Subarachnoid Hemorrhage

• Initial hemorrhage and acute intracranial hypertension: Rupture of a cerebral vessel (typically an intracranial aneurysm) causes immediate extravasation of blood into the subarachnoid space. This sudden increase in intracranial volume produces acute elevation in intracranial pressure (ICP) by the Monro-Kellie doctrine, which maintains that the skull contains three non-compressible components (brain tissue, blood, cerebrospinal fluid). The acute rise in ICP may transiently exceed cerebral perfusion pressure, causing loss of consciousness at the moment of hemorrhage. Elevated ICP also compresses cranial nerves (particularly CN III and VI) and distorts brainstem structures, explaining the immediate neurological deficits.

• Meningeal irritation and inflammatory cascade: Blood in the subarachnoid space triggers profound meningeal irritation, activating the innate immune system. Erythrocytes undergo lysis in the subarachnoid space, releasing hemoglobin and iron, which catalyzes free radical production through Fenton chemistry. This generates reactive oxygen species (ROS) including hydroxyl radicals, superoxide, and hydrogen peroxide. Simultaneously, microglial activation releases pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), complement activation proceeds via the classical pathway, and neutrophil infiltration amplifies tissue damage. Oxyhemoglobin and methemoglobin directly cause vasculitis of the vessel walls, particularly affecting large conducting arteries (Circle of Willis distribution). This inflammatory milieu explains the classic "meningismus" (neck stiffness, photophobia, headache) and contributes to delayed ischemic complications.

• Vasospasm and delayed cerebral ischemia: Beginning 48-72 hours after hemorrhage and persisting for 7-14 days, large cerebral vessels develop narrowing termed vasospasm. The mechanism involves a transition from acute inflammation to vascular remodeling: hemoglobin breakdown products (oxyhemoglobin, bilirubin oxidation products) directly injure endothelial cells and smooth muscle. Endothelin-1, a potent vasoconstrictor, is upregulated and acts on endothelin-A receptors on vascular smooth muscle. Simultaneously, nitric oxide (NO) production is impaired through scavenging by oxyhemoglobin, and superoxide reacts with NO to form peroxynitrite, further reducing bioavailable NO. Loss of the endothelium-dependent vasodilatory response increases vascular tone. Additionally, serotonin, prostaglandins, and catecholamines contribute to sustained vasoconstriction. This vasospasm produces regional cerebral blood flow reduction, which in conjunction with increased metabolic demand from the initial injury, causes delayed cerebral ischemia (DCI)—symptomatic vasospasm with infarction occurring in 20-30% of patients.

• Cerebral autoregulation impairment: Normal cerebral autoregulation maintains constant cerebral blood flow across a mean arterial pressure (MAP) range of 50-150 mmHg through myogenic and metabolic mechanisms. SAH disrupts this critical physiological process. Elevated ICP compresses vessels, smooth muscle is directly damaged by hemoglobin, and impaired NO signaling prevents appropriate vasodilatory responses to hypotension. The result is a narrowed autoregulatory window and pressure-passive cerebral perfusion, rendering the brain vulnerable to both hypotension and hypertensive breakthrough phenomena.

• Hydrocephalus development: Blood clots and inflammatory debris obstruct cerebrospinal fluid (CSF) flow through the foramen magnum and basal cisterns (communicating hydrocephalus), or less commonly, blood directly obstructs ventricular outflow (obstructive hydrocephalus). CSF reabsorption at the arachnoid granulations is impaired by hemoglobin-induced dysfunction. Ventricular enlargement produces increased ICP and can cause acute deterioration requiring ventriculostomy placement.

• Seizure pathophysiology: Cortical irritation from blood, superficial cortical siderosis (iron deposition), and altered ion homeostasis lower seizure threshold. Excitotoxicity from glutamate release in damaged cortical zones contributes to acute seizures and post-hemorrhage epilepsy.

