External multicenter validation of the eSAH score for predicting outcomes after subarachnoid hemorrhage.

After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I-III) and poor (WFNS IV-V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0-3 was considered a good outcome and an mRS score of 4-6 was considered a poor outcome. Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14-7.46; p=0.03) and good outcome (OR 4.01, 97.5% CI 1.63-10.53; p=0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p<0.001), and poor WFNS grade (p<0.001) were associated with poor outcome. Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.

Purpose: To investigate the incidence and relative factors of Terson’s syndrome (TS) in patients with subarachnoid hemorrhage (SAH) in China.Materials and Methods: A case series study was conducted from November 2009 to June 2010 on 155 patients (310 eyes) with aneurysmal and traumatic SAH. A thorough, direct funduscopic examination was performed on all participants and the incidence of TS analyzed. Associations between TS and gender, state-of-consciousness, Glasgow Coma Scale (GCS) score, Hunt-Hess grade, anatomical location of ruptured aneurysms, and mortality rates were analyzed.Results: TS was diagnosed in 20 of 155 SAH patients (30 eyes), and detected in 16 (14.16%) of 113 patients with aneurysmal SAH and four (9.52%) of 42 patients with traumatic SAH. No correlations were found between state-of-consciousness, GCS scores, and presence of TS in patients with traumatic SAH. Among patients suffering from aneurysmal SAH, however, significant relationships were observed between state-of-consciousness, GCS scores, Hunt-Hess grades, and incidence of TS (p < 0.01). No statistically significant difference was observed between men and women with regard to the incidence of TS (χ2 = 0.821, p = 0.365). Furthermore, no correlation was found between location of ruptured aneurysms (p = 1.000), mortality rates (p = 0.146), and incidence of TS.Conclusions: Compared with traumatic SAH, a higher incidence of TS was observed in patients with aneurysmal SAH, a condition significantly associated with a person’s overall condition. Therefore, aneurysmal SAH patients with consciousness-disturbance, lower GCS scores, and higher Hunt-Hess grades should be paid particular attention by ophthalmologists when performing fundus examinations. The question of whether SAH with TS is prognostic of spontaneous SAH is an area in need of further study.

The pathogenesis leading to poor functional outcome after aneurysmal subarachnoid haemorrhage (aSAH) is multifactorial and not fully understood. We evaluated a machine learning approach based on easily determinable clinical and CT perfusion (CTP) features in the course of patient admission to predict the functional outcome 6 months after ictus. Out of 630 consecutive subarachnoid haemorrhage patients (2008-2015), 147 (mean age 54.3, 66.7% women) were retrospectively included (Inclusion: aSAH, admission within 24 h of ictus, CTP within 24 h of admission, documented modified Rankin scale (mRS) grades after 6 months. Exclusion: occlusive therapy before first CTP,previous aSAH, CTP not evaluable). A random forests model with conditional inference trees was optimised and trained on sex, age, World Federation of Neurosurgical Societies (WFNS) and modified Fisher grades, aneurysm in anterior vs. posterior circulation, early external ventricular drainage (EVD), as well as MTT and Tmax maximum, mean, standard deviation (SD), range, 75th quartile and interquartile range to predict dichotomised mRS (≤ 2; > 2). Performance was assessed using the balanced accuracy over the training and validation folds using 20 repeats of 10-fold cross-validation. In the final model, using 200 trees and the synthetic minority oversampling technique, median balanced accuracy was 84.4% (SD 0.7) over the training folds and 70.9% (SD 1.2) over the validation folds. The five most important features were the modified Fisher grade, age, MTT range, WFNS and early EVD. A random forests model trained on easily determinable features in the course of patient admission can predict the functional outcome 6 months after aSAH with considerable accuracy. • Features determinable in the course of admission of a patient with aneurysmal subarachnoid haemorrhage (aSAH) can predict the functional outcome 6 months after the occurrence of aSAH. • The top five predictive features were the modified Fisher grade, age, the mean transit time (MTT) range from computed tomography perfusion (CTP), the WFNS grade and the early necessity for an external ventricular drainage (EVD). • The range between the minimum and the maximum MTT may prove to be a valuable biomarker for detrimental functional outcome.

