Impairment In Essential Tremor Research Articles

Prevalence of and Annual Conversion Rates to Mild Cognitive Impairment and Dementia: Prospective, Longitudinal Study of an Essential Tremor Cohort.

Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort. Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients. The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations. We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193-1204.

Cognitive impairment in essential tremor assessed by the cerebellar cognitive affective syndrome scale.

Essential tremor (ET) is a movement disorder characterized by cerebellar neurodegenerative changes. ET is also associated with non-motor symptoms including cognitive impairment. The neuropsychologic profile of a patient with ET could relate to cerebellar cognitive affective syndrome (CCAS). This study aimed to assess the prevalence of cognitive impairment in patients with ET and identify whether the cognitive impairment in ET corresponds to a CCAS. Cognitive functions were evaluated with the CCAS-Scale (CCAS-S) in 20 patients with ET and 20 controls matched for age, sex, and level of education. The results of the CCAS-S were compared between patients and controls. The underlying determinant of CCAS inpatients with ET was identified through the correlation between the results of the CCAS-S and age at onset of symptoms, disease duration, and the Essential Tremor Rating Assessment Scale (TETRAS). On a group level, ET patients performed significantly worse than matched controls. In total, 13 individuals with ET had a definite CCAS (CCAS-S failed items ≥ 3). ASO and TETRAS scores significantly correlated with CCAS-S performances in ET patients. CCAS is highly prevalent in patients with ET which supports the cerebellar pathophysiology of associated cognitive impairment and supports a more systematic use of the CCAS-S to cognitively assessed patients with ET.

Cognitive Performance as a Function of MAPT Haplotype: A Prospective Longitudinal Study of an Essential Tremor Cohort.

Cognitive impairment is a feature of essential tremor (ET). There are no studies of the genetic drivers of this association. We examined whether the microtubule-associated protein tau (MAPT) H1 haplotype is associated with cognitive performance in ET. ET cases genotyped for the MAPT H1 and H2 haplotypes completed a battery of neuropsychological tests at baseline and four follow-up evaluations. Chi-square, t-tests, and analyses of covariance examined associations between the presence of the MAPT H1 haplotype, cognitive diagnoses of normal, mild cognitive impairment (MCI), and dementia, and performance in specific cognitive domains. We observed no evidence of cognitive differences as a function of the presence of the MAPT H1 haplotype. Specifically, cases with (n = 57) and without (n = 42) this haplotype did not differ with respect to the prevalence of diagnoses of MCI or dementia, p ≥ 0.87. Moreover, cases with vs without this haplotype did not differ in either the age or point in the disease course at which observed conversions to MCI or dementia occurred, p's ≥ 0.51. Finally, no haplotype-related differences were observed in performance in the cognitive domains of attention, executive function, language, memory, visuospatial or global ability, p's ≥ 0.21, or in changes in performance in these domains across time, p's ≥ 0.08. The study in an ET cohort revealed no influence of MAPT haplotypes on cognitive performance. This study serves as a valuable foundation for future studies to expand our understanding of the genetic drivers of cognitive impairment in ET. This study found no evidence of cognitive differences between individuals with and without the MAPT H1 haplotype. Our work provides a valuable foundation for future work to expand our knowledge of the genetic drivers of cognitive impairment in ET.

Brain microstructural changes in essential tremor patients and correlations with clinical characteristics: a diffusion kurtosis imaging study.

Essential tremor (ET) is the second most common movement disorder; however, the pathophysiological mechanism of ET is unclear. We aimed to investigate the microstructural degeneration of gray matter (GM) and white matter (WM) and their correlations with cognition and tremor in patients with ET. The participants were 63 patients with ET and 63 matched healthy controls (HCs) who underwent 3D-T1 weighted and diffusion kurtosis images (DKI). Microstructural degeneration was measured using high-level diffusion parameters derived from DKI. A voxel-wise analysis of the means of the GM-based spatial statistics and tract-based spatial statistics were conducted to assess differences in diffusion parameters between the ET and HC groups. The volume differences between the two groups were also assessed, and tremor severity and multi-domain cognitive performance were evaluated. Finally, the relationship between microstructural degeneration and clinical characteristics were assessed. The ET group had significantly lower mean kurtosis of the temporal, parietal, and occipital lobes and the cerebellum and lower radial kurtosis in several tracts. These microstructural changes in GM and WM were correlated with tremor and cognitive scores. However, no significant difference in volume was found between the groups. Our findings suggest that ET entails extensive GM and WM microstructural alterations, which support the neurodegenerative hypothesis of ET. Our study contributes to a better understanding of the mechanisms underlying tremor and cognitive impairment in ET.

