Does the endogenous opiate system play a role in the Restless Legs Syndrome?: A pilot post-mortem study

Walters, Arthur S.; Ondo, William G.; Zhu, Wen; Le, Weidong

doi:10.1016/j.jns.2008.12.022

Cited by 97 publications

(49 citation statements)

References 23 publications

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“…A review of potential nondopaminergic systems led to the consideration that increased glutamatergic system activation may produce the RLS arousal pattern. Thalamic abnormalities have been associated with RLS symptoms, 9,10 and the thalamocortical system serves critical functions that if overactive could disrupt…”

Section: Discussionmentioning

confidence: 99%

Thalamic glutamate/glutamine in restless legs syndrome

et al. 2013

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Objective: To evaluate possible abnormal increase in thalamic glutamate/glutamine levels for restless legs syndrome (RLS) indicating increased glutamatergic activity producing arousal that at night disrupts and shortens sleep. Methods:1 H MRS of the right thalamus was performed using a 1.5 T GE MRI scanner and the PROBE-P (PRESS) on 28 patients with RLS and 20 matched controls. The Glx signal (combination of mostly glutamate [Glu] and glutamine [Gln]) was assessed as a ratio to the total creatine (Cr). This study tested 2 primary hypotheses: 1) higher thalamic Glx/Cr for patients with RLS than controls; 2) thalamic Glx/Cr correlates with increased wake during the sleep period.Results: The Glx/Cr was higher for patients with RLS than controls (mean 6 SD 1.20 6 0.73 vs 0.80 6 0.39, t 5 2.2, p 5 0.016) and correlated significantly with the wake time during the sleep period (r 5 0.61, p 5 0.007) and all other RLS-related polysomnographic sleep variables (p , 0.05) except for periodic leg movements during sleep (PLMS)/hour. Conclusions:The primary findings introduce 2 new related dimensions to RLS: abnormalities in a major nondopaminergic neurologic system and the arousal disturbance of sleep. The strong relation of the arousal sleep disturbance to glutamate and the lack of relation to the PLMS motor features of RLS contrasts with the reverse for dopamine of a limited relation to arousal sleep disturbance but strong relation to PLMS. Understanding this dichotomy and the interaction of these 2 differing systems may be important for understanding RLS neurobiology and developing better treatments for RLS. Neurology 1 H MRS 5 proton magnetic resonance spectroscopy; mI 5 myo-inositol; NAA 5 N-acetylaspartate; PLMS 5 periodic leg movements during sleep; PSG 5 polysomnography; RLS 5 restless legs syndrome; SWS 5 slow-wave sleep; VMB 5 ventral midbrain; WDSP 5 wake during the sleep period.Restless legs syndrome (RLS) is a rest-induced, movement-responsive, mostly nocturnal, urge to move the legs commonly associated with periodic leg movements during sleep (PLMS).1 Sleep disruption is the primary factor producing most of the morbidity of moderate to severe RLS. 2Patients with RLS, however, rarely report problems with excessive daytime sleep despite total sleep times averaging less than 5.5 hours.3 Untreated subjects with RLS who have no other sleep disorders (e.g., sleep apnea) have not been found in any clinical study to have a problem falling asleep while driving nor do they show the degree of frontal lobe cognitive deficits expected from their sleep loss. 4 Dopaminergic treatments provide effective treatment for RLS symptoms and dramatically reduce PLMS but in most studies fail to significantly reduce the sleep loss, arousals during sleep, 5-7 and abnormal cycling alternating pattern of sleep occurring with RLS. 8 Dopaminergic systems do not appear to be primary for producing the RLS sleep/wake arousal.If not dopamine, then what produces this RLS arousal pattern? A review of potential nondopaminergic systems led t...

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Section: Discussionmentioning

confidence: 99%

Thalamic glutamate/glutamine in restless legs syndrome

et al. 2013

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“…Therefore a decrease in iron concentration may affect the availability of dopamine. The endogenous opiate system has been suspected as having a role in the pathophysiology of RLS by stabilizing dopaminergic substantia nigra degeneration under conditions of iron deprivation (56,57). Since many conditions associated with RLS are also associated with inflammatory/immune changes it has been suggested that RLS may be mediated or affected through inflammatory mechanisms.…”

Section: Paradigm Of Questions For Epidemiology Studies Of Rlsmentioning

confidence: 99%

Sleep disorders during pregnancy

Sarberg

2015

Linköping University Medical Dissertations

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“…PET scan study [17] showed radioactive post-synaptic opiate receptor binding that was inversely correlated to the severity of RLS symptoms [17]. We recently performed a post-mortem study of RLS patients versus controls and found a statistically significant decrease in the endogenous opioids Beta endorphin and Metenkephalin in thalamus of RLS patients of about 30% [18].…”

Section: Introductionmentioning

confidence: 99%