Abstract
Objective: The study aim was to investigate the association between initiating mobilization within 7 days after onset and symptomatic cerebral vasospasm (SCV) in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: This was a retrospective multicenter case-control study in Japan. Patients with a diagnosis of aSAH who underwent physical therapy with/without occupational therapy were included and categorized into 2 groups according to the presence or absence of SCV. Initiating mobilization was defined as sitting on the bed edge (at least once, with/without assist, regardless of duration) within 7 days after aSAH onset. Cox proportional hazards regression analysis was performed to evaluate the association between initiating mobilization within 7 days after onset and SCV. Results: The analysis included 510 patients. Among all included patients, 57 (11.2%) patients had SCV. In the univariate Cox proportional hazards regression analysis, initiating of mobilization was not associated with SCV (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.45–1.32). In the multivariate analysis, only the modified Fisher scale was significantly associated with SCV (HR = 26.23; 95% CI = 1.21–571.0). Conclusion: Initiating mobilization within 7 days after aSAH onset was not associated with SCV in patients with aSAH.
Keywords: Aneurysmal subarachnoid hemorrhage, Symptomatic cerebral vasospasm, Mobilization, Rehabilitation
Aneurysmal subarachnoid hemorrhage (aSAH) is a serious disease. The proportion of aSAH is the lowest among all stroke types, ranging from 1% to 5%1). However, the case fatality rate is as high as 25%−30%1). Furthermore, several complications, such as rebleeding, symptomatic cerebral vasospasm (SCV), hydrocephalus, and seizures can occur 2). Therefore, treatment after aSAH is very complicated and difficult2–4). Among the potential complications, SCV is strongly associated with poor functional outcome and mortality5–7). SCV is observed in approximately 20%−30% of patients with aSAH8–10). SCV may occur 4−14 days after onset11,12) and most frequently occurs approximately 7 days after onset13,14). In this period, rehabilitation and mobilization require attention to SCV.
Various factors are known to be associated with increasing risk of SCV, such as age8,9,15), clinical grade8,9,15), thick subarachnoid hematoma8,9,15,16), and aneurysm location13,16). However, the impact of mobilization during the early phase after aSAH on SCV is uncertain. Several clinical guidelines recommend early rehabilitation and mobilization after stroke, but protocols for rehabilitation and mobilization after aSAH are not mentioned2,4,17,18).
Few studies have investigated the association between mobilization and SCV. A previous study suggested that early mobilization did not increase the incidence of SCV19). In contrast, another study found that early mobilization initiated 2–5 days after onset was caused by delayed cerebral ischemia20). Mobilization may increase intracranial pressure and decrease cerebral perfusion pressure, which may exacerbate cerebral vasospasm and delayed cerebral ischemia21,22). Cerebral blood flow autoregulation may be disrupted after aSAH23). Changes in head position due to mobilization may decrease cerebral blood flow, and there is a concern that this decrease in blood flow could induce SCV. However, in a previous study examining the effect of head-up on cerebral blood flow in patients with subarachnoid hemorrhage who had cerebral vasospasm, head-up did not decrease cerebral blood flow24). Data on the association between mobilization and SCV are limited. Furthermore, only single-center studies in small samples of patients have been conducted. To the best of our knowledge, no multicenter study has investigated the association between mobilization and SCV.
We hypothesized that initiating mobilization within 7 days after aSAH onset, a period when SCV often occurs, is not associated with SCV. If initiating mobilization after aSAH onset is not associated with SCV, this study may contribute to a strategy for promoting early mobilization in patients with aSAH. Therefore, we conducted a multicenter case-control study in Japan to investigate the association between initiating mobilization within 7 days after onset and SCV in patients with aSAH.
Methods
Study design
We conducted a retrospective multicenter case-control study in 5 hospitals in Japan (Naha City Hospital, Saitama Medical Center, Akita Cerebrospinal and Cardiovascular Center, Sapporo Shiroishi Memorial Hospital, and Yuuai Medical Center). This study was part of a project entitled Safety and Efficacy of Acute Rehabilitation in Subarachnoid Hemorrhage (the SEASAH study) and was approved by the ethics committee of Naha City Hospital (2021a11), Saitama Medical Center (2286), Akita Cerebrospinal and Cardiovascular Center (19-18), Sapporo Shiroishi Memorial Hospital (A01-2021), and Yuuai Medical Center (R01R045). The principles of the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were followed. The requirement for informed consent was waived in all participating hospitals because this study only involved retrospective analysis of anonymous preexisting data.
