Intracerebral hemorrhage evacuation with minimally invasive surgery by neurointerventionalists: a review

Introduction

Background

Spontaneous intracerebral hemorrhage (ICH) is a nontraumatic bleed into the brain tissue, usually caused by rupture of small arteries or arterioles due to vascular disease. The leading causes are chronic hypertension, resulting in small-vessel damage, and cerebral amyloid angiopathy (CAA), which commonly affects older adults and leads to lobar bleeds. Other causes include anticoagulant use, vascular malformations, cerebral venous thrombosis, vasculitis, and tumors (1). ICH remains the deadliest stroke subtype, with 1-year mortality approaching 43–59% (2-4). Evidence-based treatment of ICH is limited to blood pressure control and reversal of anticoagulation (5). Conventional craniotomy for ICH did not improve functional recovery in randomized trials (6,7). The inconsistency of offering ICH evacuation is out of proportion to that explained by patient characteristics (8). Minimally invasive surgery (MIS) for ICH is a promising treatment currently under study. Although not universally practiced, its use is expanding as evidence supporting its safety and efficacy accumulates (9,10).

Rationale and knowledge gap

If emergent MIS hematoma evacuation becomes standard of care, patient access to potentially lifesaving treatment will be limited by an already strained neurosurgical workforce. This would be especially pronounced in low- and middle- income countries where there is a lower density of neurosurgeons yet a higher burden of ICH (11,12). Addressing these disparities requires targeted public health interventions and improved healthcare infrastructure; however, this takes time and resources (11,12).

Objective

This review focuses on supratentorial ICH and summarizes recent advances in MIS for ICH. We propose an alternative pathway for ICH management within comprehensive stroke centers.

Pathophysiology

Primary ICH most commonly results from chronic hypertension, CAA, or anticoagulation. Hypertension leads to deep perforating artery vasculopathy (arteriolosclerosis), weakening vessel walls and predisposing to rupture, while amyloid deposition in CAA typically causes lobar hemorrhages by damaging cortical and leptomeningeal vessels. Anticoagulant therapy increases bleeding risk by impairing hemostasis (13). Causes of secondary hemorrhage include macrovascular malformations (e.g., arteriovenous malformations, aneurysms), cerebral venous thrombosis, and reversible vasoconstriction syndrome.

Primary neurologic injury in ICH is driven by the initial physical disruption in brain architecture. Secondary insults result from mass effect, and/or through the activation of an inflammatory cascade at the cellular level. Mass effect from initial hemorrhage, hematoma expansion, and perihematomal edema contribute to increased intracranial pressure (ICP) leading to altered blood flow, neurotransmitter release, mitochondrial dysfunction, and membrane depolarization. At the cellular level, thrombin binding to protease-activated receptors triggers an inflammatory cascade which activates microglia in the central nervous system and initiates the complement cascade (13-16). Potential therapeutic targets for preventable secondary brain injury include mass effect and hematotoxicity (17-19). Management guidelines recommend the following:

• Rapid neuroimaging with non-contrast computed tomography (CT) and CT angiography is essential to confirm the presence of hemorrhage, assess hematoma volume, and identify potential underlying causes (5).
• Aggressive blood pressure control—with a systolic target of <140 mmHg within 2 hours—is recommended by the American Heart Association/American Stroke Association to reduce the risk of hematoma expansion (5).
• Prompt reversal of coagulopathy involves discontinuation of anticoagulant therapy and administration of specific reversal agents (e.g., vitamin K and prothrombin complex concentrate for warfarin; idarucizumab for dabigatran) (5).
• ICP management includes head elevation, hyperosmolar therapy, and consideration of neurosurgical intervention for large hematomas or hydrocephalus (5).
• Admission to a stroke unit or neurocritical care setting is critical for close neurological monitoring and prevention of medical complications (5).

“ICH penumbra”

Reduced blood flow has been observed in perihematomal brain tissue using positron emission tomography (PET)/magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (20,21), drawing parallels to the ischemic penumbra seen in large vessel occlusion stroke. However, Qureshi et al. observed no significant decrease in perihematomal perfusion (22), while others have observed a perfusion decrement but attribute it to decreased demand. The perihematomal changes observed are more consistent with secondary injury mechanisms rather than true ischemia. Even though the existence of an “ICH penumbra” analogous to ischemic penumbra is debatable, emerging empirical data suggest that early intervention leads to improved clinical outcomes in specific ICH population subgroups (23). Weighted disability scores were proven to be better with minimally invasive lobar ICH evacuation in the ENRICH (Early Minimally Invasive Removal of Intracerebral Hemorrhage) trial (9).

