Bilateral basal ganglia hemorrhage: a systematic review of etiologies, management strategies, and clinical outcomes

Abstract

Bilateral basal ganglia hemorrhages (BBGHs) represent rare accidents, with no clear standard of care currently defined. We reviewed the literature on BBGHs and analyzed the available conservative and surgical strategies. PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies reporting patients with BBGHs. Clinical characteristics, management, and outcomes were analyzed. We included 64 studies comprising 75 patients, 25 (33%) traumatic and 50 (67%) non-traumatic. Traumatic cases affected younger patients (mean age 35 vs. 46 years, p=0.014) and males (84% vs. 71%, p=0.27) and were characterized by higher proportion of normal blood pressures at admission (66% vs. 13%, p=0.0016) compared to non-traumatic cases. Most patients were comatose at admission (56%), with a mean Glasgow Coma Scale (GCS) score of 7 and a higher proportion of comatose patients in the traumatic than in the non-traumatic group (64% vs. 52%, p=0.28). Among the traumatic group, motor vehicle accidents and falls accounted for 79% of cases. In the non-traumatic group, hemorrhage was most associated with hypertensive or ischemic (54%) and chemical (28%) etiologies. Management was predominantly conservative (83%). Outcomes were poor in 56% of patients with mean follow-up of 8 months. Good recovery was significantly higher in the traumatic than in the non-traumatic group (48% vs. 17%, p=0.019). BBGHs are rare occurrences with dismal prognoses. Standard management follows that of current intracerebral hemorrhage guidelines with supportive care and early blood pressure management. Minimally invasive surgery is promising, though substantial evidence is required to outweigh the potentially increased risks of bilateral hematoma evacuation.

Supplementary Information

The online version contains supplementary material available at 10.1007/s10143-023-02044-x.

Introduction

Intracerebral hemorrhage (ICH) is the second most common cause of stroke, accounting for 10–15% of worldwide cases and leading to major morbidity and mortality [1, 2]. Basal ganglia (BG) hemorrhages represent singular entities, mostly occurring in spontaneous ICH and less frequently in traumatic ICH [3, 4]. Bilateral basal ganglia hemorrhages (BBGHs) are extremely rare and poorly studied. In view of the BG’s deep location and highly metabolic nature, BBGHs may arise from coup-contrecoup contusions after closed-head injury, hypertensive crises, cerebral venous thrombosis, viral infections, or chemical poisoning [5–9]. Clinical presentation is severe and prognosis dismal, characterized by early neurological deterioration from hematoma expansion and corticospinal tract compression, secondary injury from perihematomal brain swelling with intracranial hypertension, and late hemotoxicity from blood degradation products [10, 11].

Several trials investigated and compared the role of conservative medical care, open surgical hematoma evacuation, minimally invasive/endoscopic hematoma aspiration, and thrombolysis in the treatment of traumatic and non-traumatic ICHs [12–15]. Although surgical intervention was generally not associated with significant improvements in outcome over standard conservative therapies, evidence suggests benefit for certain subgroups, particularly those with larger hemorrhage volumes and higher baseline Glasgow Coma Scale (GCS) scores [16, 17]. Endoscopic and minimally invasive surgical approaches appear to be more favorable in patients with deep-seated hematomas involving the BG and the thalami [18, 19]. Still, the surgical-related risks should be considered, with a particular focus on complex cases such as BBGHs.

Although operative and non-operative management strategies have been widely studied for unilateral BG ICHs, only few reports on BBGHs are currently available, heterogeneous in clinical characteristics and treatments. In this systematic review, we comprehensively summarized demographics, etiologies, clinical features, and management strategies of BBGHs, further analyzing the impact of current treatments on patient functional outcomes and survival.

Methods

Literature search

A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20]. PubMed, Scopus, Web of Science, and Cochrane were searched from database inception to March 27, 2022, using the combination of the Boolean operators “OR” and “AND” and the following search terms: “bilateral,” “basal ganglia,” and “hemorrhage.” Studies were uploaded to Mendeley, and duplicates were removed.

Study selection

A priori inclusion and exclusion criteria were defined. Studies were included if they (1) included patients with radiologically confirmed intracranial hematomas/hemorrhages involving the bilateral BG; (2) reported available data on clinical features, treatment strategies, and post-treatment outcomes; and (3) were written in English. Studies were excluded if they were (1) literature reviews, autopsy reports, or animal studies; (2) studies with unclear distinction between patients with BBGH and patients with other types of intracranial hemorrhages; and (3) studies lacking 2 or more of patients’ demographics, clinical presentation, management strategies, or post-treatment outcomes.

Two independent reviewers (G.W. and P.P.) screened titles and abstracts of all retrieved studies, and then assessed full texts of articles that met inclusion criteria. Disagreements were solved by a third reviewer (G.E.U.). Eligible studies were included based on the predefined criteria, and references were screened for additional relevant articles.

Data extraction

Data were extracted by two authors (A.C. and C.O.), and then confirmed independently by one additional author (G.W.). Missing data were either not reported or not differentiable from other non-relevant data. Extracted data included authors, year, age, gender, etiology, past medical history, level of consciousness, location of hemorrhage, dominant hemisphere, presence of concurrent intracranial hemorrhage, blood pressure, glucose level, GCS at admission and discharge, radiological exam and findings, hemorrhage volume, management type and details, complications, follow-up duration, overall survival, prognosis, and vital status. The prognosis was categorized based on the descriptions provided in the texts using the Glasgow Outcome Scale (GOS). Good recovery was defined as lack of symptoms or minor deficits not affecting activities of daily living (e.g., “No focal neurological deficits,” “GCS 15,” “Able to work as before”). Moderate disability was defined as having some disability interfering with the ability to resume work, school, or other previous activities, but the individual remains independent (e.g., “Deaf,” “Some motor weakness”). Severe disability was defined as needing partial or full assistance of activities of daily living (e.g., “Hemiparesis,” “Bilateral optic atrophy”). A vegetative state was defined as an absence of awareness of self and the environment (e.g., “Comatose”). Based on etiologies, BBGHs were divided into traumatic and non-traumatic groups.

Data synthesis and quality assessment

Primary outcomes of interest were patient demographics (age, gender, past medical history), clinical characteristics (signs and symptoms, vitals, labs, GCS), hemorrhage characteristics (postulated etiology, location, concurrent hemorrhage, hemorrhage volume), management (conservative vs. surgical), and outcomes (length of stay, follow-up, improvement in symptoms, clinical status, overall survival, prognosis). The level of evidence of each article was evaluated upon the 2011 Oxford Centre For Evidence-Based Medicine guidelines [21]. Meta-analysis was precluded because all included studies were level IV or V of evidence, and hazard ratios could not be deducted. The risk of bias of each article was independently assessed by two authors (A.C. and G.W.) using the Joanna Briggs Institute checklists for case series [22].

Statistical analysis

Descriptive analyses were performed using SPSS V.25 (IBM Corp, Armonk, NY). Continuous variables are summarized as means with standard deviation and range. Categorical variables were reported as frequencies and percentages. Comparisons between the traumatic and non-traumatic groups were conducted using chi-square tests for categorical variables or Fisher’s exact test for categories with less than five observations, and t-test for continuous variables only for the features reliably and consistently reported among each category type.

Results

Study selection

Figure 1 illustrates the study selection process. The initial search yielded 684 citations (PubMed: 197; Scopus: 321; Web of Science: 155; Cochrane: 11), of which 64 studies were finally included upon the pre-determined criteria: 4 case series (involving 9 patients) and 60 case reports (involving 66 patients), categorized as level IV and V of evidence, respectively (Table 1). Quality assessment resulted in low risk of bias for all included studies (Supplementary File 1).

