Tremor Amplitude Research Articles

Subgroup analysis of PD tremor with loading: Action tremor as a combination of classical rest and physiological tremor

BackgroundIn Parkinson disease, tremor is a challenging symptom to manage, partly due to inadequate characterization. The current (classic) model of tremor is characterized by a resting tremor with a single strong peak in 3.5–6.5Hz range. The presence of action tremor, including postural, isometric, and kinetic tremors, has been disputed in the literature but not comprehensively evaluated. Analysis of hand tremor in action compared to rest, and possible subgrouping of tremor trends, may improve characterization. MethodsTwenty Parkinson patients and 14 controls were recruited. Tremor amplitude was measured across 9 sequentially loaded tasks, in off and on medication states. Tremor energy was separated into 2 frequency bands (B1, 3.5–6.5Hz; B2=physiological tremor, 7.5–16.5Hz) across all activity levels. Automatic classification was used for subgroup analysis. FindingsAutomatic classification yielded 3 predominant tremor trends (G1, G2, and G3). These were significantly different from each other and from controls. G1 demonstrated closest resemblance to classical Parkinsonian tremor, with highest tremor energy at rest and with overall dominance in B1 for lower loads. G2–G3 did not show tremor energy dominance in either band. Medication reduced tremor energy only for G1 in both B1 and B2. InterpretationSubgrouping the loading effect on tremor is a novel and viable method of rationalizing (non-classic) action tremor in Parkinson disease. Rest and action tremors appear not to be limited to 3.5–6.5Hz and may have considerable share of physiological tremor. Finding the contribution of each frequency band to total tremor energy and their trends with load may optimize therapy options.

Intention Tremor of the Legs in Essential Tremor: Prevalence and Clinical Correlates.

To estimate the prevalence and assess the clinical correlates of intention tremor in the legs in essential tremor (ET) patients. The cerebellar features of ET are of growing interest to clinical neurologists. Arm tremor has an intentional component in many ET patients. Intention tremor in the legs, however, has never been systematically evaluated. One-hundred-twenty-eight ET patients were enrolled in a clinical-epidemiological study at Columbia University. A videotaped neurological examination included 10 toe-to-target movements with each foot. Videotapes were independently reviewed by two movement disorder neurologists who noted the presence vs. absence of intentional leg tremor. Two patients underwent quantitative computerized tremor analysis to study the physiological characteristics of the tremor. Thirty-five patients (27.3%) had intentional leg tremor; in 21, tremor was unilateral and in 14 it was bilateral. The 35 patients with intentional leg tremor did not differ from the remaining 93 patients in their clinical characteristics. Analyses comparing the 14 patients with bilateral intentional leg tremor to the 93 patients with no intentional leg tremor showed trends towards longer disease duration and more severe intentional arm tremor in the former. Tremor analysis showed a 3-fold increase in average tremor amplitude from movement onset to the point just prior to touching the target. Our data suggest that intentional leg tremor, another cerebellar feature, is common in ET patients. The tremor may be associated with longer disease duration and more severe intentional arm tremor, but these preliminary trends need to be assessed in larger study samples.

The nature of tremor circuits in parkinsonian and essential tremor

Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient's own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson's disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50-77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34-74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson's disease, P=0.0078, subthalamic stimulation in Parkinson's disease, P=0.0312; ventrolateral thalamic stimulation in essential tremor, P=0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P=0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control.

Movement induced tremor in musicians and non-musicians reflects adaptive brain plasticity.

Evidence exists that motor dexterity is associated with a higher tremor amplitude of physiological tremor. Likewise, lower frequencies are associated with motor control. So far only case reports of a higher amplitude of physiological tremor in musicians exist. Moreover, no study has investigated lower frequencies during a finger movement task in musicians who can be regarded as a model of motor expertise. We developed a model and derived three hypotheses which we investigated in this study: (1) Tremor amplitude is higher in the range of physiological tremor and (2) higher for frequency ranges of dystonic tremor in musicians compared to non-musicians; (3) there is no difference in tremor amplitude at frequencies below 4 Hz. We measured tremor during a finger flexion-extension movement in 19 musicians (age 26.5 ± 8.2 years) and 24 age matched non-musicians (age 26.5 ± 8.7). By using empirical mode decomposition in combination with a Hilbert transform we obtained the instantaneous frequency and amplitude, allowing to compare tremor amplitudes throughout the movement at various frequency ranges. We found a significantly higher tremor amplitude in musicians for physiological tremor and a tendency toward a higher amplitude during most of the movement in the frequency range of 4–8 Hz, which, however, was not significant. No difference was found in the frequency range below 4 Hz for the flexion and for almost the entire extension movement. Our results corroborate findings that the 8–12 Hz oscillatory activity plays a role in motor dexterity. However, our results do not allow for the conclusion that tremor at the frequency range of 4–8 Hz is related to either plasticity induced changes that are beneficial for motor skill development nor to maladaptive changes as, e.g., focal dystonia.

