Edited by: Magdy Selim, Harvard Medical School, United States
Reviewed by: Chuanyuan Tao, Sichuan University, China; Dale Ding, University of Louisville, United States
This article was submitted to Stroke, a section of the journal Frontiers in Neurology
†These authors have contributed equally to this work
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Spontaneous intracerebral hemorrhage (sICH) is the most common type of hemorrhagic stroke, accounting for 10–15% of all strokes (
Accumulated evidence has shown that large hematoma and low Glasgow Coma Scale (GCS) scores are strong predictors of high mortality and poor outcome in sICH (
The Surgical Trial in Intracerebral Hemorrhage (STICH) I and STICH II studies (
Recently, a slight decrease in mortality attributable to the surgical intervention was reported in the results of the Minimally Invasive Surgery Plus rt-PA for Intracerebral Hemorrhage Evacuation (MISTIE) phase III trial (
In the present study, the records of sICH inpatients in Tangdu hospital admitted between January 1, 2015, and June 30, 2018 were reviewed. Finally, a retrospective analysis of the 6-months clinical outcomes was conducted in patients with hemorrhage volume ≥ 40 ml and GCS score ≤ 8. The long-term effects of the opening craniotomy and minimally invasive techniques, including stereotactic aspiration and endoscopy, were evaluated.
The present study was designed to compare the 6-months mortality rate and modified Rankin Scale (mRS) score of spontaneous basal ganglia hematoma patients with an initial GCS score ≤ 8 who underwent treatment with one of the following three surgical approaches: stereotactic aspiration, endoscopic evacuation, and open craniotomy. This study was approved by the Biological and Medical Ethics Committee of Tangdu Hospital (No. TDLL-2014115) and performed in Tangdu Hospital strictly following the Declaration of Helsinki (2013). All participants or relatives gave their informed consents to participate in the present study. The medical records of all patients with sICH at Tangdu Hospital between January 1, 2015, and June 30, 2018, were reviewed retrospectively.
Patients were selected according to the following criteria.
Diagnosis of intracerebral hemorrhage in the primary basal ganglion region by computerized tomography (CT).
Hematoma volume ≥ 40 ml.
Initial GCS score ≤ 8.
18–80 years of age.
Treatment with stereotactic aspiration, endoscopic evacuation, or craniotomy.
Admission within 24 h of ictus.
Intracerebral hemorrhage caused by tumor, arteriovenous malformation, aneurysm, or coagulopathy.
Traumatic brain injury.
Multiple intracerebral hemorrhages.
Advanced dementia or disability before onset.
Concurrent serious illness that would interfere with the safety assessments, including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinological, immunological, or hematological disease.
Malignant disease or a life expectancy of fewer than 6 months due to comorbidities.
Concurrent serious infectious disease (human immunodeficiency virus, tuberculosis, etc.).
Concurrent coagulation disorders or the use of antiplatelet or anticoagulant drugs.
Pregnant or lactation.
Participation in another simultaneous trial of intracerebral hemorrhage treatment.
Refusal of follow-up.
All patients were admitted to and managed in the neurological intensive care unit (NICU) with best medical treatment and care according to the recommendations of the American Heart Association/American Stroke Association (AHA/ASA) (
In the clinical treatment process, surgery approaches were selected by the surgeons according to the location, volume, and progression of the hematoma, the doctors' experience, and the patient's general condition.
All surgeries were conducted by a well-trained surgical team. The surgical technique was determined according to the location, volume, and progression of the hematoma, the surgeons' experience, and the patient's general condition. The principles of minimally invasiveness were followed. The surgery procedures were based on the methods described in previous studies (
For the stereotactic aspiration group, a burr hole (1–1.5 cm diameter) was drilled and a soft catheter was inserted along the long axis into the hematoma cavity under general anesthesia. Clot aspiration was done with a 5 mL handheld syringe until the first resistance. Postoperative CT was done to confirm the positioning of the catheter and stability of the residual hematoma. Then, Urokinase was injected directly into the clot through the catheter, at 10,000–30,000 units in 2 mL followed by 3 mL flush every 12 h, for up to 3 days.
