Effects of herbal medicines (Eunkyosan/Yin qiao san and Samsoeum/Shen su yin) for treating the common cold: A randomized, placebo-controlled, multicenter clinical trial.

Background: Eunkyosan (EKS) and Samsoeum (SSE), which are called Yin qiao san and Shen su yin in Chinese, are commonly used herbal medicines for the common cold in East Asian countries. This study aimed to evaluate the effectiveness and safety of EKS and SSE for treating the common cold. Methods: A randomized, patient-assessor-blind, placebo-controlled, parallel, and multicenter clinical trial was conducted. Adult participants who had one or more cold within 48 h before screening, were randomly allocated to EKS, SSE, or placebo groups. The recruitment goal was planned to be 375 participants. They took an EKS, SSE, or placebo, thrice daily for up to 8 days. The primary outcome was the change in the total score of the Wisconsin Upper Respiratory Symptom Scale-21-Korean version (WURSS-21-K) on day 6 compared to the baseline. The secondary outcomes included visual analog scale (VAS) scores and the duration of symptoms was assessed throughout the trial. Results: A total of 128 participants were enrolled and 44, 42, and 42 were allocated to the EKS, SSE, and placebo groups, respectively. This study was prematurely terminated due to the COVID-19 pandemic, and we were unable to recruit all the planned participants (n = 375). EKS showed significant clinical effectiveness over the placebo group in the treatment of the common cold, as assessed by the total, symptom, and quality of life scores of WURSS-21-K and VAS, whereas SSE showed significant improvement over the placebo group in terms of WURSS-21-K symptom score. No severe adverse events were reported. Conclusions: Although EKS and SSE demonstrated statistically significant clinical effectiveness and safety in patients with the common cold, we failed to recruit our pre-planned number of participants. Future definitive full-scale studies are needed to confirm these results. Trial registration: ClinicalTrials. gov, registration number: NCT04073511. Registered on 29 August 2019.

Traditional medicine for the treatment of common cold in Korean adults: A nationwide population-based study.

BACKGROUND: Traditional medicines (TMs) have been used to treat common cold in Asia, but no studies have been conducted to examine the trend of use for several years. The objective of this study was to analyze the prescription patterns of TMs for common cold using national claims data accrued over 7 years in Korea. This will contribute to the scientific evidence enhancing the understanding of TM use for the treatment of common cold. METHODS: This study analyzed national claims data from the Health Insurance Review and Assessment Service database. We extracted data for diagnosis of common cold (Korean Standard Classification of Diseases: J00, Acute nasopharyngitis) and prescriptions of TMs for adults who visited all types of oriental medical institutions during 2010-2016. We estimated the prescription patterns of TMs by sex, age group, and year. RESULTS: We extracted 3,014,428 prescriptions. The total number of prescriptions increased by 125.1% in 2016 compared to that in 2010. For all ages and periods, the number of prescriptions in women was higher than that in men. The age range with the most prescriptions was 70-79 years. The seven most prescribed TMs for common cold were Socheongnyongtang, Samso-eum, Yeongyopaedoksan, Insampaedoksan, Gumigohwaltang, Galgeuntang, and Hyeonggae-yeongyotang. CONCLUSION: This was the first study to analyze the prescription patterns of TMs for common cold using National Health Insurance data in Korea. This study provides scientific evidences on the disease burden and the utilization pattern of TMs for common cold to support decision making on initiatives such as allocation and management of health resources.

Eunkyosan for the common cold: A PRISMA-compliment systematic review of randomised, controlled trials.

