Fatigue after subarachnoid haemorrhage: a systematic review

BackgroundFatigue is common and debilitating symptom in many neurological disorders and it has been reported in patients after non-traumatic subarachnoid haemorrhage (SAH).ObjectivesWe undertook a systematic review to identify and critically appraise all published studies that have reported frequency, severity and time course of fatigue after SAH, the factors associated with its development and the impact of fatigue on patients' life after SAH.MethodsWe searched Medline, EMBASE, CINAHL, PsycINFO, AMED, PubMed and included in the review all studies published in English, recruiting at least 10 patients (> 18 years old) after SAH, which reported fatigue.ResultsWe identified 13 studies (total number of subjects 737) meeting our inclusion criteria. The frequency of fatigue ranged from 31 to 90%. Fatigue remained common even several years after the ictus. According to some studies fatigue after SAH was associated with sleep disturbances, anxiety, depression, posttraumatic stress disorder, cognitive and physical impairment, but these could not explain all cases of fatigue. Fatigue reduces quality of life and life satisfaction in patients after SAH.ConclusionsFatigue is common after SAH and seems to persist. Further research is needed to clarify its time course and identify factors associated with its development.     

Effect of nimodipine on platelet function in patients with subarachnoid hemorrhage

We studied platelet function in 41 patients with subarachnoid hemorrhage who were randomized to receive either nimodipine or placebo in a double-blind fashion. Nimodipine was given to 21 patients, intravenously for 7-10 days and then orally until 21 days after the subarachnoid hemorrhage. The other 20 patients received placebo in a similar manner. Nimodipine did not significantly influence platelet aggregability. For the first 1-5 days after the subarachnoid hemorrhage, nimodipine treatment did not have any notable effect on adenosine diphosphate-induced platelet thromboxane B2 release, but a significant (p less than 0.05) inhibitory effect was observed thereafter. During intravenous administration, nimodipine prevented the increase in thromboxane release otherwise observed after subarachnoid hemorrhage. Concomitant with the decrease in thromboxane release, nimodipine increased the platelet count both before and after surgery so that the capacity for thromboxane formation per liter of blood decreased less than expected on the basis of thromboxane release per 10(7) platelets. Our study suggests that nimodipine might diminish the chance of cerebral ischemia by inhibiting platelet thromboxane release.     

尼莫地平对创伤性蛛网膜下腔出血的临床疗效简

目的探讨尼莫地平对创伤性蛛网膜下腔出血（tSAH）的临床疗效O方法将62例tSAH患者按人院顺序分为治疗组及对照组,每组31例;对照组给予保守治疗,治疗组在对照组治疗基础上加用尼莫地平。分别于治疗前、治疗后3、5、7、10、14、21d进行GCS评分,颅骨钻孔放置脑实质型颅内压探头连续监测颅内压14天,分别于治疗前及治疗后3＼5、7、14、21天行经颅多普勒超声检查检测伤侧大脑中动脉（MCV）的收缩峰血流速度（vp）,伤后3月进行GOS评分。结果治疗7d后,治疗组GCS评分显著高于对照组（JP〈0．05）,而颅内压显著低于对照组（P〈0．05）。治疗后3d,治疗组MCVVp明显低于对照组（P〈0．05）。治疗组脑血管痉挛（MCAVp〉120cm／s）发生率（11／31,35．5％）明显低于对照组（18／31,51．6％,P〈0．05）,治疗组预后良好率（83．9％,26／31;GOS4～5分）明显高于对照组（58．1％,18／31;GOS1-3分,P〈0．05）。结论在tSAH患者伤后早期应用尼莫地平可以减少CVS的发生,改善tSAH患者预后。     

Effect of nimodipine on cerebral blood flow and cerebrovascular reactivity after subarachnoid haemorrhage

The aim of the present study was to investigate the effect of nimodipine on autoregulation of cerebral blood flow (CBF), CO2 reactivity and cerebral oxygen metabolism (CMRO2) in patients with subarachnoid haemorrhage (SAH). Eight patients with severe SAH were studied with repeated CBF and CMRO2 measurements on the first day of the bleeding and after at least 12 h of treatment of nimodipine. An initial resting study, an autoregulation study and a hyperventilation study was performed. CBF was measured using the 133-Xenon intravenous method. CMRO2 was calculated as AVDO2 x CBF. Nimodipine did not significantly change CBF and CMRO2 in the initial resting study. After induced arterial hypotension intact autoregulation was found before as well as after treatment with nimodipine. Beneficial effects of nimodipine were found on CO2 reactivity and CMRO2 during hypotension that may be explained as a positive effect on cerebral ischaemia.     