Population subgroups

Non-modifiable factors associated with better outcomes after ICH surgery include young age, urban dwelling (23), large hematoma volume (24,25), non-eloquent location, lobar location, lack of intraventricular hemorrhage (IVH) (18,25), and absent computed tomography angiography (CTA) spot sign (26), while modifiable factors include earlier intervention and a larger extent of clot removal (27). Table 1 lists modifiable and non-modifiable factors associated with improved outcomes after ICH evacuation.

Timing

An actively bleeding vessel is frequently identified when early ICH evacuation is performed on patients with signs of hematoma expansion on CT or CTA (17,19,34,35). This group of patients would likely benefit from early hematoma evacuation before further brain damage occurs. However, early ICH evacuation was historically met with resistance (6,7,31,36). Landmark trials STICH (I & II) and MISTIE did not show significant improvement in disability from early ICH evacuation (7,31,37). Furthermore, surgery within 4 hours of ictus has been associated with an increased risk of rebleeding due to difficult hemostasis (36). Recently, advanced hemostatic techniques in MIS minimize rebleeding risk (34,36). The ENRICH trial reignited interest in utilizing MIS for ICH when they showed better functional outcomes in patients treated with hematoma evacuation within 24 hours since last known well (9). Early operation also resulted in reduced brain edema, reduced length of hospital stay and better survival (9,19). Wang et al. found early craniopuncture to improve functional outcomes in small basal ganglia hemorrhage (38) (Table 2). As reproducible data of benefit from early hematoma evacuation is accumulating, hospitals must prepare themselves to accommodate emergency ICH evacuation. One alternative is to modify existing stroke programs to provide MIS for ICH.

MIS technique

MIS offers several advantages in ICH evacuation including hematoma volume reduction, ICP control, intracavitary visualization, hemostasis and decreased secondary inflammation, while minimizing iatrogenic disruption of healthy brain (10,18,39). The spectrum of minimally invasive ICH evacuation techniques, from least to most invasive based on the size of parenchymal entry, includes craniopuncture, stereotactic aspiration, and endoscopic techniques (including endoscopic-assisted and endoport-mediated approaches) (40).

In China, craniopuncture is considered the standard treatment for ICH. This minimally invasive procedure uses a special instrument called a YL-1 needle, which is made up of a 3-mm hollow tube (cannula) with a puncture needle inside. The surgeon drills the needle through the skull into hematoma. Once the correct position is reached, the cannula is secured to the skull, and some of the accumulated blood is drained. After the initial drainage, a thrombolytic solution containing either urokinase or recombinant tissue plasminogen activator (rtPA) is injected into the hematoma to help break down the remaining clot. This medication is typically administered every 6 to 12 hours. A follow-up CT scan is performed 1 to 3 days later to assess how much blood remains. The drainage needle is usually kept in place for 3 to 5 days to allow ongoing removal of the liquefied hematoma (41,42). When neurosurgical services are limited, performance of this procedure by non-neurosurgeons is accepted in China (1).

Stereotactic aspiration using the MISTIE (efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation) protocol involves confirming clot stability with an initial 6-hour follow-up CT scan followed by introducing a 14-F (4.7 mm) cannula under stereotactic guidance, aspirating clot until resistance is felt, placing a ventricular drain through the cannula and removing the cannula, and serially injecting rtPA until an endpoint is reached (37).

The endoport provides a corridor through which bimanual technique can be utilized in a broad range of neurosurgical operations. The ENRICH trial, using an endoport placed under image guidance, showed improved weighted disability scores for ICH with a volume of 30–80 mL when operated within 24 hours. However, this benefit was driven by patients with supratentorial lobar hemorrhages (9). The MISTIE III trial, using stereotactic aspiration, did not find significant improvement in functional outcomes however it is worth noting that “clot stability” was a requirement for trial inclusion (37). In addition, candidates with life-threatening hematomas with significant mass effect enough to need lifesaving surgery were excluded. This means surgery was not done early and those patients who would otherwise have benefited significantly from surgery were excluded from the trial. None the less, exploratory analysis of MISTIE III data suggested an association between the extent of clot removal and good functional outcome. Specifically, the subgroup of patients with <15 mL residual hematoma after evacuation had 10.5% increased chance of modified Rankin scale (mRS) of 0–3 compared to medical management alone (37).

An intermediate tract size between the relatively larger port-based hematoma evacuation and the smaller catheter-based aspiration/craniopuncture is endoscopic surgery (ES). ES provides direct visualization of hematoma as it is drained in real time. This enhances extent of hematoma volume evacuated (43,44). In addition, advances in endoscopy now enable the surgeon to secure hemostasis more effectively potentially benefitting those patients operated early and with a risk of hematoma expansion (34,44,45). The endoscope also allows simultaneously addressing IVH if there is extensive casting of ventricles (46,47). In summary, ES offers unique advantages in MIS ICH evacuation as it enhances the extent of hematoma evacuation through direct visualization, minimizes brain injury and may prevent hematoma expansion/rebleeding through effective hemostasis leading to improved outcomes (30,45,48,49). Several RCTs have now demonstrated the survival and/or functional outcome benefit of ES for ICH (30,33,50-53). Ongoing trials NESICH (54), EMINENT-ICH (55) and INVEST (56) are expected to clarify endoscopy’s role in ICH (Table 3).

