Standardizing Prognostication and Management of Spontaneous Basal Ganglia Hemorrhage: A Novel Scoring System

DOI: https://doi.org/10.21203/rs.3.rs-1868474/v1

Abstract

Background: Factors that are used in spontaneous ICH prognostication score cannot be generalized to basal ganglia haemorrhages. Our study aimed in developing a novel scoring system for prognosticating and management of basal ganglia haemorrhages, including factors likely to influence mortality or survival. 

Methods: A prospective study was performed of 351 patients with spontaneous basal ganglia haemorrhage. The patients were either managed conservatively or underwent operative intervention. Mortality at 90 days was recorded. Using univariate and multivariable logistic regression, the association between various plausible factors and 90-day mortality was tested. Factors found to be significant were used to develop a novel scoring system and the association between 90-day mortality and modified ICH score was calculated. This score was subsequently used to standardize the management with a score correlation to treatment guidelines, thus advocating either conservative or operative management depending upon the score. Thus based on this scoring system, we tried to develop a range below which conservative management was advisable, a score favouring operative intervention, and a score above which operative intervention was futile, since both conservative and surgical treatment resulted in the same outcome.

Results: We analyzed 339 cases, overall, 90-day mortality was 37.75% (n=128). The survival rate in patients having modified ICH score of 7 or less than 7 was 91.66%, however, it decreased to 12.19% in patients having a score > 7. A modified ICH score of 7 or less than 7 could predict the survival in 93.8% (95% CI 89.7-96.7) of patients and had a specificity of 85.9%%. The positive predictive value of modified ICH score 7 or < 7 was 91.7% (95%CI 87.1-95.0). In patients with score of 6, surgery was advisable in almost 50% of cases and the mortality was 100 percent even after surgical intervention in patients having score of 10 or more.

Conclusion: Modified ICH score is a useful tool for predicting 90-days mortality, the area under the ROC curve was 93% which was higher than any other studies for spontaneous ICH. This scoring system can also aid in deciding the line of management of basal ganglia bleed patients.

Trial registration: retrospectively registered

Introduction

According to the latest report by Global Burden of disease for those aged 25 years or older, the estimated global lifetime risk of stroke has increased from 22.8% in 1990 to 24.9% in 2016.1The prevalence of stroke is expected to increase gradually over the years. With 55 million (95% uncertainty interval) deaths related to stroke in 2016, stroke is the second biggest cause of death globally.2 Stroke with intracranial haemorrhage (ICH) accounts for 13–20% of all first-time strokes.

Since the cortical-subcortical connection is affected, ICH is characterized as lobar haemorrhages, which often spread to the pia-arachnoid region. On the contrary, deep ICH affects the subcortical structures such as the thalamus, basal ganglia, and brain stem. Etiologically, ICH is classified into primary ICH, which includes hypertensive ICH, amyloid angiopathy-related ICH, and idiopathic ICH, whereas secondary ICH is caused by an underlying medical or structural condition.

Basal ganglia haemorrhage accounts for 60% of all hypertensive intracerebral haemorrhages, and the commonest aetiology is the small vessel vasculopathy secondary to long-term chronic hypertension.

Rapid diagnosis and careful management in basal ganglia hematoma patients are crucial because early deterioration is common in such patients. Surgical management has unique advantages as it can effectively remove the hematoma and decrease the intracranial pressure and associated complications.

However, there are no clear-cut guidelines for managing basal ganglia hematoma. Moreover, a large randomized clinical trial has failed to show significant benefits of surgery over conservative medical treatment.3Furthermore, the AHA/ASA Guidelines for Managing Spontaneous Intracerebral Haemorrhage suggested that the effectiveness of the craniotomy approach for basal ganglia haemorrhage is still uncertain. 4

In many ICH treatment studies, patients have been selected based on different criteria. This difference in the selection criteria, with different studies advocating the significance of one or the other prognostic indicators entirely rejected by others, serves to emphasize that there is no standard, widely accepted early predictive model or clinical grading scale for basal ganglia haemorrhages analogous to those used for cerebral infarction, SAH, or traumatic brain injury.

Predictive indicators after hematoma evacuation include age, Glasgow Coma Scale (GCS) score at presentation, hematoma volume (including intraventricular extension), midline shift (MLS), and hydrocephalic alteration, which have been the subject of numerous epidemiological and observational studies. This study aimed to develop a clinical grading scale taking into account different clinical and radiological parameters that are found to be associated with mortality or survival in basal ganglia hematoma patients. This scale helps to decide the management strategy and allows prognostication of surgical outcomes based on 90 days survival rate. Hence, the present study tried to develop a clinical grading system that may help to standardize clinical treatment protocols, clinical research studies and prognosticate the outcome in terms of 90 days survival rate.

