Abstract
Purpose
Surgical outcomes are typically poor for patients with spontaneous large intracerebral hemorrhage (ICH) complicated by intraventricular hemorrhage (IVH). The optimal treatment strategy remained undetermined —either external ventricular drainage (EVD) alone or in combination with craniotomy. Here, we evaluated shunt-related complications of such patients treated primarily with EVD combined with intraventricular thrombolysis, aiming to provide evidence that may lead to future treatment guidelines.
Materials and Methods
From January 2010 to December 2021, a total of 114 patients with spontaneous large ICH (> 30 mL) extending into the ventricular system treated only primarily with EVD and intraventricular thrombolysis were retrospectively enrolled. Hematoma and ventricular volumes were assessed based on imaging data. Cerebrospinal fluid (CSF) parameters—including biochemistry and cell counts—were analyzed in relation to permanent shunt dependency and one-year mortality.
Results
The mean age of the patients was 67.6 ± 11 years, with a male-to-female ratio of 1.7:1. Their mean best Glasgow Coma Scale (GCS) motor score was 3.7 ± 1.9. Mean ICH/IVH volume was 70.9 ± 47 mL. Average daily CSF drainage was 104 ± 52.2 mL, with a mean drainage duration of 16.5 ± 9.4 days. The average number of EVD replacements was 1.9 ± 0.8. WBC/RBC counts(/mm3) in CSF were 110.4 ± 250.3/28997.8 ± 104,400.2 at the first EVD procedure and 5.4 ± 9.0/532 ± 761.9 at the last procedure. Multivariate analysis identified the narrower width of the temporal horn (p < 0.01) and CSF lymphocyte count at the initial EVD procedure (p < 0.05) as independent risk factors for needing a permanent shunt. One-year mortality was significantly associated with pupil size (p < 0.01), daily CSF drainage volume (p < 0.05), and presence of periventricular lucency (p < 0.05). The primary predictor of central nervous system (CNS) infection was CSF WBC count at the final EVD procedure (p < 0.05).
Conclusion
The prolonged and repeated use of external ventricular drainage (EVD) in patients with large intracerebral hemorrhage (ICH) complicated by intraventricular hemorrhage (IVH) appears to be a practical and recognizable treatment approach. Early identification of imaging and CSF markers would likely help optimize management strategy for this high-risk population.
Graphical Abstract
Keywords: Intracerebral haemorrhage, Intraventricular haemorrhage, External ventricular drainage, Ventricular-peritoneal shunt, Intraventricular thrombolysis, Central nervous system infection, Mortality
Introduction
Spontaneous intracerebral hemorrhage (ICH) is defined as non-traumatic bleeding within the brain parenchyma. Its annual prevalence is estimated at approximately 25 cases per 100,000 individuals [1, 2]. The occurrence of intraventricular hemorrhage (IVH) in ICH patients significantly worsens prognosis, being strongly associated with a higher mortality rate and poorer neurological recovery [3]. However, it remains unclear regarding the optimal management of patients with large ICH complicated by IVH, specifically -either external ventricular drainage (EVD) alone or EVD combined with craniotomy [4, 5].
Intraventricular extension of ICH occurs in 30–50% of cases and leads to hydrocephalus in nearly half of the cases [6]. The presence of IVH predicts worse outcomes, not only because of the clot burden but also due to blood breakdown products, which trigger inflammatory meningitis and obstructive hydrocephalus [7]. Placement of an EVD serves as a critical intervention to relieve intracranial hypertension and facilitate clearance of intraventricular blood, thereby improving survival [8–10]. In patients with moderate-to-large IVH, EVD alone has been associated with better survival compared with conservative management [8, 9]. Thus, in patients with limited ICH and IVH, EVD is generally regarded as an important measure to reduce mortality.
By contrast, the benefit of EVD in patients with severe spontaneous ICH, massive IVH, and depressed consciousness is less well established [8–10]. One large registry analysis of 2,486 ICH patients reported that EVD placement reduced 90-day mortality [5]. Conversely, a retrospective study comparing surgical and non-surgical interventions found no significant survival difference, although the surgical cohort included a higher proportion of patients with large hematomas (≥ 30 mL) and IVH. In that study, advanced age, low Glasgow Coma Scale (GCS) score, and the presence of IVH were independent predictors of mortality, suggesting that the survival benefit of surgery may be limited in patients with severe ICH and poor baseline neurological status [4].
Given these observations, we sought to evaluate long-term outcomes in patients with large ICH (> 30 mL) and IVH managed primarily with EVD combined with intraventricular thrombolysis. In such patients, prolonged EVD placement is frequently required due to the slow resolution of large hematoma. Specifically, we investigated the rates of permanent ventriculoperitoneal (VP) shunt placement, shunt revision, CNS infection, and one-year mortality. In this study, we aimed to clarify the long-term effectiveness and safety of EVD-based strategies in this high-risk patient population.
Materials and methods
Patient population
This retrospective cohort study covered a period from January 2010 and December 2021, with the patients treated at Taichung Veterans General Hospital, Taiwan. These patients were diagnosed with spontaneous intracerebral hemorrhage (ICH) > 30 mL including intraventricular extension (IVH). Our study was approved by the Ethical Committee of Taichung Veterans General Hospital (No. CE25398A).
Patient data were first collected from a hospital-based database. We reviewed electronic medical records using a standardized evaluation protocol. Upon presentation to the emergency department, patients with acute neurological deterioration or focal neurological deficits underwent immediate cranial computed tomography (CT) imaging. The diagnosis of acute spontaneous ICH and IVH was established based on clinical presentation and radiological findings on cranial CT.
