SBP up to 180-220 mmHg in select cases to support cerebral perfusion, guided by close hemodynamic monitoring to minimize blood pressure variability.[65]ICP management begins with nonpharmacologic measures, including elevation of the head of the bed to 30 degrees to promote venous drainage while maintaining neutral neck alignment to avoid jugular compression. In cases of elevated ICP with signs of herniation, such as pupillary asymmetry or Cushing's triad, hyperosmolar therapy with mannitol (0.5-1 g/kg) or hypertonic saline is administered to reduce brain edema and achieve brain relaxation, with serial monitoring to assess response.[65] Corticosteroids are not recommended due to lack of efficacy and potential for complications like hyperglycemia and infection.[65]Seizure prophylaxis is considered in high-risk patients, such as those with Fisher Grade 3-4 SAH or ruptured middle cerebral artery aneurysms, using levetiracetam (preferred over phenytoin due to fewer adverse effects and no need for serum level monitoring) for up to 7 days to prevent early seizures that could precipitate rebleeding or ischemia.[65] Routine prophylaxis is not recommended for all patients, as the risks of antiseizure medications, including cognitive side effects, may outweigh benefits in low-risk cases (Class 2b; Level of Evidence C-LD).[65]All patients require prompt admission to a neuro-ICU for intensive monitoring, including serial neurological examinations every 1-4 hours to detect deterioration, continuous telemetry to identify cardiac arrhythmias (common in SAH due to catecholamine surge), and invasive arterial blood pressure monitoring. Continuous electroencephalography (cEEG) is advised for high-grade SAH patients with altered mental status to detect nonconvulsive seizures.[65] Euvolemia is maintained with isotonic fluids to support hemodynamic stability without inducing hyponatremia.[65]
Aneurysm Securing
Securing the ruptured aneurysm is a cornerstone of management in aneurysmal subarachnoid hemorrhage (SAH), aimed at preventing rebleeding by repairing or isolating the lesion. Guidelines recommend prompt intervention, ideally within 24 hours of symptom onset, with treatment within 72 hours strongly advised for patients in good clinical condition to minimize risks. Without securing, the rebleeding risk is approximately 4% in the first 24 hours, rising to a cumulative 40% within the first four weeks, which significantly worsens mortality and morbidity. Early securing reduces this risk to less than 5%, with meta-analyses confirming lower rates of death and dependency when performed within 0-3 days compared to later intervals.[65][96][97]Endovascular coiling involves catheter-based deployment of platinum coils into the aneurysm sac to promote thrombosis and occlusion, achieving initial complete or near-complete occlusion rates of around 80-90% in ruptured cases. This minimally invasive approach is preferred for aneurysms in the posterior circulation, such as basilar or posterior cerebral artery lesions, due to reduced procedural morbidity. The International Subarachnoid Aneurysm Trial (ISAT), a landmark randomized study, demonstrated that coiling yields better one-year outcomes, with a 7% absolute and 24% relative risk reduction in death or dependency compared to surgical clipping in eligible anterior circulation aneurysms.[98][99]66976-5/fulltext)Surgical clipping entails microsurgical exposure of the aneurysm via craniotomy, followed by placement of a titanium clip across the neck to exclude the lesion from circulation, resulting in high occlusion rates exceeding 90-95% and low recurrence. This method is particularly suitable for wide-necked aneurysms, those with complex morphology, or anterior circulation locations like the middle cerebral artery, where endovascular access may be challenging. Clipping provides durable exclusion but carries higher risks of infection or wound complications in select patients.[100][101]Flow diversion using devices like the Pipeline Embolization Device deploys a braided stent across the aneurysm neck to redirect blood flow and induce sac thrombosis, primarily for large or fusiform aneurysms. While effective for unruptured lesions with occlusion rates over 90% at follow-up, its use in acute ruptured SAH remains cautious due to the need for dual antiplatelet therapy, which elevates hemorrhage risks; feasibility has been shown in small series for blister or dissecting aneurysms, but it is not first-line.