Analyzing the Loss and the Recovery of Consciousness: Functional Connectivity Patterns and Changes in Heart Rate Variability During Propofol-Induced Anesthesia.

The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.

COVID-19 severity impacts on long-term neurological manifestation after hospitalisation

BackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. Methodsfrom a sample of 208 consecutive non-neurological patients hospitalized for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardized clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%), and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses. Conclusionspremorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

The clinical spectrum of encephalitis in COVID-19 disease: the ENCOVID multicentre study

ImportanceSeveral preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet. Objectiveto describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment. DesignThe ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded. ResultsOut of 45 cases screened, twenty-five cases of encephalitis positive for SARS-CoV-2 infection with full available data were included. The most common symptoms at onset were delirium (68%), aphasia/dysarthria (24%) and seizures (24%). CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis. Conclusions and relevanceWe found a wide clinical spectrum of encephalitis associated with COVID19 infection, underlying different pathophysiological mechanisms. Response to treatment and final outcome strongly depended on specific CNS-manifestations. Questionwhat are the phenotypes of encephalitis associated to SARS-CoV-2 infection? Findings25 cases of encephalitis in SARS-CoV-2 infection were included in a prospective observational multi-centre study. Encephalitis cases in COVID-19 exhibited a wide heterogeneity in terms of clinical features, CSF, MRI findings, response to treatment and outcomes with 13 cases with normal MRI, 7 with heterogeneous MRI alterations and rarer ADEM/limbic encephalitis cases. Meaningheterogeneity of presentation, response to treatment and outcomes of encephalitis of COVID-19 underlines different pathophysiological mechanisms

COVID-19 impact on consecutive neurological patients admitted to the emergency department

ObjectiveAim of this study was to analyse the impact of COVID-19 on clinical and laboratory findings and outcome of neurological patients consecutively admitted to the emergency department (ED) of a tertiary hub center. MethodsAll adult patients consecutively admitted to the ED for neurological manifestations from February 20th through April 30th 2020 at Spedali Civili of Brescia entered the study. Demographic, clinical, and laboratory data were extracted from medical records and compared between patients with and without COVID-19. ResultsOut of 505 consecutively patients evaluated at ED with neurological symptoms, 147 (29.1%) tested positive for SARS-CoV-2. These patients displayed at triage higher values of CRP, AST, ALT, and fibrinogen but not lymphopenia (p<0.05). They were older (73.1 {+/-} 12.4 vs 65.1 {+/-} 18.9 years, p=0.001) had higher frequency of stroke (34.7% vs 29.3%), encephalitis/meningitis (9.5% vs 1.9%) and delirium (16.3% vs 5.0%). Compared to patients without COVID, they were more frequently hospitalized (91.2% vs 69.3%, p<0.0001) and showed higher mortality rates (29.7% vs 1.8%, p<0.0.001) and discharge disability, independently from age. ConclusionsCOVID-19 impacts on clinical presentation of neurological disorders, with higher frequency of stroke, encephalitis and delirium, and was strongly associated with increased hospitalisation, mortality and disability.

Clinical features and outcomes of inpatients with neurological disease and COVID-19

ObjectiveTo report the clinical and laboratory characteristics, as well as treatment and clinical outcomes of patients admitted for neurological diseases with COVID-19 in a Neuro-COVID unit compared to patients without COVID-19. MethodsIn this retrospective, single centre cohort study, we included all adult inpatients with confirmed COVID-19, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records. Results173 patients were included in this study, of whom 56 resulted positive for COVID-19 and 117 resulted negative for COVID-19. Patients with COVID-19 were older, had a different distribution regarding admission diagnoses, including cerebrovascular disorders, and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (all p<0.05). In-hospital mortality rates and incident delirium were significantly higher in the COVID-19 group (all p<0.05). COVID-19 and non-COVID patients with stroke had similar baseline characteristics but patients with COVID-19 had higher modified Rankin scale scores at discharge (p<0.0001), with a significantly lower number of patients with a good outcome (p<0.0001). Multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio 4.47, 95% CI 1.21-16.5; p=0.025), lower platelet count (0.98, 0.97-0.99; p=0.005) and higher lactate dehydrogenase (1.01, 1.00-1.03; p=0.009) on admission. ConclusionsCOVID-19 patients admitted with neurological disease, including stroke, have a significantly higher in-hospital mortality, incident delirium and higher disability than patients without COVID-19.

Steroid-responsive severe encephalopathy in SARS-CoV-2 infection

Covid-19 infection has the potential for targeting the central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of a 60-year old subject with SARS-CoV-2 infection but only mild respiratory abnormalities who developed an akinetic mutism due to encephalitis. MRI was negative whereas EEG showed generalized theta slowing. CSF analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased IL-8 and TNF- concentrations while other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of CSF parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to Covid-19.

Interhemispherical Anatomical Disconnection in Disorders of Consciousness Patients.

In patients with disorder of consciousness (DOC), the corpus callosum (CC) and subcortical white matter (SWM) integrity were shown to discriminate between diagnostic categories. The aims of the study were: (1) to clarify the link between the integrity of CC and of SWM and the clinical status in DOC patients, disentangling the role played by the different brain injuries (traumatic or hemorrhagic brain injury); (2) to investigate the relationship between the CC integrity and the brain metabolism. We assessed the diagnostic accuracy of the CC and SWM integrity, using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (sMRI), in a sample of DOC individuals, well balanced for diagnosis and etiology. The CC DTI-derived measures were correlated with the brain metabolism, computed with fluorodeoxyglucose positron emission tomography. Our results showed that the CC macrostructural DTI-derived measures discriminate between diagnosis and correlate with the clinical status of DOC patients irrespective of the etiology. Moreover, the CC DTI-derived measures strongly correlate with the metabolism of the right hemisphere. No significant diagnostic accuracy emerged for the CC sMRI evaluation and the SWM measures. Our results indicate that: (1) the degree of the interhemispherical anatomical disconnection is a marker of the level of consciousness independent from the type of brain injury; (2) CC alterations might be the consequence of the reduced brain metabolism. Remarkably, our results suggest that the functional interplay between the two hemispheres is linked tightly to the level of consciousness.