• Ruptured intracranial aneurysm (85% of non-traumatic SAH): This is the most common cause of spontaneous SAH. Saccular (berry) aneurysms develop at branch points of major cerebral arteries where hemodynamic stress is greatest—85% occur at the anterior communicating artery (AComm), middle cerebral artery (MCA) bifurcation, or posterior communicating artery (PComm). The pathophysiology involves focal weakness in the tunica media and internal elastic lamina at high-flow zones. Familial clustering occurs with autosomal dominant polycystic kidney disease (ADPKD), accounting for 8% of aneurysms. The annual rupture risk for aneurysms <5 mm is approximately 0.1% per year, increasing to 1% per year for aneurysms 7-10 mm. Hypertension, smoking, and female sex increase aneurysm prevalence. Large anterior communicating artery aneurysms commonly cause hemiparesis and aphasia through local mass effect before rupture. Posterior communicating artery aneurysms compress CN III, causing ipsilateral pupil dilation and ptosis when expanding.

• Arteriovenous malformation (AVM) rupture (5-10% of non-traumatic SAH): AVMs are abnormal communications between arteries and veins lacking intervening capillary beds, creating high-flow, low-pressure shunts. Rupture occurs in approximately 2-4% of AVMs annually, with cumulative lifetime risk of 50-70%. AVMs are commonly located in the distribution of the middle cerebral artery. Associated risk factors include aneurysm formation within the AVM (increases rupture risk to 7% annually), deep venous drainage, and eloquent cortex location. The Spetzler-Martin grading system (size, location, venous drainage) predicts hemorrhage risk and surgical morbidity.

• Cerebral amyloid angiopathy (CAA): This condition involves amyloid-β deposition in cortical and leptomeningeal vessels, predominantly affecting elderly patients (age >60 years). CAA causes lobar (cortical and subcortical white matter) hemorrhages with recurrent bleeding in 10-37% at 5 years. Amyloid-β accumulates around small- to medium-sized arteries, causing microinfarcts, vessel wall breakdown, and microhemorrhages. CAA-related inflammation (CAA-I) presents with acute cognitive decline and may mimic vasculitis. Genetic mutations (amyloid precursor protein, presenilin-1) and apolipoprotein E-ε4 genotype increase CAA risk.

• Reversible cerebral vasoconstriction syndrome (RCVS): RCVS presents with recurrent thunderclap headaches and segmental vasoconstriction on angiography, with spontaneous resolution within 1-3 months. Associated triggers include pregnancy/postpartum state, sympathomimetic use (cocaine, amphetamines, decongestants), serotonergic drugs (SSRIs, SNRIs), immunosuppressants (tacrolimus, interferon-α), and hemorrhage itself. The pathophysiology involves endothelial dysfunction and impaired NO signaling. Approximately 50% of RCVS cases present with SAH from small arterial ruptures.

• Hypertension: Chronic hypertension increases aneurysm development and rupture risk through vascular remodeling and medial hypertrophy. Acute hypertension at hemorrhage onset reflects catecholamine surge and pain response.

• Smoking: Active smoking increases aneurysm prevalence and rupture risk 2-3 fold through endothelial dysfunction, oxidative stress, and impaired vascular repair. Smoking cessation reduces risk but benefits plateau after 10 years.

• Coagulopathy and anticoagulation: Warfarin, direct oral anticoagulants (DOACs), and antiplatelet agents increase hemorrhage risk in those with structural lesions. Intrinsic coagulopathy (hemophilia, thrombocytopenia <50,000/μL) can cause SAH without aneurysm.

• Connective tissue disorders: Marfan syndrome (FBN1 mutations), Ehlers-Danlos syndrome (COL3A1 mutations), and α1-antitrypsin deficiency increase aneurysm prevalence through defective extracellular matrix synthesis.

• Genetic syndromes: Autosomal dominant polycystic kidney disease (ADPKD) with PKDH1 mutation causes aneurysms in 8% of patients. Neurofibromatosis type 1 (dysplasia of media and elastic lamina).

• Stimulant use: Cocaine and amphetamines precipitate acute hypertension and vasculitis, causing SAH even without pre-existing aneurysm.

