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1.
Neurology ; 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1551285

ABSTRACT

BACKGROUND AND OBJECTIVES: In patients with severe coronavirus disease 2019 (COVID-19), disorders of consciousness (COVID-DoC) have emerged as a serious complication. The prognosis and pathophysiology of COVID-DoC remain unclear, complicating decisions about continuing life-sustaining treatment. We describe the natural history of COVID-DoC and investigate its associated brain connectivity profile. METHODS: In a prospective, longitudinal study, we screened consecutive patients with COVID-19 at our institution. We enrolled critically ill adult patients with a DoC unexplained by sedation or structural brain injury, and who were planned to undergo a brain MRI. We performed resting state functional MRI and diffusion MRI to evaluate functional and structural connectivity, as compared to healthy controls and patients with DoC resulting from severe traumatic brain injury (TBI). We assessed the recovery of consciousness (command-following) and functional outcomes (Glasgow Outcome Scale Extended [GOSE] and the Disability Rating Scale [DRS]) at hospital discharge, three months post-discharge, and six months post-discharge. We also explored whether clinical variables were associated with recovery from COVID-DoC. RESULTS: After screening 1,105 patients with COVID-19, we enrolled twelve with COVID-DoC. The median age was 63.5 years [interquartile range 55-76.3]. Excluding one who died shortly after enrollment, all of the remaining eleven patients recovered consciousness, after 0-25 days (median 7 [5-14.5]) following the cessation of continuous intravenous sedation. At discharge, all surviving patients remained dependent - median GOSE 3 [1-3], median DRS 23 [16-30]. However ultimately, except for two patients with severe polyneuropathy, all returned home with normal cognition and minimal disability - at three months, median GOSE 3 [3-3], median DRS 7 [5-13]; at six months, median GOSE 4 [4-5], median DRS 3 [3-5]. Ten patients with COVID-DoC underwent advanced neuroimaging; functional and structural brain connectivity in COVID-DoC was diminished compared to healthy controls, and structural connectivity was comparable to patients with severe TBI. DISCUSSION: Patients who survived invariably recovered consciousness after COVID-DoC. Though disability was common following hospitalization, functional status improved over the ensuing months. While future research is necessary, these prospective findings inform the prognosis and pathophysiology of COVID-DoC. TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov, NCT04476589, submitted 7/2020, first enrolled 7/20/2020, https://clinicaltrials.gov/ct2/show/NCT04476589.

2.
Acad Radiol ; 2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1458676

ABSTRACT

INTRODUCTION: Clinical validation studies have demonstrated the ability of accelerated MRI sequences to decrease acquisition time and motion artifact while preserving image quality. The operational benefits, however, have been less explored. Here, we report our initial clinical experience in implementing fast MRI techniques for outpatient brain imaging during the COVID-19 pandemic. METHODS: Aggregate acquisition times were extracted from the medical record on consecutive imaging examinations performed during matched pre-implementation (7/1/2019-12/31/2019) and post-implementation periods (7/1/2020-12/31/2020). Expected acquisition time reduction for each MRI protocol was calculated through manual collection of acquisition times for the conventional and accelerated sequences performed during the pre- and post-implementation periods. Aggregate and expected acquisition times were compared for the five most frequently performed brain MRI protocols: brain without contrast (BR-), brain with and without contrast (BR+), multiple sclerosis (MS), memory loss (MML), and epilepsy (EPL). RESULTS: The expected time reductions for BR-, BR+, MS, MML, and EPL protocols were 6.6 min, 11.9 min, 14 min, 10.8 min, and 14.1 min, respectively. The overall median aggregate acquisition time was 31 [25, 36] min for the pre-implementation period and 18 [15, 22] min for the post-implementation period, with a difference of 13 min (42%). The median acquisition time was reduced by 4 min (25%) for BR-, 14.0 min (44%) for BR+, 14 min (38%) for MS, 11 min (52%) for MML, and 16 min (35%) for EPL. CONCLUSION: The implementation of fast brain MRI sequences significantly reduced the acquisition times for the most commonly performed outpatient brain MRI protocols.