P 6 Visuomotor adaptation is impaired in Essential Tremor

Introduction: Evidence has accumulated to support the theory that the cerebellum is crucially involved in the primary pathophysiology of Essential Tremor (ET). The cerebellum is critical for integration of sensorimotor information to create an internal model of movement using prediction errors. Neurological disorders causing cerebellar injury, such as degenerative cerebellar ataxia or cerebellar stroke, disrupt visuomotor integration and impede error-based learning. We hypothesized that cerebellar dysfunction in ET is also associated with impairment of visuomotor integration and error-based learning. Materials & Methods: To test this hypothesis, mildly to moderately affected ET patients (N=34; mean TETRAS score: 32.15 ± 13.78) and age-matched healthy controls performed a visuomotor adaptation task (Fig. 1A). The task was displayed on a PC monitor and movements were captured using a digital tablet. The experiment was divided into 3 phases (Fig. 1C): a baseline phase (BL), including simple center-to-target movements; an adaptation phase (ADP), in which a 30° visuomotor perturbation was introduced and a de-adaptation phase (DA), in which this perturbation was removed. The angle between the hand path and the center-target path, termed angular error, was calculated to assess visuomotor adaptation (Fig. 1B). Adaptation indices (AI; AI1 = ADP1 – BL2; AI2 = ADP8 – BL2; AI3 = DA1 – ADB8) were evaluated to assess the differences in angular error in each phase of the task (Fig. 2B). Covariates recorded were: clinical characteristics of ET patients, such as disease duration, alcohol responsivity, current medication, clinical measures of tremor and ataxia (as indexed by the TETRAS and SARA score), and basic motor performance as assessed by reaction and movement times. Results: AIs were significantly lower in ET patients compared to controls (Fig. 2A). No differences were found between ET patients and controls at BL or at DA, suggesting that the effects were specific to the adaptation phase. No differences in basic motor performance between groups were evident (all p>0.2), indicating that adaptation deficits in ET were not caused by impaired motor functions. In addition, there was no association between clinical parameters of ET and visuomotor adaptation abilities, suggesting that the reduced ability to adapt the motor response to the visual perturbation was unlikely to result from the tremulous movement. Conclusion: We found that visuomotor adaptation was impaired in ET, specifically in the adaptation phase. These results provide further evidence for linking ET to cerebellar dysfunction. Because the impairment was unrelated to clinical measures of tremor or ataxia and to basic motor performance, cerebellar dysfunction underlying visuomotor impairment in ET may be differentiated from the pathophysiological origin of other cerebellar diseases.

Does essential tremor increase risk of cognitive impairment and dementia? Yes.

Essential Tremor (ET), by definition, is a disorder of movement. Yet over the years, epidemiologic, clinical, pathologic, and neuroimaging studies have converged to reveal a cognitive side of ET. The cognitive symptoms in ET are heterogeneous and are likely to reflect heterogeneous underlying mechanisms. In this chapter, we review and synthesize a diverse set of studies from both population-based settings to cohorts with more detailed investigations into cognition to consider the various mechanisms by which cognitive symptoms may emerge in a subset of individuals with ET. As part of our analysis, we consider questions surrounding ET diagnosis and the possibility of comorbid disease as potential factors that, upon closer examination, appear to strengthen the argument in favor of ET as a risk factor for dementia. Importantly, we also consider the clinical relevance of cognitive impairment in ET. While ET is not universally characterized by significant cognitive deficits, the data from epidemiological, cognitive, neuroimaging, and postmortem neuropathologic studies converge to reveal an increased risk for cognitive impairment and dementia among individuals with ET. We conclude by offering directions for future research, and a neurocognitive framework with which to consider existing findings and to use in the design of novel studies dedicated to clarifying the basis, nature, and course of cognitive impairments in ET.