Materials And Methods

This prospective study of 351 patients with basal ganglia bleeds was conducted at a tertiary care neurosurgical center from December 2018 to November 2020.

Written informed consent from all the patients and Institutional Ethics Committee (Ethics Committee, PGIMER, Dr RML Hospital, New Delhi, Registration no ECR/78/Inst/DL/2013/RR-19 issued under New Drugs and Clinical Trials Rules, 2019) approval was obtained before starting the study. The decision for operative intervention or conservative management was decided accordingly by independent neurosurgeons in a double-blinded manner taking into account the patient's age, comorbidities, GCS score, and various radiological parameters.

Adult patients >18 years of age with basal ganglia haemorrhage and ictus < 3 days of duration were included in our study. Secondary basal ganglia haemorrhage, GCS score 3 with dilated fixed pupils at presentation, or co-existing brain stem extension of basal ganglia bleed were excluded from the study. The study also excluded patients with rebleeds, those requiring second surgery, or those with severe comorbid illnesses that rendered them unfit for surgery, as well as patients with pure thalamic haemorrhages.

Patient evaluation

Patients were screened and evaluated according to protocol with a detailed medical history and complete neurological examination. Standard lab investigations with CT scans were done at the earliest feasible period.

The volume of hematoma was calculated on CT scan by ABC/2 method5 in which A is the greatest diameter on the largest haemorrhage slice, B is the diameter perpendicular to A, and C is the approximate number of axial slices with haemorrhage multiplied by the slice thickness, and midline shift was calculated at the level of the third ventricle.

Based on clinical-radiological parameters, patients were assessed and evaluated according to the following scoring system (Table 1), a modification of the ICH scale devised by Hemphill et al. in 2001. 6

Table 1: Indicates the specific point assignments used in calculating the modified ICH Score

Parameters

Score 

Age; years

<60

0

>60

1

Comorbidity

Absent

0

Present

1

Side of bleed

Right

1

Left 

2

GCS score

13-15

0

8-12

1

<8

2

Hematoma volume; cc

<15 

1

15-30

2

>30

3

Intraventricular extension

Absent

0

Present

1

With hydrocephalus                                         

2

Midline shift; mm

≤5

0

>5

1

Management 

According to the American Heart Association/American Stroke Association guideline for the initial management of cerebrovascular accidents, patients were initially managed in the emergency department.7 Systolic blood pressure was maintained <140 mmHg using antihypertensive agents. Increased ICP was controlled with osmotic diuretics such as mannitol. No prophylactic antiepileptic drugs were administered.  Whenever feasible, anticoagulation or antiplatelet drugs were discontinued for at least 5 days from the time of admission. CSF diversion was made independent of their need for surgical decompression in patients with basal ganglia bleed with intraventricular haemorrhage (IVH) with hydrocephalus. 

Follow up

Whether conservatively managed or after surgical evacuation, all patients were monitored in the neurosurgical intensive care unit, and multimodality care was given. Strict monitoring and control of blood pressure and blood sugar were done. Any post-operative or ventilator-associated complication was managed accordingly. All patients underwent post-operative CT scans according to their neurological condition. Patients were followed up for at least three months after treatment.

Modified ICH score

The ICH score developed by Hemphill et al. was based on a logistic regression model for all ICH patients. This ICH score was devised both for supratentorial and infratentorial haemorrhage. However, factors that determine the clinical outcome vary significantly in both groups. Apart from the 5 characteristics determined to be independent predictors of 30-day mortality in ICH score advocated by J. Claude Hemphill et al., we found few other factors likely to influence the outcome in basal ganglia bleed patients based on their strength of association. 

According to Nisar et al., 8 restratification of the weight of individual variables in the ICH equation with modification of the ICH score can potentially more accurately establish mortality risk in ICH patients.

The incidence of IVH related to basal ganglia bleed is significantly higher than cerebellar hemorrhages9 or lobar hematomas.IVH, one of the major determinants of outcome in basal ganglia bleeds 10 does not carry the same weightage in infratentorial haemorrhages until associated with acute hydrocephalus. Among patients with intraventricular extension of haemorrhage in the subcortical region or cerebellar region,    hydrocephalus was associated with adverse outcome.11Even in patients not undergoing hematoma evacuation in the subcortical region; associated IVH had adverse outcomes worsening more with concurrent hydrocephalus12 - 14, so the importance of IVH and associated hydrocephalus cannot be ruled out requiring additional points in the grading system.

