Cervico-Ocular Reflex in Normal Subjects and Patients with Unilateral Vestibular Hypofunction

Objective: To determine whether the cervico-ocular reflex contributes to gaze stability in patients with unilateral vestibular hypofunction. Study Design: Prospective study. Setting: Tertiary referral center. Patients: Patients with unilateral vestibular hypofunction (n = 3) before and after vestibular rehabilitation and healthy subjects (n = 7). Interventions: Vestibular rehabilitation. Main Outcome Measures: We measured the cervico-ocular reflex in patients with unilateral vestibular hypofunction before and after vestibular rehabilitation and in healthy subjects. To measure the cervico-ocular reflex, we recorded eye movements with a scleral search coil while the trunk moved at 0.3, 1.0, and 1.5 Hz beneath a stabilized head. To determine whether the head was truly stabilized, we measured head movement using a search coil. Results: We found no evidence of cervico-ocular reflex in any of the seven healthy subjects or in two of the patients with unilateral vestibular hypofunction. In one patient with chronic unilateral vestibular hypofunction, the cervico-ocular reflex was present before vestibular rehabilitation only for leftward trunk rotation (relative head rotation toward the intact side). After 5 weeks of placebo exercises, there was no change in the cervico-ocular reflex. After an additional 5 weeks that included vestibular exercises, cervico-ocular reflex gain for leftward trunk rotation had increased threefold. In addition, there was now evidence of a cervico-ocular reflex for rightward trunk rotation, potentially compensating for the vestibular deficit. Conclusion: The cervico-ocular reflex appears to be a highly inconsistent mechanism. The change of the cervico-ocular reflex in one patient after vestibular exercises suggests that the cervico-ocular reflex may be adaptable in some patients

A Prototype Head-Motion Monitoring System for In-Home Vestibular Rehabilitation Therapy

This work reports the use of a head-motion monitoring system to record patient head movements while completing in-home exercises for vestibular rehabilitation therapy. Based upon a dual-axis gyroscope (yaw and pitch, ± 500-degrees/sec maximum), angular head rotations were measured and stored via an on-board memory card. The system enabled the clinician to document exercises at home. Several measurements were recorded in one patient with unilateral vestibular hypofunction: The total time of exercise for the week (118 minutes) was documented and compared with expected weekly exercise time (140 minutes). For gaze stabilization exercises, execution time of 60 sec was expected, and observed times ranged from 75-100 sec. An absence of rest periods between each exercise instead of the recommended one minute rest period was observed. Maximum yaw head velocities from approximately 100-350 degrees/sec were detected. A second subject provided feedback concerning the ease of use of the HAMMS device. This pilot study demonstrates, for the first time, the capability to capture the head-motion “signature” of a patient while completing vestibular rehabilitation exercises in the home and to extract exercise regime parameters and monitor patient adherence. This emerging technology has the potential to greatly improve rehabilitation outcomes for individuals completing in-home gaze stabilization exercises 1

Oculomotor Strategies and Their Effect on Reducing Gaze Position Error

Objective: Vestibular adaptation exercises have been shown to improve gaze stability during active head rotation in individuals with vestibular hypofunction. Little is known, however, of the types of eye movements used during passive head rotation and their effect on gaze stability in individuals with vestibular hypofunction. The primary purpose of this study was to determine differences in oculomotor strategies and their effect on stabilizing gaze during ipsilesional passive and active head rotations in vestibular hypofunction. Patients: Subjects with unilateral (n = 4) and bilateral (n = 3) vestibular hypofunction and healthy subjects (n = 4) based on bithermal caloric and rotational chair testing. Intervention: Diagnostic. Main Outcome Measure: Head and eye velocity and position data measured with scleral search coil. Results: Subjects with unilateral and bilateral vestibular hypofunction generated 3 types of gaze-stabilizing eye movements with ipsilesional head impulses: slow vestibular ocular reflex, compensatory, and corrective saccades. The types of eye movements generated during active and passive head impulses were highly individualized. Gaze position error was reduced when compensatory saccades were recruited as part of the gaze-stabilizing strategy. Conclusion: Rehabilitation for individuals with vestibular hypofunction should identify individuals' unique gaze stability preferences and attempt to facilitate compensatory saccades

Treatment for Vestibular Disorders: How Does Your Physical Therapist Treat Dizziness Related to Vestibular Problems?