Upper limb function is normal in patients with restless legs syndrome (Willis-Ekbom Disease)

ObjectiveRestless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED on motor function. The current study investigated upper limb function in RLS/WED patients. We hypothesised that RLS/WED patients exhibit subtle changes in tremor amplitude but normal dexterity and movement speed and rhythmicity compared to healthy controls. MethodsRLS/WED patients (n=17, 59±7years) with moderate disease and healthy controls (n=17, 58±6years) completed screening tests and five tasks including object manipulation, maximal pinch grip, flexion and extension of the index finger (tremor assessment), maximal finger tapping (movement speed and rhythmicity assessment), and the grooved pegboard test. Force, acceleration, and/or first dorsal interosseus EMG were recorded during four of the tasks. ResultsTask performance did not differ between groups. Learning was evident on tasks with repeated trials and the magnitude of learning did not differ between groups. ConclusionsHand function, tremor, and task learning were unaffected in RLS/WED patients. Patients manipulated objects in a normal manner and exhibited normal movement speed, rhythmicity, and tremor. SignificanceFurther research is needed to assess other types of movement in RLS/WED patients to gain insight into the motor circuitry affected and the underlying pathophysiology.

Effective Therapy for Essential Tremor and Rare Tremors

Essential tremor, the most common movement disorder, occurs in =3.9% of the population, with tremor amplitude and associated disability increasing with age [Elble RJ. Neurology 2000]. Treatment is important because tremor can cause disability or social embarrassment, and many patients change jobs or retire as a result of essential tremor. This article discusses the medical therapy of essential tremor, the use of invasive and experimental therapies for the treatment of essential tremor, and management of rare tremors.

Remotely triggered nonvolcanic tremor in Sumbawa, Indonesia

AbstractWe present, for the first time, evidence for triggered tremor beneath the island of Sumbawa, Indonesia. We show triggered tremor in response to three teleseismic earthquakes: the Mw9.0 2011 Tohoku earthquake and two oceanic strike‐slip earthquakes (Mw 8.6 and Mw8.2) offshore of Sumatra in 2012. We constrain an apparent triggering threshold of 1 mm/s ground velocity that corresponds to about 8 kPa dynamic stress. Peak tremor amplitudes of about 180 nm/s are observed, and scale with the ground velocity induced by the remote earthquakes. Triggered tremor responds to 45–65 s period surface waves and predominantly correlates with Rayleigh waves, even though the 2012 oceanic events have stronger Love wave amplitudes. We could not locate the tremor because of minimal station coverage, but data indicate several potential source volumes including the Flores Thrust, the Java subduction zone, or Tambora volcano.

Analysis of dystonic tremor in musicians using empirical mode decomposition

ObjectiveTest the hypotheses that tremor amplitude in musicians with task-specific dystonia is higher at the affected finger (dystonic tremor, DT) or the adjacent finger (tremor associated with dystonia, TAD) than (1) in matched fingers of healthy musicians and non-musicians and (2) within patients in the unaffected and non-adjacent fingers of the affected side within patients. MethodsWe measured 21 patients, 21 healthy musicians and 24 non-musicians. Participants exerted a flexion–extension movement. Instantaneous frequency and amplitude values were obtained with empirical mode decomposition and a Hilbert-transform, allowing to compare tremor amplitudes throughout the movement at various frequency ranges. ResultsWe did not find a significant difference in tremor amplitude between patients and controls for either DT or TAD. Neither differed tremor amplitude in the within-patient comparisons. ConclusionBoth hypotheses were rejected and apparently neither DT nor TAD occur in musician’s dystonia of the fingers. SignificanceThis is the first study assessing DT and TAD in musician’s dystonia. Our finding suggests that even though MD is an excellent model for malplasticity due to excessive practice, it does not seem to provide a good model for DT. Rather it seems that musician’s dystonia may manifest itself either as dystonic cramping without tremor or as task-specific tremor without overt dystonic cramping.

Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor

Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design. Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed. Th-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain. Dystonic head tremor and dystonia can be improved with Th-DBS.

Decrypting geophysical signals at Stromboli Volcano (Italy): Integration of seismic and Ground-Based InSAR displacement data.

We present the integration of seismic and Ground-Based Interferometric Synthetic Aperture Radar system (GBInSAR) displacement data at Stromboli Volcano. Ground deformation in the area of summit vents is positively correlated with both seismic tremor amplitude and cumulative amplitudes of very long period (VLP) signals associated with Strombolian explosions. Changes in VLP amplitudes precede by a few days the variations in ground deformation and seismic tremor. We propose a model where the arrival of fresh, gas-rich magma from depth enhances gas slug formation, promoting convection and gas transfer throughout the conduit system. At the shallowest portion of the conduit, an increase in volatile content causes a density decrease, expansion of the magmatic column and augmented degassing activity, which respectively induce inflation of the conduit, and increased tremor amplitudes. The temporal delay between increase of VLP and tremor amplitudes/conduit inflation can be interpreted in terms of the different timescales characterizing bulk gas transfer versus slug formation and ascent.

Gas burst vs. gas-rich magma recharge: A multidisciplinary study to reveal factors controlling triggering of the recent paroxysmal eruptions at Mt. Etna

Since January 2011, Mt. Etna volcano has been affected by more than forty paroxysmal eruptions at the summit (New South East Crater; NSEC). On the basis of their very variable duration, seven eruptions have been selected among the twenty-five of 2011–2012 in order to decipher potential differences in their triggering mechanism. Paroxysms have been investigated through a multidisciplinary approach that integrates data from volcanic tremor and petrology (textures and micro-analysis on plagioclase crystals). Our results lead to the conclusion that close relationships exist between the duration of the eruptions and the temporal evolution of the volcanic tremor amplitude, especially during the Strombolian phase preceding the paroxysmal activity. In this regard, we distinguished: 1) paroxysms preceded by long-lasting initial Strombolian phases, characterized by low rate of volcanic tremor amplitude increase; and 2) eruptions preceded by short initial Strombolian phases, showing high rate of volcanic tremor amplitude increase. Based on the pattern of volcanic tremor amplitude increase, the former mainly showed a ramp-shaped morphology, while the latter a bell-shaped trend. Location of the volcanic tremor centroid during the quiescent intervals between the paroxysmal eruptions has highlighted the presence of a magmatic volume at 1–2kma.s.l. beneath the North East Crater (NEC). During the syn-eruptive Strombolian and lava fountaining phases, the centroid of volcanic tremor migrates below the NSEC. This leads to the consideration that the magma batch residing beneath NEC played an important role in the volcanic activity at NSEC during the considered period. Also the textures and compositional zoning (anorthite and iron variations) in selected plagioclase crystals of the analyzed lavas suggest relations between duration of the paroxysms and dynamics of pre-eruptive magmatic processes at depth. Particularly, two mechanisms have been accounted for triggering of eruptions at the NSEC on the basis of the concordant or discordant behavior of anorthite and iron in plagioclase coupled with disequilibrium textures at the rim. Concordant anorthite and iron increases in plagioclase crystals with sieve-textured rims indicate recharge by more mafic, gas-rich magma. This textural-compositional behavior has been related to long-lasting eruptions, whose volcanic tremor amplitude evolution produced ramp-shaped increase of the volcanic tremor amplitude before the paroxysmal phase. On the contrary, crystals with sieve-textures at the rim, characterized by increasing iron at rather constant or decreasing anorthite, suggest the prominent role of gas injections into the residing system. In this instance, the compositional behavior has been linked with short-lasting eruptions, whose volcanic tremor amplitude evolution led to a sudden increase of the seismic amplitude before the climax of the eruption. Thus, our work put forward the idea that the evolution and duration of the Strombolian phase preceding the paroxysmal eruptions of 2011–2012 at Mt. Etna are strongly controlled by the eruption triggering mechanism, which can be either gas burst or gas-rich magma recharge.