We included those patients with spontaneous large-volume ICH > 30 mL accompanied by IVH. We excluded patients with traumatic ICH or other secondary causes of hemorrhage (e.g., aneurysms, arteriovenous malformations, hemorrhagic tumors).
During the study period, a total of 188 patients met the criteria for spontaneous large-volume intracerebral hemorrhage (ICH > 30 mL) accompanied by intraventricular hemorrhage (IVH). Among them, 41 patients underwent craniectomy and were therefore excluded. Consequently, only patients who did not receive craniotomy or craniectomy were included in the present analysis.
We also excluded those patients with initial poor conditions, like GCS of E1V1M1, and full bilateral pupil dilation.
Clinical and data assessment
The data that we collected were baseline demographics, clinical and laboratory parameters, imaging findings, and treatment-related outcomes. Imaging parameters included ICH/IVH volume, Evans index, presence of periventricular lucency, and volumes and the largest width of the temporal and frontal horns. We also recorded CSF analytical results obtained at the first external ventricular drainage procedure and the time point of the last EVD removal. If the interval of EVD drainage had exceeded 7 or 8 days with the follow up CT still revealing persistent IVH, the EVD was changed. Upon the insertion of EVD, urokinase application through the EVD at 6000U q8h was performed the next day, and for three consecutive days thereafter. In general, 6000 U urokinase was slowly injected into to the ventricle via EVD tube for 5 min, then the EVD was closed for one hour and then reopened. ICH/ICH volumes were assessed by the surface area times slice thickness calculated using the PACS system. The volume is equal to the product of the surface area of each slice and the slice thickness [6].
Our primary objective was to assess outcomes related to initial EVD placement, specifically the association with CNS infection, shunt dependency, and mortality. Our secondary objective was to determine the correlations between clinical/imaging variables and adverse outcomes, including CNS infection, requirement for ventriculoperitoneal (VP) shunting, shunt revision, and 1-year mortality.
Statistical analyses
Descriptive statistics were analyzed according to standard representation, like mean ± standard deviation or median value and range. Statistical methods included both univariate and multivariate analyses. While univariate analysis was used for preliminary exploration of associations, multivariate logistic regression was performed to identify independent predictors of adverse outcomes. A two-tailed p value of < 0.05 was considered statistically significant.
Result
Patient demography
We initially identified 147 patients with spontaneous large-volume intracerebral hemorrhage (ICH > 30 mL) accompanied by intraventricular hemorrhage (IVH) and who did not undergo craniotomy or craniectomy. Among these patients, 21 were excluded because they presented with bilateral fixed pupil dilation and a Glasgow Coma Scale (GCS) score of E1V1M1, indicating extremely poor neurological status. The locations of hemorrhage in these cases included the cerebellar vermis (n = 2), thalamus or basal ganglia (BG) (n = 9), and pons (n = 10). An additional 12 patients were excluded due to incomplete biochemical data in CSF. The final analysis therefore included a total of 114 patients.
Their median age was 70 years (interquartile range: 60–76 years). Males comprised 63.2% (n = 72), and females 36.8% (n = 42). At admission, their median systolic and was 176 mmHg (143–216) and diastolic blood pressures was 95 mmHg (84–117), respectively. The mean initial GCS score was 8.1 ± 4.2, and the mean best motor scores was 3.7 ± 1.9. Asymmetric pupils were observed in 21.1% of patients, while 63.2% showed a positive light reflex.
Among the 114 patients, 40 had lobar hemorrhage, 56 had thalamic or basal ganglia hemorrhage (BG), and 18 had cerebellar hemorrhage. The laterality distribution included 55 cases in the right hemisphere and 59 in the left. The mean hematoma volume (ICH/IVH) was 70.9 ± 47 mL. Volumetric analyses included Evans index, presence of periventricular lucency, width of the largest temporal horn, volume of the temporal horn, and total volume of the bilateral frontal horns (Table 1). On the average, patients underwent 1.9 ± 0.8 external ventricular drainage (EVD) procedures. Complications included urinary tract infection (UTI) in 24 cases (21.1%) and pneumonia in 62 cases (54.4%) (Table 1).
Table 1.
Demography of the patients (n = 114)
| Parameter | Mean ± SD | Median(range) | |
|---|---|---|---|
| Age | 67.6 ± 11.0 | 70 (60–76) | |
| M/F | 72/42 | N/A | |
| HR (/min) | 84.4 ± 19.4 | 82 (72–97) | |
| SBP (mmHg) | 180.6 ± 42.5 | 176 (143–216) | |
| DBP (mmHg) | 100.9 ± 24.4 | 95 (84–117) | |
| GCS scores | 8.1 ± 4.2 | 7 (4–10) | |
| Best GCS motor scores | 3.7 ± 1.9 | 4 (2–5) | |
| Asymmetric pupil size, n (%) | 24 (21.1%) | N/A | |
| The largest pupil size (mm) | 2.8 ± 1.0 | 3 (2–4) | |
| Positive Light reflex, n (%) | 72 (63.2%) | N/A | |
| Focal motor weakness, n (%) | 62 (54.4%) | N/A | |
| ICH Location | Lobe | 40 (35.1%) | N/A |
| Thalamus/BG | 56 (49.1%) | ||
| Cerebellum | 18 (15.8%) | ||
| Hemisphere | Right | 55 (48.2%) | N/A |
| Left | 59 (51.8%) | ||
| Volume of ICH/IVH (ml) | 70.9 ± 47.0 | 99.5 (70–126.8) | |
| Evan index (ratio) | 0.3 ± 0.1 | 0.3 (0.2–0.36) | |
| Width of largest temporal horn (mm) | 10.5 ± 6.6 | 9.3 (5.1–14) | |
| Temporal horn volume (ml) | 4.5 ± 4.6 | 2.8 (1.3–7.7) | |
| Total volume of bilateral frontal horn (ml) | 5.0 ± 4.6 | 3.2 (1.4–8.5) | |
| Periventricular lucency, n (%) | 26 (22.8%) | N/A | |
| Times in EVD procedure | 1.9 ± 0.8 | 2 (1–2) | |
| UTI, n (%) | 24 (21.1%) | N/A | |
| Pneumonia, n (%) | 62 (54.4%) | N/A | |
CSF biochemistry and drainage data
Their mean duration of CSF drainage was 16.5 ± 9.4 days, with a total drainage volume of 1691.7 ± 1222.5 mL, corresponding to a daily average of 104.0 ± 52.2 mL.
