|Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury.
|Year of Publication
|Fridman EA, Osborne JR, Mozley PD, Victor JD, Schiff ND
|2019 07 01
|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
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.
|PubMed Central ID
|UL1 TR000457 / TR / NCATS NIH HHS / United States
R21 NS093268 / NS / NINDS NIH HHS / United States