SLEEP 2011 Abstract Supplement

B. Clinical Sleep Science V. Sleep Disorders – Movement Disorders
0579
ELEVATED C-REACTIVE PROTEIN (CRP), BUT NOT
INTERLEUKIN-6 (IL-6) OR TUMOR NECROSIS FACTOR
ALPHA (TNF-A), IS ASSOCIATED WITH PERIODIC LIMB
MOVEMENTS (PLMS)
Trotti L 1 , Rye DB 1 , De Staercke C 2 , Hooper C 2 , Quyyumi A 3 ,
Bliwise DL 1
1
Program in Sleep/Department of Neurology, Emory University School
of Medicine, Atlanta, GA, USA, 2 Division of Blood Disorders, Center
for Disease Control and Prevention, Atlanta, GA, USA, 3 Division of
Cardiology, Emory University School of Medicine, Atlanta, GA, USA
Introduction: The inflammatory markers CRP, IL-6, and TNF-a are associated
with cardiovascular disease risk and with some conditions of
disordered sleep, including obstructive sleep apnea. While restless legs
syndrome is known to be associated with cardiovascular disease, the
mechanism for this relationship is unknown. We evaluated the association
between PLMS and inflammation as a possible mechanism for this
relationship.
Methods: A convenience sample was assembled of 167 RLS and/or
PLMS patients evaluated at the Emory Sleep Center for whom leg actigraphy
(PAM-RL, Philips Respironics) results were available while the
patients were not taking dopaminergic, opiate, or gabapentin medications.
Banked plasma was assayed for hsCRP by nephelometry (Dade-
Behring) and for IL-6 and TNF-a by fluorokine multianalyte profiling
(R&D Systems). CRP was categorized as low-normal ( 10 were excluded as likely reflecting acute inflammation.
IL-6 and TNF-a were divided into quartiles and lowest versus
highest quartiles compared. Information about subjects’ demographic
and clinical features was collected from research and clinical databases.
Results: Mean PLMI was significantly higher among those with elevated
CRP levels (40.2/hr vs 26.1/hr, t = -2.10, p = 0.04), but did not
differ between those with high versus low IL-6 or high versus low TNFa.
In an unadjusted logistic regression model, the OR for each PLM/hr
was 1.015 (95% CI 1.003, 1.03). After adjustment for age, race, gender,
diabetes, hypertension, hyperlipidemia, CRP-lowering medications, and
clinically-suspected sleep apnea, the OR for each incremental PLM/hr
was 1.016 (1.001, 1.03).
Conclusion: PLMS are associated with increased CRP, with a single
PLM per hour corresponding to a 1.5% increased risk for elevated CRP.
After controlling for relevant confounders, the relationship between
PLMS and CRP remains apparent. Further investigation into the relationship
between PLMS and inflammation is warranted.
Support (If Any): KL2 RR-025009 (LMT)
0580
THE MU OPIATE RECEPTOR KNOCK-OUT MOUSE SHOWS
INCREASED SENSITIVITY TO PAIN, INCREASED MOTOR
ACTIVITY DURING THE SLEEP PERIOD AND DECREASED
SERUM IRON PARALLEL TO HUMAN RESTLESS LEGS
SYNDROME
Walters AS 1 , DeAndrade MP 2,3 , Doroodchi A 3 , Li Y 2,3
1
Neurology, Vanderbilt University School of Medicine, Nashville, TN,
USA, 2 Graduate Biomedical Sciences - Pathobiology and Molecular
Medicine, University of Alabama, Birmingham, AL, USA, 3 Center for
Neurodegeneration and Experimental Therapeutics, Department of
Neurology, University of Alabama, Birmingham, AL, USA
Introduction: Opioids are a well accepted second line therapeutic agent
for Restless Legs Syndrome(RLS). The opioid effect is opiate receptor
specific based upon receptor blocking studies. We have previously
shown in an autopsy study and in an in-vitro animal model that hypofunction
of the endogenous opioid system seems to play a role in RLS.
Our data and the data of others, in combination, suggest that RLS is
characterized by relative deficiencies in the endogenous opioid, dopamine
and iron systems.
Methods: In the current in-vivo study we utilized mu opiate receptor
Oprm1 knock-out mice and control (wild type) mice. We studied serum
iron and the circadian pattern of motor activity as measured by wheel
running.
Results: The Oprm1 knock out mouse is characterized by an increased
sensitivity to pain as has been demonstrated in human RLS in 2 different
studies. In mice the sleeping period is during the day. In the Oprm
1 knock out mouse there is increased motor activity during the normal
sleeping period compared to controls as in human RLS (P