Cell counts At initial EVD, the counts of CSF white blood cells (WBC) was 110.4 ± 250.3/mm3, declining to 5.4 ± 9.0/mm3 at the last procedure. The corresponding red blood cell (RBC) counts were 28,997.8 ± 104,400.2/mm3 initially and 532.0 ± 761.9/mm3 at the last procedure. Initial neutrophil and lymphocyte counts were 21.8 ± 30.1 and 6.7 ± 8.9/mm3, respectively; data at the last procedure were not available due to small values.
Protein and glucose CSF protein decreased from 99.9 ± 86.0 mg/dL at initial EVD to 70.4 ± 44.9 mg/dL at the last procedure. CSF glucose levels decreased from 181.6 ± 52.2 mg/dL initially to 96.8 ± 21.5 mg/dL at the last procedure.
Systemic data Data on general serum markers, including C-reactive protein (CRP), albumin, and hematological parameters, are summarized in Table 2.
Table 2.
Laboratory data analysis
| Parameters | Mean ± SD | Median (Range) |
|---|---|---|
| Interval of CSF drainage (days) | 16.5 ± 9.4 | 15.0(9–23) |
| Volume of CSF/day (ml/day) | 104.0 ± 52.2 | 99.5(70–126.8) |
| Total volume of CSF (ml) | 1691.7 ± 1222.5 | 1709.0(526–2421) |
| WBC in CSF at EVD (/mm3) | 110.4 ± 250.3 | 18.0(5.8–87.3) |
| WBC in CSF at last procedure (/mm3) | 5.4 ± 9.0 | 2.0(1–5) |
| RBC in CSF at EVD (/mm3) | 28,997.8 ± 104,400.2 | 2740.0(1050–14887.5) |
| RBC in CSF at last procedure (/mm3) | 532.0 ± 761.9 | 203.0 (25–998.5) |
| Neutrophil in CSF at EVD (/mm3) | 21.8 ± 30.1 | 5.0(1–35.5) |
| Lymphocyte in CSF at EVD (/mm3) | 6.7 ± 8.9 | 2.0(1–11) |
| CSF protein at EVD (mg/dl) | 99.9 ± 86.0 | 75.0(49.8–112.8) |
| CSF protein at last procedure (mg/dl) | 70.4 ± 44.9 | 66.0(44–90) |
| CSF sugar at EVD (mg/dl) | 181.6 ± 52.2 | 186.0(137.8–216.8) |
| CSF sugar at last procedure (mg/dl) | 96.8 ± 21.5 | 90.0(87.8–101) |
| CRP at EVD (mg/dl) | 4.3 ± 6.1 | 2.1(0.7–6.6) |
| Albumin at EVD (mg/dl) | 3.3 ± 0.6 | 3.2(2.9–3.5) |
| Blood WBC (/mm3) | 12,709.8 ± 4691.3 | 11,820.0(9645–16,025) |
| Blood neutrophil (%) | 77.5 ± 14.6 | 82.9(73–89) |
| Blood lymphocyte (%) | 15.9 ± 12.4 | 12.0(6.5–19.6) |
Risk factor of CNS infection
Six patients developed shunt-associated infections during hospitalization. Three had positive CSF cultures (Staphylococcus spp., Escherichia coli, and MRSA). The remaining three were diagnosed by infectious disease specialists based on fever, neurological deterioration, and elevated CSF WBC counts with biochemical changes.
CSF findings At the last EVD, the mean CSF WBC count in the infection group was significantly higher (20.3 ± 26.5/mm3) compared with the non-infection group (4.5 ± 6.2/mm3, p < 0.05). Initial neutrophil counts were also elevated in the infection group (39.7 ± 45.8/mm3 vs. 20.8 ± 29.0/mm3, p < 0.05).
Protein levels CSF protein levels at both initial and final procedures were significantly higher in the infection group (p < 0.05).
EVD frequency The number of EVD procedures was not significantly different between the two groups (Table 3).
Table 3.