For the endoscopic evacuation group, skin incision and a 3–5 cm diameter bone flap were made under general anesthesia according to the position of the hematoma showed on CT scan. The dura mater was coagulated and incised in a cruciate fashion. After the puncturing cannula was positioned in the predetermined center of the hematoma, the cannula core was removed. Clot aspiration was done with a 5 mL handheld syringe to reduce intracranial pressure. Then, the transparent sheath was introduced along the puncturing cannula to the bottom of the hematoma. Irrigation and aspiration were repeated to evacuate the hematoma through the transparent sheath.
For the craniotomy group, a traditional craniotomy was performed. After opening the dura, the neurosurgeon accessed the hematoma cavity via a transcortical/transtemporal approach under microscopic assistance and evacuate the hematoma. Decompressive craniotomy and tracheotomy were conducted if the neurosurgeon considered necessary. All the patients received the best medical treatment after surgery. A postoperative CT scan was performed 24 h after surgery to evaluate the residual hematoma for every patient.
Basic information (sex, age, diagnosis, etc.) was obtained from the patient information management department of our hospital. Disease history (smoking, diabetes, hypertension, and craniocerebral disease) and treatment information (surgical technique, decompressive craniectomy, and tracheotomy) were collected from the inpatient medical record system of our hospital. The preoperative status of the patients was assessed by the preoperative GCS score, herniation, the time interval between onset and surgery and the hematoma volume, which were also obtained from the inpatient medical record system.
The hematoma volume was calculated from CT scans using the formula A*B*C/2, where A is the greatest diameter on the largest hemorrhage slice, B is the maximal diameter perpendicular to A, and C is the vertical hematoma depth.
The participants were followed by calling to record their prognostic information at 1, 3, and 6 months after surgery. The primary outcome was the 6-months mortality rate after surgery. The secondary outcome was the 6-months neurological functional status, which was evaluated by mRS score. The researchers, who collected the information, and the statistician, who conducted the statistical analysis were blinded to the treatments the subjects received.
Given the selection bias inherent to retrospective observational studies, the Chi-squared test was used to test the intergroup balance of the possible confounding factors (
The inter-group balance tests of possible confounding factors among different surgical techniques.
Gender | Male | 157 | 57 (36.3%) | 39 (24.8%) | 61 (38.9%) | 0.6365 | 75 | 18 (24.0%) | 29 (38.7%) | 28 (37.3%) | 0.6875 |
