METHODS: We take advantage of improved contrast seen on magnetic resonance (MR) images of patients with acute and early subacute SICH and introduce an automated algorithm for haematoma and oedema segmentation from these images. To our knowledge, there is no previously proposed segmentation technique for SICH that utilises MR images directly. The method is based on shape and intensity analysis for haematoma segmentation and voxel-wise dynamic thresholding of hyper-intensities for oedema segmentation.
RESULTS: Using Dice scores to measure segmentation overlaps between labellings yielded by the proposed algorithm and five different expert raters on 18 patients, we observe that our technique achieves overlap scores that are very similar to those obtained by pairwise expert rater comparison. A further comparison between the proposed method and a state-of-the-art Deep Learning segmentation on a separate set of 32 manually annotated subjects confirms the proposed method can achieve comparable results with very mild computational burden and in a completely training-free and unsupervised way.
CONCLUSION: Our technique can be a computationally light and effective way to automatically delineate haematoma and oedema extent directly from MR images. Thus, with increasing use of MR images clinically after intracerebral haemorrhage this technique has the potential to inform clinical practice in the future.
DESIGN: MRI substudy nested within the double-blind randomised controlled Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 trial (ISRCTN93732214).
SETTING: International multicentre hospital-based study.
PARTICIPANTS: Eligible adults consented and randomised in the TICH-2 trial who were also able to undergo MRI scanning. To address the primary hypothesis, a sample size of n=280 will allow detection of a 10% relative increase in prevalence of diffusion-weighted imaging (DWI) hyperintense lesions in the TXA group with 5% significance, 80% power and 5% imaging data rejection.
INTERVENTIONS: TICH-2 MRI substudy participants will undergo MRI scanning using a standardised protocol at day ~5 and day ~90 after randomisation. Clinical assessments, randomisation to TXA or placebo and participant follow-up will be performed as per the TICH-2 trial protocol.
CONCLUSION: The TICH-2 MRI substudy will test whether TXA increases the incidence of new DWI-defined ischaemic lesions or reduces perihaematomal oedema or final ICH lesion volume in the context of SICH.
ETHICS AND DISSEMINATION: The TICH-2 trial obtained ethical approval from East Midlands - Nottingham 2 Research Ethics Committee (12/EM/0369) and an amendment to allow the TICH-2 MRI sub study was approved in April 2015 (amendment number SA02/15). All findings will be published in peer-reviewed journals. The primary outcome results will also be presented at a relevant scientific meeting.
TRIAL REGISTRATION NUMBER: ISRCTN93732214; Pre-results.
METHODS: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect.
RESULTS: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (pinteraction=0.031) and agent (pinteraction<0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth.
INTERPRETATION: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent.
PROSPERO REGISTRATION NUMBER: CRD42019141136.
METHODS: This observational study was conducted at the Emergency Department of Sulaymaniyah General Teaching Hospital and Shar Hospital from September 1st, 2014 to August 31st, 2015. Fifty patients who developed acute spontaneous hypertensive intracerebral hemorrhage (ICH) and 50 patients who developed acute non-traumatic subarachnoid hemorrhage (SAH) were included in the study. All patients underwent resting 12-lead ECG within half an hour of admission. The QTc interval was calculated and analyzed in those 100 patients.
RESULTS: Females (62%) outnumbered males (38%) with a female to male ratio of 1.6:1. Forty percent of the patients were between 60-69 years of age. Hypertension was seen in 82% of patients while left ventricular hypertrophy was documented in 40% of patients. The QTc was prolonged in 38 patients (17 patients in the ICH group and 21 patients in the SAH group). In both groups, males demonstrated QTc prolongation more than females. However, there were no statistically significant gender difference between both groups and within the same group. There was a statistically significant association between SAH and QTc prolongation (p-value<0.001); the ICH group did not demonstrate any significant relationship with QTc prolongation.
CONCLUSION: Prolongation in the QTc interval was "statistically" associated with acute SAH only. No gender difference was noted; whether this observation is clinically significant or not, it needs further analytic studies.
METHODS: Patients who were 10-80 years old and presented with a Graeb score of more than six were randomised into endoscopic washout and EVD treatment groups. A CT brain was repeated on each patient within 24 hours after surgery, and if a patient's Graeb score was still more than six, a repeat endoscopic washout was performed to clear the remaining clots. All patients were monitored for shunt dependency at two weeks and three months, and clinical outcomes were measured at six months after the procedure.
RESULTS: A total of 39 patients were recruited; 19 patients were randomised into the endoscopic washout group, and 20 were randomised into the EVD group. However, three patients in the endoscopic group refused that treatment and opted for EVD insertion. Patients treated with endoscopic washout had significantly less drainage dependency at two weeks (P < 0.005) and at three months (P < 0.004) as compared to patients in the external ventricular drainage group. The reduction in Graeb scores was also significantly greater in the endoscopic washout group (P < 0.001). However, the functional outcome at six months measured via a modified Rankin scale score was no different in the two groups of patients. The difference in the functional outcome of the patients was mainly dependent on the initial pathology, with those presenting with a thalamic bleed with IVH showing a poor functional outcome. This parameter was also influenced by the Glasgow Coma Scale (GCS) score on admission, with those patients with a score of 12 or less having a poor functional outcome (MRS 5-6) at three and six months after the surgery.
CONCLUSIONS: The use of neuroendoscopy in patients with a massive IVH significantly reduced drainage dependency. However, it did not alter the final functional outcome.
OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH).
DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial.
SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK).
PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset.
EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK.
CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events.
FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214.
FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.