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Narcolepsy And Skin Temperature

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#1 ayesart



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Posted 29 October 2009 - 10:33 AM

I found this article I had stored for quite a long time in my computer files. I download a lot of articles I find on the Internet in an attempt to help myself and my wife. Hopefully this one might be of some help to someone in terms of understanding how one's environment can trigger onsets and episodes. Smells, fumes, and now a study has been done upon skin temperature. Every little bit of new data helps. I hope....

I am including a URL that will take you to research that is being done in China on various conditions involving the nervous system. Stem cells are being used to help a lot of people who have traveled there seeking relief from their symptoms. Its interesting reading.


Keep an open mind.



To order reprints of this article go to:
To subscribe to Journal of Neurology, Neurosurgery, and Psychiatry go to:
Downloaded from jnnp.bmj.com on 27 April 2009
Manipulation of skin temperature improves nocturnal
sleep in narcolepsy
R Fronczek,1,2 R J E M Raymann,1 S Overeem,2,3 N Romeijn,1 J G van Dijk,2
G J Lammers,2 E J W Van Someren1,4
1 Netherlands Institute for
Neuroscience, Amsterdam, The
Netherlands; 2 Department of
Clinical Neurology and
Neurophysiology, Leiden
University Medical Center,
Leiden, The Netherlands;
3 Center for Sleep–Wake
Disorders ‘‘Kempenhaeghe,’’
Heeze, The Netherlands;
4 Department of Clinical
Neurophysiology, Neurology and
Medical Psychology, VU
University Medical Center,
Amsterdam, The Netherlands
Correspondence to:
Dr R Fronczek, Leiden University
Medical Centre, Department of
Neurology (K5Q), PO Box 9600,
2300 RC, Leiden, The
Received 4 January 2008
Revised 21 May 2008
Accepted 1 June 2008
Published Online First
30 July 2008
Objective: Besides excessive daytime sleepiness, disturbed
nocturnal sleep is a major complaint of patients
with narcolepsy. Previously, alterations in skin temperature
regulation in narcoleptic patients have been shown to
be related to increased sleepiness. This study tests the
hypothesis that direct control of nocturnal skin temperature
might be applied to improve the disturbed sleep of
narcoleptic patients.
Methods: Participants were eight patients (five males)
diagnosed as having narcolepsy with cataplexy according
to the ICSD-2 criteria, mean (SD) age 28.6 (6.4) years,
range 18–35 years. During two nights, sleep was
recorded polysomnographically while proximal and distal
skin temperature were manipulated using a comfortable
thermosuit that induced skin temperature to cycle slowly
with an amplitude of only 0.4uC within the comfortable
range normally observed during sleep. Logistic regression
was used to evaluate the effect of skin temperature
manipulation on the probability of occurrence of different
sleep stages and nocturnal wakefulness.
Results: Proximal skin warming significantly suppressed
wakefulness and enhanced slow wave sleep (SWS). In
contrast, distal skin warming enhanced wakefulness and
stage 1 sleep at the cost of SWS and REM sleep. The
optimal combination of proximal skin warming and distal
skin cooling led to a 160% increase in SWS, a 50%
increase in REM sleep and a 68% decrease in
wakefulness, compared with the least beneficial combination
of proximal skin cooling and distal skin warming.
Interpretation: Subtle skin temperature manipulations
under controlled conditions significantly improved the
typical nocturnal sleep problems in narcolepsy.
The four classical symptoms of narcolepsy are
excessive daytime sleepiness, cataplexy, hypnagogic
hallucinations and sleep paralysis.1 In recent
years, disturbed nocturnal sleep has gained increasing
attention as a fifth core symptom that severely
affects quality of life.1 Nocturnal polysomnography
in patients with narcolepsy shows a fragmentation
of the normal sleep pattern with frequent arousals
and a decrease in slow wave sleep.2–4 Several
hypnotics, including sodium oxybate (gammahydroxybutyrate),
are currently used to improve
nocturnal sleep in narcolepsy.5 Narcolepsy is
caused by a loss of the neuropeptide hypocretin
(orexin), a neurotransmitter that is produced by
neurons in the lateral hypothalamus.6 7
There is a relation between sleep and both core
body and skin temperature.8 9 In everyday life and
under laboratory conditions with a comfortable to
warm environmental temperature, core body temperature
is lower and the average skin temperature is
