Title | Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Fridman EA, Osborne JR, Mozley PD, Victor JD, Schiff ND |
Journal | Brain |
Volume | 142 |
Issue | 7 |
Pagination | 1887-1893 |
Date Published | 2019 07 01 |
ISSN | 1460-2156 |
Keywords | Adult, 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. |
DOI | 10.1093/brain/awz118 |
Alternate Journal | Brain |
PubMed ID | 31505542 |
PubMed Central ID | PMC6598636 |
Grant List | UL1 TR000457 / TR / NCATS NIH HHS / United States R21 NS093268 / NS / NINDS NIH HHS / United States |