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1.
J Trauma Nurs ; 28(5): 298-303, 2021.
Article in English | MEDLINE | ID: covidwho-1455396

ABSTRACT

BACKGROUND: The high mortality rate of comatose patients with traumatic brain injury is a prominent public health issue that negatively impacts patients and their families. Objective, reliable tools are needed to guide treatment decisions and prioritize resources. OBJECTIVE: This study aimed to evaluate the prognostic value of the bispectral index (BIS) in comatose patients with severe brain injury. METHODS: This was a retrospective cohort study of 84 patients with severe brain injury and Glasgow Coma Scale (GCS) scores of 8 and less treated from January 2015 to June 2017. Sedatives were withheld at least 24 hr before BIS scoring. The BIS value, GCS scores, and Full Outline of UnResponsiveness (FOUR) were monitored hourly for 48 hr. Based on the Glasgow Outcome Scale (GOS) score, the patients were divided into poor (GOS score: 1-2) and good prognosis groups (GOS score: 3-5). The correlation between BIS and prognosis was analyzed by logistic regression, and the receiver operating characteristic curves were plotted. RESULTS: The mean (SD) of the BIS value: 54.63 (11.76), p = .000; and GCS score: 5.76 (1.87), p = .000, were higher in the good prognosis group than in the poor prognosis group. Lower BIS values and GCS scores were correlated with poorer prognosis. Based on the area under the curve of receiver operating characteristic curves, the optimal diagnostic cutoff value of the BIS was 43.6, and the associated sensitivity and specificity were 85.4% and 74.4%, respectively. CONCLUSION: Taken together, our study indicates that BIS had good predictive value on prognosis. These findings suggested that BIS could be used to evaluate the severity and prognosis of severe brain injury.


Subject(s)
Brain Injuries , Coma , Coma/diagnosis , Electroencephalography , Glasgow Coma Scale , Humans , Prognosis , Retrospective Studies
2.
BMJ Case Rep ; 14(8)2021 Aug 11.
Article in English | MEDLINE | ID: covidwho-1354558

ABSTRACT

A 60-year-old patient presented with respiratory distress, after recently being tested COVID-19 positive and was mechanically ventilated for 15 days. After cessation of sedation, he remained in deep comatose state, without any reaction on pain stimuli (Glasgow Coma Score 3). MRI of the brain showed diffuse leukoencephalopathy and multiple (>50) microbleeds. Diffuse COVID-19-associated leukoencephalopathy with microhaemorrhages is associated with a poor prognosis. However, 3 months later, our patient showed a remarkable recovery and was able to walk independently. This case report shows COVID-related leukoencephalopathy and intracerebral microbleeds, even with persistent comatose state, may have a favourable clinical outcome and prolonged treatment should be considered in individual cases.


Subject(s)
COVID-19 , Leukoencephalopathies , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/diagnostic imaging , Coma/chemically induced , Glasgow Coma Scale , Humans , Leukoencephalopathies/diagnosis , Leukoencephalopathies/diagnostic imaging , Male , Middle Aged , SARS-CoV-2
3.
N Engl J Med ; 384(24): 2283-2294, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1275997

ABSTRACT

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).


Subject(s)
Fever/therapy , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest/therapy , Aged , Body Temperature , Cardiopulmonary Resuscitation/methods , Coma/etiology , Coma/therapy , Female , Fever/etiology , Humans , Hypothermia, Induced/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/mortality , Single-Blind Method , Treatment Outcome
4.
Crit Care Med ; 49(9): 1524-1534, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1191508

ABSTRACT

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.


