Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature

In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat-sensitivity/Uhthoff's phenomenon). While the impact of heat-sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a novel quantitative sensory test. Eight relapsing-remitting MS patients (3M/5F; 51.4 ± 9.1 y; EDSS score: 2.8 ± 1.1) and 8 age-matched controls (CTR; 5M/3F; 47.4 ± 9.1 y) rated perceived magnitude of two cold (26; 22°C) and warm (34; 38°C) stimuli applied to the dorsum of the hand, pre and post 30-min cycling in the heat (30°C air; 30% RH). Exercise produced similar increases in mean body temperature in MS (+0.39°C [95%CI: +0.21, +0.53] P = 0.001) and CTR (+0.41°C [95%CI: +0.25, +0.58] P = 0.001). These changes were sufficient to significantly decrease thermosensitivity to all cold (26°C stimulus: -9.1% [95%CI: -17.0, -1.5], P = 0.006; 22°C stimulus: -10.6% [95%CI: -17.3, -3.7], P = 0.027), but not warm, stimuli in MS. Contrariwise, CTR showed sensitivity reductions to colder stimuli only (22°C stimulus: -9.7% [95%CI: -16.4, -3.1], P = 0.011). The observation that reductions in thermal-sensitivity in MS were confined to the myelinated cold-sensitive pathway, and extended across a wider (including milder/colder) temperature range than what is observed in CTR, provides novel evidence on the impact of rising body temperature on afferent neural function in MS. Also, our findings support the use of our novel approach to investigate afferent sensory function in MS during heat stress. This article is protected by copyright. All rights reserved

Cold water ingestion improves exercise tolerance of heat-sensitive people with MS

© 2018 Lippincott Williams and Wilkins. All rights reserved. Purpose Heat intolerance commonly affects the exercise capacity of people with multiple sclerosis (MS) during bouts of hot weather. Cold water ingestion is a simple cooling strategy, but its efficacy for prolonging exercise capacity with MS remains undetermined. We sought to identify whether cold water ingestion blunts exercise-induced rises in body temperature and improves exercise tolerance in heat-sensitive individuals with MS. Methods On two separate occasions, 20 participants (10 relapsing-remitting MS (expanded disability status scale, 2-4.5); 10 age-matched healthy controls) cycled at ∼40% VO 2max at 30°C and 30% relative humidity until volitional exhaustion (or a maximum of 60 min). Every 15 min, participants ingested 3.2 mL·kg -1 of either 1.5°C (CLD) or 37°C (NEU) water. Rectal (T re ) temperature, mean skin (T sk ) temperature, and heart rate (HR) were measured throughout. Results All 10 controls but only 3 of 10 MS participants completed 60 min of exercise in NEU trial. The remaining 7 MS participants all cycled longer (P = 0.006) in CLD (46.4 ± 14.2 min) compared with NEU (32.7 ± 11.5 min), despite a similar absolute T re (NEU: 37.32°C ± 0.34°C; CLD: 37.28°C ± 0.26°C; P = 0.44), change in T re (NEU: 0.38°C ± 0.21°C; CLD: 0.34°C ± 0.24°C), absolute T sk (NEU: 34.48°C ± 0.47°C; CLD: 34.44°C ± 0.54°C; P = 0.82), and HR (NEU: 114 ± 20 bpm; CLD: 113 ± 18 bpm; P = 0.38) for the same exercise volume. Conclusions Cold water ingestion enhanced exercise tolerance of MS participants in the heat by ∼30% despite no differences in T re , T sk or HR. These findings support the use of a simple cooling strategy for mitigating heat intolerance with MS and lend insight into the potential role of cold-afferent thermoreceptors that reside in the abdomen and oral cavity in the modulation of exercise tolerance with MS in the heat

Temperature sensitivity in multiple sclerosis: an overview of its impact on sensory and cognitive symptoms

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by demyelination of the central nervous system (CNS). The exact cause of MS is still unknown; yet its incidence and prevalence rates are growing worldwide, making MS a significant public health challenge. The heterogeneous distribution of demyelination within and between MS patients translates in a complex and varied array of autonomic, motor, sensory and cognitive symptoms. Yet a unique aspect of MS is the highly prevalent (60–80%) temperature sensitivity of its sufferers, where neurological symptoms are temporarily exacerbated by environmental- or exercise-induced increases (or decreases) in body temperature. MS temperature sensitivity is primarily driven by temperature-dependent slowing or blocking of neural conduction within the CNS due to changes in internal (core) temperature; yet changes in skin temperature could also contribute to symptom exacerbation (e.g. during sunlight and warm ambient exposure). The impact of temperature sensitivity, and particularly of increases in core temperature, on autonomic (e.g. thermoregulatory/cardiovascular function) and motor symptoms (e.g. fatigue) is well described. However, less attention has been given to how increases (and decreases) in core and skin temperature affect sensory and cognitive symptoms. Furthermore, it remains uncertain whether changes in skin temperature alone could also trigger worsening of symptoms. Here we review the impact of temperature sensitivity on MS sensory and cognitive function and discuss additional factors (e.g. changes in skin temperature) that potentially contribute to temperature-induced worsening of symptoms in the absence of alteration in core temperature

Effects of exercise-induced increases in body temperatures on local skin thermal sensitivity in Multiple Sclerosis patients

