Cervical Dystonia Research Articles

Visual dysfunction of superior colliculus and lateral geniculate nucleus in idiopathic blepharospasm

BackgroundThe etiology and pathophysiology of idiopathic blepharospasm (BP) are still largely unknown. It has been hypothesized that BP is the consequence of a dysfunction of the basal ganglia loop, although cortical areas, cerebellum, and other brainstem structures may be involved. There is some evidence that the superior colliculus (SC), a sensorimotor brainstem structure, is involved in another adult-onset focal dystonia, the cervical dystonia. To date, there is no data concerning the implication of the SC in BP. ObjectivesOur study aims to investigate the role of the SC in people with idiopathic BP compared to controls using fMRI and a visual stimulation paradigm based on luminance contrast variations. MethodsPeople with idiopathic BP and controls underwent brain fMRI using a standardized protocol, allowing modulation of visual activity in the SC, the lateral geniculate nucleus (LGN), and the primary visual cortex (V1), at increasing luminance levels (1 %, 3 %, 5 %, 9 %). ResultsTen BP women and ten sex- and age-matched controls were enrolled. Compared to controls, the BP group showed no modulation of visual responses at all luminance levels (p < 0.05) in both SC and LGN. In BP, BOLD responses in V1 were significantly lower at 5 % (p = 0.001), and 9 % (p = 0.002) luminance level. ConclusionsOur findings support the concept of SC and LGN dysfunction in idiopathic BP. Brain fMRI, targeting these sub-cortical visual structures, could play a future important role both as a biomarker and in our understanding of the pathophysiology of adult-onset focal dystonias.

External Factors Modulating Pain and Pain-Related Functional Impairment in Cervical Dystonia.

Little is known about factors modulating pain and pain-related functional impairment in isolated cervical dystonia (CD). The aim was to assess the prevalence and interrelationship between pain-modulating factors and pain-related determinants of functional impairment and quality of life in CD. We analyzed pain-aggravating and pain-relieving external factors, the degree of pain-related functional impact on routine activities, and the relationship between these and pain severity, using cross-sectional data collected using the Pain in Dystonia Scale (PIDS) from 85 participants with CD. Pairwise correlation analyses and age- and sex-adjusted linear regression models estimated the relationship between pain-modulating factors and pain severity, and the impact of pain severity, dystonia severity, and psychiatric symptoms on pain-related functional impairment and disease-specific quality of life (measured using the Craniocervical Dystonia Questionnaire-24). Stress and prolonged fixed position were the most frequent and impacting pain triggers, with women reporting larger impact. The average impact of pain-relieving factors was lower than that of pain triggers. Physical exercise and social gatherings were the most impacted activities by pain in CD. The intensity of external modulating factors was a predictor of pain severity. Severity of pain, CD, and psychiatric symptoms independently predicted pain-related functional impairment, whereas quality of life was predicted by pain severity, pain-related functional impairment, and psychiatric symptom severity, but not dystonia severity. The PIDS provides insight into external modulation and functional impact of pain in CD. The pattern of external modulation of pain in CD is in line with a multifactorial modulation and complex physiology.

Dysphagia and Muscle Weakness Secondary to Botulinum Toxin Type A Treatment of Cervical Dystonia: A Drug Class Analysis of Prescribing Information.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Predisposing factors to pattern change in cervical dystonia.

Cervical dystonia (CD) patterns may change with Botulinum toxin (BoNT) treatment. To evaluate the time within those changes usually occur, the most predisposed phenotypes and predisposing factors. We divided idiopathic CD patients into two groups- change YES and NO, collecting general clinical and demographic variables. We also evaluated duration of BoNT treatment, Tsui total scores and subscores - assessed at T0 - before BoNT start - and at T1- time to chenge in the YES group or last visit in the NO group. The risk of pattern change was assessed by Kaplan Meyer curves and Cox regression analysis. Finally, Multivariate linear regressions were employed to assess if Tsui severity correlated with the change. Among 100 patients (60 women), 37 experienced a phenotype switch, mostly in the first five years of BoNT treatment, YES and NO groups were comparable. Multivariate Cox Regression revealed the presence of laterocollis or rotatocollis at T0 as predictors of switch (respectively P = 0.01, HR = 3.5; P = 0.03, HR = 1.5). Multivariate linear regressions revealed that high Tsui subscores for the tilt and low Tsui total scores were risk factors for the change of pattern (respectively P = 0.002, OR = 6; P = 0.03, OR = 0.8). Latero and Rotatocollis are the CD phenotypes most predisposed to change. CD characterized by neck tilt are more likely to change phenotype following treatment. Dystonias with a low degree of severity are more predisposed to switch. Both, the different degree of muscle activation and BoNT mechanism of action, may impact on that phenomenon.

