Longitudinal assessment of hemodynamic alterations after mild traumatic brain injury in adolescents: Selected case study review

Alterations in the neurovasculature after traumatic brain injury (TBI) represents a significant sequelae. However, despite theoretical and empirical evidence supporting the near-ubiquity of vascular injury, its pathophysiology remains elusive. Although this has been shown for all grades of TBI, the vascular changes after injuries with the broad mild traumatic brain injuries (mTBI) classification, remain particularly difficult to describe. Our group has previously demonstrated hemodynamic alterations in mTBI by utilizing transcranial Doppler ultrasound and cerebrovascular reactivity in a cross-sectional study. That work identified a phasic progression of deviations over varying days post-injury. These phases were then characterized by a set of inverse models that provided a hypothetical process of hemodynamic dysfunction after mTBI. This model set provides a framework with the potential for guiding clinical treatment over the course of recovery. However, it is still unclear if individual patients will progress through the phases of dysfunction similar to that found at the population level. The work presented here explores six individual patients with high-density data collected during their post-injury recovery. Breath-hold index (BHI) was found to be the most robust feature related to mTBI longitudinally. All six subjects exhibited BHI recovery curves that followed the population model's progression. The changes in pulsatile features lacked the universality of BHI, but were present in subjects with higher self-reported symptom scores and longer periods of recovery. This work suggests neurovascular dysfunction after an mTBI may be a robust phenomenon. Additionally, the capabilities of TCD in capturing these changes highlights its potential for aiding clinicians in monitoring patient's recovery post mTBI.

Intracranial Flow Velocity Quantification Using Non-Contrast Four-Dimensional Flow MRI: A Prospective Comparative Study with Transcranial Doppler Ultrasound

Four-dimensional (4D) flow magnetic resonance imaging (MRI) allows three-dimensional velocity encoding to measure blood flow in a single scan, regardless of the intracranial artery direction. We compared blood flow velocity quantification by non-contrast 4D flow MRI and by transcranial Doppler ultrasound (TCD), the most widely used modality for measuring velocity. Twenty-two patients underwent both TCD and non-contrast 4D flow MRI. The mean time interval between TCD and non-contrast 4D flow MRI was 0.7 days. Subsegmental velocities were measured bilaterally in the middle cerebral and basilar arteries using TCD and non-contrast 4D flow MRI. Intracranial velocity measurements using TCD and non-contrast 4D flow MRI demonstrated a strong correlation in the bilateral M1, especially at the proximal segment (right r = 0.74, left r = 0.78; all p < 0.001). Mean velocities acquired with 4D flow MRI were approximately 8 to 10% lower than those acquired with TCD according to the location of M1. Intracranial arterial flow measurements estimated using non-contrast 4D flow MRI and TCD showed strong correlation. 4D flow MRI enables simultaneous assessment of vascular morphology and quantitative hemodynamic measurement, providing three-dimensional blood flow visualization. 4D flow MRI is a clinically useful sequence with a promising role in cerebrovascular disease.

Association Between Patent Foramen Ovale and Overt Ischemic Stroke in Children With Sickle Cell Disease

Ischemic stroke is one of the most devastating complications of sickle cell anemia (SCA). Previous studies have shown that intracardiac shunting including patent foramen ovale (PFO) can be a potential risk factor for stroke in children with SCA. This study investigates the association between PFO and overt ischemic stroke in the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort of 5,247 children with SCA of whom 1,414 had at least one clinical non-contrast transthoracic echocardiogram. Presence of PFO was taken from the clinical report. Further, we assessed the association between PFO and other clinical and hemolytic factors in children with SCA such as history of abnormal sickle stroke screen [elevated Transcranial Doppler ultrasound (TCD) velocity] and patient's baseline hemoglobin. In 642 children for whom all data were available, the adjusted odds ratio (OR) for overt stroke was higher in those with PFO but this was not statistically significant (OR: 1.49, 95% CI: 0.20–11.03, p = 0.6994). With an OR of 0.85, the study suggested less PFOs in those with abnormal TCD, but this was not statistically significant (95% CI: 0.17–4.25, p = 0.8463). Overall, the prevalence of PFO in this large sub study of non-contrast echocardiography amongst children with SCA is much lower than previous smaller studies using bubble contrast echocardiography. Overt stroke was non-statistically more common in children with SCA and PFO, but there was no evidence that PFO was more common in those with abnormal TCD, the most important pediatric sickle stroke screen.

Circulating microRNAs in Symptomatic and Asymptomatic Carotid Stenosis

Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA.Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed.Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features.Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.

Silent Strokes May Be Involved in Neurocognitive Impairment in Children With Sickle Cell Disease

Neurological complications are frequent occurrences in children and adolescents with sickle cell disease (SCD). This research has investigated the prevalence of neurovascular and neurocognitive impairments in 17 patients with SCD from Northern Brazil, with aged 6-16 years. Transcranial Doppler Ultrasound (TDU) examinations were performed on patients employing the STOP protocol as a risk score to predict stroke. Neuropsychological assessments were also performed: the Wechsler Intelligence Scale for Children - 4th Edition (WISC-IV). Fisher's Exact Test was used for statistical analyses (p ≤0.05) of the collected dataset. Frequent headaches were a common clinical finding, occurring in over 75% of the children. There were no alterations in cerebral hemodynamics on TDU for over 70% of the patients. In general, patients had below-average scores on most cognitive domains. There was a tendency for correlation between transcranial Doppler results and the WISC-IV indices of total Intelligence Quotient (p = 0.069) and Processing Speed Index (p = 0.082). Conclusion: Most SCD patients showed impairments on cognitive tests, but there was no statistically significant correlation between the presence of neurovascular damage and worse performance on the tests.