Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease.

The COVID-19 pandemic has devastated individuals, families, and institutions throughout the world. Despite the breakneck speed of vaccine development, the human population remains at risk of further devastation. The decision to not become vaccinated, the protracted rollout of available vaccine, vaccine failure, mutational forms of the SARS virus, which may exhibit mounting resistance to our molecular strike at only one form of the viral family, and the rapid ability of the virus(es) to hitch a ride on our global transportation systems, means that we are will likely continue to confront an invisible, yet devastating foe. The enemy targets one of our human physiology's most important and vulnerable life-preserving body tissues, our broncho-alveolar gas exchange apparatus. Notwithstanding the fear and the fury of this microbe's potential to raise existential questions across the entire spectrum of human endeavor, the application of an early treatment intervention initiative may represent a crucial tool in our defensive strategy. This strategy is driven by evidence-based medical practice principles, those not likely to become antiquated, given the molecular diversity and mutational evolution of this very clever "world traveler".

Identification and treatment of the visual processing asymmetry in MS patients with optic neuritis: The Pulfrich phenomenon.

BACKGROUND: The Pulfrich phenomenon (PF) is the illusory perception that an object moving linearly along a 2-D plane appears to instead follow an elliptical 3-D trajectory, a consequence of inter-eye asymmetry in the timing of visual object identification in the visual cortex; with optic neuritis as a common etiology. OBJECTIVE: We have designed an objective method to identify the presence and magnitude of the PF, in conjunction with a cooresponding strategy by which to abolish the effect; with monocular application of neutral density filters to the less affected fellow eye, in patients with MS and a history of optic neuropathy (e.g. related to acute optic neuritis or subclinical optic neuropathy). METHODS: Twenty-three MS patients with a history of acute unilateral or bilateral optic neuritis, and ten healthy control subjects (HC) were recruited to participate in a pilot study to assess our strategy. Subjects were asked to indicate whether a linearly moving pendulum ball followed a linear 2-D path versus an illusory 3-D elliptical object-motion trajectory, by reporting the ball's approximation to one of nine horizontally-oriented colored wires that were positioned parallel to one another and horizontal to the linear pendulum path. Perceived motion of the bob that moved along wires behind or in front (along the 'Z' plane) of the middle reference wire indicated an illusory elliptical trajectory of ball motion consistent with the PF. RESULTS: When the neutral density filter titration was applied to the fellow eye the severity of the PF decreased, eventually being fully abolished in all but one patient. The magnitude of neutral density filtering required correlated to the severity of the patient's initial PF magnitude (p < 0.001). CONCLUSIONS: We ascertained the magnitude of the visual illusion associated with the PF, and the corresponding magnitude of neutral density filtering necessary to abolish it.

Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis.

Importance: A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. Objective: To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. Design, Setting, and Participants: The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). Main Outcomes and Measures: Association of pupillary response characteristics with alterations in retinal architecture. Results: Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). Conclusions and Relevance: In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.

Aquatic training in MS: neurotherapeutic impact upon quality of life.

Three fundamental principals associated with aquatic therapy differentiate it with respect to exercise on land, and in air. These are buoyancy (reduction in weight of the body within the buoyant medium of water), viscosity (a "drag force" is generated when moving within water, when compared with the same movement in air), and the thermodynamic aspect of water exercise, during which the heat capacity of water is about 1000 times greater than that of an equivalent amount of air; equating to a heat transfer from the body into water at a rate 25 times faster than that of air. Aquatic conditioning, can improve neurologic functioning, with dividends favorably impacting activities of daily living, health maintenance, safety, and ultimately quality of life. Here, we review the application of aquatic exercise training in MS patients.

Ocular motor signatures of cognitive dysfunction in multiple sclerosis.

The anatomical and functional overlap between ocular motor command circuitry and the higher-order networks that form the scaffolding for cognition makes for a compelling hypothesis that measures of ocular motility could provide a means to sensitively interrogate cognitive dysfunction in people with multiple sclerosis (MS). Such an approach may ultimately provide objective and reproducible measures of cognitive dysfunction that offer an innovative capability to refine diagnosis, improve prognostication, and more accurately codify disease burden. A further dividend may be the validation and application of biomarkers that can be used in studies aimed at identifying and monitoring preventative, protective and even restorative properties of novel neurotherapeutics in MS. This Review discusses the utility of ocular motor measures in patients with MS to characterize disruption to wide-ranging networks that support cognitive function.