The Early Minimally Invasive Removal of Intracerebral Hemorrhage: A Critical Appraisal

Dear Editor, Hemorrhagic stroke (HS) is characterized by the abrupt rupture of small blood vessels located in the brain parenchyma, leading to the accumulation of blood that causes damage to surrounding brain structures and can lead to catastrophic outcomes.[1] Concerning HS, it is well-known that it is a primary subtype of stroke, estimated to account for 10%–15% of all stroke cases in North America and Europe and up to 20%–30% in parts of Asia. Worldwide,[2] HS is a significant public health problem, contributing significantly to long-term disability and increasing health care costs. As to pathobiology, the underlying mechanisms of HS are multifactorial. In patients with chronic uncontrolled arterial hypertension, HS represents 60%–70% of cases. It is well-known that hypertension leads to lipo hyalinosis, microaneurysm formation, and eventually, rupture of small penetrating arteries, particularly within the basal ganglia, thalamus, cerebellum, and brain stem.[3] HS also correlates with conditions such as cerebral amyloid angiopathy, particularly in older people, where amyloid protein deposition weakens vascular walls, predisposing to lobar hemorrhages. It is essential to mention that anticoagulant therapy, such as warfarin or direct oral anticoagulants (DOACs), may also have etiological implications. The management of HS is a challenge for neurosurgeons and requires multidisciplinary management.[4] In connection with the objective, focusing on stabilizing the patient, limiting the expansion of the hematoma, and controlling complications such as elevated intracranial pressure, seizures, and neurological deterioration is a priority.[5] Prognosis following spontaneous intracerebral hemorrhage (SICH) depends on several factors, including the volume of the hematoma, location, patient’s age, the Glasgow Coma Scale (GCS) score at presentation, and the presence of intraventricular hemorrhage. Patients with larger hematomas, deep-seated hemorrhages (e.g., in the brainstem), and low GCS scores are at higher risk of poor outcomes. For patients on anticoagulants, rapid reversal of anticoagulation is essential. Vitamin K and prothrombin complex concentrates are used to reverse warfarin. At the same time, specific reversal agents like idarucizumab (for dabigatran) and exanet alfa (for factor Xa inhibitors) are now available for DOACs. Despite significant advances in the acute treatment of SICH, it is essential to highlight that no specific neuroprotective agent has been approved and can be used routinely in neurocritical care. Regarding the surgical evacuation of the hematoma, this decision can be considered for young patients who present with extensive lobar hemorrhages or in patients presenting mass effects associated with deterioration of the state of consciousness. Research results using minimally invasive surgery (MIS), such as stereotaxic aspiration and endoscopic evacuation, may reduce surgical morbidity. However, MIS plus rtPA for Evacuation of ICH (MISTIE III) demonstrated that while MIS was safe, the benefits in terms of functional outcomes are not entirely clear. Functional recovery is variable, with many survivors experiencing long-term neurological deficits, including hemiparesis, aphasia, cognitive impairment, and behavioral changes. Rehabilitation, including physical, occupational, and speech therapy, is essential for maximizing functional outcomes. Supportive care and management of comorbidities such as hypertension, diabetes, and atrial fibrillation are crucial in preventing recurrence. According to recent guidelines from the American Heart Association (AHA) and American Stroke Association (ASA), they use strict blood pressure control in the acute setting to prevent further hematoma expansion. Systolic blood pressure is generally reduced to a target of 140 mmHg using intravenous antihypertensives such as nicardipine, labetalol, or clevidipine. Results of Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 have shown that ultra-low blood pressure targets (<120 mmHg) may not provide additional benefit and could increase the risk of adverse renal events. THE EARLY MINIMALLY INVASIVE REMOVAL OF INTRACEREBRAL HEMORRHAGE Neurosurgical management has shown positive results in terms of mortality but not in terms of functional prognosis. Results have been validated in previous clinical trials (STITCH, STITCH II). The early Minimally invasive Removal of ICH trial was designed to investigate any benefit of early MIS trans-sulcal parafascicular surgery (MIPS) in superficial ICH.[6] This was a multicenter, two-arm, randomized, adaptive design. With block randomization 1:1 m, this trial was stratified by ICH location (anterior basal ganglia vs. lobar) and Index GCS (<9 or ≥9). Out of 300 enrolled patients, 30.7% had anterior basal ganglia hemorrhages, while 69.3% had lobar hemorrhages. The intervention consists of early evacuation of the ICH within 24 h, but ideally <8 h, using minimal techniques and a trans-sulcal to fascicular surgery (MIPS) approach associated with standard management.[7] In both groups, AHA/ASA guidelines were implemented. Aggressive resuscitation management, Blood pressure, correction of bleeding diathesis, and traditional surgical techniques permitted, like external ventricular drain craniectomy, were also used if required. Based on the utility-weighted mean modified Rankin Scale score at 180 days, a benefit was evident in patients with lobar hemorrhage, 0.458 (surgical group) versus 0.374 (control group), lobar ICH (0.513 vs. 0.371, difference of 0.127, 95% Cr I 0.035–0.219). However, no significant difference was observed in those with anterior basal ganglia involvement. Secondary and safety outcomes showed that, compared with the control group, the surgical group had a more significant reduction in hematoma volume (−43.9 vs. 4.0 mL; difference of − 47.9 mL, 95% confidence interval [CI] −53.6 to −42.4 mL), without apparent significant differences in the score of ≤3 On the modified Rankin scale at 180 days (50.3% vs. 41.0%; difference of 9.2%, 95% CIr-2.0-20.3%). On the other hand, the surgical group had a shorter ICU stay (6.9 vs. 9.7 days; difference of −2.8 days, 95% CI −4.5 to −1.1 days), shorter hospital stay (14.9 vs. 18.1 days; difference of −3.1 days, 95% CrI −5.9 to −0.4 days), and a lower percentage of serious adverse events (63.3% vs. 78.7%; difference of −15.3%, 95% CrI −25.4 to −5.2%). The strengths include a well-planned study methodologically, with evidence supporting the development of the clinical trial, and a patient-centered primary endpoint focused on functional outcomes. Baseline characteristics were well-balanced between intervention and control groups. It should be noted that this study was multicenter, randomized, and had a minimal loss to follow-up (8/300). Bias in subjective Menopause Rating Scale reporting was minimized by involving the caregivers in assessments and conducting blinded reviews by a neuropsychologist. The neurosurgical intervention successfully reduced hematoma volume with a low rebleeding rate. The prepublished statistical analysis plan ensured methodological transparency. Among the weaknesses is the study’s external validity, which is limited by its single-country setting; a high group of patients with compressive craniectomy was included. The latter may alter the conclusions considering the functional impact. Although these results are based on a small population, they are promising and demonstrate their effects at a functional level. Neurosurgical management and decision-making rely on a team determining the best patient approach. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.