This study aimed to evaluate age as a prognostic factor and develop a comprehensive prognostic model for patients undergoing clipping surgery for World Federation of Neurosurgical Societies (WFNS) grade I/II aneurysmal subarachnoid haemorrhage (SAH). We retrospectively investigated 188 patients with WFNS grade I/II SAH who underwent microsurgical clipping at our institute between December 2010 and January 2020. The data of 176 patients (75 with grade I and 101 with grade II) were analysed. Data on patient demographics, aneurysm characteristics, SAH factors, surgical details, and clinical outcomes were collected. Prognostic factors were assessed using bivariate and multivariable logistic regression analyses, and recursive partitioning analysis. Favourable outcomes (mRS 0–2) were observed in 76% of patients. Age, a significant negative prognostic factor in multivariable analysis (odds ratio 0.55, 95% confidence interval 0.40–0.76, p < 0.001), was cutoff at 70 years by the receiver operating characteristic curve. Patients aged ≤ 70 years had significantly better outcomes than those aged > 70 years (84% vs. 46%, respectively; p < 0.001). Epileptic seizures were significantly associated with poor outcomes in older adults (p < 0.001). A prognostic model (favourable, intermediate, and poor) based on age and postoperative adverse events showed significantly different outcomes between age groups (p < 0.001). Age was a stronger prognostic factor than WFNS grading for patients with grade I/II SAH undergoing microsurgical clipping. For patients aged ≤ 70 years, precise microsurgeries with fewer complications were associated with favourable outcomes beyond WFNS grade. For older patients, postoperative intensive seizure management may prevent poor outcomes.

The aim of this study was to evaluate the effect of treatment modality (surgical clipping vs. endovascular coiling) and lumbar puncture (LP) in patients with aneurysmal subarachnoid hemorrhage (SAH) based on neurologic status on admission and clinical outcome. One hundred forty-eight consecutive patients with ruptured intracranial aneurysms treated via endovascular or surgical methods were included in our study. Patients who refused further therapy or received only supportive therapy because of bad neurologic status were excluded. Severity of SAH was evaluated using the Fisher score. World Federation of Neurosurgical Societies (WFNS) and Hunt and Hess (H&H) scores were used for evaluation of neurologic status. Glasgow Outcome Scale scores and modified Rankin scores were used for outcome evaluation. We found that modified Rankin scores were significantly lower in the surgical clipping group (1.1 ± 1.4) than in the endovascular coiling group (1.7 ± 1.8) (p: 0.04). The positive lumbar puncture [LP(+)] group had similar outcome scores as the negative lumbar puncture [LP(-)] group, although the LP(+) group had worse initial SAH evaluation scores (WFNS 1.64 ± 0.95-1.23 ± 0.61, p: 0.0004 and H&H 2.18 ± 1.07-1.65 ± 0.88, p: 0.001). Surgical clipping might improve clinical outcome better than endovascular coiling, although a more confident conclusion requires absolute randomization of patients for both treatments. LP could also improve clinical outcome in patients with high initial SAH evaluation scores.

Background: Skeletal muscle mass is an important factor for various diseases’ outcomes. As for its indicators, temporal muscle thickness (TMT) and temporal muscle area (TMA) on the head computed tomography are useful, and TMT and TMA were reported as potential prognostic factors for aneurysmal subarachnoid hemorrhage (SAH). We examined the clinical characteristics, including TMT and TMA, of SAH patients aged 75 or younger.Methods: We retrospectively investigated 127 SAH patients with all World Federation of Neurosurgical Societies (WFNS) grades and treated by clipping between 2009 and 2019. Clinical outcome was measured with the modified Rankin Scale (mRS) at 6 months, with favorable outcome defined as mRS 0–2. The associations between the clinical variables and the outcomes were analyzed.Results: The mean age was 60.6 (32–74) years, and 65% were women. The mean ± standard deviation of WFNS grade was 2.8 ± 1.4. TMT and TMA were larger in the favorable outcome group than the poor one. Multivariate analysis revealed that age, smoking, WFNS grade, and TMT or TMA were associated with favorable outcome. Receiver operating characteristic analysis found that the threshold of TMT was 4.9 mm in female and 6.7 mm in male, and that of TMA was 193 mm2 in female and 333 mm2 in male.Conclusion: The odds ratios for TMT and TMA related to clinical outcome were lower than for smoking and WFNS grade; however, on multivariate analysis they remained independent prognostic factors in SAH patients aged 75 or younger treated by clipping. Further studies are needed to confirm these findings.