Network Fingerprint of Stimulation-Induced Speech Impairment in Essential Tremor.

This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p < 0.001) of the variance of stimulation-induced change in intelligibility in a leave-one-out analysis. This study demonstrates that SID in essential tremor patients is associated with both motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in essential tremor patients with thalamic DBS. ANN NEUROL 2021;89:315-326.

Hippocampal impairment in patients with Essential Tremor

IntroductionThere is growing evidence that a proportion of patients with Essential Tremor (ET) may develop a memory impairment over time. However, no studies have evaluated whether hippocampal damage really occur in ET. This study investigated the macro and micro-structural integrity of the hippocampus in ET subjects using a multimodal MRI approach. MethodsNeuropsychological and MRI data were acquired from 110 participants (60 patients with ET and 50 age-, sex-, and education-matched healthy controls [HC]). Whole-brain T1-weighted and Diffusion Tensor Imaging (DTI) were performed to assess macro-and microstructural alterations. MRI parameters (volume; mean diffusivity [MD]; fractional anisotropy [FA]) of bilateral hippocampi were obtained. In order to evaluate the relationship between MRI alterations and neurocognitive impairment, hippocampal parameters were also correlated with cognitive test scores. ResultsCompared to controls, ET patients showed a subclinical memory impairment with significantly lower memory scores, but within the normal ranges. Despite the subclinical damage, however, ET patients showed a significant increase in MD values in the bilateral hippocampi in comparison with HC. A significant correlation was also found between MD and memory scores in ET. ConclusionThis study improves the knowledge on memory impairment in ET, as our results demonstrate for the first time the hippocampal microstructural damage related to subclinical memory impairment in ET patients. Further studies are needed before these findings can be considered predictive of a distinct ET subtype or suggestive of a co-occurent dementia.

A turn for the worse: Turning performance in Parkinson's disease and Essential tremor

BackgroundTurning is an activity of daily living known to elicit falls in older adults and particularly in persons with movement disorders. Specifically, those with Parkinson's disease have marked impairments in forward walking and turning. Although recent work has identified gait impairment in those with Essential tremor, turning has not been extensively evaluated. As the cerebellum is key in the pathophysiology of Essential tremor, complex tasks like turning, may be impaired for this population. The purpose of this study was to investigate turning behavior and falls in those with Essential tremor and Parkinson's disease. Methods15 persons with Essential tremor and 15 persons with Parkinson's disease performed forward walking and turns on an instrumented walkway. t-tests compared groups and a regression was performed to predict fall frequency. FindingsDuring turning, those with Essential tremor had lower cadence (p = .042) and took more time (p = .05). No other variables, including forward walking variables, differed between groups. When pooling groups, the significant fall frequency predictor model (p = .003) included decreased forward cadence, increased turning cadence, and female sex. Overall, the model explained 40.7% of the variance. InterpretationWhile forward gait performance was similar between groups, those with Essential tremor had increased turn time, a measure often associated with turning impairment. Together, these results suggest overall gait impairment in Essential tremor is more prevalent than recognized. Walking performance, both turning and forward, and sex were predictive of fall frequency. Therapeutic interventions in these populations should include both forward walking and turns to mitigate fall risk.

White matter rather than gray matter damage characterizes essential tremor.

We investigated changes in gray matter (GM) and white matter (WM) in the whole brain, including both cortical and subcortical structures, and their relationship with tremor severity, psychiatric symptoms, and cognitive impairment in patients affected by essential tremor (ET). We studied 19 ET patients and 15 healthy subjects (HS). All the subjects underwent a 3-T MRI study based on 3D-T1 and diffusion tensor images. For the GM analysis, cortical thickness was assessed by using the Computational Anatomy Tool, basal ganglia and thalamus volumes by using the FMRIB software library, and cerebellum lobular volumes by using the spatial unbiased atlas template. For the WM assessment, we performed a voxel-wise analysis by means of tract-based spatial statistics. Patients' tremor severity and psychiatric and cognitive disorders were evaluated by means of standard clinical scales. Neuroimaging data were correlated with clinical scores. We found significantly smaller right and left thalamic volumes in ET patients than in HS, which correlated with cognitive scores. We did not observe any significant differences either in cortical thickness or in cerebellar lobular volumes between patients and HS. WM abnormalities were detected in most hemisphere bundles, particularly in the corticospinal tract, cerebellar peduncles, and corpus callosum. The WM abnormalities significantly correlated with tremor severity, cognitive profile, and depression. Our study indicates that ET is characterized by several GM and WM changes of both infra- and supratentorial brain structures. The results may help to better understand mechanisms underlying tremor severity and psychiatric and cognitive impairment in ET. • We performed a comprehensive evaluation of gray and white matter in the same sample of patients with essential tremor using recently developed data analysis methods. • Essential tremor is characterized by widespread gray and white matter changes in both infra- and supratentorial brain structures. The results may help to better understand motor and non-motor symptoms in patients with essential tremor.

