Iftakher Hossain

Background: Cortical contusions are common in moderate-severe traumatic brain injury (TBI). Cortical contusions often expand, potentially causing neuro-worsening several hours to days post-trauma. While contusion expansion (CE) may affect outcome, potential clinical and radiological markers that can predict CE have been insufficiently explored. In the present single-center retrospective observational cohort study, we evaluated clinical outcome by the Glasgow Outcome Scale extended (GOSE) scale and evaluated risk factor for CE. Method: Adult TBI patients > 18 years of age, and of all injury severities, were included. Main variables of interest were low platelet count, defined as < 150 × 10⁹/L, presence of bifrontal contusions and CE, defined as absolute contusion volume increase in cm³. Factors associated with CE and clinical outcome according to GOSE were analyzed. Results: Between 2012–2022, 272 patients were included. Contusion size on admission correlated positively with CE, as did the Marshall and Rotterdam radiological classification scores. Bifrontal contusions were significantly larger at admission, experienced larger CE, and had a worse outcome than contusions in other locations. Patients with a platelet count < 150 × 10⁹/L experienced a greater volume CE and had a worse outcome when compared to patients with a normal platelet count. In a multivariate analysis, CE remained significantly associated with a poor outcome six months post- injury. Conclusion: Contusion volume at admission, Marshall CT classification and Rotterdam CT score, positively correlated to CE. Bifrontal contusions and a platelet count < 150 × 10⁹/L were associated with CE, and a poor clinical outcome. Large CE volumes were associated with a worse clinical outcome, and CE was per se associated with outcome in a multivariate analysis. Management of these risk factors for CE in the acute post-injury setting may be needed to attenuate contusion expansion and to improve clinical outcome in TBI patients suffering from cortical contusion injuries.

Decompressive craniectomy (DC) is a surgical procedure in which a large section of the skull is removed, and the underlying dura mater is opened widely. After evacuating a traumatic acute subdural hematoma, a primary DC is typically performed if the brain is bulging or if brain swelling is expected over the next several days. However, a recent randomized trial found similar 12-month outcomes when primary DC was compared with craniotomy for acute subdural hematoma. Secondary removal of the bone flap was performed in 9% of the craniotomy group, but more wound complications occurred in the craniectomy group. Two further multicenter trials found that, whereas early neuroprotective bifrontal DC for mild to moderate intracranial hypertension is not superior to medical management, DC as a last-tier therapy for refractory intracranial hypertension leads to reduced mortality. Patients undergoing secondary last-tier DC are more likely to improve over time than those in the standard medical management group. The overall conclusion from the most up-to-date evidence is that secondary DC has a role in the management of intracranial hypertension following traumatic brain injury but is not a panacea. Therefore, the decision to offer this operation should be made on a case-by-case basis. Following DC, cranioplasty is warranted but not always feasible, especially in low- and middle-income countries. Consequently, a decompressive craniotomy, where the bone flap is allowed to “hinge” or “float,” is sometimes used. Decompressive craniotomy is also an option in a subgroup of traumatic brain injury patients undergoing primary surgical evacuation when the brain is neither bulging nor relaxed. However, a high-quality randomized controlled trial is needed to delineate the specific indications and the type of decompressive craniotomy in appropriate patients.

Neurofilament light (NF-L) is an axonal protein that has shown promise as a traumatic brain injury (TBI) biomarker. Serum NF-L shows a rather slow rise after injury, peaking after 1–2 weeks, although some studies suggest that it may remain elevated for months after TBI. The aim of this study was to examine if plasma NF-L levels several months after the injury correlate with functional outcome in patients who have sustained TBIs of variable initial severity. In this prospective study on 178 patients with TBI and 40 orthopaedic injury controls, we measured plasma NF-L levels in blood samples taken at the follow-up appointment on average nine months after injury. Patients with TBI were divided into two groups [mild (mTBI) vs. moderate to severe (mo/sTBI)] according to the severity of injury assessed with the Glasgow Coma Scale upon admission. Recovery and functional outcome were assessed using the Extended Glasgow Outcome Scale (GOSE). Higher levels of NF-L at the follow-up correlated with worse outcome in patients with moderate to severe TBI (Spearman’s rho = -0.18; p < 0.001). In addition, in CT-positive mTBI group, the levels of NF-L were significantly lower in patients with GOSE 7–8 (median 18.14; IQR 9.82, 32.15) when compared with patients with GOSE <7 (median 73.87; IQR 32.17, 110.54; p = 0.002). In patients with mTBI, late NF-L levels do not seem to provide clinical benefit for late-stage assessment, but in patients with initially mo/sTBI, persistently elevated NF-L levels are associated with worse outcome after TBI and may reflect ongoing brain injury. Keywords: traumatic brain injury, outcome, biomarker, Neurofilament light, NF-L

Blood biomarkers have been studied to improve the clinical assessment and prognostication of patients with moderate-severe traumatic brain injury (mo/sTBI). To assess their clinical usability, one needs to know of potential factors that might cause outlier values and affect clinical decision making. In a prospective study, we recruited patients with mo/sTBI ( n = 85) and measured the blood levels of eight protein brain pathophysiology biomarkers, including glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), neurofilament light (Nf-L), heart-type fatty acid-binding protein (H-FABP), interleukin-10 (IL-10), total tau (T-tau), amyloid β40 (Aβ40) and amyloid β42 (Aβ42), within 24 h of admission. Similar analyses were conducted for controls ( n = 40) with an acute orthopedic injury without any head trauma. The patients with TBI were divided into subgroups of normal versus abnormal ( n = 9/76) head computed tomography (CT) and favorable (Glasgow Outcome Scale Extended [GOSE] 5–8) versus unfavorable (GOSE Q3 + 1.5 IQR. A logical explanation was found for almost all cases, except the amyloid proteins. Explanations for outlier values included extremely severe injury, especially for GFAP and S100B. In the case of H-FABP and IL-10, the explanation was extracranial injuries (thoracic injuries for H-FABP and multi-trauma for IL-10), in some cases these also were associated with abnormally high S100B. Timing of sampling and demographic factors such as age and pre-existing neurological conditions (especially for T-tau), explained some of the abnormally high values especially for Nf-L. Similar explanations also emerged in controls, where the outlier values were caused especially by pre-existing neurological diseases. To utilize blood-based biomarkers in clinical assessment of mo/sTBI, very severe or fatal TBIs, various extracranial injuries, timing of sampling, and demographic factors such as age and pre-existing systemic or neurological conditions must be taken into consideration. Very high levels seem to be often associated with poor prognosis and mortality (GFAP and S100B).