DOI: 10.1136/bmjopen-2025-111789 ISSN: 2044-6055

Evolution of blood biomarkers reflective of brain tissue damage and inflammation in the perioperative course of intracerebral haemorrhage evacuation in a phase II proof-of-concept trial

Tim Jonas Hallenberger, Eline Willemse, Catherine Brégère, Nilabh Ghosh, Leo H Bonati, Aleksandra Maleska Maceski, Pascal Benkert, Urs Fischer, Jehuda Soleman, David Leppert, Raphael Guzman, Jens Kuhle
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Background

Whether surgical haematoma evacuation leads to reduced brain damage in patients with spontaneous supratentorial intracerebral haemorrhage (SSICH) remains unknown. Blood biomarkers reflecting brain damage could aid in prognosticating the clinical outcome and hence support quantifying the benefit of surgical interventions.

Methods

Blood samples from 10 patients with SSICH in the phase II early minimally invasive image-guided endoscopic evacuation of intracerebral hemorrhage (EMINENT-ICH) pilot study ( NCT04805177 , completed) were collected longitudinally (at baseline, 24 hours, 3 days, 1 week, 1 month and 6 months after surgical haematoma evacuation). Neurofilament light chain (NfL), glial fibrillar acidic protein (GFAP), calcium-binding protein S100B and the inflammatory markers interferon-gamma, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were quantified. The perioperative and long-term course of concentrations and association with clinical outcome measures were assessed. A favourable outcome was defined as a modified ranking scale ≤3.

Results

Favourable outcome was observed in 60% (6/10) of patients (median age 72.5 years (IQR 67.5–79.8), 70% male), and in 70% (7/10) of patients, the preset goal of a postsurgery haematoma volume below 15 mL was achieved. On average, patients with unfavourable outcomes at 6 months had twofold higher NfL and sixfold higher GFAP concentrations compared with those with favourable outcomes (p NfL =0.127, p GFAP =0.017); concentrations of both markers were higher in patients with unsatisfactory haematoma evacuation (3.7-fold for NfL, p=0.0072 and 12.4-fold for GFAP, p=0.0122). Concentrations of other markers, especially ILs, were not indicative of functional outcomes.

Conclusions

Based on our results, we provide preliminary evidence that lower serum NfL and GFAP levels are associated with favourable clinical outcomes and successful haematoma evacuation in SSICH.

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