Risk factors for CNS infection
| No (n = 108) | Yes (n = 6) | p value | ||||
|---|---|---|---|---|---|---|
| Mean | ± SD | Mean | ± SD | |||
| ICH location | Lobe | 37(34.3%) | 3(50.0%) | 0.747 | ||
| Thalamus/GB | 54(50.0%) | 2(33.3%) | ||||
| Cerebellum | 17(15.7%) | 1(16.7%) | ||||
| WBC in CSF at EVD (/mm3) | 104.1 | ± 246.3 | 223.5 | ± 318.0 | 0.159 | |
| WBC in CSF at last procedure (/mm3) | 4.5 | ± 6.2 | 20.3 | ± 26.5 | 0.037 | |
| RBC in CSF at EVD (/mm3) | 30,409.0 | ± 107,107.2 | 3596.7 | ± 3069.7 | 0.594 | |
| RBC in CSF at last procedure (/mm3) | 534.8 | ± 778.1 | 481.5 | ± 398.0 | 0.251 | |
| Neutrophil in CSF at EVD (/mm3) | 20.8 | ± 29.0 | 39.7 | ± 45.8 | 0.039 | |
| Lymphocyte in CSF at EVD (/mm3) | 6.7 | ± 9.0 | 7.7 | ± 7.6 | 0.203 | |
| CSF protein at EVD (mg/dl) | 94.7 | ± 82.1 | 192.8 | ± 110.2 | 0.031 | |
| CSF protein at last procedure (mg/dl) | 64.7 | ± 30.1 | 174.2 | ± 112.3 | 0.016 | |
| CSF sugar at EVD (mg/dl) | 180.3 | ± 53.3 | 204.3 | ± 17.9 | 0.168 | |
| CSF sugar at last procedure (mg/dl) | 96.7 | ± 22.1 | 99.2 | ± 5.2 | 0.130 | |
| CRP at EVD (mg/dl) | 4.5 | ± 6.2 | 1.1 | ± 1.0 | 0.077 | |
| Albumin at EVD (mg/dl) | 3.2 | ± 0.6 | 3.6 | ± 0.2 | 0.016 | |
| Blood WBC (/mm3) | 12,915.1 | ± 4723.2 | 9015.0 | ± 1643.3 | 0.021 | |
| Blood neutrophil (%) | 78.0 | ± 14.5 | 70.0 | ± 16.0 | 0.100 | |
| Blood lymphocyte (%) | 15.7 | ± 12.4 | 20.4 | ± 12.2 | 0.174 | |
| UTI | 22(20.4%) | 2(33.3%) | 0.604 | |||
| Pneumonia | 58(53.7%) | 4(66.7%) | 0.678 | |||
| Times in EVD procedure | 1.9 | ± 0.7 | 2.0 | ± 0.9 | 0.680 | |
Mann–Whitney test. Chi-Square test. Fisher's exact test
Univariate analysis revealed that the cerebrospinal fluid (CSF) white blood cell (WBC) count at the final external ventricular drainage (EVD) procedure, as well as both the initial and final CSF protein levels, were significant predictors of central nervous system (CNS) infection. In contrast, the location of intracerebral hemorrhage (ICH) showed no significant association with the incidence of CNS infection. Multivariate analysis further confirmed that the CSF WBC count at the final EVD remained an independent predictor of CNS infection (Table 4).
Table 4.
Risk factors analysis of CNS infection
| Simple model | Multiple model | |||||
|---|---|---|---|---|---|---|
| OR | (95% CI) | p value | OR | (95% CI) | p value | |
| WBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.281 | |||
| Thalamus/GB ICH | 0.46 | (0.07-2.87) | 0.403 | |||
| Cerebellum ICH | 0.73 | (0.07-7.49) | 0.788 | |||
| WBC in CSF at last procedure (/mm3) | 1.09 | (1.03-1.16) | 0.005 | 1,08 | (1.01-1.15) | 0.02 |
| RBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.372 | |||
| RBC in CSF at last procedure (/mm3) | 1.00 | (1.00-1.00) | 0.867 | |||
| Neutrophil in CSF at EVD (/mm3) | 1.02 | (0.99-1.04) | 0.152 | |||
| Lymphocyte in CSF at EVD (/mm3) | 1.01 | (0.93-1.10) | 0.791 | |||
| CSF protein at EVD (mg/dl) | 1.01 | (1.00-1.01) | 0.017 | 1.00 | (0.99-1.01) | 0.703 |
| CSF protein at last procedure (mg/dl) | 1.03 | (1.01-1.05) | 0.005 | 1.03 | (1.00-1.07) | 0.077 |
| CSF sugar at EVD (mg/dl) | 1.01 | (0.99-1.02) | 0.277 | |||
| CSF sugar at last procedure (mg/dl) | 1.00 | (0.97-1.04) | 0.783 | |||
| CRP at EVD (mg/dl) | 0.65 | (0.34-1.25) | 0.196 | |||
| Albumin at EVD (mg/dl) | 3.21 | (0.81-12.71) | 0.097 | |||
| Blood WBC (/mm3) | 1.00 | (1.00-1.00) | 0.055 | |||
| Blood neutrophil (%) | 0.97 | (0.93-1.02) | 0.205 | |||
| Blood lymphocyte (%) | 1.03 | (0.97-1.09) | 0.369 | |||
| UTI | 1.95 | (0.34-11.37) | 0.456 | |||
| Pneumonia | 1.72 | (0.30-9.81) | 0.539 | |||
| Times in EVD procedure | 1.25 | (0.43-3.62) | 0.681 | |||
| Logistic regression | ||||||
Factors associated permanent shunt placement
Permanent ventriculoperitoneal (VP) shunts were required in 38 patients (33.3%).
Imaging predictors: Width of the largest temporal horn was significantly greater in the no-shunt group (11.5 ± 7.3 mm vs. 8.5 ± 4.6 mm, p < 0.05).
CSF predictors: RBC counts at the first EVD (56,155.8 ± 164,980.7/mm3 vs. 15,418.8 ± 49,329.0/mm3, p < 0.001) and last EVD (680.1 ± 819.0/mm3 vs. 458.0 ± 726.0/mm3, p < 0.01) were significantly higher in the permanent shunt group. Neutrophil (28.4 ± 30.3 vs. 18.6 ± 29.7/mm3, p < 0.05) and lymphocyte counts (11.3 ± 11.5 vs. 4.4 ± 6.3/mm3, p < 0.001) were also elevated. Interestingly, patients in the permanent shunt group underwent slightly fewer EVD procedures (1.8 ± 0.7 vs. 2.1 ± 0.7, p < 0.05) (Table 5).
Table 5.
