The incidence of neurological complications in mechanically ventilated COVID-19 ICU patients: An observational single-center cohort study in three COVID-19 periods.

BACKGROUND: Neurological complications in COVID-19 patients admitted to an intensive care unit (ICU) have been previously reported. As the pandemic progressed, therapeutic strategies were tailored to new insights. This study describes the incidence, outcome, and types of reported neurological complications in invasively mechanically ventilated (IMV) COVID-19 patients in relation to three periods during the pandemic. METHODS: IMV COVID-19 ICU patients from the Dutch Maastricht Intensive Care COVID (MaastrICCht) cohort were included in a single-center study (March 2020 - October 2021). Demographic, clinical, and follow-up data were collected. Electronic medical records were screened for neurological complications during hospitalization. Three distinct periods (P1, P2, P3) were defined, corresponding to periods with high hospitalization rates. ICU survivors with and without reported neurological complications were compared in an exploratory analysis. RESULTS: IMV COVID-19 ICU patients (n=324; median age 64 [IQR 57-72] years; 238 males (73.5%)) were stratified into P1 (n=94), P2 (n=138), and P3 (n=92). ICU mortality did not significantly change over time (P1=38.3%; P2=41.3%; P3=37.0%; p=.787). The incidence of reported neurological complications during ICU admission gradually decreased over the periods (P1=29.8%; P2=24.6%; P3=18.5%; p=.028). Encephalopathy/delirium (48/324 (14.8%)) and ICU-acquired weakness (32/324 (9.9%)) were most frequently reported and associated with ICU treatment intensity. ICU survivors with neurological complications (n=53) were older (p=.025), predominantly male (p=.037), and had a longer duration of IMV (p<.001) and ICU stay (p<.001), compared to survivors without neurological complications (n=132). A multivariable analysis revealed that only age was independently associated with the occurrence of neurological complications (ORadj=1.0541; 95% CI=1.0171-1.0925; p=.004). Health-related quality-of-life at follow-up was not significantly different between survivors with and without neurological complications (n = 82, p=.054). CONCLUSIONS: A high but decreasing incidence of neurological complications was reported during three consecutive COVID-19 periods in IMV COVID-19 patients. Neurological complications were related to the intensity of ICU support and treatment, and associated with prolonged ICU stay, but did not lead to significantly worse reported health-related quality-of-life at follow-up.

On the merits and potential of advanced neuroimaging techniques in COVID-19: A scoping review.

Many Coronavirus Disease 2019 (COVID-19) patients are suffering from long-term neuropsychological sequelae. These patients may benefit from a better understanding of the underlying neuropathophysiological mechanisms and identification of potential biomarkers and treatment targets. Structural clinical neuroimaging techniques have limited ability to visualize subtle cerebral abnormalities and to investigate brain function. This scoping review assesses the merits and potential of advanced neuroimaging techniques in COVID-19 using literature including advanced neuroimaging or postmortem analyses in adult COVID-19 patients published from the start of the pandemic until December 2023. Findings were summarized according to distinct categories of reported cerebral abnormalities revealed by different imaging techniques. Although no unified COVID-19-specific pattern could be subtracted, a broad range of cerebral abnormalities were revealed by advanced neuroimaging (likely attributable to hypoxic, vascular, and inflammatory pathology), even in absence of structural clinical imaging findings. These abnormalities are validated by postmortem examinations. This scoping review emphasizes the added value of advanced neuroimaging compared to structural clinical imaging and highlights implications for brain functioning and long-term consequences in COVID-19.

Implications of Post-recanalization Perfusion Deficit After Acute Ischemic Stroke: a Scoping Review of Clinical and Preclinical Imaging Studies.

The goal of reperfusion therapy for acute ischemic stroke (AIS) is to restore cerebral blood flow through recanalization of the occluded vessel. Unfortunately, successful recanalization does not always result in favorable clinical outcome. Post-recanalization perfusion deficits (PRPDs), constituted by cerebral hypo- or hyperperfusion, may contribute to lagging patient recovery rates, but its clinical significance remains unclear. This scoping review provides an overview of clinical and preclinical findings on post-ischemic reperfusion, aiming to elucidate the pattern and consequences of PRPD from a translational perspective. The MEDLINE database was searched for quantitative clinical and preclinical studies of AIS reporting PRPD based on cerebral circulation parameters acquired by translational tomographic imaging methods. PRPD and stroke outcome were mapped on a charting table, creating an overview of PRPD after AIS. Twenty-two clinical and twenty-two preclinical studies were included. Post-recanalization hypoperfusion is rarely reported in clinical studies (4/22) but unequivocally associated with detrimental outcome. Post-recanalization hyperperfusion is more commonly reported (18/22 clinical studies) and may be associated with positive or negative outcome. PRPD has been replicated in animal studies, offering mechanistic insights into causes and consequences of PRPD and allowing delineation of possible courses of PRPD. Complex relationships exist between PRPD and stroke outcome. Diversity in methods and lack of standardized definitions in reperfusion studies complicate the characterization of reperfusion patterns. Recommendations are made to advance the understanding of PRPD mechanisms and to further disentangle the relation between PRPD and disease outcome.

