Incidence & Outcomes

• Incidence: ~9 per 100,000 person-years worldwide; higher in Finland and Japan (~20 per 100,000)
• Peak age: 50–60 years; female:male ratio ~1.6:1
• Case fatality rate: ~35% at 30 days; ~50% overall mortality (including pre-hospital deaths)
• ~12–15% of patients die before reaching hospital
• Of survivors, ~30% have moderate-to-severe disability; only ~33% achieve good functional recovery
• SAH accounts for ~5% of all strokes but disproportionate share of stroke-related lost productive life years (younger patients)

Risk Factors

Modifiable Risk Factors

• Cigarette smoking: Strongest modifiable risk factor; ~3–4× increased risk; dose-dependent; risk declines after cessation
• Hypertension: ~2.5× increased risk; promotes aneurysm formation, growth, and rupture
• Heavy alcohol consumption: ≥150 g/week (≥~10 drinks/week); binge drinking especially risky
• Cocaine and sympathomimetic drug use: Acute hypertensive surges → rupture; cocaine is a major risk factor in young patients

Non-Modifiable Risk Factors

• Family history: First-degree relative with SAH → 3–7× increased risk; two or more affected first-degree relatives → screening recommended
• Female sex: Especially post-menopausal (estrogen may be protective)
• Prior SAH: ~2% per year risk of new SAH from a different aneurysm

Associated Genetic & Connective Tissue Conditions

• Autosomal Dominant Polycystic Kidney Disease (ADPKD): ~8–12% harbor intracranial aneurysms (vs. 2–3% general population); screening recommended, especially with family history of SAH
• Ehlers-Danlos syndrome type IV (vascular type): Defective type III collagen → arterial fragility; aneurysms and dissections
• Fibromuscular dysplasia (FMD): ~7% have intracranial aneurysms; “string of beads” on angiography
• Coarctation of the aorta: Associated with intracranial aneurysms, possibly due to hemodynamic stress
• Marfan syndrome: Modest association with intracranial aneurysms (less strong than ADPKD or Ehlers-Danlos IV)
• Hereditary hemorrhagic telangiectasia (HHT): Associated with pulmonary AVMs and rarely cerebral aneurysms

Aneurysm Types

Aneurysm Locations & Frequency

• General population aneurysm prevalence: ~2–3% (autopsy and MRA studies); most are small (<7 mm) and never rupture
• ~85% of aneurysms are in the anterior circulation; ~15% in the posterior circulation
• ~20–30% of patients have multiple aneurysms — identification of the ruptured aneurysm is critical (location of blood, largest aneurysm, irregular shape, daughter bleb)
• Aneurysm rupture risk increases with size (>7 mm), posterior circulation location, irregular morphology, and “daughter sac” or bleb

Classic Features

• “Thunderclap headache”: Sudden-onset, maximal-intensity headache reaching peak within seconds — classically described as the “worst headache of my life”
• Present in ~80% of cases; often occipital or diffuse
• May occur during exertion, straining (Valsalva), coitus, or at rest
• Brief loss of consciousness at onset in ~50% (acute rise in ICP)
• Nausea and vomiting: Very common; from meningeal irritation and elevated ICP

Sentinel Headache (Warning Leak)

• Occurs in 10–40% of patients in the days to weeks before major SAH
• Represents a small “herald bleed” or aneurysmal expansion
• Typically severe, unusual headache that resolves spontaneously
• Frequently misdiagnosed as tension headache or migraine — missed sentinel headaches carry high morbidity; patients who present with sentinel headache and are correctly diagnosed have significantly better outcomes

Meningeal Signs

• Meningismus: Nuchal rigidity, photophobia, Kernig sign (pain with knee extension when hip flexed), Brudzinski sign (involuntary hip/knee flexion with passive neck flexion)
• May take 3–12 hours to develop after hemorrhage onset (time for RBC lysis and meningeal irritation)
• Absence of meningismus in the first few hours does NOT exclude SAH