BACKGROUND: Eunkyosan (EKS), also known as the Yinqiaosan formula, is widely applied for the common cold in East Asia. Many clinical trials have reported the efficacy and safety of the EKS formula for the treatment of the common cold. OBJECTIVES: This study aimed to assess the clinical evidence for and against the use of EKS formula as a treatment for the common cold. DATA SOURCES: The following databases were searched from inception to the present: MEDINLE, EMBASE, CENTRAL, AMED CINAHL for English articles; OASIS, the Korean Traditional Knowledge Portal, the Korean Studies Information Service System, KoreaMed, the Korean Medical Database and DBPIA); and 3 Chinese databases, including CNKI (i.e., the China Academic Journal, the China Doctoral Dissertations and Master's Theses Full-text Database, the China Proceedings of Conference Full-Text Database and the Century Journal Project), Wanfang and VIP. In addition, we searched a Japanese database and conduct non-electronic searches of conference proceedings. STUDY ELIGIBILITY CRITERIA: Prospective randomised controlled trials (RCTs) evaluating the effectiveness of EKS for the common cold were included in this review. PARTICIPANTS: All types of common colds were eligible for inclusion. Participants who had both the common cold and other conditions were excluded. There were no restrictions based on other factors, such as age, sex, or symptom severity. INTERVENTIONS: Studies that evaluated any type of formulation (ie, decoction, tablet, pill, powder) of EKS were eligible for inclusion. STUDY APPRAISAL AND SYNTHESIS METHODS: Differences between intervention and control groups were assessed. Mean differences with 95% confidence intervals (CIs) were used to measure the effects of treatment for continuous data. METHODS AND ANALYSIS: Fourteen databases were searched in March 2018. We included RCTs examining EKS decoctions for any type of common cold. All RCTs of decoctions or modified decoctions were included. The methodological qualities of the RCTs were assessed using the Cochrane Collaboration tool for assessing risk of bias; confidence in the cumulative evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. RESULTS: A total of 315 potentially relevant studies were identified, and 4 RCTs met our inclusion criteria. Four RCTs tested the effects of EKS on the common cold, and all RCTs showed that EKS was superior regarding the treatment effect. LIMITATIONS: All RCTs were conducted in China, and the generalisation of these results to other countries might be limited. Most trials did not use internationally recognised reliability and validity outcome measurements. Moreover, the result of the response rate can be distorted by the practitioner. Future trials in compliance with international standards in the evaluation of treatment effects may resolve this issue. CONCLUSION: Our systemic review and meta-analysis provides suggestive evidence of the superiority of EKS over other therapies for treating the common cold. The level of evidence is low because of the high risk of bias. IMPLICATIONS OF KEY FINDINGS: The results of this systematic review and meta-analysis provide suggestive evidence of the superiority of EKS alone or combined with conventional drugs. REGISTRATION NUMBER: CRD42018087694.

Herbal medicines (Eunkyosan and Samsoeum) for treating the common cold: a protocol for a randomized, placebo-controlled, multicenter clinical trial.

BACKGROUND: The common cold is the most frequent acute respiratory illness that places a burden on society, both personally and economically. There is no standard therapy; only symptomatic therapy remains the mainstay of common cold treatment. Thus, interest in herbal medicines is on the rise. Eunkyosan and Samsoeum are used for the common cold in East Asian countries. Although Eunkyosan and Samsoeum are clinically used for the treatment of the common cold, their effectiveness and safety have yet to be studied. Therefore, we aimed to evaluate their effectiveness and safety. METHODS: This study is a randomized, patient-assessor blind, controlled, parallel, and multicenter clinical trial. A total of 375 participants diagnosed with the common cold will be enrolled via four hospitals. The common cold patients will take a daily dose of Eunkyosan or Samsoeum or a placebo, three times a day for eight days. The primary outcome is the change in total Wisconsin Upper Respiratory Symptom Scale-21-Korean version (WURSS-21-K) score between baseline and six days. The secondary outcome includes the visual analogue scale (VAS). Safety is evaluated and adverse events are assessed throughout the trial. Written informed consent will be obtained from all study participants before enrollment. DISCUSSION: This results will be published in a peer-reviewed journal and disseminated in related conferences. TRIAL REGISTRATION: ClinicalTrials. gov, registration number: NCT04073511.

