Magnetic resonance imaging findings predict the recurrence of chronic subdural hematoma.

The exact predictive factors for postoperative recurrence of chronic subdural hematoma (CSDH) are still unknown. Based on the preoperative magnetic resonance imaging (MRI), low recurrence rate of T1-hyperintensity hematoma was previously reported. We investigated the other types of radiological findings which are related to the recurrence rate of CSDH in large number of patients analyzed by multivariate logistic regression model. Preoperative MRI and postoperative computed tomography (CT) were performed and the influence of the preoperative use of antiplatelet or anticoagulant drugs was also studied. The overall recurrence rate was 9.3% (47 of 505 hematomas). The MRI T1-iso/hypointensity group showed a significantly higher recurrence rate (18.2%, 29 of 159) compared to the other groups (5.2%, 18 of 346; p < 0.001). Multivariate logistic regression analysis showed T1 classification was the solo significant prognostic predictor among various factors such as bilateral hematoma, antiplatelet or anticoagulant drug usage, residual hematoma on postoperative CT, and MRI classification (p < 0.001): adjusted odds ratio for the recurrence in T1-iso/hypointensity group relative to the T1-hyperintensity group was 5.58 [95% confidence interval (CI), 2.09-14.86] (p = 0.001). Postoperative residual hematoma and antiplatelet or anticoagulant drug usage did not increase the recurrence risk. The preoperative MRI findings, especially T1WI findings, have predictive value for postoperative recurrence of CSDH and the T1-iso/hypointensity group can be assumed to be a high recurrence risk group.

Introduction

Chronic subdural hematoma (CSDH) is a common intracranial hemorrhagic disease with a constant postoperative recurrence rate. Many parameters have been suggested as risk factors for CSDH recurrence, such as antiplatelet and anticoagulant drug use, the depth of hematoma, bilateral hematoma, preoperative computed tomography (CT) findings, and postoperative massive subdural air collection.[1–7)] However, there is still no exact consensus on the ability of these factors to predict CSDH recurrence. We reported that hematoma showing as hyperintensity on T1-weighted image (T1WI) with preoperative magnetic resonance imaging (MRI) was correlated with a low recurrence rate.[8)] However, there is little other information in the literature on the relationships between radiological findings and CSDH recurrence rate. In this study, we reviewed preoperative MRI findings and postoperative CT findings in 414 patients with CSDHs, who had unilateral or bilateral burr-hole surgery at our single institution, and evaluated the impact of the radiological findings on the recurrence rate of CSDH. We also examined the influence of the preoperative use of antiplatelet or anticoagulant drugs on the recurrence rate.

Materials and Methods

There were 429 consecutive adult CSDH patients who underwent burr-hole surgery in our hospital (Aizu Chuo Hospital, Fukushima, Japan) from January 2004 to March 2010, and 414 patients with available preoperative T1 and T2 MRI and postoperative CT scans were analyzed. Preoperative MRI (1.5 Tesla) was performed in all of these patients on admission using a spin-echo sequence with repetition/ echo times of 525/17 ms for T1WI and 3,600/98 ms for T2-weighted image (T2WI). Postoperative CT scans were obtained just after surgery. Fifteen cases were excluded because preoperative T1 and T2 MRI or postoperative CT scans could not be obtained. Ninety-one patients had bilateral hematomas; thus, a total of 505 operative lesions were studied. All hematomas were evacuated using a single burr-hole procedure. The hematoma cavity was irrigated and replaced with sterile saline; a closed drainage system with a silicone tube was left in place for 1 day.

Based on the preoperative T1WI and T2WI, we classified the 505 hematomas into 4 groups: hyper-intensity, isointensity or hypointensity, mixed intensity, and layered pattern (Fig. 1), as previously reported.[8,9)] Isointensity was considered to reflect gray matter.

Fig. 1.

Classification of hematomas based on magnetic resonance imaging (MRI) findings. Hematomas that showed uniform hyperintensity compared to the intensity of gray matter were classified into a hyperintensity group based on both T1WI and T2WI. Hematomas with uniform iso- or hypointensity compared to gray matter were classified into an iso/hypointensity group. Hematomas that showed diffuse heterogeneity in intensity were classified into a mixed-intensity group. Hematomas with a distinct niveau were classified into a layered-intensity group. T1WI: T1-weighted image, T2WI: T2-weighted image.