[102][103]Adjunctive techniques enhance these primary methods, including balloon remodeling during coiling, where temporary balloon inflation in the parent artery allows better coil positioning in wide-necked aneurysms without increasing thrombotic events. Antifibrinolytic agents like ε-aminocaproic acid may be used briefly (up to 72 hours) as a bridge to securing to inhibit clot lysis, though evidence is mixed and their routine use is controversial due to potential cerebral ischemia risks without overall outcome benefits.[104][105][65]Complications of aneurysm securing include intraprocedural perforation (approximately 5% with coiling, leading to rebleeding) and ischemia (5-10% across both coiling and clipping, from thromboembolism or vessel occlusion). Patient selection hinges on aneurysm characteristics—size, location, neck width—and clinical factors like age and comorbidities, with multidisciplinary evaluation guiding the choice between approaches to optimize outcomes.[106][107][108]
Rebleeding Prevention
Rebleeding after subarachnoid hemorrhage (SAH) carries a mortality rate of up to 80%, making its prevention a critical component of management to potentially halve the overall risk of poor outcomes.[109] Early strategies focus on pharmacological interventions and supportive care to stabilize the hematoma while awaiting definitive aneurysm securing. These measures aim to address fibrinolysis, hemodynamic instability, and coagulopathy without introducing undue risks such as delayed cerebral ischemia (DCI).Antifibrinolytic therapy with tranexamic acid, administered ultra-early (within hours of onset) and for a short duration (up to 24 hours), reduces the incidence of rebleeding by approximately 30% compared to placebo, as demonstrated in the ULTRA trial where rates dropped from 14% to 10%.[110] However, this benefit is offset by a potential increase in DCI risk, with meta-analyses reporting a relative risk of 1.2 for cerebral ischemia, particularly when therapy extends beyond 72 hours.[111] Routine long-term use of antifibrinolytics is therefore discouraged due to lack of improvement in functional outcomes and heightened complication risks.[112]Blood pressure management plays a pivotal role in rebleeding prevention, with the 2023 AHA/ASA guidelines recommending gradual reduction for severe hypertension (SBP >180 mmHg) while avoiding hypotension, targeting SBP below 160 mmHg pre-securing and maintaining permissive hypertension up to 180 mmHg post-securing to support cerebral perfusion unless DCI requires higher targets.[65] Intravenous agents such as nicardipine infusions are preferred for their rapid titration and short half-life, allowing precise adjustment while avoiding hypotension (mean arterial pressure <65 mmHg), which could exacerbate ischemia.[113]In patients with pre-existing coagulopathy, prompt reversal is essential to mitigate bleeding propensity. For warfarin-associated anticoagulation, prothrombin complex concentrate (PCC) provides rapid correction of international normalized ratio, superior to fresh frozen plasma in speed and volume overload risk, often combined with intravenous vitamin K for sustained effect.[114] This approach facilitates safer aneurysm treatment and reduces expansion risk, though routine antifibrinolytic use remains avoided long-term.[115]Supportive bedside measures complement pharmacological strategies by reducing intracranial pressure fluctuations and physiological stressors. Maintaining normothermia (36-37°C) prevents fever-induced vasodilation and coagulopathy exacerbation, while avoiding straining through stool softeners and laxatives minimizes Valsalva maneuvers that could elevate transmural pressure.[116] Cautious early mobilization, with head-of-bed elevation at 30 degrees, optimizes venous drainage without promoting dislodgement.[96]Ongoing monitoring for rebleeding involves serial non-contrast CT scans in cases of suspected expansion, typically within 6-24 hours if clinical deterioration occurs, alongside vigilant assessment for signs such as worsening headache, neurological deficits, or hemodynamic instability.[117] These combined approaches, when implemented promptly, significantly attenuate the high mortality associated with recurrent hemorrhage.[118]
Vasospasm and Ischemia Management
Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major contributor to morbidity, occurring in 20-30% of patients primarily between days 4 and 14 post-hemorrhage, and is characterized by focal neurological deficits or a decrease in Glasgow Coma Scale score of at least 2 points lasting for 1 hour or more.[65] Cerebral vasospasm, a key pathophysiological mechanism, narrows large cerebral arteries and can lead to DCI, accounting for significant long-term disability when untreated.[65] Early detection and multimodal management are essential to mitigate these effects, with DCI responsible for up to 25% of poor outcomes in aSAH survivors.[65]Monitoring for vasospasm and DCI relies on non-invasive and invasive techniques to guide interventions. Transcranial Doppler (TCD) ultrasonography is recommended for daily screening, with mean middle cerebral artery flow velocities exceeding 200 cm/s or a Lindegaard ratio (mean flow velocity divided by extracranial internal carotid artery velocity) of 3 or greater indicating moderate to severe vasospasm; TCD has a sensitivity of 90% and specificity of 71% for predicting DCI.[65]CT perfusion imaging identifies regions of hypoperfusion with a positive predictive value of 0.67 for DCI risk when interpreted by experts, while CT angiography offers 91% sensitivity for detecting central vasospasm.[65]Digital subtraction angiography (DSA) serves as the gold standard for confirmation, particularly in cases warranting endovascular therapy, providing detailed visualization of vessel narrowing.[65] The 2023 American Heart Association/American Stroke Association (AHA/ASA) guidelines endorse multimodal monitoring combining these modalities for optimal detection (Class I, Level of Evidence B-NR).[65]Pharmacological prevention of DCI centers on nimodipine, a calcium channel blocker that reduces the incidence of poor neurological outcomes by approximately 34% without significantly affecting vasospasm incidence itself. Administered orally at 60 mg every 4 to 6 hours for 21 consecutive days starting within 96 hours of aSAH onset, nimodipine is a Class I recommendation (Level of Evidence A) in the 2023 AHA/ASA guidelines due to its proven impact on functional recovery.[65] For refractory cases, endothelin receptor antagonists like clazosentan have been investigated; the CONSCIOUS-1 trial demonstrated a 65% reduction in angiographic vasospasm with clazosentan doses of 5 mg/hour or higher, though it did not improve overall clinical outcomes, leading to limited routine adoption.70164-7/fulltext)Management of symptomatic vasospasm and DCI prioritizes hemodynamic optimization and endovascular rescue therapies. Induced hypertension, targeting systolic blood pressure of 180-220 mmHg in euvolemic patients using vasopressors like norepinephrine, is used to augment cerebral perfusion and is considered reasonable for DCI (Class IIb, Level of Evidence B-NR), though evidence from the HIMALAIA trial shows mixed benefits without hypervolemia or hemodilution components of traditional triple-H therapy.[65] Prophylactic triple-H therapy is not recommended due to potential harm, including increased morbidity from fluid overload (Class III: Harm, Level of Evidence B-R).[65] For severe, refractory vasospasm, endovascular interventions include balloon angioplasty to mechanically dilate proximal vessels, reducing DCI risk (Class IIb, Level of Evidence B-NR), and intra-arterial administration of vasodilators such as verapamil, nicardipine, or milrinone, which reverse vasospasm in distal segments with improved vessel diameters observed in trials.[65] DSA-guided selection ensures these procedures are targeted to symptomatic territories.Recent advances emphasized in the 2023 AHA/ASA guidelines include integrated multimodal monitoring protocols and exploration of novel agents, though clazosentan and similar endothelin antagonists remain investigational pending further outcome data.[65] Early detection through vigilant monitoring remains critical, as timely intervention can prevent progression to irreversible ischemia and improve survival rates.[65]
Hydrocephalus and Other Complications