Exercise and concomitant increases in body temperature reduces local skin thermal sensitivity via hypothesized analgesic-effects. Abnormal thresholds for thermal sensations and heat-sensitivity are well-established symptoms and modulatory factors, respectively, of Multiple Sclerosis. However, it is unknown whether increases in body temperature modulate sensory abnormalities in MS. We therefore investigated the hypothesis that changes in local skin thermal sensitivity are reduced in relapsing-remitting MS patients during cycling in the heat (30°C; 35%RH). Seven MS patients (age 54±7 y; body mass 76.1±10.9 kg; body surface area 1.9±0.2 m2), with increased warmth thresholds (0.61±0.58°C) compared to 4 age-, mass- and body surface area-matched healthy controls (CTR) (53±9 y; 75.6±14.0 kg; 1.9±0.2 m2; warmth threshold: 0.38±0.25°C); were asked to perform 30-min cycling at an intensity of 3.3 W/kg of total body mass. A quantitative thermo-sensory test, consisting of reporting (visual analogue scale) perceived magnitude of local warm (38°C) and cold (22°C) thermal stimuli (25 cm2-thermal probe) applied to the dorsum of the hand, was performed before and after every 10 min of cycling. Rectal temperature increased similarly between MS (+0.20±0.17°C) and CTR (+0.15±0.09°C) (p=0.619), whereas changes in mean skin temperature were greater in MS (1.41±0.38°C) than CTR (0.96±0.28°C) (p=0.077). 30 min of cycling reduced CTR thermo-sensitivity to warm (−10.5±10.0%) and cold (−14.1±8.5%) thermal stimuli. MS patients also experienced exercise-induced reductions in local thermo-sensitivity, however these were of smaller magnitude, both for warm (−2.7±16.4%) and cold (−10.4±8.6%) thermal stimuli. In line with previous research, exercise-induced increases in body temperature reduce skin thermo-sensitivity providing an analgesic effect in healthy controls. However, MS diminishes the magnitude of such effect

Blunted sweating does not alter the rise in core temperature in people with multiple sclerosis exercising in the heat

Purpose: To determine whether thermoregulatory capacity is altered by MS during exercise in the heat. Methods: Sixteen MS (EDSS: 2.9±0.9; 47±8 y; 77.6±14.0 kg) and 14 healthy (CON) control participants (43±11 y; 78.6±17.0 kg) cycled at a heat production of 4 W.kg-1 for 60 minutes at 30˚C, 30%RH (WARM). A subset of 8 MS (EDSS: 2.6±0.5; 44±8 y; 82.3±18.2 kg) and 8 CON (44±12 y; 81.2±21.1 kg) also exercised at 35°C, 30%RH (HOT). Rectal (Tre), mean skin (Tsk) temperature, and local sweat rate on the upper-back (LSRback) and forearm (LSRarm), were measured. Results: All CON, yet only 9 of 16, and 7 of 8 MS participants completed 60 min of exercise in WARM and HOT trials, respectively. All MS participants unable to complete exercise stopped with ∆Tre between 0.2-0.5˚C. The time to reach a ∆Tre of 0.2˚C was similar (MS:28±15 min, CON: 32±18 min; P=0.51). For MS participants completing 60-min of exercise in WARM, ∆Tre (P=0.13), ∆Tsk (P=0.45), LSRback (P=0.69) and LSRarm (P=0.54) were similar to CON, but ΔTb (MS:0.16±0.13˚C, CON:0.07±0.06˚C; P=0.02) and onset time (MS:16±10 min, CON:8±5 min; P=0.02) for sweating were greater. Similarly, in HOT, ∆Tre (P=0.52), ∆Tsk (P=0.06), LSRback (P=0.59) and LSRarm (P=0.08) were similar, but ΔTb (MS: 0.19±0.16˚C, CON: 0.06±0.04˚C; P=0.04) and onset time (MS:13±7 min, CON:6±3 min; P=0.02) for sweating were greater with MS. Conclusion: Even at 35˚C, a delayed sweating onset didn't alter heat loss to sufficiently affect exercise-induced rises in core temperature. Heat intolerance with MS does not seem attributable to thermoregulatory impairments

Linear Regression Model.

<p>Linear Regression Model.</p

Correlation with LCVA.

<p>Correlation with LCVA.</p

sj-docx-1-tan-10.1177_17562864231180734 – Supplemental material for Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method

Supplemental material, sj-docx-1-tan-10.1177_17562864231180734 for Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method by Ralf Gold, Michael Barnett, Andrew Chan, Huiyu Feng, Kazuo Fujihara, Gavin Giovannoni, Xavier Montalbán, Fu-Dong Shi, Mar Tintoré, Qun Xue, Chunsheng Yang and Hongyu Zhou in Therapeutic Advances in Neurological Disorders</p

Predictors of first treatment discontinuation.

<p>Abbreviations: n: number, HR: Hazard Ratio, CI: Confidence Interval, IFN: Interferon, IM: intramuscular, SC: Subcutaneous, GA: Glatiramer Acetate, EDSS: Expanded Disability Status Scale.</p><p>Treatment initiations n = 760 excluding Natalizumab (n = 11).</p>α<p>Cox Proportional Hazards Regression.</p><p>Multivariable Cox Proportional Hazards model was adjusted for sex, disease duration, age at treatment start, treatment and EDSS.</p><p># Proportional hazards test: p = 0.3747.</p>*<p>No EDSS score available at the time of treatment start.</p

Proportion of patients class switching from first to second IFNβ preparation.

<p>Proportion of patients class switching from first to second IFNβ preparation.</p