Tremor Rating Scale Scores Research Articles

Responsive Versus Continuous Deep Brain Stimulation for Speech in Essential Tremor: A Pilot Study.

Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET). To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression. Eight ET participants with thalamic DBS underwent unilateral rDBS. Both speech evaluations and tremor severity were assessed across three conditions (DBS OFF, cDBS ON, and rDBS ON). Speech was analyzed using intelligibility ratings. Tremor severity was scored using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). During unilateral cDBS, participants experienced reduced speech intelligibility (P = 0.025) compared to DBS OFF. rDBS was not associated with a deterioration of intelligibility. Both rDBS (P = 0.026) and cDBS (P = 0.038) improved the contralateral TRS score compared to DBS OFF. rDBS maintained speech intelligibility without loss of tremor suppression. A larger prospective chronic study of rDBS in ET is justified. © 2024 International Parkinson and Movement Disorder Society.

Topologically Disrupted Gray Matter Networks in Drug-Naïve Essential Tremor Patients With Poor Sleep Quality

BackgroundSleep disturbances are widespread among patients with essential tremor (ET) and may have adverse effects on patients' quality of life. However, the pathophysiology underlying poor quality of sleep (QoS) in patients with ET remains unclear. Our study aimed to identify gray matter (GM) network alterations in the topological properties of structural MRI related to QoS in patients with ET.MethodWe enrolled 45 ET patients with poor QoS (SleET), 59 ET patients with normal QoS (NorET), and 66 healthy controls (HC), and they all underwent a three-dimensional T1-weighted MRI scan. We used a graph-theoretical approach to investigate the topological organization of GM morphological networks, and individual morphological brain networks were constructed according to the interregional similarity of GM volume distributions. Furthermore, we performed network-based statistics, and partial correlation analyses between topographic features and clinical characteristics were conducted.ResultsGlobal network organization was disrupted in patients with ET. Compared with the NorET group, the SleET group exhibited disrupted topological GM network organization with a shift toward randomization. Moreover, they showed altered nodal centralities in mainly the frontal, temporal, parietal, and cerebellar lobes. Morphological connection alterations within the default mode network (DMN), salience, and basal ganglia networks were observed in the SleET group and were generally more extensive than those in the NorET and HC groups. Alterations within the cerebello-thalamo-(cortical) network were only detected in the SleET group. The nodal degree of the left thalamus was negatively correlated with the Fahn-Tolosa-Marin Tremor Rating Scale score (r = −0.354, p =0.027).ConclusionOur findings suggest that potential complex interactions underlie tremor and sleep disruptions in patients with ET. Disruptions within the DMN and the cerebello-thalamo-(cortical) network may have a broader impact on sleep quality in patients with ET. Our results offer valuable insight into the neural mechanisms underlying poor QoS in patients with ET.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System

ObjectivesPatients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. Materials and MethodsSix advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. ResultsThere was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. ConclusionsIn this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor.

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.

Quantifying Tremor in Essential Tremor Using Inertial Sensors-Validation of an Algorithm.

Background Assessment of essential tremor is often done by a trained clinician who observes the limbs during different postures and actions and subsequently rates the tremor. While this method has been shown to be reliable, the inter- and intra-rater reliability and need for training can make the use of this method for symptom progression difficult. Many limitations of clinical rating scales can potentially be overcome by using inertial sensors, but to date many algorithms designed to quantify tremor have key limitations. Methods We propose a novel algorithm to characterize tremor using inertial sensors. It uses a two-stage approach that 1) estimates the tremor frequency of a subject and only quantifies tremor near that range; 2) estimates the tremor amplitude as the portion of signal power above baseline activity during recording, allowing tremor estimation even in the presence of other activity; and 3) estimates tremor amplitude in physical units of translation (cm) and rotation (°), consistent with current tremor rating scales. We validated the algorithm technically using a robotic arm and clinically by comparing algorithm output with data reported by a trained clinician administering a tremor rating scale to a cohort of essential tremor patients. Results Technical validation demonstrated rotational amplitude accuracy better than ±0.2 degrees and position amplitude accuracy better than ±0.1 cm. Clinical validation revealed that both rotation and position components were significantly correlated with tremor rating scale scores. Conclusion We demonstrate that our algorithm can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.