Expanding the workforce: rationale and applicability

Internationally, ICH remains an “orphan disease”, lacking a distinct specialty providing comprehensive and consistent care (1,59-61). Pessimistic attitudes and an overreliance on imperfect prognostication tools are so common that Becker et al. found the strongest predictor of poor outcome to be the decision to withdraw therapy. This is true even in patients who could have achieved an acceptable outcome (mRS ≤3) (62). The need for effective ICH treatment is dire. While early MIS ICH evacuation is promising, there is concern that access to life-altering care will be limited should it be necessary to operate ultra early. Added demand on neurosurgeons is likely to be unmet, particularly in the developing world where neurosurgeon density is 0.12 per 100,000 population compared to 2.44 per 100,000 in high income countries (63). As acute ICH patients typically present as “code strokes”, established stroke systems of care could be leveraged to improve access to ICH care. Emergent external ventricular drain insertion has been safely performed in the neuroangiography suite utilizing flat detector (FD) CT and an integrated navigation system (64). Similarly, neuroangiography suites at thrombectomy capable centers could be used to perform acute ICH evacuation, saving time lost otherwise while transferring patients to centers with neurosurgical services.

Neurointervention is a subspecialty at the cross-section of neurology, neurosurgery, and neuroradiology centered around the diagnosis and treatment of neurovascular diseases using image-guided procedures (65). The scope of neurointervention continues to expand as more and more minimally invasive strategies are devised for a wide range of pathologies. Neurointerventionists (NIRs) are trained to care for complex neurocritical conditions like aneurysmal subarachnoid hemorrhage. The better long-term outcome of endovascular treatment compared to open surgery and patients’ tendency to choose minimally invasive treatment has led to a shift toward endovascular management of intracranial aneurysms (66). The recent advent of flow diverters and endosaccular devices has virtually made the term “uncoilable” obsolete. Endovascular shunt for hydrocephalus (67), percutaneous spinal cord stimulation for failed back surgery or complex regional pain syndrome (68), balloon compression for trigeminal neuralgia (69), and unpublished reports of trans-vascular drainage of chronic subdural hematomas showcase the versatility of neurointervention. While MIS ICH hematoma evacuation is not routinely performed by NIRs, a properly trained NIR who practices in an established stroke program would be well-positioned to increase patient access to acute MIS ICH evacuation. This would allow thrombectomy-capable centers to provide acute care to patients with both ischemic and hemorrhagic stroke.

Training background of neurointervention includes management of complex disorders like aneurysmal subarachnoid hemorrhage and other vascular malformations prone to result in parenchymal bleeding. From the initial diagnostic considerations to specific management, NIRs are already involved in managing ICH patients. In addition, NIRs are strategically placed in stroke centers with established “code strokes” which have the potential to be modified to adopt for a “code ICH”. Furthermore, neurointervention skill set entails performing procedures by looking at a screen distant to the intervention site. We believe these reasons justify training NIRs to perform MIS for ICH

The major concern raised while enabling NIRs to perform MIS for ICH is safety. Life-saving cranial surgery has been demonstrated to be safely performed in underserved communities by healthcare workers with limited neurosurgical training (70-73). General surgeons in Cambodia safely performed craniotomies and bur holes for trauma after a 4-week training (72). Where formally trained neurosurgeons were not widely available in Tanzania, non-neurosurgeons have been able to safely perform life-saving neurosurgery using a “train forward” method (73).

Refined hand-eye coordination guided by visualization on a screen distant to the surgical site is an integral part of neurointerventional training and practice. Endoscopic MIS is a different version of the same concept. An initial cadaveric training, supervised practice then solo performance has been demonstrated to be safe in MIS for ICH by Tekle et al. (74). We recommend a similar training pathway for all interested and capable NIRs. This includes a didactic course on performing bur holes and basic neurosurgical equipment, neurosurgeon-led cadaveric training sessions, a neurosurgeon-assisted practice in live patients, and a neurosurgeon-supervised performance before solo practice. These procedures will initially be conducted in the operating theatre, but the authors suggest utilizing the angiosuite as an option. The added advantage of a post-procedure FD CT acquisition in the angiosuite may improve efficacy of the procedure by confirming satisfactory volume reduction, which has been found to be correlated with better outcomes (27). The role of the NIR would then be to provide a comprehensive stroke procedural care with neurosurgical oversite for ICH evacuation. However, the safety of ICH MIS performed by NIRs needs to be reproduced before higher level recommendations can be made. The authors also recommend rigorous quality assurance measures led by the appropriate neurosurgical societies.

