A very close look at the lives and brains of a few very dedicated research participants at UCSD may reveal a more complete picture of Essential Tremor (ET).
ET is one of the most common movement disorders. It is characterized by tremor of the hands and forearms (although it may also affect the head, neck, legs, voice, or face), occurring during voluntary movements such as drinking, pouring, eating, or writing. Despite a growing body of research, the neurology of ET is still poorly understood. Emerging studies suggest that cognitive impairments, personality changes, and a lower quality of life often accompany this disease. Yet, the underlying anatomical structures and brain networks responsible for Essential Tremor and its behavioral manifestations are still unclear. The Brain Observatory is working with a very dedicated small group of local research participants who live in San Diego. In line with our trademark multimodal approach, we assess their neurological conditions and neuropsychological profile, and collect structural magnetic resonance imaging (sMRI) data, including diffusion weighted imaging (DTI), on a regular basis. We also use a new instrument to record the frequency and amplitude of the tremor. With all of these methods combined, we hope to be able to draw a complete picture of this disease for each patient.
There are many questions about ET that remain unanswered. Most notably, unlike in other movement disorders, like Parkinson’s disease, the pathogenesis of ET is still not well characterized. Amongst the several brain structures that have been proposed to play a role in ET are the cerebellum, the brainstem, the frontal lobes, and the thalamus. It may also be that a dysfunction in neural pathways connecting these areas causes the symptoms observed in ET. Support for these theories comes from neuroimaging, neuropsychological, as well as neuropathological studies. DTI studies have revealed widespread white matter pathology in the brains of ET patients. Neuropsychological studies have pointed into the direction of prefrontal cortex dysfunction. The successful treatment of ET by means of deep brain stimulation of the thalamus suggests that this subcortical structure may be involved. Transmagnetic stimulation of the cerebellum, as well as the consumption of ethanol (affecting cerebellar function) has been found to temporarily relieve tremor symptoms. All these studies have brought us closer to understanding ET. However, to-date no one has combined available imaging methods and experimental approaches. The Brain Observatory is unique in that we are able to work with a selected group of subjects who live with ET and who are committed to finding out what is happening in their brain. Also, by working closely with our cohort of subjects, we will have the chance to learn how differently ET affects each person in the performance of daily tasks and how it may impact their personal life. The examination of multiple family members will allow us to evaluate the genetic influence on the phenotype. The goal is to combine results from different research approaches to achieve a more integrated, more complete picture of ET.
But this picture may not be static. What is the impact of ageing on ET? The possibility that ET is a progressive neurodegenerative disease is still being debated. Previous research has shown that advanced age is associated with an increased risk of developing ET and that ET is associated with a faster cognitive decline than that seen in healthy control subjects. Moreover, older-onset ET has been linked to an increased risk of developing dementia. It would be important to distinguish between the neurological markers of the tremor and those structural changes that occur as a consequence of aging. A rigorous, morphometric longitudinal imaging study conducted on the same subjects, combined with accurate quantitative diagnosis, could provide the data that is necessary to understand the long-term temporal dynamics of the tremor and how factors such as age and personal habits affect its progression.
Perhaps the most important aspect of the ongoing research is that our friends have made the generous decision to donate their brains after they pass away, which will allow us to establish the crucial link between the information collected during the study with the direct examination of the brain. Histo-pathologic changes associated with ET are currently grouped into two distinct phenomena; Purkinje cell loss in the cerebellum and presence of Lewy bodies in the brainstem. Both these structural changes are hallmarks of neuronal loss and degeneration, which would indicate that ET is indeed a progressive and predictable neurological disorder. Yet, post-mortem studies of ET are still very limited and need to be integrated within a bigger picture. Our research project will ultimately allow us to combine neurobehavioral information with the direct observation of the brain in the same individual. In time, these well-studied individuals with ET will be preserved in The Digital Brain Library (http://thebrainobservatory.ucsd.edu/content/digital-brain-library-0), making all data accessible to other researchers for comparisons and retrospective collaborative studies.
The Brain Observatory welcomes the participation of other patients whose life is being affected by Essential Tremor in this preliminary phase of the work. Extending the study to a larger number of subjects means adding significance and reliability to our study. In other words, the larger the group of participants the higher the potential impact of our study.
For more information, please contact us by phone or by e-mail.
Article by Ruth Klaming and Jacopo Annese