Fatigue is one of the most common symptoms in patients in the chronic phase of traumatic brain injury (TBI). Despite the frequency of fatigue, and its impact on the daily life of these patients, there are no evidencebased treatments for this symptoms, nor any objective ways for diagnosis.
OSU6162 showed safe to use, causing only minor side effects. However, there were no treatment effects on fatigue after 4 weeks of treatment at a maximum dose of 15 mg twice daily. fMRI revealed effects of treatment with OSU6162, but only in regions not related to fatigue.
fMRI showed that fatigue after TBI is related to alterations in striato-thalamic-cortical loops. The differences in BOLD signal in the caudate nucleus showed high diagnostic accuracy with a sensitivity of 81% and a specificity of 91%.
A clinical trial with a double-blind placebo-controlled design has been performed to examine whether the dopamine stabilizer OSU6162 has any effects on fatigue in patients with TBI. Fatigue has been examined with self-assessment scales, neuropsychological tests and functional magnetic resonance imaging (fMRI)
A cross-sectional study has been performed to investigate whether fMRI can be used to assess and diagnose fatigue in patients with TBI. Patients with TBI and age- and gender-matched healthy controls completed self-assessment questionnaires of fatigue, underwent an extensive neuropsychological test battery, and was examined with fMRI while performing a 27-minute fatiguing attention task.
Currently, another cross-sectional study is investigates whether structural damage in white matter of the brain is related to fatigue and other neuropsychological functions.
Berginström N, Nordström P, Schuit R, Nordström A. The Effects of (−)-OSU6162 on Chronic Fatigue in Patients With Traumatic Brain Injury: A Randomized Controlled Trial. Journal of Head Trauma Rehabilitation 2017; 32(2): E46-E54. Berginström N, Nordström P, Ekman U, Eriksson J, Andersson M, Nyberg L, Nordström A. Fatigue after traumatic brain injury is linked to altered striato-thalamic-cortical functioning. Brain Injury: Accepted Abstracts from the International Brain Injury Association's 12th World Congress on Brain Injury, 2017;31: 755-755 Berginström N, Nordström P, Ekman U, Eriksson J, Andersson M, Nyberg L, Nordström A. Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: Changes Linked to Altered Striato-Thalamic-Cortical Functioning. Journal of Head Trauma Rehabilitation 2018; 33(4): 266-274. Berginström N, Nordström P, Ekman U, Eriksson J, Nyberg L, Nordström A. Pharmaco-fMRI in Patients with Traumatic Brain Injury: A Randomized Controlled Trial with the Monoaminergic Stabilizer (-)-OSU6162. Journal of Head Trauma Rehabilitation 2018. Published Ahead of Print. doi: 10.1097/HTR.0000000000000440