Focal Neurological Deficits

• CN III palsy: PCom or basilar tip aneurysm → ipsilateral pupil dilation, ptosis, “down and out”
• CN VI palsy: Often bilateral; non-localizing sign from elevated ICP (false localizing sign)
• Hemiparesis: From intracerebral extension of hemorrhage or vasospasm
• Visual field defects: ACom aneurysm compressing optic chiasm → bitemporal hemianopia
• Lower cranial nerve palsies: PICA/vertebral aneurysms → CN IX, X, XII deficits

Terson Syndrome

• Intraocular hemorrhage (vitreous, subhyaloid, or retinal) associated with SAH
• Occurs in ~13–20% of SAH patients
• Mechanism: Acute ICP elevation → transmitted pressure along optic nerve sheath → retinal venous outflow obstruction
• Associated with higher-grade SAH and worse prognosis
• Fundoscopy may show subhyaloid hemorrhage (dome-shaped collection layering in front of retina)
• Usually resolves spontaneously; vitrectomy may be needed if vision remains impaired

Hunt & Hess Scale

• Clinical grading based on symptoms and exam at presentation
• Correlates with surgical risk and overall prognosis

World Federation of Neurosurgical Societies (WFNS) Scale

• Based on GCS score and presence of focal deficits
• More objective than Hunt & Hess; better inter-rater reliability

Modified Fisher Scale

• Based on CT appearance of hemorrhage; predicts risk of vasospasm and delayed cerebral ischemia
• Thick SAH and presence of intraventricular hemorrhage (IVH) confer highest vasospasm risk

• Thick SAH = ≥1 mm clot in cisterns or fissures; thin SAH = <1 mm
• Modified Fisher 3 and 4 carry the highest risk of symptomatic vasospasm

Non-Contrast CT Head

• First-line test for suspected SAH — rapid, widely available
• Sensitivity by time from onset:
  • <6 hours: ~98–100% (essentially rules out SAH if negative on modern scanners)
  • 6–12 hours: ~95–98%
  • 12–24 hours: ~93%
  • Day 3: ~80%
  • Day 5: ~70%
  • Day 7: ~50%
  • >2 weeks: <30%
• CT findings: Hyperdense blood in basal cisterns (suprasellar, interpeduncular, ambient, sylvian fissures), interhemispheric fissure, ventricles (IVH)
• Distribution of blood helps localize the ruptured aneurysm:
  • Interhemispheric fissure → ACom
  • Sylvian fissure (asymmetric) → MCA bifurcation
  • Prepontine/perimesencephalic cisterns → basilar tip or perimesencephalic non-aneurysmal SAH

Lumbar Puncture

• Required when CT is negative but clinical suspicion for SAH remains high
• Timing: Wait at least 6–12 hours after headache onset to allow xanthochromia to develop (RBC lysis → oxyhemoglobin/bilirubin)
• Key findings:
  • Elevated opening pressure
  • RBCs that do NOT clear from tube 1 to tube 4 (traumatic tap shows decreasing RBC count)
  • Xanthochromia: Yellow discoloration of supernatant after centrifugation — the most reliable finding; caused by RBC breakdown products; distinguishes SAH from traumatic tap
  • Elevated protein; may have pleocytosis (inflammatory response to blood)
• Spectrophotometry (UK standard) is more sensitive for xanthochromia than visual inspection
• A negative LP obtained ≥6h after onset with no xanthochromia and no RBCs effectively excludes SAH

CT Angiography (CTA)

• Sensitivity: >95–98% for aneurysms ≥3 mm; lower for <3 mm
• Rapid, non-invasive; available at most centers
• Can identify aneurysm location, size, morphology, and relationship to parent vessel
• Often obtained simultaneously with NCCT in the acute SAH workup (CT + CTA protocol)
• CTA “spot sign” (contrast extravasation) suggests active bleeding and higher rebleed risk

Digital Subtraction Angiography (DSA)