Simultaneous combined unilateral ventralis intermedius (VIM) thalamotomy and contralateral VIM deep brain stimulation for head tremor: A case report

AbstractHead tremor usually requires bilateral deep brain stimulation of ventralis intermedius nucleus of thalamus. Ablation of VIM nucleus (VIM thalamotomy) is applied for limb tremor unilaterally because of serious complications from bilateral thalamotomy. Therefore, effects of thalamotomy on head tremor have been rarely reported. We report a successful long‐term outcome of head tremor with combined unilateral VIM thalamotomy and contralateral VIM‐DBS simultaneously. The patient was a 49‐year‐old man with head and bilateral hand tremors. His Fahn‐Tolosa‐Marin Tremor Rating Scale scores (head tremor score, range 8‐0, higher scores indicate greater severity) before and after the surgery were 8 and 0, respectively. Only transient tongue numbness was confirmed as a surgical complication. At the final follow‐up (36 months), the patient was completely free from tremor of the head and bilateral hands. Combined thalamotomy and DBS can be an alternative treatment option for head tremor.

Outcomes and Adverse Effects of Deep Brain Stimulation on the Ventral Intermediate Nucleus in Patients with Essential Tremor

Objective This study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET). Methods An extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients' tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses. Results Forty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0 ± 17.3 months). The midline and extremity symptoms showed consistent improvement (P = 0.440), and the results of the comparison of postural and kinetic tremor were the same (P = 0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR = 2.759, P = 0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P < 0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively. Conclusion VIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Long-term efficacy and cognitive effects of voltage-based deep brain stimulation for drug-resistant essential tremor

ObjectivesTo analyze the long-term efficacy and cognitive effects of voltage-based deep brain stimulation (DBS) for drug-resistant essential tremor (ET). Patients and MethodsPatients with drug-resistant ET and treated by voltage-based DBS of the ventral intermediate nucleus (VIM-DBS) were continuously enrolled. Seizure outcomes were assessed by blinded observers using the Tremor Rating Scale (TRS). The full-scale intelligence quotient, full-scale memory quotient, Hamilton Depression Scale, Hamilton Anxiety Scale, and Quality of Life in Essential Tremor Questionnaire were assessed as measures of cognitive function. ResultsEleven patients met the inclusion criteria, and two of them were excluded because of loss to follow-up. The patient follow-up times ranged from 48 to 66 months (median 51 months). TRS scores decreased by 60.4% and 46.0% at the 12- and 48-month follow-ups, respectively. Both changes were highly significant. During the follow-up period, the patients’ intelligence and memory had not significantly changed; depression, anxiety, and quality of life significantly improved. After long-term follow-up, the stimulation efficacy and quality of life gradually decreased, and the depression and anxiety levels increased. ConclusionFor patients with drug-resistant ET, voltage-based DBS can provide acceptable benefits on tremor, cognitive function, and quality of life. However, the efficacy of VIM-DBS decreased over time.

Distinct non-motor features of essential tremor with head tremor patients.

There have been few comprehensive scale studies on the non-motor symptoms (NMS) of patients with essential tremor (ET) with head tremor (ETh) and those with ET without head tremor (ETol). We aimed to explore the motor symptoms and NMS of these two subgroups. We enrolled 199 patients with ET (125, ETol; 74 ETh) and 132 healthy controls. We evaluated motor symptoms using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and NMS using the Non-Motor Symptom Scale (NMSS). We compared NMSS scores and the prevalence of each NMS between the patient subgroups. Finally, we conducted a logistic regression analysis of the correlation between head tremor and NMS severity, as well as other determinants. There were no significant between-subgroup differences in demographic characteristics. Further, they presented similar tremor clinical manifestation; however, the ETh subgroup showed a higher prevalence of rest tremor, feeling of sadness, forgetting things or events, and swallowing difficulty, as well as TRS scores, compared with the ETol subgroup. Both patient subgroups showed high scores and prevalence (>50%) in difficulty falling asleep. Logistic regression analysis indicated age as a tremor severity determinant; further, head tremor and tremor severity were NMS determinants. Both patient subgroups presented various NMS including sleep disturbances, cognitive deficits, and affective disorders. The ETh subgroup showed a high prevalence of certain NMS aspects including memory and affective disorder; further, they had aggravated NMS. ET with both upper limb tremor and head tremor may be regarded as a more severe clinical subtype.