Various studies have shown a strong association of comorbidities with survival in basal ganglia haemorrhages patients, thus implicating their role in prognostication.15 – 18.Furthermore, the location of hematoma on the dominant side also had a brunt on the outcome compared to the non-dominant side.19 However; no such side-dependent association is seen with hematoma at the cerebellar region. 

The impact of local mass effect varies depending upon the location of hematoma, with basal ganglia bleed producing a more detrimental effect than cortical bleed because of its vicinity to nearby vital structures.  Thus compared to swelling at other locations, basal ganglia swelling have greater association with poor outcome20

 Last but not the least, Hong et al advocated that both ICH and Surgical Swedish ICH (SwICH) scores are the good predictor of morbidity than mortality in patients undergoing surgical intervention for ICH.21So it was the need of time to develop a new ICH score specific to basal ganglia hematomas taking into account various factors likely to influence the outcome independent of management.

We performed a prospective study in basal ganglia bleed patients and tried to develop a scoring system including statistically significant variables associated with survival or mortality which may be used for standardization of care, management and prognostication.

The present study agrees with previous Indian studies, where patients were younger than their Western counterparts. Incidence of young age is uniformly reported from India. It appears to be a characteristic feature of the SICH in the Indian subcontinent.22 –24Hence the cut-off value of age was taken as 60 years which was also proven to be statistically significant (P <0.01).

The GCS can be used objectively to determine patient’s level of consciousness in variety of acute medical and trauma situations. This score has been accepted worldwide to summarize the overall severity and maybe a more appropriate method of neurological assessment for ICH grading scales than the National Institutes of Health Stroke Scale (NIHSS).Moreover, because of varying results of scales that use NIHSS, we followed the GCS score for neurological assessment.

We have used the same classification in head injury patients because of its easy remembrance and reproducibility without providing any alterations to the severity scale, minimizing the chance of errors. Many studies have shown that GCS <8 was associated with poor outcomes in ICH patients. 24, 25

Size of the hematoma in subcortical bleed is the major determinant in decision making for conservative management or operative intervention, with bigger bleeds extending to other vital areas at times, even up to the cortex. Hence it was dichotomized into three categories based on the volume of ICH. Volume<15 cc was mainly associated with conservative management, whereas most patients in the other two groups had an operative intervention. The third group with hematoma volume >30 cc was chosen because it represented a cut point for increased mortality in our cohort, is easy to remember, and is similar to ICH volume cut points used in prior models. Additional points were not assigned for larger hematomas (e.g., >60 cm3) because Rao et al. 26 reported 100% mortality for spontaneous ICH having volume >60 cc. Moreover, when tested, this also did not improve the accuracy of the original ICH Score.

Based on the strength of association of individual parameters, an outcome risk stratification scale (modified ICH score) was developed with 90 days mortality in all patients models. Candidate variables were those with a biologically plausible link to outcome after spontaneous basal ganglia bleed based on prior publication or those associated with the outcome on univariate analysis. Variables assessed include age, sex, bleeding side, comorbidity, GCS score, smoking/alcoholism, antiplatelets (AP) and oral anticoagulants (OAC), hematoma volume, IVH, midline shift. Multivariate logistic regression analyses, initially including all potential predictor variables in the model, were performed, with stepwise elimination of variables not contributing to the model (P>0.05).

In order to determine the modified ICH Score, continuous variables were categorized and assigned certain points: GCS score of 13 to 15 (0 points), 8 to 12 (1 point) and < 8 (2 points); Volume of the hematoma was divided into 3 categories;<15cc (1 point), 15-30cc (2 point) >30cc (3 points); and age was divided into 2 categories, <60 years (0 points), >60 years (1 points). For the same purpose, points were assigned to 2 categorical variables: IVH absent (0 points), IVH present (1 point), and IVH associated with hydrocephalus (2 points); MLS was categorized into less than 5mm (0 points) and more than 5mm (1 point).

Statistical analysis 

Statistical analysis was performed with SPSS (version 10.0) and Stata (version 5.0), and P<0.05 was considered statistically significant. Variables studied include age, sex, comorbidity, GCS, hematoma volume, IVH, MLS, bleeding side, antiplatelet/oral anticoagulants, and smoking/alcoholism.