Subject(s)
COVID-19/drug therapy , Coma/etiology , Hospital Mortality , Hypnotics and Sedatives/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Aged , Analgesics/therapeutic use , Brain/diagnostic imaging , Brain/pathology , COVID-19/complications , COVID-19/mortality , Female , Humans , Hypnotics and Sedatives/adverse effects , Logistic Models , Male , Middle Aged , Neuromuscular Blocking Agents/therapeutic use , Propensity Score , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Retrospective Studies
5.
Neurol Neuroimmunol Neuroinflamm ; 7(6)2020 11.
Article in English | MEDLINE | ID: covidwho-1105773

ABSTRACT

OBJECTIVE: To investigate the pathophysiologic mechanism of encephalopathy and prolonged comatose or stuporous state in severally ill patients with coronavirus disease 2019 (COVID-19). METHODS: Eight COVID-19 patients with signs of encephalopathy were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the serum and CSF using a Food and Drug Administration-approved and independently validated ELISA. Blood-brain barrier (BBB) integrity and immunoglobulin G (IgG) intrathecal synthesis were further tested using albumin and IgG indices. The CSF was also tested for autoimmune encephalitis antibodies and 14-3-3, a marker of ongoing neurodegeneration. RESULTS: All patients had anti-SARS-CoV-2 antibodies in their CSF, and 4 of 8 patients had high titers, comparable to high serum values. One patient had anti-SARS-CoV-2 IgG intrathecal synthesis, and 3 others had disruption of the blood-brain barrier. The CSF in 4 patients was positive for 14-3-3-protein suggesting ongoing neurodegeneration. In all patients, the CSF was negative for autoimmune encephalitis antibodies and SARS-CoV-2 by PCR. None of the patients, apart from persistent encephalopathic signs, had any focal neurologic signs or history or specific neurologic disease. CONCLUSIONS: High-titer anti-SARS-CoV-2 antibodies were detected in the CSF of comatose or encephalopathic patients demonstrating intrathecal IgG synthesis or BBB disruption. A disrupted BBB may facilitate the entry of cytokines and inflammatory mediators into the CNS enhancing neuroinflammation and neurodegeneration. The observations highlight the need for prospective CSF studies to determine the pathogenic role of anti-SARS-CoV-2 antibodies and identify early therapeutic interventions.


Subject(s)
Autoantibodies/cerebrospinal fluid , Betacoronavirus/isolation & purification , Blood-Brain Barrier/metabolism , Coma/cerebrospinal fluid , Coronavirus Infections/cerebrospinal fluid , Nervous System Diseases/cerebrospinal fluid , Pneumonia, Viral/cerebrospinal fluid , Stupor/cerebrospinal fluid , Aged , Aged, 80 and over , Biomarkers/cerebrospinal fluid , COVID-19 , Coma/diagnosis , Coronavirus Infections/diagnosis , Female , Humans , Male , Middle Aged , Nervous System Diseases/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Stupor/diagnosis , Treatment Outcome
6.
J Healthc Qual Res ; 36(3): 156-159, 2021.
Article in Spanish | MEDLINE | ID: covidwho-1099180

ABSTRACT

INTRODUCTION: The SARS-CoV-2 pandemic has generated a mortality rate 10times higher than normal influenza according to the World Health Organization (WHO), yet they do not mention palliative care in their action guidelines on maintaining essential health services during this crisis. The aim of this study was to analyse the death process of patients who died from SARS-CoV-2 at the Hospital Costa del Sol. MATERIAL AND METHODS: Descriptive cross-sectional study of the period in which all patients who died of SARS-CoV-2 from February to April 2020 were analysed. Sociodemographic characteristics, sample characterization and a set of variables related to the death process were collected in the death event. RESULTS: A total of 16 deaths were recorded out of a total of 103 admissions positive for SARS-CoV-2. Limitation of therapeutic effort was decided in 68.8% of the patients, and admission to the intensive care unit was refused in 56.3%. Support devices had not been removed in any of the cases on the day of death, 43.8% had palliative sedation, and 18.8% were in induced coma. CONCLUSIONS: Quality standards were maintained in the death process in patients who died from SARS-CoV-2, although there were aspects that could be improved. Palliative care is an essential component of the response to SARS-CoV-2 that must be incorporated into all health care settings.


