Poor grade aneurysmal subarachnoid hemorrhage

Poor grade aneurysmal subarachnoid hemorrhage

Poor-grade subarachnoid hemorrhage (SAH), that is, World Federation of Neurosurgical Societies grading Grades IV and V, have high morbidity and mortality rates.

A total of 104 consecutive patients with poor-grade aSAH from the Department of Neurosurgery, The Second Hospital of Shandong University, Jinan, were enrolled between January 2010 and December 2017. All these patients underwent early microsurgical clipping or endovascular coiling within three days after onset. Microsurgical clipping or endovascular coiling was selected according to aneurysm patterns, patient clinical status, interdisciplinary consultation, and the decision-making of the family. The individual prognosis was evaluated using the modified Rankin scale (mRS), while the prognostic factors were analyzed using multivariate logistic regression analysis.

There were 58 patients with grade IV aSAH and 46 patients with grade V aSAH. Microsurgical clipping was performed in 71 cases, while endovascular coiling was performed in 33 cases. According to the statistical results, microsurgical clipping was preferred by patients with CT Fishergrade III-IV, WFNS grade V, cerebral hernia, intracranial hematoma and preoperative rebleeding. At six months after onset, the overall rate of favorable outcome (mRS ≤ 2) was 36.5%. Furthermore, the favorable outcome rate was 56.9% in grade IV patients and 11.1% in grade V patients. Moreover, the univariate and multivariate logistic regression analyses revealed that CT Fisher grade I-II, WFNS grade IV and endovascular coiling were associated with a favorable prognosis, while the CT low-density area was slightly correlated to a poor prognosis.

The treatment of aSAH at the early stage by microsurgical clipping or endovascular coiling should be highlighted, especially for patients with WFNS grade IV. CT Fisher grade I-II, WFNS grade IV and endovascular coiling may predict a favorable prognosis, and the CT low-density area appeared to be a possible risk factor for poor prognosis 1).


Goldberg et al., performed a retrospective analysis of the Bernese SAH database for poor-grade (World Federation of Neurosurgical Societies grade IV and V) elderly patients (age ≥60 years) suffering from aSAH admitted to our institution from 2005 to 2017. Patients were divided into 3 age groups (60-69, 70-79, and 80-90 years). Survival analysis was performed to estimate mean survival and hazard ratios for death. Binary logarithmic regression was used to estimate the odds ratio for favorable (modified Rankin Scale score of 0-3) and unfavorable (modified Rankin Scale score of 4-6) outcome. Results- Increasing age was associated with an increasing risk of death after aSAH. The hazard ratio increased by 6% per year of age ( P<0.001; hazard ratio, 1.06; 95% CI, 1.03-1.09) and 76% per decade ( P<0.001; hazard ratio, 1.76; 95% CI, 1.35-2.29). Mean survival was 56.3±8 months (patients aged 60-69 years), 31.6±7.6 months (70-79 years), and 7.6±5.8 months (80-90 years). Unfavorable outcomes 6 to 12 months after aSAH were strongly related to older age. The odds ratio increased by 11% per year of age ( P<0.001; odds ratio, 1.11; 95% CI, 1.05-1.18) and 192% per decade ( P<0.001; odds ratio, 2.92; 95% CI, 1.63-5.26). Conclusions- Risk for death and unfavorable outcome increases markedly with older age in elderly patients with poor-grade aSAH. Despite a high initial mortality, treatment resulted in a reasonable proportion of favorable outcomes up to 79 years of age and only a small number of patients who were moderately or severely disabled 6 to 12 months after aSAH. Mean survival and proportion of favorable outcomes decreased markedly in patients older than 80 years 2).


During the period 2004-2014, 248 patients with poor-grade SAH were treated in our institution. Poor-grade SAH was defined as World Federation of Neurological Surgeons grades IV-V on admission. Data including patient characteristics, treatment modality, radiologic features, and functional neurologic outcome were assessed and further analyzed. Outcome was assessed according to the modified Rankin Scale after 6 months and stratified into favorable (modified Rankin Scale score 0-2) versus unfavorable (modified Rankin Scale score 3-6). A multivariate analysis was performed to identify predictors of functional outcome.

A favorable outcome was achieved in 24% of patients with poor-grade SAH. Patients with a favorable outcome were significantly younger (P = 0.005), harbored significantly smaller aneurysms (P = 0.004), and had a lower initial World Federation of Neurological Surgeons grade (P < 0.0001). An unfavorable outcome was significantly more frequent in patients with additional space-occupying hematoma compared with patients without additional space-occupying hematoma (P = 0.0009). On multivariate analysis, patient age, World Federation of Neurological Surgeons grade V, signs of cerebral herniation, aneurysm size, and presence of space-occupying hematoma were identified as significant predictors of unfavorable outcome in patients with poor-grade SAH.