Drowsiness and motor responses to consecutive daily doses of promethazine and loratadine

ObjectivesLimited information is available regarding sedation and motor function following repeat dosing of antihistamines. This study examined how promethazine and loratadine affect day-time drowsiness, the commencement of voluntary movement, and involuntary movement when administered on consecutive days. MethodsTen healthy young subjects (24±5years) were recruited into a double-blind, placebo-controlled, three-way crossover study. Subjects ingested either promethazine, loratadine or a placebo, and ingested the same drug 24h later. Measures of drowsiness, simple reaction time (SRT), choice reaction time (CRT), and postural tremor were obtained pre-ingestion, 1h post-ingestion and 2h post-ingestion on each day. ResultsConsecutive daily doses of promethazine and loratadine affected SRT and CRT, respectively, whereby reaction time deficits were less pronounced following the repeat dose. A reduced tremor response was also observed following consecutive daily dosing of promethazine, in contrast to loratadine which caused an increase in tremor amplitude with the consecutive daily dose. ConclusionsReaction time and tremor responses differed following the single dose compared to consecutive doses. SignificanceSufferers of allergic rhinitis often require antihistamine dosing regimens that continue over multiple days. Future studies will benefit from examining drowsiness and movement responses following single doses as well as consecutive dosing.

Task‐related changes in sensorimotor integration influence the common synaptic input to motor neurones

The purpose of this investigation was to understand how visual information, when used to guide muscle activity, influences the frequency content of the neural drive to muscles and the gain of afferent feedback. Subjects maintained static, isometric contractions of the tibialis anterior muscle by matching a visual display of their ankle dorsiflexion force to a target set at 10% of their maximum voluntary contraction level. Two visual feedback conditions were studied. The first was a high-sensitivity feedback, in which small changes in force were of large on-screen visual magnitude. The second was a low-sensitivity feedback, in which the on-screen scaling of feedback was reduced by a factor of 10, making small force fluctuations difficult to perceive. Force tremor and Hoffmann reflex (H-reflex) amplitudes were compared between the two conditions, as well as coherence among single motor unit spike trains derived from high-density EMG recordings. The high-sensitivity feedback condition was associated with lower error, larger force tremor (4-12 Hz) and larger H-reflex amplitudes relative to the low-sensitivity feedback condition. In addition, the use of high-sensitivity feedback was associated with lower 1-5 Hz coherence among pairs of motor units, but larger coherence at high frequencies (6-12, approx. 20, >30 Hz). Alteration of visual feedback influences nearly the entire frequency spectrum of common input to motor neurones, as well the gain of afferent feedback. We speculate that task-related modulation of afferent feedback could be the origin of many of the observed changes in the neural drive to muscles.

Optic Ataxia: From Balint’s Syndrome to the Parietal Reach Region

Optic ataxia is a high-order deficit in reaching to visual goals that occurs with posterior parietal cortex (PPC) lesions. It is a component of Balint's syndrome that also includes attentional and gaze disorders. Aspects of optic ataxia are misreaching in the contralesional visual field, difficulty preshaping the hand for grasping, and an inability to correct reaches online. Recent research in nonhuman primates (NHPs) suggests that many aspects of Balint's syndrome and optic ataxia are a result of damage to specific functional modules for reaching, saccades, grasp, attention, and state estimation. The deficits from large lesions in humans are probably composite effects from damage to combinations of these functional modules. Interactions between these modules, either within posterior parietal cortex or downstream within frontal cortex, may account for more complex behaviors such as hand-eye coordination and reach-to-grasp.

