Medical Applications:
Multiple-Sclerosis, Epilepsy, Spinal Cord Injury, Menopause

Multiple Sclerosis and Cooling Research

Am J Phys Med Rehabil. 2000 Sep-Oct;79(5):427-34.
Physiologic and functional responses of MS patients to body cooling.
Ku YT, Montgomery LD, Lee HC, Luna B, Webbon BW.
Lockheed Martin Engineering & Sciences, Moffett Field, California, USA.

OBJECTIVE: The objective of this study was to compare the responses of multiple sclerosis (MS) patients to short-term cooling therapy using three different vest configurations. DESIGN: Each garment was used to cool 13 male and 13 female MS subjects (31-67 yr). Oral and right and left ear temperatures were logged manually every 5 min. Arm, leg, chest, and rectal temperatures, heart rate, and respiration were recorded continuously on a Biolog ambulatory monitor. Each subject was given a series of subjective and objective evaluation tests before and after cooling. RESULTS: The Life Enhancement Technologies and Steele vests test groups had similar, significant (P < 0.01) cooling effects on oral and ear canal temperatures, which decreased approximately 0.4 degrees C and 0.3 degrees C, respectively. The Life Enhancement Technologies active liquid cooling vest produced the coldest (P < 0.01) skin temperature and provided the most improvement on subjective and objective performance measures. CONCLUSIONS: These results show that the various garment configurations tested do not produce similar thermal responses in all MS patients. The circulating liquid cooling vest was found to be more effective than either of the two passive cooling garments tested.


Am J Phys Med Rehabil. 1999 Sep-Oct;78(5):447-56.
Physiologic and thermal responses of male and female patients with multiple sclerosis to head and neck cooling.
Ku YT, Montgomery LD, Wenzel KC, Webbon BW, Burks JS.
Lockheed Martin Engineering & Sciences, NASA Ames Research Center, Moffett Field, California 94035, USA.

Personal cooling systems are used to alleviate symptoms of multiple sclerosis and to prevent increased core temperature during daily activities. The objective of this study was to determine the thermal and physiologic responses of patients with multiple sclerosis to short-term maximal head and neck cooling. A Life Support Systems, Inc. Mark VII portable cooling system and a liquid cooling helmet were used to cool the head and neck regions of 24 female and 26 male patients with multiple sclerosis in this study. The subjects, seated in an upright position at normal room temperature (approximately 22 degrees C), were cooled for 30 min by the liquid cooling garment, which was operated at its maximum cooling capacity. Oral, right, and left ear temperatures and cooling system parameters were logged manually every 5 min. Forearm, calf, chest, and rectal temperatures, heart rate, and respiration rate were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. This protocol was performed during the winter and summer to investigate the seasonal differences in the way patients with multiple sclerosis respond to head and neck cooling. No significant differences were found between the male and female subject group's mean rectal or oral temperature responses during any phase of the experiment. The mean oral temperature decreased significantly (P < 0.05) for both groups approximately 0.3 degrees C after 30 min of cooling and continued to decrease further (approximately 0.1-0.2 degrees C) for a period of approximately 15 min after removal of the cooling helmet. The mean rectal temperatures decreased significantly (P < 0.05) in both male and female subjects in the winter studies (approximately 0.2-0.3 degrees C) and for the male subjects during the summer test (approximately 0.2 degrees C). However, the rectal temperature of the female subjects did not change significantly during any phase of the summer test. These data indicate that head and neck cooling may, in general, be used to reduce the oral and body temperatures of both male and female patients with multiple sclerosis by the approximate amount needed for symptomatic relief as shown by other researchers. However, thermal response of patients with multiple sclerosis may be affected by gender and seasonal factors, which should be considered in the use of liquid cooling therapy.

Neurology. 2003 Jun 24;60(12):1955-60.
A randomized controlled study of the acute and chronic effects of cooling therapy for MS.
Schwid SR, Petrie MD, Murray R, Leitch J, Bowen J, Alquist A, Pelligrino R, Roberts A, Harper-Bennie J, Milan MD, Guisado R, Luna B, Montgomery L, Lamparter R, Ku YT, Lee H, Goldwater D, Cutter G, Webbon B; NASA/MS Cooling Study Group.
University of Rochester, Rochester, NY, USA.

