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Abstract of the Week


September Topic: COVID-19 Neurologic Implications

No 532: September 11, 2020

Neurological and Musculoskeletal Features of COVID-19: A Systematic Review and Meta-Analysis

Abdullahi A, Candan SA, Abba MA, et al. Neurological and Musculoskeletal Features of COVID-19: A Systematic Review and Meta-Analysis. Front Neurol. 2020;11:687. Published 2020 Jun 26. doi:10.3389/fneur.2020.00687
Importance: Some of the symptoms of COVID-19 are fever, cough, and breathing difficulty. However, the mechanism of the disease, including some of the symptoms such as the neurological and musculoskeletal symptoms, is still poorly understood. 
Objective: The aim of this review is to summarize the evidence on the neurological and musculoskeletal symptoms of the disease. This may help with early diagnosis, prevention of disease spread, and treatment planning. 
Data Sources: MEDLINE, EMBASE, Web of Science, and Google Scholar (first 100 hits) were searched until April 17, 2020. The key search terms used were "coronavirus" and "signs and symptoms." Only studies written in English were included. 
Study Selection: The selection was performed by two independent reviewers using EndNote and Rayyan software. Any disagreement was resolved by consensus or by a third reviewer. 
Data Extraction and Synthesis: PRISMA guidelines were followed for abstracting data and assessing the quality of the studies. These were carried out by two and three independent reviewers, respectively. Any disagreement was resolved by consensus or by a third reviewer. The data were analyzed using qualitative synthesis and pooled using a random-effect model. Main Outcome(s) and Measure(s): The outcomes in the study include country, study design, participant details (sex, age, sample size), and neurological and musculoskeletal features. 
Result: Sixty studies (n = 11, 069) were included in the review, and 51 studies were used in the meta-analysis. The median or mean age ranged from 24 to 95 years. The prevalence of neurological and musculoskeletal manifestations was 35% for smell impairment (95% CI 0-94%; I 2 99.63%), 33% for taste impairment (95% CI 0-91%; I 2 99.58%), 19% for myalgia (95% CI 16-23; I 2 95%), 12% for headache (95% CI 9-15; I 2 93.12%), 10% for back pain (95% CI 1-23%; I 2 80.20%), 10% for dizziness (95% CI 3-19%; I 2 86.74%), 3% for acute cerebrovascular disease (95% CI 1-5%; I 2 0%), and 2% for impaired consciousness (95% CI 1-2%; I 2 0%). 
Conclusion and Relevance: Patients with COVID-19 present with neurological and musculoskeletal symptoms. Therefore, clinicians need to be vigilant in the diagnosis and treatment of these patients
PMID: 32676052


No 531: September 8, 2020

Exploring the clinical association between neurological symptoms and COVID-19 pandemic outbreak: a systematic review of current literature

Di Carlo DT, Montemurro N, Petrella G, Siciliano G, Ceravolo R, Perrini P. Exploring the clinical association between neurological symptoms and COVID-19 pandemic outbreak: a systematic review of current literature [published online ahead of print, 2020 Aug 1]. J Neurol. 2020;1-9. doi:10.1007/s00415-020-09978-y
Object: The novel severe acute respiratory syndrome (SARS)-CoV-2 outbreak has been declared a pandemic in March, 2020. An increasing body of evidence suggests that patients with the coronavirus disease (COVID-19) might have a heterogeneous spectrum of neurological symptoms METHODS: A systematic search of two databases was performed for studies published up to May 29th, 2020. PRISMA guidelines were followed.
Results: We included 19 studies evaluating 12,157 patients with laboratory-confirmed COVID-19 infections. The median age of patients was 50.3 (IQR 11.9), and the rate of male patients was 50.6% (95% CI 49.2-51.6%). The most common reported comorbidities were hypertension and diabetes (31.1%, 95% CI 30-32.3% and 13.5%, 95% CI 12.3-14.8%, respectively). Headache was reported in 7.5% of patients (95% CI 6.6-8.4%), and dizziness in 6.1% (95% CI 5.1-7.1%). Hypo/anosmia, and gustatory dysfunction were reported in 46.8 and 52.3%, of patients, respectively. Symptoms related to muscular injury ranged between 15 and 30%. Three studies reported radiological confirmed acute cerebrovascular disease in 2% of patients (95% CI 1.6-2.4%).
Conclusions: These data support accumulating evidence that a significant proportion of patients with COVID-19 infection develop neurological manifestations, especially olfactory, and gustatory dysfunction. The pathophysiology of this association is under investigation and warrants additional studies, Physicians should be aware of this possible association because during the epidemic period of COVID-19, early recognition of neurologic manifestations otherwise not explained would raise the suspect of acute respiratory syndrome coronavirus 2 infection.
PMID: 32740766



