Dystonia Patients Research Articles

The correlation between motor improvement and disability in activities of daily living after DBS in Parkinson’s disease, tremor and dystonia

BackgroundDeep brain stimulation (DBS) for Parkinson’s disease (PD), essential tremor (ET), and dystonia is a well-established treatment option. The correlation between motor symptom improvement and effect on disability is inconclusive. ObjectivesTo assess the correlation between DBS-induced improvements of motor symptoms and disability for PD, ET and dystonia. MethodsDisability and motor scores were obtained before and six to twelve months after surgery for 324 PD, 35 ET and 40 dystonia patients. ResultsThere was a modest and significant correlation for PD (Rho=0.284, p < 0.001), a substantial and significant correlation for ET (Rho=0.542, p < 0.001) and no correlation for dystonia (Rho=0.238, p = 0.138) between motor score and disability improvement. ConclusionsThe effect of DBS on motor symptoms and disability is not uniformly for dystonia. Possible reasons for this are that the scales used might not be responsive or other symptoms than motor symptoms might have a greater impact on disability.

Pallidal neuronal activity in Gilles de la Tourette syndrome and dystonic patients: A comparative study.

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single-neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low-frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes.

Clinical and physiological characteristics of tremor in a large cohort of focal and segmental dystonia

ObjectiveTremor is a frequent co-occurring feature in patients with dystonia, especially in focal and segmental dystonia. Clinical studies have shown that tremor is more commonly observed when dystonia spreads to contiguous body regions. However, there is insufficient characterization of tremor physiology in focal and segmental forms of dystonia. We aimed to ascertain the characteristics of tremor presenting in these specific subtypes.MethodsWe enrolled dystonia patients with head and arm tremors presenting to our center. We categorized these participants as focal and segmental dystonia following the Movement Disorders Society guidelines. We recorded the frequency, amplitude, rhythmicity, burst duration, and discharge pattern on accelerometer and electromyography recordings. We compared the physiology of tremors in focal vs. segmental dystonia. We determined whether the physiology was affected by clinical features such as demographics, age at onset, dystonia duration, alcohol responsiveness, family history, and botulinum toxin responsiveness.Results72 patients, mainly focal cervical dystonia and focal cervical + arm or cranial dystonia (segmental) were enrolled. In the analysis of the head tremor recordings (n = 66; frequency range 3–6.5 Hz), we found that focal vs. segmental dystonia comparisons revealed a significantly lower frequency (mean ± standard deviation; 4.0 ± 0.9 Hz vs. 4.7 ± 1.0 Hz; p = 0.02), lower amplitude (0.004 ± 0.008 g2/Hz vs. 0.006 ± 0.008 g2/Hz; p = 0.03) and longer muscle burst durations (111.1 ± 40.4 ms vs. 91.5 ± 24 ms; p = 0.04). In the analysis of arm tremor recordings (n = 31; frequency range 3.5–7 Hz), we found focal vs. segmental dystonia comparison revealed a lower amplitude (0.04 ± 0.07 g2/Hz vs. 0.06 ± 0.06 g2/Hz; p = 0.045). In the stepwise regression analysis, the age at evaluation (β - 0.44; p = 0.006) and age at onset (β - 0.61; p = 0.005) significantly predicted the head tremor frequency whereas the alcohol responsiveness tended to predict the amplitude of the head tremor (β - 0.5; p = 0.04) and the arm tremor (β - 0.6; p = 0.02).ConclusionOur study found that the physiological characteristics of tremor in focal and segmental dystonia are somewhat distinct, suggesting that the spread of dystonia symptoms from one body region to another may have a bearing on the physiology of co-occurring tremor. The frequency of head tremors in younger participants was observed to be higher compared to older participants. The head and arm tremor tended be less severe in patients reporting alcohol responsiveness.