Participants
The study included consecutive patients with a diagnosis of aSAH admitted to participating hospitals between April 2014 and March 2019, all of whom had undergone physical therapy with/without occupational therapy. The exclusion criteria were as follows: (1) patients who had died, (2) those without aneurysm treatment, (3) those with a recurrence of aSAH, (4) those who had undergone reoperation, (5) those who underwent aneurysm treatment >72 hours after the onset of aSAH, (6) those who were <20 years old, (7) those diagnosed with SCV before initiating mobilization, and (8) those for whom data were lacking. The included patients were divided into the SCV group (diagnosed) and the non-SCV group (no SCV present).
Outcome and clinical variables
Data were collected retrospectively through the electronic medical records of the participating hospitals by local study investigators. The primary outcome in this study was the incidence of SCV. The diagnosis of SCV was made by a neurosurgeon on the basis of the radiological examination and presence of delayed neurological worsening. The patient characteristics and clinical data included age, sex, history of hypertension and diabetes mellitus, the World Federation of Neurosurgical Societies (WFNS) grading system25) and modified Fisher score (MFS)26) on admission, aneurysm location, and treatment based on type, presence of SCV, days from aSAH onset to diagnosis of SCV, and initiating or not initiating mobilization within 7 days after aSAH onset. Age was dichotomized into <65 years (non-elderly patients) and ≥65 years (elderly patients). WFNS grade was dichotomized into 1–3 (mild–moderate condition) and 4–5 (severe condition). MFS was dichotomized into 1–2 (thin subarachnoid hematoma) and 3–4 (thick subarachnoid hematoma). Aneurysm location was dichotomized into anterior circulation (anterior cerebral artery, anterior communicating artery middle cerebral artery, internal carotid posterior communicating artery) and posterior circulation (posterior cerebral artery, posterior communication artery, vertebral-basilar artery). Type of aneurysm treatment was dichotomized into surgical and endovascular. Initiating mobilization was defined as sitting on the bed edge (at least once, with/without assist, regardless of duration) within 7 days after aSAH onset. Mobilization was initiated after aneurysm treatment and guided by a physical therapist or an occupational therapist. In participating hospitals, criteria and risk management of initiating mobilization depended on individually defined thresholds of vital sign and parameters, such as arterial blood pressure, intracranial pressure, heart rate, oxygenation, respiratory rate, body temperature, neurological symptoms, and subjective symptoms. These criteria and risk management were determined by a neurosurgeon and a therapist in the participating hospitals.
Statistical analysis
Categorical variables are presented as a number (%), and continuous variables are presented as a median with interquartile range. We performed the χ2 test or Fisher’s exact test to compare categorical variables between the SCV group and non-SCV group, and we performed univariate and stepwise multivariate Cox proportional hazards regression analysis to estimate predictors of SCV. Multivariate Cox proportional hazards regression analysis was adjusted by age, history of hypertension and diabetes mellitus, WFNS grade, MFS, aneurysm location, and initiating or not initiating mobilization within 7 days after aSAH onset. These covariates, other than initiating mobilization, have been found to be associated with SCV in previous studies8,9,13,15,16,27). Cox proportional hazards regression analysis results were expressed as a hazard ratio (HR) with 95% confidence interval (CI). The difference in the incidence of SCV between with and without initiating mobilization was assessed by Kaplan–Meier curves and compared by performing the log-rank test. To assess the robustness of our findings, we performed three sensitivity analyses. We repeated the primary analysis (multivariate Cox proportional hazards regression analysis) after considering stricter definitions for mobilization and eligibility criteria. Mobilization was defined as initiating mobilization within 5 days after aSAH onset (Model 1) and within 9 days after aSAH onset (Model 2). Finally, we repeated the primary analysis after including only MFS 3 and 4 patients at high risk of SCV (Model 3).
To assess the characteristics of patients with mobilization initiated within 7 days and those with mobilization initiated after 7 days, we performed the χ2 test or Fisher’s exact test and Mann–Whitney U-test to compare between the groups. Furthermore, we repeated the same analysis to compare values between the groups in only patients with SCV.
Values of P <0.05 were considered to be indicative of statistical significance. All statistical analyses were performed using the SPSS statistical software (IBM SPSS Statistics for Windows, Version 22.0, Released 2013; IBM, Armonk, NY, USA).
