Non-traumatic subarachnoid (= meningeal) hemorrhages

Subarachnoid hemorrhages (SAH) or "meningeal hemorrhages" refer to bleeding into the subarachnoid space. When excluding traumatic cases, they represent a form of hemorrhagic stroke, with the most common etiology being the rupture of an arterial aneurysm. Besides general and symptomatic management, an urgent etiological treatment is typically required.

They account for approximately 5% of hemorrhagic strokes (1 case per 10,000 people per year), but they are the most common type in people under 50 and result in the highest morbidity and mortality in this age group. Mortality ranges from 20% to 50%, with 10% dying before reaching the hospital. The peak incidence is 55 years for men and 60 years for women, with a female-to-male sex ratio of about 1.5 to 1.

Etiologies

• 60 to 85% of cases: aneurysm rupture, which is a weakness in the internal elastic lamina of the vascular wall, most commonly occurring at the division of a vessel, leading to dilation and formation of a sac that can rupture.
  • Congenital origin accounts for the vast majority of cases
    • Mostly non-hereditary.
    • Hereditary malformation diseases may justify screening in cases of polycystic kidney disease or in patients with at least two first-degree relatives who had subarachnoid hemorrhages.
  • Infectious vasculitis (responsible for 2.5% of aneurysms, often termed "mycotic aneurysms," although this term is inaccurate): rare.
    • Bacterial: primarily from endocarditis, borreliosis, etc.
    • Fungal: from aspergillus, phycomycetes, etc., usually involving regional infections (e.g., sphenoid sinusitis) or endocarditis from Candida.
    • Viral: post-herpes zoster vasculitis, HIV, etc.
  • Non-infectious vasculitis: systemic lupus erythematosus, polyarteritis nodosa, Horton’s disease, Churg-Strauss, Wegener’s disease, Behçet’s disease, primary vasculitis, toxic (cocaine), etc.
  • Hemoglobinopathies: primarily sickle cell disease due to repeated arterial occlusions.
  • Arterial dissections: related to vasculitis, trauma, fibromuscular dysplasia, or spontaneous. These aneurysms carry a very high risk of bleeding.
  • Metastatic aneurysms: embolization of tumor cells (e.g., cardiac myxoma, choriocarcinoma, bronchogenic carcinoma).
  • Cranial radiotherapy, head trauma, and surgeries (transsphenoidal, paranasal, carotid).
  • Moyamoya disease.
  • Occult aneurysms: Subarachnoid hemorrhage in the interhemispheric fissure or Sylvian fissure without an identifiable aneurysm requires repeated angiographies, as aneurysms are later found in 70% and 30% of cases, respectively, despite an initially negative angiographic workup.
• 15 to 40% of cases: same causes as intraparenchymal hemorrhages. Commonly associated with arteriovenous malformations (arteriovenous shunts, also termed "aneurysms" but this term is inaccurate) which may bleed or trigger seizures. Other causes include tumors (metastases, leptomeningeal carcinomatosis, pituitary tumors), coagulation disorders, extension of a primary intraparenchymal hemorrhage into the subarachnoid space, hemoglobinopathies, drugs (cocaine, amphetamines), cerebral amyloid angiopathies, etc.
• Up to 10% of cases remain of undetermined origin after exhaustive workup, particularly in perimesencephalic locations, which generally have a favorable prognosis with a 2-5% recurrence rate.

• The case of spinal subarachnoid hemorrhages:
  • These account for less than 1% of SAH.
  • Suspect this in the absence of an obvious cause, particularly if predominant spinal pain is present.

Risk factors

• Modifiable: smoking (relative risk x 2 to 4, up to x11 if smoking more than 20 cigarettes per day), alcohol consumption over 40g/day, hypertension (relative risk x 3 to 4), oral contraceptives (controversial), cocaine or amphetamine use, acetylsalicylic acid (controversial).
• Non-modifiable: autosomal dominant polycystic kidney disease, familial intracranial aneurysm (<10% of cases), Ehlers-Danlos syndrome (controversial).

