Evaluating the impact of patient-reported outcome measures on depression and anxiety levels in people with multiple sclerosis: a study protocol for a randomized controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients' lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient's perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety. METHODS: A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient's MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes. DISCUSSION: This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice. TRIAL REGISTRATION: This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.gov NCT04979546 . Registered on July 28, 2021.

Postnatal development of persistent inward currents in rat XII motoneurons and their modulation by serotonin, muscarine and noradrenaline.

KEY POINTS: Persistent inward currents (PICs) in spinal motoneurons are long-lasting, voltage-dependent currents that increase excitability; they are dramatically potentiated by serotonin, muscarine, and noradrenaline (norepinephrine). Loss of these modulators (and the PIC) during sleep is hypothesized as a major contributor to REM sleep atonia. Reduced excitability of XII motoneurons that drive airway muscles and maintain airway patency is causally implicated in obstructive sleep apnoea (OSA), but whether XII motoneurons possess a modulator-sensitive PIC that could be a factor in the reduced airway tone of sleep is unknown. Whole-cell recordings from rat XII motoneurons in brain slices indicate that PIC amplitude increases ∼50% between 1 and 23 days of age, when potentiation of the PIC by 5HT2 , muscarinic, or α1 noradrenergic agonists peaks at <50%, manyfold lower than the potentiation observed in spinal motoneurons. α1 noradrenergic receptor activation produced changes in XII motoneuron firing behaviour consistent with PIC involvement, but indicators of strong PIC activation were never observed; in vivo experiments are needed to determine the role of the modulator-sensitive PIC in sleep-dependent reductions in airway tone. ABSTRACT: Hypoglossal (XII) motoneurons play a key role in maintaining airway patency; reductions in their excitability during sleep through inhibition and disfacilitation, i.e. loss of excitatory modulation, is implicated in obstructive sleep apnoea. In spinal motoneurons, 5HT2 , muscarinic and α1 noradrenergic modulatory systems potentiate persistent inward currents (PICs) severalfold, dramatically increasing excitability. If the PICs in XII and spinal motoneurons are equally sensitive to modulation, loss of the PIC secondary to reduced modulatory tone during sleep could contribute to airway atonia. Modulatory systems also change developmentally. We therefore characterized developmental changes in magnitude of the XII motoneuron PIC and its sensitivity to modulation by comparing, in neonatal (P1-4) and juvenile (P14-23) rat brainstem slices, the PIC elicited by slow voltage ramps in the absence and presence of agonists for 5HT2 , muscarinic, and α1 noradrenergic receptors. XII motoneuron PIC amplitude increased developmentally (from -195 ± 12 to -304 ± 19 pA). In neonatal XII motoneurons, the PIC was only potentiated by α1 receptor activation (5 ± 4%). In contrast, all modulators potentiated the juvenile XII motoneurons PIC (5HT2 , 5 ± 5%; muscarine, 22 ± 11%; α1 , 18 ± 5%). These data suggest that the influence of the PIC and its modulation on XII motoneuron excitability will increase with postnatal development. Notably, the modulator-induced potentiation of the PIC in XII motoneurons was dramatically smaller than the 2- to 6-fold potentiation reported for spinal motoneurons. In vivo measurements are required to determine if the modulator-sensitive, XII motoneuron PIC is an important factor in sleep-state dependent reductions in airway tone.

Neuroglia and their roles in central respiratory control; an overview.

While once viewed as mere housekeepers, providing structural and metabolic support for neurons, it is now clear that neuroglia do much more. Phylogenetically, they have undergone enormous proliferation and diversification as central nervous systems grew in their complexity. In addition, they: i) are morphologically and functionally diverse; ii) play numerous, vital roles in maintaining CNS homeostasis; iii) are key players in brain development and responses to injury; and, iv) via gliotransmission, are likely participants in information processing. In this review, we discuss the diverse roles of neuroglia in maintaining homeostasis in the CNS, their evolutionary origins, the different types of neuroglia and their functional significance for respiratory control, and finally consider evidence that they contribute to the processing of chemosensory information in the respiratory network and the homeostatic control of blood gases.

A 58-Year-Old Man With Episodic Hypercapnic Respiratory Failure.

CASE PRESENTATION: A 58-year-old man presented to the ED with a 1-week history of progressive weight loss, generalized weakness, unsteadiness, and dizziness. In hospital, he experienced a witnessed episode of loss of consciousness with no observable respirations that lasted for 15 minutes. His arterial blood gas demonstrated hypercapnic respiratory failure, and he required mask ventilation and vasoactive medications. Similar episodes occurred several more times over the course of the night that required the patient to be intubated. The paroxysmal episodes persisted necessitating continued invasive ventilatory support and admission to the ICU. The episodes occurred in both awake and asleep states and required the ventilator settings to dictate a minimum rate, but minimal ventilatory support otherwise. Further history revealed other symptomatic complaints of vertigo, dysphagia, and hypophonia that had progressed over a 2-month period. The patient's medical history was pertinent for a diagnosis of prostatic carcinoma 3 years previously that was found to be castrate resistant. He had metastases to his hip, ribs, and thoracic spine. Previous treatments had included bicalutamide, docetaxel, and abiraterone; he was receiving leuprolide therapy on presentation.