Based on the postoperative CT scans, we determined whether residual hematoma was present or not. If there was a high-density area in the subdural hematoma cavity that was replaced with sterile saline or air, we regarded this as a residual hematoma (Fig. 2).

Fig. 2.

Residual hematoma based on postoperative computerized tomography (CT) scanning. Postoperative CT scans were taken just after surgery. If there were any high density areas other than that of water or air in the operated subdural space, we regarded this as residual hematoma.

We defined “hematoma recurrence” as the reaccumulation of hematoma in the operated subdural space with any concurrent symptoms such as hemiparesis, headache, and dizziness within 6 months postoperatively.

The preoperative use of antiplatelet or anticoagulant drugs was also evaluated in all patients. If a prothrombin time/international normalized ratio (PT/INR) was more than 1.35, vitamin K2 was administered intravenously until the value became lower than 1.35. No patient received a fresh-frozen plasma or platelet transfusion in this study. These drugs were suspended for about a week after the operation.

We performed a univariate analysis to assess the relationships between each variable and the recurrence of CSDH by Fisher’s exact test and Mann-Whitney’s U-test. We also performed a multivariate statistical analysis of factors by using logistic regression model. Forward and backward stepwise logistic regression analysis was used to determine associations of potential confounders with the recurrence of CSDH: uni- or bilateral hematoma, antiplatelet or anticoagulant drug usage, residual hematoma on CT, and MRI classifications. A p value < 0.05 was considered statistically significant.

Results

The age and sex distribution of the 414 patients with CSDH are shown in Table 1. There were 279 men and 135 women, and the mean age of the patients was 77.3 years. The highest incidence of both primary CSDH and recurrence of CSDH were seen in the eighth decade of life. Thirty-seven patients (8.9%) recurred and required a second operation. The average interval between the initial operation and reoperation was 34.9 days. No patient required more than one reoperation and recurred beyond 6 months.

Table 1

Sex and age distribution of chronic subdural hematoma and its recurrence

Sex	Age (yrs)										Total
	11–20	21–30	31–40	41–50	51–60	61–70	71–80	81–90	91–100	101–110
Male	1	1	2	4	18	56	122	64	11	0	279
Female	0	0	0	0	4	10	38	67	15	1	135
Total no. of cases	1	1	2	4	22	66	160	131	26	1	414
No. of recurrence	0	0	1	0	0	1	23	11	1	0	37 (8.9%)

As shown in Table 2, the recurrence rate of bilateral hematoma for which an operation was performed on both sides was not significantly different from that of unilateral hematoma, so the bilateral hematoma were counted as two hematomas independently of each other in this study. Based on the number of hematomas, 47 hematomas (9.3%) recurred among the 505 hematomas. Neither age nor sex was significantly associated with the recurrence rate.

Table 2

Factors related to recurrence of chronic subdural hematoma

Factor	No. of cases (%)		Recurrence rate	p value
	Recurrence	No recurrence
Total	47	458	9.3%
Sex
Male	34 (72.3)	307 (67.0)	10.0%	0.52
Female	13 (27.7)	151 (33.0)	7.9%
Age (y)a	77 (71.5–80.5)	79 (72.0–84.0)		0.15
Hematoma site
Unilateral	33 (70.2)	290 (66.3)	10.2%	0.34
Bilateral	14 (29.8)	168 (36.7)	7.7%
Antiplatelet or anticoagulant drug
Yes	8 (17.0)	91 (19.9)	8.1%	0.85
No	39 (83.0)	367 (80.1)	9.6%
Residual hematoma
Yes	17 (36.2)	200 (43.7)	7.8%	0.36
No	30 (63.8)	258 (56.3)	10.4%

Values are expressed as median (interquartile range).

Of the 414 patients with CSDH, there were 70 patients receiving antiplatelet drugs and 14 receiving anticoagulant drugs preoperatively. These drugs were suspended for about a week postoperatively, and no patient had adverse events during this time period. The recurrence rate in the 99 hematomas with an antiplatelet or anticoagulant drug was not significantly different from the hematomas without these drugs (Table 2).