Factors related to permanent V-P shunt
| No (n = 76) | Yes (n = 38) | p value | ||||
|---|---|---|---|---|---|---|
| Mean | ± SD | Mean | ± SD | |||
| Volume of CSF/day (ml/day) | 105.2 | ± 60.1 | 101.6 | ± 31.5 | 0.750 | |
| Total volume of CSF (ml) | 1681.9 | ± 1281.8 | 1711.3 | ± 1110.6 | 0.560 | |
| Interval of CSF drainage (days) | 16.3 | ± 9.6 | 16.8 | ± 9.2 | 0.559 | |
| Volume of ICH/IVH (ml) | 69.8 | ± 46.0 | 73.0 | ± 49.5 | 0.784 | |
| ICH location | Lobe | 22 (28.8%) | 11(28.9%) | 0.128 | ||
| Thalamus/GB | 42 (55.3%) | 21(55.2%) | ||||
| Cerebellum | 12 (15.8%) | 6(15.9%) | ||||
| Evan index (ratio) | 0.3 | ± 0.1 | 0.3 | ± 0.0 | 0.880 | |
| Width of largest temporal horn (mm) | 11.5 | ± 7.3 | 8.5 | ± 4.6 | 0.032 | |
| Temporal horn volume (ml) | 4.5 | ± 4.8 | 4.6 | ± 4.3 | 0.766 | |
| Total volume of bilateral frontal horn (ml) | 4.6 | ± 4.7 | 5.8 | ± 4.4 | 0.122 | |
| Periventricular lucency (%) | 18(23.7%) | 8(21.1%) | 0.752 | |||
| WBC in CSF at EVD (/mm3) | 86.8 | ± 223.2 | 157.6 | ± 294.8 | 0.106 | |
| WBC in CSF at last procedure (/mm3) | 3.7 | ± 5.3 | 8.6 | ± 13.1 | 0.039 | |
| RBC in CSF at EVD (/mm3) | 15,418.8 | ± 49,329.0 | 56,155.8 | ± 164,980.7 | < 0.001 | |
| RBC in CSF at last procedure (/mm3) | 458.0 | ± 726.0 | 680.1 | ± 819.0 | 0.007 | |
| Neutrophil in CSF at EVD (/mm3) | 18.6 | ± 29.7 | 28.4 | ± 30.3 | 0.040 | |
| Lymphocyte in CSF at EVD (/mm3) | 4.4 | ± 6.3 | 11.3 | ± 11.5 | 0.001 | |
| CSF protein at EVD (mg/dl) | 91.2 | ± 75.5 | 117.2 | ± 102.9 | 0.119 | |
| CSF protein at last procedure (mg/dl) | 65.0 | ± 38.8 | 81.3 | ± 54.1 | 0.069 | |
| CSF sugar at EVD (mg/dl) | 174.0 | ± 49.3 | 196.7 | ± 55.3 | 0.072 | |
| CSF sugar at last procedure (mg/dl) | 94.2 | ± 21.2 | 102.1 | ± 21.5 | 0.009 | |
| CRP at EVD (mg/dl) | 4.9 | ± 7.0 | 3.1 | ± 3.4 | 0.513 | |
| Albumin at EVD (mg/dl) | 3.2 | ± 0.6 | 3.3 | ± 0.5 | 0.742 | |
| Times in EVD procedure | 1.8 | ± 0.7 | 2.1 | ± 0.7 | 0.013 | |
Mann–Whitney test. Chi-Square test. Fisher's exact test
Logistic regression analysis revealed that a narrower width of the largest temporal horn significantly increased the odds of VP shunt placement (OR = 0.92, 95% CI 0.86–0.99, p = 0.025). Elevated CSF lymphocyte counts strongly predicted shunt placement (simple model: OR = 1.10, 95% CI 1.04–1.16, p = 0.001; multiple model: OR = 1.09, 95% CI 1.02–1.17, p = 0.012). The number of EVD procedures was significant in the simple model (OR = 1.85, 95% CI 1.08–3.16, p = 0.025), but not significant in the multiple models.
In multivariate analysis, the narrower width of the temporal horn and the cerebrospinal fluid (CSF) lymphocyte count at the initial external ventricular drainage (EVD) remained independently associated with the need for permanent shunt placement. The location of intracerebral hemorrhage (ICH) did not demonstrate a significant effect on shunt dependency (Table 6).
Table 6.
Risk factors analysis for permanent VP shunt
| Simple model | Multiple model | |||||
|---|---|---|---|---|---|---|
| OR | (95% CI) | p value | OR | (95% CI) | p value | |
| Volume of CSF/day (ml/day) | 1.00 | (0.99-1.01) | 0.729 | |||
| Total volume of CSF (ml) | 1.00 | (1.00-1.00) | 0.903 | |||
| Interval of CSF drainage (days) | 1.01 | (0.97-1.05) | 0.778 | |||
| Volume of ICH/IVH (ml) | 1.00 | (0.99-1.01) | 0.728 | |||
| Thalamus/BG ICH | 0.41 | (0.17-1.03) | 0.143 | |||
| Cerebellum ICH | 0.61 | (0.19-1.95) | 0.406 | |||
| Evan index (ratio) | 11.18 | (0.01-13,351) | 0.504 | |||
| Width of largest temporal horn (mm) | 0.92 | (0.86-0.99) | 0.025 | 0.90 | (0.83-0.97) | 0.0018 |
| Temporal horn volume (ml) | 1.00 | (0.92-1.09) | 0.942 | |||
| Total volume of bilateral frontal horn (ml) | 1.06 | (0.97-1.15) | 0.206 | |||
| Periventricular lucency | 0.86 | (0.33-2.20) | 0.752 | |||
| WBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.172 | |||
| WBC in CSF at last procedure (/mm3) | 1.07 | (1.01-1.13) | 0.016 | 1.00 | (0.94-1.06) | 0.994 |
| RBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.118 | |||
| RBC in CSF at last procedure (/mm3) | 1.00 | (1.00-1.00) | 0.148 | |||
| Neutrophil in CSF at EVD (/mm3) | 1.01 | (1.00-1.02) | 0.103 | |||
| Lymphocyte in CSF at EVD (/mm3) | 1.10 | (1.04-1.16) | 0.001 | 1.09 | (1.02-1.17) | 0.012 |
| CSF protein at EVD (mg/dl) | 1.00 | (1.00-1.01) | 0.138 | |||
| CSF protein at last procedure (mg/dl) | 1.01 | (1.00-1.02) | 0.087 | |||
| CSF sugar at EVD (mg/dl) | 1.01 | (1.00-1.02) | 0.031 | 1.01 | (1.00-1.01) | 0.166 |
| CSF sugar at last procedure (mg/dl) | 1.02 | (1.00-1.04) | 0.083 | |||
| CRP at EVD (mg/dl) | 0.94 | (0.86-1.02) | 0.149 | |||
| Albumin at EVD (mg/dl) | 1.13 | (0.56-2.27) | 0.730 | |||
| Times in EVD procedure | 1.85 | (1.08-3.16) | 0.025 | 1.69 | (0.88-3.24) | 0.117 |
| Logistic regression | ||||||
During long-term follow-up, two patients required shunt revision, occurring at 36 and 41 months after the initial procedure, respectively.