The importance of traumatic subarachnoid haemorrhage

Post-traumatic cerebral vasospasm is being increasingly recognised as a possibly significant complication after head injury. To assess the relationship between post-traumatic subarachnoid haemorrhage (tSAH) and post-traumatic vasospasm, 63 patients with severe head injury (GCS 3-8) were studied. Forty-seven patients had cerebral contusion on the initial CT scan. In 25 of these (Group I) there were only contusions, while 22 (Group II) also had tSAH. All patients had daily measurements of blood flow velocity in the basal cerebral arteries using transcranial Doppler ultrasound (TCD). The incidence of vasospasm detected by TCD was significantly higher in Group II. Furthermore there were significantly fewer good outcomes (GOS 1 and 2) in this group. These results suggest that the presence of subarachnoid blood in patients with severe head injury is associated with a risk of vasospasm, and with poorer outcome.     

A systematic review of Terson's syndrome: frequency and prognosis after subarachnoid haemorrhage

OBJECTIVE: To review systematically the frequency and prognostic significance of vitreous haemorrhage in patients with subarachnoid haemorrhage (Terson's syndrome). METHODS: Papers relating to vitreous haemorrhage in patients with subarachnoid haemorrhage were retrieved. The only studies considered were those with at least 10 consecutive cases of subarachnoid haemorrhage with or without vitreous haemorrhage. The frequency of vitreous haemorrhage in such cases was calculated in prospective and retrospective studies. Mortality was compared in patients with and without Terson's syndrome. RESULTS: 154 papers were reviewed. Three prospective studies and six retrospective studies satisfied the inclusion criteria. Of 181 patients with subarachnoid haemorrhage assessed prospectively (mean age, 51.7 years), 24 (13%) had vitreous haemorrhage; among 1086 retrospective records, 37 (3%) had documented vitreous haemorrhage (p<0.001). Patients with Terson's syndrome had higher Hunt and Hess grades than those without (mean grade, 3.6 v 2.6). Patients with Terson's syndrome were also more likely to die (13 of 30 (43%) v 31 of 342 (9%); odds ratio 4.8; p<0.001). CONCLUSIONS: Prospective studies show a higher frequency of Terson's syndrome than retrospective studies, suggesting that vitreous haemorrhage is not well documented. Vitreous haemorrhage is an adverse prognostic finding in patients with subarachnoid haemorrhage.     

Effect of cilostazol in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR = 0.47; 95% CI, 0.31–0.72; p < 0.001), severe vasospasm (RR = 0.48; 95% CI, 0.28–0.82; p = 0.007), vasospasm-related new cerebral infarctions (RR = 0.38; 95% CI, 0.22–0.67; p = 0.001), and poor outcome (RR = 0.57; 95% CI, 0.37–0.88; p = 0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm-related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH.     

Effect of pharmaceutical treatment on vasospasm,delayed cerebral ischemia,and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis

As it is often assumed that delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is caused by vasospasm, clinical trials often focus on prevention of vasospasm with the aim to improve clinical outcome. However, the role of vasospasm in the pathogenesis of DCI and clinical outcome is possibly smaller than previously assumed. We performed a systematic review and meta-analysis on all randomized, double-blind, placebo-controlled trials that studied the effect of pharmaceutical preventive strategies on vasospasm, DCI, and clinical outcome in SAH patients to further investigate the relationship between vasospasm and clinical outcome. Effect sizes were expressed in pooled risk ratio (RR) estimates with corresponding 95% confidence intervals (CI). A total of 14 studies randomizing 4,235 patients were included. Despite a reduction of vasospasm (RR 0.80 (95% CI 0.70 to 0.92)), no statistically significant effect on poor outcome was observed (RR 0.93 (95% CI 0.85 to 1.03)). The variety of DCI definitions did not justify pooling the DCI data. We conclude that pharmaceutical treatments have significantly decreased the incidence of vasospasm, but not of poor clinical outcome. This dissociation between vasospasm and clinical outcome could result from methodological problems, sample size, insensitivity of clinical outcome measures, or from mechanisms other than vasospasm that also contribute to poor outcome.     

Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: a systematic review of the literature

Severe intraventricular hemorrhage caused by extension from subarachnoid hemorrhage or intracerebral hemorrhage leads to hydrocephalus and often to poor outcome. We conducted a systematic review to compare conservative treatment, extraventricular drainage, and extraventricular drainage combined with fibrinolysis. We carried out a search in Medline of the literature between January 1966 and December 1998 and an additional hand-search from January 1990 to December 1998. Pharmaceutical companies were contacted to gather unpublished data. We reviewed the reference lists of all relevant articles. Two authors independently assessed eligibility of the studies and extracted data on characteristics of study design, patients, and treatment. Patients with primary intraventricular hemorrhage were excluded. Main outcome measures were death and poor outcome (defined as death or dependency) at the end of follow-up. No randomized clinical trial has yet been conducted so far, and we therefore reviewed only observational studies. The case fatality rate for conservative treatment (ten studies) was 78%. For extraventricular drainage (seven studies) it was 58% [relative risk versus conservative treatment (RR) 0.74; 95% confidence interval (CI) 0.55-0.99]. For extraventricular drainage with fibrinolytic agents (five studies) the case fatality rate was 6% (RR 0.08; 95% CI 0.02-0.24). The poor outcome rate for conservative treatment was 90%, that for extraventricular drainage 89% (RR 0.98; 95% CI 0.75-1.30) and that for extraventricular drainage with fibrinolytic agents 34% (RR 0.38; 95% CI 0.21-0.68). All RR values remained essentially the same after adjusting for age, sex, World Federation of Neurological Surgeons scale, study design, and year of publication for the studies that provided these data. Outcome is thus poor in patients with intraventricular extension of subarachnoid or intracerebral hemorrhage. This meta-analysis suggests that treatment with ventricular drainage combined with fibrinolytics may improve outcome for such patients, although this impression is derived only from an indirect comparison between observational studies. A randomized clinical trial is warranted.     

Axonal damage and outcome in subarachnoid haemorrhage

Background

On the basis of preliminary evidence from patients with subarachnoid haemorrhage (SAH), axonal degeneration is thought to be an underestimated pathological feature.

Methods

A longitudinal study in 17 patients with aneurysmal SAH. Ventricular CSF was collected daily for up to 14 days. The neurofilament heavy chain^SMI35 (NfH^SMI35, a biomarker for axonal damage) was quantified using a standard ELISA (upper limit of normal 0.73 ng/ml). The primary outcome measure was the Glasgow Outcome Score (GOS) at 3 months.

Results

Of 148 samples from patients with SAH, pathologically high NfH levels in the CSF were found in 78 (52.7%) samples, compared with 20 (5%) of 416 samples from the reference population (p<0.0001). A pathological increase in NfH was observed in all patients with a bad outcome (GOS 1–3) compared with 8% of those with a good outcome (GOS 4–5, p<0.0001). This increase typically became significant 7 days after the haemorrhage (p<0.01). The result was confirmed by analysing the individual mean NfH concentrations in the CSF (3.45 v 0.37 ng/ml, p<0.01), and was reinforced by the inverse correlation of NfH in the CSF with the GOS (r = −0.65, p<0.01). Severity of injury was found to be correlated to NfH^SMI35 levels in the CSF (World Federation of Neurological Surgeons, r = 0.63, p<0.01 and Glasgow Coma Score, r = −0.61, p<0.01).

Conclusion

Patients with SAH thus have secondary axonal degeneration, which may adversely affect their outcome.The presence of axonal degeneration in patients with subarachnoid haemorrhage (SAH) has recently been suggested in a longitudinal study.¹ One important finding was that damage to axons may continue after the primary injury and extend into the period of delayed cerebral ischaemia.^1,2,3,4Presence of secondary axonal degeneration in patients with SAH may be relevant to the outcome because, despite the high mortality (32–67%) during the hyperacute phase,^2,5 a considerable proportion of mostly young and otherwise healthy patients has the potential for good recovery from a limited degree of primary injury. In these patients, it is well known that secondary brain damage caused by delayed cerebral ischaemia adversely affects the potential for recovery.^2,3,4 About 50% of patients who survive do not return to their previous level of employment.^6,7,8In this longitudinal study, we monitored the development of axonal degeneration indirectly by measuring a biomarker for axonal degeneration (neurofilaments, reviewed by Petzold⁹). Firstly, we investigated whether neurofilaments would be increased early on (eg, a single peak, indicative of primary axonal injury) or rise late (eg, secondary peaks, suggestive of secondary axonal damage) in the disease course. Secondly, we tested whether the pattern of an anticipated¹ increase in neurofilament levels over time would be related to the degree of recovery.     

Evaluation of traumatic subarachnoid haemorrhage on computed tomography.