 For all patients with basal ganglia haemorrhages, only age, GCS, comorbidity, ICH volume, MLS, side of bleed,  and IVH were found to be significantly associated with mortality(P<0.05)  (Table 3)

Dichotomous variables like the side of bleed, sex, presence or absence of comorbidities, IVH, and its association with hydrocephalus were compared using the Chi-square test. In contrast, continuous variables like GCS, age, ICH volume, midline shift were categorized into different subgroups and compared subsequently using the Chi-Square test. Multivariate logistic regression analyses were performed, including all variables found significant in the model, with dropping of variables to calculate the modified ICH score not found significant in multivariate analysis (Table 4).

Results

351 were enrolled in the present study, 12 patients were lost in follow-ups, and so 339 patients were included in our study group. 

Of the patients, 25.66% were female (n=87) and 74.33% were male (n=252). The mean age was 50.9 years (25th to 75th interquartile range 42-60 years) and 28.02% (n=95) were above 60 years whereas 71.97% (n=244) were 60 or below 60 years (Table 2). 

Comorbidities were present in 69.32 % (n=235) and 30.67% (n=104) were without any comorbidities (Table 2). Of the 235 patient who had comorbidities 51.91 % (n=122) had hypertension, 29.36% (n=69) had Diabetes Mellitus, 14.04% (n=33) had hyperlipidemia, and 0.017 % (n=4) had chronic renal failure. Cardiac abnormalities in the form of heart blocks and arrhythmia were present in 2.97% (n=7) patients (Table 2).

The systolic blood pressure values ranged from 130 to 224mmHg with a mean of 170.04± 57.08 mmHg, and the diastolic blood pressure values ranged from 92 to 126 mmHg with a mean of 100.0 ±14.02mmHg.The smoking or alcohol consumption history of 160 patients was available, and 64.37% (n=103) of them were smokers, but 23.12% (n=37) had a history of alcohol consumption, whereas 12.5% (n=20) patients had a history of both smoking and alcohol consumption. Clear medical history was available for 109 patients, and 95.41% (n=104) were using antiplatelets (AP), and 4.58% (n=5) were using oral anticoagulants (OAC drugs). 35.10% (n=119) had right-sided bleeding and in 48.67% (n=165) hematoma was present on the left side (Table 2).

The volumes of the hematomas ranged from 8 to 70 cm3 with a mean of 25.28±9.58 cm3. When classified by volume, 8.2% (n=28) of the hematomas were small (<15 cm3), 65.48% (n=222) were medium (15–30 cm3) and 26.25% (n= 89) were large (> 30 cm3) (Table 2). Ventricular extension of the haemorrhage was present in 49.85% (n= 169) of patients, with associated hydrocephalus in 10.32% (n=35) (Table 2). Out of 35 patients, 68.57% (n=24) had EVD insertion with 32.42 %( n=11) had concurrent EVD insertion and hematoma evacuation.

 Midline shift >5mm was present in 51.03% (n= 173) (Table 2).The GCS neurological scores ranged from 4 to15, with a median GCS score on admission being 10 (25th to 75th interquartile range 7 to 12). 25.95% (n=88) had a GCS score < 8, 51.03% (n=173) had a GCS score between 8-12 and 23.0% (n= 78) had GCS of 13-15 (Table-2). 

   85.9%(n=67) of the patients in the group having GCS score of 13-15 survived out of 78 patients, whereas 78.6% (n=136) patients survived out of 173 patients in the GCS group having a score of 8-12 and only 9.1%(n=8) patients survived out of 88 patients having GCS score less than 8 (Table 2), this was similar to the mortality rate reported by Brodrick JP et al. 27 in their study.

Age also had a substantial impact on mortality, with people over 60 years having a mortality rate of 56.8 %( 54 out of 95 patients) (Table-2). Contrary to the original ICH score, the location of hematoma in the dominant hemisphere significantly impacted survival, with only 70 (42.42%) patients surviving out of 165 patients. In contrast, the survival rate was 74.13 %( n=129) in 174 patients in the non-dominant hemisphere (Table 2). 

Previous studies have shown that the development of hydrocephalus with IVH is associated with the adverse outcome, which was also validated in our research. Thus, an additional point was given to patients who developed hydrocephalus concurrent with IVH. In the absence of IVH, the survival rate was 92.6% which was reduced to 49.1% when IVH was present and further reduced to 8.6% in IVH with hydrocephalus (Table 2). Among 31 who died in the conservatively managed group, 25 patients had associated hydrocephalus and EVD insertion. Thus IVH associated with hydrocephalus was a major risk factor in basal ganglia bleeds patients managed conservatively. Only 3 patients with IVH and hydrocephalus survived in the conservatively managed group.

A total of 87.3 %( n=23) patients survived having ICH volume less than 15cc. The survival rate was 81.5 %( n=181) in patients having hematoma volume between 15-30cc, whereas only 7.9 %( n=7) patients survived having ICH volume >30cc (Table 2).

