Highlight
– The MIND randomized clinical trial compared minimally invasive surgery (MIS) using the Artemis Neuro Evacuation Device to guideline-based medical management alone for spontaneous supratentorial intracerebral hemorrhage (ICH).
– MIS achieved substantial hemorrhage volume reduction (median 80.7%) but did not significantly improve 180-day functional outcomes or reduce 30-day mortality versus medical management alone.
– Safety outcomes were comparable between groups, with low rates of procedure-related complications.
– Early trial termination limited power, though subgroup trends suggested possible benefit in patients with lobar hemorrhages.
Study Background and Disease Burden
Intracerebral hemorrhage (ICH), a devastating subtype of stroke characterized by bleeding into the brain parenchyma, accounts for approximately 10-15% of all strokes worldwide and bears high morbidity and mortality. Supratentorial ICH, involving brain regions above the tentorium cerebelli, is the most common form and is frequently associated with hypertension or cerebral amyloid angiopathy. Despite advances in critical care and medical management, functional outcomes remain poor, and mortality rates are substantial.
A pivotal clinical question in managing supratentorial ICH is whether surgical evacuation of the hematoma improves survival and functional recovery. Traditional open craniotomy carries risks of brain tissue injury and complications, prompting exploration of minimally invasive surgical (MIS) techniques to evacuate hematomas with less brain disruption. However, evidence supporting surgery versus medical management alone remains inconclusive, and consensus treatment guidelines vary worldwide.
This unmet clinical need motivated the MIND (Minimally Invasive Neurosurgery vs Medical Management for Intracerebral Hemorrhage) trial to rigorously compare the safety and efficacy of MIS using the Artemis Neuro Evacuation Device against guideline-based medical therapy alone.
Study Design
The MIND trial was a prospective, open-label, multicenter, randomized clinical trial conducted across 32 global sites, enrolling adult patients aged 18 to 80 years. Eligibility criteria included spontaneous supratentorial ICH volumes between 20 mL and 80 mL, baseline National Institutes of Health Stroke Scale (NIHSS) score ≥6, and Glasgow Coma Scale (GCS) score between 5 and 15.
From February 2018 to August 2023, 236 patients were randomized in a 2:1 ratio to MIS plus medical management (n=154) or medical management alone (n=82). Minimally invasive surgery was performed within 72 hours of symptom onset using the Artemis device designed for precise brain hematoma evacuation.
The primary efficacy outcome was the 180-day combined endpoint of death and disability measured by the ordinal modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death). The primary safety outcome was mortality at 30 days. Secondary endpoints included utility-weighted mRS scores, dichotomized mRS ≤2 and ≤3, length of ICU and hospital stay, and procedural adverse events.
Key Findings
The trial was stopped early after 236 patients were enrolled due to feasibility considerations following positive results from a contemporaneous ICH surgical trial.
Baseline characteristics were balanced: median age was 60 years; 36.9% female; 69.5% had deep hemorrhages, and 30.5% lobar hemorrhages. Median time to MIS was 27.5 hours, with 38.7% undergoing surgery within 24 hours.
Hemorrhage volume reduction after MIS was notable, with a median 80.7% volume decrease to 6.3 mL, and 79.2% of patients having residual volumes ≤15 mL. Similar evacuation efficiency was observed in both deep and lobar hemorrhages. Procedural complication rates were low with 12.5% requiring external ventricular drains, 1.4% conversion to craniotomy, and 6.3% requiring cauterization for hemorrhage.
However, in the intention-to-treat population, no statistically significant difference was observed in the primary outcome of 180-day ordinal mRS between MIS and medical management alone (OR 1.03, 96% CI 0.62–1.72, P=0.45 unadjusted; OR 1.10, 96% CI 0.66–1.85, P=0.35 adjusted). Similar findings persisted in the per-protocol population.
Secondary outcomes mirrored primary efficacy results: utility-weighted mRS scores and dichotomized mRS thresholds showed no meaningful difference. Length of ICU and hospital stay trended shorter with MIS but without statistical significance.
Safety analyses demonstrated comparable 30-day mortality (7.2% MIS vs 9.8% medical management; difference −2.5%, 96% CI −11.7% to 4.8%) and 180-day mortality (13.2% vs 18.3%, difference −5.1%, 96% CI −16.1% to 4.5%). Kaplan–Meier survival analysis up to 30 days revealed no significant survival difference overall but hinted at potential benefit in the lobar hemorrhage subgroup.
Expert Commentary
The MIND trial adds rigorous randomized data to ongoing debates about optimal surgical intervention in supratentorial ICH. Despite robust hematoma reduction with the Artemis device, this did not translate into statistically significant improvements in long-term functional outcomes or mortality compared to contemporary medical management alone.
These findings align with prior trials where the benefit of hematoma evacuation was inconsistent, likely reflecting ICH pathophysiology complexity, patient heterogeneity, and timing of intervention. Minimally invasive techniques reduce parenchymal trauma relative to open surgery but may still not confer sufficient benefit to overcome injury mechanisms such as perihematomal edema, inflammation, and neuronal death.
Notable strengths include prospective design, multicenter participation, and clinically meaningful endpoints. However, early termination limited statistical power to detect modest effect sizes. Additionally, the enrolled population skewed toward deep hemorrhages with fewer lobar cases where surgical benefit may differ.
Future research should explore patient selection, optimal timing, adjunctive therapies to mitigate secondary injury, and incorporate advanced neuroimaging biomarkers to personalize intervention strategies. Combination approaches addressing both hematoma evacuation and neuroprotection may ultimately improve outcomes.
Conclusion
The MIND randomized clinical trial demonstrated that minimally invasive surgery using the Artemis Neuro Evacuation Device within 72 hours of symptom onset in patients with spontaneous supratentorial ICH did not significantly reduce 30-day mortality or improve 180-day functional outcomes compared to guideline-based medical management alone.
While MIS achieved substantial hematoma volume reduction with favorable safety, it did not translate into superior clinical recovery in this trial cohort. These findings underscore the prevailing uncertainty surrounding surgical intervention benefits in ICH and reinforce the necessity of personalized treatment decisions framed by ongoing trials and emerging evidence.
Clinicians should continue adherence to evidence-based medical management while considering MIS on a case-by-case basis, especially in select subgroups such as lobar hemorrhages where trends toward benefit were noted.
References
1. Arthur AS, Jahromi BS, Saphier PS, et al; MIND Study Investigators and Collaborators. Minimally Invasive Surgery vs Medical Management Alone for Intracerebral Hemorrhage: The MIND Randomized Clinical Trial. JAMA Neurol. 2025 Sep 2:e253151. doi:10.1001/jamaneurol.2025.3151.
2. Hemphill JC 3rd, Greenberg SM, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage. Stroke. 2015;46(7):2032-2060.
3. Mendelow AD, Gregson BA, 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(9457):387-397.
4. Wang WZ, Jiang B, et al. Efficacy and Safety of Minimally Invasive Surgery for Spontaneous Intracerebral Hemorrhage: A Meta-Analysis. Neurol Res. 2020;42(2):69-77.
5. Doerfler A, Rohde V, Hastreiter P, et al. Minimally invasive surgery for spontaneous intracerebral hemorrhage using ultrasound and endoscopy: technique and initial experience. Neurosurgery. 2002;50(6):1344-1349.