Abnormal hippocampal subfields are associated with cognitive impairment in Essential Tremor.

Multi-domain cognitive impairment (CI) has been frequently described in patients with essential tremor (ET). However, the exact neuroanatomical basis for this impairment is uncertain. This study aims to ascertain the role of the hippocampal formation in cognitive impairment in ET. Forty patients with ET and 40 age, gender and education matched healthy controls (HC) were enrolled. Cognition was assessed using a structured neuropsychological battery and patients were categorized as ET with CI (ETCI) and ET without CI (ETNCI). Automatic segmentation of hippocampal subfields was performed using FreeSurfer 6.0. The obtained volumes were correlated with scores of neuropsychological tests. Significant atrophy of the left subiculum, CA4, granule-cell layer of dentate gyrus, right molecular layer, and hypertrophy of bilateral parasubiculum, right hippocampus-amygdala-transition-area, bilateral hippocampal tail (HT) and widening of right hippocampal fissure was observed in ET. Trends toward atrophy of right subiculum, and widening of left HF was also observed. Comparison of HC and ETCI revealed atrophy of right subiculum, hypertrophy of bilateral parasubiculum, HT, and widening of left HF. ETCI showed a trend toward widening of right HF. ETNCI had isolated left parasubicular hypertrophy and in comparison, to ETNCI the ETCI subgroup had atrophy of bilateral fimbria. Significant correlations were observed between the volumes of HT, HF, fimbria and scores of tests for executive function, working and verbal memory. Patients with ET have significant volumetric abnormalities of several hippocampal subfields and these abnormalities may be important contributors for some forms of cognitive impairment observed in ET.

Evaluating Mild Cognitive Impairment in Essential Tremor: How Many and Which Neuropsychological Tests?

Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018, 24, 1084-1098).

Non-amnestic Cognitive Impairment in Essential Tremor (ET): Defining the Phenotype (P6.057)

Non-amnestic Cognitive Impairment in Essential Tremor (ET): Defining the Phenotype (P6.057)

Linking Essential Tremor to the Cerebellum: Physiological Evidence.

Essential tremor (ET), clinically characterized by postural and kinetic tremors, predominantly in the upper extremities, originates from pathological activity in the dynamic oscillatory network comprising the majority of nodes in the central motor network. Evidence indicates dysfunction in the thalamus, the olivocerebellar loops, and intermittent cortical engagement. Pathology of the cerebellum, a structure with architecture intrinsically predisposed to oscillatory activity, has also been implicated in ET as shown by clinical, neuroimaging, and pathological studies. Despite electrophysiological studies assessing cerebellar impairment in ET being scarce, their impact is tangible, as summarized in this review. The electromyography-magnetoencephalography combination provided the first direct evidence of pathological alteration in cortico-subcortical communication, with a significant emphasis on the cerebellum. Furthermore, complex electromyography studies showed disruptions in the timing of agonist and antagonist muscle activation, a process generally attributed to the cerebellum. Evidence pointing to cerebellar engagement in ET has also been found in electrooculography measurements, cerebellar repetitive transcranial magnetic stimulation studies, and, indirectly, in complex analyses of the activity of the ventral intermediate thalamic nucleus (an area primarily receiving inputs from the cerebellum), which is also used in the advanced treatment of ET. In summary, further progress in therapy will require comprehensive electrophysiological and physiological analyses to elucidate the precise mechanisms leading to disease symptoms. The cerebellum, as a major node of this dynamic oscillatory network, requires further study to aid this endeavor.

White matter correlates of cognitive impairment in essential tremor.