Striato-pallidal oscillatory connectivity correlates with symptom severity in dystonia patients

Dystonia is a hyperkinetic movement disorder that has been associated with an imbalance towards the direct pathway between striatum and internal pallidum, but the neuronal underpinnings of this abnormal basal ganglia pathway activity remain unknown. Here, we report invasive recordings from ten dystonia patients via deep brain stimulation electrodes that allow for parallel recordings of several basal ganglia nuclei, namely the striatum, external and internal pallidum, that all displayed activity in the low frequency band (3–12 Hz). In addition to a correlation with low-frequency activity in the internal pallidum (R = 0.88, P = 0.001), we demonstrate that dystonic symptoms correlate specifically with low-frequency coupling between striatum and internal pallidum (R = 0.75, P = 0.009). This points towards a pathophysiological role of the direct striato-pallidal pathway in dystonia that is conveyed via coupling in the enhanced low-frequency band. Our study provides a mechanistic insight into the pathophysiology of dystonia by revealing a link between symptom severity and frequency-specific coupling of distinct basal ganglia pathways.

ID: 309247 Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: Sub-Analysis of Cervical Dystonia Patients

ID: 309247 Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: Sub-Analysis of Cervical Dystonia Patients

Cervical dystonia patients with psychiatric classification: Despite dystonia improvement less improvement in other domains after DBS surgery

BackgroundPatient satisfaction of deep brain stimulation (DBS) for cervical dystonia (CD) is heterogeneous. A high prevalence of psychiatric disorders in patients with CD is well-established. The presence of psychiatric classification in CD may affect the outcomes of DBS treatment. MethodsA cohort of 49 patients with CD and GPi-DBS was retrospectively studied in two centers. Psychiatric history was obtained from patient records. Pre- and post-operative Toronto Western Spasmodic Torticollis Rating Scores (TWSTRS, range 0–85) were compared between patients with and those without psychiatric classification. The TWSTRS disability and pain sub-scores were combined to evaluate non-motor improvement. The severity sub-score was used to assess motor improvement. ResultsTwenty (40.8 %) patients had a psychiatric classification, predominantly major depressive disorder and anxiety disorders. Following DBS treatment, the overall mean (± SD) improvement on the TWSTRS was 38.0 ± 29.2 %. Significantly, patients with a psychiatric classification experienced less improvement in the non-motor domain than the patients without a psychiatric classification (29.1 ± SD 38.2 % [range −41.7 to 96.6 %] vs. 51.9 ± 33.6 % [range −8.6 to 100.0 %]; p = 0.02). ConclusionOur findings indicate that CD patients with psychiatric classifications experience less non-motor improvement following DBS. Psychiatric comorbidities could influence the lacking experience of successful DBS treatment despite good motor outcome. Therefore, it is important to establish these comorbidities in CD patients undergoing DBS with respect to expectation management and treatment if necessary.

Treatment response to onabotulinumtoxinA in cervical dystonia patients with anterocollis and retrocollis

Anterocollis (AC) and retrocollis (RC) are less common cervical dystonia (CD) subtypes that are often under-represented in CD clinical trials. Herein we describe real-world demographics, disease characteristics, and treatment response to onabotulinumtoxinA (onabotA) in AC or RC patients from an observational, multicenter, prospective registry, CD PROBE. After three onabotA treatments, outcomes (CDIP-58, PGIC, CGIC, CD severity, TWSTRS) in patients with predominant AC or RC were compared to torticollis (TC) and all CD subtypes combined. The mean dosages at each treatment ranged from 153.5 to 195.4 U (AC) to 184.0–213.4 U (RC). After treatment, AC and RC patients reported improvements in the CDIP-58. “Much” or “very much improved” on PGIC and CGIC was reported by AC patients (n = 11/23, 48%) and clinicians (n = 14/23, 61%); and by RC patients (n = 14/24, 58%) and clinicians (n = 19/24, 83%). The mean total TWSTRS decreased from 45.7 (n = 59) to 36.1 (n = 23, 21.0% improvement) for AC patients and from 40.1 (n = 55) to 31.6 (n = 23, 21.2% improvement) for RC patients; the proportion of AC and RC patients with severe CD decreased. Outcomes for AC and RC were generally consistent with those for TC and all subtypes combined. Dysphagia was reported in 4/59 (6.8%) of AC patients (one serious), 7/55 (12.7%) of RC patients (none serious), 29/494 (5.9%) of TC patients (none serious), and 64/1012 (6.3%) of all CD patients (two serious). No new safety signals were identified. In conclusion, treatment with onabotA may relieve CD symptoms in some patients with AC and RC, consistent with results for other CD subtypes and the known safety profile of onabotA for the treatment of CD.

Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

Health-Related Quality of Life in Romanian Patients with Dystonia: An Exploratory Study.

Background/Objectives: Dystonia is a neurological movement disorder characterized by involuntary muscle contractions that lead to abnormal movements and postures; it has a major impact on patients' health-related quality of life (HRQoL). The aim of this study was to examine the HRQoL of Romanian patients with dystonia using the EQ-5D-5L instrument. Methods: Responses to the EQ-5D-5L and the visual analogue scale (VAS) were collected alongside demographic and clinical characteristics. Health profiles were analyzed via the metrics of the EQ-5D-5L, severity levels, and age groups. Using Shannon's indexes, we calculated informativity both for patients' health profile as a whole and each individual dimension. Level sum scores (LSS) of the EQ-5D-5L were calculated and compared with scores from the EQ-5D-5L index and VAS. The HRQoL measures were analyzed through demographic and clinical characteristics. Descriptive statistics, Spearman correlation, and non-parametric tests (Mann-Whitney U or Kruskall-Wallis H) were used. The level of agreement between HRQoL measures was assessed using their intraclass correlation coefficient (ICC) and Bland-Altman plots. Results: A sample of 90 patients was used, around 75.6% of whom were female patients, and the mean age at the beginning of the survey was 58.7 years. The proportion of patients reporting "no problems" in all five dimensions was 10%. The highest frequency reported was "no problems" in self-care (66%), followed by "no problems" in mobility (41%). Shannon index and Shannon evenness index values showed higher informativity for pain/discomfort (2.07 and 0.89, respectively) and minimal informativity for self-care (1.59 and 0.68, respectively). The mean EQ-5D-5L index, LSS, and VAS scores were 0.74 (SD = 0.26), 0.70 (SD = 0.24), and 0.61 (SD = 0.21), respectively. The Spearman correlations between HRQoL measures were higher than 0.60. The agreement between the EQ-5D-5L index and LSS values was excellent (ICC = 0.970, 95% CI = 0.934-0.984); the agreement was poor-to-good between the EQ-5D-5L index and VAS scores (ICC = 683, 95% CI = 0.388-0.820), and moderate-to-good between the LSS and VAS scores (ICC = 0.789, 95% CI = 0.593-0.862). Conclusions: Our results support the utilization of the EQ-5D-5L instrument in assessing the HRQoL of dystonia patients, and empirical results suggest that the EQ-5D-5L index and LSS measure may be used interchangeably. The findings from this study highlight that HRQoL is complex in patients with dystonia, particularly across different age groups.

Does botulinum toxin affect psycho-social aspects in dystonia?