Tekle et al. have demonstrated that endoscopic hematoma evacuation is safe, and patients demonstrate comparable outcomes to landmark trials when surgical intervention is performed early. A third of these procedures were performed in the neuroangiosuite making use of intraprocedural flat panel detector CT to check for significant residual hematoma (74).

Wang et al. report improved functional outcomes from MIS for ICH performed by qualified neurosurgeons and neurologists after they received a training according to a project manual (38).

NIRs are uniquely positioned to play a pivotal role in the rapid diagnosis and management of ICH. As they are already on call for acute ischemic stroke cases, their inclusion in a “Code-ICH” protocol could streamline care delivery and shorten the time from diagnosis to intervention. By integrating MIS evacuation techniques into their existing stroke response workflow, NIRs can provide timely, life-saving treatment, particularly in centers where neurosurgical availability is limited.

While the intent is not to replace neurosurgeons, appropriately trained NIRs could effectively respond to “Code ICH” activations and perform MIS hematoma evacuations as part of a collaborative, multidisciplinary stroke team. This approach may enhance access to emergent ICH care, optimize resource utilization, and serve as a practical model for expanding comprehensive stroke services, especially in resource-constrained settings.

Management strategies

Inclusion of NIRs to the ICH evacuation workforce will require a systematic approach including a formal training pathway, quality control measures and hospital systems reforms. Tekle et al. recommend a training pathway where NIRs first learn to perform bur holes and proceed to cadaveric training on endoscopy and evacuation techniques. This will be followed by 5–10 live cases proctored by a neurosurgeon. Independent practice is recommended after the responsible neurosurgeon approves and signs off on the NIR skill (74). Quality control measures should be in place with continuous monitoring to ensure outcomes are not worse than reported local figures. The authors recommend ICH evacuation to be led by neurosurgeons whenever they are available as depicted in Figure 1, below. Criteria for activating the code ICH is adopted from the craniopuncture study by Wang et al. (38).

Figure 1 Flow chart depicting workflow of MIS for ICH. Code ICH activated when these criteria are met. (I) Spontaneous hemorrhage in the basal ganglion of the brain on CT scan; (II) hemorrhage volume: 25–40 mL; (III) age range: 40–75 years; (IV) muscle strength of the paralyzed limbs: grade 0–3 on the muscle strength scale; (V) hemorrhagic duration (from stroke onset to hospital) within 72 h; (VI) Glasgow Coma Scale >8; (VII) informed consent is obtained and contraindications are absent. ICH, intracerebral hemorrhage; MIS, minimally invasive surgery; NIR, neurointerventionist; NS, neurosurgeon.

Future directions

Optimal surgical timing must balance clot stability with maximal surgical benefit. Ultra-early evacuation of ICH must become the standard of care, particularly in patients with findings associated with a higher risk of hematoma expansion.

Early evacuation is not inherently associated with increased hematoma expansion. Better prediction of patients likely to suffer hematoma expansion and refinement in hematoma evacuation techniques including better hemostasis are bound to decrease the risk of hematoma evacuation following early surgery.

NIRs are well positioned to perform MIS for ICH, given their existing skill set. All NIRs who navigate complex intravascular pathways do possess the hand to eye coordination skill that is required to perform MIS for ICH. A standardized training protocol on models or cadavers, followed by supervised practice should qualify interested NIRs to perform MIS for ICH. The authors recommend NIRs to take up this challenge and enhance reproducibility.

Expansion of the workforce should occur alongside the development of guidelines for ultra-early MIS in ICH. NIRs practicing in thrombectomy-capable centers, especially in regions with limited neurosurgical coverage, should acquire MIS training to ensure rapid access to care.

The initial part of MIS for ICH training mandates neurosurgery supervised interventions. Demonstrated ability above a defined number of procedures should suffice for independent practice.

Centers without on-site neurosurgical support can manage most complications, including hematoma expansion, using MIS techniques. The authors recommend a referral to neurosurgery-capable centers if decompressive craniectomy is anticipated. Telemedicine consultations of neurosurgeons can help guide these multidisciplinary decisions.

Limitations

This study is limited in terms of generalizability due to the heterogeneous nature of the illness and the literature on ICH. The availability of high-tech MIS tools is not universal, particularly in low- and middle-income settings, which limits the global applicability of these techniques. Furthermore, it remains uncertain whether all NIRs possess the surgical skills required for MIS ICH, raising concerns regarding scalability and standardization. Additionally, much of the current evidence, including experiences reported in single-center case series, represents a limitation, highlighting the need for larger, multicenter studies to validate safety, efficacy, and reproducibility.