Results
A total of 718 patients were screened, and 510 were included in the analysis. Figure 1 shows the flowchart of patient selection. Table 1 shows a comparison of the patients’ clinical characteristics between the SCV group and the non-SCV group. The proportions of WFNS grades 4–5 and MFS 3–4 were significantly higher in the SCV group than in the non-SCV group (WFNS grades 4–5: 45.6% vs. 27.6%; P = 0.006. MFS 3–4: 100% vs. 83.0%; P = 0.016). The proportions of initiating mobilization within 7 days were not significantly different between the SCV and the non-SCV groups (38.6% vs. 45.5%; P = 0.397). There were no significant differences in age, sex, history of hypertension and diabetes mellitus, aneurysm location, and type of aneurysm treatment between the SCV and the non-SCV groups. Figure 2 shows the cumulative incidence curves for the different categories of with/without initiating mobilization within 7 days in the Kaplan–Meier analysis. There was no significant difference in the log-rank test between the patients with/without initiating mobilization (P = 0.344). Table 2 shows the Cox proportional hazards regression analysis results. The patients who initiated mobilization within 7 days had no significant association with SCV in the univariate analysis (HR = 0.78; 95% CI = 0.45–1.32; P = 0.348). In the multivariate analysis, only MSF was significantly associated with SCV (HR = 26.23; 95% CI = 1.21–571.0; P = 0.038). Initiating mobilization, age, hypertension, diabetes mellitus, WFNS grade, and aneurysm location were not significantly associated with SCV in the multivariate analysis. Furthermore, initiating mobilization was not associated with SCV in any of the sensitivity analyses (Table 3). MFS was only associated with SCV in models 1 and 2 (HR = 26.23; 95% CI = 1.21–571.0; P = 0.038) and in model 3 (HR = 2.38; 95% CI = 1.42–4.02; P = 0.001).
Fig. 1.
Flowchart of the included patients
aSAH, aneurysmal subarachnoid hemorrhage; SCV, symptomatic cerebral vasospasm
Table 1.
Comparison of the patients’ characteristics between the SCV group and non-SCV group
| All patients (N = 510) | SCV group (n = 57) | Non-SCV group (n = 453) | P value | |
|---|---|---|---|---|
| The data are presented as number (%). | ||||
| SCV, symptomatic cerebral vasospasm; WFNS, World Federation of Neurosurgical Societies; MFS, modified Fisher scale | ||||
| Age, (years) n (%) | 0.261 | |||
| <65 | 271 (53.1) | 26 (45.6) | 245 (54.1) | |
| ≥65 | 239 (46.9) | 31 (54.6) | 208 (45.9) | |
| Sex, n (%) | 0.757 | |||
| Female | 363 (71.2) | 42 (73.7) | 321 (70.9) | |
| Male | 147 (28.8) | 15 (26.3) | 132 (29.1) | |
| Hypertension, n (%) | 0.561 | |||
| Yes | 180 (35.3) | 18 (31.6) | 162 (35.8) | |
| No | 330 (64.7) | 39 (68.4) | 291 (64.2) | |
| Diabetes mellitus, n (%) | 0.223 | |||
| Yes | 22 (4.3) | 4 (7.0) | 18 (4.0) | |
| No | 488(95.7) | 53 (93.0) | 435 (96.0) | |
| WFNS grade, n (%) | 0.006 | |||
| 1–3 | 359 (70.4) | 31 (54.4) | 328 (72.4) | |
| 4–5 | 151 (29.6) | 26 (45.6) | 125 (27.6) | |
| MFS, n (%) | 0.001 | |||
| 1–2 | 77 (15.1) | 0 (0) | 77 (17.0) | |
| 3–4 | 433 (84.9) | 57 (100) | 376 (83.0) | |
| Aneurysm location, n (%) | 0.090 | |||
| Anterior circulation | 447 (87.6) | 54 (94.7) | 393 (86.8) | |
| Posterior circulation | 63 (12.4) | 3 (5.3) | 60 (13.2) | |
| Type of aneurysmal treatment, n (%) | 0.670 | |||
| Surgical | 301 (59.0) | 32 (56.1) | 269 (59.4) | |
| Endovascular | 209 (41.0) | 25 (43.9) | 184 (40.6) | |
| Initiating mobilization within 7 days, n (%) | 0.397 | |||
| Yes | 228 (44.7) | 22 (38.6) | 206 (45.5) | |
| No | 282 (55.3) | 35 (61.4) | 247 (54.5) | |
Fig. 2.