Effects of Peer Mentoring on Self-Efficacy and Hospital Readmission After Inpatient Rehabilitation of Individuals With Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of intensive peer mentoring on patient-reported outcomes of self-efficacy and unplanned hospital readmissions for persons with spinal cord injury/disease (SCI/D) within the first 6 months after discharge from inpatient rehabilitation. DESIGN: Randomized controlled trial. SETTING: Nonprofit inpatient rehabilitation hospital specializing in care of persons with SCI/D and brain injury. PARTICIPANTS: Patients (N=158) admitted to the SCI/D rehabilitation program whose discharge location was a community setting. Participants (51% with paraplegia and 49% with tetraplegia) were 73% white and 77% men, with a mean age of 38 years. INTERVENTIONS: Participants in the experimental group received initial consult/introduction with a peer support program liaison and were assigned a peer mentor, who met with the participant weekly throughout the inpatient stay and made weekly contact by phone, e-mail, or in person for 90 days postdischarge. Participants also were encouraged to participate in regularly scheduled peer support activities. Nonexperimental group participants were introduced to peer support and provided services only on request. MAIN OUTCOME MEASURES: General Self-efficacy Scale (adapted to SCI/D), project-developed community integration self-efficacy scale, and patient-reported unplanned rehospitalizations. RESULTS: Growth rate for self-efficacy in the first 6 months postdischarge was significantly higher for experimental group participants than nonexperimental group participants. Experimental group participants also had significantly fewer unplanned hospital days. CONCLUSIONS: This study provides evidence that individuals receiving intensive peer mentoring during and after rehabilitation for SCI/D demonstrate greater gains in self-efficacy over time and have fewer days of unplanned rehospitalization in the first 180 days postdischarge. More research is needed to examine the long-term effects of this intervention on health care utilization and the relation between improved health and patient-reported quality of life outcomes.

Blood-letting therapy for the common cold: A protocol for a systematic review of controlled trials.

BACKGROUND: Many people experience the common cold, but there is currently no special treatment. For this reason, complementary and alternative medicine (CAM) therapies are used to improve the symptoms of the common cold. Blood-letting therapy (BL) is a CAM therapy that has been used for over 2000 years to treat various diseases. However, few studies have provided evidence for the efficacy and safety of BL for the common cold. This study aims to assess the effectiveness and safety of BL for the common cold. METHODS AND ANALYSIS: A total of 11 databases will be searched for studies conducted through June 2017. We will include randomized controlled trials assessing BL for the common cold. All randomized controlled trials on BL or related interventions will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Assessment Tool, while confidence in the accumulated evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation instrument. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and will also be disseminated electronically and in print. The review will be updated to inform and guide healthcare practices.

Effects of medication on turning deficits in individuals with Parkinson's disease.

BACKGROUND AND PURPOSE: People with Parkinson's disease often have difficulty executing turns. To date, most studies of turning have examined subjects ON their anti-Parkinson medications. No studies have examined what specific aspects of turning are modified or remain unchanged when medication is administered. The purpose of this study was to determine how anti-Parkinson medications affect temporal and spatial features of turning performance in individuals with Parkinson's disease. METHODS: We examined turning kinematics in 10 people with Parkinson's disease who were assessed both OFF and ON medication. For both conditions, participants were evaluated with the Unified Parkinson's Disease Rating Scale motor subscale, rated how well their medication was working on a visual analog scale, and performed straight-line walking and 180-degree in-place turns. We determined the average walking velocity, time and number of steps to execute turns, sequence of yaw rotation onsets of the head, trunk, and pelvis during turns, and amplitudes of yaw rotation of the head, trunk, and pelvis during turns. RESULTS: Medication significantly improved the Unified Parkinson's Disease Rating Scale scores (P = 0.02), visual analog scale ratings (P = 0.03), and walking velocity (P = 0.02). Although improvements in turning were not statistically significant, medication did reduce the time and number of steps required to turn, slightly increased the amplitudes of yaw rotation of the various segments, and increased the rotation of the head relative to the other segments. Medication did not improve the timing of segment rotations, which showed en bloc turn initiation in both the OFF and ON medication conditions. DISCUSSION AND CONCLUSION: These results suggest that only certain aspects of turning may be responsive to anti-Parkinson medications. As such, additional rehabilitative approaches to address turning are needed because turning may not be effectively addressed by pharmacologic approaches. These results should be interpreted cautiously given the small sample size.