higher during the night than during the day.9 10
Sleep-onset latency is negatively correlated to the
temperature of distal skin areas (hands and feet).11
There seems to be a causal relation, since mild
warming of the skin compromises sustained vigilance
12 and facilitates sleep initiation.13 Moreover,
mild active manipulation of the skin temperature
within the comfortable and circadian range affects
night-time sleep in healthy controls.14
In a previous study, we reported disturbances in
skin-temperature regulation in narcolepsy.15 Narcoleptic
subjects showed a combination of a higher
distal skin temperature and a lower proximal skin
temperature, which in healthy subjects is associated
with the process of falling asleep.11 In a follow-up
study, we were able to improve both daytime
vigilance and maintenance of wakefulness by mild
manipulation of skin temperature and core body
temperature.16 To test the hypothesis that manipulation
of skin temperature might be applied to
ameliorate the disturbed nocturnal sleep in narcolepsy
as well, we performed subtle manipulations of
proximal and distal skin temperature during two
nocturnal sleep episodes in eight narcoleptic patients.
Eight narcoleptic patients (five males, 18–35 years
of age; mean (SD): 28.6 (6.4) years) participated
with informed consent. All suffered from excessive
daytime sleepiness and typical cataplexy according
to the ICSD-2 criteria for narcolepsy with cataplexy.
17 All subjects were free of medication, except
for one female subject using oral contraceptives. All
females participated between day 4 and day 12 of
the menstrual cycle (mid-follicular phase or
pseudo-follicular phase). All subjects participated
in the summer season (July/August). The protocol
was approved by the Medical Ethics Committees
of the Academic Medical Center in Amsterdam and
the Leiden University Medical Center. The same
eight subjects were used in the aforementioned
study, where both skin temperature and core body
temperature were manipulated during daytime.16
A previously described design was used to differentially
manipulate proximal and distal skin
temperature, and to determine the effects of these
manipulations on sleep depth.14 Subjects refrained
from caffeine, alcohol and tobacco for 8 h before
reporting at the sleep laboratory at 22:00. There
they were prepared for polysomnography and
fitted with a thermosuit. At midnight, lights were
turned off, and subjects were allowed to sleep until
Research paper
1354 J Neurol Neurosurg Psychiatry 2008;79:1354–1358. doi:10.1136/jnnp.2008.143610
Downloaded from jnnp.bmj.com on 27 April 2009
06:00. From 00:30 until 06:00, their proximal and distal skin
temperatures were manipulated. After this, subjects slept one
night at home, after which they returned for a second night in
the sleep laboratory, during which the temperature manipulation
sequence (see below) was inverted to that of the first night.
Temperature manipulations and measurement
Starting at 0:30, the temperature of the proximal skin (Tskinprox)
and the temperature of the distal skin (Tskin-dist) were
differentially manipulated by slowly altering the temperature of
the water that perfused the thermosuit (fig 1). The suit
temperature (Tsuit) stayed at constant plateaus of either 15 or
30 min with slow (15 min) transitions in between. The order of
the sequences of skin temperature manipulations was different
for each subject within its group and chosen in such a way that
it resulted in an optimal uniform distribution of combinations
of high and low Tsuit-prox and Tsuit-dist levels throughout the
night over all subjects, that is at any time of night there was an
equal proportion of ‘‘warm’’ and ‘‘cool’’ periods. Tsuit cycled
between 31.9 (0.1)uC (mean (SE)) in the ‘‘cool’’ and 34.8 (0.1)uC
in the ‘‘warm’’ condition, as measured once per minute on the
isolated inflow tubes at their connections with the thermosuit
using PT100 thermistors (RTD-3-3105, Omega, Stanford). This
range was specifically chosen to match the previously reported
range of temperatures normally present in the bed microclimate.
18 The environmental temperature was kept at 21uC. Skin
and core body temperature was recorded as described previously.
Sleep recordings
Polysomnographic sleep recordings were performed according to
standard procedures.19 An experienced sleep technician blind to
the temperature conditions scored sleep stages in 30-second
epochs according to the Rechtschaffen and Kales criteria using
Somnologica software.20
Table 1 Odds ratio (OR), CI and p value for the occurrence of each sleep state as modulated by the