BACKGROUND: Cooling demyelinated nerves can reduce conduction block, potentially improving symptoms of MS. The therapeutic effects of cooling in patients with MS have not been convincingly demonstrated because prior studies were limited by uncontrolled designs, unblinded evaluations, reliance on subjective outcome measures, and small sample sizes. OBJECTIVE: To determine the effects of a single acute dose of cooling therapy using objective measures of neurologic function in a controlled, double-blinded setting, and to determine whether effects are sustained during daily cooling garment use. METHODS: Patients (n = 84) with definite MS, mild to moderate disability (Expanded Disability Status Scale score < 6.0), and self-reported heat sensitivity were randomized into a multicenter, sham-treatment controlled, double-blind crossover study. Patients had the MS Functional Composite (MSFC) and measures of visual acuity/contrast sensitivity assessed before and after high-dose or low-dose cooling for 1 hour with a liquid cooling garment. One week later, patients had identical assessments before and after the alternate treatment. Patients were then re-randomized to use the cooling garment 1 hour each day for a month or to have observation only. They completed self-rated assessments of fatigue, strength, and cognition during this time, and underwent another acute cooling session at the end of the period. After 1 week of rest, they had identical assessments during the alternate treatment. RESULTS: Body temperature declined during both high-dose and low-dose cooling, but high-dose produced a greater reduction (p < 0.0001). High-dose cooling produced a small improvement in the MSFC (0.076 +/- 0.66, p = 0.007), whereas low-dose cooling produced only a trend toward improvement (0.053 +/- 0.031, p = 0.09), but the difference between conditions was not significant. Timed gait testing and visual acuity/contrast sensitivity improved in both conditions as well. When patients underwent acute cooling following a month of daily cooling, treatment effects were similar. Patients reported less fatigue during the month of daily cooling, concurrently on the Rochester Fatigue Diary and retrospectively on the Modified Fatigue Impact Scale. 

CONCLUSIONS: Cooling therapy was associated with objectively measurable but modest improvements in motor and visual function as well as persistent subjective benefits.

Neurology. 2001 Sep 11;57(5):892-4.
Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production.
Beenakker EA, Oparina TI, Hartgring A, Teelken A, Arutjunyan AV, De Keyser J.
Department of Neurology, Academisch Ziekenhuis Groningen, The Netherlands.

Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 degrees C (active cooling) and 26 degrees C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production (p = 0.004). This effect on NO could be relevant because it blocks conduction in demyelinated axons.


Epilepsy and Cooling Research

Epilepsia. 2000 Dec;41(12):1534-9.
Distribution of seizure precipitants among epilepsy syndromes.
Frucht MM, Quigg M, Schwaner C, Fountain NB.
F. E. Dreifuss Comprehensive Epilepsy Program, Department of Neurology, University of Virginia, Charlottesville, Virginia, USA.

PURPOSE: Previous studies of patient-reported seizure precipitants have not evaluated whether different epilepsy syndromes are differentially affected. METHODS: Patients of a tertiary-care epilepsy center were consecutively surveyed with the use of a standardized questionnaire that lists precipitants that might trigger or exacerbate seizures (alcohol, caffeine, fasting, fatigue, fever or illness, flashing lights, heat or humidity, menstrual cycle, sleep, sleep deprivation, emotional stress, unknown, or other). Patients were classified into epilepsy syndromes according to International League Against Epilepsy criteria. Age and gender within groups defined by major precipitants were compared. Pearson's correlation was performed to evaluate common patterns of precipitants. RESULTS: Of 400 patients, 62% cited at least one precipitant. In order of frequency, stress (30%), sleep deprivation (18%), sleep (14%), fever or illness (14%), and fatigue (13%) were noted by at least 10% of patients. Stress, fatigue, and sleep deprivation positively correlated, but sleep tended to negatively correlate with other major precipitants. Rankings of precipitants varied within epilepsy syndromes, with patients with temporal lobe epilepsy citing sleep infrequently compared with patients with other epilepsy syndromes. Menstrual effects were ranked highly within major precipitants among women over age 12 and were especially noted by women with temporal lobe epilepsy (28%). 

