Subdural hematoma - Emerging treatments

Hinge craniotomy (HC) for acute subdural hematoma (SDH)

HC is an alternative surgical technique that allows for a degree of cerebral decompression whilst retaining the bone flap in situ in a hinged or floating manner.[149] The objective is to allow expansion of any ensuing cerebral edema while preventing the need for later cranioplasty. One scoping review of 15 studies totalling 283 patients with traumatic brain injury (TBI) or stroke (mean age 45 years) found at least equivalent control of intracranial pressure (ICP) compared with decompressive craniectomy, with lower rates of complications including infection.[149] One subsequent study covered 48 patients who underwent evacuation of an acute SDH in a single center in Japan.[150] Conventional craniotomy (CC) was performed for those with no observed brain swelling (23 patients), HC was performed for those in whom brain swelling was observed intraoperatively (23 patients) and decompressive craniectomy (DC) for 2 patients in whom the brain was too swollen to allow replacement of the bone flap. In-hospital mortality was 100% for DC, 22% for HC and 13% for CC. Only one patient who underwent HC required secondary DC.[150] The exact indications, optimum technique and outcomes remain to be fully determined but hinge craniotomy has potential to gain traction in clinical practice.[149]

Corticosteroids

Corticosteroids had been proposed as a treatment targeting inflammation and angiogenesis in chronic SDHs.[151] However, subsequent studies have confirmed that they appear to do more harm than good, whether used in addition to or as an alternative to surgery. Expert consensus recommends against the use of corticosteroids for SDH. One small series found a benefit for corticosteroid treatment for recurrent chronic SDHs.[152] However, in one UK multicenter, randomized trial among adults with symptomatic chronic SDH (n=680), most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes (defined as a score of 0 to 3 on the modified Rankin scale at 6 months) and more adverse events (e.g., hyperglycemia, new-onset diabetes, new-onset psychosis, and infections) than placebo at 6 months. However, fewer repeat operations for reaccumulation of the subdural collection were performed in the dexamethasone group.[153] In addition, another study comparing burr hole craniotomy to burr hole craniotomy plus corticosteroids showed that adding steroid treatment increased medical complications, increased hospital length of stay, and increased the number of computed tomography scans.[50] One multicenter open-label trial of 252 patients with symptomatic chronic SDH that compared conservative management with a 19-day tapering course or dexamethasone versus burr hole drainage surgery was ended early owing to safety and outcome concerns in the group who received dexamethasone. Most results with respect to functional outcomes at 3 months favored surgery, and dexamethasone was associated with more complications and a greater need for later surgery when compared with burr hole drainage (complications occurred in 59% vs. 32% respectively and additional surgery was needed in 55% vs. 6% respectively).[31] The authors concluded that dexamethasone employed as an alternative to surgery for chronic SDH is associated with fewer favorable outcomes and more adverse events.

Platelet-activating factor

Platelet-activating factor has been shown to influence the formation of the neovascular membrane associated with chronic SDHs. Blocking activation of platelet-activating factor using the platelet-activating factor antagonist etizolam has been shown in small studies to decrease the need for surgery and recurrence of chronic subdurals after surgery.[154][155]

Tranexamic acid

CRASH-3, one large randomized controlled trial (RCT) of 12,737 patients, showed a reduction in mortality in patients with mild-to-moderate head injury (baseline Glasgow Coma Scale 9-15) who were treated antifibrinolytic agent tranexamic acid within 3 hours of injury, compared with those who were not.[156] However, its results should be interpreted with some caution due to: significance only in the subgroup analysis; change in recruitment (from within 8 to within 3 hours of injury); change in primary outcome (from all-cause to disease-specific mortality); and the risk of selection and observer bias. One RCT published in 2020 (n=1280, 20 centers, and 39 emergency medical services agencies in the US and Canada) compared tranexamic acid with placebo within 2 hours of moderate or severe TBI.[157] A favorable functional neurologic outcome (measured as Glasgow Outcome Scale-Extended >4 at 6 months) occurred in 65% of patients in the tranexamic acid groups versus 62% with placebo. There was, however, no statistically significant difference in all-cause 28-day mortality, Disability Rating Scale score at 6 months, or progression of intracranial hemorrhage. So, although the results of CRASH-3 are promising, some uncertainty remains and guidance may vary. Research is ongoing to establish whether there is a role for tranexamic acid in management of chronic SDH, either to reduce the risk of recurrence of surgically managed chronic SDH or as a conservative alternative to surgical management.[158][159] One small RCT (n=193) suggested that use of tranexamic acid may be associated with a reduction in hematoma volume after burr hole surgery.[160] Evidence from small, retrospective observational studies suggests tranexamic acid may reduce hematoma volume in patients with chronic SDH who are managed conservatively.[59][161] One survey of European clinical practice, published in 2018, found that 45% of 84 neurosurgeons who responded would consider the use of tranexamic acid as an adjunct to surgery in managing patients with chronic SDH.[162]

Middle meningeal artery (MMA) embolization

MMA embolization has emerged as a minimally invasive treatment to manage chronic SDH.[163][164] It can be used both as an adjunct treatment to prevent recurrence in surgically evacuated chronic SDH and as a stand‐alone procedure to treat both asymptomatic and symptomatic chronic SDH.[53] It should not be used in lieu of surgery in a patient with symptomatic elevation of ICP. A catheter is inserted into the common femoral or radial artery and a microcatheter is then guided into the MMA, which provides a blood supply to the neovascularised dural membrane in chronic SDH and thereby contributes to hematoma expansion.[30][165] Angiography is used to select target MMA branches for embolization.[165] The aim is to eliminate the blood supply from the MMA to the membrane around the hematoma, thereby allowing gradual spontaneous resolution of the hematoma and reducing the risk of recurrence.[165] Subsequent systematic reviews and meta-analyses have also found MMAE to be a safe and effective option that reduces the need for surgical rescue and is associated with lower rates of chronic SDH recurrence.[166][167][168] One multicenter randomized trial concluded that among patients with symptomatic subacute or chronic SDH with an indication for surgical evacuation, MMAE plus surgery was associated with a lower risk of hematoma recurrence or progression leading to repeat surgery within 90 days when compared with surgery alone.[169] However, in one RCT of patients who underwent an operation for chronic SDH recurrence or a first chronic SDH episode at high risk of recurrence, MMA embolization did not lead to a significantly lower rate of recurrence at 6 months compared with standard medical care alone.[170] Further randomized trials are under way to understand appropriate patient selection, optimal embolization techniques, and timing of embolization.[171]