Treatment of severe refractory dystonic tremor associated with cervical dystonia by bilateral deep brain stimulation: A case series report

ObjectivesThe aim of the present study was to present a case series of 3 patients with longstanding, severe, debilitating dystonic head tremor (DT) coexistence with cervical dystonia (CD) treated successfully by bilateral deep brain stimulation (DBS). Pharmacological treatment including benzodiazepines and botulinum toxin injections employed to overactive muscles have failed to adequately control dystonic jerking movements of the head and neck. Patients and methodsAll patients were diagnosed with DT who accompanied CD. Two patients underwent bilateral implantation of DBS leads into the posteroventrolateral segment of the globus pallidus internus (GPi). 1 patient received combination of implantation of left lead in the nucleus ventralis intermedius of the thalamus (Vim) and the bilateral implantation of DBS leads in the GPi. All surgeries were uneventful. The formal preoperative objective assessment included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the motor score of Tremor Rating Scale (TRS). The postoperative TWSTRS, TRS assessments were done at 3, 6 months and 12 months postoperatively up to 48 months after surgery. ResultsAt the 12 months postoperative follow-up visit, the severity, disability and pain scores of TWSTRS were improved by 56 %, 52 % and 38,5 % respectively. The TRS improved by 66 % at 12 months when compared to baseline TRS score. One patient developed seroma over the implanted internal pulse generator and had some wound healing problems which solved without sequel. There were no hardware-related complications over follow-up period. ConclusionOur experience gathered in 3 patients indicates that bilateral DBS can be an effective treatment for disabling, pharmacological refractory tremulous CD.

Characterizing Thalamo-Cortical Structural Connectivity in Essential Tremor with Diffusional Kurtosis Imaging Tractography.

BackgroundNeuromodulation of the cerebello-thalamo-cortical (CTC) circuit via thalamic stimulation is an effective therapy for essential tremor (ET). In order to develop non-invasive neuromodulation approaches, clinically relevant thalamo-cortical connections must be elucidated.MethodsTwenty-eight subjects (18 ET patients and 10 controls) underwent MRI diffusional kurtosis imaging (DKI). A deterministic fiber-tracking algorithm based on DKI was used, with a seeding region placed at the ventral intermediate nucleus (Vim—located based on intraoperative physiology) to the ending regions at the supplementary motor area (SMA), pre-SMA, or primary motor cortex. One-tailed t-tests were performed to compare groups, and associations with tremor severity were determined by Pearson correlations. All p-values were adjusted for multiple comparisons using Bonferroni correction.ResultsThere was a decrease in the mean diffusivity (MD) in patients compared to controls in all three tracts: Vim-M1 (ET 0.87, control 0.96, p < 0.01), Vim-SMA (ET 0.86, control 0.96, p < 0.05), and Vim-pre-SMA (ET 0.87, control 0.95, p < 0.05). There was a significant positive correlation between Tremor Rating Scale score and MK (r = 0.471, p = 0.033) and mean FA (r = 0.438, p = 0.045) for the Vim-SMA tract, and no significant correlation for the Vim-pre-SMA or Vim-M1 tracts was found.DiscussionPatients with ET demonstrated a reinforcement of Vim-cortical connectivity, with higher Vim-SMA connectivity being associated with greater tremor severity. This finding suggests that the Vim-SMA connection is relevant to the underlying pathophysiology of ET, and inhibition of the SMA may be an effective therapeutic approach.