A kinematic and electromyographic analysis of turning in people with Parkinson disease.

BACKGROUND: Parkinson disease frequently causes difficulty turning that can lead to falls, loss of independence, and diminished quality of life. Turning in tight spaces, which may be particularly impaired in Parkinson disease, is an essential part of our daily lives, yet a comprehensive analysis of in-place turning has not been published. OBJECTIVE: This study was conducted to determine whether there are objective differences in turning between people with Parkinson disease and unimpaired people. METHODS: In-place turning with kinematics and electromyographic measures was characterized in 11 participants with Parkinson disease and 12 healthy people. Kinematic data were recorded using a 3-dimensional motion capture system in synchrony with electromyographic data from lower extremity muscles as participants turned 180 degrees . Those with Parkinson disease were tested after overnight withdrawal of medication. RESULTS: Both groups used 2 distinct turning strategies. In one, the foot ipsilateral to the turning direction initiated the turn; in the other, the foot contralateral to the turning direction initiated the turn. Kinematic analysis demonstrated a craniocaudal sequence of turning in the unimpaired group, whereas those with Parkinson disease had a simultaneous onset of yaw rotation of the head, trunk, and pelvis. They also took a longer time and more steps to complete turns. Overall, lower extremity muscle activation patterns appeared similar between groups. CONCLUSION: Differences between the groups were noted for axial control, but lower extremity muscle patterns were similar. This work may provide the foundation for development of new treatments for turning difficulty in Parkinson disease.

Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in Parkinson disease.

BACKGROUND: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. METHODS: In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity (n=42), bradykinesia (n=38), and gait speed (n=45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. RESULTS: All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. CONCLUSIONS: Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS.

Rotating treadmill training reduces freezing in Parkinson disease: preliminary observations.

Two subjects with Parkinson disease (PD) who had difficulty turning, and freezing of gait triggered by turning, participated. Subjects completed four blocks of turning trials. Three blocks were conducted in the absence of treadmill intervention. Both subjects had consistent freezing across blocks prior to training and evidenced more freezing when turning left than right. The final block of turns was performed after 10-15 min of training leftward turning on a rotating circular treadmill. Following training: (1) neither subject froze during leftward turns, (2) muscle activity normalized, and (3) turning times decreased for leftward turns.

Effects of thalamic stimulation frequency on intention and postural tremor.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus improves essential tremor. Suppression of the amplitude of the postural tremor component with VIM DBS depends on stimulation frequency. The purpose of this study was to determine the effect of DBS frequency on the intention tremor component, that is, tremor that is enhanced by target-directed movement, and to compare it to the effect of DBS frequency on postural tremor in people with essential tremor. We measured tremor frequency and amplitude during trials of postural holding and voluntary reaching between two targets at 10 different stimulation frequency settings between 0 and 185 Hz. Tremor frequency did not change with changes in stimulation frequency. Amplitude suppression of both intention and postural tremor depended on stimulation frequency. Maximal tremor reduction occurred at approximately 130 Hz for both forms of tremor. However, at optimal frequencies, the percent reduction in tremor amplitude relative to the DBS OFF condition was greater for postural than for intention tremor. These results suggest that VIM DBS stimulation frequencies near 130 Hz may provide maximal control of intention and postural tremor. Identification of optimal stimulation settings should consider assessment of intention tremor, not just postural tremor, as intention tremor may not be as well controlled as postural tremor but may be a better gauge for functional benefit.

Limited transfer of podokinetic after-rotation from kneeling to standing.