Dystonia is a movement disorder in which sustained muscle contractions give rise to abnormal postures or involuntary movements. It is a disabling and disfiguring disorder that affects activities of daily living and gives people a bizarre appearance often associated with psychological morbidity, embarrassment and social avoidance. Intramuscular injection of botulinum toxin (BoNT) is the most effective treatment for motor symptoms in focal dystonia, but little is known about its impact on the psycho-social dimension. The main aim of this study was to evaluate psycho-social changes in patients with focal dystonia after starting BoNT treatment using self-reported scales. The Beck Depression Inventory (BDI-II), the 36-Item Short Form Health Survey (SF-36), the Body Uneasiness Test (BUT), the State-Trait Anxiety Inventory (STAI) and the Visual Analogue Scale (VAS) assessing body self-image, satisfaction with physical aspects, social avoidance, self-reported depression, and self-distress were completed by 11 patients with dystonia and 9 patients with hyperhidrosis as a control group before BoNT (T0). VAS was then performed after four weeks (T1) to assess whether BoNT induced changes in the psychosocial dimension. Our results showed that only depressive symptoms and rumination about body defects improved in patients with dystonia after BoNT treatment, while improvement in self-distress and satisfaction with physical aspects was also found in hyperhidrosis. Individuals with hyperhidrosis experience poorer psychological well-being and suffer from higher levels of distress compared to dystonic patients. This suggests that individuals with this disabling condition are more vulnerable to social impact than dystonic patients.

Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is a viable and efficacious treatment option for dystonia. While the internal pallidum serves as the primary target, more recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its complex surroundings have not been studied in depth. Indeed, multiple historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the exact same target. Therefore, a thorough investigation of the neural substrates underlying effects on dystonia symptoms is warranted. Here, we analyze a multi-center cohort of isolated dystonia patients with subthalamic implantations (N = 58) and relate their stimulation sites to improvement of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions was associated with improvement in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvement in limb dystonia and blepharospasm. This dissociation was also evident for structural connectivity, where the cerebellothalamic, corticospinal and pallidosubthalamic tracts were associated with improvement of cervical dystonia, while hyperdirect and subthalamopallidal pathways were associated with alleviation of limb dystonia and blepharospasm. Importantly, a single well-placed electrode may reach the three optimal target sites. On the level of functional networks, improvement of limb dystonia was correlated with connectivity to the corresponding somatotopic regions in primary motor cortex, while alleviation of cervical dystonia was correlated with connectivity to the recently described 'action-mode' network that involves supplementary motor and premotor cortex. Our findings suggest that different types of dystonia symptoms are modulated via distinct networks. Namely, appendicular dystonia and blepharospasm are improved with modulation of the basal ganglia, and, in particular, the subthalamic circuitry, including projections from the primary motor cortex. In contrast, cervical dystonia was more responsive when engaging the cerebello-thalamo-cortical circuit, including direct stimulation of ventral thalamic nuclei. These findings may inform DBS targeting and image-based programming strategies for patient-specific treatment of dystonia.

Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia

BackgroundDystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia. Objectives and Methods-To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins. ResultsAmong 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain. ConclusionOur whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.

Genome sequencing reanalysis increases the diagnostic yield in dystonia

PurposeWe investigated the contribution of genomic data reanalysis to the diagnostic yield of dystonia patients who remained undiagnosed after prior genome sequencing. MethodsProbands with heterogeneous dystonia phenotypes who underwent initial genome sequencing (GS) analysis in 2019 were included in the reanalysis, which was performed through gene-specific discovery collaborations and systematic genomic data reanalysis. ResultsInitial GS analysis in 2019 (n = 111) identified a molecular diagnosis in 11.7 % (13/111) of cases. Reanalysis between 2020 and 2023 increased the diagnostic yield by 7.2 % (8/111); 3.6 % (4/111) through focused gene-specific clinical correlation collaborative efforts [VPS16 (two probands), AOPEP and POLG], and 3.6 % (4/111) by systematic reanalysis completed in 2023 [NUS1 (two probands) and DDX3X variants, and a microdeletion encompassing VPS16]. Seven of these patients had a high phenotype-based dystonia score ≥3. Notable unverified findings in four additional cases included suspicious variants of uncertain significance in FBXL4 and EIF2AK2, and potential phenotypic expansion associated with SLC2A1 and TREX1 variants. ConclusionGS data reanalysis increased the diagnostic yield from 11.7 % to 18.9 %, with potential extension up to 22.5 %. While optimal timing for diagnostic reanalysis remains to be determined, this study demonstrates that periodic re-interrogation of dystonia GS datasets can provide additional genetic diagnoses, which may have significant implications for patients and their families.