Table 2: Patient demographic profile of spontaneous basal ganglia hematoma

Parameters 

Alive

N (%)

Expired

N (%)

Total

(N)

Age in years

Less than 60

170 (69.7)

74 (30.3)

244

60 and above

41 (43.2)

54 (56.8)

95

Side

Left 

92  (55.8)

73 (44.2)

165

Right 

119(68.4)

55 (31.6)

174

Comorbidity 

Present

92 (88.5)

12 (11.5)

104

Absent 

119 (50.6)

116 (49.4)

235

IVH

Absent

125 (92.6)

10 (7.4)

135

Present

83 (49.1)

86 (50.9)

169

With Hydrocephalus

3  (8.6)

32 (91.4)

35

Volume; cc

<15

23 (82.1)

5 (17.9)

28

15-30

181 (81.5)

41 (18.5)

222

>30

7 (7.9)

82 (92.5)

89

GCS categories

13-15

69 (87.3)

10 (12.7)

79

8-12

114 (69.1)

51 (30.9)

165

<8

28 (29.5)

67 (70.5)

95

Midline Shift; mm

<5

150 (90.4)

16 (9.6)

166

>5

61 (35.3)

112 (64.7)

173

Sex

Male

154 (61.1)

98 (38.9)

252

Female 

57 (65.5)

30 (34.5)

87

Use of antiplatelet/

oral anticoagulants

Present

46 (42.2)

63 (57.8)

109

Absent 

108 (46.9)

122 (53.0)

230

Smoking/Alcohol

Present

98 (61.2)

62 (38.7)

160

Absent

94 (52.5)

85 (47.4)

179

Out of 339 patients, 94 patients (27.72%) were managed conservatively, whereas 69.02 %( n=234) underwent craniotomy with hematoma evacuation and 3.2% (n=11) had craniectomy with hematoma evacuation.  

At the 3-month follow-up, 62.24% (n=211) of all patients survived, and the mortality was 37.75% (n=128). Out of 245 patients operated, 148 patients were alive at the end of 3 months, and the mortality rate was 39.59%. In the conservatively managed group, 63 patients survived out of 94 patients, and mortality was 32.9%. 

The modified ICH scores range was 1 to 12 (Table 1). No patients with a modified ICH Score of 1 died, whereas all patients with a modified ICH Score of 12 died.

The survival rate in patients having modified ICH scores of 7 or less than 7 was 91.66%. However, it decreased to 12.19% in patients having a score > 7(Table 5). For patients with a score of ≥7, each increase in the ICH Score was associated with a progressive increase in 90-day mortality (P<0.05 for trend), supporting a statistically significant association between score and outcome. The mortality rates for patients with modified ICH Scores of 7, 8, 9, 10, and above were 30.7%, 71.4%, 93.5, and 100%, respectively.

  Among 128 patients who died, the mean modified ICH score was 9 (25th to 75th interquartile range 8 to 10), and for the remaining 211 patients who survived modified ICH score had a median and mode of 5 (25th to 75th interquartile range 5-6)

Table 3: Univariate analysis of characteristics of spontaneous basal ganglia hematoma cohort (n=339)

Variable

P value

Age group

<0.001

Gender

     0.47

Side of bleed

<0.001

IVH 

<0.001

Co-morbidities

<0.001

Volume of Hematoma

<0.001

GCS categories

<0.001

Midline Shift

<0.001

Use of antiplatelets/

Oral anticoagulants

      0.41

Smoking/alcoholism

     0.10

Table 4: Multivariate analysis of factors associated with survival of basal ganglia bleed patients

Parameter

AOR (95% CI)

P value

Age (Less than 60)

5.1 (1.9-13.0)

0.001

Right side

4.4 (1.7-11.4)

0.002

IVHAbsent

18.1 (2.6-124.6)

0.003

IVH Present

6.7 (1.03-43.5)

0.04

Absence of Co-morbidities

16.6(4.3-51.8)

<0.001

Volume in cc (<30)

14.9  (3.8-47.3)

<0.001

GCS categories (13-15)

4.8 (1.4-16.8)

0.01

GCS categories (8-12)

5.8 (1.9-17.0)

0.002

Midline shift <5

16.1 (4.9-53.4)

<0.001

Table 5: Diagnostic accuracy of modified ICH score in predicting survival (Cut-off of 7 for modified ICH score derived from ROC)

Total score

Outcome

Total 

Alive 

Expired

≤7

198

18

216

>7

13

110

123

Total

211

128

339

Table 6:- Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value of modified ICH score

Parameter 

Point estimate 

95 % Confidence limit

Sensitivity

93.8

89.7-96.7

Specificity

85.9

78.7-91.4

Positive predictive value

91.7

87.1-95.0

Negative predictive value

89.4

82.6-94.3

Diagnostic accuracy

90.9

87.2-93.7

 ROC analyses of modified ICH score with prognostication   

The graph was above the 45-degree line for the modified ICH score and covers 92.93% (95% CI for AUC 89.4-96.4) of the area under the ROC curve (AUC) (Fig-3), indicating that modified ICH score is a reliable predictor of survival in basal ganglia bleed patients.

