Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study.

BACKGROUND AND OBJECTIVES: Ethanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self-reported responder status to ethanol, and prior ethanol exposure. METHODS: This was a prospective, open-label, single-dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration. RESULTS: In total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found. DISCUSSION: A high percentage of patients actually respond to acute ethanol. However, their self-reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

Essential Tremor accentuates the pattern of tremor-band coherence between upper-limb muscles.

Although Essential Tremor is one of the most common movement disorders, current treatment options are relatively limited. Peripheral tremor suppression methods have shown potential, but we do not currently know which muscles are most responsible for patients' tremor, making it difficult to optimize suppression methods. The purpose of this study was to quantify the relationships between the tremorogenic activity in muscles throughout the upper limb. Muscle activity was recorded from the 15 major superficial upper-limb muscles in 24 subjects with Essential Tremor while they held various postures or made upper-limb movements. We calculated the coherence in the tremor band (4-12 Hz) between the activity of all muscle pairs and the time-varying phase difference between sufficiently coherent muscle pairs. Overall, the observed pattern somewhat mirrored functional relationships: agonistic muscle pairs were most coherent and in phase, whereas antagonist and unrelated muscle pairs exhibited less coherence and were either consistently in phase, consistently antiphase, consistently out of phase (unrelated pairs only), or else inconsistent. Patients exhibited significantly more coherence than control subjects (p<0.001) in the vast majority of muscle pairs (95 out of 105). Furthermore, differences between patients and controls were most pronounced among agonists; thus, the coherence pattern existing in control subjects was accentuated in patients with ET. We conclude that tremor-band activity is broadly distributed among the muscles of the upper limb, challenging efforts to determine which muscles are most responsible for a patient's tremor.

Distribution of tremorogenic activity among the major superficial muscles of the upper limb in persons with Essential tremor.

OBJECTIVE: Peripheral tremor suppression has the potential to reduce tremor, but we do not currently know where best to intervene. The purpose of this study was to characterize the distribution of tremorogenic activity among upper-limb muscles. METHODS: Surface electromyography was recorded from the 15 major superficial muscles of the upper limb while 25 patients with Essential Tremor performed postural and kinetic tasks. We defined tremorogenic activity as power in the tremor band (4-8 Hz) and determined the distribution of this power among muscles. RESULTS: The distribution varied considerably between patients (mean r = 0.58), but on average, the greatest power was found in the anterior deltoid and extensor carpi ulnaris muscles. Other muscles with high power included the extensor carpi radialis, pectoralis major, lateral deltoid, and brachialis muscles. This distribution was similar (mean r ≥ 0.88) for postural and kinetic tremor, various limb configurations, repetitions, and patient characteristics (sex, tremor severity, age of onset, and duration). CONCLUSIONS: We identified a rough pattern in which muscles opposing gravity appeared to have the highest tremor-band power; we hypothesize that the distribution of tremorogenic muscle activity depends in part on the distribution of voluntary activity required by the task. SIGNIFICANCE: Understanding which muscles exhibit the most tremorogenic activity is one of the steps in the pursuit of optimizing peripheral tremor suppression.

Distribution of tremor among the major degrees of freedom of the upper limb in subjects with Essential Tremor.

OBJECTIVE: Although Essential Tremor is one of the most common movement disorders, we do not currently know which muscles are most responsible for tremor. Determining this requires multiple steps, one of which is characterizing the distribution of tremor among the degrees of freedom (DOF) of the upper limb. METHODS: Upper-limb motion was recorded while 22 subjects with ET performed postural and kinetic tasks involving a variety of limb configurations. We calculated the mean distribution of tremor among the seven DOF from the shoulder to the wrist, as well as the effect of limb configuration, repetition, and subject characteristics (sex, tremor onset, duration, and severity) on the distribution. RESULTS: On average, kinetic tremor was greatest in forearm pronation-supination and wrist flexion-extension, intermediate in shoulder internal-external rotation and wrist radial-ulnar deviation and then shoulder flexion-extension and elbow flexion-extension, and least in shoulder abduction-adduction. The average distribution of postural tremor was similar except for forearm pronation-supination, which played a smaller role than in kinetic tremor. Limb configuration and subject characteristics did significantly affect tremor, but practically only in forearm pronation-supination and wrist flexion-extension. There were no significant differences between repetitions, indicating that the distribution was consistent over the duration of the experiment. CONCLUSIONS: This paper presents a thorough characterization of tremor distribution from the shoulder to the wrist. SIGNIFICANCE: Understanding which DOF exhibit the most tremor may lead to more targeted peripheral tremor suppression.