Kaplan–Meier curves for cumulative incidence rate of SCV in patients with/without initiating mobilization within 7 days after onset
There was no significant difference in the cumulative incidence rates of SCV between the initiating mobilization group and without initiating mobilization group (log-rank P = 0.344).
SCV, symptomatic cerebral vasospasm
Table 2.
Cox proportional hazards regression analysis of factors associated with SCV
| Univariate analysis | Multivariate analysis | |||||
|---|---|---|---|---|---|---|
| HR (95%CI) | P value | HR (95%CI) | P value | |||
| SCV, symptomatic cerebral vasospasm; WFNS, World Federation of Neurosurgical Societies; MFS, modified Fisher scale; HR, hazard ratio; CI, confidence interval | ||||||
| Age, (years) (ref: <65) | 1.35 | 0.80–2.27 | 0.260 | |||
| Hypertension (ref: no) | 0.84 | 0.48–1.46 | 0.531 | |||
| Diabetes mellitus (ref: no) | 1.70 | 0.62–4.70 | 0.306 | |||
| Aneurysm location (ref: posterior) | 2.65 | 0.83–8.48 | 0.100 | |||
| WFNS grade (ref: 1–3) | 2.08 | 1.23–3.50 | 0.006 | |||
| MFS (ref: 1–2) | 26.23 | 1.21–571.0 | 0.038 | 26.23 | 1.21–571.0 | 0.038 |
| Initiating mobilization within 7 days (ref: no) | 0.78 | 0.45–1.32 | 0.348 | |||
Table 3.
Sensitivity analysis
| Model 1 | Model 2 | Model 3 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| HR (95%CI) | P value | HR (95%CI) | P value | HR (95%CI) | P value | ||||
| Model 1: Mobilization was defined as initiating mobilization within 5 days after aSAH onset. Reference value was MFS 1–2. | |||||||||
| Model 2: Mobilization was defined as initiating mobilization within 9 days after aSAH onset. Reference value was MFS 1–2. | |||||||||
| Model 3: Only patients with MFS 3–4 were included. Reference value was MFS 3. | |||||||||
| MFS, modified Fisher scale; HR, hazard ratio; CI, confidence interval; aSAH, aneurysmal subarachnoid hemorrhage | |||||||||
| MFS (in Models 1 and 2; ref: 1–2) | 26.23 | 1.21–571.0 | 0.038 | 26.23 | 1.21–571.0 | 0.038 | |||
| MFS (in Model 3; ref: 3) | 2.38 | 1.42–4.02 | 0.001 | ||||||
Table 4 shows a comparison of the characteristics of the patients with mobilization initiated within 7 days and those with mobilization initiated after 7 days. The incidence of SCV was 11.2% among all patients, 9.6% in the patients with mobilization initiated within 7 days, and 12.4% in the patients with mobilization initiated after 7 days. No significant difference was observed in the incidence of SCV. The proportions of no hypertension, WFNS grades 1–3, MFS 3–4, and endovascular treatment were significantly higher in patients with mobilization initiated within 7 days than in those with mobilization initiated after 7 days (no hypertension: 69.7% vs. 60.6%; P = 0.04. WFNS grades 1–3: 79.4% vs. 63.1%; P <0.001. MFS: 88.6% vs. 81.9%; P = 0.046. Endovascular treatment: 61.8% vs. 24.1%; P <0.001). Table 5 shows a comparison of the characteristics of the patients with mobilization initiated within 7 days and those with mobilization initiated after 7 days with SCV. The median days from aSAH onset to diagnosis of SCV was 9 days among all patients, 8 days in the patients with mobilization initiated within 7 days, and 9 days in the patients with mobilization initiated after 7 days. No significant difference was observed between the groups.
Table 4.
