% pm infiltration, percentage of lung infiltration on upper body scan; CSF, cerebrospinal fluid; DM, dexamethasone; EEG, electroencephalogram; GCS, Glasgow coma scale; LBP, low blood pressure; MP, methylprednisolone; oLBP, orthostatic hypotension; sd, syndrome; Tmax, maximum body temperature; N/A, not available, VA, visual acuity. included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Notably, neurological disturbances were accompanied by laboratory evidence of CRS. Severe acute respiratory syndrome coronavirus2 (SARSCoV2) was undetectable in the cerebrospinal fluid (CSF). Hyperalbuminorrachia and increased levels of the astroglial protein S100B were suggestive of bloodbrain barrier (BBB) dysfunction. Brain magnetic resonance imaging findings comprised evidence of acute leukoencephalitis (n= 3, one of whom had a hemorrhagic form), cytotoxic edema mimicking ischaemic stroke (n= 1), or normal results (n= 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted, resulting in rapid recovery from neurological disturbances in two cases. SARSCoV2 was undetectable in 88 of the 90 patients with COVID19 who underwent Reverse TranscriptionPCR testing of CSF. == Conclusions == Patients with COVID19 can develop neurological manifestations that share clinical, laboratory and imaging similarities with those of chimeric antigen receptor Tcellrelated encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immunemediated mechanisms. Keywords:corticosteroids, COVID19, cytokine, encephalitis, intravenous immunoglobulins, kidney, neurological disorders == Introduction == Coronavirus disease 2019 (COVID19) caused by severe acute respiratory syndrome coronavirus2 (SARSCoV2) can be complicated by neurological manifestations that have an adverse impact on morbidity and Itgb2 mortality [1,2,3]. A study from China reported preliminary evidence that neurological manifestations may be present in up to 36% of hospitalized cases [1]. Severe neurological manifestations occurred in 10% of patients during their hospital stay, with severe disease and uremia acting as potential risk factors [1]. Unfortunately, the clinical detection of neurological symptoms in patients with COVID19 remains challenging because of the severity of concomitant respiratory and systemic manifestations. Moreover, the lack of insight into the presentation and pathogenesis AZD8055 of neurological complications is currently hampering effective therapeutic interventions [3]. Similar to other coronaviruses, SARSCoV2 theoretically has the potential to penetrate the central nervous system (CNS) through hematogenous or retrograde neuronal routes [4]. AZD8055 However, the question as to whether SARSCoV2 may cause neurological manifestations through a direct neuropathic effect or by promoting a hyperinflammatory reaction mounted by the host’s immune system in the form cytokine release syndrome (CRS) remains to be established [5]. It is also noteworthy that high serum levels of interleukin (IL)6 have been observed to be a strong predictor of mortality in patients with COVID19 [6]. In this longitudinal study conducted in a renal unit, we describe five patients with severe COVID19 who presented severe neurological manifestations. Extensive clinical, laboratory and imaging phenotyping was performed to gain pathophysiological insights that may guideline clinical decisionmaking, especially with respect to CRS. == Patients and AZD8055 methods == == Patients == Between 9 March and 9 April 2020, a total of 2284 patients were hospitalized with COVID19 at the Strasbourg University Hospital (Strasbourg, France). Of these, 328 were directly admitted to the intensive care unit and 58 to our renal unit. The distribution of the underlying disorders in our 58 patients was as follows: previous kidney transplantation (n= 37); endstage renal disease (n= 16); acute kidney injury (n= 4); and hyponatremia (n= 1). Seven cases (12.7%) developed severe neurological manifestations. In the context of clinical care, five of the patients underwent extensive laboratory and imaging characterization. The remaining two (presenting with coma and seizures) were excluded because of the lack of extensive laboratory and magnetic resonance imaging (MRI) data. SARSCoV2 contamination was confirmed in all cases by Reverse Transcription (RT)PCR assays targeting the RNAdependent RNA polymerase (RdRp) viral gene from nasopharyngeal swab specimens. According to current French legislation, ethical approval for retrospective studies conducted in the context of clinical care can be waived. == Clinical evaluation == All five patients underwent extensive clinical evaluation, aimed at excluding other causes of neurological impairment, such as alcohol or drug intoxication, metabolic disorders, hypoxemia, thiamine or vitamin B12 deficiencies, epilepsy, hypothermia, sepsis, antibiotic overdose, hypercapnic encephalopathy, hepatic encephalopathy, and CNS infections. All patients underwent lumbar puncture to screen for the presence of SARSCoV2 in the cerebrospinal fluid (CSF). If serum laboratory findings showed indicators of CRS, patients received dexamethasone (20 mg/day for 5 days in all cases, followed by individualized dosing).[7] Antibiotic and antithrombotic prophylaxis was offered to all participants. == Serum laboratory markers == As of the beginning of the COVID19 pandemic in France, longitudinal assessments of numerous laboratory markers were conducted as an integral part of our clinical practice in an effort to identify the occurrence of CRS, which was defined as a peak in levels of proinflammatory molecules (IL6, Creactive protein, ferritin) and indices of cytolysis.
Categories:Kisspeptin Receptor