10 Natural History and Management Options of Angionegative Subarachnoid Hemorrhage

Jorn Van Der Veken, Aye Aye Gyi, and Amal Abou-Hamden

Abstract

Angionegative subarachnoid hemorrhage (SAH) is a subset of nontraumatic SAH, in which there is no underlying cause detected on the initial vascular imaging. Compared to its aneurysmal SAH counterpart, angionegative SAH has a more favorable natural history. This impacts the overall inpatient hospital management, timing, and the degree of follow-up required.

●Perimesencephalic SAH (PMSAH): It was initially described by van Gijn et al in 19851 and has a characteristic radiographic pattern of hemorrhage restricted to the perimesencephalic cisterns on CTB.^{1,​ 2}

●Non-PMSAH or diffuse SAH (dSAH): This is characterized by a more widespread distribution of SAH with a visible extension into the anterior part of the ambient cistern or to the basal part of the Sylvian fissures, mimicking an aneurysmal SAH.^{1,​ 2}

This classification refers to the initial computed tomography of the brain (CTB) ideally performed within 24 hours after the ictus, as delayed imaging might mimic a PMSAH due to blood resorption.^{1,​ 2} Although often considered a single pathological entity, distinguishing non-PMSAH from PMSAH is particularly important as they have a different natural course and management.

In a recent systematic review and meta-analysis, demographic characteristics of patients (n = 3,853) were described in 49 of 58 included studies.³ The mean age of included patients was 53.8 years. Forty-five studies including 3,530 patients reported diagnoses stratified by bleeding pattern and found that 1,763/3,530 (49.9%) had a PMSAH and 1,577/3,530 (44.7%) had a non-PMSAH.³ Unlike aneurysmal SAH, there is a male predominance in angionegative SAH (54.3%). A summary of demographic data from the systematic review is presented in Table 10.1.³

Table 10.1 General demographics of the study patients adapted from Mohan et al³

A pooled analysis of data from 9 studies with 646 patients showed that a significantly greater number of patients in the non-PMSAH group had a poor-grade SAH (World Federation of Neurosurgical Societies [WFNS] grade  > 2) than PMSAH group (24.6 vs. 7.2%; Table 10.2).³

Table 10.2 Proportion of study participants with poor grade SAH (WFNS grade greater than 2)³

10.2 Selected Papers on the Natural History of Angionegative SAH

●Mohan M, Islim AI, Rasul FT, et al; British Neurosurgical Trainee Research Collaborative. Subarachnoid haemorrhage with negative initial neurovascular imaging: a systematic review and meta-analysis. Acta Neurochir (Wien) 2019;161(10):2013–2026

The natural history of angionegative SAH is generally more favorable compared to their angiopositive counterparts. However, complications are well recognized and these include vasospasm, hydrocephalus, permanent ischemic complications, chronic headaches, and rehemorrhage.3^{,​ 62} A pooled analysis of published data (Table 10.3) suggests that the incidence of rebleeding in the non-PMSAH group was approximately 3.5% compared to 1.1% in PMSAH group. Development of hydrocephalus was found to be considerably worse in the non-PMSAH group (25.5 vs. 9.0%) with requirement for external ventricular drainage (41 vs. 9.6%), and eventual permanent cerebrospinal fluid diversion (20.6 vs. 0%).³ Furthermore, non-PMSAH patients had higher rates of radiological vasospasm (14.0 vs. 8.3%) and seizures (5.2 vs. 2.5%) when compared to those with PMSAH patients.³ Another publication reported a higher rate of hydrocephalus and radiological vasospasm for the non-PMSAH group.⁶² A forest plot meta-analysis of available complications data from both studies^{3,​ 62} showed a higher risk of overall hydrocephalus (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.10–3.45) and radiological vasospasm (OR, 2.57; 95% CI, 1.82–3.62) for the non-PMSAH group (Fig. 10.1).

Table 10.3 Pooled analysis of published data on the complications stratified by bleeding pattern

A pooled analysis of functional outcome data stratified by bleeding patterns reported in the systematic review suggested that the non-PMSAH patients were more likely to experience poor functional outcomes (modified Rankin Scale [mRS]  ≥ 3) than those with PSAH at 3 to 6 months (12.8 vs. 6.1%) and  ≥ 1 year (14.4 vs. 7.3%).3 Ultimately, only 76% of the non-PMSAH patients achieved complete recovery and independent living, compared to 96.7% of the PMSAH patients.³

The length of hospital stay was reported in 9 studies (608 patients) with median and mean values of 10 and 8.3 days in PMSAH patients versus 8.3 and 4 days in non-PMSAH patients (Table 10.4).³

Table 10.4 Length of stay (days) for patients with angionegative SAH stratified by SAH types

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