While some trials (e.g., MISTIE III, INVEST, MISICH) suggest MIS is feasible and safe, conclusive evidence demonstrating a consistent benefit in functional outcomes is limited. Except for the ENRICH trial and that done by Wang et al. (9,38), studies are small, non-randomized, or underpowered. There is significant heterogeneity in MIS trials regarding section criteria, surgical technique, timing of hematoma evacuation and outcomes measured. Proponents of MIS may overemphasize favorable outcomes while downplaying limitations, complications, or equivocal data. There is also potential bias from conflict of interest arising due to author ties with device manufacturers. The high-tech MIS tools are not universally available, especially in low- and middle-income settings, limiting global applicability. Finally, it remains unclear whether all NIRs possess the surgical skills required for MIS ICH which raises questions about scalability and standardization.

Conclusions

Continued technological advances in MIS and reproducible data on improved outcomes are fueling an attitude shift from the pre-existing “nihilistic” self-fulfilling prophecy towards a timely multidisciplinary approach to ICH care. The continued refinement of techniques and the results of ongoing trials demonstrating MIS safety and efficacy will influence its future adoption into clinical practice. When guidelines change to support the use of early MIS ICH evacuation, it will soon be incumbent upon stroke programs to accommodate the huge “Code ICH” demand that follows. Stroke programs should be equipped with an MIS capable team and facility. Adding this demand to already thinly stretched neurosurgeons poses real potential for burnout. One alternative is to train NIRs who already run streamlined stroke codes, provide neurocritical care for stroke patients and possess the hand-to-eye coordination required in minimally invasive techniques, to perform MIS ICH evacuation using an accelerated accreditation pathway.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Adnan Siddiqui and Liqi Shu) for the series “Innovative Frontiers in Neurointervention: Expanding Horizons in Techniques and Applications” published in Journal of Neurointervention. The article has undergone external peer review.

