Multimodal neurometabolic investigation of the effects of zolpidem on leukoencephalopathy-related apathy

C. Delorme, I. Adanyeguh, D. Bendetowicz, I. Le Ber, A. Ponchel, A. Kas, M. O. Habert, F. Mochel

Research output: Contribution to journalArticlepeer-review

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Background and purpose: The symptomatic effect of zolpidem on apathy has been reported in neurological disorders such as strokes and post-anoxic brain injuries, but not in white-matter disease of the brain. Methods: A 38-year-old patient presenting with severe apathy related to a genetic leukoencephalopathy but showing marked improvement of apathy after taking 10 mg of zolpidem was studied. To understand what may mediate such a clinical effect, a multimodal neurometabolic approach using 18F fluorodeoxyglucose positron emission tomography (FDG-PET) and a dedicated magnetic resonance spectroscopy (MRS) sequence for gamma aminobutyric acid (GABA) and glutamine + glutamate metabolism was undertaken. Results: Pre-zolpidem FDG-PET showed hypometabolism in the orbitofrontal cortex, dorsolateral cortex and basal ganglia compared to healthy controls. Post-zolpidem, FDG-PET displayed increased metabolism in the orbitofrontal cortex together with improvement in the emotional and auto-activation domains of apathy. There was no improvement in the cognitive domain of apathy, and no change in metabolism in the dorsolateral frontal cortex. Post-zolpidem, MRS showed increased GABA and glutamine + glutamate levels in the frontal cortex and pallidum. Conclusion: Our multimodal neurometabolic study suggests that the effects of zolpidem on apathy are related to increased metabolism in the orbitofrontal cortex and basal ganglia secondary to GABA modulation. Zolpidem may improve apathy in other white-matter disorders.

Original languageEnglish (US)
Pages (from-to)2297-2302
Number of pages6
JournalEuropean Journal of Neurology
Issue number11
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
© 2020 European Academy of Neurology


  • GABA
  • apathy
  • leukoencephalopathy
  • zolpidem


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