Fahn-Tolosa-Marin Tremor Rating Scale Research Articles

Differential patterns of functional connectivity in tremor dominant Parkinson's disease and essential tremor plus.

Tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.

Optimizing Deep Brain Stimulation in Essential Tremor: A Randomized Controlled Trial for Target Consideration.

The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). Increasing data indicate that the posterior subthalamic area (PSA) may be superior, but high-level evidence is limited. We aimed at further comparing the intraindividual efficacy and side effect profile of PSA vs VIM DBS in ET. In this randomized, double-blind, crossover trial, 4-contact DBS leads were bilaterally implanted with single-trajectory covering the VIM and PSA. Patients were randomized postsurgery to 2 groups, receiving VIM stimulation (4-7 months) and then PSA stimulation (8-11 months) or vice versa. The primary end point was the difference in improvement from baseline to the end of the VIM vs PSA DBS period in the total score of the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). Ten patients with medically refractory ET were enrolled, and 9 completed the study. The difference between reduction of FTM-TRS total score in the PSA vs VIM DBS period was -7.4 (95% CI: -28.5 to 13.7, P = .328). Clinical benefit was achieved at significantly lower stimulation intensity under PSA DBS. Furthermore, PSA DBS provided greater improvement in head tremor subscore of FTM-TRS (PSA vs VIM: -2.2, P = .020) and disease-specific quality of life (PSA vs VIM: -13.8, P = .046) and induced fewer speech (Dysphonia Severity Index score: P = .043; diadochokinetic rate: P = .007; VDI score: P = .005) and gait disturbances compared with VIM DBS. Seven patients remained with PSA DBS after the crossover phase. Our study confirms that PSA-DBS is comparable with VIM-DBS in suppressing tremors, superior in improving disease-specific quality of life, and possibly more effective in reducing head tremor.

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

BackgroundThalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. MethodsWe retrospectively enrolled right-handed patients under bilateral thalamic DBS >12 months for ET from a cross-sectional study. They were characterized with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Scale for the Assessment and Rating of Ataxia (SARA) scores at different timepoints. Normative fiber tractographic evaluations of crossed and uncrossed cerebellothalamic pathways and volume of activated tissue (VAT) studies together with [18F]Fluorodeoxyglucose positron emission tomography were applied. ResultsA total of 29 patients met the inclusion criteria. Favoring DRTu over DRTx in the non-dominant VAT was associated with DTE (R2 = 0.4463, p < 0.01) and ataxia (R2 = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. ConclusionOur results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

The Challenge of Choosing the Right Stimulation Target for Dystonic Tremor-A Series of Instructive Cases.

Thalamic deep brain stimulation (DBS) is established for medically refractory tremor syndromes and globus pallidus stimulation (GPi-DBS) for medically refractory dystonia syndromes. For combined tremor and dystonia syndromes, the best target is unclear. We present four patients with two different profiles whose clinical course demonstrates that our current analysis of clinical symptomatology is not a sufficient predictor of surgical success. Outcome parameters were assessed with observer-blinded video ratings and included the Fahn-Tolosa-Marin-Tremor Rating Scale (FTM-TRS) and the Unified Dystonia Rating Scale (UDRS). Two patients with "predominant lateralized action tremor" of the hands and mild cervical dystonia showed no relevant tremor improvement after GPi-DBS, but UDRS improved (mean, 45%). Rescue ventral intermediate nucleus of the thalamus (Vim)-DBS electrodes were implanted and both patients benefited significantly with a mean tremor reduction of 51%.Two other patients with "axial-predominant action tremor of the trunk and head" associated with cervical dystonia underwent bilateral Vim-DBS implantation with little effect on tremor (24% reduction in mean FTM-TRS total score) and no effect on dystonic symptoms. GPi rescue DBS was implanted and showed a significant effect on tremor (63% reduction in mean FTM-TRS) and dystonia (49% reduction in UDRS). The diagnosis of dystonic tremor alone is not a sufficient predictor to establish the differential indication of GPi- or Vim-DBS. Further criteria (eg, proximal-distal distribution of tremor/dystonia) are needed to avoid rescue surgery in the future. On the other hand, the course of our patients encourages rescue surgery in such severely disabled patients if the first target fails.

Tremor in Patients with Relapsing-Remitting Multiple Sclerosis: Clinical Characteristics and Impact on Quality of Life.

