Purpose of Review
Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the ...early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications.
Recent Findings
We found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH.
Summary
Future research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients’ outcomes.
Background
Cardiovascular autonomic dysfunction may reportedly occur after a coronavirus‐disease‐2019 (COVID‐19) infection, but the available evidence is scattered. Here we sought to understand the ...acute and mid‐term effects of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection on cardiovascular autonomic function.
Methods
We performed a systematic PubMed, Embase, Web of Science, medRxiv, and bioRxiv search for cases of cardiovascular autonomic dysfunction during an acute SARS‐CoV‐2 infection or post‐COVID‐19 condition. The clinical‐demographic characteristics of individuals in the acute versus post‐COVID‐19 phase were compared.
Results
We screened 6470 titles and s. Fifty‐four full‐length articles were included in the data synthesis. One‐hundred and thirty‐four cases were identified: 81 during the acute SARS‐CoV‐2 infection (24 thereof diagnosed by history) and 53 in the post‐COVID‐19 phase. Post‐COVID‐19 cases were younger than those with cardiovascular autonomic disturbances in the acute SARS‐CoV‐2 phase (42 vs. 51 years old, p = 0.002) and were more frequently women (68% vs. 49%, p = 0.034). Reflex syncope was the most common cardiovascular autonomic disorder in the acute phase (p = 0.008) and postural orthostatic tachycardia syndrome (POTS) the most frequent diagnosis in individuals with post‐COVID‐19 orthostatic complaints (p < 0.001). Full recovery was more frequent in individuals with acute versus post‐COVID‐19 onset of cardiovascular autonomic disturbances (43% vs. 15%, p = 0.002).
Conclusions
There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID‐19. More data about the prevalence of autonomic disorders associated with a SARS‐CoV‐2 infection are needed to quantify its impact on human health.
Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for ...injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels.
Abstract
We aimed to determine the role of the European Psychiatric Association (EPA) and the European Academy of Neurology (EAN) in the management of post-COVID conditions. This is a joint statement ...from the EAN and the EPA on post-COVID. It is published in the official journals of the two associations, the
European Journal of Neurology and European Psychiatry
.
Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether ...monitoring these processes is cost-effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data.
Purpose
To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19.
Methods
In this ...prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis.
Results
Patients were 55 years of age (IQR, 49–63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age per year, adjOR (95%CI) 0.94 (0.88–1.00),
p
= 0.049, longer hospitalization per day, adjOR (95%CI) 1.07 (1.01–1.13),
p
= 0.015, impaired sleep adjOR (95%CI) 5.54 (1.2–25.61),
p
= 0.028, and anxiety adjOR (95%CI) 15.67 (3.03–80.99),
p
= 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (
n
= 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue.
Conclusion
Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.
Lumbar puncture (LP) is recommended in patients with thunderclap headache and negative computed tomography to rule out spontaneous subarachnoid haemorrhage (SAH). Blood contamination of cerebrospinal ...fluid (CSF) due to traumatic LP poses a diagnostic dilemma. Therefore, routine CSF parameters were investigated to distinguish between SAH and a traumatic LP. CSF red blood cell (RBC), white blood cell (WBC) count, total protein, CSF colour and supernatant were used for group comparisons of patients with SAH and 'symptomatic controls'. Due to variable time intervals between bleeding onset and LP in SAH patients in contrast to patients with traumatic LP, where blood contamination of CSF occurs at the time of LP, CSF variables were adjusted for decay in time to allow comparability. Logistic regression analysis identified bloody CSF odds ratio (OR) 32.6, xanthochromic supernatant OR 15.5 and WBC
OR 4.5 (per increase of 100/µl) as predictors of SAH, while age, sex and CSF total protein
were no predictors. Optimal cut-point of RBC
(determined at day 1 after bleeding) was > 3667/µl to identify SAH patients with a 97% sensitivity and 94% specificity. Combination of low RBC and clear CSF supernatant was found in none of SAH patients. Combined CSF RBC count and CSF supernatant reliably distinguished traumatic LP from SAH.