Fig. 1.

PRISMA 2020 flow diagram

Table 1.

Overview of all included studies

No.	Authors - Year	Study design – LOE	Sex	Age	Etiology*	BP	Locations	GCS1	Management	LOS (days)	Improved?	GCS2	OS** (mon)	Outcomes	Prognosis	Status
Traumatic
1	Nagano et al. – 1980 [23]	Case report – V	M	3	Penetrating head injury	-	-	-	Surgical	-	-	-	-	-	-	A
2	Lodder & Baard – 1981 [24]	Case report – V	F	75	-	-	DS	-	Conservative	-	Yes	-	-	Arm rigidity, decreased facial expression	Moderate disability	A
3	Ozgun & Castillo – 1995 [25]	Case report – V	M	32	Lightning strike	140/90	LN	-	Conservative	5	Yes	-	8	Deaf	Moderate disability	A
4	Jang et al. – 2007 [26]	Case report – V	M	50	Fall	WNL	-	15	Conservative	14	-	-	0.47	No FND	Good recovery	A
5	Ishihara et al. – 2009 [27]	Case report – V	M	0.92	Fall	WNL	CS	-	Conservative	9	Yes	-	25	No FND	Good recovery	A
6	Kaushal et al. – 2011 [28]	Case report – V	M	42	MVA	136/88	LN, EC	5	Conservative	14	Yes	15	-	Some motor weakness	Moderate disability	A
7	Aygun et al. – 2012 [29]	Case report – V	M	35	Blast injury	WNL	-	-	Conservative	7	Yes	15	-	No FND	Good recovery	A
8	Bhargava et al. – 2012 [30]	Case report – V	M	25	MVA	WNL	BG	4	Conservative	35	Yes	-	-	Dysphasia, R spastic hemiparesis	Severe disability	A
		Case report – V	M	50	MVA	WNL	BG	4	Conservative	-	Yes	-	-	Motor improvement	-	A
9	Jain et al. – 2013 [31]	Case report – V	M	38	Fall	WNL	-	15	Conservative	5	-	15	2	No FND	Good recovery	A
10	Calderon-Miranda et al. – 2014 [32]	Case report – V	M	28	MVA	WNL	-	6	Conservative	7	No	-	0.1	Dead	-	D
11	Pandey et al. – 2014 [33]	Case report – V	M	37	MVA	WNL	CG	6	Surgical	28	No	6	-	Coma	Vegetative state	A
12	Vega et al. – 2015 [34]	Case report – V	M	57	Assault	-	LN	8	Conservative	17	Yes	15	18	Memory deficits, temporal disorientation, dyscalculia	Severe disability	A
13	Baek et al. – 2016 [35]	Case report – V	M	6	MVA	-	-	6	Surgical	39	No	-	-	Vegetative state	Vegetative state	A
14	Bathla et al. – 2016 [5]	Case report – V	M	16	MVA	WNL	-	4	Surgical	6	No	-	0.2	Dead	-	D
		Case report – V	M	22	MVA	-	LN	3	Surgical	6	No	-	0.2	Dead	-	D
15	Kankane et al. – 2016 [36]	Case report – V	M	20	MVA	WNL	BG	9	Conservative	3	Yes	15	3	No FND	Good recovery	A
		Case report – V	M	45	MVA	WNL	CG	10	Conservative	5	Yes	15	3	No FND	Good recovery	A
16	Zhang et al. – 2016 [9]	Case report – V	F	45	Fall	160/100	-	8	Conservative	29	Yes	15	1	L hemiparesis	Severe disability	A
17	Reddy et al. – 2019 [37]	Case report – V	M	34	MVA	WNL	-	5	Conservative	-	No	-	0.1	Dead	-	D
		Case report – V	M	40	MVA	-	-	7	Conservative	-	Yes	14	-	-	Good recovery	A
		Case report – V	F	40	Fall	-	-	10	Conservative	20	Yes	15	-	-	Good recovery	A
18	Lee et al. – 2020 [38]	Case report – V	M	33	Assault	100/60	GP	15	Conservative	28	-	15	7	No FND	Good recovery	A
19	Mughis et al. – 2020 [39]	Case report – V	M	30	MVA	230/118	-	12	Conservative	5	Yes	15	-	No FND	Good recovery	A
20	Anh et al. – 2022 [40]	Case report – V	F	63	MVA	150/90	LN	9	Conservative	31	Yes	15	2	Initial quadriplegia and aphasia, normal strength and speech recovered 2 mo later	Good recovery	A
Non-traumatic
21	Finelli et al. – 1984 [41]	Case report – V	M	57	-	104/60	GP	-	Conservative	-	Yes	-	-	Quadriplegic, mute	Severe disability	A
22	Naheedy et al. – 1985 [42]	Case report – V	F	30	Preeclampsia	-	BG	-	-	-	-	-	-	-	-	A
23	Sato et al. – 1986 [43]	Case report – V	M	45	Anticoagulants	-	P	-	Conservative	30	Yes	-	1	Walking with cane, motor dysphasia, dysphagia, dysarthria, L hemiparesis	Severe disability	A
24	Erbguth et al. – 1991 [44]	Case series – IV	F	48	VT	-	BG	-	Conservative	73.5	Yes	-	-	Choreatic movement of R hand	Moderate disability	A
25	Fujioka et al. – 1994 [45]	Case report – V	M	69	CA	-	CS	-	-	40	No	-	1.33	Vegetative state	Vegetative state	A
26	Kabuto et al. – 1995 [46]	Case report – V	M	65	HTN	-	P, ventricles, IC	-	Conservative	-	No	-	0.13	Dead	-	D
27	Nagatomo et al. – 1995 [8]	Case report – V	F	50	VT	-	BG	-	Conservative	21	Yes	4	0.7	No FND	Good recovery	A
28	Wang & Shen – 1995 [47]	Case report – V	M	40	VT	-	BG	-	Conservative	20	-	-	1	No FND	Good recovery	A
29	Ertl-Wagner – 1999 [48]	Case report – V	F	59	DKA	-	BG	-	Conservative	7	Yes	-	-	Paraparesis, bilateral facial palsy, dysdiadochokinesis, impaired coordination and fine motor function	Moderate disability	A
30	Pidcock et al. – 1999 [49]	Case report – V	F	8	-	140/100	P	-	Conservative	30	Yes	6	-	Decreased drooling, improved language production, use of communication board	Severe disability	A
31	Raabe & Krug – 1999 [50]	Case report – V	M	46	HTN, HA	135/75	BG	-	Conservative	-	Yes	-	-	Severely disabled	Severe disability	A
32	Kohshi et al. – 2000 [51]	Case report – V	F	76	HTN	196/90	Thal, P, IC	-	Conservative	28	Yes	-	-	Slight hemiparesis	Moderate disability	A
33	Cho et al. – 2002 [52]	Case report – V	M	40	HHS	-	P	-	Conservative	-	No	-	24	Vegetative state	Vegetative state	A
34	Silliman et al. – 2003 [53]	Case report – V	M	35	HTN	180/104	P	-	Conservative	10	No	-	-	Dead	-	D
35	Caparros-Lefebvre et al. – 2005 [54]	Case report – V	M	50	EG	-	GP	-	Conservative	30	Yes	14	6	No FND	Good recovery	A
36	Sarkar et al. – 2005 [55]	Case report – V	M	40	JE	180/90	BG	-	Conservative	-	Yes	-	2	Mild emotional lability	Good recovery	A
37	Yen et al. – 2005 [56]	Case series – IV	M	55	HTN	-	P	3	Conservative	-	-	-	-	-	-	-
			M	64	HTN	-	P	6	Surgical	-	No	-	-	Dead	-	D
			M	49	HTN	-	P	3	Conservative	-	-	-	-	-	-	-
38	Ari et al. – 2007 [57]	Case report – V	M	25	Methanol	130/90	P	-	Conservative	-	Yes	-	2	Bilateral optic atrophy	Severe disability	A
39	Asimi et al. – 2007 [58]	Case report – V	M	65	HTN	190/110	P	11	Conservative	1	-	-	0.03	Dead	-	D
40	Sefidbakht et al. – 2007 [59]	Case series – IV	M	27	Methanol	-	LN	-	Conservative	-	-	-	-	-	-	A
			M	26	Methanol	-	LN	-	Conservative	-	-	-	-	-	-	A
41	Nishina et al. – 2010 [60]	Case report – V	F	74	HTN	220/90	P	4	Conservative	-	No	-	0.2	Dead	-	D
42	Terzi et al. – 2010 [61]	Case report – V	M	63	HTN	190/110	BG	-	Conservative	-	-	-	-	No FND	Good recovery	A
43	Amin et al. – 2011 [62]	Case report – V	F	28	Stroke	140/70	LN	3	Conservative	35	Yes	-	2	Dysphagia, moderate hypokinesia, rigidity	Severe disability	A
44	Takeuchi et al. – 2011 [63]	Case series – IV	M	57	HTN	183/120	P	7	Surgical	-	-	-	-	Severely disabled	Severe disability	A
			M	59	HTN	198/140	P	3	Surgical	-	No	-	-	Vegetative state	Vegetative state	A
			M	89	HTN	150/78	P	3	Conservative	-	No	-	-	Dead	-	D
45	Westover & Cohen. – 2011 [64]	Case report – V	F	58	SSRI, RCVS	-	BG	-	Conservative	30	Yes	-	1	Minimal receptive aphasia	Good recovery	A
46	Cha et al. – 2012 [65]	Case report – V	M	55	CA	69/43	BG	3	Conservative	15	No	-	0.5	Dead	-	D
47	Permpalung et al. – 2013 [66]	Case report – V	M	56	Methanol	-	BG	-	Conservative	-	Yes	-	-	-	-	A
48	Srivastava & Kadam – 2013 [67]	Case report – V	M	35	Methanol	-	P	-	Conservative	-	Yes	-	-	-	-	A
49	Thirunavukkarasu et al. – 2013 [68]	Case report – V	M	30	Methanol	-	BG	8	Conservative	-	Yes	-	-	-	-	A
50	Heck et al. – 2014 [69]	Case report – V	M	29	Aneurysm	-	BG	-	Conservative	11	-	-	18	Minor speech difficulties, could not use R hand for precise manipulations	Moderate disability	A
51	Baldawa et al. – 2015 [70]	Case report – V	M	60	HTN	220/110	BG	-	Conservative	30	No	-	-	Vegetative state	Vegetative state	A
52	Lee et al. – 2015 [7]	Case report – V	M	32	Methanol	-	BG	3	Conservative	21	-	-	0.75	Dead	-	D
53	Mahale et al. – 2015 [71]	Case report – V	M	5	JE	98/72	BG	-	Conservative	-	Yes	-	-	Akinetic-mute state	Severe disability	A
54	Zhao et al. – 2016 [72]	Case report – V	M	57	HTN	192/102	BG	5	Surgical	-	Yes	-	10	Motor weakness	Moderate disability	A
55	Boukobza & Baud – 2017 [73]	Case report – V	F	54	CA	-	CS	3	Conservative	6	No	-	-	Dead	-	D
		Case report – V	M	64	CA	-	CS	3	Conservative	7	No	-	-	Dead	-	A
56	Gupta et al. – 2018 [74]	Case report – V	-	0.0055	GBS meningitis	-	CS	-	Surgical	-	-	-	6	Developmental delay, cerebral palsy, hypsarrhythmia	Severe disability	A
57	Mahavar et al. – 2018 [75]	Case report – V	M	25	Toluene	120/80	BG	3	Conservative	-	No	-	-	Dead	-	D
58	Daci et al. – 2020 [6]	Case report – V	F	60	COVID	WNL	BG	-	-	11	-	-	0.36	Dead	-	D
59	Guo et al. – 2020 [76]	Case report – V	M	0.083	Methylmalonic acidemia	-	C	-	Conservative	14	-	14	-	No FND	-	A
60	Haddadi et al. – 2020 [77]	Case report – V	F	54	COVID	150/100	BG	10	Conservative	7	Yes	5	-	No FND	Good recovery	A
61	Schweyer et al. – 2020 [78]	Case report – V	F	51	Olanzapine	WNL	BG	-	Surgical	-	Yes	-	2	Vegetative state	Vegetative state	A
62	Shaheed et al. – 2020 [79]	Case report – V	M	62	-	WNL	LN	14	Conservative	-	-	-	-	-	-	A
63	Zhang et al. – 2020 [80]	Case report – V	F	52	HTN	180/100	BG	6	Surgical	-	Yes	2	24	Mild motor disorder, speech did not return to normal	Moderate disability	A
64	Kayastha et al. – 2022 [81]	Case report – V	M	39	-	200/100	BG	12	Conservative	9	Yes	-	-	No FND	Moderate disability	A

