Perimesencephalic Non-Aneurysmal Subarachnoid Hemorrhage: Understanding the Benign Form of SAH
Approximately 15% of patients diagnosed with subarachnoid hemorrhage (SAH) show no evidence of an intracranial aneurysm upon cerebral angiography. Among these cases, about 38% are classified as non-aneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH). This distinct subtype was first clearly defined in 1991 by Rinkel and colleagues through detailed CT and MRI imaging studies. They established diagnostic criteria indicating that the hemorrhage is primarily centered anterior to the midbrain, often extending into the basal cisterns but not fully filling the anterior interhemispheric fissure. Notably, bleeding typically does not spread laterally into the Sylvian fissures, and there is usually no associated intracerebral hematoma or significant intraventricular blood accumulation.
What Defines NAPSAH on Imaging?
One of the hallmark features of NAPSAH is its characteristic distribution on brain imaging. The bleed is predominantly confined to the perimesencephalic cisterns—spaces surrounding the midbrain—including the ambient, interpeduncular, and prepontine cisterns. Unlike aneurysmal SAH, which tends to follow vascular territories and can be widespread, NAPSAH shows a more localized pattern. This specific localization plays a crucial role in differentiating it from other forms of SAH and helps guide further diagnostic decisions.
Potential Causes Behind Angiography-Negative SAH
The exact etiology of NAPSAH remains unclear, though several theories have been proposed. While traditional aneurysms are ruled out via angiography, researchers suspect alternative sources such as small perforating artery ruptures, venous bleeding, micro-arteriovenous shunts, or even occult cavernous malformations in the brainstem. Other possible contributors include capillary telangiectasias, tiny aneurysms on pontine arteries that thrombosed before imaging, or minor leaks from dural arteriovenous fistulas in the cervical spine region.
Venous origin theories are particularly compelling—some experts suggest that bleeding may stem from the anteromesencephalic vein or its tributaries, especially if anatomical variations exist. Additionally, transient increases in intracranial pressure or impaired venous drainage due to sinus stenosis might contribute to vessel rupture without leaving a visible structural lesion on standard angiograms.
Why Are Some Aneurysms Missed Initially?
Despite advanced imaging techniques, some small or partially thrombosed aneurysms may go undetected during initial evaluations. Factors like a narrow aneurysm neck, intra-aneurysmal clotting, or technical limitations in imaging angles can lead to false-negative results. For this reason, many neurovascular specialists recommend repeating angiographic studies—particularly digital subtraction angiography (DSA)—within one week of symptom onset to increase detection rates.
Epidemiology and Risk Factors
NAPSAH tends to affect younger individuals, with a mean age of onset around 50 years. Incidence appears highest among adults between 40 and 60 years old, although recent trends suggest a potential shift toward younger populations, possibly linked to lifestyle changes, increased stress levels, and poor dietary habits. Common risk factors include hypertension, smoking, excessive physical exertion, emotional stress, diabetes, and oral contraceptive use. Interestingly, a subset of patients experiences bleeding while at rest, suggesting that hemodynamic fluctuations rather than acute strain may play a role.
Clinical Presentation: Milder Than Aneurysmal SAH
Patients with NAPSAH typically present with sudden-onset headache—often described as severe but manageable—accompanied by nausea, vomiting, and photophobia in some cases. However, compared to aneurysmal SAH, neurological deficits are rare. Most individuals remain alert and oriented, without focal weakness, seizures, or loss of consciousness. Some may report radiating pain to the neck, shoulders, or lower back due to meningeal irritation, mimicking musculoskeletal conditions.
A key distinguishing factor is the low complication rate. Cerebral vasospasm, hydrocephalus, and rebleeding—common and dangerous sequelae in aneurysmal SAH—are exceedingly rare in NAPSAH. In fact, long-term follow-up studies spanning up to eight years have shown virtually no instances of delayed complications or recurrent hemorrhage, reinforcing its benign prognosis.
Diagnostic Approach: Timing Matters
Early brain imaging is critical for accurate diagnosis. Non-contrast head CT is highly sensitive in detecting acute bleeding and should be performed immediately after symptom onset. In NAPSAH, blood is typically visualized in the perimesencephalic cisterns, prepontine area, and quadrigeminal plate cistern. Repeat CT scans within 7–10 days often show complete resolution of subarachnoid blood, underscoring the importance of prompt evaluation before the hemorrhage becomes radiologically invisible.
After a negative CT angiography (CTA), clinicians face the decision of whether to proceed with DSA. While modern CTA has high sensitivity and specificity—comparable in many studies to DSA—some experts still advocate for conventional angiography as the gold standard. Given the possibility of missed small lesions, performing two rounds of angiography (initial CTA followed by DSA if needed) significantly improves diagnostic accuracy and provides greater confidence in ruling out life-threatening aneurysms.
The Role of MRI and MRV
In select cases, magnetic resonance imaging (MRI) and MR venography (MRV) can help identify venous anomalies or subtle vascular malformations not seen on CTA. These modalities are particularly useful when clinical suspicion persists despite negative findings on standard tests. For instance, a small cavernous angioma near the tectal plate could explain isolated quadrigeminal cistern bleeding, warranting closer scrutiny.
Management and Prognosis
Treatment for NAPSAH follows general SAH protocols but with notable modifications. Since the risk of vasospasm is minimal, aggressive interventions such as prophylactic calcium channel blockers (e.g., nimodipine) or intensive monitoring for delayed ischemia are generally unnecessary. Instead, care focuses on supportive measures: managing headaches, correcting electrolyte imbalances, controlling blood pressure, and ensuring adequate hydration.
Unlike traditional SAH guidelines that mandate strict bed rest, patients with confirmed NAPSAH can gradually resume normal activities under medical supervision. Their recovery is typically rapid, with most returning to baseline function within days to weeks. However, some individuals may experience lingering fatigue, anxiety, or mild cognitive disturbances—likely related to psychological impact rather than neurological damage.
Long-Term Outlook Is Reassuring
Extensive research confirms that NAPSAH carries an excellent long-term prognosis. Mortality and morbidity rates are extremely low, and recurrence is almost unheard of. Patients do not require lifelong surveillance or surgical intervention. Nevertheless, thorough initial workup—including repeat angiography when indicated—is essential to exclude treatable causes and provide both clinical certainty and patient peace of mind.
In summary, perimesencephalic non-aneurysmal subarachnoid hemorrhage represents a unique, benign variant of SAH with distinctive imaging patterns, favorable outcomes, and minimal complications. With timely diagnosis and appropriate management, affected individuals can expect full recovery and a return to normal life without ongoing neurological risks.