Subject(s)
COVID-19/physiopathology , Death , Palliative Care , SARS-CoV-2 , Terminal Care/methods , Advance Care Planning , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Coma/chemically induced , Comorbidity , Critical Care/methods , Cross-Sectional Studies , Female , Humans , Male , Palliative Care/statistics & numerical data , Parenteral Nutrition , Patient Isolation , Respiration, Artificial , Resuscitation , Socioeconomic Factors , Spain/epidemiology , Terminal Care/statistics & numerical data , Visitors to Patients , Withholding Treatment
7.
Neurologia (Engl Ed) ; 36(2): 127-134, 2021 Mar.
Article in English, Spanish | MEDLINE | ID: covidwho-1065502

ABSTRACT

OBJECTIVES: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. PATIENTS AND METHODS: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. RESULTS: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. CONCLUSIONS: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.


Subject(s)
Brain Diseases/etiology , COVID-19/complications , Encephalitis, Viral/etiology , Pandemics , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Brain Diseases/epidemiology , Brain Diseases/virology , COVID-19/epidemiology , Cognition Disorders/epidemiology , Coma/epidemiology , Coma/etiology , Coma/virology , Comorbidity , Electroencephalography , Encephalitis, Viral/epidemiology , Encephalitis, Viral/virology , Epilepsy/epidemiology , Female , Humans , Hypertension/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Magnetic Resonance Imaging , Male , Neuroimaging , Registries , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Retrospective Studies , SARS-CoV-2/isolation & purification , Spain/epidemiology , Stroke/epidemiology
8.
Lancet Respir Med ; 9(3): 239-250, 2021 03.
Article in English | MEDLINE | ID: covidwho-1053892

ABSTRACT

BACKGROUND: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. METHODS: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. FINDINGS: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation-Sedation Scale score while on invasive mechanical ventilation was -4 (-5 to -3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p<0·0001). During the 21-day study period, patients were alive without delirium or coma for a median of 5·0 days (0·0 to 14·0). At baseline, older age, higher SAPS II scores, male sex, smoking or alcohol abuse, use of vasopressors on day 1, and invasive mechanical ventilation on day 1 were independently associated with fewer days alive and free of delirium and coma (all p<0·01). 601 (28·8%) of 2088 patients died within 28 days of admission, with most of those deaths occurring in the ICU. INTERPRETATION: Acute brain dysfunction was highly prevalent and prolonged in critically ill patients with COVID-19. Benzodiazepine use and lack of family visitation were identified as modifiable risk factors for delirium, and thus these data present an opportunity to reduce acute brain dysfunction in patients with COVID-19. FUNDING: None. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.


Subject(s)
COVID-19/psychology , Coma/epidemiology , Delirium/epidemiology , SARS-CoV-2 , Aged , Coma/virology , Critical Illness/psychology , Delirium/virology , Female , Humans , Hypnotics and Sedatives/therapeutic use , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Prevalence , Respiration, Artificial/psychology , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors
9.
Neurology ; 96(10): e1437-e1442, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1027729

ABSTRACT

OBJECTIVE: We report a case series of patients with prolonged but reversible unconsciousness after coronavirus disease 2019 (COVID-19)-related severe respiratory failure. METHODS: A case series of patients who were admitted to the intensive care unit due to COVID-19-related acute respiratory failure is described. RESULTS: After cessation of sedatives, the described cases all showed a prolonged comatose state. Diagnostic neurologic workup did not show signs of devastating brain injury. The clinical pattern of awakening started with early eye opening without obeying commands and persistent flaccid weakness in all cases. Time between cessation of sedatives to the first moment of being fully responsive with obeying commands ranged from 8 to 31 days. CONCLUSION: Prolonged unconsciousness in patients with severe respiratory failure due to COVID-19 can be fully reversible, warranting a cautious approach for prognostication based on a prolonged state of unconsciousness.