• Sudden-onset "worst headache of life" (thunderclap headache): This is the pathognomonic presenting symptom, occurring in 80-90% of patients with rupture. Patients describe instantaneous, maximal intensity pain—not gradual crescendo—reflecting the explosive release of blood into the closed cranial vault. The headache is diffuse (frontal and occipital regions), often accompanied by neck pain from meningeal irritation. Unlike migraine or tension-type headaches with prodromal symptoms, thunderclap onset is distinctive. The pain is constant, resolves minimally with analgesics, and intensifies with neck flexion (Kernig sign) and light (photophobia). Patients often recall the exact moment of hemorrhage ("felt like I was hit on the head" or "sudden explosion in my head"). Some present with sentinel headaches 6-20 days before major hemorrhage, representing warning leaks; recognition and angiographic screening can prevent catastrophic rebleeding.

• Loss of consciousness: Approximately 50% of patients lose consciousness at hemorrhage onset, reflecting acute ICP elevation exceeding cerebral perfusion pressure or immediate brainstem compression. Coma at presentation correlates with poor prognosis (Hunt-Hess grade IV-V). Even brief unconsciousness (seconds to minutes) followed by apparent recovery occurs in many patients, after which they may report memory loss of the event. Persistent unconsciousness indicates severe injury with brainstem involvement.

• Focal neurological deficits: These vary by aneurysm location. Anterior communicating artery aneurysms may cause hemiparesis, aphasia (dominant hemisphere), or abulia/behavioral changes from medial frontal/anterior cingulate lobe involvement. Posterior communicating artery aneurysms present with CN III palsy (ipsilateral ptosis, "down-and-out" pupil, loss of adduction) representing mass effect on the oculomotor nerve as it exits the midbrain. Middle cerebral artery aneurysms may cause hemiparesis, hemianopsia, or aphasia. Vertebrobasilar aneurysms present with brainstem signs (ataxia, cranial nerve palsies, spinothalamic deficits). Deficits present acutely from mass effect, hemorrhage into parenchyma, or infarction from vasospasm 3+ days post-hemorrhage.

• Meningismus: Blood irritates the meninges, causing neck stiffness (inability to flex neck without pain), positive Kernig sign (pain with passive knee extension when hip is flexed 90 degrees), and positive Brudzinski sign (reflex hip/knee flexion with passive neck flexion). These develop over 12-24 hours and peak at 48-72 hours. Photophobia (eye discomfort with light) and phonophobia (intolerance to sound) accompany meningeal irritation. Fever may occur from inflammatory response without infection.

• Autonomic symptoms: Nausea and vomiting occur in 70% from increased ICP and meningeal irritation. Hypertension is nearly universal (MAP often 120+ mmHg) from catecholamine surge and baroreceptor-mediated response to elevated ICP. Myocardial stunning from massive catecholamine release produces Takotsubo cardiomyopathy in 5-10% (apical ballooning on echocardiography, elevated troponin, reversible). Cardiac arrhythmias and ECG changes (T-wave inversions, ST depression, QT prolongation) occur from increased sympathetic tone.

• Seizures: Acute seizures occur in 10-20% at presentation, typically generalized tonic-clonic. Risk factors include lobar hemorrhage location (cortical irritation), large intraventricular hemorrhage volume, and poor grade at presentation. Post-hemorrhagic epilepsy develops in 10-30% at long-term follow-up.

• Respiratory abnormalities: Hyperventilation may occur from elevated ICP and central nervous system irritation. In comatose patients, Cheyne-Stokes respiration or ataxic patterns may develop with brainstem compression. Pulmonary edema (neurogenic pulmonary edema) results from massive sympathetic discharge causing capillary leak.

• Altered mental status: Confusion, delirium, or obtundation occurs from acute encephalopathy due to elevated ICP, blood-brain barrier disruption, and systemic inflammatory response. Some present with purely behavioral changes (personality alterations, agitation) without focal deficits, particularly with anterior communicating artery aneurysm.

• Rebleeding risk: Risk of rebleeding is highest in first 24 hours (approximately 4% per day), decreasing to 1-2% per day after 10 days. Rebleeding presents with acute deterioration, sudden return of coma, new focal deficits, or hemodynamic instability. Mortality from rebleeding exceeds 70%, driving urgent aneurysm securing via endovascular coiling or surgical clipping.

