Optic Nerve Sheath Ultrasound for the Detection and Monitoring of Raised Intracranial Pressure in Tuberculous Meningitis.

BACKGROUND: Neurological complications of tuberculous meningitis (TBM) often lead to raised intracranial pressure (ICP) resulting in high morbidity and mortality. Measurement of optic nerve sheath diameter (ONSD) by point-of-care ultrasound may aid in the identification of raised ICP in TBM. METHODS: From June 2017 to December 2019, 107 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817, NCT03100786), underwent ONSD ultrasound at ≥1 of days 0, 3, 7, 14, 21, and day ±30 after enrollment. Demographic data, TBM severity grade, HIV coinfection status, and clinical endpoints by 3 months were recorded. ONSD values were correlated with disease severity, baseline brain imaging, cerebrospinal fluid parameters, and clinical endpoints. RESULTS: 267 ONSD ultrasound scans were performed in 107 participants over the first 30 days of treatment, with measurements from 0.38-0.74 cm. Paired baseline ONSD and brain imaging were performed in 63 participants. Higher baseline ONSD was associated with more severe disease and abnormal brain imaging (abnormal imaging 0.55 cm vs 0.50 cm normal imaging, P = .01). Baseline median ONSD was significantly higher in participants who died by 3 months (0.56 cm [15/72]) versus participants who survived by 3 months (0.52 cm [57/72]) (P = .02). Median ONSD was higher at all follow-up times in participants who died by 3 months. CONCLUSIONS: Higher ONSD was associated with increased disease severity, brain imaging abnormalities, and increased death by 3 months. ONSD ultrasound has a potential role as a noninvasive, affordable bedside tool for predicting brain pathology and death in TBM.

WEB vs coiling in ruptured aneurysms: A propensity score matched comparison of safety and efficacy.

BACKGROUND: We aim to compare the safety and efficacy of WEB with coiling for acutely ruptured aneurysms.METHODS: All consecutive ruptured aneurysms with width suitable for WEB (2-10 mm) treated over 5 years (1/1/2015 to 31/12/2019) were included. We recorded WFNS, Fisher grade, patient demographics and aneurysm characteristics (size, location, D/W and aspect ratio, lobulation). Primary endpoints were mRS status at 3 months, aneurysm occlusion on latest available imaging follow-up, retreatment rate and procedural complications. We applied propensity score matching using aneurysm morphology (size, D/N ratio, ASPECT ratio and lobulation) to optimise matching for WEB versus coil comparison and minimise the effects of confounding. RESULT: A total of 493 patients were identified, 97 treated with the WEB device. 1:1 propensity score matching was used to establish a matched group of 97 patients treated with coiling. The WEB arm showed 3% procedural complication rate, with no haemorrhagic complications and use of adjunctive device in 4%. Satisfactory occlusion on follow-up (mean 14 months) was 79%, with 19% retreatment rate. The coil arm had 8% complication rate, with use of an adjunctive device in 52% of cases (balloon 44%, stent 8%). Satisfactory occlusion on follow-up (mean 22 months) was 90%, with 8% retreatment rate. CONCLUSION: Treatment of ruptured wide-necked bifurcation aneurysms with WEB has a lower complication rate than coiling with high rate of satisfactory occlusion. However, there was a higher retreatment rate when compared with patients treated with coiling. An adjunct device (balloon or stent), was used in over 50% of aneurysms in the coiling group.

pCONUS 2 and pCONUS 2-HPC in the treatment of wide-necked intracranial aneurysms: Multicentre UK experience.

BACKGROUND/PURPOSE: pCONUS 2 and pCONUS 2-HPC are neck-bridging devices that provide coiling support in the endovascular treatment of wide-necked intracranial aneurysms. To date, limited multicentre data has been published. This study provides the first pooled data from multiple UK centres regarding outcomes for these devices covering the periprocedural period to 6-month follow-up. MATERIALS/METHODS: This retrospective, single-arm study assessed 65 patients treated over 3 years from the time of procedure to 6 months post-procedure across four UK centres. Data collected included patient demographics, aneurysm characteristics and antiplatelet regimens. Outcome measures were angiographic results and procedure-related complications from the immediate periprocedural period to 6-month follow-up. RESULTS: Fifty-four unruptured (83.1%) and 11 ruptured (16.9%) aneurysms were treated. Fifty-five aneurysms were located in the anterior circulation (87.7%). There were four device-related intraprocedural complications: three cases of asymptomatic, temporary thrombus formation and one mortality associated with branch vessel occlusion and aneurysm re-bleeding in a ruptured case. There were no post-procedural device-related complications. Satisfactory occlusion was achieved in 58/65 procedures (89.2%) at time of treatment and in 44/60 (73.3%) at 6 months. Satisfactory occlusion correlated with aneurysm size and coiling packing density. Retreatment was required for five unruptured cases (7.7%) and was straightforward with the device in situ. CONCLUSION: pCONUS 2 and pCONUS 2-HPC have good short-term safety profiles. The use of pCONUS 2-HPC in the acute treatment of ruptured aneurysms with postprocedural SAPT is feasible. The devices have an intraprocedural complication rate of 4/65 (6.2%) across multiple UK centres, including a single death (1.5%).

