ReviewEssential tremor: Beyond the motor features
Introduction
Till recently our understanding of the pathophysiology of Essential Tremor (ET) has been limited, despite ET being one of the commonest movement disorders [1], [2], [3], [4]. Over the past few years our knowledge regarding the pathophysiology and motor features of ET has grown and a new non-motor dimension has been added to this illness which was initially thought to be a pure motor disorder. The purpose of this article is to review the literature on the non-motor features of ET and explain them in the context of our current understanding of the pathophysiology of ET.
Section snippets
Pathophysiology
One of the major roadblocks to an improved understanding of ET has been the lack of anatomical localization and a pathological basis for the tremor. This was primarily due to a lack of autopsy material [5]. The establishment of the Essential Tremor Centralized Brain Repository at Columbia University has enabled the study of ET brains with modern histochemical techniques [6] and have shown the presence of pathological changes which were formerly not detected.
The changes can be broadly classified
Cognition
Studies on cognition in ET have predominantly assessed two aspects; one is the association of ET with subtle neuropsychological deficits characterized by frontal executive dysfunction as compared to normal controls; the other is a more recent and worrisome observation that ET is associated with dementia. Details of the studies on cognition in patients with ET are summarized in Table 1.
Gasparini et al. [20] were among the first to find that patients with ET had significant abnormalities in
Personality
The first study on personality in ET was done as part of an epidemiological study of ET from New York [33] using the tridimensional personality questionnaire (TPQ). The TPQ measures personality traits across three dimensions – harm avoidance (HA, anxiety prone vs. risk taking), novelty seeking (NS, anger prone vs. docile), and reward dependence (RD, sentimental vs. aloof). Patients with ET had a significantly higher mean HA score than controls whereas there was no difference in the NS and RD
Anxiety
A study of secondary social anxiety [37] from Turkey was carried out in patients with hyperkinesias which included patients with ET, hemifacial spasm (HS) and cervical dystonia (CD). They were compared to healthy controls matched for age, sex and education. Secondary social anxiety was diagnosed in 30% of patients with ET as compared to 30% of patients with CD and 20% of patients with HS. Using multivariate analysis of variance, a significant difference was found between all 3 patient groups
Depression
The association between ET and depression has not been highlighted sufficiently in literature. The initial studies on depression in ET were carried out along with assessment of cognition in hospital based settings for patients undergoing pre-surgical evaluation and hence they are limited by a selection bias. However since then depression in patients with ET has been reported in community and population-based studies.
The first study to evaluate depression in ET was done by Lombardi et al. [21],
Olfactory dysfunction
Olfactory dysfunction has been found as an early feature in patients with PD, hence investigators have tried to evaluate olfactory function in patients with ET and study whether it could be used as a tool to differentiate between patients with ET and those with tremor dominant PD. However these studies have reported conflicting results.
Busenbark et al. [43] conducted the first study of olfaction in ET utilising the University of Pennsylvania Smell Identification Test (UPSIT) and found that
Hearing impairment
In a population-based study of subjects over the age of 65 years [51], 38.7% of patients with ET vs. 29.4% of controls reported hearing impairment (p = 0.002). Using adjusted logistic regression analysis they found that subjects who reported hearing impairment were more likely to be suffering from ET. In contrast subjective visual impairment was similar in subjects with ET and controls. This increased association of hearing impairment with ET persisted even after excluding patients with dementia
Sleep
There is preliminary evidence to suggest that patients with ET in hospital based settings have poorer nocturnal sleep quality without excessive day time sleepiness when compared with age and gender matched controls [53]. This study also confirmed the earlier findings of increased depressive symptoms and anxiety scores among patients with ET. They also evaluated and found higher pain and fatigue scores among patients with ET. In addition to excessive day time sleepiness, another study recently
Conclusions
In addition to tremor, ET is characterized by several increasingly recognized non-motor features. The neurobiological basis of these findings at present is not certain. One may argue that some of the non-motor findings may be secondary to co-morbid depression, medication use or secondary to the psychosocial impact of tremor itself rather than due to a primary pathological process involving the brain. However though initial studies did not control sufficiently well for potential confounders
Financial disclosure/conflict of interest
None of the authors have any financial disclosure to make or have any conflict of interest.
Source of funding
Nil.
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