Doses of Botulinum Toxin in Cervical Dystonia: Does Ultrasound Guidance Change Injection Practices?

Cervical dystonia is widely understood to benefit from botulinum toxin injections. The injection practices may be influenced by specific factors, including the method of injection. Three main guidance methods can be used: palpation of anatomical landmarks, ultrasound, and electromyography. We investigated how target muscles and doses of botulinum toxin were modified after the transition from surface anatomy (non-guided) to ultrasound (US-guided), in patients with cervical dystonia. We also determined the long-term dose trend. We studied a group of 82 patients, who received non-guided injections (median: 16.5 cycles/5.1 years) followed by US-guided injections (median: 12.0 cycles/3.8 years). More muscles, and especially deep muscles, were injected during the US-guided period. The total dose and number of injected muscles were higher when US guidance was used, but the mean dose per muscle was lower. Over the long term, the total dose stabilized, and the mean dose per muscle decreased during the US-guided period. According to our results, the guidance method has a strong impact on the botulinum toxin injection strategy in cervical dystonia (target muscles and dose). Also, the treatment appeared more stable when using US guidance; this could be explained by the good precision of such injections.

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.

Interdisciplinary Consensus in Evaluating the Severity Subscale of the Original and Revised Toronto Western Spasmodic Torticollis Rating Scale Through Video-Based Assessment: An Inter-Rater Reliability Study.

Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is widely employed for cervical dystonia (CD) evaluation. To assess the inter-rater reliability of the severity subscale of the original and revised TWSTRS using video recordings. Three raters, a PhD student with a nursing degree, a physiotherapist specialized in CD, and a neurologist-in-training independently rated all videos. The inter-rater reliability was assessed with the intra-class correlation coefficient (ICC). The total severity score of both tools demonstrated a good inter-rater reliability (ICC = 0.87 to 0.88). The inter-rater reliability of individual sub-items varied from poor (ICC = 0.29) to excellent (ICC = 0.9). The total severity score of both TWSTRS showed good inter-rater reliability in a multidisciplinary team, indicating their applicability for online patients' assessment. We recommend using the total subscale for outcome comparison. Furthermore, there is a need for more accurate definitions of duration factor and shoulder elevation.

Atrophy of cerebellar lobule VI and primary motor cortex in cervical dystonia - a region of interest-based study.

Recently, a network model of cervical dystonia (CD) has been adopted that implicates nodes and pathways involving cerebellar, basal-ganglia and cortico-cortical connections. Although functional changes in the cerebello-thalamo-cortical network in dystonia have been reported in several studies, structural information of this network remain sparse. To characterize the structural properties of the cerebellar motor network in isolated CD patients. This includes cerebellar lobules involved in motor processing, the dentate nucleus (DN), the thalamus, and the primary motor cortex (M1). Magnetic resonance imaging data of 18 CD patients and 18 healthy control subjects were acquired. In CD patients, the motor part of the Toronto Western Spasmodic Torticollis Rating Scale was assessed to evaluate motor symptom severity. The volume of cerebellar lobules I-VI and VIII, the DN and thalamus, and the cortical thickness (CT) of M1 were determined for a region of interest (ROI)-based quantitative analysis. Volumes/CT of these ROIs were compared between groups and associated with motor symptom severity in patients. The volume of lobule VI and the CT of M1 were reduced in CD patients. The volumes of the other ROIs were not different between groups. No association was identified between the structural properties of lobule VI or M1 and the severity of CD motor symptoms. Atrophy within the cerebellum and M1 contributes to CD's complex motor network pathology. Further investigations are needed to ascertain the mechanisms underlying the local volume loss.