Little is known about the prevalence and clinical characteristics of tremors in patients with multiple sclerosis (MS), their associated clinical disability, and their impact on quality of life (QoL). This study aimed to investigate the frequency and types of tremors in patients with relapsing remitting MS (RRMS) in remission, and their impact on patients' QoL. A total of 250 patients with RRMS in remission were examined for tremors. All patients were assessed using the Expanded Disability Status Scale (EDSS). Patients with tremors underwent further assessment using the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), the Beck Depression Inventory (BDI), the Montreal Cognitive Assessment (MoCA) scale, and the Short Form 36 Health Survey Questionnaire (SF-36). Brain MRI was obtained for a subgroup of patients. Tremors were detected in 36 patients (14.4%) and were associated with significantly worse EDSS scores, BDI (P = 0.021), MoCA, most SF-36 domains, higher total and last year relapses (P < 0.001) and longer disease duration (P = 0.027). Patients with tremors showed higher lesion load (P = 0.007), more infratentorial (P ≤ 0.001), cerebellar and diencephalic lesions (P = 0.024), and cortical atrophy (P = 0.012). Total FTMTRS was significantly correlated to age, EDSS, and physical functioning. Dystonia was associated with tremors in 17 patients (6.8% of total RRMS patients and 47.2% of patients with tremors). The current study confirms the common occurrence of tremors and their subtypes among patients with RRMS with mild disability and demonstrates their association with increased disability and impaired QoL.

The relationship of tremor severity with proximal and distal muscle strength and upper extremity functional skills in older adults with essential tremor

Although it is known that muscle strength training is effective in Essential Tremor (ET), it is not known which muscle groups are more affected. The study was conducted to examine the relationship between tremor severity and proximal and distal muscle strength and upper extremity functional skills in older adults with ET. A total of 40 older adults who were diagnosed with ET (mean age of 74.07 ± 4.83years) and 40 older adults without tremor (mean age of 70.10 ± 4.05years) were included in the study. Tremor severity was evaluated with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), the proximal muscular strength with digital muscle dynamometer, handgrip strength with hand dynamometer, and pinch grip strength with pinchmeter. The Arm and Shoulder Problems Questionnaire (DASH) was used to determine the functional status of the upper extremities. Fine Manual Dexterity was measured with the Nine-Hole Peg Test (NHPT). All proximal and distal muscle strengths were significantly lower, DASH and NHPT were significantly higher in the group with ET (p < 0.05). A significant negative correlation was detected between tremor severity and all proximal and distal muscular strength and a significant positive correlation between tremor severity and DASH in group with ET (p < 0.05). However, no significant correlations were found between tremor severity and NHPT in the group with ET. It was found that older adults who had tremors had low proximal and distal muscular strength, upper extremity functionality was affected and hand skills was impaired. Furthermore tremor severity is affected by both proximal and distal muscle strength.

Bilateral transcranial direct current stimulation may be a feasible treatment of Parkinsonian tremor.

Parkinsonian tremor is a common pathological tremor that affects over 6 million people worldwide. It lowers patients' quality of life and threatens their career development, especially when patients' occupation requires dexterous manipulation. In spite of current available treatments in clinics, there is a lack of low-cost, low side-effect, effective solutions for Parkinsonian tremor. Transcranial direct current stimulation (tDCS) may be an alternative treatment. In this research, we explored the immediate effect of tDCS with a novel bilateral electrode setup over Parkinsonian tremor. In such a bilateral setup, the cathode was placed over the primary cortex contralateral to the more affected side of Parkinsonian tremor while the anode symmetrically over the other hemisphere. It was designed as a modification to the traditional cathodal setup. The performance of this bilateral setup was compared with three other setups including anodal setup, cathodal setup, and sham (control). A randomized, sham-controlled, double-blind, crossover experiment was carried out over 13 qualified patients diagnosed with idiopathic Parkinson's disease (PD). Before and after the stimulus of each tDCS setup, subjects were tested before and after tDCS with four measures, including the Unified Parkinson's Disease Rating Scale (UPDRS), Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), Purdue Pegboard Test (PPT) and a self-design Continuous Tremor Signal Assessment (CTSA). Tremor intensity calculated from CTSA data were regarded as the primary outcome of the experiment. Statistical results of CTSA, FTMTRS and PPT showed both bilateral tDCS and cathodal tDCS effectively suppressed Parkinsonian tremor. A quantitative comparison of the effect in tremor suppression indicated the optimal suppressive effect was obtained with bilateral tDCS. Based on the results of UPDRS, anodal tDCS was found to benefit subjects' overall performance the most, however, it had little effect in improving Parkinsonian tremor, as revealed by the results of other evaluations. Our study suggests a beneficial immediate effect of bilateral tDCS in Parkinsonian tremor suppression. In addition, we assume there may be an underlying interhemispheric unbalance of cortical excitability which contributes to Parkinsonian tremor genesis. Identifier: ChiCTR2100054804.