Peer Review File: Available at https://jni.amegroups.com/article/view/10.21037/jni-25-44/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jni.amegroups.com/article/view/10.21037/jni-25-44/coif). The series “Innovative Frontiers in Neurointervention: Expanding Horizons in Techniques and Applications” was commissioned by the editorial office without any funding or sponsorship. A.E.H. serves as the consultant/speaker of Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care, Galaxy Therapeutics, Route 92, Perfuze, CorTech, Imago, Shockwave, Toro, NeuroVasX, Xcath, Kaneka, Plaga, Project Neu, and BioPhiliQ. A.E.H. participated on DSMB-COMAND trial. A.E.H. served as the immediate past president of SVIN and co-founders of Quantanosis.ai, SWIFT Path, 3N Neurovascular, QRA, and Quanta Therapeutikos. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Cordonnier C, Demchuk A, Ziai W, et al. Intracerebral haemorrhage: current approaches to acute management. Lancet 2018;392:1257-68. [Crossref] [PubMed]
2. Gordillo-Resina M, Aranda-Martinez C, Arias-Verdú MD, et al. Mortality, Functional Status, and Quality of Life after 5 Years of Patients Admitted to Critical Care for Spontaneous Intracerebral Hemorrhage. Neurocrit Care 2024;41:583-97. [Crossref] [PubMed]
3. Fallenius M, Skrifvars MB, Reinikainen M, et al. Spontaneous Intracerebral Hemorrhage. Stroke 2019;50:2336-43. Erratum in: Stroke 2022;53:e64. [Crossref] [PubMed]
4. Sacco S, Marini C, Toni D, et al. Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry. Stroke 2009;40:394-9. [Crossref] [PubMed]
5. Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke 2022;53:e282-361. [Crossref] [PubMed]
6. Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for intracerebral hemorrhage (STICH): a single-center, randomized clinical trial. Neurology 1998;51:1359-63. [Crossref] [PubMed]
7. Mendelow AD, Gregson BA, Rowan EN, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013;382:397-408. [Crossref] [PubMed]
8. Gregson BA, Mendelow AD. International variations in surgical practice for spontaneous intracerebral hemorrhage. Stroke 2003;34:2593-7. [Crossref] [PubMed]
9. Pradilla G, Ratcliff JJ, Hall AJ, et al. Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage. N Engl J Med 2024;390:1277-89. [Crossref] [PubMed]
10. Xu X, Zhang H, Zhang J, et al. Minimally invasive surgeries for spontaneous hypertensive intracerebral hemorrhage (MISICH): a multicenter randomized controlled trial. BMC Med 2024;22:244. [Crossref] [PubMed]
11. Parry-Jones AR, Krishnamurthi R, Ziai WC, et al. World Stroke Organization (WSO): Global intracerebral hemorrhage factsheet 2025. Int J Stroke 2025;20:145-50. [Crossref] [PubMed]
12. Song D, Xu D, Li M, et al. Global, regional, and national burdens of intracerebral hemorrhage and its risk factors from 1990 to 2021. Eur J Neurol 2025;32:e70031. [Crossref] [PubMed]
13. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet 2009;373:1632-44. [Crossref] [PubMed]
14. Sheth KN. Spontaneous Intracerebral Hemorrhage. N Engl J Med 2022;387:1589-96. [Crossref] [PubMed]
15. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 2012;11:720-31. [Crossref] [PubMed]
16. Xi G, Reiser G, Keep RF. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective? J Neurochem 2003;84:3-9. [Crossref] [PubMed]
17. Kellner CP, Song R, Ali M, et al. Time to Evacuation and Functional Outcome After Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation. Stroke 2021;52:e536-9. [Crossref] [PubMed]
18. Kellner CP, Schupper AJ, Mocco J. Surgical Evacuation of Intracerebral Hemorrhage: The Potential Importance of Timing. Stroke 2021;52:3391-8. [Crossref] [PubMed]
19. Liu S, Su S, Long J, et al. The impact of time to evacuation on outcomes in endoscopic surgery for supratentorial spontaneous intracerebral hemorrhage: a single-center retrospective study. Neurosurg Rev 2023;47:2. [Crossref] [PubMed]
20. Gómez-Lado N, López-Arias E, Iglesias-Rey R, et al. (18)F-FMISO PET/MRI Imaging Shows Ischemic Tissue around Hematoma in Intracerebral Hemorrhage. Mol Pharm 2020;17:4667-75. [Crossref] [PubMed]
21. Siddique MS, Fernandes HM, Wooldridge TD, et al. Reversible ischemia around intracerebral hemorrhage: a single-photon emission computerized tomography study. J Neurosurg 2002;96:736-41. [Crossref] [PubMed]
22. Qureshi AI, Wilson DA, Hanley DF, et al. No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage. Neurology 1999;52:266-72. [Crossref] [PubMed]
23. Bako AT, Potter T, Pan A, et al. Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage. J Am Heart Assoc 2023;12:e027403. [Crossref] [PubMed]
24. Teo KC, Fong SM, Leung WCY, et al. Location-Specific Hematoma Volume Cutoff and Clinical Outcomes in Intracerebral Hemorrhage. Stroke 2023;54:1548-57. [Crossref] [PubMed]
25. Gregson BA, Broderick JP, Auer LM, et al. Individual patient data subgroup meta-analysis of surgery for spontaneous supratentorial intracerebral hemorrhage. Stroke 2012;43:1496-504. [Crossref] [PubMed]