3.
J Neurol Sci ; 430: 120023, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1446884

ABSTRACT

OBJECTIVE: Little is known about CSF profiles in patients with acute COVID-19 infection and neurological symptoms. Here, CSF was tested for SARS-CoV-2 RNA and inflammatory cytokines and chemokines and compared to controls and patients with known neurotropic pathogens. METHODS: CSF from twenty-seven consecutive patients with COVID-19 and neurological symptoms was assayed for SARS-CoV-2 RNA using quantitative reverse transcription PCR (RT-qPCR) and unbiased metagenomic sequencing. Assays for blood brain barrier (BBB) breakdown (CSF:serum albumin ratio (Q-Alb)), and proinflammatory cytokines and chemokines (IL-6, IL-8, IL-15, IL-16, monocyte chemoattractant protein -1 (MCP-1) and monocyte inhibitory protein - 1ß (MIP-1ß)) were performed in 23 patients and compared to CSF from patients with HIV-1 (16 virally suppressed, 5 unsuppressed), West Nile virus (WNV) (n = 4) and 16 healthy controls (HC). RESULTS: Median CSF cell count for COVID-19 patients was 1 white blood cell/µL; two patients were infected with a second pathogen (Neisseria, Cryptococcus neoformans). No CSF samples had detectable SARS-CoV-2 RNA by either detection method. In patients with COVID-19 only, CSF IL-6, IL-8, IL-15, and MIP-1ß levels were higher than HC and suppressed HIV (corrected-p < 0.05). MCP-1 and MIP-1ß levels were higher, while IL-6, IL-8, IL-15 were similar in COVID-19 compared to WNV patients. Q-Alb correlated with all proinflammatory markers, with IL-6, IL-8, and MIP-1ß (r ≥ 0.6, p < 0.01) demonstrating the strongest associations. CONCLUSIONS: Lack of SARS-CoV-2 RNA in CSF is consistent with pre-existing literature. Evidence of intrathecal proinflammatory markers in a subset of COVID-19 patients with BBB breakdown despite minimal CSF pleocytosis is atypical for neurotropic pathogens.


Subject(s)
COVID-19 , Nucleic Acids , Cytokines , Humans , RNA, Viral , SARS-CoV-2
4.
The Neurohospitalist ; : 19418744211047773, 2021.
Article in English | Sage | ID: covidwho-1430366

ABSTRACT

The neurological complications of coronavirus disease 2019 (SARS-CoV-2, COVID-19) have so far included a range of para- and post-infectious neuroinflammatory syndromes inclusive of all components of the neuraxis and peripheral neuromuscular system. In comparison to the para-infectious manifestations of anosmia, ageusia, encephalopathy, and encephalitis, cases of post-infectious ADEM have rarely been reported and have most commonly affected the supratentorial component with or without spinal cord involvement. In this report, we describe a case of isolated involvement of the cervicothoracic spinal cord and medulla, occurring in association with microhemorrhages and hemosiderin deposition in the medulla, that presented fulminantly and required aggressive immunotherapy to control the inflammatory attack. We compare and contrast this case against prior reports of acute hemorrhagic leukoencephalitis (Weston Hurst syndrome) and review the atypical features of neuroinflammation reported to occur following COVID-19 infection.

5.
J Neurol Sci ; 421: 117308, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1033825

ABSTRACT

We evaluated the incidence, distribution, and histopathologic correlates of microvascular brain lesions in patients with severe COVID-19. Sixteen consecutive patients admitted to the intensive care unit with severe COVID-19 undergoing brain MRI for evaluation of coma or neurologic deficits were retrospectively identified. Eleven patients had punctate susceptibility-weighted imaging (SWI) lesions in the subcortical and deep white matter, eight patients had >10 SWI lesions, and four patients had lesions involving the corpus callosum. The distribution of SWI lesions was similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions. Collectively, these radiologic and histopathologic findings add to growing evidence that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.


Subject(s)
Brain Injuries/diagnostic imaging , COVID-19/diagnostic imaging , Magnetic Resonance Imaging/methods , Microvessels/diagnostic imaging , Severity of Illness Index , Brain/blood supply , Brain/diagnostic imaging , Brain Injuries/etiology , COVID-19/complications , Humans , Intensive Care Units/trends , Male , Microvessels/injuries , Middle Aged , Retrospective Studies
6.
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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