Of all 505 operated lesions, 217 lesions (43.0%) showed residual hematoma on postoperative CT scanning. The recurrence rate in this group was not different from that in the group without residual hematoma (Table 2).

Tables 3 and 4 show the results of relationship between MRI classification and recurrence rate. Analyzed in a manner similar to previous report,[8)] the recurrence rate in the T1-iso/hypointensity group was significantly higher than that in the other groups combined (18.2% vs. 5.2%, p < 0.001). As might be expected, the recurrence rate in the T1-hyperintensity group was significantly lower than that in the other groups combined (3.9% vs 11.2%, p = 0.013) to the contrary. The T2WI classification did not have a significant impact on the recurrence rate. Multivariate logistic regression analysis of all hematomas showed T1 classification was the solo significant prognostic predictor among various factors such as uni- or bilateral hematoma, antiplatelet or anticoagulant drug usage, residual hematoma on postoperative CT, and MRI classification (p < 0.001): adjusted odds ratio for the recurrence in T1-iso/hypointensity group relative to the T1 hyperintensity group was 5.58 (95% CI, 2.09–14.86) (p = 0.001, Table 5).

Table 3

MRI T1WI classification and recurrence rate

Classification of MRI T1WI findings	No. of cases		Recurrence rate
	Recurrence	No recurrence
Hyper	5	125	3.9%
Iso/hypo	29	130	18.2%
Mixed	10	161	5.8%
Layered	3	42	6.7%
Total	47	458	9.3%

MRI: magnetic resonance imaging, T1WI: T1-weighted image.

Table 4

MRI T2WI classification and recurrence rate

Classification of MRI T2WI findings	No. of cases		Recurrence rate
	Recurrence	No recurrence
Hyper	19	130	12.8%
Iso/hypo	9	76	10.3%
Mixed	11	184	5.6%
Layered	8	68	10.5%
Total	47	458	9.3%

MRI: magnetic resonance imaging, T2WI: T2-weighted image.

Table 5

Multivariate logistic regression analysis of factors related to recurrence of chronic subdural hematoma

Factor	OR	95% CI	p value
Bilateral hematoma	0.732	0.381–1.408	0.35
Antiplatelet or anticoagulant drug	1.209	0.546–2.674	0.64
Residual hematoma	1.368	0.734–2.551	0.32
MRI T1WI findings			0.0002
Iso/hypo relative to hyper	5.577	2.092–14.864	0.001
Mixed relative to hyper	1.553	0.518–4.659	0.43
Layered relative to hyper	1.786	0.409–7.793	0.44
MRI T2WI findings			0.15

CI: confidence interval, MRI: magnetic resonance imaging, OR: odds ratio, T1WI: T1-weighted image, T2WI: T2-weighted image.

We also analyzed the influence of these drugs only in T1-iso/hypointensity subgroup, since the patients had a high risk of recurrence in this subgroup. Among 127 patients in the T1-iso/hypointensity subgroup (159 hematomas), 21 patients were taking antiplatelet or anticoagulant drugs. The recurrence rate in these 21 patients (9.1%, 3 of 33 hematomas) was not significantly different from the recurrence rate in the patient in this subgroup who was not taking these drugs (14.3%, 18 of 126 hematomas; p > 0.05).

We also analyzed the influence of these drugs on the distribution of the T1WI classification of the hematoma. The results of this analysis showed that the use of these drugs did not change the distribution of T1WI classification; these drugs neither increased the T1-iso/hypointensity hematoma, nor decreased T1-hyperintensity hematoma (Table 6).

Table 6

Effect of antiplatelet/anticoagulant use on the distribution of the T1WI-based classification of hematoma

T1WI classification	Drug + (%)	Total (%)
Hyper	26 (26.3)	130 (25.7)
Iso/hypo	28 (28.3)	159 (31.4)
Mixed	38 (38.4)	171 (33.8)
Layered	7 (7.1)	45 (8.9)
Total	99	505

T1WI: T1-weighted image.