26. Ge C, Zhao W, Guo H, et al. Comparison of the clinical efficacy of craniotomy and craniopuncture therapy for the early stage of moderate volume spontaneous intracerebral haemorrhage in basal ganglia: Using the CTA spot sign as an entry criterion. Clin Neurol Neurosurg 2018;169:41-8. [Crossref] [PubMed]
27. Ali M, Ascanio LC, Smith C, et al. Early and effective intracerebral hemorrhage evacuation is associated with a lower 1-year residual cavity volume and better functional outcomes. J Neurointerv Surg 2024;16:994-1004. [Crossref] [PubMed]
28. Troberg E, Kronvall E, Hansen BM, et al. Prediction of Long-Term Outcome After Intracerebral Hemorrhage Surgery. World Neurosurg 2019;124:e96-e105. [Crossref] [PubMed]
29. Hattori N, Katayama Y, Maya Y, et al. Impact of stereotactic hematoma evacuation on activities of daily living during the chronic period following spontaneous putaminal hemorrhage: a randomized study. J Neurosurg 2004;101:417-20. [Crossref] [PubMed]
30. Auer LM, Deinsberger W, Niederkorn K, et al. Endoscopic surgery versus medical treatment for spontaneous intracerebral hematoma: a randomized study. J Neurosurg 1989;70:530-5. [Crossref] [PubMed]
31. Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 2005;365:387-97. [Crossref] [PubMed]
32. Kim YZ, Kim KH. Even in patients with a small hemorrhagic volume, stereotactic-guided evacuation of spontaneous intracerebral hemorrhage improves functional outcome. J Korean Neurosurg Soc 2009;46:109-15. [Crossref] [PubMed]
33. Vespa P, Hanley D, Betz J, et al. ICES (Intraoperative Stereotactic Computed Tomography-Guided Endoscopic Surgery) for Brain Hemorrhage: A Multicenter Randomized Controlled Trial. Stroke 2016;47:2749-55. [Crossref] [PubMed]
34. Ali M, Smith C, Vasan V, et al. Management of intracavitary bleeding during ultra-early minimally invasive intracerebral hemorrhage evacuation. J Neurosurg 2025;142:1003-13. [Crossref] [PubMed]
35. Ali M, Zhang X, Ascanio LC, et al. Long-term functional independence after minimally invasive endoscopic intracerebral hemorrhage evacuation. J Neurosurg 2023;138:154-64. [Crossref] [PubMed]
36. Morgenstern LB, Demchuk AM, Kim DH, et al. Rebleeding leads to poor outcome in ultra-early craniotomy for intracerebral hemorrhage. Neurology 2001;56:1294-9. [Crossref] [PubMed]
37. Hanley DF, Thompson RE, Rosenblum M, et al. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet 2019;393:1021-32. [Crossref] [PubMed]
38. Wang WZ, Jiang B, Liu HM, et al. Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China. Int J Stroke 2009;4:11-6. [Crossref] [PubMed]
39. Rindler RS, Pradilla G. Trans-sulcal, channel-based parafascicular surgery for intracerebral hematoma. In: Zada G, Pradilla G, Day JD, eds. Subcortical neurosurgery: open and parafascicular channel-based approaches for subcortical and intraventricular lesions. Cham, Switzerland: Springer, 2022:217-29.
40. Pan J, Chartrain AG, Scaggiante J, et al. A Compendium of Modern Minimally Invasive Intracerebral Hemorrhage Evacuation Techniques. Oper Neurosurg 2020;18:710-20. [Crossref] [PubMed]
41. Hannah TC, Kellner R, Kellner CP. Minimally Invasive Intracerebral Hemorrhage Evacuation Techniques: A Review. Diagnostics (Basel) 2021;11:576. [Crossref] [PubMed]
42. Hersh EH, Gologorsky Y, Chartrain AG, et al. Minimally Invasive Surgery for Intracerebral Hemorrhage. Curr Neurol Neurosci Rep 2018;18:34. [Crossref] [PubMed]
43. Zhu H, Wang Z, Shi W. Keyhole endoscopic hematoma evacuation in patients. Turk Neurosurg 2012;22:294-9. [PubMed]
44. Zhang HZ, Li YP, Yan ZC, et al. Endoscopic evacuation of basal ganglia hemorrhage via keyhole approach using an adjustable cannula in comparison with craniotomy. Biomed Res Int 2014;2014:898762. [Crossref] [PubMed]
45. Ma H, Peng W, Xu S, et al. Advancements of Endoscopic Surgery for Spontaneous Intracerebral Hemorrhage. World Neurosurg 2025;193:160-70. [Crossref] [PubMed]
46. Kellner CP, Chartrain AG, Nistal DA, et al. The Stereotactic Intracerebral Hemorrhage Underwater Blood Aspiration (SCUBA) technique for minimally invasive endoscopic intracerebral hemorrhage evacuation. J Neurointerv Surg 2018;10:771-6. [Crossref] [PubMed]
47. Mei L, Fengqun M, Qian H, et al. Exploration of Efficacy and Safety of Interventions for Intraventricular Hemorrhage: A Network Meta-Analysis. World Neurosurg 2020;136:382-389.e6. [Crossref] [PubMed]
48. Guo W, Liu H, Tan Z, et al. Comparison of endoscopic evacuation, stereotactic aspiration, and craniotomy for treatment of basal ganglia hemorrhage. J Neurointerv Surg 2020;12:55-61. [Crossref] [PubMed]
49. Fu C, Wang N, Chen B, et al. Surgical Management of Moderate Basal Ganglia Intracerebral Hemorrhage: Comparison of Safety and Efficacy of Endoscopic Surgery, Minimally Invasive Puncture and Drainage, and Craniotomy. World Neurosurg 2019;122:e995-e1001. [Crossref] [PubMed]