• Non-contrast head CT (first-line imaging): CT is 95-100% sensitive within 6 hours of onset, detecting blood as hyperdense (bright) material in the subarachnoid space. Characteristic patterns include blood filling the basal cisterns (suprasellar cistern, ambient cisterns, interpeduncular cistern), sulci, and ventricular system (indicating intraventricular hemorrhage). The distribution suggests hemorrhage source: anterior circulation aneurysms (AComm, MCA) produce frontal and Sylvian fissure predominance; posterior circulation sources cause blood in posterior fossa and fourth ventricle. CT also identifies complications: hydrocephalus (ventricular enlargement), intraparenchymal hematoma (mass effect), and subdural hematoma (traumatic SAH or unsecured aneurysm site). Sensitivity decreases after 6-12 hours as blood becomes isodense to brain. False negatives occur in 2-5% of cases, particularly with small-volume hemorrhage or repeat imaging after symptom onset.

• Lumbar puncture (if CT negative but clinical suspicion high): When CT is negative but suspicion remains high (classic thunderclap history, meningismus), LP establishes SAH diagnosis. Cerebrospinal fluid (CSF) shows: xanthochromia (yellowish discoloration from bilirubin breakdown of hemoglobin in RBCs), > 1000 RBCs/μL (non-traumatic SAH, persistent across tubes; traumatic tap shows decreasing RBC count across sequential tubes), pleocytosis (100-5000 WBCs/μL, predominantly neutrophils initially, lymphocytes by 48 hours), elevated protein (50-1000 mg/dL), and normal glucose (distinguishing from meningitis). Xanthochromia becomes apparent 12 hours post-hemorrhage and persists for 2-3 weeks, making it more specific than RBCs alone for excluding traumatic tap. LP is deferred if CT shows SAH, mass effect, or hydrocephalus (risk of herniation).

• Cerebral angiography (digital subtraction preferred): This is the gold

Immediate stabilisation (ABCs and ICP)

• Airway and head-of-bed elevation: intubate for Hunt–Hess IV–V or inability to protect the airway; elevate head of bed and treat pain/agitation, since coughing and straining spike ICP and promote rebleeding.
• Reversal of anticoagulation: per AHA/ASA 2023 aneurysmal SAH guideline, immediately reverse coagulopathy (4-factor PCC plus vitamin K for warfarin; idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors) — unsecured aneurysm plus anticoagulation is lethal.
• Blood pressure control with a titratable IV agent: dihydropyridine calcium channel blocker (nicardipine infusion) or labetalol until the aneurysm is secured. AHA/ASA advises avoiding extremes of blood pressure rather than chasing one number; many centers target systolic pressure below roughly 160 mmHg, balancing rebleeding risk against cerebral perfusion in a brain with impaired autoregulation.

Pharmacologic first-line

• Nimodipine: oral (or NG) dihydropyridine calcium channel blocker, 60 mg every 4 hours for 21 days, started as soon as possible. It is the only drug with proven mortality/functional benefit; it reduces delayed cerebral ischemia by neuroprotection, not by reversing angiographic vasospasm. Hold or split the dose for hypotension. IV nimodipine is not used in the US.
• Analgesia, antiemetics, stool softeners, and normothermia/euglycemia: reduce ICP surges and secondary injury.

Definitive management

• Early aneurysm obliteration within 24–72 hours by endovascular coiling or microsurgical clipping (AHA/ASA 2023). Coiling is preferred when the lesion is amenable to both (ISAT); clipping favors wide-necked MCA aneurysms and large clots requiring evacuation.
• External ventricular drain for acute hydrocephalus or intraventricular hemorrhage.

Delayed cerebral ischemia

• Euvolemia plus induced hypertension (vasopressor, e.g., norepinephrine) for symptomatic DCI; endovascular rescue with intra-arterial vasodilators or balloon angioplasty if refractory.

Avoid

• Prophylactic hypervolemia/hemodilution (the old triple-H), glucocorticoids, routine long-term antiseizure prophylaxis, hypotonic fluids, and routine antifibrinolytics — extended tranexamic acid did not improve outcomes and increased ischemic events.