• Gold standard for detecting and characterizing intracranial aneurysms
• Sensitivity: ~99% — can detect aneurysms as small as 1–2 mm
• Provides dynamic flow information, identifies vasospasm, and guides treatment planning
• If initial DSA is negative in confirmed SAH: repeat in 1–2 weeks (may miss aneurysm due to thrombosis or vasospasm); ~2–5% initially negative DSAs reveal aneurysm on repeat
• If repeat DSA negative → consider perimesencephalic SAH pattern (benign variant) or rare causes (spinal vascular malformation, dural AVF)
• Complication rate: ~0.5–1% risk of neurological deficit (stroke from catheter embolism)

Ottawa SAH Rule

• Clinical decision rule for alert patients ≥15 years with new severe non-traumatic headache reaching maximum intensity within 1 hour
• 100% sensitivity (but low specificity) — designed to NOT miss SAH
• High-risk features (any one triggers investigation):
  • Age ≥40 years
  • Neck pain or stiffness
  • Witnessed loss of consciousness
  • Onset during exertion
  • Thunderclap headache (instant peak)
  • Limited neck flexion on exam

Securing the Aneurysm: Clipping vs. Coiling

Surgical Clipping

• Craniotomy with placement of a metal clip across the aneurysm neck — excludes aneurysm from circulation
• Advantages: Durable, lower retreatment rates, allows evacuation of hematoma, direct visualization
• Preferred when: MCA bifurcation aneurysms (easily accessible, wide neck), associated intraparenchymal hematoma requiring evacuation, wide-necked aneurysms not amenable to coiling

Endovascular Coiling

• Catheter-based placement of platinum coils within the aneurysm sac → promotes thrombosis
• Advantages: Less invasive, shorter recovery, lower procedural morbidity
• Preferred when: Posterior circulation aneurysms (basilar tip), elderly patients, high surgical-grade patients, narrow-necked aneurysms
• Adjunctive techniques: Balloon-assisted coiling, stent-assisted coiling (requires dual antiplatelet therapy), flow diverters (Pipeline Embolization Device — for large/giant, wide-necked aneurysms)

ISAT Trial (International Subarachnoid Aneurysm Trial, 2002)

• Largest RCT comparing clipping vs. coiling (2,143 patients with ruptured aneurysms amenable to either treatment)
• Results: Coiling had 23.5% relative risk reduction in death or dependency at 1 year (23.7% coiling vs. 30.6% clipping); absolute risk reduction ~7%
• Long-term follow-up: Survival benefit of coiling maintained at 7 years; however, higher rebleeding rate with coiling (2.9% vs. 0.9% over 10 years)
• Bottom line: Coiling is preferred when both options are feasible, but clipping may be preferred for certain anatomies (MCA, wide neck) or when long-term durability is prioritized

BRAT Trial (Barrow Ruptured Aneurysm Trial, 2012)

• Randomized all SAH patients (not just those amenable to both); crossover from coil to clip was allowed
• Similar outcomes between groups at 1 year; at 6 years, no significant difference in poor outcome
• Confirmed that posterior circulation aneurysms had better outcomes with coiling
• MCA aneurysms had better outcomes with clipping

Timing of Intervention

• Early aneurysm securing (<24 hours, ideally <12 hours) is the standard of care
• Rationale: Reduces rebleeding risk (highest in first 24h — ~4% on day 1, ~1.5%/day for next 14 days)
• Early securing also allows aggressive treatment of vasospasm (induced hypertension) without fear of rebleeding
• Ultra-early treatment (<6 hours) may further reduce rebleeding

Pre-Intervention Blood Pressure Management

• Target SBP <160 mmHg (AHA/ASA guidelines) before aneurysm is secured
• Balance between preventing rebleed (lower BP) and maintaining cerebral perfusion
• Agents: Nicardipine infusion (preferred — titratable), labetalol, clevidipine
• Avoid nitroprusside (increases ICP) and hydralazine (unpredictable drops)

Antifibrinolytic Therapy (Bridge to Definitive Treatment)