Risk factors of one year mortality
Eighteen patients (15.8%) died within one year after surgery: 14 from pneumonia, 2 from UTI, and 2 of unknown causes.
Clinical predictors Patients with higher diastolic blood pressure at admission (110.1 ± 20.1 vs. 99.2 ± 24.8 mmHg, p < 0.05) and asymmetric pupils (44.4% vs. 16.0%, p < 0.05) had higher mortality. Larger pupil size was similarly significant (3.4 ± 1.3 mm vs. 2.7 ± 0.9 mm, p < 0.01).
Imaging predictors Wider temporal horns (13.7 ± 5.3 mm vs. 9.9 ± 6.7 mm, p < 0.01) and higher prevalence of periventricular lucency (44.4% vs. 16.6%, p < 0.01) were associated with mortality.
CSF and systemic markers Elevated RBC and lymphocyte counts in CSF, as well as higher counts in blood neutrophils and lymphocytes, were significant predictors of 1 year mortality (Table 7).
Table 7.
Factors related to one year mortality
| No (n = 96) | Yes (n = 18) | p value | ||||
|---|---|---|---|---|---|---|
| Mean | ± SD | Mean | ± SD | 67.2 | ||
| Age | 67.2 | ± 11.1 | 69.6 | ± 10.7 | 0.042 | |
| DBP (mmHg) | 99.2 | ± 24.8 | 110.1 | ± 20.1 | 0.199 | |
| GCS scores | 8.2 | ± 4.1 | 7.2 | ± 4.6 | 0.132 | |
| Best GCS motor scores | 3.9 | ± 1.9 | 3.1 | ± 2.0 | 0.023 | |
| Asymmetric pupil size, n (%) | 16 | (16.7%) | 8 | (44.4%) | 0.006 | |
| The largest pupil size (mm) | 2.7 | ± 0.9 | 3.4 | ± 1.3 | 0.466 | |
| Light reflex, n (%) | 62 | (64.6%) | 10 | (55.6%) | 0.254 | |
| Focal motor weakness, n (%) | 50 | (52.1%) | 12 | (66.7%) | 0.027 | |
| Volume of CSF/day (ml/day) | 108.8 | ± 53.3 | 78.1 | ± 36.8 | 0.926 | |
| Total volume of CSF (ml) | 1658.0 | ± 1116.5 | 1871.6 | ± 1711.0 | 0.578 | |
| Interval of CSF drainage (days) | 16.0 | ± 8.7 | 19.3 | ± 12.8 | 0.444 | |
| Volume of ICH/IVH (ml) | 69.3 | ± 45.9 | 79.5 | ± 52.9 | 67.2 | |
| ICH location | Lobe | 33(34.4%) | 7(38.9%) | 0.908 | ||
| Thalamus/BG | 48(50.0%) | 8(44.4%) | ||||
| Cerebellum | 15(15.6%) | 3(16.7%) | ||||
| Evan index (ratio) | 0.3 | ± 0.1 | 0.3 | ± 0.1 | 0.969 | |
| Width of largest temporal horn (mm) | 9.9 | ± 6.7 | 13.7 | ± 5.3 | 0.008 | |
| Periventricular lucency (%) | 18(18.8%) | 8(44.4%) | 0.029 | |||
| WBC in CSF at EVD (/mm3) | 104.3 | ± 226.3 | 142.7 | ± 359.1 | 0.649 | |
| RBC in CSF at EVD (/mm3) | 27,244.4 | ± 104,499.1 | 38,349.6 | ± 106,372.5 | 0.034 | |
| RBC in CSF at last procedure (/mm3) | 263.4 | ± 477.0 | 582.4 | ± 796.0 | 0.021 | |
| Neutrophil in CSF at EVD (/mm3) | 23.9 | ± 30.8 | 11.1 | ± 24.0 | 0.307 | |
| Lymphocyte in CSF at EVD (/mm3) | 3.4 | ± 4.9 | 7.4 | ± 9.4 | 0.043 | |
| Blood neutrophil (%) | 74.1 | ± 10.4 | 78.2 | ± 15.2 | 0.014 | |
| Blood lymphocyte (%) | 18.4 | ± 9.4 | 15.5 | ± 12.9 | 0.031 | |
| UTI | 20(20.8%) | 4(22.2%) | 1.0 | |||
| Pneumonia | 52(54.2%) | 10(55.6%) | 0.914 | |||
| Times in EVD procedure | 1.9 | ± 0.8 | 1.7 | ± 0.7 | 0.206 | |
Mann–Whitney test. Chi-Square test. Fisher's exact test
Logistic regression
In univariate analysis, asymmetric pupils were significantly associated with one-year mortality (odds ratio [OR] = 4.00, 95% confidence interval [CI] 1.37–11.70, p = 0.011), although this association did not persist in the multivariate model. Pupil size remained a robust predictor of mortality, achieving statistical significance in both univariate (OR = 1.95, 95% CI 1.20–3.18, p = 0.007) and multivariate analyses (OR = 1.95, 95% CI 1.06–3.59, p = 0.033).