50. Miller CM, Vespa P, Saver JL, et al. Image-guided endoscopic evacuation of spontaneous intracerebral hemorrhage. Surg Neurol 2008;69:441-6; discussion 446. [Crossref] [PubMed]
51. Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for supratentorial intracerebral hemorrhage: a randomized feasibility study. Stroke 1999;30:1833-9. [Crossref] [PubMed]
52. Cho DY, Chen CC, Chang CS, et al. Endoscopic surgery for spontaneous basal ganglia hemorrhage: comparing endoscopic surgery, stereotactic aspiration, and craniotomy in noncomatose patients. Surg Neurol 2006;65:547-55; discussion 555-6. [Crossref] [PubMed]
53. Feng Y, He J, Liu B, et al. Endoscope-Assisted Keyhole Technique for Hypertensive Cerebral Hemorrhage in Elderly Patients: A Randomized Controlled Study in 184 Patients. Turk Neurosurg 2016;26:84-9. [PubMed]
54. Wang L, Zhou T, Wang P, et al. Efficacy and safety of NeuroEndoscopic Surgery for IntraCerebral Hemorrhage: A randomized, controlled, open-label, blinded endpoint trial (NESICH). Int J Stroke 2024;19:587-92. [Crossref] [PubMed]
55. Hallenberger TJ, Fischer U, Bonati LH, et al. Early minimally invasive image-guided endoscopic evacuation of intracerebral hemorrhage (EMINENT-ICH): a randomized controlled trial. Trials 2024;25:692. [Crossref] [PubMed]
56. Fiorella D, Arthur AS, Mocco JD. 305 The INVEST trial: a randomized, controlled trial to investigate the safety and efficacy of image-guided minimally invasive endoscopic surgery with Apollo vs best medical management for supratentorial intracerebral hemorrhage. Neurosurgery 2016;1:187. [Crossref]
57. Kellner CP, Song R, Pan J, et al. Long-term functional outcome following minimally invasive endoscopic intracerebral hemorrhage evacuation. J Neurointerv Surg 2020;12:489-94. [Crossref] [PubMed]
58. Noiphithak R, Yindeedej V, Ratanavinitkul W, et al. Treatment outcomes between endoscopic surgery and conventional craniotomy for spontaneous supratentorial intracerebral hemorrhage: a randomized controlled trial. Neurosurg Rev 2023;46:136. [Crossref] [PubMed]
59. Rosales J, Carbonera LA, De Souza AC, et al. Intracerebral haemorrhage management practices and adherence to the INTERACT3 care bundle in Latin America: Results from an international survey. J Stroke Cerebrovasc Dis 2025;34:108419. [Crossref] [PubMed]
60. Toyoda K, Palesch YY, Koga M, et al. Regional Differences in the Response to Acute Blood Pressure Lowering After Cerebral Hemorrhage. Neurology 2021;96:e740-51. [Crossref] [PubMed]
61. Fahlström A, Tobieson L, Redebrandt HN, et al. Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients. Acta Neurochir (Wien) 2019;161:955-65. [Crossref] [PubMed]
62. Becker KJ, Baxter AB, Cohen WA, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology 2001;56:766-72. [Crossref] [PubMed]
63. Gupta S, Gal ZT, Athni TS, et al. Mapping the global neurosurgery workforce. Part 1: Consultant neurosurgeon density. J Neurosurg 2024;141:1-9. [Crossref] [PubMed]
64. Fiorella D, Peeling L, Denice CM, et al. Integrated flat detector CT and live fluoroscopic-guided external ventricular drain placement within the neuroangiography suite. J Neurointerv Surg 2014;6:457-60. [Crossref] [PubMed]
65. Chen H, Marino J, Stemer AB, et al. Emerging Subspecialties in Neurology: Interventional Neurology: A Starter Guide for Neurology Residents. Neurology 2023;101:e1939-42. [Crossref] [PubMed]
66. Lawton MT, Vates GE. Subarachnoid Hemorrhage. N Engl J Med 2017;377:257-66. [Crossref] [PubMed]
67. Lylyk P, Lylyk I, Bleise C, et al. First-in-human endovascular treatment of hydrocephalus with a miniature biomimetic transdural shunt. J Neurointerv Surg 2022;14:495-9. [Crossref] [PubMed]
68. Padwal J, Georgy MM, Georgy BA. Spinal cord stimulators in an outpatient interventional neuroradiology practice. J Neurointerv Surg 2014;6:708-11. [Crossref] [PubMed]
69. Huo X, Sun X, Zhang Z, et al. Dyna-CT-assisted percutaneous microballoon compression for trigeminal neuralgia. J Neurointerv Surg 2014;6:521-6. [Crossref] [PubMed]
70. Bishop CV, Drummond KJ. Rural neurotrauma in Australia: implications for surgical training. ANZ J Surg 2006;76:53-9. [Crossref] [PubMed]
71. Ellegala DB, Simpson L, Mayegga E, et al. Neurosurgical capacity building in the developing world through focused training. J Neurosurg 2014;121:1526-32. [Crossref] [PubMed]
72. Hu J, Sokh V, Nguon S, et al. Emergency Craniotomy and Burr-Hole Trephination in a Low-Resource Setting: Capacity Building at a Regional Hospital in Cambodia. Int J Environ Res Public Health 2022;19:6471. [Crossref] [PubMed]
73. Attebery JE, Nuwas E, Mayegga E, et al. Global Neurosurgery: A Retrospective Cohort Study to Compare the Effectiveness of Two Training Methods in Resource-Poor Settings. Neurosurgery 2024;94:263-70. [Crossref] [PubMed]
74. Tekle W, Benites G, Miller S, et al. Minimally invasive surgery for evacuation of intracerebral hematoma by neurointerventionalists: initial experience. J Neurointerv Surg 2025;17:1223-8. [Crossref] [PubMed]