• Aminocaproic acid (Amicar) or tranexamic acid (TXA)
• Short-term use (<72 hours) while awaiting aneurysm repair to reduce rebleeding
• Mechanism: Inhibit fibrinolysis → stabilize clot at rupture site
• AHA/ASA Class IIa recommendation for short-term antifibrinolytic therapy when there is an unavoidable delay in aneurysm treatment
• NOT for prolonged use — historical studies showed long-term use increased thrombotic complications (DVT, hydrocephalus, vasospasm) without net benefit

Definitions & Timeline

• Angiographic vasospasm: Arterial narrowing on DSA or CTA; occurs in ~70% of SAH patients
• Clinical (symptomatic) vasospasm: New neurological deficit attributable to vasospasm; occurs in ~30%
• Delayed cerebral ischemia (DCI): Clinical deterioration or new infarct on imaging attributed to vasospasm; the clinically meaningful endpoint
• Timeline:
  • Onset typically day 3 after SAH
  • Peak: days 7–10
  • Can persist through day 14–21
  • Mnemonic: “4-14 rule” — vasospasm peaks between days 4–14
• Risk factors for vasospasm: Thick clot (Modified Fisher 3–4), higher Hunt & Hess grade, cigarette smoking, cocaine use, younger age

Monitoring

Transcranial Doppler (TCD)

• Non-invasive, bedside, daily monitoring for vasospasm during the at-risk period
• Measures mean flow velocity (MFV) in basal cerebral arteries (especially MCA)
• MCA MFV interpretation:
  • <120 cm/s = normal
  • 120–200 cm/s = mild-to-moderate vasospasm
  • >200 cm/s = severe vasospasm
• Lindegaard ratio = MCA MFV / extracranial ICA MFV
  • Distinguishes vasospasm from hyperemia (high flow state from systemic causes)
  • <3: Hyperemia (elevated velocities from increased cardiac output, not vessel narrowing)
  • 3–6: Moderate vasospasm
  • >6: Severe vasospasm
• TCD can miss distal vessel vasospasm and ACA/PCA spasm

Other Monitoring Modalities

• CT perfusion (CTP): Detects regional perfusion deficits before clinical deterioration; increasing role in vasospasm assessment
• Continuous EEG: Alpha/delta ratio changes may detect early ischemia
• DSA: Gold standard for confirming vasospasm; also allows endovascular treatment

Treatment of Vasospasm & DCI

Nimodipine

• The ONLY medication proven to improve outcomes after SAH (Pickard et al., 1989)
• Dosing: 60 mg PO (or via enteral tube) every 4 hours for 21 days
• Reduces DCI and improves neurological outcomes; does NOT significantly reduce angiographic vasospasm
• Mechanism: Likely neuroprotective (calcium channel blockade in neurons) rather than preventing large-vessel vasospasm
• Side effect: Hypotension — if SBP drops, can give 30 mg q2h instead; do NOT stop nimodipine, reduce dose instead
• IV nimodipine is NOT approved in the US (IV formulation available in Europe); do NOT give oral tablets IV (risk of severe hypotension and cardiac arrest)

Induced Hypertension

• Current standard of care for symptomatic vasospasm (after aneurysm is secured)
• Uses vasopressors (phenylephrine or norepinephrine) to raise MAP and improve CBF through narrowed vessels
• Typical target: SBP 180–220 mmHg (individualized based on clinical response)
• Replaces “Triple-H therapy” (Hypertension, Hypervolemia, Hemodilution) — hypervolemia and hemodilution are no longer recommended (no evidence of benefit; increased complications including pulmonary edema, dilutional anemia)
• Euvolemia is the goal — avoid both hypovolemia (reduces perfusion) and hypervolemia (no benefit, increases pulmonary edema)