PageRank for Earthquakes

Using Hi‐Net data in southwest Japan, Obara (2002) discovered a new type of seismic source that he called nonvolcanic tremor due to its similarity to volcanic tremor, but distinct origin. Tremor is characterized by weak signals, typically of deep (>30 km) origin, that are most prominent in the 1–10 Hz frequency band. At about the same time, slow‐slip events and tectonic tremor were found to be strongly correlated indicating that tremor accompanied these events (Obara, 2002; Rogers and Dragert, 2003). Tectonic tremor is challenging to locate because it is an extended and persistent signal, and lacks the clear P ‐ and S ‐wave arrivals that are typical of earthquakes. Despite this, there is clear modulation of tremor amplitudes that can be tracked between stations and used to locate the tremor source. Several envelope techniques (Obara, 2002; McCausland et al. , 2005; Wech and Creager, 2008; Aguiar et al. , 2009) were developed for this purpose. Low‐frequency earthquakes (LFEs) were discovered by Katsumata and Kamaya (2003) and have since proven to be critical to understanding the genesis of tectonic tremor. Shelly et al. (2006) showed that LFEs correlate strongly with times of tremor and that they occur on the plate interface. Shelly et al. (2007a) showed that tremor consists of swarms of LFEs, and by inference occurred on the plate interface as well. Follow‐up work (Ide, Shelly, Beroza, 2007) demonstrated that LFEs per tremor occurred as shear slip and hence were part of a family of slow earthquakes (Ide, Beroza, et al. , 2007). Initially, LFEs were found through visual inspection by enterprising network analysts in Japan (Beroza and Ide, 2011). LFEs have been identified as periods of high‐amplitude arrivals by the same visual inspection technique (Shelly, 2009). Because LFEs have proven so useful for studying tremor, other methods have been developed to …

Different phase delays of peripheral input to primate motor cortex and spinal cord promote cancellation at physiological tremor frequencies

Neurons in the spinal cord and motor cortex (M1) are partially phase-locked to cycles of physiological tremor, but with opposite phases. Convergence of spinal and cortical activity onto motoneurons may thus produce phase cancellation and a reduction in tremor amplitude. The mechanisms underlying this phase difference are unknown. We investigated coherence between spinal and M1 activity with sensory input. In two anesthetized monkeys, we electrically stimulated the medial, ulnar, deep radial, and superficial radial nerves; stimuli were timed as independent Poisson processes (rate 10 Hz). Single units were recorded from M1 (147 cells) or cervical spinal cord (61 cells). Ninety M1 cells were antidromically identified as pyramidal tract neurons (PTNs); M1 neurons were additionally classified according to M1 subdivision (rostral/caudal, M1r/c). Spike-stimulus coherence analysis revealed significant coupling over a broad range of frequencies, with the strongest coherence at <50 Hz. Delays implied by the slope of the coherence phase-frequency relationship were greater than the response onset latency, reflecting the importance of late response components for the transmission of oscillatory inputs. The spike-stimulus coherence phase over the 6–13 Hz physiological tremor band differed significantly between M1 and spinal cells (phase differences relative to the cord of 2.72 ± 0.29 and 1.72 ± 0.37 radians for PTNs from M1c and M1r, respectively). We conclude that different phases of the response to peripheral input could partially underlie antiphase M1 and spinal cord activity during motor behavior. The coordinated action of spinal and cortical feedback will act to reduce tremulous oscillations, possibly improving the overall stability and precision of motor control.

On the Use of Fixed‐Intensity Functional Electrical Stimulation for Attenuating Essential Tremor

A great proportion of essential tremor (ET) patients have not so far been able to receive functional benefits from traditional therapies. In this regard, the use of functional electrical stimulation (FES) has been proposed for reducing tremor amplitude by stimulating muscles in antiphase with respect to the trembling motion. Although some studies have reported success in terms of tremor attenuation, drawbacks still exist that prevent the method from being used in real-life applications. In this article, we explore an alternative approach: a strategy based on the hypothesis that FES-induced constant muscle contraction may provide functional benefit for tremor patients. To evaluate the proposed strategy, experiments were conducted in which stimulation was intermittently turned on and off while the subjects performed a static motor task. The results of the proposed experimental protocol indicate that tremor attenuation using this strategy is feasible, as consistent tremor attenuation levels were obtained in eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous for all successful trials, indicating that prior training with FES may improve the overall response. Furthermore, although simpler assistive devices may potentially be designed based on this technique, some experimental difficulties still exist, which suggests that further studies are necessary.

Treatment of Essential Tremor with Long-Chain Alcohols: Still Experimental or Ready for Prime Time?