CONCLUSIONS: Most patients with epilepsy identify a precipitant that triggers or exacerbates seizures. The high correlation of stress, sleep deprivation, and fatigue suggests that they act through common mechanisms to worsen seizure control. Through identification of the effect of both endogenous and exogenous precipitants among syndromes, more research and counseling can be directed to specific precipitants.


Spinal Cord Injury and Cooling Research


Med Sci Sports Exerc. 2004 Mar;36(3):411-7.
Foot cooling reduces exercise-induced hyperthermia in men with spinal cord injury.
Hagobian TA, Jacobs KA, Kiratli BJ, Friedlander AL.
Clinical Studies Unit, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA.

The number of individuals with spinal cord injury (SCI) participating in sports at recreational and elite levels is on the rise. However, loss of autonomic nervous system function below the lesion can compromise thermoregulatory capacity and increase the risk of heat stress relative to able-bodied (AB) individuals. PURPOSE: To test the hypotheses that exercise in a heated environment would increase tympanic temperature (TTY) more in individuals with SCI than AB individuals, and that foot cooling using a new device would attenuate the rise in TTY during exercise in both groups. METHODS: Six subjects with SCI (lesions C5-T5) and six AB controls were tested in a heated environment (means +/- SEM, temperature = 31.8 +/- 0.2 degrees C, humidity = 26 +/- 1%) for 45 min at 66% +/- 5 of arm cranking VO2peak and 30 min of recovery on two separate occasions with foot cooling (FC) or no foot cooling (NC) in randomized order. RESULTS: During exercise and recovery in both trials, SCI TTY was elevated above baseline (P < 0.001) but more so in the NC versus FC trial (1.6 +/- 0.2 degrees C vs 1.0 +/- 0.2 degrees C, respectively, P < 0.005). Within the AB group, TTY was elevated above baseline for both trials (P < 0.001) with peak increases of 0.5 +/- 0.2 degrees C and 0.3 +/- 0.2 degrees C for NC and FC, respectively. TTY, face, and back temperature were higher in both SCI trials compared with AB trials (P < 0.05). Heart rate during exercise and recovery was lower in the SCI FC versus SCI NC (P < 0.05). 

CONCLUSION: These results suggest that extraction of heat through the foot may provide an effective way to manipulate tympanic temperature in individuals with SCI, especially during exercise in the heat.

Post-menopausal Hot Flashes and Cooling

Mayo Clin Proc. 2003 May;78(5):603-12.
Skin blood flow in adult human thermoregulation: how it works, when it does not, and why.
Charkoudian N.
Department of Anesthesiology, Mayo Clinic, Rochester, Minn 55905, USA. charkoudian.nisha@mayo.edu

The thermoregulatory control of human skin blood flow is vital to the maintenance of normal body temperatures during challenges to thermal homeostasis. Sympathetic neural control of skin blood flow includes the noradrenergic vasoconstrictor system and a sympathetic active vasodilator system, the latter of which is responsible for 80% to 90% of the substantial cutaneous vasodilation that occurs with whole body heat stress. With body heating, the magnitude of skin vasodilation is striking: skin blood flow can reach 6 to 8 L/min during hyperthermia. Cutaneous sympathetic vasoconstrictor and vasodilator systems also participate in baroreflex control of blood pressure; this is particularly important during heat stress, when such a large percentage of cardiac output is directed to the skin. Local thermal control of cutaneous blood vessels also contributes importantly--local warming of the skin can cause maximal vasodilation in healthy humans and includes roles for both local sensory nerves and nitric oxide. Local cooling of the skin can decrease skin blood flow to minimal levels. During menopause, changes in reproductive hormone levels substantially alter thermoregulatory control of skin blood flow. This altered control might contribute to the occurrence of hot flashes. In type 2 diabetes mellitus, the ability of skin blood vessels to dilate is impaired. This impaired vasodilation likely contributes to the increased risk of heat illness in this patient population during exposure to elevated ambient temperatures. Raynaud phenomenon and erythromelalgia represent cutaneous microvascular disorders whose pathophysiology appears to relate to disorders of local and/or reflex thermoregulatory control of the skin circulation.