temperature of the thermosuit warming the distal (Tsuit-dist) and proximal (Tsuit-prox) skin (per 1uC)
Tsuit-prox Tsuit-dist
OR (95% CI) p Value OR (95% CI) p Value
Wake 0.81 (0.77 to 0.84) ,0.001 1.11 (1.06 to 1.16) ,0.001
S1 0.98 (0.93 to 1.03) NS 1.22 (1.16 to 1.28) ,0.001
S2 1.02 (0.99 to 1.05) NS 1.01 (0.98 to 1.04) NS
SWS 1.23 (1.17 to 1.29) ,0.001 0.85 (0.81 to 0.89) ,0.001
REM 0.98 (0.93 to 1.03) NS 0.87 (0.83 to 0.92) ,0.001
REM, rapid-eye-movement sleep; S1, stage 1 sleep; S2, stage 2 sleep; SWS, slow-wave sleep.
Figure 1 (A) Example of a temperature profile induced in one patient during a single night. The lower traces show the temperature of the proximal
(solid line) and distal (dotted line) parts of the thermosuit. The upper traces show the actually induced proximal and distal skin temperatures. (B)
Graphical representation of the proportion of the sleep stages during the optimal (distal cooling and proximal warming) and least beneficial (distal
warming and proximal cooling) manipulation scheme. The proportions were derived in separate logistic regressions for each sleep stage. For graphical
purposes only, the figure was rescaled to 100%. REM, rapid-eye-movement sleep; S1, stage 1 sleep; S2, stage 2 sleep; SWS, slow-wave sleep.
Research paper
J Neurol Neurosurg Psychiatry 2008;79:1354–1358. doi:10.1136/jnnp.2008.143610 1355
Downloaded from jnnp.bmj.com on 27 April 2009
Statistical analysis
The main outcome measures of this study were the effects of
proximal and distal skin warming or cooling on the odds ratios for
the occurrence of each sleep stage (stage 1, stage 2, slow-wave
sleep, REM sleep and wakefulness). Mixed effect (or multilevel)
regression modelling was applied to account for the interdependency
of the data points inherent to the hierarchical structure of
the dataset: sleep epochs within nights within subjects (MLwiN
software, Centre for Multilevel Modelling, Institute of Education,
London).21 The analyses included all epochs during the skin
temperature cycles (from 00:30 until 6:00). To determine the
effects of skin temperature manipulation on the probability of
occurrence of each sleep stage or wakefulness, longitudinal
multilevel logistic regressions were applied for each sleep stage
classification, with the current presence or absence of that stage as
dummy coded dichotomous dependent variable and Tsuit-prox and
Tsuit-dist as predictor variables. Two-tailed significance levels were
set at 0.05. For a graphical representation, odds ratios (OR) were
translated into whole-night sleep stage probabilities for two
conditions, reflecting the most and least profitable combination of
upper (34.8 (0.1)uC) and lower (31.9 (0.1)uC) Tsuit levels (see
results). These probabilities can easily be calculated using the
transformation ex/(1+ex), where x represents the regressor part of
the best-fitting regression model.
Induced temperatures
With the thermosuit approach, we were able to differentially
manipulate proximal and distal skin temperature (see example of
one night in one patient in fig 1). The temperature manipulations
of the proximal part of the thermosuit accounted for 53.8% of the
variance in mean Tskin-prox. Tskin-prox averaged 35.1 (0.1)uC (mean
(SEM) at the warmest level versus 34.7 (0.1)uCat the coolest level.
Likewise, the independently manipulated temperature of the
distal part of the thermosuit accounted for 44.0% of the variance
in mean Tskin-dist. Tskin-dist averaged 35.5 (0.05)uC at the warmest
level versus 35.1 (0.05)uC at the coolest level. Thus, the
manipulations forced the skin temperature to cycle slowly within
a very subtle 0.4uC range (see temperature graph in fig 1). The
manipulations left core body temperature virtually unchanged
(skin temperature manipulations accounted for only 2.5% of the
variance in core body temperature).
Effect of temperature manipulation on sleep stage distribution
Thermosuitmanipulation of the temperature of the proximal and
distal skin significantly affected sleep depth and the occurrence of
wakefulness. Table 1 shows that proximal warming suppressed
wakefulness (OR 0.81, CI (0.77 to 0.84), p,0.001) and enhanced
slow-wave sleep (OR 1.23 (1.17 to 1.29), p,0.001; all OR
expressed per 1uC increase in Tsuit). In contrast, distal warming
enhanced wakefulness (OR 1.11 (1.06 to 1.16), p,0.001) and stage
1 sleep (OR 1.22 (1.16 to 1.28), p,0.001) sleep at the cost of slowwave
sleep (OR 0.85 (0.81 to 0.89), p,0.001) and REM sleep (OR
0.87 (0.83 to 0.92), p,0.001). There were no significant effects on
