|Institution:||Universiteit van Amsterdam|
|Full text PDF:||http://hdl.handle.net/11245/1.506761|
This thesis focusses on the neural correlates and treatment of the neurological movement disorder essential tremor (ET). ET, one of the most common movement disorders in clinical neurology, is characterized by an action and intention tremor of mainly the hands, hampering daily life activities. Effects of symptomatic therapy, including propranolol, anti-epileptic drugs and stereotactic neurosurgery, differ between patients. Involvement of the cerebello-thalamo-cortical network, and the cerebellar system in particular, seems likely. However, exact mechanisms are unclear, and are the topic of this thesis. Disease and treatment mechanisms are studied with functional and structural brain imaging methods, combined with clinical neurophysiology applying advanced analysis methods. A well-defined group of propranolol-sensitive, familial ET patients, showed functional involvement of the bilateral cerebellum, together with hyperactive cerebellar outflow tracts, entailing the dentate nucleus and thalamus, and a striking lack of structural changes. In addition, these studies indicated tremor attenuation induced by the beta-blocker propranolol through a central mechanism of action, possibly by changing Renshaw cell sensitivity within the spinal cord. Furthermore, a group of ET patients showed, after therapeutic thalamotomy, structural lesioning effects outside the thalamus, in the cerebellar outflow tracts. The results within this thesis and previous studies support functional involvement of the cerebello-thalomo-cortical network in ET, and especially indicate both the cerebellar cortex and dentate nucleus to be critical players in the pathophysiology of ET. Future insights in the pathophysiology and physiology of treatment of ET will hopefully aid in the development of more effective symptomatic, and even curative, treatment for this disorder.