August Topic: Postural Threat Influences in Vestibular Function

No 530: August 26, 2020

The Effect of Unilateral Vestibular Loss on Standing Balance During Postural Threat
Cleworth TW, Allum JHJ, Luu MJ, Lea J, Westerberg BW, Carpenter MG. The Effect of Unilateral Vestibular Loss on Standing Balance During Postural Threat. Otol Neurotol. 2020 Aug;41(7):e945-e951. doi: 10.1097/MAO.0000000000002485.
Objective: Vestibular deficit patients have an increased fall risk and fear of falling. Postural threat, known to increase balance-related fear and anxiety, influences vestibular gains during quiet standing in young healthy adults. The current study examined whether there is a similar relationship for peripheral unilateral vestibular loss (UVL) patients in comparison to age-matched healthy controls (HC).
Setting: University laboratory.
Study design: Prospective laboratory study.
Patients and controls: Eleven UVL patients, nine with vestibular neurectomy. Eleven aged-matched HCs.
Main outcome measures: Subjects stood on a hydraulic lift placed at two heights: low (0.8 m, away from the edge) and high (3.2 m, at the edge). Amplitude (root mean square), mean power frequency (MPF), and mean position were analyzed for center of foot pressure (COP) and 90% ranges for angle amplitude and velocity for trunk sway.
Results: Group interactions were strongest for anterior-posterior (AP) COP and trunk pitch angle. AP lean away from the edge was greater in HCs than UVLs. HCs, but not UVLs had a decrease in root mean square AP COP with height. Trunk pitch sway was changed similarly. Both groups had increased trunk pitch velocity at height. Changes with height were less for roll: MPF of lateral COP increased with height for UVLs with no changes for HCs, and trunk roll amplitude decreased for both groups.
Conclusions: This report provides evidence for a differential effect of height induced postural threat on balance control between UVLs and HCs presumably due to the reduced vestibular-spinal gain in UVL subjects.
PMID: 32658112
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No 529: August 20, 2020

Postural threat influences vestibular-evoked muscular responses

Lim SB, Cleworth TW, Horslen BC, Blouin JS, Inglis JT, Carpenter MG. Postural threat influences vestibular-evoked muscular responses. J Neurophysiol. 2017 Feb 1;117(2):604-611. doi: 10.1152/jn.00712.2016. Epub 2016 Nov 9.


Standing balance is significantly influenced by postural threat. While this effect has been well established, the underlying mechanisms of the effect are less understood. The involvement of the vestibular system is under current debate, and recent studies that investigated the effects of height-induced postural threat on vestibular-evoked responses provide conflicting results based on kinetic (Horslen BC, Dakin CJ, Inglis JT, Blouin JS, Carpenter MG. J Physiol 592: 3671-3685, 2014) and kinematic (Osler CJ, Tersteeg MC, Reynolds RF, Loram ID. Eur J Neurosci 38: 3239-3247, 2013) data. We examined the effect of threat of perturbation, a different form of postural threat, on coupling (cross-correlation, coherence, and gain) of the vestibulo-muscular relationship in 25 participants who maintained standing balance. In the "No-Threat" conditions, participants stood quietly on a stable surface. In the "Threat" condition, participants' balance was threatened with unpredictable mediolateral support surface tilts. Quiet standing immediately before the surface tilts was compared to an equivalent time from the No-Threat conditions. Surface EMG was recorded from bilateral trunk, hip, and leg muscles. Hip and leg muscles exhibited significant increases in peak cross-correlation amplitudes, coherence, and gain (1.23-2.66×) in the Threat condition compared with No-Threat conditions, and significant correlations were observed between threat-related changes in physiological arousal and medium-latency peak cross-correlation amplitude in medial gastrocnemius (r = 0.408) muscles. These findings show a clear threat effect on vestibular-evoked responses in muscles in the lower body, with less robust effects of threat on trunk muscles. Combined with previous work, the present results can provide insight into observed changes during balance control in threatening situations.
New & noteworthy: This is the first study to show increases in vestibular-evoked responses of the lower body muscles under conditions of increased threat of postural perturbation. While robust findings were observed in hip and leg muscles, less consistent results were found in muscles of the trunk. The present findings provide further support in the ongoing debate for arguments that vestibular-evoked balance responses are influenced by fear and anxiety and explain previous threat-related changes in balance
PMID: 26631147
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No 528: August 7, 2020

Comparing the Suppression Head Impulse Paradigm and the Head Impulse Paradigm in Vestibular Neuritis

Naranjo EN, Cleworth TW, Allum JHJ, Inglis JT, Lea J, Westerberg BD, Carpenter MG. Vestibulo-spinal and vestibulo-ocular reflexes are modulated when standing with increased postural threat. J Neurophysiol. 2016 Feb 1;115(2):833-42. doi: 10.1152/jn.00626.2015. Epub 2015 Dec 2.


We investigated how vestibulo-spinal reflexes (VSRs) and vestibulo-ocular reflexes (VORs) measured through vestibular evoked myogenic potentials (VEMPs) and video head impulse test (vHIT) outcomes, respectively, are modulated during standing under conditions of increased postural threat. Twenty-five healthy young adults stood quietly at low (0.8 m from the ground) and high (3.2 m) surface height conditions in two experiments. For the first experiment (n = 25) VEMPs were recorded with surface EMG from inferior oblique (IO), sternocleidomastoid (SCM), trapezius (TRP), and soleus (SOL) muscles in response to 256 air-conducted short tone bursts (125 dB SPL, 500 Hz, 4 ms) delivered via headphones. A subset of subjects (n = 19) also received horizontal and vertical head thrusts (∼150°/s) at each height in a separate session, comparing eye and head velocities by using a vHIT system for calculating the functional VOR gains. VEMP amplitudes (IO, TRP, SOL) and horizontal and vertical vHIT gains all increased with high surface height conditions (P < 0.05). Changes in IO and SCM VEMP amplitudes as well as horizontal vHIT gains were correlated with changes in electrodermal activity (ρ = 0.44-0.59, P < 0.05). VEMP amplitude for the IO also positively correlated with fear (ρ = 0.43, P = 0.03). Threat-induced anxiety, fear, and arousal have significant effects on VSR and VOR gains that can be observed in both physiological and functional outcome measures. These findings provide support for a potential central modulation of the vestibular nucleus complex through excitatory inputs from neural centers involved in processing fear, anxiety, arousal, and vigilance.
PMID: 26631147
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