"Lombard Effect" and Voice Changes in Adductor Laryngeal Dystonia: A Pilot Study.

The aim was to describe the acoustic, auditory-perceptive, and subjective voice changes under the Lombard effect (LE) in adductor laryngeal dystonia (AdLD) patients. Subjective perception of vocal effort (OMNI Vocal Effort Scale OMNI-VES), Maximum Phonation Time (MPT), and the perceptual severity of dysphonia (GRBAS scale) were assessed in condition of stillness and under LE in 10 AdLD patients and in 10 patients with typical voice. Speakers were asked to produce the sustained vowel /a/ and to read a phonetically balanced text aloud. Using the PRAAT software, the following acoustic parameters were analyzed: Mean Pitch (Hz), Minimum and Maximum Intensity (dB), the Fraction of Locally Unvoiced Frames, the Number of Voice Breaks, the Degree of Voice Breaks (%), the Cepstral Peak Prominence-Smoothed (CPPS) (dB). Under LE, the AdLD group showed a decrease of both G and S parameters of GRBAS and subjective effort, mean MPT increased significantly; in the controls there were no significant changes. In both groups under LE, pitch and intensity of the sustained vowel /a/ significantly increased consistently with LE. In the AdLD group the mean gain of OMNI-VES score and the mean gain of each parameter of the speech analysis were significantly greater than the controls' ones. Auditory feedback deprivation obtained under LE improves subjective, perceptual-auditory, and acoustics parameters of AdLD patients. These findings encourage further research to provide new knowledge into the role of the auditory system in the pathogenesis of AdLD and to develop new therapeutic strategies. 4 Laryngoscope, 134:3754-3760, 2024.

Prediction of subthalamic stimulation efficacy on isolated dystonia via support vector regression

IntroductionDeep brain stimulation (DBS) of subthalamic nucleus (STN) has been well-established and increasingly applied in patients with isolated dystonia. Nevertheless, the surgical efficacy varies among patients. This study aims to explore the factors affecting clinical outcomes of STN-DBS on isolated dystonia and establish a well-performed prediction model. MethodsIn this prospective study, thirty-two dystonia patients were recruited and received bilateral STN-DBS at our center. Their baseline characteristics and up to one-year follow-up outcomes were assessed. Implanted electrodes of each subject were reconstructed with their contact coordinates and activated volumes calculated. We explored correlations between distinct clinical characteristics and surgical efficacy. Those features were then trained for the model in outcome prediction via support vector regression (SVR) algorithm and testified through cross-validation. ResultsPatients demonstrated an average clinical improvement of 56 ± 25 % after STN-DBS, significantly affected by distinct symptom forms and activated volumes. The optimal targets and activated volumes were concentratedly located at the dorsal posterior region to STN. Most patients had a rapid response to STN-DBS, and their motor score improvement within one week was highly associated with long-term outcomes. The trained SVR model, contributed by distinct weights of features, could reach a maximum prediction accuracy with mean errors of 11 ± 7 %. ConclusionSTN-DBS demonstrated significant and rapid therapeutic effects in patients with isolated dystonia, by possibly affecting the pallidofugal fibers. Early improvement highly indicates the ultimate outcomes. SVR proves valid in outcome prediction. Patients with predominant phasic and generalized symptoms, shorter disease duration, and younger onset age may be more favorable to STN-DBS in the long run.

Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: Sub-analysis of Cervical Dystonia Patients (P1-3.018)

Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: Sub-analysis of Cervical Dystonia Patients (P1-3.018)

1137 Prospective, Multicenter, International Registry of Deep Brain Stimulation for Dystonia: A Sub-analysis of Cervical Dystonia Patients

INTRODUCTION: Management of dystonia using Deep Brain Stimulation (DBS) is a well-established therapeutic approach. However, optimal DBS target sites in patients with cervical (focal) versus generalized dystonia are thought to diverge and be specific for particular connections (Horn 2022). DBS devices equipped with capabilities such as directionality and Multiple Independent Current Control (MICC) may offer potential for improved clinical outcomes. METHODS: This is a sub-analysis of patients with focal (cervical) dystonia only or cervical dystonia in the context of segmental or generalized dystonia assessed as part of a prospective, multicenter, international dystonia registry (NCT02686125). All patients receive an MICC-based, directional DBS system (Vercise, Boston Scientific). Patients are followed up to 3-years (post-implant). Several study assessments are being collected to evaluate their dystonia symptoms (e.g., TWSTRS), quality of life, and overall satisfaction. Adverse Events are also collected. RESULTS: A total of 43-patients (mean age 56.9-years, 58% females) with focal (cervical) dystonia only and 83 patients (mean 41.95-years, 61% females) with cervical dystonia in context of segmental or generalized dystonia have been evaluated. Both groups reported significant improvement in overall TWSTRS scores – however the extent varied. In the cervical-only cohort, a 19.9-point improvement was noted at 6-months (n = 25) and sustained up to 1-year (23.2-point improvement, n = 20). In those with cervical dystonia within frame of segmental or generalized dystonia, a 9.7-point and 7.3-point improvement in overall TWSTRS scores was noted at 6- (n = 50) and 12-months (n = 38), respectively. Updated data will be reported. CONCLUSIONS: This registry represents the first comprehensive, large-scale collection of real-world outcomes associated with dystonia patients implanted with a directional DBS system capable of MICC. Preliminary results demonstrate significant improvement in patients with cervical dystonia (alone or in context of segmental or generalized dystonia) following DBS.

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome

ObjectiveIndividual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. MethodsPatients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. ResultsAmong the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). ConclusionIn our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Pallidal multifractal complexity is a new potential physiomarker of dystonia

ObjectiveLow-frequency 4–12 Hz pallidal oscillations are being considered as potential physiomarkers for dystonia. We suggest investigating the multifractal properties of pallidal activity as an additional marker. MethodsWe employed local field potentials (LFP) recordings from 23 patients with dystonia who were undergoing deep brain stimulation (DBS) surgery to explore the connection between disease severity and the multifractal characteristics of pallidal activity. Furthermore, we performed an analysis of LFP recordings from four patients, following the externalization of DBS lead electrodes, to investigate the impact of DBS and neck muscle vibration on multifractal parameters. ResultsGreater dystonia severity exhibited a correlation with a narrower multifractal spectrum width but higher multifractal spectral asymmetry. Both GPi DBS and muscle vibration in dystonia patients expanded the multifractal spectrum width while restoring multifractal spectral symmetry. Notably, the threshold peak intensities for an increase in multifractal spectrum width substantially overlapped with the optimal volume of tissue activated. A broader multifractal spectrum during DBS corresponded to more favorable clinical outcomes. ConclusionsMultifractal properties of pallidal neuronal activity serve as indicators of neural dysfunction in dystonia. SignificanceThese findings suggest the potential of utilizing multifractal characteristics as predictive factors for the DBS outcome in dystonia.

Effect of Thalamic versus Pallidal Deep Brain Stimulation on Head Tremor in Dystonic and Essential Tremor Patients-A Retrospective Video-Blinded Study.

Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically-refractory cases. In most DBS-centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi- versus Vim-DBS in dystonic or essential head tremor. All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short- (mean 10 months) and long-term follow-up (41 months) by two blinded video-raters. Twenty-two patients with dystonic head tremor received either GPi- (n = 12) or Vim-stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim-stimulation. The reduction in head tremor from baseline to short- and long-term follow-up was 60-70% and did not differ significantly between the three groups. GPi-DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim-DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim-DBS on head tremor in ET.