Subarachnoid hemorrhage is a life-threatening disease associated with high mortality and morbidity. A substantial number of patients develop systemic inflammatory response syndrome. We aimed to ...identify risk factors for systemic inflammatory response syndrome development and to evaluate the role of systemic inflammatory response syndrome on patients' outcome.
Retrospective observational cohort study of prospectively collected data.
Neurocritical care unit at a tertiary academic medical center.
Two-hundred and ninety-seven consecutive nontraumatic subarachnoid hemorrhage patients admitted to the neurologic ICU between 2010 and 2017.
Systemic inflammatory response syndrome was diagnosed based on greater than or equal to two criteria (hypo-/hyperthermia, tachypnea, leukopenia/leukocytosis, tachycardia) and defined as early (≤ 3 d) and delayed (days 6-10) systemic inflammatory response syndrome burden (systemic inflammatory response syndrome positive days within the first 10 d). Using multivariate analysis, risk factors for the development of early and delayed systemic inflammatory response syndrome and the relationship of systemic inflammatory response syndrome with poor 3-month functional outcome (modified Rankin Scale score ≥ 3) were analyzed.
Seventy-eight percent of subarachnoid hemorrhage patients had early systemic inflammatory response syndrome, and 69% developed delayed systemic inflammatory response syndrome. Median systemic inflammatory response syndrome burden was 60% (interquartile range, 10-90%). Risk factors for early systemic inflammatory response syndrome were higher admission Hunt and Hess grade (odds ratio, 1.75; 95% CI, 1.09-2.83; p = 0.02), aneurysm clipping (odds ratio, 4.84; 95% CI, 1.02-23.05; p = 0.048), and higher modified Fisher Scale score (odds ratio, 1.88; 95% CI, 1.25-2.89; p = 0.003). Hunt and Hess grade and pneumonia were independently associated with delayed systemic inflammatory response syndrome development. Systemic inflammatory response syndrome burden (area under the curve, 0.84; 95% CI, 0.79-0.88) had a higher predictive value for 3-month poor outcome compared with early systemic inflammatory response syndrome (area under the curve, 0.76; 95% CI, 0.70-0.81; p < 0.001).
Systemic inflammatory response syndrome is common after subarachnoid hemorrhage and independently contributes to poor functional outcome. Systemic inflammatory response syndrome burden more accurately predicts poor outcome than early systemic inflammatory response syndrome.
There is a substantial amount of evidence from animal models that early brain injury (EBI) may play an important role for secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). ...Cerebral microdialysis (CMD) allows online measurement of brain metabolites, including the pro-inflammatory cytokine interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9), which is indicative for disruption of the blood-brain barrier.
Twenty-six consecutive poor-grade aSAH patients with multimodal neuromonitoring were analyzed for brain hemodynamic and metabolic changes, including CMD-IL-6 and CMD-MMP-9 levels. Statistical analysis was performed by using a generalized estimating equation with an autoregressive function.
The baseline cerebral metabolic profile revealed brain metabolic distress and an excitatory response which improved over the following 5 days (P <0.001). Brain tissue hypoxia (brain tissue oxygen tension of less than 20 mm Hg) was common (more than 60% of patients) in the first 24 hours of neuromonitoring and improved thereafter (P <0.05). Baseline CMD-IL-6 and CMD-MMP-9 levels were elevated in all patients (median = 4,059 pg/mL, interquartile range (IQR) = 1,316 to 12,456 pg/mL and median = 851 pg/mL, IQR = 98 to 25,860 pg/mL) and significantly decreased over days (P <0.05). A higher pro-inflammatory response was associated with the development of delayed cerebral ischemia (P = 0.04), whereas admission disease severity and early brain tissue hypoxia were associated with higher CMD-MMP-9 levels (P <0.03). Brain metabolic distress and increased IL-6 levels were associated with poor functional outcome (modified Rankin Scale of more than 3, P ≤0.01). All models were adjusted for probe location, aneurysm securing procedure, and disease severity as appropriate.
Multimodal neuromonitoring techniques allow insight into pathophysiologic changes in the early phase after aSAH. The results may be used as endpoints for future interventions targeting EBI in poor-grade aSAH patients.
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