Brainstem morphology and movement disorders

Abstract

The control of movement involves complex neural circuits that span several brain regions. One brain region that is important for movement is a brainstem structure called the substantia nigra. The importance of this brain region is evidenced by the motor signs that accompany Parkinson's disease, a movement disorder characterised by degeneration of neurons in the substantia nigra. Substantia nigra morphology is difficult to assess in humans with standard clinical MRI but it can be readily viewed with transcranial sonography. Use of this technique has shown that the substantia nigra is abnormally bright and enlarged in patients with Parkinson's disease, and the abnormality (hyperechogencity) is present in 78–90% of patients. Because of this, the technique is now being used in some countries as a diagnostic aid for Parkinson's disease. Substantia nigra hyperechogenicity has also been observed in ∼9% of healthy adults. The presence of this abnormality in healthy older adults is a significant risk factor for Parkinson's disease. Healthy older adults with this abnormality are 17 times more likely to be diagnosed with Parkinson's disease over a 3-year period than people without the abnormality (Berg et al 2011 Arch Neurol 68:932-7). Our research team has demonstrated that substantia nigra hyperechogenicity in healthy older adults is associated with altered neuronal circuitry in a functionally connected brain region (motor cortex) and altered fine motor function. The changes share similarities with de novo patients diagnosed with Parkinson's disease. Our results support use of transcranial ultrasound as a diagnostic aid and early disease marker for Parkinson's disease. Our research has also identified a young-adult population that has a high prevalence of substantia nigra hyperechogenicity – individuals that have used the drug methamphetamine or ‘ice’. Methamphetamine is toxic to the same neurons that undergo neurodegeneration in Parkinson's disease. Our research shows that two thirds of young adults that have used methamphetamine, as little as five times, have substantia nigra hyperechogenicity and use of the drug is associated with clinical signs of parkinsonism. This observation is alarming because methamphetamine is a significant health problem in many countries and there are no reports of the substantia nigra abnormality returning to normal in the literature (in any population), despite tens of thousands of people having undergone the procedure world-wide. Our research suggests that substantia nigra hyperechogenicity in healthy adults is associated with changes characteristic of Parkinson's disease and supports its role as a marker of vulnerability for this disorder.