Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.

BACKGROUND AND AIMS: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). METHODS: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL. RESULTS: We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively. CONCLUSIONS: Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.

The multifaceted role of neurofilament light chain protein in non-primary neurological diseases.

The advancing validation and exploitation of cerebrospinal fluid and blood neurofilament light chain protein as a biomarker of neuroaxonal damage has deeply changed the current diagnostic and prognostic approach to neurological diseases. Further, recent studies have provided evidence of potential new applications of this biomarker also in non-primary neurological diseases. In the present review we summarise the current evidence, future perspectives, but also limitations, of neurofilament light chain protein as a cerebrospinal fluid and blood biomarker in several medical fields, including intensive care, surgery, internal medicine and psychiatry. In particular, neurofilament light chain protein is associated with the degree of neurologic impairment and outcome in patients admitted to intensive care units or in the perioperative phase and it seems to be highly interconnected with cardiovascular risk factors. Beyond that, interesting diagnostic and prognostic insights have been provided by the investigation of neurofilament light chain protein in psychiatric disorders as well as in the current coronavirus disease 19 (COVID-19) pandemic and in normal aging. Altogether, current data outline a multifaceted applicability of cerebrospinal fluid and blood neurofilament light chain protein ranging from the critical clinical setting to the development of precision medicine models suggesting a strict interplay between the nervous system pathophysiology and the health-illness continuum.

Impact of National Lockdown on the Hyperacute Stroke Care and Rapid Transient Ischaemic Attack Outpatient Service in a Comprehensive Tertiary Stroke Centre During the COVID-19 Pandemic.

Background: The COVID-19 pandemic is having major implications for stroke services worldwide. We aimed to study the impact of the national lockdown period during the COVID-19 outbreak on stroke and transient ischemic attack (TIA) care in London, UK. Methods: We retrospectively analyzed data from a quality improvement registry of consecutive patients presenting with acute ischemic stroke and TIA to the Stroke Department, Imperial College Health Care Trust London during the national lockdown period (between March 23rd and 30th June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting with stroke or TIA in the same period of 2019. Results: Between March 23rd and 30th June 2020, we documented a fall in the number of stroke admissions by 31.33% and of TIA outpatient referrals by 24.44% compared to the same period in 2019. During the lockdown, we observed a significant increase in symptom onset-to-door time in patients presenting with stroke (median = 240 vs. 160 min, p = 0.020) and TIA (median = 3 vs. 0 days, p = 0.002) and a significant reduction in the total number of patients thrombolysed [27 (11.49%) vs. 46 (16.25%, p = 0.030)]. Patients in the 2020 cohort presented with a lower median pre-stroke mRS (p = 0.015), but an increased NIHSS (p = 0.002). We registered a marked decrease in mimic diagnoses compared to the same period of 2019. Statistically significant differences were found between the COVID and pre-COVID cohorts in the time from onset to door (median 99 vs. 88 min, p = 0.026) and from onset to needle (median 148 vs. 126 min, p = 0.036) for thrombolysis whilst we did not observe any significant delay to reperfusion therapies (door-to-needle and door-to-groin puncture time). Conclusions: National lockdown in the UK due to the COVID-19 pandemic was associated with a significant decrease in acute stroke admission and TIA evaluations at our stroke center. Moreover, a lower proportion of acute stroke patients in the pandemic cohort benefited from reperfusion therapy. Further research is needed to evaluate the long-term effects of the pandemic on stroke care.

Delivering telemedicine consultations for patients with transient ischaemic attack during the COVID-19 pandemic in a comprehensive tertiary stroke centre in the United Kingdom.

