Neuroimaging Studies of Essential Tremor: How Well Do These Studies Support/Refute the Neurodegenerative Hypothesis?

BACKGROUND Tissue-based research has recently led to a new patho-mechanistic model of essential tremor (ET)-the cerebellar degenerative model. We are not aware of a study that has reviewed the current neuroimaging evidence, focusing on whether the studies support or refute the neurodegenerative hypothesis of ET. This was our aim. METHODS References for this review were identified by searches of PubMed (1966 to February 2014). RESULTS Several neuroimaging methods have been used to study ET, most of them based on magnetic resonance imaging (MRI). The methods most specific to address the question of neurodegeneration are MRI-based volumetry, magnetic resonance spectroscopy, and diffusion-weighted imaging. Studies using each of these methods provide support for the presence of cerebellar degeneration in ET, finding reduced cerebellar brain volumes, consistent decreases in cerebellar N-acetylaspartate, and increased mean diffusivity. Other neuroimaging techniques, such as functional MRI and positron emission tomography (PET) are less specific, but still sensitive to potential neurodegeneration. These techniques are used for measuring a variety of brain functions and their impairment. Studies using these modalities also largely support cerebellar neuronal impairment. In particular, changes in (11)C-flumazenil binding in PET studies and changes in iron deposition in an MRI study provide evidence along these lines. The composite data point to neuronal impairment and likely neuronal degeneration in ET. DISCUSSION Recent years have seen a marked increase in the number of imaging studies of ET. As a whole, the combined data provide support for the presence of cerebellar neuronal degeneration in this disease.