<strong>Aim:</strong> To review current literature on long-chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET). <strong>Background:</strong> Currently available and recommended pharmacotherapies for ET are often limited by suboptimal treatment effects, frequent adverse effects, and drug interactions. While ethanol is reported to profoundly decrease tremor severity in the majority of patients with ET, preclinical experience suggests that longchain alcohols such as 1-octanol might lead to a comparable tremor reduction without ethanol’s typical side effects of sedation and intoxication. Here, we review the literature on the first clinical trials on 1-octanol and its metabolite octanoic acid (OA) for the treatment of ET. <strong>Methods:</strong> The literature on preclinical and clinical trials on long-chain alcohols as well as OA was reviewed and summarized, and an outlook given on next phases of development. <strong>Discussion:</strong> 1-octanol was demonstrated to be safe and effective in a double-blind, placebo-controlled low-dose trial, and open-label data showed excellent tolerability and dose-dependent efficacy up to 128 mg/kg. Despite 1-octanol’s efficacy, its future viability as an effective therapy is limited by its pharmacological properties that require large volumes to be orally administered. Pharmacokinetic data indicate that OA is the active metabolite of 1-octanol. Preclinical efficacy data for OA are positive, and human pilot data demonstrated excellent safety as well as efficacy in secondary outcome measures of tremor amplitudes. OA also has more favorable pharmacological properties for drug delivery; hence, OA may be worth developing as a pharmaceutical.

Treatment of essential tremor with long-chain alcohols: still experimental or ready for prime time?

AimTo review current literature on long-chain alcohols and their derivatives as novel pharmacotherapy for the treatment of essential tremor (ET).BackgroundCurrently available and recommended pharmacotherapies for ET are often limited by suboptimal treatment effects, frequent adverse effects, and drug interactions. While ethanol is reported to profoundly decrease tremor severity in the majority of patients with ET, preclinical experience suggests that long-chain alcohols such as 1-octanol might lead to a comparable tremor reduction without ethanol’s typical side effects of sedation and intoxication. Here, we review the literature on the first clinical trials on 1-octanol and its metabolite octanoic acid (OA) for the treatment of ET.MethodsThe literature on preclinical and clinical trials on long-chain alcohols as well as OA was reviewed and summarized, and an outlook given on next phases of development.Discussion1-octanol was demonstrated to be safe and effective in a double-blind, placebo-controlled low-dose trial, and open-label data showed excellent tolerability and dose-dependent efficacy up to 128 mg/kg. Despite 1-octanol’s efficacy, its future viability as an effective therapy is limited by its pharmacological properties that require large volumes to be orally administered. Pharmacokinetic data indicate that OA is the active metabolite of 1-octanol. Preclinical efficacy data for OA are positive, and human pilot data demonstrated excellent safety as well as efficacy in secondary outcome measures of tremor amplitudes. OA also has more favorable pharmacological properties for drug delivery; hence, OA may be worth developing as a pharmaceutical.

Load-induced changes in older individual's hand-finger tremor are ameliorated with targeting

The purpose of this study was to investigate hand–finger tremor dynamics when a load was applied to the finger in a group of healthy older adults. Moreover, we sought to determine if projecting a representation of the subject's finger tremor on a target was capable of overcoming the effects of loading so that hand–finger interactions returned to a state that was similar to normal tremor. Eight healthy older males (67±1year) performed a postural pointing task, where tremor was assessed using lightweight accelerometers attached to the hand and finger. Tremor was then assessed when a laser pointer was attached to the finger and switched off (the load), and then with the laser pointer attached and switched on pointing at targets of 40mm and 20mm in diameter. The main findings of this study were that 1) loading the finger resulted in a reduction in finger tremor amplitude and increased finger tremor regularity, but no change in hand tremor, 2) loading caused increased hand–finger 8–12Hz cross wavelet coherence and phase synchrony, and 3) pointing at different targets while the finger was loaded resulted in an increase in finger tremor amplitude, and changes in inter-segmental coupling to the extent that hand–finger dynamics reflected normal unloaded conditions. Overall, these results illustrate that the damping effects of limb loading can be offset, in part, by altering the accuracy demands of the task to make the pointing action more challenging.