We assessed whether the motor component of the Glasgow Coma Scale (GCSm) is independently associated with unfavorable outcomes in aggressively treated poor-grade subarachnoid hemorrhage (SAH) patients. Retrospective cohort of poor-grade SAH patients (World Federation of Neurosurgical Societies (WFNS) grades IV and V). The best GCSm score achieved within 24 h of admission was stratified into four categories (<4, 4, 5 or 6). Outcomes were classified as favorable [modified Rankin Scale (mRS) ≤ 2] or unfavorable (mRS ≥ 3). Multivariable logistic regression was performed to identify independent predictors of unfavorable outcome. A total of 179 patients were admitted during the study period (mean age 55.9 ± 12.1; 68.2% female). Thirty-three patients (33/179 - 18%) died before aneurysm treatment, one patient had missing GCSm data at 24 h and sixteen patients (16/179; 9%) were lost to follow-up. One hundred and twenty-nine patients (129/179 - 72%) were included in the final analysis. No patient with GCSm < 4 had a favorable outcome (sensitivity 22.4%, specificity 100%, positive predictive value 100% and negative predictive value 67.8% for unfavorable outcome). Delayed cerebral ischemia-related cerebral infarction (odds ratio (OR) 4.06; 1.56-11.11 95% CI, p = 0.004) and the best GCSm score were independently associated with unfavorable outcome. There was a stepwise decrease in the rate of unfavorable outcome from GCSm < 4 to GCSm = 6 (<4 = 100%; 4 = 80%; 5 = 46% and 6 = 20%). Each one-point decrease in GCSm score was associated with an OR of 3.52 (1.77-7.92 95% CI, p = < 0.001) for unfavorable outcome. The GCSm score was independently associated with unfavorable outcome. All patients with a GCSm score < 4 experienced an unfavorable outcome.

The cerebral angiography result is negative for an underlying vascular lesion in 15-20% of patients with nontraumatic subarachnoid hemorrhage (SAH). Patients with angiogram-negative SAH include those with perimesencephalic SAH and diffuse SAH. Consensus suggests that perimesencephalic SAH confers a more favorable prognosis than diffuse SAH. Limited data exist to contextualize the clinical course and prognosis of diffuse SAH in relation to aneurysmal SAH in terms of critical care complications, neurologic complications, and functional outcomes. Here we compare the clinical course and functional outcomes of patients with perimesencephalic SAH, diffuse SAH, and aneurysmal SAH to better characterize the prognostic implications of each SAH subtype. We conducted a retrospective cohort study that included all patients with nontraumatic SAH admitted to a tertiary care referral center between January 1, 2012, and December 31, 2017. Bleed patterns were radiographically adjudicated, and patients were assigned to three groups: perimesencephalic SAH, diffuse SAH, and aneurysmal SAH. Patient demographics, complications, and clinical outcomes were reported and compared. Eighty-six patients with perimesencephalic SAH, 174 with diffuse SAH, and 998 with aneurysmal SAH presented during the study period. Patients with aneurysmal SAH were significantly more likely to be female, White, and active smokers. There were no significant differences between patients with diffuse SAH and perimesencephalic SAH patterns. Critical care complications were compared across all three groups, with significant between-group differences in hypotension and shock (3.5% vs. 16.1% vs. 38.4% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01) and endotracheal intubation (0% vs. 26.4% vs. 48.8% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01). Similar trends were noted with long-term supportive care with tracheostomy and gastrostomy tubes and length of stay. Cerebrospinal fluid diversion was increasingly required across bleed types (9.3% vs. 54.6% vs. 76.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively, p < 0.001). Vasospasm and delayed cerebral ischemia were comparable between perimesencephalic SAH and diffuse SAH but significantly lower than aneurysmal SAH. Patients with diffuse SAH had intermediate functional outcomes, with significant rates of nonhome discharge (23.0%) and poor functional status on discharge (26.4%), significantly higher than patients with perimesencephalic SAH and lower than patients with aneurysmal SAH. Diffuse SAH similarly conferred an intermediate rate of good functional outcomes at 1-6months post discharge (92.3% vs. 78.6% vs. 47.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.016). We confirm the consensus data that perimesencephalic SAH is associated with a more benign clinical course but demonstrate that diffuse SAH confers an intermediate prognosis, more malignant than perimesencephalic SAH but not as morbid as aneurysmal SAH. These results highlight the significant morbidity associated with diffuse SAH and emphasize need for vigilance in the acute care of these patients. These patients will likely benefit from continued high-acuity observation and potential support to avert significant risk of morbidity and neurologic compromise.