Abbreviations: BG, basal ganglia; CA, cardiac arrest; CG, capsuloganglionic; CS, corpus striatum; DKA, diabetic ketoacidosis; DS, dorsal striatum; FND, focal neurological deficits; EC, external capsule; EG, ethylene glycol; GBS, group B Streptococcus; GCS, Glasgow Coma Scale; GCS1, admission GCS; GCS2, discharge or last known GCS; GP, globus pallidus; HA, headache; HHS, hyperglycemic hyperosmolar syndrome; HTN, hypertension; IC, internal capsule; JE, Japanese encephalitis; LOE, level of evidence; LOS, length of stay; LN, lentiform nuclei; MVA, motor vehicle accident; OS, overall survival; P, putamen; RCVS, reversible cerebral vasoconstriction syndrome; SSRI, selective serotonin reuptake inhibitor; Thal, thalamus; Tx, treatment; VT, venous thrombosis; WNL, within normal limits

*Postulated etiology

**If patient alive, this refers to months of follow-up

Demographics and clinical characteristics

There were 75 patients with BBGHs that met our inclusion criteria, 25 (33%) traumatic and 50 (67%) non-traumatic hemorrhages (Table 2). Patients were mostly male (76%) with a mean age of 42 years (range 0.006–89 years). When grouped by traumatic versus non-traumatic hemorrhage, cases of hemorrhage associated with trauma had a significantly younger mean age (35 vs. 46 years, p=0.014), a higher proportion of males (84% vs. 71%, p=0.27), and a significantly higher proportion of unremarkable past medical history (88% vs. 37%, p=0.0016). A minority of patients (9%) were on anticoagulant or antiplatelet medications or were reported to have coagulation factor deficiencies. The most common comorbidities were hypertension (41%) or diabetes (16%). Clinical characteristics are reported in Table 3. Overall, the most common presentation involved motor symptoms (26%), such as weakness, and headaches (11%). Among the 14 cases that described the laterality of weakness, most patients experienced unilateral weakness (79%), with a nearly equal distribution of right- (47%) and left-sided hemiplegia or hemiparesis. The non-traumatic group had a slightly higher proportion of constitutional and neurologic abnormalities though this was not statistically significant. Blood pressure at admission was within normal limits in 36% of patients, with a significantly higher proportion of normal readings reflected in the traumatic versus non-traumatic group (66% vs. 13%, p=0.0016). Most of the reported glucose levels were within normal limits (70–110 mg/dL) (64%), with a higher proportion of normal glucose levels in the traumatic versus non-traumatic group (77% vs. 50%, p=0.16). Most patients were comatose at admission (56%), with a mean GCS of 7. The traumatic group had a significantly higher GCS mean at admission when compared to the non-traumatic group (8 vs. 6, p = 0.046). A higher proportion of patients in the traumatic group were comatose at admission (64% vs. 52%, p = 0.28).