A Voxel-Based Magnetic Resonance Imaging Morphometric Study of Cerebral and Cerebellar Gray Matter in Patients Under 65 Years with Essential Tremor.

BACKGROUND The aim of this study was to compare the morphological changes in cerebral and cerebellar gray matter in patients with essential tremor under 60-years-of-age, with age-matched and gender-matched normal healthy volunteer control subjects, using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) analysis. MATERIAL AND METHODS A retrospective, controlled, comparative clinical study included 17 patients with essential tremor, <60 years-of-age, and 17 age-matched and gender-matched healthy volunteer control subjects, recruited between June 2010-July 2012. MRI and VBM analysis were used to compare cerebral and cerebellar gray matter density between groups. The Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale was used to assess tremor severity in the patient group. Clinical and demographic characteristics were recorded for all study participants. RESULTS MRI and VBM analysis showed significant bilateral expansion of the cerebellum, occipital fusiform cortices, right inferior temporal gyrus, and precentral lobes in patients with essential tremor (P<0.005); reduction in gray matter was found in the left parietal lobe. The region of interest (ROI) analysis showed volume enlargement in the thalamus, midbrain, and the precuneus (P<0.005). No significant correlation between changes in gray matter and changes in clinical variables, including age, gender, tremor duration, the activity of daily living (ADL) scale, the mini-mental state examination (MMSE) scale, family history, and tremor severity were found. CONCLUSIONS Predominantly cerebellar gray matter expansion in patients less than 60 years-of-age with essential tremor might be the result of compensation for the decline in cerebellar function.

The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor.

OBJECTIVE: To investigate the effect of octanoic acid (OA) on the peripheral component of tremor, as well as OA's differential effects on the central and peripheral tremor component in essential tremor (ET) patients. METHODS: We analyzed postural tremor accelerometry data from a double-blind placebo-controlled cross-over study evaluating the effect of 4 mg/kg OA in ET. The weighted condition was used to identify tremor power for both the central and peripheral tremor components. Exploratory non-parametric statistical analyses were used to describe the relation between the central and peripheral component of tremor power. RESULTS: A peripheral tremor component was identified in 4 out of 18 subjects. Tremor power was reduced after OA administration in both the central and the peripheral tremor component. There was a positive correlation of tremor power between the central and peripheral component, both after placebo and OA. CONCLUSIONS: When present, the peripheral component was closely related to the central tremor component. We hypothesize that the magnitude of the peripheral mechanical component of tremor is determined by that of the central component. SIGNIFICANCE: Both central and peripheral component of tremor are reduced after OA, with the central component providing the energy driving the peripheral component.

Infant sleep and feeding patterns are associated with maternal sleep, stress, and depressed mood in women with a history of major depressive disorder (MDD).

Our goal was to examine associations of infant sleep and feeding patterns with maternal sleep and mood among women at risk for postpartum depression. Participants were 30 women (age ± SD = 28.3 ± 5.1 years) with a history of MDD (but not in a mood episode at enrollment) who completed daily sleep diaries, wore wrist actigraphs to estimate sleep, and had their mood assessed with the Hamilton Depression Rating Scale (HAM-D-17) during four separate weeks of the perinatal period (33 weeks pregnancy and weeks 2, 6, and 16 postpartum). They logged their infants' sleep and feeding behaviors daily and reported postnatal stress on the Childcare Stress Inventory (CSI) at week 16. Mothers' actigraphically estimated sleep showed associations with infant sleep and feeding patterns only at postpartum week 2. Shorter duration of the longest infant-sleep bout was associated with shorter maternal sleep duration (p = .02) and lower sleep efficiency (p = .04), and maternal sleep efficiency was negatively associated with the number of infant-sleep bouts (p = .008) and duration of infant feeding (p = .008). Neither infant sleep nor feeding was associated with maternal sleep at 6 or 16 weeks, but more disturbed infant sleep and more frequent feeding at 6 weeks were associated with higher HAM-D scores at 6 and 16 weeks and higher CSI scores. Sleep in the mother-infant dyad is most tightly linked in the early postpartum weeks, but mothers continue to experience disturbed sleep and infant sleep and feeding behaviors continue to be associated with mothers' depressive symptoms and stress ratings as long as 16 weeks postpartum. These data imply that interventions designed to improve maternal sleep and postpartum mood should include both mothers and infants because improving infant sleep alone is not likely to improve maternal sleep, and poor infant sleep is linked to postpartum depression and stress.