Female | 101 | 42 (41.6%) | 21 (20.8%) | 38 (37.6%) | 52 | 16 (30.8%) | 19 (36.5%) | 17 (32.7%) | |||
Age (years) | <60 | 140 | 44 (31.4%) | 39 (27.9%) | 57 (40.7%) | 82 | 21 (25.6%) | 34 (41.5%) | 27 (32.9%) | 0.5089 | |
≥60 | 118 | 55 (46.6%) | 21 (17.8%) | 42 (35.6%) | 45 | 13 (28.9%) | 14 (31.1%) | 18 (40.0%) | |||
Smoking | Yes | 74 | 21 (28.4%) | 22 (29.7%) | 31 (41.9%) | 40 | 7 (17.5%) | 17 (42.5%) | 16 (40.0%) | 0.2780 | |
No | 184 | 78 (42.4%) | 38 (20.7%) | 68 (37.0%) | 87 | 27 (31.0%) | 31 (35.6%) | 29 (33.3%) | |||
Diabetes | Yes | 19 | 9 (47.4%) | 5 (26.3%) | 5 (26.3%) | 0.5241 | 7 | 2 (28.6%) | 1 (14.3%) | 4 (57.1%) | 0.3539 |
No | 239 | 90 (37.7%) | 55 (23.0%) | 94 (39.3%) | 120 | 32 (26.7%) | 47 (39.2%) | 41 (34.2%) | |||
Hypertension | Yes | 215 | 85 (39.5%) | 51 (23.7%) | 79 (36.7%) | 0.4806 | 107 | 29 (27.1%) | 40 (37.4%) | 38 (35.5%) | 0.9706 |
No | 43 | 14 (32.6%) | 9 (20.9%) | 20 (46.5%) | 20 | 5 (25.0%) | 8 (40.0%) | 7 (35.0%) | |||
History of craniocerebral disease | Yes | 28 | 13 (46.4%) | 5 (17.9%) | 10 (35.7%) | 0.6118 | 9 | 4 (44.4%) | 3 (33.3%) | 2 (22.2%) | 0.4364 |
No | 230 | 86 (37.4%) | 55 (23.9%) | 89 (38.7%) | 118 | 30 (25.4%) | 45 (38.1%) | 43 (36.4%) | |||
Herniation | Yes | 84 | 18 (21.4%) | 10 (11.9%) | 56 (66.7%) | 31 | 2 (6.5%) | 6 (19.4%) | 23 (74.2%) | ||
No | 174 | 81 (46.6%) | 50 (28.7%) | 43 (24.7%) | 96 | 32 (33.3%) | 42 (43.8%) | 22 (22.9%) | |||
Interval between onset and operation (hours) | ≤8 | 88 | 34 (38.6%) | 12 (13.6%) | 42 (47.7%) | 34 | 9 (26.5%) | 9 (26.5%) | 16 (47.1%) | 0.1875 | |
>8 | 170 | 65 (38.2%) | 48 (28.2%) | 57 (33.5%) | 93 | 25 (26.9%) | 39 (41.9%) | 29 (31.2%) | |||
Hematoma volume (ml) | 40–80 | 151 | 68 (45.0%) | 40 (26.5%) | 43 (28.5%) | 80 | 28 (35.0%) | 31 (38.8%) | 21 (26.3%) | ||
≥80 | 107 | 31 (29.0%) | 20 (18.7%) | 56 (52.3%) | 47 | 6 (12.8%) | 17 (36.2%) | 24 (51.1%) | |||
Rehabilitation treatment | PRT | 76 | 22 (28.9%) | 24 (31.6%) | 30 (39.5%) | 0.3953 | 70 | 19 (27.1%) | 24 (34.3%) | 27 (38.6%) | 0.7390 |
NPRE | 46 | 14 (30.4%) | 19 (41.3%) | 13 (28.3%) | 43 | 12 (27.9%) | 19 (44.2%) | 12 (27.9%) | |||
NRT | 26 | 4 (15.4%) | 10 (38.5%) | 12 (46.2%) | 14 | 3 (21.4%) | 5 (35.7%) | 6 (42.9%) | |||
Decompressive craniectomy | Yes | 100 | 6 (6.0%) | 11 (11.0%) | 83 (83.0%) | 48 | 2 (4.2%) | 9 (18.8%) | 37 (77.1%) | ||
No | 158 | 93 (58.9%) | 49 (31.0%) | 16 (10.1%) | 79 | 32 (40.5%) | 39 (49.4%) | 8 (10.1%) | |||
Tracheotomy | Yes | 72 | 21 (29.2%) | 20 (27.8%) | 31 (43.1%) | 0.1609 | 47 | 10 (21.3%) | 17 (36.2%) | 20 (42.6%) | 0.3751 |
No | 186 | 78 (41.9%) | 40 (21.5%) | 68 (36.6%) | 80 | 24 (30.0%) | 31 (38.8%) | 25 (31.3%) |
The result of the univariate analyses to explore the independent risk factors associated with mortality and low mRS score.