Precipitating factors

Physical exertion (sports, sexual activity, coughing, defecation) precedes 50% of SAH cases, as does staying at altitudes over 2500 meters, and acute intoxication with cocaine, alcohol, or tobacco.

Clinical Presentation

Classic triad:

• Sudden, severe headache described as "thunderclap" or "the worst headache of my life" – the cardinal symptom.
  • Any acute, unusual headache without an obvious cause should raise suspicion for a subarachnoid hemorrhage.
  • In 10-40% of cases, there may be a history of a transient “sentinel” headache in the weeks preceding the rupture.
• Nausea and vomiting (inconsistent).
• Brief loss of consciousness, mimicking syncope (lasting 1-2 minutes) – rarely found.

Other frequent signs and symptoms:

• Seizures.
• Focal neurological signs:
  • Oculomotor paralysis (due to posterior cerebral artery aneurysm).
  • Lower limb weakness (due to anterior cerebral artery aneurysm).
  • Nystagmus or cerebellar syndrome (due to posterior fossa aneurysm).
  • Aphasia, hemiparesis, or visual neglect (due to middle cerebral artery aneurysm).
• Agitation and altered consciousness.
• Hypertension and hyperglycemia.
• Meningeal signs (neck stiffness, Lasègue, Kernig, Brudzinski), often absent in the first hours.
• Vitreous hemorrhage (Terson syndrome).
• Neck pain, torticollis.
• Typically a few days after the bleed: lumbar or dorsal pain, sciatica.

Urgent Additional Examinations

To establish the positive diagnosis:

• Non-contrast CT scan (always performed if there is a positive history with the clinical triad, > 90% positive in the first 12 hours, as blood appears hyperdense). Despite a significant rate of false negatives (Fisher 1 SAH), it remains the diagnostic gold standard. An MRI (T1, FLAIR, T2*) may be considered for pregnant women.
  • It is important to note that blood can appear isodense in anemic patients ("false" Fisher 1 SAH, especially if Hb < 10 g/dl), thus necessitating a contrast CT scan or MRI to detect it.
• Lumbar puncture to look for red blood cells in cases of high clinical suspicion with a negative CT scan. However, if positive, neither the "three-tube method" nor the search for crenated red blood cells nor comparison with the blood formula can definitively differentiate from traumatic puncture. A xanthochromic appearance of cerebrospinal fluid and the presence of bilirubin are strong arguments for a non-traumatic origin, but these features are only present after the twelfth hour of bleeding. In cases of clear positivity or doubt, performing a CT angiogram is necessary.

To establish the etiological diagnosis:

• CT angiogram is highly effective for locating an aneurysm or an arteriovenous malformation. However, since conventional angiography will be performed in all cases at a later stage, its utility is limited to situations where immediate access to angiography is not available for pre-interventional assessment.
• The role of MRI angiography is not well-defined.
• Conventional angiography remains the gold standard for diagnosing any vascular malformation and is therapeutic for most arterial aneurysms.
• Depending on the context: blood cultures and echocardiography (if infectious aneurysms are suspected), renal ultrasound (for polycystic kidney disease), skin biopsies, and biological tests (for vasculitis and collagen diseases).

Common Early Complications

In addition to the initial bleeding, three types of complications contribute equally to the mortality of a subarachnoid hemorrhage: rebleeding, vasospasm, and general complications (++ arrhythmias, heart failure, infections, multi-system failure).