Targeting the posterior subthalamic area for essential tremor: proposal for MRI-based anatomical landmarks.

Deep brain stimulation (DBS) of the posterior subthalamic area (PSA) is an alternative to thalamic DBS for the treatment of essential tremor (ET). The dentato-rubro-thalamic tract (DRTT) has recently been proposed as the anatomical substrate underlying effective stimulation. For clinical purposes, depiction of the DRTT mainly depends on diffusion tensor imaging (DTI)-based tractography, which has some drawbacks. The objective of this study was to present an accurate targeting strategy for DBS of the PSA based on anatomical landmarks visible on MRI and to evaluate clinical effectiveness. The authors performed a retrospective cohort study of a prospective series of 11 ET patients undergoing bilateral DBS of the PSA. The subthalamic nucleus and red nucleus served as anatomical landmarks to define the target point within the adjacent PSA on 3-T T2-weighted MRI. Stimulating contact (SC) positions with reference to the midcommissural point were analyzed and projected onto the stereotactic atlas of Morel. Postoperative outcome assessment after 6 and 12 months was based on change in Tremor Rating Scale (TRS) scores. Actual target position corresponded to the intended target based on anatomical landmarks depicted on MRI. The total TRS score was reduced (improved) from 47.2 ± 15.7 to 21.3 ± 10.7 (p < 0.001). No severe complication occurred. The mean SC position projected onto the PSA at the margin of the cerebellothalamic fascicle and the zona incerta. Targeting of the PSA based on anatomical landmarks representable on MRI is reliable and leads to accurate lead placement as well as good long-term clinical outcome.

The clinical significance of lower limb tremors

IntroductionTo explore the prevalence, clinical course and associated features of lower limb tremor in the most common tremor syndromes. MethodsThis retrospective chart review studied lower limb tremor patients as defined by a Tremor Rating Scale score ≥1 in either lower limb. We compared and correlated their characteristics, also comparing them with patients without lower limb tremor. ResultsOf the 283 patients with lower limb tremor (58.3% males, age: 65.0 ± 16.0 years, tremor duration: 25.6 ± 17.9 years), 255 patients within six tremor syndrome groups were included in the final analysis. Prevalence of patients with lower limb tremor (either rest, postural or kinetic) was lowest (28.6%) in the essential tremor (ET) group and highest (69%) in the parkinsonian tremor (PT) group. Lower limb tremor score was higher in patients classified as having intention tremor (IT) compared to ET and dystonic tremor (DT). Total tremor score was highest in IT and lowest in ET. We found a positive correlation between total lower limb tremor score and total tremor score in most groups. In addition, there was a positive correlation between lower limb tremor score and upper limb tremor score. Finally, compared to patients without lower limb tremor, all diagnostic groups with lower limb tremor, with the exception of functional tremor (FT), had worse total tremor score; and disease duration was longer in ET-plus, DT and PT patients with lower limb tremor compared to those without. ConclusionsLower limb tremor is less commonly observed in ET than other tremor syndromes, is a marker of symptom severity of the underlying disease condition in all tremor syndromes except FT, and reflects longer disease duration in ET-plus, DT and PT.

Spatiotemporal gait parameters and tremor distribution in essential tremor

BackgroundEssential Tremor is characterized by an action tremor of the upper extremities, which may or may not be accompanied by a head, voice, leg or trunk tremor. Problems with gait and balance have also been identified in persons with Essential Tremor. Therefore, understanding gait performance is an important area of focus for clinicians and researchers. Research questionWe sought to 1) conduct a factor analysis on a broad spectrum of spatiotemporal gait parameters 2) build upon the normative database of gait measures in persons with Essential Tremor 3) understand the influence of age on gait speed in persons with Essential Tremor and 4) identify the relationships between gait performance and clinical measures of disease severity. MethodsGait data and Tremor Rating Scale scores were retrospectively collected from one hundred and forty-two ambulatory participants with a diagnosis of Essential Tremor. A factor analysis was used to characterize spatiotemporal gait parameters and regression models were applied to associate tremor scores to gait performance factors. ResultsThree domains of gait performance factors were identified in persons with Essential Tremor. Specifically, we observed a pace, rhythm, and stability factor. In sum, these factors accounted for 91.9% of the variance in gait performance. Only the pace and stability factors were associated with disease severity, suggesting these factors are most sensitive to disease severity compared to the rhythm factor. Our linear regression analysis revealed a significant influence of age on gait speed. Gait speed decreased with age significantly by 0.64 cm/s/year. SignificanceReference values for 12 gait parameters will be highly useful for assessing gait performance in individuals with Essential Tremor. Our observations suggest that a clinical assessment of gait and balance would be an important measure to consider in routine clinical practice when treating persons with Essential Tremor.