Surgical methods | SA | 99 | 65 (65.7%) | 34 (34.3%) | 34 | 24 (70.6%) | 10 (29.4%) | ||
EE | 60 | 12 (20.0%) | 48 (80.0%) | 48 | 24 (50.0%) | 24 (50.0%) | |||
OC | 99 | 54 (54.5%) | 45 (45.5%) | 45 | 19 (42.2%) | 26 (57.8%) | |||
Age (years) | <60 | 140 | 58 (41.4%) | 82 (58.6%) | – | – | – | ||
≥60 | 118 | 73 (61.9%) | 45 (38.1%) | – | – | – | |||
Smoking | Yes | 74 | 34 (45.9%) | 40 (54.1%) | 0.3251 | – | – | – | |
No | 184 | 97 (52.7%) | 87 (47.3%) | – | – | – | |||
Herniation | Yes | 84 | 53 (63.1%) | 31 (36.9%) | 31 | 11 (35.5%) | 20 (64.5%) | ||
No | 174 | 78 (44.8%) | 96 (55.2%) | 96 | 56 (58.3%) | 40 (41.7%) | |||
Interval between onset and operation (hours) | ≤8 | 88 | 54 (61.4%) | 34 (38.6%) | – | – | – | ||
>8 | 170 | 77 (45.3%) | 93 (54.7%) | – | – | – | |||
Hematoma Volume (ml) | 40–80 | 151 | 71 (47.0%) | 80 (53.0%) | 0.1518 | 80 | 49 (61.3%) | 31 (38.8%) | |
≥80 | 107 | 60 (56.1%) | 47 (43.9%) | 47 | 18 (38.3%) | 29 (61.7%) | |||
Decompressive craniectomy | Yes | 100 | 52 (52.0%) | 48 (48.0%) | 0.7542 | 48 | 20 (41.7%) | 28 (58.3%) | |
No | 158 | 79 (50.0%) | 79 (50.0%) | 79 | 47 (59.5%) | 32 (40.5%) |
The result of the multivariate logistic regression model to explore the independent risk factors associated with mortality or low mRS score.
Surgical methods (reference is EE) | SA | 6.858 | (3.146, 14.953) | 0.501 | (0.192, 1.308) |
OC | 3.315 | (1.497, 7.341) | 0.774 | (0.257, 2.335) | |
Age (year) (reference is <60) | ≥60 | 2.237 | (1.290, 3.877) | – | – |
Herniation (reference is no) | Yes | 2.257 | (1.172, 4.348) | 1.724 | (0.648, 4.608) |
Interval between onset and operation (hours) (reference is >8) | ≤8 | 1.421 | (0.785, 2.572) | – | – |
Hematoma volume (ml) (reference is 40–80) | ≥80 | – | – | 2.044 | (0.930, 4.495) |
Decompressive craniectomy (reference is no) | Yes | – | – | 0.682 | (0.243, 1.912) |
The mRS score was dichotomized as a poor outcome (mRS score = 3–5) and a favorable outcome (mRS score = 0–2). The Chi-squared test was used to analyze the categorical variables. The hospital stay was expressed as Mean ± SEM. The unpaired
A total of 1,573 consecutive sICH patients admitted between January 1, 2015, and June 30, 2018 were reviewed retrospectively. Finally, 258 patients with volume ≥ 40 ml and GCS score ≤ 8 were enrolled according to the inclusion and exclusion criteria. The patient numbers at each stage of study were shown in a flow diagram (
Enrollment in this study. A total of 1,573 consecutive sICH patients were reviewed. A total of 258 patients, including 131 non-survivors and 127 survivors, were enrolled according to the selection criteria.
Information about gender, age, smoking, diabetes, hypertension, history of craniocerebral disease, herniation, interval between onset and operation, hematoma volume, rehabilitative treatment, decompressive craniectomy, and tracheotomy was collected (
Intergroup equilibrium analysis was conducted to identify the potential confounding factors. Age (
In the stereotactic aspiration group, six patients received decompressive craniectomy. All of them were performed after the initial surgery when deterioration happened. In the endoscopic evacuation group, a total of 11 patients received decompressive craniectomy. 72.7% (8/11) of them were performed in the initial surgery, and 27.3% (3/11) of them were performed after the initial surgery when deterioration happened. In the open craniotomy group, a total of 83 patients received decompressive craniectomy. 92.8% (77/83) of them were performed in the initial surgery, and 7.2% (6/83) of them were performed after the initial surgery when deterioration happened.