Hydrocephalus is a common complication following aneurysmal subarachnoid hemorrhage (aSAH), occurring in 15% to 87% of cases in the acute phase due to obstruction from blood products or impaired cerebrospinal fluid (CSF) absorption.[65] In patients with acute hydrocephalus presenting with neurological decline or elevated intracranial pressure (ICP) exceeding 20 mmHg, urgent CSF diversion via external ventricular drain (EVD) placement is recommended to improve outcomes (Class 1, Level of Evidence B-NR).[65] EVD management should incorporate bundled protocols for insertion, maintenance, and monitoring to minimize complications such as over-drainage or infection.[65] For chronic hydrocephalus, which develops in 10% to 20% of patients and may persist after EVD weaning, permanent ventriculoperitoneal (VP) shunt placement is indicated based on clinical symptoms and imaging findings (Class 1, Level of Evidence B-NR).[65]Seizures occur in approximately 8% to 15% of aSAH patients and are associated with worse outcomes, particularly if nonconvulsive.[65] Routine prophylactic antiseizure medication is not recommended beyond the initial 3 to 7 days post-hemorrhage due to lack of benefit in preventing late seizures and potential cognitive harm (Class 3: No Benefit, Level of Evidence B-NR), though short-term prophylaxis may be considered in high-risk cases such as those with cortical involvement or hydrocephalus (Class 2b, Level of Evidence B-NR).[65]Levetiracetam is preferred over phenytoin for prophylaxis or treatment owing to better tolerability and avoidance of metabolic interactions that may reduce nimodipine efficacy.[65] For patients with new-onset clinical seizures, antiseizure medication should be continued for up to 7 days (Class 1, Level of Evidence B-NR).[65] Continuous electroencephalography (EEG) is advised in high-risk patients with altered mental status or fluctuating exams to detect nonconvulsive seizures, which can mimic delayed cerebral ischemia (Class 2a, Level of Evidence B-NR).[65]Hyponatremia affects up to 30% of aSAH patients and arises primarily from syndrome of inappropriate antidiuretic hormone (SIADH), characterized by euvolemic hyponatremia due to water retention, or cerebral salt wasting (CSW), involving hypovolemic sodium loss from renal mechanisms.[65] Distinguishing between SIADH and CSW guides therapy, with volume status assessment via central venous pressure or clinical signs being essential.[65] Fluid restriction, appropriate for SIADH in non-neurological contexts, is contraindicated in aSAH due to risks of hypovolemia and cerebral ischemia (Class 3: Harm, Level of Evidence B-R).[65] Instead, euvolemia should be maintained through isotonic fluids, with hypertonic saline used for symptomatic or severe hyponatremia in CSW to correct sodium levels and support cerebral perfusion.[65]Fludrocortisone, a mineralocorticoid, is reasonable for managing CSW-related natriuresis by promoting sodium retention, though it does not consistently improve neurological outcomes and requires monitoring for hypokalemia (Class 2a, Level of Evidence B-R).[65]Infections, particularly ventriculitis associated with EVD placement, complicate 5% to 15% of aSAH cases requiring CSF diversion.[65] Bundled protocols for EVD care, including sterile technique, daily assessment, and prompt weaning, are essential to reduce infection rates (Class 1, Level of Evidence B-NR).[65] Fever in aSAH patients warrants comprehensive workup, including CSF analysis for cell count, glucose, protein, and culture, to differentiate infectious ventriculitis from noninfectious inflammation or central fever.[65] Suspected ventriculitis requires immediate empirical antibiotics tailored to local resistance patterns, with EVD removal or exchange if confirmed.[65]Venous thromboembolism (VTE) prophylaxis is critical in immobilized aSAH patients, who face elevated risks post-aneurysm securing.[65]Intermittent pneumatic compression devices should be initiated immediately upon admission, followed by pharmacologic prophylaxis with subcutaneous heparin or low-molecular-weight heparin starting 24 to 48 hours after aneurysm treatment to balance bleeding risks (Class 1, Level of Evidence B-NR).[65] Routine screening with lower extremity ultrasound is not recommended unless symptomatic, as VTE incidence remains low with combined mechanical and pharmacologic approaches.[65]Anemia occurs in over 50% of aSAH patients and correlates with poor outcomes, prompting evaluation of transfusion thresholds. The 2024 SAHARA randomized trial compared liberal (transfusion if hemoglobin <10 g/dL) versus restrictive (<7 g/dL or symptomatic) strategies in 542 patients with acute aSAH and anemia, finding no significant difference in unfavorable neurological outcomes at 3 months (42% vs. 44%; relative risk 0.94, 95% CI 0.75-1.18). Thus, a restrictive approach appears safe and is not inferior to liberal transfusion in this population.