Imaging Interstitial Fluid With MRI: A Narrative Review on the Associations of Altered Interstitial Fluid With Vascular and Neurodegenerative Abnormalities.

Interstitial fluid (ISF) refers to the fluid between the parenchymal cells and along the perivascular spaces (PVS). ISF plays a crucial role in delivering nutrients and clearing waste products from the brain. This narrative review focuses on the use of MRI techniques to measure various ISF characteristics in humans. The complementary value of contrast-enhanced and noncontrast-enhanced techniques is highlighted. While contrast-enhanced MRI methods allow measurement of ISF transport and flow, they lack quantitative assessment of ISF properties. Noninvasive MRI techniques, including multi-b-value diffusion imaging, free-water-imaging, T2 -decay imaging, and DTI along the PVS, offer promising alternatives to derive ISF measures, such as ISF volume and diffusivity. The emerging role of these MRI techniques in investigating ISF alterations in neurodegenerative diseases (eg, Alzheimer's disease and Parkinson's disease) and cerebrovascular diseases (eg, cerebral small vessel disease and stroke) is discussed. This review also emphasizes current challenges of ISF imaging, such as the microscopic scale at which ISF has to be measured, and discusses potential focus points for future research to overcome these challenges, for example, the use of high-resolution imaging techniques. Noninvasive MRI methods for measuring ISF characteristics hold significant potential and may have a high clinical impact in understanding the pathophysiology of neurodegenerative and cerebrovascular disorders, as well as in evaluating the efficacy of ISF-targeted therapies in clinical trials. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

The dependence of cerebral interstitial fluid on diffusion-sensitizing directions: A multi-b-value diffusion MRI study in a memory clinic sample.

Three-component intravoxel incoherent motion (3C-IVIM) imaging with spectral analysis provides a proxy for interstitial fluid (ISF) (e.g., in perivascular spaces (PVS), granting a potential marker for altered cerebral clearance. When 3C-IVIM images are acquired with three orthogonal diffusion-sensitizing directions, these are often averaged into the Trace image. This may result in loss of valuable direction-specific information, particularly in PVS-rich regions (basal ganglia (BG) and centrum semiovale (CSO)). This study assessed the dependence of individual diffusion-sensitizing directions to the ISF fraction in PVS-rich regions. Additionally, we explored the value of diffusion direction-specific information on ISF characteristics in distinguishing thirty-one patients with cognitive impairment (CI) (Alzheimer's disease (n = 15) or Mild Cognitive Impairment (n = 16)) from thirty cognitively healthy elderly controls (CON). Multi-b-value diffusion-weighted images were acquired in three orthogonal directions (L-R (left-right), A-P (anterior-posterior) and S-I (superior-inferior)) at 3 T. Voxel-based spectral analysis using non-negative least squares was conducted to independently analyze the L-R, A-P, S-I, and Trace images. 3C-IVIM measures were first compared between diffusion-sensitizing directions and the Trace within the BG using repeated measures ANOVA. Subsequently, the 3C-IVIM measures were compared per direction between the CI and CSO group in the BG and CSO with multivariable linear regression. Our results show that the ISF fraction significantly differs between all diffusion-sensitizing directions and Trace in the BG, with the highest ISF fraction detected using S-I. Solely using S-I, a higher ISF fraction was identified in CI compared to CON in the BG (p = .020) and CSO (p = .046). Thereby, this study found that the measured ISF fraction depends on the acquired diffusion-sensitizing direction, where S-I is most sensitive to detect ISF and differences between CI and CON. The Trace approach is not always sensitive enough to ISF characteristics. Solely acquiring S-I may offer an alternative to reduce scanning time.

White matter integrity moderates the relation between experienced childhood maltreatment and fathers' behavioral response to infant crying.

The ability to provide appropriate responses to infant distress is vital to paternal care, but may be affected by fathers' experiences of childhood maltreatment. Detrimental effects of childhood maltreatment have been found in the adult brain's white matter fibers, accompanied with impaired emotional and cognitive functioning. In the current study (N = 121), we examined new and expectant fathers' childhood maltreatment experiences (i.e. emotional and physical abuse and neglect), current behavioral responses (i.e. handgrip force) to infant cry sounds, and white matter integrity using diffusion tensor imaging. First, more exposure to childhood maltreatment was associated with more use of excessive handgrip force in response to infant crying by fathers. Second, the association between experienced childhood maltreatment and white matter integrity was not significant in whole-brain analyses. Lastly, we found that the association between maltreatment exposure and excessive handgrip force during infant crying was absent in fathers with high tract integrity in the bilateral uncinate fasciculus. These findings possibly point to insufficient behavioral inhibition or emotional dysregulation in fathers who experienced childhood maltreatment, but buffering for this effect in those with larger integrity in brain fibers connecting the amygdala and prefrontal cortex.