Subject(s)
COVID-19/complications , Coma/etiology , Respiratory Insufficiency/complications , Adult , Aged , Coma/diagnostic imaging , Coma/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Respiratory Insufficiency/etiology , Time Factors , Treatment Outcome , White Matter/diagnostic imaging , White Matter/pathology
10.
J Stroke Cerebrovasc Dis ; 30(3): 105609, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1012468

ABSTRACT

The case of a 70-year-old male presenting an ischemic stroke related to COVID-19 infection is described. He was initially admitted to the hospital with respiratory insufficiency syndrome secondary to pneumonia caused by SARS Co2. In the next days, he developed rapid neurological deterioration characterized by drowsiness which progressed to deep coma. D-dimer was elevated. Brain CT scan showed bilateral massive ischemic stroke located in the anterior circulation, CT angiogram showed occlusion in the left internal carotid artery and the right middle cerebral artery. The deterioration of the patient continued and he subsequently died. Large vessel occlusion has been reported in COVID-19 patients, but this clinical presentation is usually unilateral. Cases of bilateral occlusion of large vessels have not been previously reported in COVID-19 patients. This report shows that bilateral massive stroke may occur in COVID-19 cases and it should be suspected in patients who show rapid neurological deterioration without focal deficits.


Subject(s)
Arterial Occlusive Diseases/etiology , COVID-19/complications , Ischemic Stroke/etiology , Aged , Brain/diagnostic imaging , COVID-19/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/etiology , Coma/etiology , Computed Tomography Angiography , Fibrin Fibrinogen Degradation Products/analysis , Humans , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/etiology , Ischemic Stroke/diagnostic imaging , Male , Nervous System Diseases/etiology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Thrombectomy
11.
Clin Neurophysiol ; 132(1): 202-203, 2021 01.
Article in English | MEDLINE | ID: covidwho-893695
12.
Clin Neurophysiol ; 132(1): 218-225, 2021 01.
Article in English | MEDLINE | ID: covidwho-807009

ABSTRACT

OBJECTIVE: Encephalopathy is a major neurological complication of severe Coronavirus Disease 2019 (COVID-19), but has not been fully defined yet. Further, it remains unclear whether neurological manifestations are primarily due to neurotropism of the virus, or indirect effects, like cerebral hypoxia. METHODS: We analysed the electroencephalograms (EEGs) of 19 consecutive patients with laboratory-confirmed COVID-19, performed at peak disease severity as part of their clinical management. Disease severity, respiratory failure, immune and metabolic dysfunction, sedation status, and neurological examination on the day of the EEG were noted. RESULTS: Severe encephalopathy was confirmed in 13 patients, all with severe COVID-19; 10 remained comatose off sedation, and five of them had alpha coma (AC). Disease severity, sedation, immune and metabolic dysfunction were not different between those with AC and those without. CONCLUSIONS: Severe COVID-19 encephalopathy is a principal cause of persisting coma after sedation withdrawal. The relatively high incidence of the rare AC pattern may reflect direct SARS-CoV-2 neurotropism with a predilection for the brainstem ascending reticular system. SIGNIFICANCE: Systematic early EEG detection of encephalopathy related to severe COVID-19 is important for the acute care and the management of long-term neurological and cognitive sequelae, and may help our better understanding of its pathophysiology.


Subject(s)
Brain Diseases/physiopathology , Brain/physiopathology , COVID-19/physiopathology , Coma/physiopathology , Adult , Aged , Aged, 80 and over , Brain Diseases/etiology , COVID-19/complications , Coma/etiology , Electroencephalography , Female , Humans , Male , Middle Aged , Retrospective Studies
13.
Mol Neurobiol ; 58(2): 564-575, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-808452