Prognosis
Immediate Outcomes
Subarachnoid hemorrhage (SAH) carries a high risk of immediate mortality, with overall case fatality rates ranging from 35% to 50% within the first month following onset. Approximately 10-15% of patients die prior to hospital arrival, often due to the initial hemorrhage or early complications, while in-hospital mortality among those admitted is around 25%. Patients presenting with Hunt-Hess grade V SAH, characterized by deep coma and decerebrate posturing, face near-100% mortality rates in the acute phase without aggressive intervention.[119][120][16][121]Among survivors, morbidity remains substantial, with approximately 30% experiencing significant dependency at 3 months post-SAH, defined as modified Rankin Scale (mRS) scores of 3-5 indicating moderate to severe disability. These outcomes are strongly influenced by patient age, initial clinical grade such as World Federation of Neurosurgical Societies (WFNS) scale, and the occurrence of delayed cerebral ischemia (DCI). Rebleeding, if it occurs before aneurysm securing, dramatically worsens prognosis by roughly doubling the mortality risk compared to initial hemorrhage alone.[122][123]In the intensive care unit (ICU), SAH patients typically require a median length of stay of 14 days, often prolonged by mechanical ventilation needs and monitoring for complications. DCI contributes to about 23% of adverse outcomes, including mortality and severe morbidity, while hydrocephalus accounts for roughly 12% of such events, frequently necessitating external ventricular drainage. Prediction models combining WFNS clinical grading with the Fisher scale for radiographic blood load provide reliable estimates of 30-day mortality and poor functional outcome risks, aiding early decision-making.[124][125][126][127]Recent advancements in neurocritical care and endovascular techniques have contributed to improved immediate outcomes, with overall mortality rates declining to around 25% in high-volume centers as of 2023 data.[65]
Long-Term Sequelae
Survivors of subarachnoid hemorrhage (SAH) frequently face long-term neurological deficits that can profoundly affect daily functioning. Hemiparesis, characterized by weakness on one side of the body, occurs in a substantial proportion of cases, with focal neurological signs such as this being common in severe hemorrhages. Aphasia, impairing language comprehension and expression, and cranial nerve palsies, which may cause visual disturbances or facial weakness, are also prevalent sequelae, often persisting beyond the acute phase.[128][129]Cognitive impairments represent another major long-term challenge, with executive dysfunction—such as difficulties in planning and decision-making—and memory loss affecting up to 70% of survivors, particularly in those with severe initial injury. Verbal memory deficits, in particular, show impairment rates ranging from 14% to 61%, contributing to challenges in learning and recall. Fatigue, both mental and physical, is reported in 50-70% of patients even years post-event, exacerbating overall cognitive burden and reducing quality of life.[130][131][132]Psychological effects further compound these issues, with post-traumatic stress disorder (PTSD) emerging in 19-37% of survivors, often linked to the traumatic nature of the event. Depression affects approximately 30% of patients, persisting and correlating with poorer functional recovery. Return to work remains limited, with fewer than 50% of survivors resuming employment at one year, and rates as low as 6-17% returning to previous occupations, influenced by combined cognitive and emotional factors.[133][134][130]Vascular risks persist lifelong, with SAH survivors facing elevated chances of stroke recurrence, particularly if modifiable factors like hypertension and smoking are not controlled. Persistent smoking post-SAH increases recurrence risk in a dose-dependent manner, while hypertension amplifies overall cerebrovascular vulnerability, necessitating rigorous blood pressure management and smoking cessation.[135][136]Multidisciplinary rehabilitation, incorporating physical therapy (PT) for mobility, occupational therapy (OT) for daily activities, and speech therapy for communication deficits, is essential for optimizing outcomes. Such programs improve physical, cognitive, and functional recovery, with younger patients demonstrating better long-term results due to greater neuroplasticity and fewer comorbidities. Early initiation of rehabilitation enhances these benefits, supporting gradual independence.[137][138]Recent studies in 2025 have advanced prediction of functional outcomes using AI models, such as machine learning algorithms that forecast modified Rankin Scale (mRS) scores at six months based on clinical and laboratory data, aiding personalized rehabilitation planning in poor-grade SAH cases. These tools, including interpretable models for short-term poor outcomes, show promise in identifying high-risk patients early.[139][140]