Table 2.

Summary of patient demographics. The number of patients for which values are reported for traumatic and non-traumatic cases is denoted in parenthesis. Analyses performed using the chi-square test for categorical values or Fisher’s exact test for categories with less than five observations, or t-test for numerical values with alpha < 0.05 being statistically significant (denoted in bold)

Characteristics	Overall	Non-traumatic	Traumatic	p-value
Cohort size	75	50	25
Age (n = 75)
Mean ± SD, range (years)	42 ± 20, 0.006–89	46 ± 19, 0.006–89	35 ± 18, 0.9–75	0.014
Gender (n = 75)
Female (%)	18 (24%)	14 (29%)	4 (16%)	0.27
PMH
Unremarkable (n = 55)	29 (53%)	15 (37%)	14 (88%)	0.0016
Coagulopathy* (n = 46)	4 (9%)	3 (12%)	1 (5%)	0.62
PMH conditions (n = 26)
Cardiovascular	27 (61%)	24 (62%)	3 (60%)	1.0
HTN	18 (41%)	17 (44%)	1 (20%)
Stroke	2 (5%)	2 (5%)	-
DVT	1 (2%)	1 (3%)	-
Thalassemia minor	1 (2%)	1 (3%)	-
Venous stasis ulcers	1 (2%)	1 (3%)	-
CHF	2 (5%)	1 (3%)	1 (20%)
Atrial fibrillation	2 (5%)	1 (3%)	1 (20%)
Endocrinologic
DM	7 (16%)	6 (15%)	1 (20%)	1.0
Cancer
Rectal adenocarcinoma	1 (2%)	1 (3%)	-	1.0
Other	9 (20%)	8 (21%)	1 (20%)	1.0
Hepatitis B/C virus	2 (5%)	1 (3%)	1 (20%)
OSA	1 (2%)	1 (3%)	-
PE	1 (2%)	1 (3%)	-
Asthma	1 (2%)	1 (3%)	-
Depression	1 (2%)	1 (3%)	-
GERD	1 (2%)	1 (3%)	-
Migraine	1 (2%)	1 (3%)	-
Quadriparesis	1 (2%)	1 (3%)	-

Abbreviations: CHF, congestive heart failure; DM, diabetes mellitus; DVT, deep venous thrombosis; ESRD, end-stage renal disease; HTN, hypertension; GERD, gastroesophageal reflux disease; MI, myocardial infarction; OSA, obstructive sleep apnea; PE, pulmonary embolism; PMH, past medical history; SD, standard deviation

*Yes, if patient was reported to be on anticoagulant or antiplatelet agents, or had a known bleeding disorder

Table 3.

Clinical characteristics. The number of patients for which values are reported for traumatic and non-traumatic cases is denoted in parenthesis (n = no. of cases). Analyses performed using the chi-square test for categorical values or Fisher’s exact test for categories with less than five observations, or t-test for numerical values with alpha < 0.05 being statistically significant (denoted in bold)

Categories	Overall	Non-traumatic	Traumatic	p-value
Signs and symptoms (n = 54)
Constitutional	17 (15%)	16 (16%)	1 (6%)	0.70
N/V	8 (7%)	7 (7%)	1 (6%)
Fever	4 (3%)	4 (4%)	-
Cough	2 (2%)	2 (2%)	-
Malaise	2 (2%)	2 (2%)	-
Dyspnea	1 (1%)	1 (1%)	-
Neurologic	19 (16%)	17 (17%)	2 (13%)	1.0
Headache	13 (11%)	11 (11%)	2 (13%)
Seizures	4 (3%)	4 (4%)	-
Dizziness	1 (1%)	1 (1%)	-
Urinary incontinence	1 (1%)	1 (1%)	-
System deficits	55 (47%)	49 (49%)	6 (38%)	0.60
Visual	6 (5%)	6 (6%)	-
Speech, language, swallowing	8 (7%)	8 (8%)	-
Sensory	5 (4%)	5 (5%)	-
Motor	30 (26%)	26 (26%)	4 (25%)
Weakness	12 (10%)	10 (10%)	2 (13%)
Hypertonia	6 (5%)	6 (6%)	-
Hypotonia	3 (3%)	3 (3%)	-
Tremors	1 (1%)	-	1 (6%)
Other*	2 (2%)	1 (1%)	1 (6%)
Coordination	2 (2%)	2 (2%)	-
Gait	3 (3%)	1 (1%)	2 (13%)
Reflexes	30 (26%)	24 (24%)	6 (38%)	0.22
Positive Babinski	13 (11%)	10 (10%)	3 (19%)
Impaired PLR	8 (7%)	6 (6%)	2 (13%)
Hyperreflexia	4 (3%)	3 (3%)	1 (6%)
Hyporeflexia	3 (3%)	3 (3%)	-
Absent brainstem reflexes	2 (2%)	2 (2%)	-
Other	2 (2%)	1 (1%)	1 (6%)	0.24
Abdominal pain	1 (1%)	1 (1%)	-
Hypersalivation	1 (1%)	-	1 (6%)
Vitals and labs
BP (n = 41)
WNL	15 (36%)	3 (13%)	12 (66%)	0.0016
Systolic mean ± SD, range	160 ± 41, 69–230	162 ± 41, 69–220	153 ± 43, 100–230	0.63
Diastolic mean ± SD, range	92 ± 20, 43–140	93 ± 21, 43–140	91 ± 19, 60–118	0.88
Glucose (mg/dl) (n = 25)
WNL	16 (64%)	6 (50%)	10 (77%)	0.16
Mean ± SD, range	170 ± 122, 25–404	199 ± 145, 25–404	115 ± 14, 106–132	0.37
GCS (n = 40)
At admission	7 ± 4, 3–15	6 ± 4, 3–14	8 ± 4, 3–15	0.046
LOC at admission (n = 75)
Awake	13 (17%)	9 (18%)	4 (16%)
Confused	3 (4%)	3 (6%)	-
Disoriented	1 (1%)	1 (2%)	-
Lethargic	8 (11%)	5 (10%)	3 (12%)
Stuporous	3 (4%)	2 (4%)	1 (4%)
Comatose	42 (56%)	26 (52%)	16 (64%)	0.28
Altered, NOS	5 (7%)	4 (8%)	1 (4%)

*Includes 1 limb ballism in the traumatic group, and 1 bradykinesia in the non-traumatic group

Abbreviations: GCS, Glasgow Coma Scale; LOC, level of consciousness; NOS, not otherwise specified; N/V, nausea/vomiting; PLR, pupillary light reflex; WNL, within normal limits; SD, standard deviation

BBGHs were mostly associated with hypertension (21%), motor vehicle accidents (20%), and methanol toxicity (10%) (Table 4). Among the traumatic group, motor vehicle accidents and falls accounted for 79% of cases. In the non-traumatic group, hemorrhage was most associated with vascular or ischemic (55%) and chemical (28%) etiologies. The putamen was the most denoted location (39%), followed by BG not otherwise specified (37%) and globus pallidus (20%). When analyzing by traumatic versus non-traumatic hemorrhage groups, traumatic cases had a higher proportion of globus pallidus locations (37% vs. 16%, p=0.073) and a lower proportion of BG not otherwise specified (16% vs. 38%, p=0.098). Most articles referred to the BBGH lesions as ICH (76%), while others referred to them as hemorrhagic infarction (21%) or hemorrhagic necrosis (3%). Concurrent intracranial hemorrhage (e.g., subarachnoid, epidural, or subdural hemorrhage) was present in a minority of cases overall (24%), with a significantly higher presence in the traumatic versus non-traumatic group (44% vs. 13%, p=0.0074). In the 10 cases that reported hemorrhage volume, there was an average estimate of 22 mL on each side. A larger average combined hematoma volume was observed for the non-traumatic group than for the traumatic group, but this was not statistically significant (27 vs. 15 mL, p=0.18).