Endovascular Rescue Therapies

• For vasospasm refractory to medical management
• Intra-arterial vasodilators: Verapamil, nicardipine, milrinone injected directly into spastic vessel via catheter → transient effect; may need repeated treatments
• Balloon angioplasty: Mechanical dilation of spastic proximal vessels (ICA, MCA M1, basilar, vertebral); more durable effect than pharmacologic vasodilators; risk of vessel rupture (~1–4%); only for proximal, accessible vessels

Rebleeding

• Most feared early complication — carries ~70% mortality
• Highest risk in first 24 hours (~4% on day 1); ~1–2% per day for the next 2 weeks if untreated
• Without treatment: ~20% rebleed within 14 days, ~50% within 6 months
• Prevention: Early aneurysm securing (<24h), BP control (SBP <160), short-term antifibrinolytics, bed rest, stool softeners, avoid Valsalva
• Clinical signs: Sudden deterioration, new headache severity, decreased consciousness, new focal deficits

Hydrocephalus

Acute Hydrocephalus (Hours to Days)

• Occurs in ~20–30% of SAH patients
• Mechanism: Blood in the ventricular system or basal cisterns → obstruction of CSF pathways (obstructive/non-communicating hydrocephalus)
• Presentation: Decreased level of consciousness, downward gaze deviation, enlarged ventricles on CT
• Treatment: External ventricular drain (EVD) placement — also allows ICP monitoring and CSF drainage

Chronic Hydrocephalus (Weeks to Months)

• Occurs in ~15–20% of SAH survivors
• Mechanism: Communicating hydrocephalus from impaired CSF absorption at arachnoid granulations (fibrosis/scarring from blood products)
• Presentation: Failure to improve cognitively, gait difficulty, incontinence (normal pressure hydrocephalus triad)
• Treatment: Ventriculoperitoneal (VP) shunt placement

Seizures

• Acute symptomatic seizures: Occur in ~6–10% at onset or within 24 hours
• Risk factors: Higher-grade SAH, thick clot, MCA aneurysm location, rebleeding, intraparenchymal hemorrhage
• Prophylactic antiepileptics are controversial:
  • AHA/ASA 2012 guidelines: Consider short-term (3–7 day) prophylaxis in the immediate post-hemorrhagic period
  • Phenytoin should be AVOIDED — associated with worse cognitive outcomes and fever in SAH (Naidech et al.)
  • If prophylaxis used, levetiracetam is preferred over phenytoin
  • Long-term AEDs only if documented seizure occurs

Hyponatremia: SIADH vs. Cerebral Salt Wasting

• Hyponatremia occurs in ~30–50% of SAH patients and is associated with worse outcomes
• Critical to distinguish between the two because treatment is opposite

Cardiac Complications

• Cardiac injury occurs in ~20–30% of SAH patients from massive sympathetic surge (“catecholamine storm”)
• ECG changes: Widespread T-wave inversions (“cerebral T waves”), QT prolongation, ST-segment changes mimicking STEMI, U waves
• Troponin elevation: Common (~30%); from myocardial contraction band necrosis (catecholamine-mediated), NOT coronary atherosclerosis
• Takotsubo (stress) cardiomyopathy: Apical ballooning with reduced EF; triggered by catecholamine surge; typically reversible within 1–2 weeks
• Wall motion abnormalities: May reduce cardiac output and worsen cerebral perfusion
• Arrhythmias: Sinus bradycardia, atrial fibrillation, ventricular tachycardia, torsades de pointes (from QTc prolongation)
• Management: Echocardiography to assess function; optimize hemodynamics; avoid excessive beta-blockade (need adequate cardiac output for cerebral perfusion)

Neurogenic Pulmonary Edema

• Rapid-onset pulmonary edema within minutes to hours of SAH (or any acute brain injury)
• Mechanism: Massive sympathetic discharge → systemic vasoconstriction → blood shifts to pulmonary vasculature + increased pulmonary capillary permeability
• CXR: Bilateral pulmonary edema without cardiomegaly; low PCWP (non-cardiogenic) or may have transient high PCWP initially
• Treatment: Supportive — mechanical ventilation with lung-protective strategies; optimize ICP; usually resolves within 24–72 hours