Fever and Cooling

Emerg Med Serv. 2004 Jul;33(7):34.
Handle with care.
Ayling J.

Approximately 4% of children experience febrile seizures, making it one of the most common childhood neurologic disorders. Most incidences occur between six months and three years of age, and 30%-40% of these children will experience a recurrence. The priorities in emergent management of pediatric seizures are airway maintenance, seizure termination and correction of reversible causes. When a child experiences a febrile seizure, gradual passive cooling will assist the child in terminating it. The exact cause of febrile seizures is still uncertain, but studies seem to suggest that the height of the fever is less of a factor than the rapidity of its rise. In other words, a child is more likely to seize if his or her temperature rises rapidly, even if it reaches a lower maximum temperature. The same child may slowly increase his/her temperature to a higher maximum without suffering a seizure. In this case, the patient obviously had a respiratory infection that was the source of the fever. It is important to reassure the parents in such a case of the benign nature of febrile seizures and that less than 5% of children experiencing them will develop a seizure disorder. The seizure in this case was terminated with i.v. Atvan, a drug that has been shown to work well as an anticonvulsant in children. But in most circumstances, a febrile seizure will end spontaneously or with gentle cooling. Either acetaminophen or ibuprofen can be given to treat the fever, and rectal forms of these medicines are preferred in the early treatment phase. Oral forms of the medicine can be administered after the child has stopped seizing and is not vomiting. The child should be exposed to a cooler, but not cold, environment, and the airway supported. Tepid baths can help to bring down a fever, but alcohol rubdowns or any fast cooling measures should be avoided because they may induce shivering and further elevate the fever.

J Neurosurg Anesthesiol. 2003 Oct;15(4):313-8.
Treatment of refractory fever in the neurosciences critical care unit using a novel, water-circulating cooling device. A single-center pilot experience.
Carhuapoma JR, Gupta K, Coplin WM, Muddassir SM, Meratee MM.
Neurosciences Critical Care Program, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. jcarhuap@med.wayne.edu

Fever after acute brain injury affects neuronal function and recovery. Standard therapies have proven to be inadequate in treating hyperthermia in this patient population. We report on safety/efficacy pilot data collected using a noninvasive, novel, water-circulating cooling device in febrile acute brain injury patients. We enrolled patients who developed fever (rectal temperature > or =38.0 degrees C) refractory to pharmacological therapy. The treatment device uses an ice water circulating system embedded in hydrogel-coated, energy transfer pads. Its thermoregulatory feedback control uses cold water (4.0 degrees C-42.0 degrees C) and was set at 36.5 degrees C for this study. We analyzed the temperature response during 600 consecutive minutes of treatment. Six consecutive patients were enrolled and seven episodes of fever were recorded; the mean age of the patients was 59.7 years (range 46-71 years; five male, one female). Diagnoses were as follows: subarachnoid hemorrhage (two), severe traumatic brain injury (two), status epilepticus following massive cerebral infarction (one), and intracerebral/intraventricular hemorrhage (one). Hand warming was applied at treatment onset on all patients; shivering only responsive to meperidine occurred in five of them. Fever of 38.4 degrees C (range 38.0 degrees C-38.9 degrees C) was reduced to 36.9 degrees C (range 36.0 degrees C-38.0 degrees C) after 120 minutes (P<0.001). Core temperature remained "locked" during the remainder of the treatment (36.6 degrees C, P=0.5; 36.6 degrees C, P=0.9; and 36.5 degrees C, P=0.9 at 180, 300, and 600 minutes, respectively). Skin integrity under the pads was preserved in all study subjects. Our results indicate that use of this novel technique is safe, rapidly effective, and able to maintain sustained normothermia following fever in a cohort of critically ill neurologic/neurosurgical patients.