 Modified ICH score of 7 or less than 7  (Table-5, Fig-2) could predict the survival in 93.8% (95% CI 89.7-96.7) of patients of basal ganglia bleed who were alive after 90 days (sensitivity) and had a specificity of 85.9%% (Table-6)

Out of 211 patients who were alive, including both conservatively managed and those who underwent operative intervention modified ICH score of less than or equal to seven was present in 198 patients. The positive predictive value of modified ICH score 7 or < 7 was 91.7% (95%CI 87.1-95.0) (Table-6)

Thus, a modified ICH score of 7 or less than 7  showed significant association with survival, with the sensitivity of 93.8% and the positive predictive value of 91.7% (95%CI 87.1-95.0) (Table-6)

The diagnostic accuracy is 90.9% (95% CI 87.2-93.7) (Fig-3)

ROC analysis of modified ICH score and choice of management

Ignoring the outliners the graph is well above the 45 degree line (Figure 4). The AUC obtained for the modified ICH score in deciding the management is 62.4% (95% CI for AUC 55.3-69.4). On looking at the coordinates of ROC curve at cut off of 6.50, sensitivity of modified ICH score in predicting surgery is 49.8% (true positive) however, there are 34% chances that decision can lead to false negative outcome. . Thus in patients with modified ICH score of 6 or above surgery can be opted (p value<0.001). 

Discussion

In practice, a variety of grading systems are used to standardize the clinical classification, prognosis, and management of patients with acute neurological disorders. Many such grading systems for prognosis of spontaneous ICH have been developed in the past, but several of these scales used complex algebraic expressions for outcome prediction. An ideal grading scale should be simple to use, requiring no special statistical knowledge while maintaining efficacy and sensitivity. It is likely that the lack of a clinical grading system specific to basal ganglia bleed has resulted in disparities in clinical care, management, and prognosis.

Thus factors like age, GCS score, presence of comorbidities, hematoma volume, side of bleed, midline shift>5mm, and IVH were found to be statistically significant and were included in our decision-making and grouped to develop a modified ICH score. These factors impact patient treatment and prognosis, influencing the result either way. The patient's final score was calculated. It was analyzed statistically to find the best possible score below which the patient had at least 90 days survival rate irrespective of the type of management. Also, we tried to find out a minimum score above which surgery was advisable and a score above which the outcome was adverse despite of surgical management.

Age is an important factor that significantly affects post-operative recovery and response to conservative management. There is a greater mortality rate among the oldest-old regardless of ICH features. However, evidence from cohort studies are limited to sustenance this claim. According to Hegde et al., 28age was an independent predictor of mortality with age more than 70 years was associated with poor outcomes. However, because of the relatively younger age of incidence in the Indian population, we took 60 years as a cut-off value which was statistically proven significant.

A study by Gonzalez-Perez et al. assessed 30-day mortality and concluded that age, apart from increasing the prevalence of ICH, also increased the 30-day mortality rate.29 Sacco et al. also reported similar findings in a prospective analysis of 549 patients with ICH.30

On the other hand, a retrospective study published by Forti et al. in 2016 concluded that increasing age did not affect 1-year mortality in elderly subjects with acute supratentorial ICH.31 In our study, we found that patients more than 60 years of age had a significantly high mortality rate of 56.8%.

We also found a significant correlation between comorbidities like hypertension and diabetes   with mortality in basal ganglia bleed patients. For ICH, hypertension is the most evidence-based and consistent risk factor. It was significantly associated with the worst clinical outcome.