Lower daily cerebrospinal fluid (CSF) output was independently associated with increased mortality (univariate model: OR = 0.98, 95% CI 0.97–0.998, p = 0.023; multivariate model: OR = 0.98, 95% CI 0.96–0.996, p = 0.019). The maximal width of the temporal horn was significant in the univariate model (OR = 1.08, 95% CI 1.01–1.16, p = 0.032) and showed borderline significance in multivariate analysis.
Periventricular lucency emerged as one of the strongest predictors of one-year mortality (univariate model: OR = 3.47, 95% CI 1.20–10.02, p = 0.022; multivariate model: OR = 4.13, 95% CI 1.18–14.40, p = 0.026).
In summary, larger pupil size, reduced daily CSF drainage, and the presence of periventricular lucency were the major independent predictors of one-year mortality (Table 8).
Table 8.
Risk factors analysis in one year mortality
| Simple model | Multiple model | |||||
|---|---|---|---|---|---|---|
| OR | (95% CI) | p value | OR | (95% CI) | p value | |
| Age | 1.02 | (0.97-1.07) | 0.406 | |||
| DBP (mmHg) | 1.02 | (1.00-1.04) | 0.084 | |||
| GCS scores | 0.94 | (0.83-1.07) | 0.349 | |||
| Best GCS motor scores | 0.81 | (0.62-1.06) | 0.131 | |||
| Asymmetric pupil size | 4.00 | (1.37-11.70) | 0.011 | 1.75 | (0.44-6.99) | 0.428 |
| The largest pupil size (mm) | 1.95 | (1.20-3.18) | 0.007 | 1.95 | (1.06-3.59) | 0.033 |
| Light reflex | 0.69 | (0.25-1.90) | 0.468 | |||
| Focal motor weakness | 1.84 | (0.64-5.30) | 0.259 | |||
| Volume of CSF/day (ml/day) | 0.98 | (0.97-0.998) | 0.023 | 0.98 | (0.96-0.996) | 0.019 |
| Total volume of CSF (ml) | 1.00 | (1.00-1.00) | 0.496 | |||
| Interval of CSF drainage (days) | 1.04 | (0.99-1.09) | 0.168 | |||
| Volume of ICH/IVH (ml) | 1.00 | (0.99-1.02) | 0.398 | |||
| Thalamus/GB ICH | 0.79 | (0.26-2.38) | 0.669 | |||
| Cerebellum ICH | 0.94 | (0.21-4.16) | 0.938 | |||
| Evan index (ratio) | 0.88 | (0.00-6729.65) | 0.978 | |||
| Width of largest temporal horn (mm) | 1.08 | (1.01-1.16) | 0.032 | 1.09 | (0.99-1.19) | 0.066 |
| Periventricular lucency | 3.47 | (1.20-10.02) | 0.022 | 4.13 | (1.18-14.40) | 0.026 |
| WBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.553 | |||
| RBC in CSF at EVD (/mm3) | 1.00 | (1.00-1.00) | 0.682 | |||
| Neutrophil in CSF at EVD (/mm3) | 0.98 | (0.96-1.00) | 0.114 | |||
| Lymphocyte in CSF at EVD (/mm3) | 0.92 | (0.84-1.01) | 0.095 | |||
| Blood neutrophil (%) | 0.98 | (0.95-1.01) | 0.278 | |||
| Blood lymphocyte (%) | 1.02 | (0.98-1.06) | 0.367 | |||
| UTI | 1.09 | (0.32-3.66) | 0.895 | |||
| Pneumonia | 1.06 | (0.38-2.91) | 0.914 | |||
| Times in EVD procedure | 0.62 | (0.30-1.28) | 0.199 | |||
| Logistic regression | ||||||
Discussion
In this retrospective cohort study, we analyzed 114 patients with spontaneous large-volume intracerebral hemorrhage (ICH) together with intraventricular extension (IVH), in terms of the clinical outcomes of initial external ventricular drainage (EVD). We focused on permanent ventriculoperitoneal (VP) shunt placement, shunt revision, central nervous system (CNS) infection, and one-year mortality. Overall, 33.3% of patients required permanent VP shunt placement, 15.8% experienced one-year mortality, and 1.8% required shunt revision. These findings demonstrated the substantial morbidity associated with this population and highlighted the need for early identification of prognostic markers to optimize management strategies.
Shunt dependency and radiographic predictors
Approximately one-third of our patients required a permanent VP shunt placement, a ratio that is consistent with prior studies. For example, Li et al. reported a comparable shunt dependency rate of 33.5% in 179 patients, identifying strong predictors being modified Graeb score ≥ 8 and bicaudate index > 0.16 for long-term CSF diversion [11]. Similarly, Brazdzionis et al. found that Evans’ index ≥ 0.31 had high sensitivity and specificity for predicting the need of VP shunt [12], while Tian et al. demonstrated that intraventricular CSF volume, acute hydrocephalus, and IVH severity had independently predicted shunt dependency [13]. Collectively, these studies reinforce that approximately one-third of patients with IVH develop long-term dependence on CSF drainage, and that radiographic burden at admission is a critical factor in risk stratification.
