Disruption to the dopaminergic system following traumatic brain injury (S9.008)

Objective: To investigate whether: 1) traumatic brain injury (TBI) reduces striatal dopamine transporter (DAT) levels; 2) TBI causes structural changes to the substantia nigra and/or nigrostriatal tract; 3) DAT levels following TBI correlate with substantia nigra or nigrostriatal tract damage; 4) DAT levels relate to behavioural measures of apathy and/or speed of processing. Background: Persistent cognitive problems following TBI are common. The heterogeneous nature of TBI means that the basis of cognitive dysfunction is likely to be multi-factorial. Animal and human studies have shown dopaminergic disruption following TBI. However, the cause of this disruption is unclear and may relate to damage to the dopaminergic nuclei or their ascending projections. Design/Methods: 32 moderate/severe TBI patients with persistent cognitive problems and 15 healthy controls had an ioflupane ( 123 I) SPECT scan (DaTscan), MRI and full neuropsychological assessment. DAT levels in the striatum were measured. MRI was used to calculate substantia nigra volumes and nigrostriatal tract diffusion metrics. Results: Quantitative assessment showed reduced DAT levels in TBI patients. Patients had substantia nigra atrophy, as well as increased mean diffusivity in the nigrostriatal tract. There was a significant relationship between (1) DAT levels and substantia nigra volumes in patients and (2) mean diffusivity in the nigrostriatal tract and anterior striatal DAT levels. DAT levels showed a significant relationship with apathy measures but not speed of processing. Conclusions: A proportion of TBI patients with persistent cognitive problems have reduced striatal DAT levels implying a disruption to their dopaminergic system. DAT levels are correlated with structural changes in the substantia nigra and nigrostriatal tract. This supports a causal relationship between damage to these regions by TBI and functional dopaminergic dysfunction. Reduced DAT levels also relate to apathy. Dopaminergic therapies may therefore benefit those patients with evidence of disruption to their dopaminergic systems. Study Supported by: Guarantors of Brain NIHR Disclosure: Dr. Jenkins has nothing to disclose. Dr. De Simoni has nothing to disclose. Dr. Bourke has nothing to disclose. Dr. Cole has nothing to disclose. Dr. Sharp has nothing to disclose.