Patients with significantly high blood pressure on admission and persistent inadequate blood pressure control adversely affect the prognosis in hypertensive intracerebral haemorrhage. 15

Likewise, DM also adversely affected the outcome in basal ganglia bleed patients. This could be attributed to the increased incidence of IVH and infectious complications in diabetic patients. Arboix et al. concluded that diabetes mellitus was an independent risk factor associated with mortality among ICH patients. In the diabetic and non-diabetic groups, the overall in-hospital mortality rate was 54.3% and 26.3% (P < 0.001), respectively.18 Similarly, Passero et al. also found in their study of 764 patients with ICH that high plasma glucose was associated with a greater incidence of infectious and cerebral complications and served as an independent predictor of 30-day and 3-month mortality.16 In addition to this, preictal history of heart disease has also been associated with the increase in the 30-day mortality rate in basal ganglia bleed patients.17

Left hemispheric sites of ICH were identified as significant and independent predictors of 30-day mortality19, which was consistent in our study.

GCS score32 hematoma volume 33, midline shift34, and intraventricular hemorrhage35, with or without hydrocephalus36 were independent risk factors associated with mortality and a significant determinant of surgical outcome. 

In a study of 30-day mortality rates based on ICH volume, Broderick et al. 27 found that ICH volumes <30 cm3 had a 23% mortality rate for basal ganglia bleeds, ICH volumes between 30 and 59 cm3 had 64% mortality for deep haemorrhages, and ICH volumes >60 cm3  was associated with  93 percent deaths. Our mortality rates (19.4%) were similar to those reported by Broderick et al. for deep haemorrhage having hematoma volume <30 cc (23%). However, mortality rates were 92.1% for hematoma volume > 30cc in our study group. This difference in mortalities can be attributed to relatively more patients with hematoma volume greater than 60 cc in our third group ((volume >30cc).

Panchal et al. 37 reported a nearly10 percent survival rate in people with ICH with hematoma volume >30cc, consistent with our study.

OAC may be an independent predictor of mortality in basal ganglia bleed patients. Still, according to Houben et al., the addition of OAC use did not increase the predictive value of the original ICH score. 38However, in our study population, most of the patients were on antiplatelet, and the use of OAC was limited to a few patients only.

Likewise, smoking was also not associated with an increase in 30 days mortality in our study population, as published by Juvela39 and Thrift et al 40.

Management of Basal Ganglia bleeds

There is a consensus for management for cerebellar haemorrhages with mass effects or lobar haemorrhages in young patients with worsening neurologic status, in which emergent decompressive surgery is indicated. However, there are no clear-cut guidelines regarding the management of basal ganglia bleed as treatment protocol is decided considering multiple factors like size of bleed, intraventricular extension, GCS score, etc. Moreover, there is a paucity of evidence-based guidelines regarding its surgical management. There is no doubt that early diagnosis and attentive care of patients with basal ganglia bleeding are superior and crucial, given the likelihood of rapid deterioration in the first few hours after onset and early hematoma evacuation can reduce the physical and chemical damage to the surrounding brain.

Randomized trials comparing surgery to conservative management have not demonstrated a clear-cut benefit for surgical intervention, whereas some have strongly advocated surgical management.

 In 1995 a landmark multi-central trial for intracerebral haemorrhage (STITCH TRIAL) randomized 1033 patients with spontaneous supratentorial intracerebral haemorrhage within twenty-four hours to early surgery or initial conservative best medical therapy. It concluded that there is no benefit from early craniotomy in supratentorial intracerebral haemorrhage compared to initial conservative management. But there was significant crossover from conservative to surgical treatments thereby possibly reducing the unfavourable outcome percentage in conservatively managed group which could have been higher in the absence of crossover. This raises a question on the generalizability of the results of such trials. Furthermore, large numbers of patients were excluded in the STICH II trial (> 3300) at randomization because of either impaired level of consciousness or at risk of herniation, adding additional selection bias to the study. 

Two prospective randomized trials and three meta-analyses have been completed in the recent past that compared surgery versus conservative treatment for ICH.41-43

For the past few years, various surgical options have been considered ranging from decompressive craniectomies to minimally invasive endoscopic approaches. A meta-analysis was done by Zhou et al. in 2012 44, and Gregson et al. 45 in 2013 suggested the superiority of minimally invasive techniques over craniotomy. Still, methodological issues with this analysis have been raised. In the STITCH trial, around 77% of cases, craniotomy was the surgical procedure of choice. The remaining patients had similar numbers of hematomas removed via burr hole, endoscopy, or stereotaxy. Majority of cases in our surgical managed group underwent craniotomy and hematoma evacuation with decompressive craniectomies limited to few patients only.

Various recent retrospective studies have advocated the role of decompressive craniectomies in patients with GCS score<8, large hematomas having midline shift, and ICP not responding to medical management. 46, 47,48 In our study, 234 (69.02%) patients had craniotomies, while 11(3.2%) underwent decompressive craniectomies with hematoma evacuation. The decision for decompressive craniectomy was taken intraoperatively when even after removing the hematoma, the brain was tensed and/or nonpulsatile, and it was impossible to replace the bone.