Impairment of cognitive functions occurs in essential tremor, though the mechanism is largely unknown. The aim of this study was to find microstructural correlates of cognitive dysfunction seen in essential tremor by using DTI and neuropsychological assessment. Fifty-five patients with essential tremor and 55 matched healthy controls were evaluated. Essential tremor was diagnosed by using the National Institutes of Health criteria. Subjects were assessed by using a structured neuropsychological battery. DTI data were acquired by using 3T MR imaging and were analyzed by using tract-based spatial statistics. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity were analyzed. Patients were considered cognitively impaired when the test score was 1.5 SDs below or above the mean of healthy controls (depending on the type of test) in ≥3 neuropsychological tests. Patients with cognitive impairment had significantly higher mean diffusivity, radial diffusivity, and axial diffusivity values in the bilateral frontoparietal regions. In patients with cognitive impairment, mean diffusivity, radial diffusivity, and axial diffusivity showed correlations with various neuropsychological test scores. Executive function correlated with DTI measures of the frontal white matter, cingulum, inferior superior longitudinal and uncinate fasciculi, anterior thalamic radiations, and posterior lobe of the cerebellum. Visuospatial function correlated with the right parieto-occipital lobe, whereas visual-verbal memories correlated with the anterior thalamic radiations, inferior longitudinal and uncinate fasciculi, and the posterior lobe of the cerebellum. No significant correlations were found between fractional anisotropy and any of the neuropsychological test scores. The present study demonstrates a correlation between neuropsychological test scores and DTI measures, suggesting a neuroanatomic basis for cognitive impairment seen in patients with essential tremor.

Association between cortical volume loss and cognitive impairments in essential tremor

Impairment of cognitive functions occurs in essential tremor (ET) although the mechanism is largely unknown. A possible association between cognitive performance and brain atrophy in ET patients was examined using neuropsychological tests and voxel-based morphometry (VBM). Twenty-five patients with ET and 25 matched healthy controls were evaluated. ET was diagnosed using the National Institutes of Health collaborative genetic criteria. Severity of tremor was assessed using the Fahn-Tolosa-Marin (FTM) tremor rating scale. Subjects were assessed using a structured neuropsychological battery. Brain images were acquired using a 3T magnetic resonance imaging scanner. VBM analysis was performed using Statistical Parametric Mapping 8. The age of the patients was 45.0±10.7 years and of controls 45.4±10.7years. Tremor duration was 9.84±6.63years and total FTM score was 37.34±17.67. Patients were divided into two groups: ETCI with cognitive impairment (three or more abnormal neuropsychological tests, 1.5 standard deviation criterion) and ETNCI without cognitive impairment. Compared with controls, the ETCI group had significantly impaired performance in neuropsychological tests. One-way analysis of variance was performed between the three groups (ETCI, ETNCI, controls) followed by the two-sample t test. Compared with controls, grey matter volume (GMV) loss was observed in ETCI in the cerebellum (anterior and posterior lobes) and medial frontal gyrus. GMV loss was observed in ETCI compared with ETNCI in the medial frontal gyrus, post central gyrus, anterior cingulate and insula. Impairment in neuropsychological tests significantly correlated with GMV of the medial frontal gyrus, superior parietal lobe, middle temporal gyrus, occipital lobe, lentiform nucleus, insular and cingulate cortices and cerebellum posterior lobe in ETCI. A correlation between neurocognitive deficits in ETCI and GMV was observed suggesting that grey matter atrophy appears to be a correlate of cognitive impairment in ET.

The cognitive side of essential tremor: what are the therapeutic implications?