• Rebleeding:
  • Occurs in 5-10% of cases within the first 72 hours. Mortality > 70%.
• Vasospasm:
  • This is a prolonged and reversible segmental reduction of the lumen of an artery in the subarachnoid space, occurring near or distant from the source of the subarachnoid hemorrhage. The maximum risk occurs within 15 days. Most are asymptomatic. Depending on the series, 30-70% of cases are "incidental" angiographic findings. 15-20% of vasospasms evolve into established ischemic stroke.
    • Early vasospasms (affecting 10% of SAH cases): Occurs from 0 to 4 hours post-hemorrhage. A high WFNS score predicts its presence but does not predict the occurrence of late vasospasm. If symptomatic and identified during angiography, it must be treated urgently along with the aneurysm. If it's an incidental angiographic finding (asymptomatic), it does not require speeding up the intervention.
    • Late vasospasms:
      • Typically occur between days 4 and 14.
      • This is the leading cause of morbidity and mortality in the subacute phase.
      • Predictive factors: High modified Fisher score, age < 50 years, hyperglycemia.
      • Clinical features: Fever (a contributing and aggravating factor that may result from SIRS due to bleeding or spasm), altered consciousness, worsening headaches, focal deficits, hypertension. Symptoms develop over minutes to hours.
      • Laboratory and blood gases: Possible hyperleukocytosis, hyponatremia, hypercapnia, acidosis.
      • Screening: Regular transcranial duplex ultrasound.
      • In cases of suspected symptomatic vasospasm: Exclude other causes of neurological deterioration → consider diagnostic and therapeutic angiography.
• Hydrocephalus
• Hyponatremia (affects 10-30% of patients but usually does not require correction).
  • Two possible mechanisms:
    • The classic SIADH → hyponatremia, no hypovolemia, oliguria, hemodilution.
    • Salt-wasting syndrome (CSWS)
      • Its very existence is debated. One hypothesis suggests it is due to inappropriate secretion of natriuretic peptides.
      • It is characterized by hyponatremia with high diuresis, signs of hypovolemia, hemoconcentration, and dehydration. Urinary osmolality >> blood osmolality.
    • Clinically, the distinction is unimportant. In any case, the usual fluid restriction for SIADH should be avoided in this context, and NaCl infusions ± urea should be used instead.
• Diabetes insipidus (due to post-hypophyseal or hypothalamic injury)
  • Should be suspected in cases of urine output > 300 ml/h or hypernatremia.
  • Diagnostic criteria: hourly urine output > 4 ml/kg + low urinary osmolality + low urine specific gravity.
  • Uncommon. Treated with desmopressin.
• Complications Common to All Stroke and (Semi-)Intensive Care Patients: neurogenic pulmonary edema, arrhythmias, seizures, nosocomial infections, thromboembolic complications, etc.

Approach in cases of sudden neurological deterioration after subarachnoid hemorrhage

Urgently perform:

• Laboratory tests: Electrolyte or metabolic disturbances?
• Electrocardiogram: Arrhythmias, signs of myocardial ischemia?
• Chest X-ray: Infection?
• CT scan: Acute hydrocephalus? Rebleeding?
• Electroencephalogram: Seizure?
• Transcranial duplex (not very sensitive): Vasospasm?

If these tests are negative and/or transcranial duplex is positive:

• Angiography: Vasospasm?

Clinical Follow-up and Prognostic Elements

General overview

The overall one-year mortality rate ranges from 30-60% depending on the series. 25% of survivors have disabling deficits. The main prognostic factor for good recovery is age: 86% for ages 18-29, 26% for those > 70 years.

• Cumulative percentage (according to the most pessimistic series) of deaths by:
  • 1st day = ~10%
  • 1st week = 27%
  • 6 weeks = 55%
  • 1 year = 63%

However, death is often due to rebleeding (a second hemorrhage is usually more severe than the first) → highlighting the importance of urgent etiological treatment and post-treatment monitoring. Risk of bleeding in the absence of treatment or aneurysmal repermeabilization:

• from a previously bled aneurysm: 50% within 6 months, then 3%/year (cumulative risk)
• from a previously bled arteriovenous malformation: 3%/year (cumulative risk)
• from an intact aneurysm (discovered by chance or during screening): 1%/year (cumulative risk)

Hunt and Hess Score

This score stages the severity of subarachnoid hemorrhages (SAH). It should be correlated with the WFNS score, which has established prognostic value.