Table 4.

Hemorrhage characteristics. The number of patients for which values are reported for traumatic and non-traumatic cases is denoted in parenthesis (n = no. of cases). Analyses performed using the chi-square test for categorical values or Fisher’s exact test for categories with less than five observations, or t-test for numerical values with alpha < 0.05 being statistically significant (denoted in bold)

Categories	Overall	Non-traumatic	Traumatic	p-value
Etiology (n = 70)
Traumatic
MVA	14 (20%)	-	14 (58%)	-
Fall	5 (7%)	-	5 (21%)	-
Assault	2 (3%)	-	2 (8%)	-
Blast injury	1 (1%)	-	1 (4%)	-
Lightning	1 (1%)	-	1 (4%)	-
Penetrating head injury	1 (1%)	-	1 (4%)	-
Spontaneous
Vascular
HTN	15 (21%)	15 (33%)	-	-
Cardiac arrest	4 (6%)	4 (9%)	-	-
Venous thrombosis	3 (4%)	3 (7%)	-	-
Aneurysm	1 (1%)	1 (2%)	-	-
Preeclampsia	1 (1%)	1 (2%)	-	-
Migraine	1 (1%)	1 (2%)	-	-
Chemical
Methanol	7 (10%)	7 (16%)	-	-
Ethylene glycol	1 (1%)	1 (2%)	-	-
Methylmalonic acidemia	1 (1%)	1 (2%)	-	-
Olanzapine	1 (1%)	1 (2%)	-	-
Toluene	1 (1%)	1 (2%)	-	-
Anticoagulants	1 (1%)	1 (2%)	-	-
SSRI	1 (1%)	1 (2%)	-	-
Infectious
COVID	2 (3%)	2 (4%)	-	-
Japanese encephalitis	2 (3%)	2 (4%)	-	-
GBS meningitis	1 (1%)	1 (2%)	-	-
Endocrinologic
DKA	1 (1%)	1 (2%)	-	-
HHS	1 (1%)	1 (2%)	-	-
Unknown	1 (1%)	-	1 (4%)	-
Location (n = 75)
Basal ganglia
Putamen	32 (39%)	25 (39%)	7 (37%)	1.00
Globus pallidus	17 (20%)	10 (16%)	7 (37%)	0.073
Caudate nucleus	7 (8%)	5 (8%)	2 (11%)	0.65
Basal ganglia, NOS	27 (33%)	24 (38%)	3 (16%)	0.098
Lesion referred As (n = 75)
ICH (%)	57 (76%)	34 (68%)	23 (92%)	0.023
Hemorrhagic infarction (%)	16 (21%)	14 (28%)	2 (8%)	0.072
Hemorrhagic necrosis (%)	2 (3%)	2 (4%)	-	1.0
Concurrent hemorrhage (n = 71)
Yes (%)	17 (24%)	6 (13%)	11 (44%)	0.0074
Hemorrhage volume* (n = 10)
Mean volume ± SD, range (mL)	22 ± 19, 1–74	27 ± 20, 1–74	15 ± 15, 3–42	0.18

*Volume for one side

Abbreviations: DKA, diabetic ketoacidosis; DM, diabetes mellitus; GBS, group B Streptococcus; HHS, hyperosmolar hyperglycemic state; HTN, hypertension; MVA, motor vehicle accident; NOS, not otherwise specified; SSRI, selective serotonin reuptake inhibitor

Management and outcomes

Management strategies are reported in Table 5. Patients were mostly managed conservatively (83%). Among studies that reported medical treatment, mannitol (26%) and phenytoin (for seizure prophylaxis) (19%) were the most often employed agents in traumatic cases. Meanwhile, unspecified hypertensive agents (12%) and heparin (for deep venous thrombosis prophylaxis) (10%) were most often used in non-traumatic cases. A higher proportion of medications involved antiepileptics in the traumatic group compared to the non-traumatic group (26% vs. 6%, p=0.081), all of which were used prophylactically without mention of seizures during admission nor history of seizures. In the eleven studies that reported surgical treatment, hematoma evacuation or drainage (including external ventricular drainage) was the predominant procedure overall (55%), followed by decompressive craniectomy (27%), third ventriculostomy (9%), and intracranial pressure (ICP) monitor placement (9%). The most frequently performed surgical procedure was hematoma evacuation in the non-traumatic group (67%) compared to decompressive craniectomy in the traumatic group (40%).

Table 5.

Management. The number of patients for which values are reported for traumatic and non-traumatic cases is denoted in parenthesis (n = no. of cases). Analyses performed using the chi-square test for categorical values or Fisher’s exact test for categories with less than five observations, or t-test for numerical values with alpha < 0.05 being statistically significant (denoted in bold)

Categories		Overall	Non-traumatic	Traumatic	p-value
Management type (n = 72)
Conservative		60 (83%)	40 (85%)	20 (80%)	0.82
Medical treatment* (n = 39)
Pressure management		34 (55%)	18 (58%)	16 (52%)	0.61
ACE inhibitor
Enalapril		1 (2%)	1 (3%)	-
Vasodilator
Hydralazine		1 (2%)	1 (3%)	-
Inopressor
Dopamine		1 (2%)	1 (3%)	-
DHP CCB
Amlodipine		1 (2%)	1 (3%)	-
Nimodipine		1 (2%)	1 (3%)	-
Loop diuretic
Furosemide		5 (8%)	1 (3%)	4 (13%)
Beta-blocker
Labetalol		1 (2%)	-	1 (3%)
Combination antihypertensives
Perindopril/amlodipine		1 (2%)	-	1 (3%)
Irbesartan/hydrochlorothiazide		1 (2%)	1 (3%)	-
Antihypertensives, NOS		4 (6%)	4 (13%)	-
Osmotic agents
Glycerin		1 (2%)	1 (3%)	-
Hypertonic saline		2 (3%)	-	2 (6%)
Human albumin		1 (2%)	1 (3%)	-
Mannitol		9 (15%)	1 (3%)	8 (26%)
Osmotic diuretic, NOS		2 (3%)	2 (6%)	-
Antiedema, NOS		2 (3%)	2 (6%)	-
Pain
Naproxen		1 (2%)	1 (3%)	-
Antiepileptics		10 (16%)	2 (6%)	8 (26%)	0.081
Phenytoin		7 (11%)	1 (3%)	6 (19%)
Antiepileptic, NOS		3 (5%)	1 (3%)	2 (6%)
Thrombolytics
Urokinase		3 (5%)	2 (6%)	1 (3%)	1.0
Anticoagulant		4 (6%)	4 (13%)	-
Nafamostat mesilate		1 (2%)	1 (3%)	-
Heparin		3 (5%)	3 (10%)	-
	Other	10 (16%)	4 (13%)	6 (19%)	0.73
Haloperidol		1 (2%)	-	1 (3%)
Statin		2 (3%)	2 (6%)	-
Steroid		2 (3%)	2 (6%)	-
Benzodiazepine		4 (6%)	-	4 (13%)
Phenobarbital		1 (2%)	-	1 (3%)
Surgical treatment (n = 11)
Hematoma evacuation**		6 (55%)	4 (67%)	2 (40%)	1.0
Decompressive craniectomy***		3 (27%)	1 (17%)	2 (40%)	0.30
Third ventriculostomy		1 (9%)	1 (17%)	-	-
ICP monitor		1 (9%)	-	1 (20%)	-

