Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. METHODS: Electrocardiogram and beat-to-beat blood pressure were continuously recorded during 8-10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. RESULTS: Groups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). CONCLUSION: These data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

Voluntary Cooling during Exercise Is Augmented in People with Multiple Sclerosis Who Experience Heat Sensitivity.

INTRODUCTION: We tested the hypothesis that people with multiple sclerosis (MS) who experience heat sensitivity voluntarily engage in cool-seeking behavior during exercise to a greater extent than healthy controls. METHODS: In a 27.0°C ± 0.2°C, 41% ± 2% RH environment, seven participants with relapsing-remitting MS who exhibited heat sensitivity and seven healthy controls completed two randomized trials cycling for 40 min (EX) at 3.5 W·kg-1 metabolic heat production, followed by 30 min recovery (REC). In one trial, participants were restricted from engaging in cooling (CON). In the other trial, participants voluntarily pressed a button to receive 2 min of ~2°C water perfusing a top (COOL). Mean skin and core temperatures and mean skin wettedness were recorded continuously. Total time in cooling provided an index of cool-seeking behavior. RPE, total symptom scores (MS only), and subjective fatigue (MS only) were recorded every 10 min. RESULTS: Core temperature (+0.5°C ± 0.1°C) and skin wettedness (+0.53 ± 0.02 a.u.) increased but were not different between groups or trials at end exercise (P = 0.196) or end recovery (P = 0.342). Mean skin temperature was reduced in COOL compared with CON at end exercise (P ≤ 0.002), with no differences between groups (P ≥ 0.532). MS spent more total time in cooling during EX (MS, 13 ± 3 min; healthy, 7 ± 4 min; P < 0.001) but not REC (MS, 2 ± 1 min; healthy, 0 ± 1 min; P = 0.496). RPE was greater at end exercise in MS (P = 0.001). Total symptom scores increased during exercise (P = 0.005) but was not different between trials (P = 0.321), whereas subjective fatigue was not attenuated in the cooling trial (P = 0.065). CONCLUSION: Voluntary cooling is augmented in MS but does not consistently mitigate perceptions of heat-related symptoms or subjective fatigue.

Individualized analysis of skin thermosensory thresholds and sensitivity in heat-sensitive people with multiple sclerosis.

We investigated whether and how multiple sclerosis (MS) alters thresholds for perceiving increases and decreases in local skin temperature, as well as the sensitivity to progressively greater temperature stimuli, amongst heat-sensitive people with MS. Eleven MS patients (5 M/6 F; 51.1 ± 8.6 y, EDSS 5.7 ± 1.9) and 11 healthy controls (CTR; 7 M/4 F; 50.3 ± 9.0 y) performed warm and cold threshold tests on a hairy skin site, on both sides of the body. They also underwent a thermosensitivity test where they rated (visual analogue scale) perceived magnitude of 4 local skin stimuli (i.e. 22, 26, 34, 38°C). Individual thresholds and slopes of linear regression for thermosensitivity were z-transformed for each MS patient, and used to determine individual thermosensory abnormalities. When considering both threshold and thermosensitivity, six out of our 11 heat-sensitive patients (54.5%) exhibited skin thermosensory abnormalities. Those abnormalities varied amongst patients in terms of type (threshold vs. thermosensitivity), quality (warm vs. cold), location (left vs. right side of the body) and extent. Each of those six patients presented unique thermosensory profiles. While some patients experienced thermosensory loss in both thresholds and sensitivity and on both sides of the body, others experienced cold thermosensory loss on one side of the body only. The observed individual variability in thermosensory function among heat-sensitive MS patients highlight the need for a patient-centered approach to assessing thermosensory dysfunction and its potential implications for heat stress vulnerability in this patient group.