Dizziness is very common, but it is never normal. Dizziness can make performing daily activities, work, and walking difficult. Many people get dizzy when they turn their head, which can cause problems with walking and makes people more likely to fall. Most of the time dizziness is not from a life-threatening disease. Often dizziness is because of a disorder of the vestibular (or inner ear balance) system. People can get vestibular disorders from infections in the ear, problems with the immune system, medications that harm the inner ear, and rarely from diabetes or stroke because of a lack of blood flow to the inner ear. Stress, poor sleep, migraines, overdoing some activities, and feeling sad can increase symptoms. New guidelines for the treatment of vestibular disorders were published in the April 2016 issue of the Journal of Neurologic Physical Therapy. The guideline describes which exercises are best to treat the dizziness and balance problems commonly seen with an inner ear disorder

Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Evidence-Based Clinical Practice Guideline: From the American Physical Therapy Association Neurology Section

Background: Uncompensated vestibular hypofunction results in postural instability, visual blurring with head movement, and subjective complaints of dizziness and/or imbalance. We sought to answer the question, \ Is vestibular exercise effective at enhancing recovery of function in people with peripheral (unilateral or bilateral) vestibular hypofunction?\ Methods: A systematic review of the literature was performed in 5 databases published after 1985 and 5 additional sources for relevant publications were searched. Article types included meta-analyses, systematic reviews, randomized controlled trials, cohort studies, case control series, and case series for human subjects, published in English. One hundred thirty-five articles were identified as relevant to this clinical practice guideline. Results/Discussion: Based on strong evidence and a preponderance of benefit over harm, clinicians should offer vestibular rehabilitation to persons with unilateral and bilateral vestibular hypofunction with impairments and functional limitations related to the vestibular deficit. Based on strong evidence and a preponderance of harm over benefit, clinicians should not include voluntary saccadic or smooth-pursuit eye movements in isolation (ie, without head movement) as specific exercises for gaze stability. Based on moderate evidence, clinicians may offer specific exercise techniques to target identified impairments or functional limitations. Based on moderate evidence and in consideration of patient preference, clinicians may provide supervised vestibular rehabilitation. Based on expert opinion extrapolated from the evidence, clinicians may prescribe a minimum of 3 times per day for the performance of gaze stability exercises as 1 component of a home exercise program. Based on expert opinion extrapolated from the evidence (range of supervised visits: 2-38 weeks, mean = 10 weeks), clinicians may consider providing adequate supervised vestibular rehabilitation sessions for the patient to understand the goals of the program and how to manage and progress themselves independently. As a general guide, persons without significant comorbidities that affect mobility and with acute or subacute unilateral vestibular hypofunction may need once a week supervised sessions for 2 to 3 weeks; persons with chronic unilateral vestibular hypofunction may need once a week sessions for 4 to 6 weeks; and persons with bilateral vestibular hypofunction may need once a week sessions for 8 to 12 weeks. In addition to supervised sessions, patients are provided a daily home exercise program. Disclaimer: These recommendations are intended as a guide for physical therapists and clinicians to optimize rehabilitation outcomes for persons with peripheral vestibular hypofunction undergoing vestibular rehabilitation

Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical prostatectomy: functional outcomes 18 months after diagnosis from a national cohort study in England.

BACKGROUND: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted without robust evidence comparing its functional outcomes against laparoscopic radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP) approaches. This study compared patient-reported functional outcomes following RARP, LRP or ORP. METHODS: All men diagnosed with prostate cancer in England during April - October 2014 who underwent radical prostatectomy were identified from the National Prostate Cancer Audit and mailed a questionnaire 18 months after diagnosis. Group differences in patient-reported sexual, urinary, bowel and hormonal function (EPIC-26 domain scores) and generic health-related quality of life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour characteristics, were estimated using linear regression. RESULTS: In all, 2219 men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%) ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual function scores compared with LRP (3·5 point difference; 95% CI: 1.1-5.9, P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not meet the threshold for a minimal clinically important difference (10-12 points). There were no significant differences in other EPIC-26 domain scores or HRQoL. CONCLUSIONS: It is unlikely that the rapid adoption of RARP in the English NHS has produced substantial improvements in functional outcomes for patients

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Balance Function and Dysfunction and the Vestibular System

Book Summary: In two freestanding but linked volumes, Textbook of Neural Repair and Rehabilitation provides comprehensive coverage of the science and practice of neurological rehabilitation. This volume, Medical Neurorehabilitation, can stand alone as a clinical handbook for neurorehabilitation. It covers the practical applications of the basic science principles presented in volume 1, provides authoritative guidelines on the management of disabling symptoms, and describes comprehensive rehabilitation approaches for the major categories of disabling neurological disorders. Emphasizing the integration of basic and clinical knowledge, this book and its companion are edited and written by leading international authorities. Together they are an essential resource for neuroscientists and provide a foundation for the work of clinical neurorehabilitation professionals