*Does not report detoxification agents (e.g., dialysis, fomepizole), vitamins (e.g., folate), or specific treatments for etiologies associated with the onset of BBGH (e.g., antibiotics for infection) other than vascular or pressure management

**Includes 2 EVDs (1 traumatic, 1 non-traumatic)

***Includes 1 case of external decompression with debridement of cerebral contusion and removal of bone fragments (traumatic)

Abbreviations: ACE, angiotensin-converting enzyme; CCB, calcium channel blocker; DHP, dihydropyridine; ICP, intracranial pressure; NOS, not otherwise specified

Among cases of surgical intervention, none reported which hemisphere was dominant nor mentioned consideration of cerebral dominance. Of cases with explicitly reported coagulopathic status (n = 6), none was on anticoagulant or antiplatelet medications nor had any known bleeding disorder. There were also no reports of chronic kidney disease or other renal abnormalities in this surgical subgroup, and no mention of postcritical management. One case referred to the lesion as a hemorrhagic infarction. In all cases of BG hematoma evacuation reporting details of the procedure (n = 3), drainage was performed bilaterally. Hemorrhage volume was slightly asymmetric with an average of 10 mL difference, and total volume ranged from 16.2 to 30 mL per side. In all three patients, draining catheters were left in place on both sides with subsequent thrombolysis and clot aspiration. BG hemorrhage was larger on the left side in one case and the right side in two cases. The patient with the greater hemorrhage on the left side was left with non-fluent aphasia post-operatively.

Urokinase dissolved in normal saline was used in two patients with associated intraventricular hemorrhage. In an older adult (57 year old female), 5000 IU urokinase in 3 mL normal saline was administered every 12 h for up to 4 doses, whereas in a child (6 year old male), 8000 IU urokinase in 3 mL normal saline was administered every 8 h over 2 days. In both cases of urokinase irrigation, complications related to the procedure arose. In the first adult case, signs of intracranial hypertension were observed 1.5 h after clamping the catheter following the initial urokinase infusion (20,000 IU in 3 mL normal saline), which was relieved upon opening the catheter valve. This prompted a change in administration schedule to urokinase infusion every 12 h for up to 4 doses (presumably 5000 IU each). In the second pediatric case, severe brain swelling developed 2 days following hematoma evacuation and 1 day after the administration of 8000 IU of urokinase in 3 mL of normal saline every 8 h. This prompted a decompressive huge craniectomy and duroplasty with ventriculoperitoneal shunting and cranioplasty at post-operative day 39.

Patients stayed in the hospital for a mean of 19 days overall (Table 6). This was shorter in the traumatic group than in the non-traumatic group (16 vs. 21 days, p=0.21). Follow-up duration was a mean of 8 months. Most patients were alive (78%). Of patients who were deceased, the overall survival was a mean of 0.2 months (6 days). Among cases that reported prognosis, most patients had a poor outcome (dead, vegetative state, or severe disability) (56%). A significantly higher proportion of good recovery was observed in the traumatic group (48% vs. 17%, p=0.019). Among cases of surgical intervention with reported outcomes (n = 10), patients were dead (20%), remained in a vegetative state (40%), or were severely (20%) or moderately (20%) disabled.

Table 6.

Outcomes. The number of patients for which values are reported for traumatic and non-traumatic cases is denoted in parenthesis (n = no. of cases). Analyses performed using the chi-square test for categorical values or Fisher’s exact test for categories with less than five observations, or t-test for numerical values with alpha < 0.05 being statistically significant (denoted in bold)

Categories	Overall	Non-traumatic	Traumatic	p-value
Length of stay (n = 43)
Mean days ± SD, range	19 ± 14, 1–73.5	21 ± 16, 1–73.5	16 ± 12, 3–39	0.21
Follow-up (n = 29)
Mean months ± SD, range	8 ± 8, 0.2–25	9 ± 8, 0.2–24	7 ± 8, 0.5–25	0.49
Status (n = 73)
Alive (%)	57 (78%)	36 (75%)	21 (84%)	0.56
Overall survival (n = 11)
Mean months ± SD, range	0.2 ± 0.2, 0–0.8	0.3 ± 0.3, 0–0.8	0.2 ± 0.06, 0.1–0.2	0.38
Prognosis (n = 64)
Good recovery	18 (28%)	7 (17%)	11 (48%)	0.019
Moderate disability	10 (16%)	7 (17%)	3 (13%)	1.0
Severe disability	13 (20%)	10 (24%)	3 (13%)	0.35
Vegetative state	7 (11%)	5 (12%)	2 (9%)	1.0
Dead	16 (25%)	12 (29%)	4 (17%)	0.37

Abbreviations: SD, standard deviation

Discussion

The BG is the most commonly reported location for non-traumatic ICH, with the putamen being implicated in nearly a third of cases on imaging series [82]. However, BBGH is a rare occurrence limited to case reports and brief case series. Based on the presence of trauma, BBGH has been categorized as traumatic or “non-traumatic” in etiology, with the latter being associated with a variety of vascular, chemical, infectious, and endocrinologic triggers. The deep-seated nature of these lesions and often acute presentation of loss of consciousness raise questions as to whether neurosurgical intervention can bring any meaningful change to outcomes. The bilateral nature of the bleed also presents unique factors that should be taken into consideration during management. In this systematic review, we assess the literature on BBGH and discuss the etiologies, management strategies, and clinical outcomes.

Etiology

The BG are a collection of deep subcortical gray matter structures that typically consist of the caudate nucleus, putamen, nucleus accumbens, globus pallidus, substantia nigra, and subthalamic nucleus. Blood supply arises from anterior circulation via the lenticulostriate arteries of primarily the middle and sometimes anterior cerebral arteries, with slight variations from person to person. The anterior choroidal artery of the internal carotid artery provides further vascular supply to BG [83–85]. Selective BG hemorrhage is likely possible due to anatomic and metabolic factors rendering this region particularly vulnerable to hypoxic and chemical injury. Specifically, terminal blood supply with a lack of anastomoses between parenteral vessels [85] and high excitotoxic and oxidative stress [86] predisposes the BG to damage following ischemic or toxic insult. Certain individuals may have an increased risk for hemorrhage due to geometric feature variations of the middle cerebral artery that promote wall stress and injury [87], and the presence of other comorbid conditions such as hypertension, heart disease, diabetes, excessive alcohol consumption, and smoking [88, 89].

Understanding the etiology and mechanism of injury in BG hemorrhage is important to evaluate the benefit, if any, of surgical intervention, where the principal effects are related to the dissipation of mass effect and removal of extravasated blood products. It is perhaps even more crucial in cases of bilateral hemorrhage, as surgical intervention presents additional potential risks such as contralateral clot destabilization or herniation if only one side is aspirated or increased cortical injury if both sides are targeted. During primary injury, an expanding hematoma can compress surrounding tissues, including vasculature, potentially altering blood flow if sufficiently large. However, the extent to which this occurs in BBGH may be minimized by a stanching effect of the contralateral hematoma and relative theoretical laxity of gray matter in this region in comparison to white matter and the cerebral cortex [90, 91], which may contain the bleed and limit significant tissue displacement. This remains speculative as studies on viscoelastic properties of the brain cannot simulate all aspects of a BBGH in humans [92]. Secondary injury is attributed to the proinflammatory and neurotoxic effects of thrombin and red blood cell contents such as hemoglobin, hemin, and iron following cell lysis, which then can lead to edema with subsequent increased intracranial pressure and herniation [93, 94].