WFNS Score

The WFNS (World Federation of Neurologic Surgeons) score has validated prognostic value (GOS = functional prognosis at 6 months) for subarachnoid hemorrhages.

Fisher Scale

The Fisher scale is a radiological severity score for subarachnoid hemorrhages.

Modified Fisher Scale

The modified Fisher scale is a radiological severity score for subarachnoid hemorrhages, with validated predictive value for the occurrence of cerebral infarction due to vasospasm.

Treatments and Management in Acute and Subacute Phases

Management of hemorrhagic strokes

Similar to the general acute management of ischemic strokes, with the following exceptions:

• Consensus: Maintain blood pressure below 180/105 mmHg (excessive reduction risks worsening peri-lesional ischemia, while insufficient reduction increases the risk of bleeding and recurrence).
• Discontinue all anticoagulant (as a general rule, even in cases of formal indications such as a mechanical valve—although this should be discussed on a case-by-case basis) or antiplatelet treatments, and administer antidotes if necessary. Specifically:
  • In embolic conditions, suspending anticoagulant therapy for 10 to 14 days increases the risk of embolic events by 1 to 20%, depending on the condition.
  • Resumption of therapeutic-dose anticoagulants has been shown to be safe between Day 10 and Day 14, provided there is no radiological worsening or recurrence.
• Prophylactic doses of heparin or LMWH can be started on Day 2 (with aPTT/anti-Xa monitoring), provided there is no radiological worsening or recurrence.

The management of a hemorrhagic stroke should begin in intensive care or the emergency department and continue in a neurosurgical unit or stroke unit. Multiple hemorrhagic lesions, coexisting ischemic areas, or occurrence in immunocompromised patients should raise suspicion of central nervous system vasculitis or cerebral venous thrombosis. Fever, immunosuppression, or peripheral emboli should prompt consideration of infectious endocarditis. In the absence of evidence of vascular malformation in a non-hypertensive patient, cerebral venous thrombosis must be ruled out.

Specific management of subarachnoid hemorrhage (SAH)

Consider purely palliative care if:

• Initial Hunt and Hess Grade V + age > 70 years + Fisher Grade 4 with major brain destruction.

Otherwise, begin:

• General management of hemorrhagic strokes (see above) with the following adaptations:
  • EEG monitoring is recommended in cases of altered consciousness (these are highly epileptogenic lesions, except for those in the posterior fossa). There is no consensus on anti-epileptic prophylaxis (some advocate preventive treatment for "high-risk" patients: Fisher Grades 3 and 4, intraparenchymal lesions, coma, subdural hematoma, etc., although this is not evidence-based).
  • Infusion of NaCl 0.9% ~40 ml/kg/day + 20 mEq KCl/l.
  • Hyponatremia is common (SIADH vs. CSCW) but does not require correction if asymptomatic and > 125 mmol/l. If correction is needed, favor NaCl infusions (± urea) and avoid fluid restriction.
  • In the event of diabetes insipidus → 1-deamino-8-D-arginine vasopressin SC.
  • For cerebral edema, medical treatment is preferred. Decompressive or evacuation surgery is only useful if:
    • Compressing cerebellar hematoma or diameter > 3 cm.
    • Lobar hematoma > 50 cm³ with clinical deterioration (but Glasgow > 4) despite appropriate medical management.
    • Imminent herniation.
• Etiological treatment = prevention of rebleeding (maximum risk within 72 hours):
  • Arterial aneurysms: To be discussed between neurosurgeons and interventional radiologists. Generally:
    • Endovascular treatment (coiling) = first choice.
    • Microneurosurgery (for threatening hematomas or high-risk aneurysms).
  • Arteriovenous malformations: Also to be discussed between neurosurgeons and interventional radiologists. Generally:
    • Endovascular treatment (glue injection) = first choice.
    • Microneurosurgery = second choice.
    • Gamma Knife (takes 1 to 3 years to be effective → reserved for unreachable microvessels or as a complement to or in case of failure of other techniques).
  • Miscellaneous for other etiologies.
• Prevention of vasospasm:
  • Vasospasm can occur regardless of the cause of the hemorrhage, though the risk is higher with aneurysmal origin. EBM supports nimodipine only for aneurysmal hemorrhage → discontinue if aneurysm presence is reasonably excluded.
    • Nimodipine (Nimotop) 60 mg 6x/day orally (1-2 mg/hour IV if oral route is impossible) for 21 days, half-dose in cases of liver failure – no direct evidence of effect on vasospasm, but improved 1-year functional prognosis.
  • Decubitus
  • Statins: Some small studies suggest a favorable trend, but no EBM yet available. Given their relative safety and potential effectiveness, they may be considered (prefer long half-life statins: atorvastatin > rosuvastatin >>> lovastatin > simvastatin > pravastatin > fluvastatin). Example: atorvastatin 40 mg/day orally for 21 days.
  • Triple-H therapy has never demonstrated effectiveness. Never initiate hyperhydration or vasopressors (outside of shock) on untreated aneurysms (increases rebleeding risk).
• Vasospasm treatment:
  • Triple-H Therapy:
    • Consists of:
      • Hypervolemia and Hemodilution: Human albumin or macromolecule infusions. However, maintain hematocrit > 35%. Inhibition of natriuresis with fludrocortisone may be useful.
      • Induced Hypertension: Low-dose dobutamine (monitoring PCP to maintain 14-16 mmHg if high doses are required) to increase SBP by 20 mmHg, aiming for 18-20 cmHg and a cardiac index of 3 to 3.5 l/min/m².
    • Complications: Cardiac decompensation, myocardial ischemia, hyponatremia, recurrent cerebral hemorrhage, cerebral edema, acute renal failure.
    • No EBM justifying this approach, though it is still commonly used empirically.
  • Prolong nimodipine up to 6 weeks.
  • Consider endovascular treatment (balloon angioplasty and/or papaverine, nimodipine, or milrinone injection).
• Management of acute symptomatic hydrocephalus:
  • Placement of a ventricular drain with prophylactic antibiotics (replace with ventriculoperitoneal shunt if needed > 10 days) and maintain ICP ~15 mmHg. Alternative: ventriculostomy.
  • In cases of intraventricular hemorrhage with obstructive hydrocephalus and intracranial hypertension: consider intraventricular fibrinolysis (4 mg rt-PA injected into the lateral ventricles) repeated over 1-3 days until cleaned (monitored by CT scan)... to be discussed on a case-by-case basis as prognosis is generally poor in these situations.

Late complications

• Rebleeding: The most frequent late complication (recanalization of embolized aneurysm, occult aneurysm, etc.).
• Normotensive hydrocephalus (→ triad of gait, cognitive, and sphincter disturbances) due to arachnoid scarring at the Pacchionian granulations. Rare.
• Superficial siderosis of the central nervous system. Exceptional.

Primary and secondary prevention

• Education of professionals and the public, eradication of modifiable risk factors.
• Screening (CT angiography) of at-risk populations: dominant familial renal polycystic disease or >2 first-degree relatives (or up to third-degree according to some authors) with a history of aneurysmal hemorrhage.
• Systematic treatment of aneurysms, whether they have bled (urgently) or not. This rule, however, has several exceptions (depending on the location and morphology of the aneurysm), which must be discussed multidisciplinary (radiologists and neurosurgeons).

Bibliography

AHA / ASA, 2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association, 2023

Caplan RL, Caplan's Stroke. A clinical approach, 4th ed, Saunders, 2009