While essential tremor (ET) has traditionally been categorized as a pure motor disease, cross-sectional and longitudinal studies of cognition in ET have demonstrated that these patients may have cognitive dysfunction. Recent epidemiological studies demonstrate an association between ET (particularly with onset after age 65) and increased risk for cognitive impairment and dementia. Although existing studies have generally conceptualized cognitive changes in ET as consistent with a 'frontosubcortical' or 'corticocerebellar' profile, results from these same studies suggest that cognitive impairment in ET may in fact be heterogeneous. Furthermore, the underlying mechanisms remain uncertain. Cognitive changes could be a byproduct of the cerebellar dysfunction of ET itself; alternately, they may be a feature of concomitant neurodegenerative diseases that have been associated in several studies with ET, including Alzheimer's disease, Parkinson's disease or progressive supranuclear palsy. While the study of cognitive dysfunction in ET has received research attention in recent years, the results of these studies have not been translated into the clinical domain and clinical practice. This review first summarizes the current literature on the potential relationships between ET and cognitive change. We then suggest areas of further clinical evaluation and treatment; these suggestions are directed at physicians caring for ET patients who may demonstrate or complain of cognitive impairment. As we discuss, clinicians should ideally screen ET patients for possible signs or symptoms of cognitive impairment in addition to assessing for psychiatric comorbidity and quality of life. These recommendations are in contrast to most current clinical practice, which does not routinely include such assessment among ET patients. To our knowledge, there have been no pharmacotherapeutic trials to date of any agent for cognitive change associated with ET. We believe that studies for this indication are now called for. Future efforts in this direction will also need to take into account the pathobiology of cognitive changes in ET, which itself is an area that is ripe for future investigations.

The balance and gait disorder of essential tremor: what does this mean for patients?

Essential tremor (ET), once considered a monosymptomatic disease, is now viewed as a syndrome characterized by action tremor as well as a variety of other neurological features. These features include deficits of both balance (i.e. the ability to maintain the body within its base of support) and gait. Balance and gait abnormalities in ET have been studied most extensively in the laboratory, with the disability and burden on life, as experienced by patients with ET, being a subject of relatively less scrutiny. In this paper, we review the data on balance and gait impairment in ET. These include data both from objective assessments (bedside examination or laboratory gait analysis) and subjective assessments (patients' reports of imbalance). We discuss the clinical implications of the current data, and suggest a tiered approach to begin to address the still unanswered questions in this field. This tiered approach starts with an attempt to isolate a subpopulation of patients who are at greatest risk of difficulty with balance and gait, and then later focuses on this subgroup to assess the burden of any balance and gait impairments as well as the impact of potential therapeutic interventions.

Balance and Motor Speech Impairment in Essential Tremor

The pathogenesis of essential tremor (ET) is still under debate. Several lines of evidence indicate that ET is associated with cerebellar dysfunction. The aim of the present study was to find corroborating evidence for this claim by investigating balance and speech impairments in patients with ET. In addition, the effect of deep brain stimulation (DBS) on balance and speech function was studied. A group of 25 ET patients including 18 with postural and/or simple kinetic tremor (ETpt) and seven ET patients with additional clinical signs of cerebellar dysfunction (ETc) was compared to 25 healthy controls. In addition, 12 ET patients with thalamic DBS participated in the study. Balance control was assessed during gait and stance including tandem gait performed on a treadmill as well as static and dynamic posturography. Motor speech control was analyzed through syllable repetition tasks. Signs of balance impairment were found in early stages and advanced stages of ET. During locomotion, ET patients exhibited an increased number of missteps and shortened stride length with tandem gait. ETc patients and, to a lesser extent, ETpt patients had increased postural instability in dynamic posturography conditions that are sensitive to vestibular or vestibulocerebellar dysfunction. ETc but not ETpt patients exhibited significantly increased syllable durations. DBS had no discernable effect on speech performance or balance control. We conclude that the deficits in balance as well as the subclinical signs of dysarthria in a subset of patients confirm and extend previous findings that ET is associated with an impairment of the cerebellum.

Cognitive Impairment in Essential Tremor without Dementia

Background and purposeSeveral clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, there are no published data regarding detailed neuropsychological assessments of ET without dementia. We therefore conducted a case-control study of cognitive function in patients with ET.MethodsThe cohort for this study comprised 34 consecutive patients with ET without dementia and 33 age-matched controls, all of who completed a dementia-screening questionnaire and underwent a detailed neuropsychological investigation.ResultsSevere impairments were observed in most domains for the ET group compared to the controls, including attention, part of language function, verbal memory, and frontal executive functions.ConclusionsOur results support the finding that the subclinical cognitive deficits characterized by attention, verbal memory impairments, and executive dysfunction are a clinical feature of ET. In addition, our results also support the finding that age at examination and educational status are the most important risk factors associated with cognitive deficits in patients with ET.