Comparison of the characteristics of the patients with mobilization initiated within 7 days and those with mobilization initiated after 7 days
| All patients (N = 510) | Within 7 days group (n = 228) | After 7 days group (n = 282) | P value | |
|---|---|---|---|---|
| The data are presented as number (%). | ||||
| WFNS, World Federation of Neurosurgical Societies; MFS, modified Fisher scale; SCV, symptomatic cerebral vasospasm | ||||
| Age, (years) n (%) | 0.061 | |||
| <65 | 271 (53.1) | 132 (57.9) | 139 (49.3) | |
| ≥65 | 239 (46.9) | 96 (42.1) | 143 (50.7) | |
| Sex, n (%) | 0.624 | |||
| Female | 363 (71.2) | 165 (72.4) | 198 (70.2) | |
| Male | 147 (28.8) | 63 (27.6) | 84 (29.8) | |
| Hypertension, n (%) | 0.04 | |||
| Yes | 180 (35.3) | 69 (30.3) | 111 (39.4) | |
| No | 330 (64.7) | 159 (69.7) | 171 (60.6) | |
| Diabetes mellitus, n (%) | 0.513 | |||
| Yes | 22 (4.3) | 8 (3.5) | 14 (5.0) | |
| No | 488 (95.7) | 220 (96.5) | 268 (95.0) | |
| WFNS grade, n (%) | <0.001 | |||
| 1–3 | 359 (70.4) | 181 (79.4) | 178 (63.1) | |
| 4–5 | 151 (29.6) | 47 (20.6) | 104 (36.9) | |
| MFS, n (%) | 0.046 | |||
| 1–2 | 77 (15.1) | 26 (11.4) | 51 (18.1) | |
| 3–4 | 433 (84.9) | 202 (88.6) | 231 (81.9) | |
| Aneurysm location, n (%) | 0.344 | |||
| Anterior circulation | 447 (87.6) | 196 (86.0) | 251 (89.0) | |
| Posterior circulation | 63 (12.4) | 32 (14.0) | 31 (11.0) | |
| Type of aneurysmal treatment, n (%) | <0.001 | |||
| Surgical | 301 (59.0) | 87 (38.2) | 214 (75.9) | |
| Endovascular | 209 (41.0) | 141 (61.8) | 68 (24.1) | |
| SCV | 0.397 | |||
| Yes | 57 (11.2) | 22 (9.6) | 35 (12.4) | |
| No | 453 (88.8) | 206 (90.4) | 247 (87.6) | |
Table 5.
Comparison of the characteristics of the patients with mobilization initiated within 7 days and those with mobilization initiated after 7 days in patient with SCV
| All patients (N = 57) | Within 7 days group (n = 22) | After 7 days group (n = 35) | P value | |
|---|---|---|---|---|
| The data are presented as number (%) or median (interquartile range). | ||||
| SCV, symptomatic cerebral vasospasm; WFNS, World Federation of Neurosurgical Societies; MFS, modified Fisher scale; aSAH, aneurysmal subarachnoid hemorrhage; N/A, not applicable | ||||
| Age, (years) n (%) | 0.785 | |||
| <65 | 26 (45.6) | 11 (50.0) | 15 (42.9) | |
| ≥65 | 31 (54.4) | 11 (50.0) | 20 (57.1) | |
| Sex, n (%) | 1 | |||
| Female | 42 (73.7) | 16 (72.7) | 26 (74.3) | |
| Male | 15 (26.3) | 6 (27.3) | 9 (25.7) | |
| Hypertension, n (%) | 0.381 | |||
| Yes | 18 (31.6) | 5 (22.7) | 13 (37.1) | |
| No | 39 (68.4) | 17 (77.3) | 22 (62.9) | |
| Diabetes mellitus, n (%) | 0.635 | |||
| Yes | 4 (7) | 2 (9.1) | 2 (5.7) | |
| No | 53 (93) | 20 (90.9) | 33 (94.3) | |
| WFNS grade, n (%) | 0.111 | |||
| 1–3 | 31 (54.4) | 15 (68.2) | 16 (45.7) | |
| 4–5 | 26 (45.6) | 7 (31.8) | 19 (54.3) | |
| MFS, n (%) | N/A | |||
| 1–2 | 0 (0) | 0 (0) | 0 (0) | |
| 3–4 | 57 (100) | 22 (100) | 35 (100) | |
| Aneurysm location, n (%) | 1 | |||
| Anterior circulation | 54 (94.7) | 21 (95.5) | 33 (94.3) | |
| Posterior circulation | 3 (5.3) | 1 (4.5) | 2 (5.7) | |
| Type of aneurysmal treatment, n (%) | 0.1 | |||
| Surgical | 32 (56.1) | 9 (40.9) | 23 (65.7) | |
| Endovascular | 25 (43.9) | 13 (59.1) | 12 (34.3) | |
| Days from aSAH onset to diagnosis of SCV, days | 9 (7, 9) | 8 (7.25, 9) | 9 (7, 12) | 0.262 |
Discussion
To the best of our knowledge, this is the first multicenter study to investigate the association between initiating mobilization and the incidence of SCV in patients with aSAH. After adjustment for variables, we found that initiating mobilization within 7 days was not significantly associated with the incidence of SCV. This finding may contribute to developing a strategy for promoting early mobilization in patients with aSAH.