More than 10 years have passed since the two best-known clinical trials of ruptured aneurysms (International Subarachnoid Aneurysm Trial [ISAT] and Barrow Ruptured Aneurysm Trial [BRAT]) indicated that endovascular coiling (EC) was superior to surgical clipping (SC). However, in recent years, the development of surgical techniques has greatly improved; thus, it is necessary to reanalyze the impact of the differences in treatment modalities on the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). The authors retrospectively reviewed all aSAH patients admitted to their institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). In-hospital complications, hospital charges, and risk factors derived from multivariate logistic regression were analyzed in the SC and EC groups after 1:1 propensity score matching (PSM). The area under the receiver operating characteristic curve was used to calculate each independent predictor's prediction ability between treatment groups. A total of 844 aSAH patients were included. After PSM to control for sex, aneurysm location, Hunt and Hess grade, World Federation of Neurosurgical Societies (WFNS) grade, modified Fisher Scale grade, and current smoking and alcohol abuse status, 329 patients who underwent SC were compared with 329 patients who underwent EC. Patients who underwent SC had higher incidences of unfavorable discharge and 90-day outcomes (46.5% vs 33.1%, p < 0.001; and 19.6% vs 13.8%, p = 0.046, respectively), delayed cerebral ischemia (DCI) (31.3% vs 20.1%, p = 0.001), intracranial infection (20.1% vs 1.2%, p < 0.001), anemia (42.2% vs 17.6%, p < 0.001), hypoproteinemia (46.2% vs 21.6%, p < 0.001), and pneumonia (33.4% vs 24.9%, p = 0.016); but a lower incidence of urinary tract infection (1.2% vs 5.2%, p = 0.004) and lower median hospital charges ($12,285 [IQR $10,399-$15,569] vs $23,656 [IQR $18,816-$30,025], p < 0.001). A positive correlation between the number of in-hospital complications and total hospital charges was indicated in the SC (r = 0.498, p < 0.001) and EC (r = 0.411, p < 0.001) groups. The occurrence of pneumonia and DCI, WFNS grade IV or V, and age were common independent risk factors for unfavorable outcomes at discharge and 90 days after discharge in both treatment modalities. EC shows advantages in discharge and 90-day outcomes, in-hospital complications, and the number of risk factors but increases the economic cost on patients during their hospital stay. Severe in-hospital complications such as pneumonia and DCI may have a long-lasting impact on the prognosis of patients.

In 2012, a new computed tomography (CT) grading scale was introduced by the Barrow Neurological Institute group ("BNI scale") to predict angiographic and symptomatic vasospasm in aneurysmal subarachnoid hemorrhage. To address the question of whether BNI grading is reliable in the prediction of cerebral infarction and clinical outcome and to compare BNI scores to existing radiographic and clinical models of outcome prediction. Consecutive data of 260 patients with aneurysmal subarachnoid hemorrhage was retrospectively analyzed with respect to radiographic and clinical parameters. Patients presenting with more severe BNI grades were older ( P = .002), displayed lower Glasgow Coma Scale scores at admission ( P < .001) and were more often diagnosed with intraventricular hemorrhage ( P < .001). An increasing BNI grade was associated with higher rates of severe angiographic vasospasm ( P = .007), the occurrence of new cerebral infarction ( P < .001), and poor patient outcome ( P < .001). In contrast, analysis according to the Fisher grading system did not show a significant relationship to any outcome parameter. Multivariate analysis combining radiographic and clinical parameters showed significant results for clinical scores (Hunt and Hess and World Federation of Neurosurgical Societies) with radiographic information losing its predictive capability. The BNI scale is easily applicable and superior to the original Fisher scale regarding prediction of angiographic vasospasm, new cerebral infarction, and patient outcome. Presence of intraventricular hemorrhage and intracerebral hemorrhage are additional radiographic factors with outcome relevance that are not part of the BNI scale. Established clinical scores like World Federation of Neurosurgical Societies and Hunt and Hess grading were more relevant for outcome prediction than any radiographic information.

Objective To evaluate the safety and effectiveness of one-stage intravascular interventional treatment for intracranial multiple aneurysms. Methods From January 1, 2010 to January 1, 2018, the data of patients with multiple intracranial aneurysm undergoing one-stage endovascular embolization in the Department of Nerurosurgery, Puning People's Hospital, Guangdong Province were analyzed retrospectively. The clinical and angiographic findings at discharge and follow-up were evaluated. Results A total of 16 patients with multiple intracranial aneurysms received one-stage endovascular treatment were enrolled. Among them, 10 were females and 6 were males; their age was 49.5±17.2 years; 5 patients were subarachnoid hemorrhage caused by rupture of intracranial aneurysms, three of them were classified as grade Ⅰ and two were classified as grade Ⅱ by the World Federation of Neurosurgical Societies (WFNS). There are a total of 35 aneurysms, 13 patients had 2 intracranial aneurysms, and 3 had 3 intracranial aneurysms. There were 3 posterior circulation aneurysms and 32 anterior circulation aneurysms; the mean diameter of the aneurysms was 6.9±3.3 mm. Fifteen aneurysms were only treated with coil embolization, and 20 aneurysms were treated with stent-assisted coil embolization. No treatment-related complications occurred. Thirteen patients were followed up for a total of 17.7±6.4 months (range, 6-28 months). The modified Rankin Scale score of 12 patients was 0 and 1 was 6 (died of rebleeding). The imaging follow-up data of 23 aneurysms in 10 patients were obtained. They were followed up for 10.2±3.3 months (range, 6-15 months), 20 aneurysms did not recur and 3 (3/23, 13.0%) recurred. Conclusions One-stage endovascular embolization is a safe and effective treatment for multiple intracranial aneurysms, and its long-term outcome should be further evaluated. Key words: Intracranial aneurysm; Embolization, therapeutic; Treatment outcome

Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a high risk to die or remain in a dependent state. The initial hemorrhage causes early brain inury (EBI) which subsequently initiates a cascade of secondary brain injuries. Above this, a recurrent hemorrhage can occur in the first few hours after the initial hemorrhage and leads to additional damage to the already vulnerable brain. These problems make this type of hemorrhage a medical emergency. The goal of physicians who are specialized in the treatment and management of aSAH patients is to prevent complications and treat the secondary brain injuries. The selection of the right patients for the right treatment is mandatory in this process and the majority of the decisionmaking is done in the first days after the initial hemorrhage. The articles presented below describe management and treatment options that can be applied to aSAH patients in the first days after hemorrhage. Article 1 investigates the risk for the development of one of the secondary brain injuries, being delayed cerebral ischemia (DCI) in a cohort of 6,713 patients. The results, existing of patient data from different continents and therefore generalizable, show that female sex is independently associated with a higher risk for DCI. The influence of sex hormones was investigated but plays probably no role in causing this difference. These results help physicians in the decision-making process regarding the risk calculation for secondary brain injuries. Article 2 shows an in-hospital mortality rate of 13.9% in 1,669 patients who were treated for a ruptured intracranial aneurysm. Independent predictors were recurrent hemorrhage, cerebral infarction attributed to DCI and aneurysm treatment, and intraventricular hemorrhage. Preventing a recurrent hemorrhage from the aneurysm at the earliest possible opportunity with the treatment option that results in the lowest risk of posttreatment infarction will have a relevant impact on the reduction of in-hospital mortality. Patients who are at highest risk to achieve an unfavorable outcome after hospital discharge, including those with a poor clinical condition at admission (World Federation of Neurosurgical Societies (WFNS) grade 4 and 5), are studied in Article 3. The results show that, despite an initial poor clinical condition, these patients are able to achieve a favorable outcome in 30-45%. Therefore, in patients with a poor neurological condition (Glasgow Coma Scale (GCS) ≤12) the treatment should not be delayed or postponed because these patients have an acceptable chance to survive without significant neurological deficits. Nevertheless, a substantial part of patients who are admitted in a poor clinical condition still die in the hospital. In Article 4 we found that 43% of patients in poor clinical condition die. The major cause of death was withdrawal of life support (WOLS; 71%) followed by brain death (15%). The data were collected from hospitals in Europe and North-America and showed differences in the major causes of death, probably due to cultural and referral differences. As WOLS is a decision of the team of physicians, future studies need to investigate the exact reason that lead to WOLS in order to improve the care of patients who are admitted in poor clinical condition. What if patients used antiplatelet agents before the hemorrhage? The management options of different hospitals are summarized in Article 5 and show a large variety regarding discontinuing the antiplatelet agent and transfusing thrombocytes. This emphasizes the importance of evidence-based guidelines for the management of prehemorrhage antiplatelet agent use. As mentioned previously, the prevention of recurrent hemorrhage might have a relevant impact on in-hospital mortality. This was proven by the results in Article 6, which compares patients who received the antifibrinolytic agent tranexamic acid (TXA) or not. Early administration of TXA resulted in a significant reduction of in-hospital mortality with an odds ratio of 0.42. Early pharmacological thromboprophylaxis (PTP) is known to reduce venous thromboembolisms. However, PTP could potentially be harmful in patients with recently treated aneurysms or absence of an aneurysm on the first digital subtraction angiography (DSA). In Article 7 we reviewed the safety profile of early administration of PTP and concluded that this can be done safely in treated aneurysms and non-aneurysmal hemorrhage.

Unfavorable Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage WFNS Grade I

Prognostic Assessment of Aneurysmal Subarachnoid Patients with WFNS Grade V by CT Perfusion on Arrival

To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1–3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L’s relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood–brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.