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

The purpose of this study is to determine whether thermoregulatory capacity is altered by multiple sclerosis (MS) during exercise in the heat. Sixteen MS participants (EDSS: 2.9 ± 0.9; 47 ± 8 yr; 77.6 ± 14.0 kg) and 14 healthy control (CON) participants (43 ± 11 yr; 78.6 ± 17.0 kg) cycled at a heat production of 4 W·kg-1 for 60 min at 30°C, 30% relative humidity (RH) (Warm). A subset of eight MS (EDSS: 2.6 ± 0.5; 44 ± 8 yr; 82.3 ± 18.2 kg) and 8 CON (44 ± 12 yr; 81.2 ± 21.1 kg) also exercised at 35°C, 30% RH (Hot). Rectal temperature (Tre), mean skin (Tsk) temperature, and local sweat rate (LSR) on the upper back (LSRback) and forearm (LSRarm) were measured. All CON, and only 9 of 16 and 7 of 8 MS participants completed 60 min of exercise in Warm and Hot trials, respectively. All MS participants who were unable to complete exercise stopped with a ΔTre between 0.2 and 0.5°C. The time to reach a ΔTre 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, ΔTre (P = 0.13), ΔTsk (P = 0.45), LSRback (P = 0.69), and LSRarm (P = 0.54) was similar to CON, but ΔTb (body temperature) (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 in MS. Similarly, in Hot, ΔTre (P = 0.52), ΔTsk (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 in MS. Even at 35°C, a delayed sweating onset did not alter heat loss to sufficiently affect exercise-induced rises in core temperature. Heat intolerance with MS does not seem attributable to thermoregulatory impairments.

Skin tattooing impairs sweating during passive whole body heating.

Tattooing of the skin involves repeated needle insertions to deposit ink into the dermal layer of the skin, potentially damaging eccrine sweat glands and the cutaneous vasculature. This study tested the hypothesis that reflex increases in sweat rate (SR) and cutaneous vasodilation are blunted in tattooed skin (TAT) compared with adjacent healthy skin (CON) during a passive whole body heat stress (WBH). Ten individuals (5 males and 5 females) with a sufficient area of tattooed skin participated in the study. Intestinal temperature (Tint), skin temperature (Tskin), skin blood flow (laser Doppler flux; LDF), and SR were continuously measured during normothermic baseline (34°C water perfusing a tube-lined suit) and WBH (increased Tint 1.0°C via 48°C water perfusing suit). SR throughout WBH was lower for TAT compared with CON (P = 0.033). Accumulated sweating responses during WBH (area under curve) were attenuated in TAT relative to CON (23.1 ± 12.9, 26.9 ± 14.5 mg/cm2, P = 0.043). Sweating threshold, expressed as the onset of sweating in time or Tint from the initiation of WBH, was not different between TAT and CON. Tattooing impeded the ability to obtain LDF measurements. These data suggest that tattooing functionally damages secretion mechanisms, affecting the reflex capacity of the gland to produce sweat, but does not appear to affect neural signaling to initiate sweating. Decreased sweating could impact heat dissipation especially when tattooing covers a higher percentage of body surface area and could be considered a potential long-term clinical side effect of tattooing.NEW & NOTEWORTHY This study is the first to assess the reflex control of sweating in tattooed skin. The novel findings are twofold. First, attenuated increases in sweat rate were observed in tattooed skin compared with adjacent healthy non-tattooed skin in response to a moderate increase (1.0°C) in internal temperature during a passive whole body heat stress. Second, reduced sweating in tattooed skin is likely related to functional damage to the secretory mechanisms of eccrine sweat glands, rendering it less responsive to cholinergic stimulation.

Congenital Disseminated Pyogenic Granuloma: Characterization of an Aggressive Multisystemic Disorder.