In this study, the proportion of all included patients who had SCV was 11.1%, which is less than the proportions previously reported (20%–30%)8–10). Our study included patients with aSAH who underwent physical therapy with/without occupational therapy, therefore, we did not screen patients with aSAH who did not undergo physical therapy with/without occupational therapy, which explains the difference in the proportions of patients with SCV between this study and previous studies cited above. However, another study that investigated the effect of rehabilitation reported that the incidence of SCV was 14% in the early rehabilitation group and 29% in the controls19), which was similar to our results.
In a prospective interventional study, early mobilization did not increase SCV or worsen the frequency and severity of cerebral vasospasm19). In another study, mobilization with active exercise within 4 days reduced SCV in patients with aSAH28). This study found no association between initiating mobilization within 7 days after aSAH and SCV. This result was consistent with those of previous studies. Furthermore, we conducted sensitivity analysis to assess the robustness of our findings. The results of the three sensitivity analyses were similar to those of the primary analysis.
In patients with aSAH, cerebral autoregulation may be impaired, and mobilization may induce reduction of cerebral blood flow. In two previous studies, head-of-bed elevation (45°–90°) did not significantly affect cerebral blood flow24,29). Thick subarachnoid hematoma has been reported as a risk for SCV8,9,15,16). The head-shaking method with a subarachnoid hematoma draining effect has been reported to reduce SCV30). Since the head moves and the head position changes during mobilization, the effects of those head movements may be similar to the effect in the head-shaking method. In a laboratory study, mobilization with active exercise was not found to increase an injury marker (inducible nitric oxide synthase) in a rodent aSAH model28). Based on these mechanisms and evidence, our results suggest that initiating mobilization within 7 days after onset was not associated with SCV. In contrast, early mobilization initiated 2–5 days after onset was found to be the cause of cerebral vasospasm and delayed cerebral ischemia 20). This previous study compared the early mobilization group (mobilization initiated 2–5 days after onset) with the non-early mobilization group (mobilization initiated after 12 days after onset), whereas this study compared the early mobilization group (mobilization initiated within 7 days after onset) with the non-early group (mobilization initiated after 7 days after onset). In the non-early group in both studies, the date of initiating mobilization differs by 5 days. Additionally, the subjects of previous study were in a mild-to-moderate condition, whereas the subjects of this study were in a mild-to-sever condition. These may be the reasons for the difference between the results of both studies.
Previous studies that investigated the characteristics of patients with subarachnoid hemorrhage who can mobilize in the acute phase are limited. Our study showed that the proportion of mild-to-moderate condition was higher in the group with mobilization initiated within 7 days, which is consistent with previous studies22,31). The proportion of endovascular treatment was also higher in this group. Endovascular treatment was less invasive than surgical treatment, which may have facilitated mobilization. The proportion of MFS 3–4, a risk factor for SCV8,9,15,16), was higher in the group with mobilization initiated within 7 days. Nevertheless, SCV was not significantly increased in this group compared with the group with mobilization initiated after 7 days. This finding may support the main analysis of this study.
One of the strengths of our study is that it was conducted in multiple centers. The number of patients with aSAH was less than the number of those with cerebral infarctions or cerebral hemorrhages1). Because this was a multicenter study, it had the advantage of being able to investigate a larger patient sample. However, there were several study limitations that should be considered. First, this was a case-control study, which may have introduced selection bias. In this study, the neurosurgeons or physiatrists at the participating hospitals prescribed rehabilitation as needed; therefore, patients with asymptomatic or fatal conditions may not have been eligible for prescription. However, the patients in this study were those with a high need for rehabilitation, which was considered valid for this study. Second, this was a retrospective study, and although we could analyze the association between mobilization and SCV using multivariate analysis, we could not identify causal relationships as in a prospective study. Third, we controlled for measured confounding factors using multivariate Cox proportional hazards regression analysis. However, we were not able to control for unmeasured factors. Fourth, the influence of the race of the patients was not investigated. We only included Japanese patients. However, no evidence of an association between race and SCV was found in a previous review32). Fifth, the diagnosis of SCV was not unified as each hospital. At each facility, the diagnosis of SCV is made by neurosurgeons on the basis of the radiological examination and presence of delayed neurological worsening; therefore, it is considered reliable. However, in order to improve the accuracy of the diagnosis, it is necessary to unify the diagnostic criteria at each hospital in further studies. Sixth, although we investigated the impact of initiating mobilization on SCV, we could not collect detailed information about mobilization, such as the level, duration, frequency, and intensity of mobilization. In addition, we could not collect detailed information except for timing of initiating mobilization such as positioning, range of motion exercise, resistance exercise, and patient self-activity that may affect SCV. Furthermore, the decision to initiate mobilization was not made randomly, possibly leading to confounding by the indication used for each patient to initiate mobilization. Although mobilization was initiated as early as possible in each hospital, confounding was possible. Because of these limitations, the study results should be interpreted with caution because they lack information about the level, frequency, and duration of mobilization, which limits their generalizability. Thus, further study is needed to confirm the level, duration, frequency, and intensity of mobilization and their possible impact on SCV.
