Mild Luminal Stenosis of Parent Artery and Neurologic Deterioration After Acute Lacunar Stroke

BACKGROUND Early neurologic deterioration (END) occurs in a quarter of acute lacunar infarcts, but the underlying pathophysiological features are poorly understood. We sought to determine the association between luminal stenosis (<50%) of the parent artery and END. METHODS This observational study included consecutive patients with lacunar stroke from the ischemic stroke registries of New York University Langone Health and Brown University. All included patients were admitted for acute lacunar stroke, which was defined as a subcortical infarct <1.5 cm on computed tomography or <2 cm on diffusion‐weighted imaging without significant stenosis (>50%) in the parent vessel and no cardioembolic source. We defined END as any neurologic deterioration referable to the acute lacunar stroke and not related to a medical or noncerebrovascular neurological complication. We used univariate and logistic regression analyses to determine associations between luminal stenosis (<50%) and the odds of END. Furthermore, we attempted to validate findings using the Columbia University Medical Center stroke registry and perform a meta‐analysis combining the derivation and validation groups because of the expected small samples and event rates. RESULTS The New York University Langone Health and Brown University sample included 205 patients, of whom 41 (20%) had END. In adjusted models, we found no definite association between luminal stenosis (<50%) and END (adjusted odds ratio [OR], 1.74; 95% CI, 0.73–4.14). From Columbia University Medical Center, 361 total patients were included, of whom 59 (16%) had END. In adjusted models, we found an association between luminal stenosis (<50%) and END (adjusted OR, 2.28; 95% CI, 1.15–4.50). Meta‐analysis of both cohorts found luminal stenosis (<50%) associated with END (relative risk, 1.69; 95% CI, 1.17–2.43). CONCLUSIONS In this multicenter study, luminal stenosis (<50%) may be associated with END following an acute lacunar infarct. Larger studies using vessel wall imaging are needed to validate our findings.

Quantitative Electroencephalography (EEG) Predicting Acute Neurologic Deterioration in the Pediatric Intensive Care Unit: A Case Series

Introduction: Continuous neurologic assessment in the pediatric intensive care unit is challenging. Current electroencephalography (EEG) guidelines support monitoring status epilepticus, vasospasm detection, and cardiac arrest prognostication, but the scope of brain dysfunction in critically ill patients is larger. We explore quantitative EEG in pediatric intensive care unit patients with neurologic emergencies to identify quantitative EEG changes preceding clinical detection. Methods: From 2017 to 2020, we identified pediatric intensive care unit patients at a single quaternary children's hospital with EEG recording near or during acute neurologic deterioration. Quantitative EEG analysis was performed using Persyst P14 (Persyst Development Corporation). Included features were fast Fourier transform, asymmetry, and rhythmicity spectrograms, “from-baseline” patient-specific versions of the above features, and quantitative suppression ratio. Timing of quantitative EEG changes was determined by expert review and prespecified quantitative EEG alert thresholds. Clinical detection of neurologic deterioration was defined pre hoc and determined through electronic medical record documentation of examination change or intervention. Results: Ten patients were identified, age 23 months to 27 years, and 50% were female. Of 10 patients, 6 died, 1 had new morbidity, and 3 had good recovery; the most common cause of death was cerebral edema and herniation. The fastest changes were on “from-baseline” fast Fourier transform spectrograms, whereas persistent changes on asymmetry spectrograms and suppression ratio were most associated with morbidity and mortality. Median time from first quantitative EEG change to clinical detection was 332 minutes (interquartile range: 201-456 minutes). Conclusion: Quantitative EEG is potentially useful in earlier detection of neurologic deterioration in critically ill pediatric intensive care unit patients. Further work is required to quantify the predictive value, measure improvement in outcome, and automate the process.

DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

Objective. Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. Methods. Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. Results. A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups ( P < 0.05 ). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups ( P < 0.05 ). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups ( P < 0.05 ). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups ( P < 0.05 ). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group ( P < 0.05 ). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group ( P < 0.05 ). Conclusion. The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

Abstract P674: Markers of Atherosclerotic Disease but Not Small Vessel Disease Predict Neurologic Deterioration in Acute Lacunar Strokes

Introduction: Neurologic deterioration (ND) occurs in a quarter of acute lacunar infarct patients and may lead to severe disability. The underlying pathophysiology of ND in these patients is not clearly understood. We sought to identify risk factors and clinical characteristics associated with ND. Methods: This retrospective study included consecutive patients admitted to NYU Langone Medical Center and Brown University for lacunar-type strokes from 2017-2019. Lacunar infarct was defined as subcortical infarct <1.5cm on CT or <2cm on diffusion-weighted imaging without significant stenosis (>50%) in the parent vessel and no cardioembolic source. Available non-invasive imaging (CTA or MRA) was reviewed by a neuroradiologist or vascular neurologist to determine the presence or absence of stenosis (<50%) or luminal irregularity without stenosis in the stem artery segment at the location of the perforator corresponding to the infarct. Fazekas score was determined from available MRI T2 images. We defined ND as those with any neurologic deterioration during their hospitalization referable to lacunar stroke and not related to a medical or non-cerebrovascular neurological complication. We compared clinical and radiographic characteristics of those with and without ND. Results: Among 242 lacunar stroke patients (mean age 68.9±12.2 years, 43.8% women, 61.2% white, 12.8% black, and 13.2% Hispanic), we identified 46 (19%) with ND. There were no demographic differences between those with and without ND. Those with ND were more likely to have systemic atherosclerotic disease (34.8% vs 19.9%, p=0.049) and higher low-density lipoprotein (111 vs 100 mg/dL, p=0.034). Those with ND had less white matter disease on MRI (lower Fazekas score) and were less likely to have chronic lacunes than those without ND. We did not find any association between radiographic subclinical perforator atherosclerotic disease and ND (odds ratio [95% confidence interval]: 1.83 [0.81-4.14], p=0.147). Conclusions: In this multi-ethnic population, patients with neurologic deterioration following an acute lacunar stroke were more likely to have markers of atherosclerotic disease and less likely to have imaging findings suggestive of chronic small vessel disease.