Risk factors of social anxiety in patients with essential tremor.

To study the risk factors of social anxiety (SA) in essential tremor (ET) patients. Motor, cognition, and SA were evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), Mini-Mental State Examination (MMSE), and Liebowitz Social Anxiety Scale (LSAS) for each subject. The potential risk factors of SA in ET were analyzed using univariate analysis. A total of 80 ET patients and 85 healthy controls completed the evaluation. The LSAS evaluation showed that the prevalence of SA in the ET group was 48.8%, higher than that in controls (12.9%, P < 0.001). Female (OR = 4.959, P = 0.014), younger age (OR = 4.172, P = 0.037), and head tremor (OR = 4.707, P = 0.025) were risk factors of SA among ET patients. SA is prevalent in patients with ET. Risk factors, such as female sex, age, and head tremor, should be considered for the prevention and intervention of SA in ET patients.

Combined thalamic and pallidal deep brain stimulation for dystonic tremor

BackgroundDeep brain stimulation (DBS) has been proposed to treat disabling dystonic tremor (DT), but there is debate about the optimal target. DBS of the globus pallidus interna (GPi) may be insufficient to control tremor, and DBS of the ventral intermediate thalamic nucleus (VIM) may inadequately control dystonic features, raising the question of combining both targets. ObjectivesTo report the respective effects on DT symptoms of high-frequency stimulation of the VIM, the GPi and both targets simultaneously stimulated. MethodsThree patients with DT treated by bilateral high frequency DBS of 2 targets (VIM and GPi) were assessed 12 months after surgery in 4 conditions (VIM and GPi-DBS; GPi-DBS only; VIM-DBS only; DBS switched Off for both targets) by 3 independent movement disorders specialists blinded to the condition. ResultsThe Fahn-Tolosa-Marin-tremor-rating-scale (FTM-TRS) and Burke-Fahn-Marsden-dystonia-rating-scale (BFM-DRS) scores were more improved by combined DBS than VIM alone or GPi alone. Compared to Off/Off condition, mean total FTM-TRS score decrease was 34%, 42% and 63% respectively with VIM only, GPi only and combined VIM and GPi stimulation. Mean total BFM-DRS score decrease was 34%, 37% and 60% respectively with VIM only, GPi only and combined VIM and GPi stimulation, compared to Off/Off condition. Improvement concerned both motor, functional and activities of daily living sub-scores. No complications or adverse events were observed. ConclusionCombined VIM- and GPi-DBS, by modulating the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network, both involved in DT pathophysiology, may be more efficient than single DBS targeting only one of them.

Ventral Intermediate Nucleus of the Thalamus versus Posterior Subthalamic Area: Network Meta-Analysis of DBS Target Site Efficacy for Essential Tremor

Background: Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (Vim) of the thalamus or the posterior subthalamic area (PSA) are effective treatments for essential tremor (ET). However, their relative efficacy is unknown. Objective: Here, we present the first systematic review and network meta-analysis, examining the efficacy of Vim versus PSA DBS for treating medically refractory ET. Methods: We included all primary studies that reported validated Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores pre-/postimplantation or on-/off-stimulation postimplantation, for patients receiving either Vim or PSA DBS. The primary outcome was FTM-TRS score reduction; the secondary outcome was percent reduction in score. We categorized all outcomes as short-term (≤12 months) or long-term (>12 months). Results: For pre-/postimplantation comparisons, 19 and 11 studies met inclusion criteria for short- and long-term follow-ups, respectively. For on-/off-stimulation tremor score comparisons, 8 studies met inclusion criteria for short-term follow-up. Network meta-analysis of pre-/postimplantation tremor scores showed greater tremor reduction with PSA implantation short-term (absolute tremor reduction: PSA: −30.94 [95% confidence interval (CI): −34.93, −26.95]; Vim: −26.26 [95% CI: −33.39, −19.12]; relative tremor reduction: PSA: 63.3% [95% CI: 61.8%–64.8%]; Vim: 57.8% [95% CI: 56.5%–59.0%]). However, there was no difference in efficacy between PSA and Vim DBS when comparing tremor on-versus off-stimulation at short-term follow-up or pre- versus postimplantation tremor reduction long-term. Conclusion: Our systematic review highlighted both heterogeneity in scoring systems used and lack of transparency in reporting total scores, limiting direct comparison across studies. We found a modestly superior efficacy with PSA stimulation in the short term, but no difference in tremor reduction long-term.

