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Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury.

TitlePresynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury.
Publication TypeJournal Article
Year of Publication2019
AuthorsFridman, Esteban A., Osborne Joseph R., Mozley Paul D., Victor Jonathan D., and Schiff Nicholas D.
JournalBrain
Volume142
Issue7
Pagination1887-1893
Date Published2019 07 01
ISSN1460-2156
KeywordsAdult, Brain Injuries, Traumatic, Corpus Striatum, Dextroamphetamine, Dopamine, Dopamine Plasma Membrane Transport Proteins, Female, Humans, Levodopa, Male, Persistent Vegetative State, Positron-Emission Tomography, Presynaptic Terminals, Raclopride, Receptors, Dopamine D2, Substantia Nigra, Tegmentum Mesencephali, Thalamus, Young Adult
Abstract

Dopaminergic stimulation has been proposed as a treatment strategy for post-traumatic brain injured patients in minimally conscious state based on a clinical trial using amantadine, a weak dopamine transporter blocker. However, a specific contribution of dopaminergic neuromodulation in minimally conscious state is undemonstrated. In a phase 0 clinical trial, we evaluated 13 normal volunteers and seven post-traumatic minimally conscious state patients using 11C-raclopride PET to estimate dopamine 2-like receptors occupancy in the striatum and central thalamus before and after dopamine transporter blockade with dextroamphetamine. If a presynaptic deficit was observed, a third and a fourth 11C-raclopride PET were acquired to evaluate changes in dopamine release induced by l-DOPA and l-DOPA+dextroamphetamine. Permutation analysis showed a significant reduction of dopamine release in patients, demonstrating a presynaptic deficit in the striatum and central thalamus that could not be reversed by blocking the dopamine transporter. However, administration of the dopamine precursor l-DOPA reversed the presynaptic deficit by restoring the biosynthesis of dopamine from both ventral tegmentum and substantia nigra. The advantages of alternative pharmacodynamic approaches in post-traumatic minimally conscious state patients should be tested in clinical trials, as patients currently refractory to amantadine might benefit from them.

DOI10.1093/brain/awz118
Alternate JournalBrain
PubMed ID31505542
PubMed Central IDPMC6598636
Grant ListUL1 TR000457 / TR / NCATS NIH HHS / United States
R21 NS093268 / NS / NINDS NIH HHS / United States

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