Overview & Diagnosis

• Accounts for ~10–15% of all spontaneous SAH
• Benign prognosis — no vasospasm, no rebleeding, excellent functional outcomes
• Probable source: Perimesencephalic venous or capillary rupture (not arterial)

Characteristic CT Pattern

• Blood confined to the perimesencephalic cisterns (interpeduncular, ambient, prepontine cisterns)
• Center of blood is ANTERIOR to the brainstem (not extending to Sylvian fissures or interhemispheric fissure)
• No significant extension into lateral sylvian fissures or anterior interhemispheric fissure
• No frank intraventricular hemorrhage (small amount of layering blood acceptable)

Diagnostic Requirements

• Classic perimesencephalic blood distribution on CT
• Negative DSA (mandatory — must rule out basilar tip or vertebral aneurysm)
• If initial DSA is negative, some guidelines recommend one repeat DSA; increasingly, CTA is considered sufficient if DSA is negative
• Cannot diagnose perimesencephalic SAH without negative angiography

Key Differences from Aneurysmal SAH

• No vasospasm (or exceedingly rare)
• No rebleeding
• Hydrocephalus is uncommon
• Patients typically present with good clinical grade (Hunt & Hess 1–2)
• No long-term neurological deficits in most cases; can resume normal activities

Rupture Risk: ISUIA Data

• International Study of Unruptured Intracranial Aneurysms (ISUIA, 2003) — largest prospective study of unruptured aneurysm natural history
• 5-year cumulative rupture rates by size and location:

• Key takeaway: Posterior circulation and PCom aneurysms carry significantly higher rupture risk at every size
• Limitation of ISUIA: Selection bias (higher-risk patients may have been treated, leaving lower-risk ones in observation group); small anterior circulation aneurysms (<7 mm) may have more rupture risk than ISUIA suggested — most ruptured aneurysms in clinical practice are <10 mm

PHASES Score

• Validated score predicting 5-year rupture risk for unruptured aneurysms
• Components:
  • P — Population (North American/European vs. Japanese/Finnish)
  • H — Hypertension
  • A — Age (≥70 vs. <70)
  • S — Size of aneurysm (<7, 7–9.9, 10–19.9, ≥20 mm)
  • E — Earlier SAH from a different aneurysm
  • S — Site (ICA, MCA, ACA/PCom/posterior circulation)
• Higher score = higher rupture risk; helps guide shared decision-making

Treatment Thresholds & Decision-Making

• Generally consider treatment when:
  • Aneurysm ≥7 mm (anterior circulation) or any size if posterior circulation/PCom
  • Symptomatic aneurysm (cranial nerve palsy, headache from mass effect)
  • Documented growth on serial imaging
  • Irregular morphology (daughter sac, multilobed)
  • Family history of SAH
  • Patient anxiety affecting quality of life
• Observation may be appropriate when:
  • Small (<5–7 mm) anterior circulation aneurysm in patients without risk factors
  • Elderly patients with significant comorbidities (limited life expectancy)
  • High procedural risk location
• If observing: Serial imaging (MRA or CTA) at 6–12 months, then annually, then every 2–3 years if stable
• Modifiable risk factor management: Smoking cessation (most important), BP control, avoid cocaine/sympathomimetics

Screening Recommendations

• Screen with MRA (non-invasive, no radiation) in:
  • ≥2 first-degree relatives with intracranial aneurysm or SAH
  • ADPKD patients (especially with family history of aneurysm/SAH)
  • Coarctation of the aorta
  • Ehlers-Danlos type IV, FMD (consider screening)
• Do NOT routinely screen the general population (prevalence ~2–3%, but most never rupture; harms of false-positive testing and anxiety outweigh benefits)
• One first-degree relative with SAH: Screening is controversial; AHA/ASA suggests it may be reasonable (Class IIb)
• If screening reveals an aneurysm, follow-up imaging and management per rupture risk assessment