Deep Brain Stimulation for Arm Tremor: A Randomized Trial Comparing Two Targets.

ObjectiveDeep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) effectively suppresses arm tremor. Uncontrolled studies suggest the posterior subthalamic area (PSA) may be superior. We compared the intra‐individual efficacy of VIM‐ versus PSA‐DBS on tremor suppression and arm function.MethodsWe performed a randomized, double‐blind, crossover trial at Oslo University Hospital in patients (18–80 years) with isolated or combined action tremor affecting at least one arm. Four‐contact DBS leads were implanted (bi‐ or unilaterally) with a trajectory to cover the VIM (upper two contacts) and PSA (lower two contacts). Patients were randomized (1:1 ratio) post‐surgery to: Group 1, VIM‐stimulation months 0–3 (period 1), then PSA‐stimulation months 4–6 (period 2); Group 2, PSA‐stimulation first, then VIM‐stimulation. Primary endpoint was the difference in improvement from baseline to the end of the VIM‐ versus PSA‐period in the sum of the dominant arm tremor scores of the Fahn‐Tolosa‐Marin Tremor Rating Scale (FTMTRS), items 5/6 + 10−14.ResultsForty‐five patients were randomized to Group 1 (n = 23) or 2 (n = 22). In the primary endpoint per‐protocol analysis (mixed model, n = 40), mean difference in the sum FTMTRS score improvement for the dominant arm was −2.65 points (95% CI −4.33 to −0.97; p = 0.002). The difference in favour of PSA stimulation was highly significant in period 2, but not period 1.InterpretationOur randomized trial demonstrated that PSA stimulation provided superior tremor suppression compared with VIM stimulation. A period effect reducing tremor for up to three months in both groups was most likely attributed to a post‐surgery stun effect. ANN NEUROL 2022;91:585–601

Patients' self-assessment of essential tremor severity by a validated scale: A useful tool in telemedicine?

IntroductionThere are some validated rating scales to assess severity of Essential tremor (ET), the most common cause of action tremor. Clinical evaluation through telematic consultations has been expanding in the last decade. Patients' self-assessment of tremor severity at home could constitute a useful tool in telemedicine. This paper aims to assess intrarater and interrater reliability of ET severity using Fahn-Tolosa Marin Tremor Rating Scale (FTMTRS) for patients' and neurologists' ratings. Material and methodsPatients were instructed on how to perform and rate the FTMTRS tasks. Supervised by neurologists, each patient performed one FTMTRS self-assessment at the hospital, which was rated in a blinded way by two neurologists, and six more self-assessments at home afterwards. Postural, intention and specific-tasks tremor were rated. A cumulative linked mixed model was used to assess intrarater and interrater reliability. ResultsA total of 161 self-assessments from 19 patients were analyzed. Intrarater reliability of patients' self-ratings at home showed ICCs between 0.843 and 0.962. Interrater ICCs of neurologists' ratings were also excellent for all tremor types (0.903–0.987). Concordance between neurologists' and patients' assessments showed ICCs ranging from 0.407 to 0.824, with the higher agreement for writing/drawing-related tremor (0.824; CI 95% 0.634–0.989). ConclusionsThe rating of ET severity from FTMTRS self-assessments performed by well-trained patients at home could be a suitable clinical measure to assess tremor in non-face-to-face medical consultations. The assessment of tremor during specific tasks could be the most efficient measure for the patient self-assessment at home. These results could be useful in telemedicine.

Safety and Outcomes of Dentate Nucleus Deep Brain Stimulation for Cerebellar Ataxia.