Safety of dual antiplatelet therapy using aspirin and low-dose Prasugrel with platelet reactivity testing in flow diverter treatment of intracranial aneurysms.

BACKGROUND: Dual antiplatelet therapy (DAPT) is standard care for intracranial stenting to prevent thrombotic complications. Clopidogrel resistance has resulted in patients receiving newer P2Y12 inhibitors like Prasugrel, which may reduce thrombotic complications but could increase haemorrhagic complications. This study, utilising platelet reactivity testing, compared thrombotic and haemorrhagic complications associated with Clopidogrel or 20 mg Prasugrel loading in patients treated with flow diverters (FD) for intracranial aneurysms. METHODS: We retrospectively analysed prospectively collected data from 225 consecutive FD procedures. All patients received aspirin. 147 cases received Clopidogrel and 82 received Prasugrel. All patients had VerifyNow testing before the procedure. RESULTS: P2Y12 non-responders were significantly more likely to have thrombotic complications than responders and hyper-responders (7% vs. 2%, p = 0.01). Low-dose Prasugrel resulted in a significantly lower rate of non-responders when compared with Clopidogrel (7% vs. 25%, p < 0.01). We found no statistically significant difference in rates of haemorrhage between the Clopidogrel and Prasugrel groups (2.4% vs. 3.9%, p = 0.47). There were 12 complications (≤7 days) in the Clopidogrel group versus 6 in the Prasugrel group (9% vs. 7.8%, respectively, p = 0.91) and a non-significant reduction in thrombotic complications in the Prasugrel group (5.2% vs. 3.9%, p = 0.88). No significant difference was shown in long-term complications between the groups (p = 0.33). CONCLUSION: These results support the use of platelet reactivity testing and the safety of low-dose Prasugrel for FD treatment of intracranial aneurysms.

Early experience treating intracranial aneurysms using Accero: a novel, fully visible, low profile braided stent with platinum-nitinol composite wire technology.

BACKGROUND: Accero is an innovative, fully visible, self-expanding braided stent with platinum-nitinol composite wire technology, produced by Acandis. OBJECTIVE: To assess the technical success and safety of this new stent by evaluating the intraprocedural behavior and complication rate, and the short-term follow-up results. METHODS: Forty-one consecutive patients suitable for stent-assisted coiling were selected for the use of Accero in an 11-month period. Clinical, procedural, and angiographic data, as well as 30-day morbidity, were recorded. The angiographic results, clinical follow-up at 30 days, and early imaging follow-up at 3 or 6 months were analyzed, when available. RESULTS: Forty-one aneurysms were treated with stent-assisted coiling. All cases were elective, of which 19 were previously untreated aneurysms and 22 were recurrent aneurysms. Aneurysm location was anterior communicating artery complex (16), basilar (12 cases), middle cerebral artery bifurcation (9 cases), and internal cerebral artery (4 cases). The stent was successfully deployed and aneurysm occlusion with coils achieved in 100% of our patients. One case of on table in-stent thrombosis occurred, which resolved after administration of glycoprotein IIB/IIIA inhibitor, with no clinical consequence, and one case of postoperative hematoma at the arteriotomy site, which was managed conservatively. On early follow-up, available for 37 patients, the complete occlusion rate was 76%, with only two recurrences needing further treatment. Satisfactory aneurysm occlusion was therefore achieved in 95% of cases. CONCLUSION: Stent-assisted coiling with the Accero braided stent proved safe and effective.

A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults.

Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (Pheterogeneity = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A2 and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.

The deadliest form of tuberculosis is tuberculosis meningitis (TBM), which causes inflammation in the brain. Even with the best treatment available, about half of patients with TBM become disabled or die, often because they have a stroke. Strokes are caused by blood clots or other blockages in blood vessels in the brain. Aspirin is known to prevent blood clots and helps reduce inflammation. Some scientists wonder if it might help patients with TBM by preventing blockages in blood vessels. Now, Nguyen et al. show that adding aspirin to existing TBM treatments may reduce strokes in some patients. In the experiments, 120 patients with TBM were randomly assigned to receive a low dose of aspirin (81 mg/day), a high dose of aspirin (1000mg/day), or an identical tablet that contained no medication. All the patients also took the anti-tuberculosis drugs and steroids usually used to treat the condition. Both doses of aspirin appeared to be safe. Patients who received aspirin were less likely to have a stroke or die in the first two months of treatment than patients who received the fake pill. But the difference was so small it could have been caused by chance. In the 92 patients with clear evidence of tuberculosis bacteria in their brains, the benefit of aspirin was larger and unlikely to be due to chance. The benefit was greatest for those who received the higher dose of aspirin, only 10.7% of these patients died or had a stroke, compared with 14.8% of those who received a low dose of aspirin, or 34% of those who received the fake pill. Next, Nguyen et al. looked at brain fluid taken from the TBM patients before and after they received the aspirin or fake medication. The experiments showed that patients treated with high dose aspirin had much lower levels of a clot-promoting substance called thromboxane A2 and more anti-inflammatory molecules. Larger studies are needed in children and adults to confirm that aspirin helps prevent strokes or death in patients with TBM. Studies are also needed on patients who have both TBM and HIV infections. But if more studies show aspirin is safe and effective, adding this medication to TBM treatment may be an inexpensive way to prevent death or disability.