OBJECTIVE: To describe the clinical, radiologic, and histopathologic features of "congenital disseminated pyogenic granuloma" involving various organs with high morbidity related to cerebral hemorrhagic involvement. STUDY DESIGN: We searched the database of the Vascular Anomalies Center at Boston Children's Hospital from 1999 to 2019 for patients diagnosed as having multiple vascular lesions, visceral vascular tumors, congenital hemangiomatosis, multiple pyogenic granulomas, or multiple vascular lesions without a definite diagnosis. A retrospective review of the medical records, photographs, histopathologic, and imaging studies was performed. Only patients with imaging studies and histopathologic diagnosis of pyogenic granuloma were included. RESULTS: Eight children (5 male, 3 female) had congenital multifocal cutaneous vascular tumors. Lesions also were found in the brain (n = 7), liver (n = 4), spleen (n = 3), muscles (n = 4), bone (n = 3), retroperitoneum (n = 3), and intestine/mesentery (n = 2). Less commonly affected were the spinal cord, lungs, kidneys, pancreas, and adrenal gland (n = 1 each). The mean follow-up period was 21.8 months. The cerebral and visceral lesions were hemorrhagic with severe neurologic sequelae. The histopathologic diagnosis was pyogenic granuloma with prominent areas of hemorrhage and necrosis. The endothelial cells had enlarged nuclei, pale cytoplasm and were immunopositive for CD31 and negative for D2-40 and glucose transporter 1. CONCLUSIONS: Congenital disseminated pyogenic granuloma is a distinct multisystemic aggressive disorder that primarily affects the skin, brain, visceral organs, and musculoskeletal system. Differentiation of this entity from other multiple cutaneous vascular lesions is critical because of possible cerebral hemorrhagic involvement.

Impaired Thermoregulatory Function during Dynamic Exercise in Multiple Sclerosis.

INTRODUCTION: Impairments in sudomotor function during passive whole-body heating have been reported in multiple sclerosis (MS), a demyelinating disease of the CNS that disrupts autonomic function. However, the capability of the thermoregulatory system to control body temperature during exercise has never been assessed in MS. Thus, the aim of the present study was to test the hypothesis that thermoregulatory function is impaired in MS patients compared with healthy controls (CON) exercising at similar rates of metabolic heat production. METHODS: Sweating and skin blood flow responses were compared between 12 individuals diagnosed with relapsing-remitting MS (9 females, 3 males) and 12 sex-, age-, mass-, and BSA-matched CON during a single bout of cycling exercise (rate of metabolic heat production: ∼4.5 W·kg) for 60 min in a climate-controlled room (25°C, 30% RH). RESULTS: Individuals with MS exhibited an attenuated increase in cumulative whole-body sweat loss after 30 min (MS, 72 ± 51 g; CON, 104 ± 37 g; P = 0.04) and 60 min (MS, 209 ± 94 g; CON, 285 ± 62 g; P = 0.02), as well as lower sweating thermosensitivity (MS, 0.49 ± 0.26 mg·cm·min·°C; CON, 0.86 ± 0.30 mg·cm·min·°C; P = 0.049). Despite evidence for thermoregulatory dysfunction, there were no differences between MS and CON in esophageal or rectal temperatures at 30- or 60-min time points (P > 0.05). Cutaneous vasculature responses were also not different in MS compared with CON (P > 0.05). CONCLUSION: Taken together, MS blunts sweating responses during exercise while cutaneous vasculature responses are preserved. Altered mechanisms of body temperature regulation in persons with MS may lead to temporary worsening of disease symptoms and limit exercise tolerance under more thermally challenging conditions.

Core temperature is not elevated at rest in people with relapsing-remitting multiple sclerosis.

PURPOSE: To reassess the notion that people with multiple sclerosis (MS) do not demonstrate an elevated resting core temperature when measured using best-practice precision thermometry. METHOD: Across two international data collection sites (Australia and USA), twenty-eight relapsing-remitting MS patients and 27 aged-matched controls (CON) were exposed to either 30 °C, 30% relative humidity (RH) (Sydney) or 25 °C, 30% RH (Dallas). Resting rectal (Tre) and esophageal (Teso) temperature and resting oxygen consumption (VO2) was measured in MS (n = 28) and CON (n = 27) groups who completed the 25 °C and 30 °C trials. Tympanic membrane (Ttym) temperature was measured in MS (n = 16) and CON (n = 15) groups in the 30 °C condition. A modified fatigue impact scale (MFIS) questionnaire was used to assess subjective measures of psychosocial, physical and cognitive fatigue in the 30 °C condition. RESULTS: Irrespective of ambient temperature, no group differences were observed for Tre (MS: 37.07 ±â€¯0.30 °C; CON: 37.18 ±â€¯0.30 °C; P = 0.29), Teso (MS: 36.84 ±â€¯0.42 °C; CON: 36.92 ±â€¯0.29 °C; P = 0.36) or resting VO2 (MS: 3.89 ±â€¯0.18 ml⋅kg-1⋅min-1; CON: 3.98 ±â€¯0.17 ml⋅kg-1⋅min-1; P = 0.67). Similarly, no group differences were observed for Ttym (MS: 36.52 ±â€¯0.38 °C; CON: 36.61 ±â€¯0.33 °C; P = 0.55) in the 30 °C condition. Resting Tre did not correlate with subjective measures of fatigue: physical: r = -0.11, P = 0.67; cognitive: r = -0.14, P = 0.60; and psychosocial: r = 0.05, P = 0.84. CONCLUSION: Contrary to recent reports, resting core temperature is not elevated in relapsing-remitting MS patients compared to healthy controls when measured using precision thermometry. Furthermore, no association was observed between resting Tre and any subjective measures of fatigue in a subset of participants with MS.