Cerebellar symptoms remain orphan of treatment options despite being prevalent and incapacitating. Investigate whether dentate nucleus deep brain stimulation (DN DBS) is safe and leads to improvements in cerebellar symptoms when compared to sham stimulation. This randomized double-blind crossover pilot trial enrolled five patients with spinocerebellar ataxia type 3 or post-lesion ataxia. Active or sham phases were randomly performed three months apart. The primary outcome was ataxia improvement as measured by the Scale for the Assessment and Rating of Ataxia (SARA) after the active compared to the sham period. Secondary outcome measures included safety and tolerability, the Fahn-Tolosa-Marin Tremor Rating Scale (FTMRS), quality of life measurements, and patients' global impression of change. The effects on ataxia were numerically better in four out of five patients after active versus sham stimulation. The composite SARA score did not change after comparing active to sham stimulation (8.6 ± 3.6 versus 10.1 ± 4.1; p = 0.223). The FTMRS showed significant improvement after active stimulation versus sham (18.0 ± 17.2 versus 22.2 ± 19.5; p = 0.039) as did patients' global impression of change (p = 0.038). The quality of life was not modified by stimulation (p = 0.337). DN DBS was well tolerated without serious adverse events. One patient had the electrode repositioned. DN DBS is a safe and well tolerated procedure that is effective in alleviating cerebellar tremor. In this small cohort of ataxic patients, DN DBS did not achieve statistical significance for ataxia improvement.

No evidence of iron deposition in essential tremor: a susceptibility-weighted imaging study

To evaluate the role of iron deposition in subcortical nuclei of patients with essential tremor (ET). Twenty-three patients with ET underwent a standardized 3T-MRI protocol. We specifically assessed iron deposition using susceptibility-weighted angiography (SWAN) images in seven specific regions of interest (ROIs): the thalamus, putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus, and dentate nucleus. Tremor in ET patients was clinically assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). ET patient data were compared with data obtained from 23 Parkinson's disease (PD) patients and 14 healthy subjects (HS). No differences in iron deposition in the seven ROIs were found between ET patients and HS. Conversely, PD patients showed increased iron deposition in the substantia nigra in comparison with both ET patients and HS. Our results indicate the absence of iron deposition in subcortical nuclei of ET patients, which is generally considered a marker of neurodegeneration.

Impaired integrity of commissural and association fibers in essential tremor patients: Evidence from a diffusion tensor imaging study

Background/aimThe evolving understanding of essential tremors (ET) has led to a new definition of neurodegenerative disease, pointing to diffuse brain network involvement with a wide spectrum of associated motor and nonmotor symptoms. Considering the fact that white matter should also be affected by the nature of the disease, our study aimed to evaluate the integrity of white matter and its clinical correlations in ET patients. Materials and methodsApproximately 40 patients diagnosed with ET and 40 age-and sex-matched control subjects (ranging between 18–80 years old) were included in the study. The sociodemographic characteristics and clinical features of the patients were recorded. Tremors were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). Diffusion Tensor Imaging (DTI) was performed to evaluate the integrity of white matter. The selected white matter regions used for DTI assessment were the corpus callosum (CC) (i.e., the largest commissural tract in the human brain), the superior longitudinal fasciculus (SLF), and the inferior longitudinal fasciculus (ILF) (i.e., the largest association fiber bundles). Results The mean age of the ET patients and control subjects was 44.23 ± 18.91 and 37.45 ± 10.95 years old (P = 0.542). The fractional anisotropy (FA) values of the CC body (P = 0.003), ILF (p = 0.016), average diffusion coefficient (ADC) values of the CC body (p = 0.001), genu (P = 0.049), SLF (V < 0.001), and ILF (P < 0.001) differed between groups. After controlling for age and sex, there was no correlation between tremor severity and DTI parameters, but impaired integrity in the genu of CC FA (P = 0.035, r = 0.442) and the splenium of CC ADC (P = 0.007, r = 0.543) were related with a longer duration of tremor. Finally, positive family history was correlated with the splenium of CC FA and ADC (P = 0.008, r = 0.536; P = 0.027, r = 0.461) and ILF ADC (P = 0.011, r = –0.519).Conclusion In our study, major white matter structure changes were found in the ET patients. The results suggest that possible neurodegeneration also affects white matter structures in ET patients and that the duration of the tremor and family history are related with impaired integrity of white matter.

Botulinum Toxin Monotherapy for the Treatment of Essential Tremor: Life Quality Effect.

