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May 28, 2013; 80 (22) Article

Thalamic glutamate/glutamine in restless legs syndrome

Increased and related to disturbed sleep

Richard P. Allen, Peter B. Barker, Alena Horská, Christopher J. Earley
First published April 26, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318294b3f6
Richard P. Allen
From the Departments of Neurology (R.P.A., C.J.E.) and Radiology (P.B.B., A.H.), Johns Hopkins University, Baltimore, MD.
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Peter B. Barker
From the Departments of Neurology (R.P.A., C.J.E.) and Radiology (P.B.B., A.H.), Johns Hopkins University, Baltimore, MD.
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Alena Horská
From the Departments of Neurology (R.P.A., C.J.E.) and Radiology (P.B.B., A.H.), Johns Hopkins University, Baltimore, MD.
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Christopher J. Earley
From the Departments of Neurology (R.P.A., C.J.E.) and Radiology (P.B.B., A.H.), Johns Hopkins University, Baltimore, MD.
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Citation
Thalamic glutamate/glutamine in restless legs syndrome
Increased and related to disturbed sleep
Richard P. Allen, Peter B. Barker, Alena Horská, Christopher J. Earley
Neurology May 2013, 80 (22) 2028-2034; DOI: 10.1212/WNL.0b013e318294b3f6

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Abstract

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: 1H 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 ± SD 1.20 ± 0.73 vs 0.80 ± 0.39, t = 2.2, p = 0.016) and correlated significantly with the wake time during the sleep period (r = 0.61, p = 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.

GLOSSARY

Cho=
choline-containing compounds;
Cr=
creatine/phosphocreatine;
Gln=
glutamine;
Glu=
glutamate;
Glx=
glutamine plus glutamate;
1H MRS=
proton magnetic resonance spectroscopy;
mI=
myo-inositol;
NAA=
N-acetylaspartate;
PLMS=
periodic leg movements during sleep;
PSG=
polysomnography;
RLS=
restless legs syndrome;
SWS=
slow-wave sleep;
VMB=
ventral midbrain;
WDSP=
wake during the sleep period

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 2006

  • Received November 5, 2012.
  • Accepted in final form January 24, 2013.
  • © 2013 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Thalamic glutamate/glutamine in restless legs syndrome: Increased and related to disturbed sleep
    • Iain Jordan, North Dublin Mental Health Servicemsorenson@neurology.org
    • Declan Murray, Dublin
    Submitted October 01, 2013
  • Potential effects of comorbid anxiety?
    • Dario M Zagar, Neurologist, Fairfield, CT Dzagar@anscneuro.com
    Submitted June 13, 2013
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