History and Research Directions
Historical Developments
The concept of subarachnoid hemorrhage (SAH) emerged from early pathological observations of apoplexy, with Johann Jakob Wepfer providing one of the first detailed descriptions in 1695 through postmortem examinations that identified cerebral hemorrhage, including blood extravasation into the subarachnoid space, as the cause of sudden neurological collapse.[141] Nearly two centuries later, in 1924, Charles Symonds formalized the recognition of non-traumatic SAH by coining the term "spontaneous subarachnoid hemorrhage" in a seminal paper, linking it to ruptured intracranial aneurysms based on clinical symptoms like sudden headache and lumbar puncture evidence of bloody cerebrospinal fluid.[142] These early insights shifted understanding from vague notions of apoplexy to specific vascular pathology, though diagnosis remained challenging without imaging.Diagnostic progress accelerated in the 20th century, beginning with Egas Moniz's invention of cerebral angiography in 1927, which by the 1940s enabled preoperative visualization of saccular aneurysms as the primary cause of SAH in most cases.[143] The advent of computed tomography (CT) in the 1970s, with refinements and broader adoption in the 1980s, transformed SAH detection by allowing non-invasive identification of hyperdense blood in the basal cisterns, achieving sensitivity over 95% within the first 24 hours and drastically reducing reliance on invasive lumbar punctures or postmortem confirmation.[144] Concurrently, the 1980s saw the description of non-aneurysmal SAH subtypes, notably perimesencephalic hemorrhage by van Gijn and colleagues in 1985, characterized by localized blood around the midbrain on CT with negative angiography, representing about 10% of cases and carrying a more favorable prognosis due to lower rebleeding risk.[36]Therapeutic milestones paralleled diagnostic improvements, starting with surgical interventions. In 1937, Walter Dandy performed the first direct clipping of an intracranial aneurysm at the neck using a silver clip, establishing a curative approach to prevent rebleeding in ruptured cases and laying the foundation for modern neurosurgery.[145] Endovascular techniques emerged in the 1990s with Guido Guglielmi's development of detachable platinum coils in 1990, which allowed occlusion of aneurysm sacs via catheter without craniotomy, offering a safer option for high-risk patients.[146] Pharmacological breakthroughs included 1980s randomized trials of nimodipine, a calcium antagonist, which demonstrated reduced cerebral vasospasm and ischemic deficits, improving neurological outcomes by up to 40% in good-grade patients when administered orally for 21 days post-SAH.[147] The landmark 2002 International Subarachnoid Aneurysm Trial further validated coiling's superiority over clipping, showing a 23% absolute reduction in death or dependency at one year for eligible ruptured aneurysms.[148]These cumulative advances—spanning pathology, imaging, surgery, and pharmacotherapy—have driven a substantial decline in SAH case-fatality rates, from over 50% in the mid-20th century (with rates as high as 57% reported from 1945–1974 due to delayed diagnosis and limited interventions) to approximately 42% by the 1980s, and stabilizing around 40% today through multidisciplinary care emphasizing early securing of aneurysms and complication prevention.[149]
Recent Advances and Future Perspectives
