Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial.

OBJECTIVE: To examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE). DESIGN: Double-blind pilot randomised controlled trial. SETTING: Eight neonatal units in South Asia. PATIENTS: Neonates (≥36 weeks) with moderate or severe HIE admitted between 31 December 2022 and 3 May 2023. INTERVENTIONS: Erythropoietin (500 U/kg daily) or to the placebo (sham injections using a screen) within 6 hours of birth and continued for 9 days. MRI at 2 weeks of age. MAIN OUTCOMES AND MEASURES: Feasibility of randomisation, drug administration and assessment of brain injury using MRI. RESULTS: Of the 154 neonates screened, 56 were eligible; 6 declined consent and 50 were recruited; 43 (86%) were inborn. Mean (SD) age at first dose was 4.4 (1.2) hours in erythropoietin and 4.1 (1.0) hours in placebo. Overall mortality at hospital discharge occurred in 5 (19%) vs 11 (46%) (p=0.06), and 3 (13%) vs 9 (40.9%) (p=0.04) among those with moderate encephalopathy in the erythropoietin and placebo groups. Moderate or severe injury to basal ganglia, white matter and cortex occurred in 5 (25%) vs 5 (38.5%); 14 (70%) vs 11 (85%); and 6 (30%) vs 2 (15.4%) in the erythropoietin and placebo group, respectively. Sinus venous thrombosis was seen in two (10%) neonates in the erythropoietin group and none in the control group. CONCLUSIONS: Brain injury and mortality after moderate or severe HIE are high in South Asia. Evaluation of erythropoietin monotherapy using MRI to examine treatment effects is feasible in these settings. TRIAL REGISTRATION NUMBER: NCT05395195.

Emergency Imaging of Intracerebral Haemorrhage.

Spontaneous intracerebral haemorrhage (ICH) is a devastating condition with high mortality and morbidity despite advances in neurocritical care. Early deterioration is common in the first few hours after ICH onset, secondary to rapid haematoma expansion and growth. Rapid diagnosis and aggressive early management of these patients are therefore crucial. Imaging plays a key role in establishing the diagnosis and the underlying aetiology of ICH, identifying complications and predicting patients who are at high risk for haematoma expansion. In this chapter, we present an evidence-based imaging framework for the management of spontaneous ICH in the acute setting. Non-enhanced computed tomography is long established as the gold standard for ICH diagnosis but has limitations in demonstrating the underlying aetiology in cases of secondary ICH. There is now growing evidence for the ability of non-invasive angiography to establish the underlying aetiology and to predict further haematoma expansion. The presence of small enhancing foci within the haematoma on computed tomography angiography (CTA), the CTA Spot Sign, has been prospectively validated as a predictor of haematoma expansion. Early identification of patients at risk of haematoma expansion allows for the appropriate escalation of care to a neurosurgical team, admission to a neurocritical care unit, appropriate supportive therapy and targeted novel medical and surgical interventions. Catheter angiography, which remains the gold standard for identifying underlying secondary vascular lesions, should be used in selected cases. However, non-invasive vascular imaging should be considered as an important step in the diagnosis and early management of secondary ICH patients. Previous concerns related to the radiation dose, contrast-induced nephropathy and cost are addressed in this chapter. Recently, animal models have enabled the qualitative assessment of haematoma expansion, and our increased understanding of ICH may inform future trials of targeted medical and surgical therapies.

Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort.

OBJECTIVES: To describe brain magnetic resonance imaging (MRI) abnormalities in newly diagnosed neuropsychiatric lupus (NPSLE). To correlate them with clinical and laboratory data. METHODS: This retrospective cross-sectional study included patients presenting NPSLE undergoing brain MRI within 6 months after onset between 2003 and 2012. Clinical and laboratory data were recorded. MRI findings were defined as inflammatory-like, large-vessel disease (LVD), and small-vessel disease (SVD); SVD was classified as white-matter hyperintensities (WMH), recent small subcortical infarcts, lacunes, microbleeds, and brain atrophy. RESULTS: We included 108 patients (mean 40.6 ± 14.2 years; range 14-77), 91.7% women. The most frequent syndromes were headache (28.5%), cerebrovascular disease (15.5%), seizure (15.5%), and cognitive dysfunction (11.4%). Brain abnormalities were found in 59.3%. SVD was the most common (55.6%), followed by LVD (13%) and inflammatory-like lesions (6.5%). The most frequent SVD findings were WMH (53.7%), atrophy (18.5%), microbleeds (13.7%) and lacunes (11.1%). Cerebrovascular syndrome correlated with LVD (p = 0.001) and microbleeds (p = 0.002), cognitive dysfunction with WMH (p = 0.045) and myelopathy with inflammatory-like lesions (p = 0.020). Low C4 and CH50 correlated with inflammatory-like lesions (p < 0.001, p = 0.019) and lupus anticoagulant with WMH (p = 0.018), microbleeds (p = 0.002) and atrophy (p = 0.008). CONCLUSIONS: Vascular disease is the hallmark of NPSLE. Certain syndromes and immunological patterns are prone to more extensive brain damage. MRI could provide significant clinical information and insights into the pathological substrate.