Reduction In Tremor Amplitude Research Articles

Estimating Change in Tremor Amplitude Using Clinical Ratings: Recommendations for Clinical Trials.

Tremor rating scales are the standard method for assessing tremor severity and clinical change due to treatment or disease progression. However, ratings and their changes are difficult to interpret without knowing the relationship between ratings and tremor amplitude (displacement or angular rotation), and the computation of percentage change in ratings relative to baseline is misleading because of the ordinal nature of these scales. For example, a reduction in tremor from rating 2 to rating 1 (0–4 scale) should not be interpreted as a 50% reduction in tremor amplitude, nor should a reduction in rating 4 to rating 3 be interpreted as a 25% reduction in tremor. Studies from several laboratories have found a logarithmic relationship between tremor ratings R and tremor amplitude T, measured with a motion transducer: logT = α·R + β, where α ≈ 0.5, β ≈ –2, and log is base 10. This relationship is consistent with the Weber–Fechner law of psychophysics, and from this equation, the fractional change in tremor amplitude for a given change in clinical ratings is derived: (Tf−Ti)/Ti=10α(Rf−(Ri)−1, where the subscripts i and f refer to the initial and final values. For a 0–4 scale and α = 0.5, a 1‐point reduction in tremor ratings is roughly a 68% reduction in tremor amplitude, regardless of the baseline tremor rating (e.g., 2 or 4). Similarly, a 2‐point reduction is roughly a 90% reduction in tremor amplitude. These Weber–Fechner equations should be used in clinical trials for computing and interpreting change in tremor, assessed with clinical ratings.

The placebo effect on resting tremor in Parkinson's disease: an electrophysiological study

IntroductionThe aim of our study was to investigate the effect of apomorphine and placebo on resting tremor in tremor-dominant Parkinson's disease (tPD) patients. MethodsFifteen tPD patients were enrolled. Each patient underwent two treatments on two consecutive days: on day one the patients received a subcutaneous injection of placebo, while on day two they received apomorphine. On each day, the patients underwent three electrophysiological recording sessions: T0, T1, and T2: before, 30 min, and 60 min after the treatment respectively. Electrophysiological changes in tremor amplitude were evaluated using a triaxial accelerometer. ResultsPlacebo was effective in improving resting tremor in all tPD patients (p = 0.009) at T1, but not at T2. Eight out of 15 tPD patients (53.3%) responded to placebo with an at least 70% reduction in tremor amplitude compared to the basal condition (responders). By contrast, seven out of 15 tPD patients (46.7%) did not show any variation in tremor amplitude after placebo administration (non-responders). Apomorphine induced a marked reduction in tremor amplitude at 30 min and 60 min in all investigated tPD patients. Of note, the decrease in tremor amplitude in placebo responders was similar to that achieved with dopaminergic stimulation induced by apomorphine. ConclusionsOur study demonstrates that placebo was very effective in reducing resting tremor in about half of patients with tPD. The decrease in tremor amplitude in placebo responders was similar to that induced by apomorphine. The cerebral mechanisms underlying the placebo effect on resting tremor need further investigations.

Upper Limb Intention Tremor in Multiple Sclerosis: An Evidence-Based Review of Assessment and Treatment.

To present the current knowledge on the characteristics, assessment, and treatment of upper limb intention tremor to inform and improve future intervention studies in patients with multiple sclerosis (MS), we conducted a literature review for articles on upper limb intention tremor in patients with MS. Two reviewers conducted searches in PubMed, Web of Science, and MEDLINE (Ovid). Relevant articles, sorted on inclusion criteria, were examined for descriptions and assessments of upper limb intention tremor, and intervention studies were evaluated based on treatment type. Eight descriptive studies were found reporting on the incidence and severity of tremor, impairments, and lesion load. Ten studies focused on measurement of tremor using various assessments. Intervention studies included eight articles using a diverse set of noninvasive techniques mainly showing transient reduction in tremor amplitude and temporary increase in function. Eighteen studies on pharmacologic interventions were found, with most displaying positive outcomes and mediation of tremor; others showed little to no benefit. Surgical interventions included 17 studies on thalamotomy and 20 on deep brain stimulation. Most studies showed tremor improvement after surgery; however, most sample sizes were small, and interventions were highly invasive, with potential adverse effects resulting from surgery. The literature on upper limb intention tremor in MS is relatively sparse. More studies are required to determine mechanism of action and to provide more suitable and sustainable interventions to decrease upper limb intention tremor and improve quality of life of individuals with MS.

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar – but not cerebral – coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.