In the entire cohort, the overall 6-months mortality rate was 50.8% (131/258 patients). In the surviving patients, the rate of poor 6-months neurological functional outcome was 81.9% (104/127 patients). The 6-months mortality rate in the stereotactic aspiration, endoscopic evacuation, and craniotomy groups was 65.7% (65/99 patients), 20.0% (12/60 patients), and 54.5% (54/99 patients) respectively. The 6-months poor neurological functional outcome rate in survivors in the stereotactic aspiration, endoscopic evacuation, and craniotomy groups was 67.6% (23/34 patients), 87.5% (42/48 patients), and 86.7% (39/45 patients), respectively. The 6-months mortality rate and 6-months mRS scores of patients with an initial GCS score of 3–5 or 6–8 are also calculated. The mRS score distribution is shown in
Functional outcome of patients in each group. The functional outcome was assessed by the mRS score. The scores ranged from 0 to 6, with 0 indicating no symptoms; 1, no clinically significant disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; 5, severe disability; and 6, death. A score of 3–5 was recognized as a poor outcome. The percentages of patients by score are shown in each cell.
The unbalanced characteristics were included in the univariate analysis to investigate whether they were relevant to the mortality rate or mRS score (
Multivariate analysis showed that the mortality rate was significantly higher in the stereotactic aspiration group (OR 6.858, 95% CI 3.146–14.953) and the open craniotomy group (OR 3.315, 95% CI 1.497–7.341) than in the endoscopic evacuation group. Age (OR 2.237, 95% CI 1.290–3.877) and herniation (OR 2.257, 95% CI 1.172–4.348) were independent predictors for mortality (
The neurological functional status in the stereotactic aspiration group (OR 0.501, 95% CI 0.192–1.308) and the craniotomy group (OR 0.774, 95% CI 0.257–2.335) was not significantly different from that in the endoscopic evacuation group. However, the patients with a hematoma volume of ≥ 80 ml had a trend of higher mRS scores (HR 2.044, 95% CI 0.930–4.495) than the patients with a hematoma volume = 40–80 ml. Herniation (HR 1.724, 95% CI 0.648–4.608), and Decompressive Craniectomy (HR 0.682, 95% CI 0.243–1.912) showed no independent association with functional recovery (
In the survivors, the average length of a hospital stay is 11.18 ± 1.167, 12.52 ± 0.80, and 15.45 ± 0.81 days in the stereotactic aspiration, endoscopic evacuation, and craniotomy group, respectively. The stereotactic aspiration group (
The difference in reoperation rate among these three groups had no statistical significance. In the entire cohort, 18 (7.0%) patients required reoperation, which included 7 (7.1%) in the stereotactic aspiration group, 4 (6.7%) in the endoscopic evacuation group, and 7 (7.1%) in the craniotomy group.
Stroke is the second most common cause of death worldwide (
The treatment of patients with sICH remains controversial. Conservative management and surgical evacuation are the main treatment choices for sICH. The surgical evacuation is an effective way to reduce the hematoma volume, and the stereotactic aspiration, endoscopic evacuation, and craniotomy are the most techniques used in such conditions. Multiple clinical trials comparing surgical to conservative management have failed to demonstrate a clear clinical benefit of hemorrhage evacuation (
Recently, the results of the MISTIE III trial were published. The primary results of MISTIE III showed that the proportion of patients with a good functional outcome was not significantly higher in the surgical treatment group (44.2%) than in the medical treatment group (41.7%) (
It is believed that different treatment strategies might be suitable for different groups of patients with particular characteristics (such as GCS score, hematoma volume, and lesion location). However, subgroup analysis is inadequate till now, which might lead to an underestimate of the impact of confounding factors (
Recently, with the development of less invasive surgical techniques, minimally invasive approaches, including the endoscopic evacuation and stereotactic aspiration, had shown several advantages over the traditional open craniotomy (
In our series, the overall 6-months mortality rate for the patients with a hematoma volume of ≥40 ml and GCS score ≤ 8 was 50.78%. More importantly, the 6-months mortality rate in the endoscopic evacuation group was 20.00%, which was significantly lower than that in the stereotactic aspiration and craniotomy groups.
