Arm tremor in cervical dystonia—Is it a manifestation of dystonia or essential tremor?

The classification of arm tremor in cervical dystonia is a controversial issue. There have been many, at times passionate disputes in the movement disorder community about whether it should be classified as a manifestation of dystonia or essential tremor associated with dystonia. There are arguments in favor of both views. Settling the issue might be relevant to the understanding of the etiological, presumably genetic, background because phenomenological grouping is the starting point for genetic analyses. From this point of view, we outline this tremor debate and add some new clinical data. © 2011 Movement Disorder Society     

Is essential tremor a single entity?

Essential tremor (ET) is a frequent movement disorder. The new tremor classification has subdivided ET into the classical form with bilateral action tremor of the hands with or without involvement of further tremor locations and without any other explaining signs or symptoms for the tremor and into ‘ET plus’ which comes additionally with further neurological signs of unknown origin. This will provide a better foundation for subclassifying the condition. The immediate cause of ET is a preformed oscillating network within the central nervous system as revealed with electrophysiological methods. The reason why this network is getting into the tremor mode is unclear. Pathology has so far not convincingly proved neurodegeneration for the condition but possibly adaptive changes of the brain particularly in the cerebellum are likely. Genetics have not yet provided insight into the molecular causes of the condition but several genetic diseases presenting with an ET syndrome have been uncovered. Treatment options cover medication (propranolol, primidone, topiramate) and surgical interventions with deep brain stimulation, gamma‐knife surgery and the recently introduced magnetic resonance imaging guided focused ultrasound lesioning. Further progress is awaited from the better integration of large prospective cohort assessment and basic science studies on the possible etiologies. In particular, aging‐related tremor may explain a large number of the patients seen in clinical practice. Currently ET is considered a clinically relatively uniform condition with presumably various underlying etiologies.     

Common misdiagnosis of a common neurological disorder: how are we misdiagnosing essential tremor?

BACKGROUND: As a common neurological disorder, the diagnosis of essential tremor (ET) is considered routine. Despite this, previous work suggests that misdiagnoses may be common. Among other things, these misdiagnoses can lead to treatment errors. OBJECTIVES: To estimate how often other tremor disorders are misdiagnosed as ET and to identify factors that increase the odds of misdiagnosing ET and to precisely quantify the extent to which they do so. DESIGN: Seventy-one consecutive patients underwent an evaluation at the Neurological Institute of New York, New York, between January 1, 2000, and December 31, 2005; these patients had a pre-evaluation diagnosis of ET. The criteria for ET were adapted from the consensus statement of the Movement Disorder Society. RESULTS: Twenty-six patients (37%) were misdiagnosed as having ET ("false ET"). Their true diagnoses were Parkinson disease (11 patients [15%]), dystonia (6 patients [8%]), Parkinson disease with ET (5 patients [7%]), and other disorders (4 patients [6%]). Factors associated with misdiagnosed ET included unilateral arm tremor (odds ratio, 10.5; 95% confidence interval, 1.2-95.4; P=.02), spooning of the hands and other dystonic postures (odds ratio, 16.3; 95% confidence interval, 4.0-66.4; P<.001), and other unusual features (isolated thumb tremor, isolated leg tremor, and non-rhythmic tremor) (odds ratio, 49.4; 95% confidence interval, 2.7-895.0; P<.001). CONCLUSIONS: About 1 in 3 patients with tremor was misdiagnosed as having ET, with the most frequent false diagnoses being Parkinson disease and dystonia. Several factors that increased the odds of misdiagnosing ET were identified. These factors could be incorporated into improved diagnostic algorithms.     

What is the functional significance of nondominant arm tremor in essential tremor?

Tremor in the dominant arm is often the focus of clinical attention in essential tremor (ET) yet many daily activities require both arms. The functional relevance of nondominant arm tremor has rarely been studied. In 181 right‐handed patients with ET, action tremor in each arm was rated using a clinical rating scale. Tremor disability was self‐reported and a performance‐based test of function was administered. Independently of tremor on the right, greater tremor severity on the left was associated with greater self‐reported disability (P = 0.02) and greater performance‐based dysfunction (P < 0.001). In 5.0% of patients, tremor was largely restricted to the nondominant arm. Nondominant arm tremor, independent of dominant arm tremor, had a significant functional correlate, contributing to both greater perceived and greater observable functional difficulty. In 5% of patients, tremor in the nondominant arm was the likely motivator for seeking care, which is another indication of its functional significance. © 2010 Movement Disorder Society.     

Essential tremor: Is the word “essential” really essential?

Essential tremor (ET) is among the common movement disorders. A surge in research in recent years has considerably improved our understanding of disease etiology and pathogenesis, and its associated clinical phenomenology and natural history. With this progress have emerged a multitude of new questions and conundrums and newly proposed terminologies. Amidst these various related discussions, it is worth revisiting the essence of the nomenclature, “essential tremor”, to assess how well it continues to fit the growing understanding of this entity.Here we revisit the historical underpinnings of the nomenclature, its accuracy, pitfalls of eliminating the word, and advantages of removing the word. There are two primary historical bases for using the word “essential”: (i) idiopathic or unclear etiology, (ii) a unitary (single-featured) trait perceived as a constitutional feature. Numerous studies indicate that ET is neither truly idiopathic nor is fully isolated, making the use of “essential” technically incorrect. There are pitfalls and advantages of eliminating the term “essential” and both are succinctly described in this article. Yet in the absence of any flawless alternatives at present, we conclude that it is preferable for now to persist with “essential” tremor, thereby respecting the historical continuity of this one-and-a-half-century old nomenclature.     

Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its pathogenesis

Essential tremor (ET) encompasses a group of progressive neurological diseases in which the primary clinical feature is kinetic tremor of the arms. There is accumulating evidence to suggest that the cerebellum is involved in the pathogenesis of ET; the clinical presentation, neurophysiological data, and functional and metabolic abnormalities revealed by neuroimaging studies all point toward the dysregulation of cerebellar circuits. Recent neuropathological findings at postmortem demonstrate that Purkinje neurons, and some brainstem neurons, play an integral role in the pathogenesis of this common neurological disorder. The assessment of Purkinje cell linear density shows that Purkinje density is abnormal in ET brains. Specific efforts need be devoted to understanding the molecular and cellular events occurring in the Purkinje neurons of the cerebellar cortex, which are emerging as being of particular importance in the pathogenesis of ET in a subgroup of patients. © 2013 International Parkinson and Movement Disorder Society.     

Mild tremor in relatives of patients with essential tremor: what does this tell us about the penetrance of the disease?

BACKGROUND: Mild tremor may occur in relatives of patients with essential tremor (ET). However, this phenomenon has not been studied quantitatively or with a comparison group. Such a study may provide information on the penetrance of ET. OBJECTIVE: To obtain data on the magnitude of tremor in case and control relatives who did not meet diagnostic criteria for ET. METHODS: Cases with ET and control subjects from the Washington Heights-Inwood community in northern Manhattan, NY, were enrolled in a family study. Their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor, assigning a total tremor score (0-36 [maximum]). Data were analyzed on 201 case relatives and 212 control relatives who did not meet diagnostic criteria for ET. RESULTS: The mean total tremor score of first-degree case relatives was higher than that of first-degree control relatives (4.9 vs 3.9; P<.003). Total tremor scores for second-degree relatives did not differ (4.1 vs 4.2; P =.68). A larger percentage (55.2% vs 36.6%; P =.01) of first-degree case relatives had total tremor scores of 4 or more. Among first-degree relatives who were older than 60 years, 13 case relatives (59.1%) and 18 control relatives (45.0%) had total tremor scores of 4 or more. CONCLUSIONS: A considerable number of seemingly normal case relatives may have a genetic predisposition for tremor. Even among older case relatives (> or =60 years of age), there was an increased prevalence of higher tremor scores, suggesting that in that age group, subclinical ET may be present and penetrance still may not be complete.     

Polymorphism of NACP-Rep1 in Parkinson's disease: an etiologic link with essential tremor?

An allele (263bp) of the nonamyloid component of plaques (NACP)-Repl polymorphism has shown association with sporadic PD in a German population. The authors studied this polymorphism in 100 American PD patients and 100 healthy controls. The authors also studied 46 essential tremor (ET) and 55 Huntington's disease (HD) patients. Allele 263bp was significantly higher in PD patients (OR = 3.86) and ET patients (OR = 6.42) but not HD patients, compared with healthy controls. The association of allele 263bp with PD and ET suggests a possible etiologic link between these two conditions.     

Alzheimer's-related changes in non-demented essential tremor patients vs. controls: Links between tau and tremor?

BackgroundIn addition to tremor, patients with essential tremor (ET) may exhibit non-motor features, including a range of cognitive deficits. Several prospective, population-based epidemiological studies have reported an association between ET and incident dementia, especially Alzheimer's disease (AD). Moreover, in a brain repository-based study, a larger than expected proportion of ET patients also developed pathological changes characteristic of progressive supranuclear palsy, further suggesting a link between ET and tau pathology.MethodsWe selected a group of ET patients that were free of dementia clinically and without AD on postmortem examination. Our hypothesis was that neuronal tauopathic burden would be higher in the brains of these ET patients compared to controls. We compared Braak stage for neuronal tangles and Consortium to Establish a Registry for Alzheimer's Disease (CERAD) scores for neuritic plaques in the two groups.ResultsThe two groups were similar in age (82.6 ± 6.0 vs. 80.4 ± 8.1, p = 0.22). The 40 ET patients had a higher Braak neurofibrillary stage than 32 controls (means: 2.2 ± 1.2 vs. 1.2 ± 1.1; medians: 2.0 vs. 1.0, p < 0.001). Meanwhile, CERAD scores for neuritic plaques were similar in patients and controls (means: 0.6 ± 0.9 vs. 0.5 ± 0.6; medians: 0.0 vs. 0.0, p = 0.83).ConclusionWhile ET itself is not a tauopathy (i.e., a neurodegenerative disorder among whose main features are accumulation of hyperphosphorylated tau protein), ET may predispose individuals to accumulate more widespread cellular tau aggregates, and thus tau could play a central role in the cognitive impairment that can accompany ET.