Reduced Resting and Increased Elevation of Heart Rate Variability With Cognitive Task Performance in Concussed Athletes.

OBJECTIVE: To examine heart rate variability (HRV) at rest and with a 2-Back cognitive task involving executive function and sustained attention in athletes during the acute phase following concussion and compare them with the controls. PARTICIPANTS: Twenty-three male and female collegiate athletes (20 ± 1 years) following (4 ± 1 days) a sports-related concussion and 23 sports- and sex-matched noninjured controls. PROCEDURE: Continuous R-R interval was acquired using 3-lead electrocardiogram for 3 minutes each at rest and during the 2-Back task. HRV was quantified as percent high-frequency (HF) power. RESULTS: At rest, lower percent HF power was observed in the concussed athletes (23 ± 11) compared with the controls (38 ± 14; P = .0027). However, with the 2-Back task, an increase in HF power was observed in the concussed group (39 ± 12; P = .0008) from rest and was comparable with the controls (36 ± 15). No difference in HF power between rest and 2-Back task was observed in the controls. CONCLUSION: Lower HRV was observed at rest following concussion. An increase in HRV, suggestive of enhanced prefrontal cortex (PFC) functioning, was observed during a cognitive task in the concussed athletes. Therefore, cognitive tasks as early as 4 days after injury may increase PFC functioning from rest and expedite return to learn in collegiate athletes.

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.

Thermoregulatory dysfunction in multiple sclerosis.

Multiple sclerosis (MS) is a progressive neurologic disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurologic symptoms with heat exposure (Uhthoff's phenomenon). This heat intolerance in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. Isolating and interpreting mechanisms responsible for autonomic dysfunction due to MS can be difficult as it may involve sensory impairments, altered neural integration within the central nervous system, impaired effector responses, or combinations of all of these factors. MS lesions occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacologic) for the MS patient to preserve function and decrease symptom worsening during heat stress. This review focuses on four main themes influencing current understanding of thermoregulatory dysfunction in MS: (1) heat intolerance; (2) central regulation of body temperature; (3) thermoregulatory effector responses; and (4) countermeasures to improve or maintain function during thermal stress.

Cold Water Ingestion Improves Exercise Tolerance of Heat-Sensitive People with MS.

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% V˙O2max 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 of either 1.5°C (CLD) or 37°C (NEU) water. Rectal (Tre) temperature, mean skin (Tsk) 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 Tre (NEU: 37.32°C ± 0.34°C; CLD: 37.28°C ± 0.26°C; P = 0.44), change in Tre (NEU: 0.38°C ± 0.21°C; CLD: 0.34°C ± 0.24°C), absolute Tsk (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 Tre, Tsk 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.

Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc.

Catheter-Directed Thrombolysis in a Child with Bilateral Renal Artery Graft Thrombosis.

A 5-year-old boy with midaortic syndrome who had undergone aortic bypass and bilateral renal artery grafts presented to the emergency department 1 year after surgery with symptoms of nausea, vomiting, and abdominal pain. Because of delay in diagnosis of bilateral renal artery thrombosis, his condition progressed to anuric renal failure. He underwent catheter-directed thrombolysis 7 days after presentation with administration of tissue plasminogen activator and heparin infusion over a 24-hour period. There was successful resolution of thrombus and complete recovery of renal function to baseline. The patient had normal renal function at 6-month follow-up.