A favorable outcome was achieved in 24% of severely ill patients with poor-grade SAH. Therefore, treatment of patients with poor-grade SAH should not be omitted. Careful individualized decision making is necessary for each patient 3).


118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6-28 months).

47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome.

Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH 4).


The purpose of a study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients.

Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed.

Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm (n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%.

This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies 5).


Timing of surgery for poor-grade aneurysmal subarachnoid hemorrhage is still controversial, therefore this study aimed to identify the optimal time to operate on patients admitted in poor clinical condition.

Ninety-nine patients meeting the inclusion criteria were randomly assigned into three treatment groups. The early surgery group received operation within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the intermediate surgery group received operation from days 4 to 7, and surgery was performed on the late surgery group after day 7. Follow-up was performed 1, 3, and 6 months after aneurysm clipping. Primary indicators of outcome included the Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary indicators of outcome were assessed using the Barthel Index and mortality.

This was the first prospective, single-center, observer-blinded, randomized controlled trial to elucidate optimal timing for surgery in poor-grade subarachnoid hemorrhage patients. The results of this study will be used to direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage, thus improving clinical outcomes for patients 6)


A prospective investigation was conducted in 149 patients with SAH (mean age 50.9 +/- 12.9 years); these patients were studied for 162 +/- 84 hours (mean +/- standard deviation). Lesions were classified as low-grade SAH (WFNS Grades I-III, 89 patients) and high-grade SAH (WFNS Grade IV or V, 60 patients). After approval by the local ethics committee and consent from the patient or next of kin, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clip placement. The microdialysates were analyzed hourly for extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol. The 6- and 12-month outcomes according to the Glasgow Outcome Scale and functional disability according to the modified Rankin Scale were assessed. In patients with high-grade SAH, cerebral metabolism was severely deranged compared with those who suffered low-grade SAH, with high levels (p < 0.05) of lactate, a high L/P ratio, high levels of glycerol, and, although not significant, of glutamate. Univariate analysis revealed a relationship among hyperglycemia on admission, Fisher grade, and 12-month outcome (p < 0.005). In a multivariate regression analysis performed in 131 patients, the authors identified four independent predictors of poor outcome at 12 months, in the following order of significance: WFNS grade, patient age, L/P ratio, and glutamate (p < 0.03).

Microdialysis parameters reflected the severity of SAH. The L/P ratio was the best metabolic independent prognostic marker of 12-month outcome. A better understanding of the causes of deranged cerebral metabolism may allow the discovery of therapeutic options to improve the prognosis, especially in patients with high-grade SAH, in the future 7).


A prospectively audited, nonselected series of 177 consecutive poor-grade (i.e., World Federation of Neurological Surgeons Grades IV and V) patients with aneurysmal subarachnoid hemorrhage managed during a 9-year period was analyzed. A management policy of aggressive ultraearly surgery (not selected by age or by grade) was followed. Coiling was not available. Outcomes were assessed at 3 months.

Despite the aggressive management policy, surgery could be performed in only 132 poor-grade patients (75%). Twenty percent of all patients were 70 years of age or older (15% of the surgical cases). All surgery was performed within 12 hours of subarachnoid hemorrhage (majority <6 h). Preoperative rebleeding occurred within the first 12 hours (>85% within 6 h) in 20% of the patients, which is four times the rate found in good-grade patients managed according to the same policy. Outcome assessment performed at 3 months in the 132 poor-grade surgical patients revealed that 40% were independent, 15% were dependent, and 45% had died. There was no significant difference in outcomes for young and old (70+ yr) poor-grade surgical patients (P > 0.05).

The high ultraearly rebleeding rate indicates a need to urgently secure the ruptured aneurysm by performing surgery or coiling, and this indication is more pronounced for poor-grade patients than for good-grade patients. The outcome results of ultraearly surgery indicate that a nonselective policy does not lead to a large number of dependent survivors, even among elderly poor-grade patients 8).