This study aims to evaluate the effectiveness of botulinum toxin therapy, as a monotherapy, and its effect on quality of life in patients with essential tremor (ET) who are resistant to medical treatment or cannot tolerate optimum drug doses in the population. This retrospective research was conducted between February 2019 and December 2019 with 15 adult patients (9 men and 6 women) in the 50-to-70 age group, who had a definite diagnosis of ET as evaluated by the same clinician. With the help of electroneuromyography, intramuscular onabotulinum toxin A (BoNT-A) injection was administered to the related muscles, not exceeding 100 U in total. Demographic characteristics and duration of disease of all patients were recorded. The tremor severity of patients before the injection, 1 month after the injection, and 3 months after the injection was assessed by the Fahn-Tolosa-Marín Tremor Rating Scale (FTM-TRS), applied by the same clinician during the face-to-face interviews, in addition to the Questionnaire for Essential Tremor (QUEST), which was filled out by participants. The first month and third month mean QUEST and FTM-TRS scores were statistically lower than that before the procedure in patients with ET after BoNT-A injection (P = 0.001, P = 0.001, P = 0.001, and P = 0.001). In addition, the mean FTM-TRS and QUEST scores for the first month after the procedure were significantly lower than the mean FTM-TRS and QUEST scores for the third month (P = 0.005 and P = 0.007). We believe that our study is valuable because there is no research on the effect of BoNT-A administration on ET treatment in the our country population and because the effect of BoNT-A treatment on quality of life in patients with ET was evaluated using the ET-specific QUEST scale.

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.

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.

Efficacy of low dose rituximab in treatment-resistant CIDP with antibodies against NF-155

We herein to describe the response and the potential treatment mechanism of low dose rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against neurofascin-155 (NF-155). Patients received 100 mg rituximab once weekly for 4 weeks followed by 100 mg per month for 2 additional doses. Clinical function scores, Fahn- Tolosa-Marin Tremor Rating Scale (FTMTRS) and flow cytometry of peripheral blood were scheduled before and at 1, 3, 6 months after rituximab treatment. All clinical function score including MRC, INCAT, Hughes, mRS, ODSS and FTMTRS scores showed obvious improvement at the post-treatment follow-up 1,3,6 months in comparison with baseline values. The proportion of CD19 + CD27+, CD19 + CD38+ and CD138 in lymphocytes of all patients declined at 1,3,6 month and the proportion of CD19 + CD24hiCD38hi in one patient was increased at 6 months after rituximab treatment. Low dose rituximab can significant improve disease severity and disabling tremor of CIDP patients with anti-NF155 antibody by the powerful role of B cell depletion within six months and subsequent reestablishment of B-cell subsets including increasing regulatory B cells, inhibiting memory B cells and reducing plasmablasts.

Clinical Efficacy of Bilateral Deep Brain Stimulation Does Not Change After Implantable Pulse Generator Replacement but the Impedances Do: A Prospective Study

Deep brain stimulation (DBS) is an approved therapy option for movement disorders such as Parkinson's disease (PD), essential Tremor (ET), and dystonia. While current research focuses on rechargeable implantable pulse generators (IPGs), little is known about changes of the motor functions after IPG replacement and the consequences of additionally implanted hardware. To assess changes of the motor functions, the therapy impedances, and the total electric energy delivered (TEED) after elective IPG replacement. We prospectively acquired the data of 47 patients with PD, ET, and dystonia treated with bilateral DBS. Motor functions were rated prior to and after surgery using the revised Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTM-TRS), and the Unified Dystonia Rating Scale (UDRS). Furthermore, the therapy impedances and TEED were assessed at the aforementioned times. While preoperative motor scores were 48.32 ± 17.16 in PD, 39.71 ± 12.28 in ET, and 18.48 ± 16.30 in dystonia patients, postoperative scores were 47.84 ± 24.33, 32.86 ± 15.82, and 15.02 ± 15.17, respectively. Only in dystonia patients, motor scores significantly differed. Perioperative therapy impedance changes were 142.66 ± 105.35 Ω (Kinetra® to Activa® PC), -68.75 ± 43.05 Ω (Activa® PC to Activa® PC), and - 51.38 ± 38.75 Ω (Activa® PC to Activa® RC). Perioperative TEED changes were - 37.15 ± 38.87 μJ, 2.03 ± 35.91 μJ, and 12.39 ± 6.31 μJ in that first, second, and third group, respectively. Both the therapy impedances and TEED significantly differed between groups. Although there were no statistically significant changes in the motor functions of all patients after elective IPG replacement, the therapy impedances were significantly higher and TEED was significantly lower after IPG replacement with concurrent Pocket Adapter implantation.