The result of the present study showed that herniation occurred in 32.6% (84/258) patients with the hematoma volume ≥40 ml and GCS score ≤ 8. Meanwhile, herniation has been demonstrated to be one of the most critical independent indicators of high mortality in the present study. Thus, early surgical intervention is recommended for these patients to avoid herniation and reduce mortality.
Sufficient evidence has demonstrated that decompressive craniectomy plus external ventricular drainage is suitable for patients with large hematomas and low GCS scores with a significant midline shift (
Brain injury caused by ICH can be described as a biphasic process. Primary brain injury causes direct traumatic damage to regional neurons (
Hematoma removal surgery is speculated to be an appropriate ICH treatment option because it can alleviate the mass-effect of the hematoma and reduce neurotoxic blood degradation products. Thus, these surgeries can lower intracranial pressure, improve perfusion, alleviates brain edema, and attenuate neuronal damage. However, the surgical procedure brings new damage to the patient meanwhile. The net benefits brought by surgery removal for spontaneous ICH patients remains controversial. In the present study, the net benefit of endoscopic surgery is more than the open craniotomy and stereotactic aspiration in the basal ganglia hemorrhage patients with GCS score ≤ 8 and hemorrhage volume ≥ 40 ml. The present results indicate that endoscopic evacuation could effectively alleviate secondary brain injury, resulting in a decreased mortality rate. However, as indicated by our data, no significant difference in the neurological outcome of the survivors was detected among these three groups. This result suggests that primary brain injury, which is caused by direct damage to regional neurons, may not be mitigated by current surgical approaches.
Currently, the hematoma removal surgeries include open craniotomy surgery and minimally invasive surgery. Open craniotomy is the most studied approach in this clinical scenario. However, due to the deep location of basal ganglia, open craniotomy might cause iatrogenic damage to the healthy cerebral tissue (
Comparing with stereotactic aspiration, the endoscopic evacuation surgery provides the surgeon with a good visible operation field and more operating space, which makes it possible to deal with the hematoma and surrounding tissues delicately. The hematoma can be removed rapidly and thoroughly with less surgical trauma by endoscopic evacuation. Besides, the endoscopic evacuation surgery can remove the blood accumulation in the third ventricle, fourth ventricle, and lateral ventricles in some situations. Therefore, the secondary injury caused by mass effect and neurotoxic blood degradation products might be alleviated more effectively by endoscopic evacuation (
Of course, there are several limitations to the present study. First, because of its retrospective nature, the possibility of selection bias cannot be excluded. Second, potential methodological limitations might influence the results of the present study. Third, the present results are derived from a single center and have limited generalizability. Further prospective randomized trials are needed to confirm the findings of this study.
Endoscopic evacuation significantly decreases the 6-months mortality rate of patients with GCS score ≤ 8 and basal ganglia ICH volume ≥ 40 ml. Besides, the low mortality rate is more likely to be achieved in patients who were under 60 years of age and without herniation. Thus, early surgical intervention is recommended for these patients to avoid herniation. These results would be helpful for neurosurgeons to decrease the mortality of sICH. However, the 6-months neurological outcome showed no difference between different surgical methods. The optimal surgical technique, intervention timing, and patient selection might allow appropriate patients to benefit from hematoma evacuation. These preliminary results warranted a further large, prospective, randomized study.
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
The studies involving human participants were reviewed and approved by Biological and Medical Ethics Committee of Tangdu Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
YQ and WG conceived and supported this research. HL and XW designed, conducted the present study, and drafted the manuscript. YQ, HG, and HB revised the manuscript. ZT and BW conducted the statistic analyze and interpreted the data. HL, WC, LZ, FS, and XZ collected the primary data. RF, PW, WJ, and JG completed the follow-up and collected the associated data. All authors of this work met ICMJE criteria for authorship, made substantial contributions to the conception and design, acquisition of data, analysis and interpretation of data, drafting, critical revising, and final approval of this manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.