The image of essential tremor: Current neuroimaging and clues to disease localization, pathogenesis, and diagnosis

Introduction Essential tremor (ET) is among the most common movement disorders; prevalence estimates range from 0.4% (all ages) to 21.7% among those greater than 95 years of age [1]. Despite this high prevalence, its pathophysiology is not well understood. Previously thought to be benign and monosymptomatic, ET is increasingly recognized as a more complex entity with both motor and non-motor features. New insights into ET in recent years have prompted a renewed interest in its clinical features and pathophysiology. The primary motor finding of ET is kinetic tremor of the arms, but tremor in the arms may additionally be present during sustained arm extension (i.e., postural tremor), at rest, or with intention; tremors may also involve cranial structures (neck, jaw, voice) [2]. Mild problems with force and timing of motion (e.g., mild dysmetria or ataxia) [3] are also common. Non-motor features include anxiety, depressive symptoms and depression, personality features, cognitive impairment, and even dementia [4]. Research over the past 5–10 years has begun to coalesce on several elemental questions. These are as follows: (1) Does the disease process originate in the cerebellum or a cerebellar motor loop system, or does it originate in the brainstem? (2) Is ET neurodegenerative? (3) Can one use neuroimaging as a diagnostic tool to distinguish ET from Parkinson’s disease (PD)? This chapter will set out to address each of these three emerging questions; the emphasis will be on the review of available neuroimaging data, inclusive of magnetic resonance imaging (MRI) as well as other modalities. To complement postmortem (i.e., pathological) studies, MRI and other imaging methods offer a valuable non-invasive approach for understanding in vivo functional anatomy and metabolic abnormalities in disease. Though the underlying pathophysiology of ET is not well understood, there are two current alternative hypotheses: (1) aberrant activity of primary cerebellar–thalamic pathways with impaired central inhibition and/or γ-aminobutyric acid (GABA) dysfunction in tremorigenesis, and (2) the presence of a central pacemaker, possibly in the brainstem, that drives abnormal downstream cerebellar–thalamic pathway activity. In the past, routine neuroimaging in ET was thought to be unremarkable, but more recent advances in the field now exploit a broad array of neuroimaging techniques, including MRI, for studying ET.