ABSTRACT

COVID-19 is a highly infectious viral disease caused by the novel coronavirus SARS-CoV-2. While it was initially regarded as a strictly respiratory illness, the impact of COVID-19 on multiple organs is increasingly recognized. The brain is among the targets of COVID-19, and it can be impacted in multiple ways, both directly and indirectly. Direct brain infection by SARS-CoV-2 may occur via axonal transport via the olfactory nerve, eventually infecting the olfactory cortex and other structures in the temporal lobe, and potentially the brain stem. A hematogenous route, which involves viral crossing of blood-brain barrier, is also possible. Secondary mechanisms involve hypoxia due to respiratory failure, as well as aberrant immune response leading to various forms of encephalopathy, white matter damage, and abnormal blood clotting resulting in stroke. Multiple neurological symptoms of COVID-19 have been described. These involve anosmia/ageusia, headaches, seizures, mental confusion and delirium, and coma. There is a growing concern that in a number of patients, long-term or perhaps even permanent cognitive impairment will persist well after the recovery from acute illness. Furthermore, COVID-19 survivors may be at increased risk for developing neurodegenerative diseases years or decades later. Since COVID-19 is a new disease, it will take months or even years to characterize the exact nature, scope, and temporal extent of its long-term neurocognitive sequelae. To that end, rigorous and systematic longitudinal follow-up will be required. For this effort to succeed, appropriate protocols and patient registries should be developed and put in place without delay now.


Subject(s)
Anosmia/virology , Brain/virology , COVID-19/complications , Coma/virology , Delirium/virology , Headache/virology , Seizures/virology , Blood-Brain Barrier/virology , Humans
14.
Neurol India ; 68(3): 560-572, 2020.
Article in English | MEDLINE | ID: covidwho-640338

ABSTRACT

COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.


Subject(s)
Ageusia/physiopathology , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Encephalitis/physiopathology , Guillain-Barre Syndrome/physiopathology , Headache/physiopathology , Olfaction Disorders/physiopathology , Pneumonia, Viral/physiopathology , Stroke/physiopathology , Ageusia/etiology , Betacoronavirus , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , Blood-Brain Barrier , Brain Ischemia/blood , Brain Ischemia/etiology , Brain Ischemia/immunology , Brain Ischemia/physiopathology , COVID-19 , Coma/etiology , Coma/physiopathology , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/immunology , Delirium/etiology , Delirium/physiopathology , Encephalitis/etiology , Encephalitis/immunology , Encephalomyelitis, Acute Disseminated/etiology , Encephalomyelitis, Acute Disseminated/immunology , Encephalomyelitis, Acute Disseminated/physiopathology , Fatigue/etiology , Fatigue/physiopathology , Guillain-Barre Syndrome/etiology , Headache/etiology , Humans , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/physiopathology , Leukoencephalitis, Acute Hemorrhagic/etiology , Leukoencephalitis, Acute Hemorrhagic/immunology , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Myalgia/etiology , Myalgia/physiopathology , Olfaction Disorders/etiology , Pandemics , Personal Protective Equipment/adverse effects , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS-CoV-2 , Stroke/blood , Stroke/etiology , Stroke/immunology
15.
Ann Neurol ; 88(4): 851-854, 2020 10.
Article in English | MEDLINE | ID: covidwho-625491

ABSTRACT

Many patients with severe coronavirus disease 2019 (COVID-19) remain unresponsive after surviving critical illness. Although several structural brain abnormalities have been described, their impact on brain function and implications for prognosis are unknown. Functional neuroimaging, which has prognostic significance, has yet to be explored in this population. Here we describe a patient with severe COVID-19 who, despite prolonged unresponsiveness and structural brain abnormalities, demonstrated intact functional network connectivity, and weeks later recovered the ability to follow commands. When prognosticating for survivors of severe COVID-19, clinicians should consider that brain networks may remain functionally intact despite structural injury and prolonged unresponsiveness. ANN NEUROL 2020;88:851-854.


Subject(s)
Brain/diagnostic imaging , Coma/diagnostic imaging , Coronavirus Infections/physiopathology , Persistent Vegetative State/diagnostic imaging , Pneumonia, Viral/physiopathology , Recovery of Function , Betacoronavirus , Brain/physiopathology , COVID-19 , Coma/physiopathology , Coronavirus Infections/therapy , Electroencephalography , Functional Neuroimaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neural Pathways , Pandemics , Persistent Vegetative State/physiopathology , Pneumonia, Viral/therapy , Prognosis , Renal Insufficiency/physiopathology , Respiration, Artificial , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Shock/physiopathology
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