Conclusion
Our results showed that initiating mobilization within 7 days after aSAH onset was not associated with SCV. Although initiating mobilization may not increase SCV, further studies are needed to confirm the association between mobilization and SCV.
Acknowledgments
The authors thank Takahiro Shinya at Naha City Hospital; Yuki Ishikawa and Mayu Hamada at Saitama Medical Center; Kouji Kinjou and So Yamada at Yuuai Medical Center; and Yuto Nagakubo, Takuji Tsukada, and Madoka Hattori at Sapporo Shiroishi Memorial Hospital for their assistance in data retrieval. They also thank Naoki Tomiyama at Naha City Hospital, Junta Moroi at Akita Cerebrospinal and Cardiovascular Center, and So Yamada at Yuuai Medical Center for their technical advice.
Conflict of Interest
The authors declare no conflicts of interest.
References
- 1). Feigin VL, Lawes CMM, et al. : Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol. 2009; 8: 355–369. [DOI] [PubMed] [Google Scholar]
- 2). Connolly ES, Jr, Rabinstein AA, et al. : Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart association/American Stroke Association. Stroke. 2012; 43: 1711–1737. [DOI] [PubMed] [Google Scholar]
- 3). Macdonald RL, Schweizer TA: Spontaneous subarachnoid haemorrhage. Lancet. 2017; 389: 655–666. [DOI] [PubMed] [Google Scholar]
- 4). Committee for Guidelines for Management of Aneurysmal Subarachnoid Hemorrhage, Japanese Society on Surgery for Cerebral Stroke : Evidence-based guidelines for the management of aneurysmal subarachnoid hemorrhage. English Edition. Neurol Med Chir (Tokyo). 2012; 52: 355–429. [DOI] [PubMed] [Google Scholar]
- 5). Takemoto Y, Hasegawa Y, et al. : Predictors for functional outcome in patients with aneurysmal subarachnoid hemorrhage who completed in-hospital rehabilitation in a single institution. J Stroke Cerebrovasc Dis. 2019; 28: 1943–1950. [DOI] [PubMed] [Google Scholar]
- 6). Rosengart AJ, Schultheiss KE, et al. : Prognostic factors for outcome in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2007; 38: 2315–2321. [DOI] [PubMed] [Google Scholar]
- 7). Ozono I, Ikawa F, et al. : Risk factor for poor outcome in elderly patients with aneurysmal subarachnoid hemorrhage based on post hoc analysis of the modified WFNS scale study. World Neurosurg. 2020; 141: e466–e473. [DOI] [PubMed] [Google Scholar]
- 8). Mijiti M, Mijiti P, et al. : Incidence and predictors of angiographic vasospasm, symptomatic vasospasm and cerebral infarction in Chinese patients with aneurysmal subarachnoid hemorrhage. PLoS One. 2016; 11: e0168657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9). Charpentier C, Audibert G, et al. : Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage. Stroke. 1999; 30: 1402–1408. [DOI] [PubMed] [Google Scholar]
- 10). Banik S: The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial (Journal club). J Neuroanaesth Crit Care. 2014; 1: 221–222. [DOI] [PubMed] [Google Scholar]
- 11). Harders AG, Gilsbach JM: Time course of blood velocity changes related to vasospasm in the circle of Willis measured by transcranial Doppler ultrasound. J Neurosurg. 1987; 66: 718–728. [DOI] [PubMed] [Google Scholar]
- 12). Budohoski KP, Guilfoyle M, et al. : The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2014; 85: 1343–1353. [DOI] [PubMed] [Google Scholar]
- 13). Qureshi AI, Sung GY, et al. : Early identification of patients at risk for symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. Crit Care Med. 2000; 28: 984–990. [DOI] [PubMed] [Google Scholar]
- 14). Toi H, Matsumoto N, et al. : Prediction of cerebral vasospasm using early stage transcranial Doppler. Neurol Med Chir (Tokyo). 2013; 53: 396–402. [DOI] [PubMed] [Google Scholar]