The 2023 American Heart Association/American Stroke Association (AHA/ASA) guidelines for the management of aneurysmal subarachnoid hemorrhage (aSAH) introduced updated evidence-based recommendations emphasizing multimodal monitoring to detect cerebral vasospasm and delayed cerebral ischemia (DCI), including the use of transcranial Doppler ultrasonography, computed tomography angiography, and continuous electroencephalography in high-grade cases (Class I, Level of Evidence B-NR).[65] These guidelines also advocate for euvolemia maintenance to prevent DCI and discourage prophylactic induced hypervolemia through transfusions due to associated complications without outcome benefits (Class III, Level of Evidence B-R).[65] Early rehabilitation by multidisciplinary teams, initiated using validated screening tools for cognitive deficits, is recommended to identify discharge needs and improve functional recovery (Class I, Level of Evidence B-NR).[65] Complementing these, the 2024 SAHARA trial demonstrated that a restrictive transfusion strategy (hemoglobin threshold of 8 g/dL) was noninferior to a liberal approach (10 g/dL) in preventing unfavorable neurologic outcomes at 12 months, with rates of 37.7% versus 33.5% (risk ratio 0.88, 95% CI 0.72-1.09), supporting conservative transfusion practices to minimize risks like fluid overload.[150]Progress in biomarkers has advanced DCI prediction, with glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) emerging as promising indicators of neuronal damage and astrocytic activation in aSAH. Elevated serum GFAP levels at admission predict mortality and poor outcomes in intracerebral and subarachnoid hemorrhage cohorts, correlating with brain tissue injury severity.[151] Similarly, NfL elevations reflect axonal damage and have been associated with DCI risk in early post-aSAH cerebrospinal fluid analyses, though prospective validation in larger 2024-2025 cohorts remains ongoing.[152] Artificial intelligence models have enhanced outcome forecasting, achieving accuracies exceeding 80% in predicting mortality and functional status using routine clinical data like coagulation parameters and liver function; for instance, logistic regression models outperformed other algorithms in spontaneous aSAH mortality prediction with area under the curve values up to 0.85.[153] Interpretable deep learning approaches further integrate pretherapy variables to forecast modified Rankin Scale scores, aiding personalized risk stratification.[154]Therapeutic innovations focus on neurorepair and inflammation modulation. Stem cell therapies, particularly mesenchymal stem cell-derived extracellular vesicles, show preclinical promise in reducing brainedema and improving neurological function post-aSAH by promoting neurogenesis and anti-inflammatory effects, with phase I/II trials from 2023-2025 reporting safety and modest efficacy in related hemorrhagic strokes.[155]Anti-inflammatory agents targeting interleukin-1 (IL-1), such as IL-1 receptor antagonists (e.g., anakinra), have demonstrated reduced cerebral vasospasm and apoptosis in animal models, with phase II human trials confirming safety and lowered IL-6 levels in cerebrospinal fluid, though larger efficacy studies are needed.[156] Remote ischemic preconditioning, involving brief limb ischemia, has proven feasible and safe in aSAH patients, with 2025 pilot trials showing potential reductions in DCI incidence by enhancing cerebral blood flow and neuroprotection via increased BDNF levels.[157]Advances in critical care include multimodal neuromonitoring integrating brain tissue oxygenation, microdialysis for metabolic assessment, and intracranial pressure tracking, which guide targeted interventions in high-grade aSAH and correlate with improved outcomes by enabling early DCI detection (e.g., oxygenation thresholds below 20 mmHg prompting therapy escalation).[158] Personalized transfusion strategies, informed by the SAHARA trial, tailor thresholds to individual anemia severity and comorbidities, avoiding routine liberal approaches to reduce complications like pulmonary edema.[150] Looking ahead, gene therapy targeting somatic mutations in aneurysmpathogenesis, such as SOX17 activation via CRISPR-based editing, holds potential for preventing rupture in high-risk families by stabilizing vessel walls, with preclinical models showing reduced aneurysm formation.[159] Wearable intracranial pressure monitors, leveraging noninvasive cranial extensometry and machine learning, promise continuous outpatient tracking post-aSAH, with 2025 prototypes achieving nanometer resolution for early hydrocephalus detection.[160]Persistent challenges include addressing health disparities, where Black and Hispanic patients experience higher aSAH mortality and lower treatment access due to socioeconomic factors and geographic barriers, necessitating targeted interventions to equalize outcomes.[161] Ongoing long-term cognitive trials highlight persistent deficits in 75% of survivors, affecting memory and executivefunction, with multimodal rehabilitation protocols under evaluation to mitigate neuroinflammation-related impairment at 1-6 years post-event.[162]