In our study ROC curve analysis clearly showed that surgery can be opted in basal ganglia bleed patients having modified ICH score of 6 and above and patients with score of 10 or more surgery was futile as there was 100 percent mortality at this score. Thus, apart from prognostication, our scale may also help in deciding the appropriate management strategy. 

 

Various outcome predictor scales like the ICH score 6 have been developed in past for ICH that helps in predicting the functional outcome or mortality. While prognostication is undoubtedly essential to assess treatment benefits and risks and provide patients and families with information regarding the severity of illness, these scales failed to comment on management strategies. Our scale is different from these scales as rather than merely a prognostic value, it also helps in deciding the best possible management and surgical outcome in terms of mortality.

With regard to outcome in terms of 3 months mortality, our score offers excellent or out-standing discrimination between patients in comparison to all other scales. A 93% area under the ROC curve was found to be the highest of any study for spontaneous ICH.

 Among various scales used for spontaneous ICH, Essen ICH and secondary ICH score (sICH) have the highest AUCs for in-hospital mortality, 3-month mortality, and 3-month poor functional outcome. Still, they do not incorporate any radiographic characteristics 49, limiting its usefulness as a therapeutic scale since radiological parameters are significant determinants of therapeutic intervention.

 Existing ICH grading scales had limited usefulness in patients of ICH with intraventricular or subarachnoid extension. Patients with incorrectly predicted mortality (indicated by a disagreement between the maximum Youden Index and mortality for the given scale) have a higher proportion of IVH than patients with correctly predicted mortality.

This difference is statistically significant in a few scales like New ICH, original ICH (oICH),   modified ICH-A (mICH-A). However, in our study, precedence was given to IVH with an additional point to IVH associated with hydrocephalus which was also proven statistically.

Furthermore, the importance of the etiological factor in causing spontaneous ICH in cortical-subcortical and infratentorial regions cannot be ruled out. ICH associated with vascular malformations has been shown to have lower mortality rates and improved functional outcomes than other types of spontaneous ICH. 50 Our study incorporated pure hypertensive basal ganglia bleed excluding bleed due to other etiological factors, thereby eliminating the confounding effect of different aetiologies.

Prognosis after subcortical bleed is often a fundamental question. There is no scale available specific to basal ganglia bleed that can be used to provide initial information regarding this. In addition to prognostication, a modified ICH score offers a framework for clinical decision-making and a reliable criterion for assessing the efficacy of new treatments. Thus improved standardization of clinical assessment with a grading scale such as the modified ICH Score is likely to provide more consistency in clinical care and clinical research for subcortical bleed; just as similar assessment scales have provided consistency in traumatic brain injury, aneurysmal SAH, and ischemic stroke. Our scale can thus help translate current research into effective interventions.

Limitations

The operated cases were not pure basal ganglia bleeds. It often extended to a cortical- subcortical junction or the cortex and or thalamus. The incidence of using oral anticoagulants was significantly less in our study group, so there is a possibility of altering the result with an increase in the number of patients on oral anticoagulants. Our findings are limited by some shortcomings. There could have been other possible variables which were statistically significant in influencing the outcome.

Conclusions

The modified ICH score offers excellent prognostication and guides therapeutic interventions. Patients with a score of 7 or  less than 7 had a better outcome, while patients with a score greater than 7 had a poorer outcome.

At scores of 6 and above, surgical intervention was recommended, and 100% of patients died at scores of 10 and more regardless of procedure.

Declarations

Ethical Approval 

-- Ethical approve was taken from Institutional Ethics Committee (Ethics Committee, PGIMER, Dr RML Hospital, New Delhi, Registration no ECR/78/Inst/DL/2013/RR-19 issued under New Drugs and Clinical Trials Rules, 2019)

-- Informed consent was taken for the case series as well as for medical management and surgical procedure

--Any portion of the contents of the paper was not presented previously

-- Routine treatment was done as per literature and in this case series no animal was used.

Competing interests 

The authors report no competing interests.

Authors' contributions 

Author 1:-Dr Rahul Varshney-- provided the research idea, prepared the manuscript and supervised the research work

Author 2:- Dr. Nitish Arora-- data collection and lab work

Author 3:-Dr Varun Khullar-- helped in data collection and statistical part

Funding 

--No financial and material support taken from any organization.

--No external funding was received

Availability of data and materials 

-- Datasets generated and/or analysed during the current study are available with reasonable request from the corresponding author.

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