Structural control and biomechanical tremor suppression: Comparison between different types of passive absorber

Active and semi-active control devices can be used as advanced and accurate controllers to reduce the undesired vibration of a structure. However, some of these controllers may have a complex design, especially for systems excited with multi-degree-of-freedom frequencies, which demand the use of high anti-fatigue material properties, and others that may require a large power source. So, improvements in the design of passive controllers are of high interest for researchers. These controllers have a very simple design and aim to counteract vibration with no power requirements. In this paper, six different passive controllers were designed to analyze and compare their performance. The performance is considered in terms of the percentage of reduction in the primary system’s displacement amplitude and the bandwidth of each designed passive controller. The system of interest is taken as the three-degree-of-freedom dynamic hand system reflecting the behavior of Parkinsonian patients. Four joint muscles operating at two resonance harmonic excitation frequencies are considered to produce movements. Each controller was attached to the forearm of the hand set in the horizontal plane to analyze their capability in reducing the rest tremor (3–7 Hz) at the proximal joint. The dual series elastic–viscous absorber is shown to be a very effective controller. It is formed from a series connection between an elastic absorber (mass–spring) and a viscous absorber (mass–dashpot). It causes about 80% reduction in tremor amplitude with 4 Hz wide frequency band at the shoulder, elbow and wrist joints. This range of operational frequency is close to that of healthy cases, 4.5 Hz.

Muscle-Cooling Intervention to Reduce Fatigue and Fatigue-Induced Tremor in Novice and Experienced Surgeons: A Preliminary Investigation.

A localized, intermittent muscle-cooling protocol was implemented to determine cooling garment efficacy in reducing upper extremity muscular fatigue and tremor in novice ( n = 10) and experienced surgeons ( n = 9). Subjects wore a muscle-cooling garment while performing multiple trials of a forearm exercise and paired suturing task to induce muscular fatigue and exercise-induced tremor. A reduction in tremor amplitude and an extension in time to fatigue were expected with muscle cooling as compared with control trials. Each subject completed an intervention session (5°C cooling condition) and a control session (32°C or thermal neutral condition). A paired samples t test indicated that tremor amplitude was significantly reduced ( t [8] = 1.89458; p < 0.05) in experienced surgeons in two dimensions (up and down, and back and forth). Tremor amplitude was reduced in novice surgeons but the effect was not significant. Time to fatigue and suture time improved in both cohorts with muscle cooling, but the effect did not reach significance. Results from the pilot work suggest muscle cooling as an intervention for reduction of fatigue and tremor is very promising, warranting further investigation. Surgical specialties that require prolonged procedures might benefit more from this intervention.

Adaptive Suppression of Severe Pathological Tremor by Torque Estimation Method

Tremor is a rhythmical and involuntary oscillatory movement of a body part. In addition to social embarrassment, tremor can be debilitating for daily activities. Recently, wearable active exoskeletons emerged as a noninvasive tremor suppression alternative to medication or surgery. The challenge in musculoskeletal tremor suppression is identifying and attenuating the tremor motion without adding resistance to the patient's intentional motion. In this research, an adaptive tremor suppression algorithm was designed to estimate the tremor fundamental frequency and calculate the proper suppressive force to be applied by the orthosis to the patient's arm. Stability of the closed-loop system and robustness against the parametric uncertainties were analyzed. An experimental setup was designed and developed to emulate the dynamics of a human wrist with intentional and tremor motion. A pneumatic cylinder and a sliding mode integral controller was used to apply orthotic suppressive force. The algorithm was implemented with an NI cRIO real-time controller and tested using clinical data from ten patients with severe pathological tremor. Experimental results showed tracking of the tremor frequency with less than 3-s response time, and an average 34.5 dB (98.1%) and 11.8 dB (74.3%) reduction of tremor amplitude at the fundamental and second-harmonic frequencies, respectively. The average resistance force to the intentional motion was 0.7 N and the average position error was 2.08% (0.18 dB). The results were compared with passive tremor suppression using a tunable magnetorheological damper.

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.

Continuous theta-burst stimulation of the primary motor cortex in essential tremor

ObjectiveWe investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation. Methods10 Patients with ET and 10 healthy controls underwent transcranial continuous theta-burst stimulation (cTBS) of the left primary motor hand area at 80% (real cTBS) and 30% (control cTBS) of active motor threshold in two separate sessions at least one week apart. Postural tremor was rated clinically and measured accelerometrically before and after cTBS. Corticospinal excitability was assessed by recording the motor evoked potentials (MEP) from the first dorsal interosseous muscle. ResultsReal cTBS but not control cTBS reduced the tremor total power assessed with accelerometry. This beneficial effect was subclinical as there were no significant changes in clinical tremor rating after real cTBS. Relative to control cTBS, real cTBS reduced corticospinal excitability in the stimulated primary motor cortex only in healthy controls but not in ET patients. ConclusionReal cTBS has a beneficial effect on ET. Since cTBS did not induce a parallel reduction in corticospinal excitability, this effect was not mediated by a suppression of the corticospinal motor output. Significance“Inhibitory” cTBS of M1 leads to a consistent but subclinical reduction in tremor amplitude.