In our study, we found that narrower temporal horn width was independently associated with greater odds of permanent shunt placement. Although seemingly paradoxical—since hydrocephalus is typically characterized by ventricular dilation—this may reflect early obstruction or reduced ventricular compliance preceding overt enlargement. Alternatively, a narrowed temporal horn could indicate localized IVH or ependymal inflammation, leading to impaired CSF resorption. Previous studies have focused primarily on Evans’ index and bicaudate ratio [12, 13]. Thus, the prognostic role of temporal horn width remains uncertain and needs further evaluation.
CSF inflammatory markers and hydrocephalus
A novel finding of our study was that elevated CSF lymphocyte count at the time of EVD placement independently predicted shunt dependency. This supports the hypothesis that intrathecal inflammation contributes to post-hemorrhagic hydrocephalus. Prior reports demonstrate that hemorrhage-induced immune activation, characterized by elevated CSF cytokines (e.g., IL-6, TNF-α) and pleocytosis, leads to arachnoid granulation scars, and impairing CSF absorption [14, 15]. In addition, we observed that elevated CSF WBC and protein levels were significantly associated with both shunt dependency and CNS infection. This dual relationship is biologically plausible, as increased inflammatory markers reflect both sterile inflammation and infectious processes. Notably, a large adult cohort study showed that cumulative CSF protein exposure was a strong independent risk factor for post-hemorrhagic hydrocephalus, with patients in higher protein–duration strata experiencing markedly greater rates of VP shunt placement (AUC ≈ 0.79) [16].
Mortality predictors
Our study further identified several independent predictors of one-year mortality. A larger pupil size at presentation was a robust prognostic marker, aligning with prior literature. Mazhar et al. demonstrated that abnormal pupillary indices (NPi) correlated with ICH severity markers on CT, and they were associated with worse outcomes [17]. Similarly, the ORANGE multicenter cohort found that abnormal NPi values were strong predictors of six-month mortality and poor functional outcome, with hazard ratios of ~ 5.6 per 10% increase in abnormal NPi frequency [18]. These findings corroborate with our observation in that baseline pupillary abnormalities are meaningful prognostic indicators in spontaneous ICH.
In addition, lower daily CSF drainage volume was independently linked to increased one-year mortality. In the absence of ICH-specific studies analyzing such an association, prior data suggested that EVD placement reduces mortality compared with conservative management, with reported rates of 20–22% versus 40–45%, respectively [5]. Our results are consistent with the literature in this respect, suggesting that inadequate CSF clearance likely compromise ICP control and worsen patient outcomes.
Radiographically, greater temporal horn width was associated with increased mortality risk. While not widely studied in spontaneous ICH, temporal horn dilatation reflects acute hydrocephalus, a condition which is typically associated with poor outcomes. Diringer et al. reported a mortality rate of ~ 50% in patients with hydrocephalus versus only 2% in those without [19], while Stein et al. demonstrated that marked ventricular dilation independently predicted a greater 30-day mortality [20]. Furthermore, in our analysis, periventricular lucency emerged as one of the strongest predictors of one-year mortality. As a marker of transependymal CSF migration and elevated intraventricular pressure, periventricular lucency likely reflects more severe or prolonged intracranial hypertension, thereby contributing to poor neurological outcomes.
Limitation
First, our retrospective study involved a cohort at single-center, thus limiting causal inference and generalizability of our results. Second, exclusion of patients with extremely poor neurological status and incomplete CSF data likely introduced some selection bias. Third, CSF neutrophil and lymphocyte counts at the last EVD were often unavailable, producing incomplete dataset. Fourth, the relatively small number of patients with key outcomes (e.g., infections, shunt revisions, mortality) limited statistical power. Fifth, most patients were institutionalized, preventing assessment of long-term functional outcomes such as disability or quality of life. Finally, predictive models were not externally validated, restricting their applicability to other populations. In summary, while our study has identified meaningful predictors of infection, shunt dependency, and mortality, our findings should be interpreted with cautious.
Conclusion
In patients with large-volume ICH complicated by IVH managed with EVD, CSF WBC and protein levels were significant predictors of CNS infection. Increased CSF lymphocyte counts and ventricular enlargement, particularly temporal horn width, were independently associated with permanent shunt dependency. One-year mortality was strongly influenced by the following: pupil abnormalities, reduced daily CSF drainage, ventricular enlargement, and periventricular lucency. The current study results underscore the value of combined clinical, biochemical, and imaging parameters for risk stratification and management in this high-risk population.
Acknowledgements
The author would like to thank the Biostatistics Task Force of Taichung Veterans General Hospital for their kind assistance in statistical analysis.
Author contributions
YLS, SYP and YCC prepared Table I-IV. HST and YJC prepared Table V. CCS prepared Table VI. JS and MLS prepared table VII-VIII. YLS wrote the main manuscript text. All authors reviewed the manuscript.
Funding
This work was supported by the grant MOST 111–2314-B-075A-011-MY2 from the National Science and Technology Council, Taiwan, and the grants TCVGH-1137307C, TCVGH-NCHU1137603, TCVGH-PU1138101, TCVGH-1137303D, and TCVGH-113G412 from Taichung Veteran General Hospital, Taiwan.
Data availability
All data generated and/or analyzed during this study are either included in this article or are available from the corresponding author on reasonable request. This study did not generate new unique reagents.
Declarations
Ethics approval and consent to participate
This study was approved by the Ethical Committee of Taichung Veterans General Hospital (No. CE25398A).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated and/or analyzed during this study are either included in this article or are available from the corresponding author on reasonable request. This study did not generate new unique reagents.