Traumatic BG hemorrhage is thought to be caused by tears in branches of the anterior choroidal or lenticulostriate arteries due to sudden acceleration-deceleration and shearing forces. This was first observed histologically by Mosberg and Lindenberg upon discovering a ruptured arterial twig of the anterior choroidal artery in a patient with traumatic hemorrhage of the left pallidum [95]. Mechanisms by which bilateral traumatic tears occur are likely due to the same shearing forces, with anatomical variations in the symmetry or proximity of vasculature and trajectory of the external force perhaps predisposing individuals to simultaneous rupture of arteries on both sides. Alternatively, hemorrhage occurring initially on one side with subsequent hematoma expansion [96, 97] may alter local hemodynamics and cause mass effect leading to rupture of contralateral arteries lacking normal wall integrity due to damage sustained from the initial traumatic event. This latter view may be supported by the appearance of asymmetric hemorrhage volumes and unilateral symptoms noted in most of our included cases. Compared to the traumatic unilateral BG hemorrhage series presented by Boto et al. in 2001 [98], our dataset included a lower proportion of motor vehicle accident cases (58% vs. 94%). This is likely due to their selection of severe cases through inclusion of only patients with a GCS score of 8 or less. Our traumatic cases also included etiologies of diffuse nature, such as lightning strike and blast injury, which to our knowledge has not yet been reported as manifesting with unilateral BG hemorrhage. Thus, traumatic BBGH will likely share etiologic similarities with unilateral BG hemorrhage, but may include events where trauma is sudden, diffuse, and more uniform.

Non-traumatic BG hemorrhage is associated with a variety of etiologies. Hypertension is the predominant cause with persistent elevations in arterial pressure associated with lipohyalinosis and weakening of small vessel walls, which may lead to occlusion and ischemia (lacunar stroke) or breach and hemorrhage [99]. Some cases are hypothesized to occur from a sudden rise in blood pressure causing rupture of microaneurysms or tears in the lenticulostriate artery branches [100]. Other potential causes include toxic metabolites of alcohols and glycols, anticoagulation therapy, vessel wall abnormalities (“no-reflow phenomenon”) or focal necrosis following ischemia, cerebral venous thrombosis in the great cerebral vein, and migraine-induced vascular changes. In our dataset, vascular and ischemic etiologies accounted for most cases (53%), though chemical, infectious, and endocrinologic factors were implicated in nearly half of the other cases and underscore the importance of inquiring about suicidal ideation, COVID-19 vaccination status and exposure, and glucose control in the setting of diabetes mellitus from reliable historians. The role of COVID-19 infection in BBGH may be related to hypercoagulopathy [101] or neurotropism [102] though future studies will be needed to explore this association further. Etiologies among unilateral and bilateral BGH are likely similar, though it is unclear if BBGH has higher proportions of certain etiologies as epidemiological studies of specific BGH causes are difficult to perform.

Management

Management of BBGH was predominantly conservative, resembling current themes of management in ICH and unilateral BGH cases. Options for management of BG hemorrhage include medical therapies or surgical intervention with the goal of removing the hematoma, limiting hematoma expansion, ICP monitoring, or minimizing consequences of secondary injury though the role of surgery remains controversial [103–105]. Several clinical trials have been conducted to explore each of these therapeutic approaches predominantly in the setting of non-traumatic ICH. None have demonstrated a clear benefit of surgery, though several limitations must be taken into consideration when applying these findings to cases of deep-seated BG hemorrhage. In 2005, the Surgical Trial in Intracerebral Haemorrhage (STICH) [14] evaluated the impact of early surgery (within 72 h) versus conservative treatment in patients with non-traumatic supratentorial ICH. One of the major limitations of this trial was in the inclusion of both lobar (39%) and BG (42%) hemorrhage within the same group and analysis. Lobar and BG hemorrhage differ markedly, with BG hemorrhage causing permanent damage to critical gray matter in the immediate vicinity of the bleed. Additionally, compared to lobar locations, hemorrhages of the BG are at higher risk for intraventricular extension and are associated with greater morbidity and mortality [106]. The lack of clear surgical benefit noted in the STICH trial may be attributed to the permanence of deficits upon BG hemorrhage as surgical intervention cannot restore what was lost. Most surgeons in the trial employed a craniotomy (75%), despite nearly 42% of hematoma originating within the BG or thalamus, raising questions as to whether a more minimally invasive surgical approach would lead to better outcomes [107]. Early surgery was associated with a slightly favorable outcome when the hematoma was located within 1 cm from the cortical surface, which may have been a reflection of the advantages of craniotomy for superficial resection, though when this subgroup was explored in a follow-up trial (STICH II) in 2013 [15], the findings remained neutral.

Minimally invasive strategies for evacuating hemorrhages in deep locations such as the BG would be preferred over a craniotomy. This approach was assessed in the MISTIE trials (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage) [108], which provided a protocol for image-guided aspiration followed by thrombolysis of the clot with alteplase administration every 8 h for up to nine doses. In 2019, MISTIE III [13] evaluated the impact of MISTIE treatment versus standard medical care on functional outcomes based on the modified Rankin Scale score at 1 year. MISTIE treatment was not associated with improvements in functional outcome; however, only 58% of cases met the clot reduction goal of less than 15 mL. Subsequent analysis of subjects that received adequate hematoma removal according to the surgical target of less than 15 mL demonstrated slight positive benefit in outcome compared to controls, and further studies with more consistent surgical results are warranted. Several smaller studies have evaluated the role of other minimally invasive surgical techniques, with mixed results on the benefit of such interventions on overall outcomes [18, 109–113].

Although studies on the impact of surgical evacuation of non-traumatic ICH are generally neutral, a 2018 meta-analysis with 15 published randomized controlled trials investigating minimally invasive surgery [114] found that it improved morbidity and mortality significantly more than medical management or craniotomy, nearly doubling the chance of independence and survival and follow-up. Though this does not include recent results from MISTIE III, minimally invasive strategies show promise, especially when surgery can be performed within 72 h of symptom onset in certain patient subgroups such as those with moderate hematoma volume 20–50 mL and GCS ≥ 9 [17]. The 2022 American Heart Association/American Stroke Association (AHA/ASA) guidelines for management of patients with spontaneous ICH reflect this with a moderate strength recommendation in regard to minimally invasive hematoma evacuation for patients with supratentorial ICH of > 20–30 mL with GCS scores of 5–12 [115]. However, the guidelines do not specify etiology or location, and it will be difficult to ascertain benefit for BBGH until future studies investigate minimally invasive strategies for unilateral BGH. In the coming years, two industry-sponsored randomized controlled trials, Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) sponsored by the NICO corporation, and Minimally Invasive Endoscopic Surgical Treatment with Apollo/Artemis in Patients with Brain Hemorrhage (INVEST) sponsored by Penumbra, will add to the minimally invasive surgical literature. Meanwhile, the Swiss Trial of Decompressive Craniectomy Versus Best Medical Treatment of Spontaneous Supratentorial Intracerebral Hemorrhage (SWITCH) will provide information on the importance of strict control of intracranial hypertension with prophylactic decompressive craniectomy in patients with non-traumatic ICH in the BG and/or thalamus.