Tremor amplitude and tremor frequency variability in Parkinson’s disease is dependent on activity and synchronisation of central oscillators in basal ganglia

Rest tremor is one of the four main clinical features of Parkinson's disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency. We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia. We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number of active central oscillators is very low, the muscle-stimulating impulses are too weak to cause clinically evident tremor. On the other hand, if central oscillator synchronisation is poor, the impulses originating from different central oscillators are not in phase and thus cancel out, again leading to reduced stimulation of muscles and reduced tremor amplitude. Our hypothesis is supported by our measurements on patients with PD and by experimental data cited in the literature. The proposed two mechanisms could have clinical implications. New medical treatments, which would specifically target only one of the proposed mechanisms (oscillator activity or synchronisation), could be effective in reducing tremor amplitude and thus supplement established antiparkinsonian treatments.

The effect of inertial loading on wrist postural tremor in essential tremor

Determine the effect of inertial loading on the strength of motor unit entrainment and the synergistic/competitive interaction between central and mechanical reflex tremor components in subjects with essential tremor (ET). Twenty-three subjects with ET and 22 controls held their hand in an outstretched position while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular activity were recorded. Inertial loading resulted in a reduction in postural tremor in all ET subjects. The largest reduction in tremor amplitude occurred between 5% and 15% loads, which was associated with spectral separation of the mechanical reflex and central tremor components in a large number of ET subjects. Despite an increase in overall neuromuscular activity with inertial loading, EMG tremor spectral power did not increase with loading. The effect of inertial loading on postural tremor amplitude appears to be mediated in large part by its effect on the interaction between mechanical reflex and central tremor components. Also, ET is associated with a constant absolute level of motor unit entrainment. The amplitude of postural tremor is dependent on both central and peripheral factors, with proportionally greater motor unit entrainment occurring at low contraction intensities.

A pilot, double‐blind, placebo‐controlled trial of pregabalin (Lyrica) in the treatment of essential tremor

We performed a pilot, double-blind, placebo-controlled, randomized trial to evaluate the efficacy and tolerability of pregabalin (PGB, Lyrica), an antiepileptic agent, in treating essential tremor (ET). Twenty two patients with ET were randomly assigned to receive PGB or placebo. PGB was initiated at 50 mg/day and was escalated by 75 mg/day every 4 days to a maximum dose of 600 mg/day. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale. There was a significant reduction in tremor amplitude in the PGB group compared with the placebo group, as measured by accelerometry, at a mean dose of 286.76+/-100.05 mg/day. Action tremor limb scores on the FTM also improved in the PGB group compared with the placebo group (P-value for multilevel modeling=0.04). PGB was fairly well tolerated, with about one-third of patients dropping out of the study because of adverse events. PGB provided significant improvements in accelerometry and in action tremor limb scores on the FTM. However, larger studies are needed to further evaluate the potential effect of PGB on ET.

Gabapentin can improve postural stability and quality of life in primary orthostatic tremor

Primary orthostatic tremor (OT) is characterized by leg tremor and instability on standing. High frequency (13-18 Hz) tremor bursting is present in leg muscles during stance, and posturography has shown greater than normal sway. We report on an open-label add-on study of gabapentin in 6 patients with OT. Six patients were studied with surface electromyography, force platform posturography, and a modified Parkinson's disease questionnaire (PDQ-39) quality of life (QOL) scale before and during treatment with gabapentin 300 mg t.d.s. If on other medications for OT, these were continued unchanged. Of the 6 patients, 4 reported a subjective benefit of 50 to 75% with gabapentin, 3 of whom showed reduced tremor amplitude and postural sway of up to 70%. Dynamic balance improved in all 3 patients who completed the protocol. QOL data from 5 patients showed improvement in all cases. No adverse effects were noted. Gabapentin may improve tremor, stability, and QOL in patients with OT, and symptomatic response correlated with a reduction in tremor amplitude and postural sway. The findings confirm previous reports of symptomatic benefit with gabapentin and provide justification for larger controlled clinical trials. Further work is required to establish the optimal dosage and to validate the methods used to quantify the response to treatment.

Effects of peripheral cooling on intention tremor in multiple sclerosis

Objective: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is...

Long-acting propranolol in essential tremor.

Long-acting propranolol (propranolol-LA) was compared with propranolol in divided doses in 18 patients with essential tremor. Three patients were unresponsive to both preparations. Propranolol-LA was preferred by 87% of patients for ease of administration and by 67% for tremor control. Propranolol-LA provided similar (53%), and in some patients greater (47%), reduction of tremor amplitude than divided dosing. Propranolol-LA should be a useful drug in essential tremor.

Treatment of resting tremor by beta-adrenergic blockade

The effect of nadolol, a peripherally acting beta-adrenergic blocker, on resting tremor was examined in eight patients with idiopathic Parkinson's disease. With the use of a double-blind, placebo-controlled study of crossover design, patients recelved 80 to 320 mg of nadolol for 6 weeks while continuing their previous treatment regimen. Accelerometer readings showed a progressive reduction in tremor amplitude, but no change in tremor frequency, with increasing nadolol dosage. Maximum benefit was achieved at 240 mg, when resting tremor improved 50% ( p < 0.01). Physician ratings confirmed these findings. The results suggest that response to beta-adrenergic blockade may not be limited to postural or intention tremor and that such agents may not reliably differentiate between the tremor of Parkinson's disease and essential tremor.