Following stepping in place on a rotating treadmill, subjects inadvertently rotate when asked to step in place without vision. This response is called podokinetic after-rotation (PKAR). The purpose of this study was to determine whether PKAR transfers across tasks with different lower limb configurations, that is, from kneeling to stepping. We hypothesized that PKAR would transfer from kneeling to stepping for two reasons. First, there have been several demonstrations of robust PKAR transfer from forward to backward walking, stepping to hopping, running to walking, and from one limb to another. Second, we thought that afferent information regarding hip rotation was likely a key source of information to guide podokinetic adaptation and since hip rotation would be preserved in both stimulation conditions we expected to see little difference between the conditions. We compared the PKAR responses recorded in standing from 13 healthy young volunteers after either standard stepping on a rotating treadmill or stepping while kneeling (kneel-stepping) on a rotating treadmill. Subjects performed two sessions of podokinetic (PK) stimulation, one stepping and one kneel-stepping on a rotating treadmill. Following the PK stimulation, subjects were blindfolded and asked to step in place in standing. Angular velocity of trunk rotation during PKAR from the two sessions was calculated and compared. The maximum angular velocities of PKAR recorded in stepping were significantly higher following the stepping session than following the kneel-stepping session (9.10 +/- 8.9 and 2.94 +/- 1.6 deg/s, respectively). This was despite the fact that hip rotation excursion during PK stimulation was significantly greater in kneel-stepping (18.7 +/- 3.6 deg) than in stepping (12.2 +/- 2.6 deg). These results indicate very little transfer from kneeling to stepping and suggest that afferent information regarding hip rotation is not the only or even the major source of limb position sense information used to drive locomotor trajectory adaptation.

Enhancement of rigidity in Parkinson's disease with activation.

Rigidity, a cardinal symptom of Parkinson's disease (PD), increases with movement of a contralateral limb. It is unclear whether this effect is specific for movement of a contralateral limb. The goal of this study was to test the hypothesis that ipsilateral or contralateral movement would enhance rigidity but that bilateral limb movements would maximally increase rigidity in people with PD. We assessed rigidity in 12 people with PD off meds, 12 matched controls, and 10 young controls, using a Rigidity Analyzer (Neurokinetics, Alberta, Canada). The elbow was passively moved repetitively into flexion and extension by the examiner, while the subjects engaged in different toe tapping conditions: no tapping, ipsilateral tapping, contralateral tapping, and bilateral tapping. Three 50-second trials were done for each condition and the order of the trials was randomized. A 2-way repeated measures ANOVA and Holm-Sidak post hoc tests were used to determine differences across conditions and groups. There was a significant effect of group, tapping conditions and an interaction of the two. Post hoc tests revealed that for the PD group, all tapping conditions were significantly different from the no tapping condition but not different from each other. There were no differences across conditions for the controls. We conclude that movement of either the contralateral or ipsilateral lower extremity can increase arm rigidity in people with PD but the effects from left and right are apparently not additive. Further, activation did not enhance muscle tone in controls suggesting that this procedure may help distinguish people with PD from controls.

Perception of active and passive turning in Parkinson disease.

BACKGROUND: Many individuals with Parkinson disease (PD) experience difficulty with turning, yet little is known about the reasons for this difficulty. OBJECTIVE: The authors sought to determine whether individuals with PD can use visual, vestibular, and proprioceptive cues to estimate how far they have turned. METHODS: Fifteen PD subjects and 11 controls performed active and passive turns to the left and right, with and without vision, with amplitudes of 90, 180, 270, and 360 degrees. For active conditions, subjects were told the direction and amplitude of the desired turn and then attempted to turn in place the specified amount via actively stepping. For passive conditions, subjects were told that the disc they stood on would turn and they were to press a button when they had traveled the specified amplitude. RESULTS: There were no differences between PD and control groups in any of the conditions, suggesting that those with PD effectively used sensory cues available in the different conditions to accurately judge distance turned. The authors found no apparent deficits in the visual, vestibular, or proprioceptive systems or in integration of these senses for performance of the turning task tested. CONCLUSIONS: Turning difficulties associated with PD may more likely relate to motor or sensorimotor integration deficits than to pure sensory or sensory integration deficits. Generalizability of the study may be limited by the fact that subjects were tested at a single velocity for passive rotations, were on medication, and had relatively mild PD (primarily H&Y 2).

Podokinetic after-rotation in Parkinson disease.