References

1)

Wang X, Han C, Xing D, Wang C, Ding X. Early management of poor-grade aneurysmal subarachnoid hemorrhage: A prognostic analysis of 104 patients. Clin Neurol Neurosurg. 2019 Feb 5;179:4-8. doi: 10.1016/j.clineuro.2019.02.003. [Epub ahead of print] PubMed PMID: 30776564.
2)

Goldberg J, Schoeni D, Mordasini P, Z’Graggen W, Gralla J, Raabe A, Beck J, Fung C. Survival and Outcome After Poor-Grade Aneurysmal Subarachnoid Hemorrhage in Elderly Patients. Stroke. 2018 Dec;49(12):2883-2889. doi: 10.1161/STROKEAHA.118.022869. PubMed PMID: 30571422.
3)

Schuss P, Hadjiathanasiou A, Borger V, Wispel C, Vatter H, Güresir E. Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Factors Influencing Functional Outcome–A Single-Center Series. World Neurosurg. 2016 Jan;85:125-9. doi: 10.1016/j.wneu.2015.08.046. Epub 2015 Sep 2. PubMed PMID: 26341439.
4)

Zhao B, Zhao Y, Tan X, Cao Y, Wu J, Zhong M, Wang S. Factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage: a multicentre retrospective analysis. BMJ Open. 2015 Apr 15;5(4):e007410. doi: 10.1136/bmjopen-2014-007410. PubMed PMID: 25877280; PubMed Central PMCID: PMC4401840.
5)

Mitra D, Gregson B, Jayakrishnan V, Gholkar A, Vincent A, White P, Mitchell P. Treatment of poor-grade subarachnoid hemorrhage trial. AJNR Am J Neuroradiol. 2015 Jan;36(1):116-20. doi: 10.3174/ajnr.A4061. Epub 2014 Jul 24. PubMed PMID: 25059694.
6)

Zhang Q, Ma L, Liu Y, He M, Sun H, Wang X, Fang Y, Hui XH, You C. Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial. BMC Neurol. 2013 Aug 19;13:108. doi: 10.1186/1471-2377-13-108. PubMed PMID: 23957458; PubMed Central PMCID: PMC3751917.
7)

Sarrafzadeh A, Haux D, Küchler I, Lanksch WR, Unterberg AW. Poor-grade aneurysmal subarachnoid hemorrhage: relationship of cerebral metabolism to outcome. J Neurosurg. 2004 Mar;100(3):400-6. PubMed PMID: 15035274.
8)

Laidlaw JD, Siu KH. Poor-grade aneurysmal subarachnoid hemorrhage: outcome after treatment with urgent surgery. Neurosurgery. 2003 Dec;53(6):1275-80; discussion 1280-2. PubMed PMID: 14633294.

Nimodipine for aneurysmal subarachnoid hemorrhage

Nimodipine for aneurysmal subarachnoid hemorrhage

Nimodipine 60 mg every four hours is administered to all patients with aneurysmal subarachnoid hemorrhage, ideally within four days of SAH. The typical dose is 60 mg every four hours by mouth or nasogastric tube. Nimodipine must be given orally or by nasogastric tube because inadvertent intravenous administration has been associated with serious adverse events, including death. Treatment is continued for 21 days.

The calcium channel blocker nimodipine was initially studied in patients with SAH as a means to prevent vasospasm. However, despite the vasodilatory effects of nimodipine on cerebral vessels, there is no convincing evidence that nimodipine affects the incidence of either angiographic or symptomatic vasospasm 1) 2) 3) 4) 5) 6).

Nevertheless, nimodipine has been demonstrated to improve subarachnoid hemorrhage outcomes and is the standard of care in these patients 7) 8) 9) 10) 11) 12) 13).


Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of a study of Kieninger et al., from the University Hospital Regensburg, was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion.

In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry.

The intended full dose of 60 mg of nimodipine given orally every 4 h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14 days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration.

Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1 mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60 mg every 4 h 14).

References

1) , 7)

Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR. Cerebral arterial spasm–a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619-24. PubMed PMID: 6338383.
2) , 8)

Philippon J, Grob R, Dagreou F, Guggiari M, Rivierez M, Viars P. Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine. Acta Neurochir (Wien). 1986;82(3-4):110-4. PubMed PMID: 3538789.
3) , 9)

Petruk KC, West M, Mohr G, Weir BK, Benoit BG, Gentili F, Disney LB, Khan MI, Grace M, Holness RO, et al. Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg. 1988 Apr;68(4):505-17. PubMed PMID: 3280746.
4) , 10)

Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, Humphrey PR, Lang DA, Nelson R, Richards P, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ. 1989 Mar 11;298(6674):636-42. PubMed PMID: 2496789; PubMed Central PMCID: PMC1835889.
5)

Barker FG 2nd, Ogilvy CS. Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg. 1996 Mar;84(3):405-14. PubMed PMID: 8609551.
6)

Feigin VL, Rinkel GJ, Algra A, Vermeulen M, van Gijn J. Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review. Neurology. 1998 Apr;50(4):876-83. Review. PubMed PMID: 9566366.
11)