Clinical features and short-term prognosis of Holmes' tremor

Objective: To explore the clinical characteristics and short-term prognosis of Holmes' tremor (HT) patients. Methods: The clinical and imaging data of HT patients in 5 teaching hospitals between January 2014 and January 2018 were retrospectively analyzed, and Fahn-Tolosa-Marin Tremor Rating Scale (TRS) was used to compare the clinical severity and short-term prognosis between the different subtypes. Results: (1) The time from primary disease to tremor onset was 2 days to 20 months (median time 29 d) in 23 patients with HT enrolled, and the most common cause of HT was cerebrovascular disease (78.3%). (2) The most common involved locations were midbrain (65.2%), thalamus (47.8%) and cerebellum (30.4%). No significant difference in total TRS scores between the isolated lesion group (12 cases) and multiple lesions group (11 cases) (P=0.57), while the scores of the mesencephalic group (15 cases) was significantly higher than the non-mesencephalic group (8 cases) (P=0.00). (3) One case was treated with deep brain stimulation (DBS), while 22 cases were treated with medical therapy. Levodopa combined with clonazepam (7/12) and single levodopa (9/20) were partially effective. (4) At the 3-month follow-up after discharge, patients received DBS had good prognosis. Among the 22 patients treated with medicine, only 8 (36.4%) patients had good outcomes. The short-term prognosis was not significantly different between the isolated and multiple lesion groups (P=0.40), while it was worse in the mesencephalic group than the non-mesencephalic group (P=0.02). Conclusion: The most common cause of HT is cerebrovascular disease, and primary lesions are midbrain, thalamus, and cerebellum. The pharmacologic agents are partially valid for disease control of HT and the short-term prognosis is poor, while the patients with mesencephalic involvement have more severe tremor and worse prognosis.

Structural connectivity-based segmentation of the thalamus and prediction of tremor improvement following thalamic deep brain stimulation of the ventral intermediate nucleus.

ObjectivesTraditional targeting methods for thalamic deep brain stimulation (DBS) performed to address tremor have predominantly relied on indirect atlas-based methods that focus on the ventral intermediate nucleus despite known variability in thalamic functional anatomy. Improvements in preoperative targeting may help maximize outcomes and reduce thalamic DBS–related complications. In this study, we evaluated the ability of thalamic parcellation with structural connectivity–based segmentation (SCBS) to predict tremor improvement following thalamic DBS.MethodsIn this retrospective analysis of 40 patients with essential tremor, hard segmentation of the thalamus was performed by using probabilistic tractography to assess structural connectivity to 7 cortical targets. The volume of tissue activated (VTA) was modeled in each patient on the basis of the DBS settings. The volume of overlap between the VTA and the 7 thalamic segments was determined and correlated with changes in preoperative and postoperative Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores by using multivariable linear regression models.ResultsA significant association was observed between greater VTA in the supplementary motor area (SMA) and premotor cortex (PMC) thalamic segment and greater improvement in TRS score when considering both the raw change (P = .001) and percentage change (P = .011). In contrast, no association was observed between change in TRS score and VTA in the primary motor cortex thalamic segment (P ≥ .19).ConclusionsOur data suggest that greater VTA in the thalamic SMA/PMC segment during thalamic DBS was associated with significant improvement in TRS score in patients with tremor. These findings support the potential role of thalamic SCBS as an independent predictor of tremor improvement in patients who receive thalamic DBS.