BACKGROUND AND PURPOSE: The global COVID-19 pandemic led many stroke centres worldwide to shift from in-person to telemedicine consultations to assess patients with transient ischaemic attacks (TIAs). We aimed to investigate the impact of telemedicine during the COVID-19 pandemic on the management and outcome of the patients with TIA. METHODS: We retrospectively analysed data from a registry of consecutive TIA patients assessed at the Stroke Department, Imperial College Health Care Trust, London, during the national lockdown period (between March 23 2020 and 30 June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting to the TIA clinic in the same period of 2019. RESULTS: Between 23 March 2020 and 30 June 2020, 136 patients were assessed using the telemedicine TIA clinic, compared to 180 patients evaluated with face-to-face consultation in the same period in 2019. Patients' characteristics were similar in both groups. At 3 months after the TIA, there were no significant differences in the proportion of patients admitted to the hospital for recurrent TIA/stroke or any other cardiovascular cause from the 2020 period compared to the same period in 2019. CONCLUSIONS: Our analysis showed that during the pandemic, our telemedicine consultations of TIA patients were not associated with an increased 3-month rate of recurrent TIA/stroke or cardiovascular hospital admissions. More robust studies looking at this model of care will be needed to assess its long-term effects on patients and health care systems.

Impact of COVID-19 Pandemic on a Regional Stroke Thrombectomy Service in the United Kingdom.

INTRODUCTION: We examined the impact of the coronavirus disease 2019 (COVID-19) pandemic on our regional stroke thrombectomy service in the UK. METHODS: This was a single-center health service evaluation. We began testing for COVID-19 on 3 March and introduced a modified "COVID Stroke Thrombectomy Pathway" on 18 March. We analyzed the clinical, procedural and outcome data for 61 consecutive stroke thrombectomy patients between 1 January and 30 April. We compared the data for January and February ("pre-COVID," n = 33) versus March and April ("during COVID," n = 28). RESULTS: Patient demographics were similar between the 2 groups (mean age 71 ± 12.8 years, 39% female). During the COVID-19 pandemic, (a) total stroke admissions fell by 17% but the thrombectomy rate was maintained at 20% of ischemic strokes; (b) successful recanalization rate was maintained at 81%; (c) early neurological outcomes (neurological improvement following thrombectomy and inpatient mortality) were not significantly different; (d) use of general anesthesia fell significantly from 85 to 32% as intended; and (e) time intervals from onset to arrival, groin puncture, and recanalization were not significantly different, whereas internal delays for external referrals significantly improved for door-to-groin puncture (48 [interquartile range (IQR) 39-57] vs. 33 [IQR 27-44] minutes, p = 0.013) and door-to-recanalization (82.5 [IQR 61-110] vs. 60 [IQR 55-70] minutes, p = 0.018). CONCLUSION: The COVID-19 pandemic has had a negative impact on the stroke admission numbers but not stroke thrombectomy rate, successful recanalization rate, or early neurological outcome. Internal delays actually improved during the COVID-19 pandemic. Further studies should examine the effects of the COVID-19 pandemic on longer term outcome.

Decreasing referrals to transient ischaemic attack clinics during the COVID-19 outbreak: results from a multicentre cross-sectional survey.

OBJECTIVE: The COVID-19 pandemic is having major implications for stroke care with a documented significant fall in hospital acute stroke admissions. We investigated whether COVID-19 has resulted in a decreased number of referrals to the transient ischaemic attack (TIA) clinics across the North West London region. SETTING AND DESIGN: All the TIA clinical leads of the North West London region received an invitation by email to participate in an online survey in May 2020. The survey questionnaire aimed to assess the number of patients with suspected TIA consecutively referred to each of the TIA clinics of the North West London region between 1 March and 30 April 2020, the COVID-19 period, and between 1 March and 30 April 2019. RESULTS: We had a response rate of 100%. During the COVID-19 period, the TIA clinics of the North West London region received 440 referrals compared with 616 referrals received between 1 March and 30 April 2019 with a fall in the number of the referrals by 28.6%. In April 2020 compared with April 2019, the number of the referrals declined by 40.1%. CONCLUSIONS: This multicentre analysis documented a significant reduction in the number of patients referred with suspected TIA to the specialised rapid access outpatient clinics in the North West London region during the COVID-19 pandemic. Future studies are needed to confirm our findings and to better characterise the incidence of cerebrovascular disease during the COVID-19 pandemic.