Mee E, Dorrance D, Lowe D, Neil-Dwyer G. Controlled study of nimodipine in aneurysm patients treated early after subarachnoid hemorrhage. Neurosurgery. 1988 Mar;22(3):484-91. PubMed PMID: 3283595.
12)

Ohman J, Heiskanen O. Effect of nimodipine on the outcome of patients after aneurysmal subarachnoid hemorrhage and surgery. J Neurosurg. 1988 Nov;69(5):683-6. PubMed PMID: 3054010.
13)

Harders A, Kakarieka A, Braakman R. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. J Neurosurg. 1996 Jul;85(1):82-9. PubMed PMID: 8683286.
14)

Kieninger M, Gruber M, Knott I, Dettmer K, Oefner PJ, Bele S, Wendl C, Tuemmler S, Graf B, Eissnert C. Incidence of Arterial Hypotension in Patients Receiving Peroral or Continuous Intra-arterial Nimodipine After Aneurysmal or Perimesencephalic Subarachnoid Hemorrhage. Neurocrit Care. 2019 Feb 6. doi: 10.1007/s12028-019-00676-w. [Epub ahead of print] PubMed PMID: 30725331.

Neutrophil to lymphocyte ratio for intracerebral hemorrhage

Inflammatory response plays a vital role in the pathological mechanism of intracerebral hemorrhage. It has been recently reported that neutrophil to lymphocyte ratio (NLR) could represent a novel composite inflammatory marker for predicting the prognosis of intracranial hemorrhage (ICH).


The clinical data of 558 consecutive patients from the Ulanqab Central Hospital, with intracerebral hemorrhage (ICH) were retrospectively analyzed. Neutrophil to lymphocyte ratio is calculated by absolute lymphocyte count divided by absolute monocyte count.

Of these patients, 166 patients experienced neurological deterioration (ND) during the first week after admission and 72 patients died within 90 days. Multivariate analysis indicated that white blood cells (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), LMR were significantly associated with ND during the initial week after ICH onset and also were associated with 90-day mortality. Moreover, NLR and LMR showed a higher predictive ability in ND during the initial week after ICH onset than 90-day mortality in receiver operating characteristic analysis. The best cut-off points of NLR and LMR in predicting ND and 90-day mortality were 10.24 and 2.21 and 16.81 and 2.19, respectively.

The results suggest that LMR on admission is a predictive factor for ND during the initial week after ICH onset, as well as 90-day mortality 1).


104 patients with acute ICH admitted to West China Hospital, Sichuan University, ChengduChina, from October 2016 to January 2018 were retrospectively enrolled. Admission absolute neutrophil count, lymphocyte count and white blood count were extracted from electronic medical records of patents with ICH. The associations between outcome and laboratory biomarkers were assessed by multivariable logistic regression analysis. The comparison of predictive power of independent predictors was evaluated by receiver operating characteristic curves (ROC).

59 ICH patients with surgical treatment exhibited unfavorable outcome, which associated with higher admission NLR (OR 0.692, 95%CI 0.518-0.925, P=0.01; OR 1.148, 95%CI 1.078-1.222, P<0.01; OR 1.215, 95%CI 1.015-1.454, P=0.03), lower GCS and larger hematoma. NLR showed the best predictive power by comparing with other laboratorial variables (area under the curve [AUC] 0.668, 95%CI 0.569-0.757, P<0.01), and was also found to linearly correlate with GCS at admission, hematoma volume, ANC, ALC and hydrocephalus. Meanwhile, the best predictive cutoff point of 6.46 for NLR was also identified.

Other than the association of prognosis of ICH patients, NLR exhibited potential independently predictive ability for 90-day functional outcome of ICH patients after surgery 2).

1)

Qi H, Wang D, Deng X, Pang X. Lymphocyte-to-Monocyte Ratio Is an Independent Predictor for Neurological Deterioration and 90-Day Mortality in Spontaneous Intracerebral Hemorrhage. Med Sci Monit. 2018 Dec 20;24:9282-9291. doi: 10.12659/MSM.911645. PubMed PMID: 30572340.
2)

F Z, C T, X H, J Q, X L, C Y, Y J, M Y. Association of neutrophil to lymphocyte ratio on 90-day functional outcome in intracerebral hemorrhage patients undergoing surgical treatment. World Neurosurg. 2018 Aug 10. pii: S1878-8750(18)31791-1. doi: 10.1016/j.wneu.2018.08.010. [Epub ahead of print] PubMed PMID: 30103056.
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