Discussion

Clinical utility of MRI findings

In our previous report,[8)] the recurrence rate in the T1-hyperintensity group was significantly lower than in the other groups combined (3.4% vs. 11.6%, p < 0.05), however, there is no knowledge about which MRI findings correlate with a high recurrence rate. The recurrence rate of the T1-hypointensity group and T1-iso/hypointensity group were 16.6% and 12.0% respectively, but they were not statistically significant. In this study, we examined a greater number of CSDH cases along with MRI findings than in our previous report, and we confirmed the high CSDH recurrence rate in the T1-iso/hypointensity group in addition to the low recurrence rate in the T1-hyperintensity group analyzed in a manner similar to that report. Moreover, in this study, multivariate logistic regression analysis was performed excluding age and sex because their effects were not significant in previous reports.[1–7)] The results showed MRI T1-classification was the solo significant prognostic predictor among various factors, and revealed T1-iso/hypointensity group have more than five times greater risk of the recurrence relative to T1-hyperintensity group.

It is well known that CSDH is encapsulated by the inner and the outer membranes. The outer membrane is reparative granulation tissue that consists of collagen fibers, fibroblasts, and micro-capillaries.[10)] There are various theories on the pathophysiology of CSDH. According to the most prevalent theory, an intermittent cycle of bleeding, coagulation, fibrinolysis, and re-bleeding from the highly vascularized outer membrane is an essential event in the CSDH growth process.[11–15)] In this model, it is assumed that the hematoma stability varies depending on the stage of the cycle, and there is some degree of correlation between the hematoma stage and radiological findings.[9)]

T1-hyperintensity hematomas are thought to represent more mature and stable hematomas, which have been present for several days since the last bleeding cycle.[8,16)] From that point of view, our result that T1-hyperintensity hematoma are associated with a lower recurrence rate suggests that T1-hyperintensity hematoma are more stable and mature.

In contrast to T1-hyperintensity hematoma, T1-iso/hypointensity hematoma in our study showed a higher recurrence rate. We speculate that T1-iso/hypointensity hematoma may represent fresh, vulnerable hematoma that develops during the bleeding/rebleeding stage. Our MRI results, especially the T1WI, may reflect the pathological stages of hematoma and may be an accurate predictor of recurrence. Thus, further investigation will be expected to clarify the correlation between the MRI findings and the components of hematoma and outer membrane.

Antiplatelet and anticoagulant therapy

Antiplatelet or anticoagulant drugs have been considered to be one of the factors that increase the postoperative recurrence rate of CSDH.[2,4,6)] Nevertheless, in our study, these drugs did not increase the recurrence rate when they were suspended perioperatively. Even in the high-risk T1-iso/hypointensity subgroup, these drugs did not increase the CSDH recurrence rate. The use of these drugs also did not increase the proportion of patients in the T1-iso/hypointensity subgroup, nor decrease the proportion in the T1-hyperintensity subgroup. These results suggest that antiplatelet or anticoagulant drugs did not influence the bleeding activity of vulnerable hematoma, nor affect the transition of stable hematoma into vulnerable hematoma. According to these results, the healing process of CSDH may not be a simple hemostatic process, but may also include some unknown process that is not affected by drugs that interfere with hemostasis. However, it is important to point out that we suspended all antiplatelet and anticoagulant drugs for about a week starting just before the operation, and this may have been one of the reasons that these drugs did not influence the recurrence rate.

Residual hematoma

In our study, the recurrence rate of cases with postoperative residual hematoma was not significantly different from that of the group without residual hematoma. We can assume that the recurrence of CSDH is attributed to microvessel rebleeding of the outer membrane, and the amount of residual hematoma has no relation with the risk of rebleeding. This result may indicate that burr-hole surgery for CSDH does not necessarily require complete irrigation to reduce the risk of recurrence.

Other risk factors

The recurrence rate of bilateral hematoma was not significantly different from that of unilateral hematoma unlike the previous report.[6)] Other risk factors such as the depth of hematoma, preoperative CT findings, and postoperative subdural air collection were not investigated in this study, but may be worthy of future investigation.

Conclusion

In this study, we confirmed high CSDH recurrence rate in the T1-iso/hypointensity group in addition to previous report demonstrating a low recurrence rate in the T1-hyperintensity group based on the preoperative MRI findings. Moreover, antiplatelet or anticoagulant drugs and postoperative residual hematoma did not affect the recurrence rate. According to these results in our study, preoperative MRI T1WI findings could be pretty useful to be an accurate predictor of CSDH recurrence.