Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study

OBJECTIVE: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW). METHODS: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients. RESULTS: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes. CONCLUSIONS: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness. SIGNIFICANCE: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM

Biomarkers for CNS injury in CSF are elevated in COVID-19 and associated with neurological symptoms and disease severity

BACKGROUND: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19) and biomarkers of CNS injury are reported to be increased in plasma but not extensively studied in CSF. This study examines CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain protein (NfL) glial fibrillary acidic protein (GFAp) and total tau) was performed and related to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL, GFAp and total-tau protein were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL correlated with disease severity, time in intensive care and level of consciousness. NfL in CSF was higher in patients with central neurological symptoms. CONCLUSION: Although limited by small sample size, our data suggest that levels of NfL, GFAp and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF work-up where pathological findings are scarce. NfL in particular, is associated with central neurological symptoms and disease severity

Seizures, CSF neurofilament light and tau in patients with subarachnoid haemorrhage

Objectives: Patients with severe subarachnoid haemorrhage (SAH) often suffer from complications with delayed cerebral ischaemia (DCI) due to vasospasm that is difficult to identify by clinical examination. The purpose of this study was to monitor seizures and to measure cerebrospinal fluid (CSF) concentrations of neurofilament light (NFL) and tau, and to see whether they could be used for predicting preclinical DCI. Methods: We prospectively studied 19 patients with aneurysmal SAH who underwent treatment with endovascular coiling. The patients were monitored with continuous EEG (cEEG) and received external ventricular drainage (EVD). CSF samples of neurofilament light (NLF) and total tau (T‐tau) protein were collected at day 4 and day 10. Cox regression analysis was applied to evaluate whether seizures and protein biomarkers were associated with DCI and poor outcome. Results: Seven patients developed DCI (37%), and 4 patients (21%) died within the first 2 months. Six patients (32%) had clinical seizures, and electrographic seizures were noted in one additional patient (4.5%). Increased tau ratio (proportion tau10/tau4) was significantly associated with DCI and hazard ratio [HR=1.33, 95% confidence interval (CI) 1.055‐1.680. P = .016]. Conclusion: Acute symptomatic seizures are common in SAH, but their presence is not predictive of DCI. High values of the tau ratio in the CSF may be associated with development of DCI

The Iowa Homemaker vol.20, no.1

Recreation that Recreates, Editor, page 1 Dual Personalities, Catherine Raymond, page 2 Married Right Out of College, Mary Ellen Lynch Brown, page 3 Sally Bows to Summer’s Sun, Kathryn Cooley, page 4 Selling Yourself, Kathryn Monson, page 6 I Want a Cotton Dress, Marcia E. Turner, page 7 Playtime Pays Dividends, Jane Wiley, page 8 Behind Closed Doors, Margaret Kumlien, page 9 Sunshine Sports, Jeanette Woodward, page 10 Packing the Convention Bag, Shirley Ambrose, page 11 What’s New in Home Economics, page 12 Veishea Presents, Adelaide Richardson, page 14 Picnic Basket, Dorothy Jo Weber, page 16 Alums in the News, Bette Simpson, page 17 Make Room for Music, Nancy Mason, page 18 Behind Bright Jackets, Betty Bice, page 20 Journalistic Spindles, Dorothy Anne Roost, page 23 Biography of a Home Economist, Eleanor White, page 2

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database

Background: Epilepsy is a serious condition which can profoundly affect an individual’s life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox’s proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. Results: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies

Intranasal Administration of poly(I:C) and LPS in BALB/c Mice Induces Airway Hyperresponsiveness and Inflammation via Different Pathways

BACKGROUND: Bacterial and viral infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. The mechanism behind this reaction is poorly understood, but pattern recognizing Toll-like receptors (TLRs) have recently been suggested to play a role. MATERIALS AND METHODS: To explore the relation between infection-induced airway inflammation and the development of AHR, poly(I:C) activating TLR3 and LPS triggering TLR4, were chosen to represent viral and bacterial induced interactions, respectively. Female BALB/c or MyD88-deficient C57BL/6 mice were treated intranasally with either poly(I:C), LPS or PBS (vehicle for the control group), once a day, during 4 consecutive days. RESULTS: When methacholine challenge was performed on day 5, BALB/c mice responded with an increase in airway resistance. The maximal resistance was higher in the poly(I:C) and LPS treated groups than among the controls, indicating development of AHR in response to repeated TLR activation. The proportion of lymphocytes in broncheoalveolar lavage fluid (BALF) increased after poly(I:C) treatment whereas LPS enhanced the amount of neutrophils. A similar cellular pattern was seen in lung tissue. Analysis of 21 inflammatory mediators in BALF revealed that the TLR response was receptor-specific. MyD88-deficient C57BL/6 mice responded to poly (I:C) with an influx of lymphocytes, whereas LPS caused no inflammation. CONCLUSION: In vivo activation of TLR3 and TLR4 in BALB/c mice both caused AHR in conjunction with a local inflammatory reaction. The AHR appeared to be identical regardless of which TLR that was activated, whereas the inflammation exhibited a receptor specific profile in terms of both recruited cells and inflammatory mediators. The inflammatory response caused by LPS appeared to be dependent on MyD88 pathway. Altogether the presented data indicate that the development of AHR and the induction of local inflammation might be the result of two parallel events, rather than one leading to another