Traumatic subarachnoid haemorrhage (TSAH) is a computed tomography (CT) scan finding frequently found in the acute phase of brain injury. However, the clinical evaluation of TSAH is controversial. The subjects in the present series consisted of 46 patients in whom the initial CT scan within 6 h after injury revealed a high density area in the subarachnoid space. The subjects were divided into three types: type 1 n = 10) had massive haemorrhage in the basal cisterns; type II (n = 9) had localized haemorrhage in the basal cisterns; and type III (n = 27) had localized haemorrhage in the cortical sulci or Sylvian fissure. The clinical and neuroradiological findings as well as the outcome of these three types of TSAH are discussed. The results of our study showed that TSAH observed at an acute stage of head trauma was associated with a great variety of intracranial pathological changes. Type I cases had either good or poor outcome, and diffuse brain injury was predominant in patients with poor outcome. The outcome was generally good in type II and III cases.     

Complications and outcome in patients with aneurysmal subarachnoid haemorrhage: a prospective hospital based cohort study in the Netherlands

OBJECTIVE: The aim of this study was to investigate prospectively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are, what the outcome is, how many of these patients have "modern treatment"-that is, early obliteration of the aneurysm and treatment with calcium antagonists-what factors cause a delay in surgical or endovascular treatment, and what the estimated effect on outcome will be of improved treatment. METHODS: A prospective, observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherlands. The condition on admission, diagnostic procedures, and treatments were recorded. If a patient had a clinical deterioration, the change in Glasgow coma score (GCS), the presence of focal neurological signs, the results of additional investigations, and the final diagnosed cause of the deterioration were recorded. Clinical outcome was assessed with the Glasgow outcome scale (GOS) at 3 month follow up. In patients with poor outcome at follow up, the cause was diagnosed. RESULTS: Of the 110 patients, 47 (43%) had a poor outcome. Cerebral ischaemia, 31 patients (28%), was the most often occurring complication. Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34% and 30% of the patients with poor outcome respectively. Of all patients 102 (93%) were treated with calcium antagonists and 45 (41%) patients had early treatment to obliterate the aneurysm. The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission, in 31% and 23% respectively. CONCLUSIONS: In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding. Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage.     

Terson haemorrhage in patients suffering aneurysmal subarachnoid haemorrhage: a prospective analysis of 60 consecutive patients

Objective

The concomitance of vitreous/subhyaloid haemorrhage (Terson syndrome; TS) and aneurysmal subarachnoid haemorrhage (aSAH) is commonly underestimated. The aim of this study was to determine the incidence of TS and to identify parameters that predispose its development, indicate the severity of the underlying disease, and predict outcome.

Methods

Sixty consecutive patients suffering from aSAH were included in this study. The admitting Glasgow Coma Scale scores (GCS), Hunt &; Hess (H&;H) and Fisher grades were documented. All participants were ophthalmologically examined. The outcome at discharge was estimated using the Glasgow Outcome Scale (GOS).

Results

Of the 60 patients admitted for aSAH, eleven (18.3%) displayed TS within 24 h after aneurysm rupture. Statistical analysis revealed a significant relation between TS and either high Fisher- (3.0 vs. 2.32; p = 0.008) or H&;H- (4.09 vs. 2.69; p = 0.001) and low GCS- (5.55 vs. 12.87; p < 0.001) scores. Compared with the non-TS group, patients with TS displayed generally worse outcomes (mean GOS 2.09 vs. 3.53; p = 0.007), including a significantly higher mortality (36.4 vs. 10.2%; p = 0.028).

Conclusion

Terson syndrome is likely to occur in severe aSAH with poor admission scores and indicates a worse functional outcome. An ophthalmological examination is strongly recommended in aSAH patients with poor admission scores.     

Incidence and outcome of subarachnoid haemorrhage: a retrospective population based study

OBJECTIVES: The purpose was to define the incidence and case fatality rates of subarachnoid haemorrhage in the population of Devon and Cornwall. METHODS: A retrospective population based design was employed with multiple overlapping methods of case ascertainment. A strict definition of subarachnoid haemorrhage was used. Age and sex specific incidence rates and relative risks for death at different time intervals are calculated. RESULTS: Eight hundred cases of first ever subarachnoid haemorrhage were identified; 77% of cases were verified by CT, 22% by necropsy, and 1% by lumbar puncture. The incidence rates are higher than those previously reported in the United Kingdom. The age standardised incidence rate (/100 000 person-years) for females was 11.9 (95% confidence interval (95% CI) 9.5-15.0), for males 7.4 (5.4-10.0), and the total rate was 9.7 (7.5-12.6). The case fatality rates at 24 hours, 1 week, and 30 days were 21 (18-24)%, 37 (33-41)%, and 44 (40-49)% respectively. The relative risk for death at 30 days for those over 60 years:under 60 years was 2.95 (2.18-3.97). CONCLUSION: The incidence of subarachnoid haemorrhage in the United Kingdom is higher than previously reported. Three quarters of the mortality occurs within 3 days.