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

NEW FINDINGS: What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although 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 new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly 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 subjects 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 and colder) temperature range than what is observed in CTR subjects provides new evidence on the impact of rising body temperature on afferent neural function in MS. Also, our findings support the use of our new approach to investigate afferent sensory function in MS during heat stress.

Impaired sweating responses to a passive whole body heat stress in individuals with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), disrupting autonomic function. The aim of this study was to test the hypothesis that individuals with MS have blunted control of thermoregulatory reflex increases in sweat rate (SR) and cutaneous vasodilation compared with controls during a passive whole body heat stress (WBH). Eighteen individuals with relapsing-remitting MS and 18 healthy controls (Con) participated in the study. Core temperature (Tcore), skin temperature, heart rate, arterial blood pressure (10-min intervals), skin blood flow (laser-Doppler flux, LDF), and SR were continuously measured during normothermic baseline (34°C water perfusing a tube-lined suit) and WBH (increased Tcore 0.8°C via 48°C water perfusing the suit). Following WBH, local heaters were warmed to 42°C, inducing peak cutaneous vasodilation at the site of LDF collection. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to mean arterial pressure and expressed as a percentage of peak achieved during local heating. Individuals with MS had attenuated SR responses to WBH (ΔSR from baseline: Con, 0.65 ± 0.27; MS, 0.42 ± 0.17 mg·cm-2·min-1, P = 0.003), whereas Δ%CVC42C from baseline was similar between groups (Con, 42 ± 16%; MS, 38 ± 12%, P = 0.39). SR responses were blunted as a function of Tcore in MS (interaction: group × Tcore, P = 0.03), of which differences were evident at ΔTcore 0.7°C and 0.8°C (P < 0.05). No interaction was observed in Δ%CVC42C Taken together, the findings show MS blunts sweating responses, whereas control of the cutaneous vasculature is preserved, in response to WBH.NEW & NOTEWORTHY This study is the first to assess the reflex control of the thermoregulatory system in individuals living with multiple sclerosis (MS). The novel findings are twofold. First, attenuated increases in sweat rate in subjects with MS compared with healthy controls were observed in response to a moderate increase (0.8°C) in core temperature via passive whole body heat stress. Second, it appears the reflex control of the cutaneous vasculature is preserved in MS.

Increased postural sway in persons with multiple sclerosis during short-term exposure to warm ambient temperatures.

BACKGROUND: Multiple sclerosis (MS) is a neurological disease marked by demyelination and axonal loss. Individuals with MS experience increases in clinical signs and symptoms during heat exposure. OBJECTIVE: To test the hypothesis that moderate heat exposure adversely affects postural sway in individuals with MS. METHODS: Ten individuals with relapsing-remitting MS (50±8y) and nine controls (47±10y) were examined under a Thermal and a Time Control trial. Following a 30min thermoneutral baseline (25°C, 30% relative humidity (RH)), stand tests randomized with eyes open and closed, were performed. For Thermal, subjects were first exposed to 60min of heating (40°C, 30%RH) followed by 60min of cooling (20°C, 30%RH). For Time Control, subjects remained in a thermoneutral environment throughout. Stand tests were repeated at consistent times in both trials. RESULTS: No difference in skin and core temperatures between groups were observed for any trial (P>0.05). During heating, postural sway was higher in MS relative to control subjects (eyes open, P=0.03; eyes closed, P=0.011). No differences in postural sway, regardless of eye status, were observed during the Time Control trial for either group (P>0.05). CONCLUSION: These data demonstrate that exposure to a moderate heating environment increases postural sway in patients with MS.

Post Junctional Sudomotor and Cutaneous Vascular Responses in Noninjured Skin Following Heat Acclimation in Burn Survivors.

