The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set. METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not. RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P -value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P -value = .69). Postoperative HV was not reduced by TXA (mean difference -8.97 95% CI -23.77, 5.82; P -value = .45). CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery.

Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. METHODS: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. CONCLUSION: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.

Surgery for Malignant Acute Ischemic Stroke: A Narrative Review of the Knowns and Unknowns.

Malignant acute ischemic stroke (AIS) is characterized by acute neurological deterioration caused by progressive space-occupying brain edema, often occurring in the first hours to days after symptom onset. Without any treatment, the result is often fatal. Despite advances in treatment for AIS, up to 80% of patients with a large hemispheric stroke or cerebellar stroke are at risk of poor outcome. Decompressive surgery can be life-saving in a subgroup of patients with malignant AIS, but uncertainties exist on patient selection, predictors of malignant infarction, perioperative management, and timing of intervention. Although survivors are left disabled, most agree with the original decision to undergo surgery and would make the same decision again. In this narrative review, we focus on the clinical and radiological predictors of malignant infarction in AIS and outline the technical aspects of decompressive surgery as well as duraplasty and cranioplasty. We discuss the current evidence and recommendations for surgery in AIS, highlighting gaps in knowledge, and suggest directions for future studies. KEY POINTS: · Acute ischemic stroke from occlusion of a proximal intracranial artery can progress quickly to malignant edema, which can be fatal in 80% of patients despite medical management.. · Decompression surgery is life-saving within 48 hours of stroke onset, but the benefits beyond this time and in the elderly are unknown.. · Decompressive surgery is associated with high morbidity, particularly in the elderly. The decision to operate must be made after considering the individual's preference and expectations of quality of life in the context of the clinical condition.. · Further studies are needed to refine surgical technique including value of duraplasty and understand the role monitoring intracranial pressure during and after decompressive surgery.. · More studies are needed on the pathophysiology of malignant cerebral edema, prediction models including imaging and biomarkers to identify which subgroup of patients will benefit from decompressive surgery.. · More research is needed on factors associated with morbidity and mortality after cranioplasty, safety and efficacy of implants, and comparisons between them.. · Further studies are needed to assess the long-term effects of physical disability and quality of life of survivors after surgery, particularly those with severe neurological deficits..

Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection.

BACKGROUND: The effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6-24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relationship with time-to-EVT treatment beyond 6 hours of stroke onset without advanced neuroimaging. METHODS: Patients who underwent EVT selected with non-contrast CT/CT angiography (without CT perfusion or MR imaging), between October 2015 and March 2020, were included from a national stroke registry. Functional and safety outcomes were assessed in both early (<6 hours) and late windows with time analyzed as a continuous variable. RESULTS: Among 3278 patients, 2610 (79.6%) and 668 (20.4%) patients were included in the early and late windows, respectively. In the late window, for every hour delay, there was no significant association with shift towards poorer functional outcome (modified Rankin Scale (mRS)) at discharge (adjusted common OR 0.98, 95% CI 0.94 to 1.01, p=0.27) or change in predicted functional independence (mRS ≤2) (24.5% to 23.3% from 6 to 24 hours; aOR 0.99, 95% CI0.94 to 1.04, p=0.85). In contrast, predicted functional independence was time sensitive in the early window: 5.2% reduction per-hour delay (49.4% to 23.5% from 1 to 6 hours, p=0.0001). There were similar rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 4.6%, p=0.54) and in-hospital mortality (12.9% vs 14.6%, p=0.33) in the early and late windows, respectively, without a significant association with time. CONCLUSION: In this real-world study, there was minimal change in functional disability, sICH and in-hospital mortality within and across the late window. While confirmatory randomized trials are needed, these findings suggest that EVT remains feasible and safe when performed in AIS patients selected without advanced neuroimaging between 6-24 hours from stroke onset.

Fahr's disease with an initial presentation of crescendo TIA.

A 51-year-old man presented with vertigo, slurred speech and left facial droop. He had been previously diagnosed with transient ischaemic attack (TIA) and had a prior lacunar infarct. Imaging showed heavy symmetrical calcification in the globus pallidus, frontal white matter and cerebellar dentate nuclei/deep white matter. The imaging was pathognomonic for Fahr's disease and diagnosis was confirmed when other secondary causes of hypercalcemia were excluded. Fahr's disease is a rare, autosomal dominant, neurological condition characterised by primary brain calcification. Patients present with progressive neurological and psychiatric symptoms; commonly, Parkinsonian movement disorders, seizures, headaches, dysarthria, cognitive decline, psychosis and personality changes. There is an association with intracerebral ischaemic events. This case supports a growing body of anecdotal evidence of this association and is the first in which crescendo TIA may be the initial presentation of Fahr's disease. Referral for genetic counselling and symptomatic relief for neurological symptoms are the main management strategies.

Outcomes in Antiplatelet-Associated Intracerebral Hemorrhage in the TICH-2 Randomized Controlled Trial.

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH-2 (Tranexamic Acid in Intracerebral Hemorrhage-2) double-blind, randomized, placebo-controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre-ICH antiplatelet therapy, and 24-hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre-ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no-antiplatelet group. Pre-ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01-1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32-1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25-2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62-0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41-0.91) with no significant interaction between pre-ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.