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor.

The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long-term reduction of benefit seen with VIM-DBS. To compare clinical outcomes and DBS programming in the long-term between VIM and cZI neurostimulation in ET-DBS patients. A retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow-up to 4 years after DBS. Student t-tests and analysis of variance (ANOVA) were used to compare variables between groups. Relative to baseline, an improvement in ON-DBS tremor scores was observed in both groups from 6 months to 4 years post-DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post-DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post-DBS. More ventral DBS contacts in the cZI region do improve tremor, however, VIM-DBS provided better long-term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results.

Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study

BackgroundConventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. ObjectivesThe current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. MethodsThis pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. ResultsThere was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5–35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8–24.3) at ClinDBS setting and to (16.5 IQR = 12–20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ2 = 16.1, p = 0.006), posture (χ2 = 15.9, p = 0.007) and with action (χ2 = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. ConclusionBiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required.

Limited correlations between clinician-based and patient-based measures of essential tremor severity.

We investigated the relation between changes in clinician-based and patient-based measures of tremor severity, within the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and Visual Analogue Scale (VAS) in essential tremor patients. Thirty-seven patients were assessed twice: on- and off-medication. Clinician-based, objective TRS assessments, consisting of part A (postures/movements) and part B (tremor-inducing tasks) were conducted by a blinded assessor using video-tapes. Patients completed TRS part C (limitations in activities of daily life) and indicated subjective tremor severity using VAS. Patients' total TRS and VAS scores improved on-medication (both p<0.001). Mean improvement was 6.3 (sd 5.4) points on the total TRS and 2.3 (sd 2.3) points on the VAS score. Within the TRS, we found moderate correlations between changes in clinician-based TRS-B and patient-based TRS-C scores (ρ=0.387, p=0.011), but not between changes in clinician-based TRS-A and TRS-C scores (ρ=0.128, p=0.232). Moreover, changes in subjective VAS scores correlated with changes in total TRS (ρ=0.422, p=0.007), changes in TRS-C scores (ρ=0.367, p=0.015) and, more weakly, with changes in TRS-B scores (ρ=0.281, p=0.049), but again: not with changes in TRS-A scores (ρ=-0.008, p=0.482). We found no correlation between changes in clinician-based TRS-A, and patient-based measures TRS-C or VAS scores, and a weak correlation between clinician-based TRS-B and VAS scores. The limited correlations between changes in clinician-based and patient-based measures of tremor severity suggest that the different scales measure different aspects of tremor severity and support the additional use of subjective patient-based assessments in clinical practice and clinical trials.

Outcome of gamma knife thalamotomy in patients with an intractable tremor.

ObjectiveTremor is a common movement disorder that interferes with daily living. Since the medication for tremor has some limitations, surgical intervention is needed in many patients. In certain patients who cannot undergo aggressive surgical intervention, Gamma Knife thalamotomy (GKT) is a safe and effective alternative.MethodsFrom June 2012 to August 2013, 7 patients with an intractable tremor underwent GKT. Four of these 7 patients had medical comorbidities, and 3 patients refused to undergo traditional surgery. Each patient was evaluated with the modified Fahn-Tolosa-Marin tremor rating scale (TRS) along with analysis of handwriting samples. All of the patients underwent GKT with a maximal dose of 130 Gy to the left ventralis intermedius (VIM) nucleus of the thalamus. Follow-up brain MRI was performed after 3 to 8 months of GKT, and evaluation with the TRS was also performed.ResultsSix patients showed objective improvement in the TRS score. Excluding one patient who demonstrated tremor progression, there was 28.9% improvement in the TRS score. However, five patients showed subjective improvement in their symptoms. On comparing the TRS scores between follow-up periods of more and less than 4 months, the follow-up TRS score at more than 4 months of GKT was significantly improved compared to that at less than 4 months of GKT. Follow-up MRI showed radiosurgical changes in 5 patients.ConclusionGKT with a maximal dose of 130 Gy to the VIM is a safe procedure that can replace other surgical procedures.