- 15). Macdonald RL, Rosengart A, et al. : Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage. J Neurosurg. 2003; 99: 644–652. [DOI] [PubMed] [Google Scholar]
- 16). McGirt MJ, Blessing R, et al. : Risk of cerebral vasospasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience. J Neurosurg. 2006; 105: 671–674. [DOI] [PubMed] [Google Scholar]
- 17). Winstein CJ, Stein J, et al. : Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016; 47: e98–e169. [DOI] [PubMed] [Google Scholar]
- 18). Hebert D, Lindsay MP, et al. : Canadian stroke best practice recommendations: stroke rehabilitation practice guidelines, update 2015. Int J Stroke. 2016; 11: 459–484. [DOI] [PubMed] [Google Scholar]
- 19). Karic T, Røe C, et al. : Effect of early mobilization and rehabilitation on complications in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2017; 126: 518–526. [DOI] [PubMed] [Google Scholar]
- 20). Milovanovic A, Grujicic D, et al. : Efficacy of early rehabilitation after surgical repair of acute aneurysmal subarachnoid hemorrhage: outcomes after verticalization on days 2-5 versus day 12 post-bleeding. Turk Neurosurg. 2017; 27: 867–873. [DOI] [PubMed] [Google Scholar]
- 21). Olkowski BF, Shah SO: Early mobilization in the neuro-ICU: how far can we go? Neurocrit Care. 2017; 27: 141–150. [DOI] [PubMed] [Google Scholar]
- 22). Karic T, Sorteberg A, et al. : Early rehabilitation in patients with acute aneurysmal subarachnoid hemorrhage. Disabil Rehabil. 2015; 37: 1446–1454. [DOI] [PubMed] [Google Scholar]
- 23). Lidington D, Wan H, et al. : Cerebral autoregulation in subarachnoid hemorrhage. Front Neurol. 2021; 12: 688362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24). Blissitt PA, Mitchell PH, et al. : Cerebrovascular dynamics with head of bed elevation in patients with mild or moderate vasospasm after aneurysmal subarachnoid hemorrhage. Am J Crit Care. 2006; 15: 206–216. [PubMed] [Google Scholar]
- 25). Drake CG: Report of World Federation of Neurological Surgeons Committee on a Universal Subarachnoid Hemorrhage Grading Scale. J Neurosurg. 1988; 68: 985–986. [DOI] [PubMed] [Google Scholar]
- 26). Frontera JA, Claassen J, et al. : Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale. Neurosurgery. 2006; 59: 21–27. [DOI] [PubMed] [Google Scholar]
- 27). Dumont T, Rughani A, et al. : Diabetes mellitus increases risk of vasospasm following aneurysmal subarachnoid hemorrhage independent of glycemic control. Neurocrit Care. 2009; 11: 183–189. [DOI] [PubMed] [Google Scholar]
- 28). Riordan MA, Kyle M, et al. : Mild exercise reduces cerebral vasospasm after aneurysm subarachnoid hemorrhage: a retrospective clinical study and correlation with laboratory investigation. Acta Neurochir Suppl. 2015; 120: 55–61. [DOI] [PubMed] [Google Scholar]
- 29). Kung DK, Chalouhi N, et al. : Cerebral blood flow dynamics and head-of-bed changes in the setting of subarachnoid hemorrhage. BioMed Res Int. 2013; 2013: 640638. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30). Kawamoto S, Tsutsumi K, et al. : Effectiveness of the head- shaking method combined with cisternal irrigation with urokinase in preventing cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg. 2004; 100: 236–243. [DOI] [PubMed] [Google Scholar]
- 31). Okamura M, Konishi M, et al. : Impact of early mobilization on discharge disposition and functional status in patients with subarachnoid hemorrhage: a retrospective cohort study. Medicine (Baltimore). 2021; 100: e28171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32). Inagawa T: Risk factors for cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a review of the literature. World Neurosurg. 2016; 85: 56–76. [DOI] [PubMed] [Google Scholar]