Thermal tolerance is improved in burn survivors following 7 days of exercise heat acclimation. It is unknown whether post junctional sudomotor and/or cutaneous vascular adaptations in noninjured skin contribute to this improvement. Thirty-three burn survivors were stratified into moderately (17-40% BSA grafted, n = 19) and highly (>40% BSA grafted, n = 14) skin-grafted groups. Nine nonburned subjects served as controls. All subjects underwent a 7-day heat acclimation protocol, which improved thermal tolerance in all groups. Before and after this heat acclimation protocol, post junctional cutaneous vascular responses were assessed by administering increasing doses of sodium nitroprusside (SNP) and methacholine (MCh) using intradermal microdialysis in noninjured skin. MCh infusion was also used to assess post junctional responses in sudomotor function in noninjured skin. Cutaneous vascular responses to SNP and MCh were not different between pre- and post heat acclimation in either group of burn survivors (both P > .05). The maximal sweating rate to MCh increased post acclimation in the control group (0.41 ± 0.20 to 0.54 ± 0.21 mg·min·cm; P = .016) but was unchanged in both groups of burn survivors (both P > .05). The number of sweat glands activated during the highest dose of MCh was elevated in the >40% BSA-grafted group (49 ± 16 to 56 ± 18 glands·cm; P = .005) but was unchanged in control subjects and the <40% BSA-grafted group (both P > .05). Given that post junctional administration of MCh and SNP did not alter sweating or skin blood flow from noninjured skin of burn survivors, improved thermal tolerance in these individuals following heat acclimation is more likely a result of either an increased sweating efficiency or an increased neural drive for sweating.

Impaired carotid baroreflex control of arterial blood pressure in multiple sclerosis.

Multiple sclerosis (MS), a progressive neurological disease, can lead to impairments in the autonomic control of cardiovascular function. We tested the hypothesis that individuals with relapsing-remitting MS (n = 10; 7 females, 3 males; 13 ± 4 yr from diagnosis) exhibit impaired carotid baroreflex control of blood pressure and heart rate compared with sex, age, and body weight-matched healthy individuals (CON: n = 10; 7 females, 3 males). At rest, 5-s trials of neck pressure (NP; +40 Torr) and neck suction (NS; -60 Torr) were applied to simulate carotid hypotension and hypertension, respectively, while mean arterial pressure (MAP; finger photoplethysmography), heart rate (HR), cardiac output (CO; Modelflow), and total vascular conductance (TVC) were continuously measured. In response to NP, there was a blunted increase in peak MAP responses (MS: 5 ± 2 mmHg) in individuals with MS compared with healthy controls (CON: 9 ± 3 mmHg; P = 0.005), whereas peak HR responses were not different between groups. At the peak MAP response to NP, individuals with MS demonstrated an attenuated decrease in TVC (MS, -10 ± 4% baseline vs. CON, -15 ± 4% baseline, P = 0.012), whereas changes in CO were similar between groups. Following NS, all cardiovascular responses (i.e., nadir MAP and HR and percent changes in CO and TVC) were not different between MS and CON groups. These data suggest that individuals with MS have impaired carotid baroreflex control of blood pressure via a blunted vascular conductance response resulting in a diminished ability to increase MAP in response to a hypotensive challenge.

Effects of vigorous walking exercise on core body temperature and inhibitory control in thermosensitive persons with multiple sclerosis.

AIM: Acute, moderate intensity aerobic exercise might improve cognition in multiple sclerosis (MS), but it is unknown if increases in core body temperature (Ctemp) that negates those effects in thermosensitive persons with MS. MATERIALS & METHODS: Fourteen fully ambulatory, thermosensitive persons with MS completed 20-min bouts of vigorous intensity treadmill walking exercise and seated quiet rest in a randomized, counterbalanced order. Ctemp was measured throughout each experimental condition. Inhibitory control (i.e., an executive function) was measured immediately prior to and following each condition. RESULTS: Ctemp was elevated (~0.6 °C) with vigorous exercise versus quiet rest (p < 0.05). There further were pre-to-post improvements in inhibitory control for vigorous exercise versus quiet rest (ηp(2) = 0.29). CONCLUSION: Exercise-related increases in Ctemp do not nullify the potential acute exercise benefits on inhibitory control in MS.