Evidence for surgical intervention in cases of traumatic ICH remains scarce, with only one randomized controlled trial published to date that was terminated prematurely due to recruitment and funding issues. The Surgical Trial in Traumatic Intracerebral Hemorrhage (STITCH) [12] was the first to investigate the impact of surgery in traumatic cases. Most surgeons opted to use craniotomy (97%) and the largest areas of hemorrhage were in the frontal or temporal lobes (92%). Although there were significantly more deaths in the first 6 months in the conservative treatment group (33% vs. 15%), sample sizes were low (n = 170). Since most cases involved lobar regions, it is difficult to translate these findings to traumatic BG hemorrhage. Surgical management of traumatic BG hemorrhage will likely depend on studies evaluating the role of minimally invasive approaches for non-traumatic ICH located in deep regions.

Taken together, these studies support conservative management for ICH especially when the hematoma resides in deep areas such as the BG, though timely minimally invasive surgery between 4 [116] and 72 h after the inciting event may be beneficial in cases where hematoma volume is moderate (20–50 mL) and GCS is above 9, and decompressive craniectomy may be considered for cases of impending herniation or neurologic worsening attributed to mass effect. Another factor to take into consideration is the laterality of the bleed in relation to the dominant cerebral hemisphere. Surgical evacuation on the dominant side may cause new post-operative aphasia, making less invasive approaches such as a decompressive craniectomy more favorable. Unfortunately, our dataset was severely limited in the number of surgical cases and surgical detail and determining whether the cause of post-operative aphasia is surgical intervention, or the inciting event may be challenging due to altered level of consciousness at admission, preventing an accurate assessment of speech and hemispheric dominance. Future studies reporting laterality of the surgical approach and post-operative deficits are needed. Limited evidence is thus available to determine whether surgical intervention on one or both sides of a BBGH confers any benefit on outcome. Medical management, particularly the use of antihypertensives for early blood pressure lowering (systolic blood pressure 130–150 mmHg) as described in the American Heart Association/American Stroke Association guidelines [115], will likely remain the mainstay of treatment for most BBGH cases.

Outcomes

Outcomes of BBGH were dismal. More than half of patients experienced vegetative state, severe disability, or death (56%), while only 28% experienced what was deemed good recovery though follow-up was limited with an average time of 8 months. Overall mortality rates were 25% and all occurred within the first month. Although this appears to be lower than ICH mortality rates of 40% at 1 month and 54% at 1 year [1, 88], BBGH appears to have higher mortality rates than unilateral basal ganglia hemorrhage cases in general (25% vs. 16%) [19]. Compared to literature reports of mostly unilateral cases, BBGHs have higher mortality rates among non-traumatic BGH (29% vs. 13–19% [117, 118]) even in cases complicated with severe intraventricular hemorrhage (29% vs. 24–28% [119]). However, BBGH cases appear to have lower mortality rates among traumatic BGH (17% vs. 35–52% [120–123]) cases. One possibility for these differences in outcomes between bilateral and unilateral disease is that in non-traumatic cases, BBGH correlates with greater burden of disease. However, in traumatic cases, BBGH may relate more to the direction or nature (e.g., diffuse, uniform) of external force rather than the intensity of impact. Assuming that patients with vegetative state, severe disability, or death correspond to a modified Rankin Scale (mRS) of at least greater than 3, spontaneous BBGH cases also appear to be associated with worse functional outcomes than spontaneous unilateral cases (65% vs. 30–50% [118, 124]).

The traumatic BBGH group tended to do better than the non-traumatic group in terms of shorter average length of stay, higher proportion of patients alive, and significantly higher proportion of patients experiencing good recovery at follow-up. This echoes findings from other studies comparing traumatic and non-traumatic ICH. In 2002, Siddique et al. found that traumatic ICH cases were associated with better outcomes (good recovery and moderate disability) than those with non-traumatic ICH (67% vs. 24%) [125]. It should be noted that traumatic hematomas were often more superficial and lobar (91%) than in the non-traumatic group (56%) which may have contributed to the starker difference in outcomes than in our dataset of exclusively deep BG hemorrhages. Cases of traumatic ICH may have more favorable prognosis than non-traumatic cases due to the often younger age of patients which was also reflected in our study (35 vs. 47), and since the etiology is related to external factors (trauma) rather than intrinsic factors (e.g., impaired vasculature) that may also hamper recovery. Specific location within the BG may also be a prognostic factor, as differences in outcomes have been observed based on which arterial territory is affected [126] and certain sites such as the putamen have been associated with a higher frequency and volume of early hemorrhage expansion [96, 97]. The bilateral nature of hemorrhage raises questions as to whether the contralateral hematoma in BBGH assists in stabilizing the clot due to a stanching effect on the surrounding vessels, though this remains speculative.

Limitations

This review is limited by the retrospective nature of case reports and case series, lack of consistent and comprehensive reporting of relevant clinical and surgical details, and differences in time periods of study which may have introduced confounding practice and technical factors. The assessment of prognosis was subjective and scored by the authors based on the information provided in the text, which ranged from being a minimal general statement of the patient’s well-being to a more detailed explanation of exact daily functioning with examples. Due to the retrospective nature of this review and differences in granularity from study to study, we could not evaluate the efficacy of any interventions. The severely limited number of cases with surgical management and differences in surgical detail prevent us from offering indications and insight into when surgical approaches would be beneficial and what postcritical management should entail. While most cases referred to the lesion as an ICH, a minority of cases referred to the lesion as a hemorrhagic infarct or hemorrhagic necrosis though the criteria for naming was not explicitly mentioned. Due to different implications on prognosis, clarity regarding the nature of the hemorrhage is important for future studies. This heterogeneity of the literature highlights the importance of standardizing the collection and reporting of data across different institutions worldwide. Case reports and series may also carry reporting biases, where authors may be more inclined to report cases if they are interesting, and thus, data reported from our cohort may not completely reflect the traumatic or non-traumatic BBGH population. Although the comparative analyses detected some significant differences between the two groups, the limited number of patients with available data within each group should be taken into account when considering the clinical power of such findings.

Conclusions

BBGH is a rare occurrence that can be associated with a wide variety of traumatic, vascular, chemical, infectious, and endocrinologic factors. The differential should be kept wide, and management generally follows that of current ICH guidelines with supportive care and early blood pressure management as the mainstays of treatment. Minimally invasive surgery is promising, though the additional risks of bilateral surgical hematoma evacuation as compared to unilateral cases of hemorrhage require stronger evidence in favor of surgical intervention to be worth pursuing, especially in cases of deep-seated lesions. The present review confirms that BG hemorrhages are associated with a poor prognosis and highlights the gaps in current scores and guidelines. There is an urgent need for improved assessment tools and recommendations regarding BGH. Future scores and trials in this field should take into consideration the specific location of hemorrhage and dominance of the injured hemisphere.

Author contributions

All authors contributed to the study conception and design. The study was conceptualized and supervised by G.E.U. and P.P. Material preparation, data collection, and analysis were performed by G.W., A.C., and C.O. The first draft of the manuscript was written by G.W. and V.C., O.B., A.S.H., S.M.P., M.S., S.S.H., B.C., G.E.U., and P.P. commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Declarations

Ethics approval

As this is a literature review, ethics approval is not applicable.

Consent to participate

As this is a literature review and no original data from new patients were collected, consent to participate is not applicable.

Consent for publication

As this is a literature review and no original data from new patients were collected, consent for publication is not applicable.

Competing interests

The authors declare no competing interests.