Neurologic emergencies

• Rebleeding: highest risk in the first 24 hours from clot lysis over an unsecured aneurysm dome. Signals: abrupt recurrence of thunderclap pain, sudden coma, new pupillary asymmetry, or Cushing reflex. Mortality exceeds that of the index bleed — emergency; repeat non-contrast CT and expedite securing the aneurysm.
• Acute hydrocephalus: blood obstructs the basal cisterns and impairs arachnoid granulation absorption. Signals: declining level of consciousness within hours to days, upgaze palsy, enlarging temporal horns on CT — emergency, treat with external ventricular drain.
• Delayed cerebral ischemia (days 3–14): hemoglobin-driven endothelin-1 excess and nitric oxide scavenging produce vasospasm and microcirculatory failure. Signals: new focal deficit or a drop of ≥2 points on GCS, rising transcranial Doppler velocities, narrowing on CTA — emergency, requires induced hypertension and possible endovascular rescue.
• Seizures and elevated ICP with herniation: cortical irritation by blood and mass effect from intraparenchymal clot.

Systemic complications

• Hyponatremia: cerebral salt wasting (natriuretic peptide–driven, hypovolemic, high urine output) versus SIADH (euvolemic). Volume status is the discriminator; fluid restriction is dangerous in cerebral salt wasting because hypovolemia precipitates DCI — use isotonic or hypertonic saline and salt supplementation.
• Neurogenic stunned myocardium / Takotsubo cardiomyopathy: catecholamine surge causes apical ballooning, troponin elevation, deep T-wave inversions and QT prolongation. The common trap is treating it as acute coronary syndrome and anticoagulating an unsecured aneurysm.
• Neurogenic pulmonary edema: sympathetic capillary leak; bilateral infiltrates with normal cardiac filling pressures.
• Terson syndrome: intraocular/vitreous hemorrhage from acute ICP rise; blurred vision, worse prognosis.

Treatment-related

• Coiling/clipping: thromboembolic infarction, intraprocedural rupture, coil compaction with recurrence, retraction injury.
• EVD: ventriculitis and catheter-tract hemorrhage; chronic communicating hydrocephalus may require VP shunt.
• Nimodipine hypotension and induced hypertension causing demand ischemia or pulmonary edema.

• "Worst headache of my life," maximal at onset: thunderclap headache is the stem's signal. Single best next step is non-contrast head CT, not MRI, not LP, not angiography.
• CT negative but story classic: next step is lumbar puncture looking for xanthochromia, which requires roughly 12 hours to develop and persists for weeks. Persistent RBC counts across tubes 1 and 4 argue against a traumatic tap. In the modern stem, CT within 6 hours read by a neuroradiologist that is negative may instead be followed by CTA.
• After SAH is confirmed, find the aneurysm: CT angiography, with digital subtraction angiography as the gold standard, then secure it within 24–72 hours by coiling or clipping (AHA/ASA 2023).
• Nimodipine is the one drug to memorize: oral, 60 mg q4h for 21 days. It improves neurologic outcome by reducing delayed cerebral ischemia — the distractor is claiming it prevents angiographic vasospasm or that it should be given IV.
• Day 3–14 new focal deficit = vasospasm/DCI until proven otherwise. Day 0–1 sudden deterioration = rebleeding. Hours-to-days depressed consciousness with big ventricles = hydrocephalus. The timeline is the answer key.
• CN III palsy with a dilated pupil = compressive posterior communicating artery aneurysm (pupillomotor fibers run superficially). A pupil-sparing third nerve palsy suggests microvascular/diabetic ischemia instead.
• Associations examiners love: ADPKD, Ehlers–Danlos type IV, smoking, hypertension, and first-degree relatives with SAH. The sentinel headache days to weeks earlier is the missed warning leak.
• Hyponatremia trap: do not fluid-restrict SAH patients. Cerebral salt wasting is hypovolemic and restriction precipitates ischemia — give saline.
• **Do not give steroids, prophylactic hypervolemia (triple-H), or routine antifibrinolytics**, and never perform LP first when CT already shows blood, mass effect, or hydrocephalus.