the occurrence of stage 2 sleep.
A graphical representation of the sleep-stage distribution is
given in fig 2. As compared with the least favourable skin
temperature combination, the optimal combination led to a
160% increase in slow-wave sleep, a 50% increase in REM sleep
and a 68% decrease in wakefulness.
This study shows that subtle manipulation of proximal and
distal skin temperatures has beneficial effects on nocturnal sleep
in narcolepsy. When the proximal skin was warmed, slow-wave
sleep increased, and wakefulness was suppressed. In contrast,
warming of the distal skin suppressed slow-wave and REM
sleep, while enhancing wakefulness and stage 1 sleep.
Fragmented nocturnal sleep is a major and difficult to treat
problem for many patients with narcolepsy. Currently, treatment
of this invalidating symptom is based on hypnotics, most
notably sodium oxybate,5 which increases slow-wave and REM
sleep, while suppressing wakefulness.3 22
The present study was designed in such a way that different
manipulation schemes were equally and randomly distributed over
the test subjects in a balanced way. As such, the effects cannot
have been caused by time of night or circadian effects, but can be
solely attributed to themanipulation of skin temperature. The fact
that subtle changes in skin temperature affect sleep in both
narcoleptic patients and healthy controls14 shows that the basic
hypothalamic circuitry involved in temperature and sleep regulation
is still responsive to manipulation in narcolepsy despite the
hypocretin deficiency. In this study, no subject experienced the
optimal or least beneficial combination of proximal and distal
manipulations continuously during a full night. Furthermore, sleep
time was restricted from midnight to 06:00. It would now be of
interest to confirm the positive effects found in this study using a
controlled trial in which the optimal or least beneficial temperature
conditions are applied continuously throughout a full night.
In conclusion, despite the hypocretin deficiency, the basic
hypothalamic circuitry involved in temperature and sleep
regulation is still responsive to manipulations in narcolepsy.
These results raise the intriguing possibility that selective
manipulation of skin temperature within the comfortable range
might in theory be applied to ameliorate one of the core
symptoms of narcolepsy; disturbed nocturnal sleep.
Acknowledgements: This work was supported by grants from The Netherlands
Organization for Scientific Research (projects SOW 014-90-001 and Innovation Grant
016.025.041) and the EU FP6 Sensation Integrated Project (FP6-507231). SO was
supported by a VENI grant from The Netherlands Organization for Scientific Research
(#916.56.103). We would like to thank J Stam (Academic Medical Center,
Amsterdam) for clinical surveillance during the protocol. Furthermore, we are very
grateful to S Wehrens, M Fisher, J Vis (NIN) and P van Someren (LUMC) for their
invaluable help during the collection and analysis of the EEG data.
Competing interests: None.
Ethics approval: Ethics approval was provided by the Medical Ethics Committees of
the Academic Medical Center in Amsterdam and the Leiden University Medical Center.
Patient consent: Obtained.
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polysomnographic measures in insomnia, depression, and narcolepsy. Biol Psychiatry
5. Billiard M, Bassetti C, Dauvilliers Y, et al. EFNS guidelines on management of
narcolepsy. Eur J Neurol 2006;13:1035–48.
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#2 sleepless sleeper

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Posted 02 November 2009 - 05:40 PM

i cannot read all that. i read a little.

i had problems with persistent fever for - i think - 9 months. i have a lot of research if u need it. i don't know why you have this research, but i'm happy to share.

#3 disordered



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Posted 03 November 2009 - 10:06 AM

Not sure if the info helps, but all of the women in family (on the maternal side) all naturally run low temps (97.5ish) and 5 have been diagnosed with sleep disorders. Yet I had a persistent low grade fever for about two years; my first normal temp occurred about 3 months ago. Also, myself, mother, and sister all have Raynaud's.

Sorry, there are probably more skin temp connections I could make, but I'm running into my sleepy brick wall.

#4 sleepless sleeper

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Posted 03 November 2009 - 12:44 PM

I understand disordered. My temp was usually 97.9.