Walking on a rotating platform for 15 min causes healthy subjects to involuntarily turn when walking without vision. This adaptive response, called podokinetic after-rotation (PKAR), uses the same kinematic patterns as voluntary turning suggesting that PKAR and voluntary turning share common mechanisms. The purpose of this study is to determine whether people with Parkinson disease (PD), a condition that produces substantial disability from turning difficulties, can adapt to the rotating platform. Initial testing of people with PD revealed that most were unable to step on the rotating platform for 15 continuous minutes. We thus tested a less intense version of the paradigm in eight healthy people. On one day, subjects walked on the platform for 15 continuous minutes; on another day, they walked on the platform for three 5-minute intervals separated by 5-minute rests. After both sessions, subjects rested for 5 min then walked in place for 30 min without vision, while we recorded rotational velocity of PKAR. Continuous and interval protocols effectively elicited robust PKAR. We then tested eight subjects with PD and matched controls using the 5-minute interval protocol and recorded PKAR responses for 10 min. There were no significant differences between the PD and control groups. We conclude that PD subjects can adapt to the rotating platform and develop PKAR from interval training. Future studies are needed to determine whether the rotating platform may act as a rehabilitative tool to reinforce motor patterns for turning and alleviate turning difficulties in people with PD.

Kinematics of podokinetic after-rotation: similarities to voluntary turning and potential clinical implications.

We examined the kinematics of voluntary turning in place at three different speeds and of inadvertent turning in place during attempts to step in place following stepping on a rotating disc (podokinetic after-rotation, PKAR). We hypothesized that voluntary turning in place, like online turning during walking, would be characterized by a top-down sequence of yaw rotations in the direction of the turn, i.e. the head would rotate first, followed by the trunk and then the foot. We also hypothesized that in place PKAR would be characterized by a bottom-up sequence of yaw rotations, i.e. the foot would rotate first, followed by the trunk and the head. The alternative possibility was that PKAR, like voluntary turning, would be initiated by the head and trunk and the foot would rotate last. As expected, voluntary turning in place was characterized by a top-down sequence similar to that noted previously during online turning in the midst of walking. Turning velocity did not alter the sequence of rotations in voluntary turning. In place PKAR was also characterized by a top-down sequence, indicating that PKAR may access the same neural circuits employed during voluntary turning. These data suggest that the rotating treadmill may be a useful training tool for addressing difficulties with turning that are experienced by individuals with Parkinson disease (PD).

Postural tremor suppression is dependent on thalamic stimulation frequency.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) reduces tremor in people with essential tremor (ET), yet the dependence of tremor suppression on stimulation frequency remains unclear. To address this issue, we tested tremor suppression for three 15-second measurements during a variety of stimulation frequencies in 11 ET patients treated with VIM DBS. Stimulation frequencies at or above 100 Hz produced maximal benefit; higher frequencies provided no additional benefit. If this short-term measure predicts long-term response in routine activities at home, then this stimulation frequency setting will prolong battery half-life compared to higher frequency settings. These findings suggest that ET patients treated with VIM DBS may receive adequate benefit from stimulation frequencies about 100 Hz and this setting compared to commonly used higher settings will prolong battery life of surgically implanted pulse generators.

Effect of stimulation frequency on tremor suppression in essential tremor.

We sought to determine the effect of deep brain stimulation (DBS) frequency on tremor suppression in essential tremor (ET) patients with deep brain stimulators implanted in the ventral intermediate nucleus (VIM) of the thalamus. A uniaxial accelerometer was used to measure tremor in the right upper extremity of subjects with a diagnosis of ET who had DBS electrodes implanted in the left VIM. The root-mean-square acceleration was used as the index of tremor magnitude and normalized to the OFF DBS condition. There was a highly significant inverse sigmoidal relationship between stimulation frequency and normalized tremor acceleration (X(2)/DoF = 0.42, r(2) = 0.997). Tremor acceleration had a nearly linear response to stimulation frequencies between 45 and 100 Hz with little additional benefit above 100 Hz. These findings have two important implications. Clinically, frequency of thalamic stimulation is an important variable for optimal tremor control with maximal benefit achieved with 100 to 130 Hz in most patients. Second, thalamic DBS provides tremor benefit in a graded manner and is not an all-or-nothing phenomenon.