Brain metabolic response to repetitive transcranial magnetic stimulation to lesion network in cervical dystonia

BackgroundA previous study identified a brain network underlying cervical dystonia (CD) based on causal brain lesions. This network was shown to be abnormal in idiopathic CD and aligned with connections mediating treatment response to deep brain stimulation, suggesting generalizability across etiologies and relevance for treatment. The main nodes of this network were located in the deep cerebellar structures and somatosensory cortex (S1), the latter of which can be easily reached via non-invasive brain stimulation. To date, there are no studies testing brain stimulation to networks identified using lesion network mapping. ObjectivesTo assess target engagement by stimulating the S1 and testing the brain's acute metabolic response to repetitive transcranial magnetic stimulation in CD patients and healthy controls. MethodsThirteen CD patients and 14 controls received a single session of continuous theta burst (cTBS) and sham to the right S1. Changes in regional brain glucose metabolism were measured using [18F]FDG-PET. ResultscTBS increased metabolism at the stimulation site in CD (P = 0.03) but not in controls (P = 0.15; group difference P = 0.01). In subcortical regions, cTBS increased metabolism in the brainstem in CD only (PFDR = 0.04). The remote activation was positively associated with dystonia severity and efficacy of sensory trick phenomenon in CD patients. ConclusionsOur results provide further evidence of abnormal sensory system function in CD and show that a single session of S1 cTBS is sufficient to induce measurable changes in brain glucose metabolism. These findings support target engagement, motivating therapeutic trials of cTBS to the S1 in CD.

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

SYNCHRONIZE: Real-World Retrospective Safety Analysis of Patients Treated with OnabotulinumtoxinA for More than One Therapeutic Indication.

OnabotulinumtoxinA (onabotA) is approved in the US for 12 therapeutic indications. Real-world data on onabotA multi-indication use are limited, often leading to delayed or reduced treatment. This study provides real-world evidence on the safety of onabotA when treating multiple indications concomitantly. SYNCHRONIZE was a multicenter, retrospective, chart-review study evaluating onabotA's safety for adults treated for ≥2 therapeutic indications within a 3-month period. The primary outcome was treatment-emergent adverse events (TEAEs) within 6 months post-treatment. A total of 279 patients were included. The most common concomitant indications treated were cervical dystonia and chronic migraine (43.4%). The average 3-month cumulative dose for multiple indications was 282.2 U. The treatment interval for multiple indications was ≤24 h for most patients (62.4%). Overall, 28.7% of patients reported ≥1 TEAE with no apparent trends in TEAEs and dose interval or cumulative dose. Reported TEAEs included UTI (5.7%), neck pain (5.0%), and headache (4.3%). No patient had a lack of effect according to clinical objective measurements. SYNCHRONIZE described the real-world safety of onabotA for patients treated concomitantly for ≥2 indications within a 3-month period. TEAEs were generally consistent with the known safety profiles of individual indications. No new safety signals were identified).

Memory-Guided Saccades and Non-Motor Symptoms Improve after Botulinum Toxin Therapy in Cervical Dystonia

Background/Objectives: Cervical dystonia (CD) is a condition characterized by involuntary activity of cervical muscles, which is often accompanied by various non-motor symptoms. Recent studies indicate impaired saccadic eye movements in CD. Local administration of botulinum toxin type A (BoNT/A), which causes temporary paralysis of the injected muscle, is the first-line treatment of focal dystonia, including CD. To our knowledge, concurrent observation of the effect of BoNT/A on smooth eye movements, voluntary saccades, memory-guided saccades, and antisaccades in CD has not yet been explored. The aim of this study was to assess the effect of BoNT/A on eye movements and non-motor symptoms in patients with CD, which, when altered, could imply a central effect of BoNT/A. Methods: Thirty patients with CD performed smooth pursuit, prosaccadic expression, memory-guided saccades, and antisaccade tasks; eye movements were recorded by an eye tracker. Motor and non-motor symptoms, including depression, anxiety, pain, disability, and cognitive changes prior to and after BoNT/A administration, were also evaluated. Results: The number of correct onward counts (p &lt; 0.001), overall correct memory-guided saccades count (p = 0.005), motor symptoms (p = 0.001), and non-motor symptoms, i.e., anxiety (p = 0.04), depression (p = 0.02), and cognition (p &lt; 0.001) markedly improved after BoNT/A administration. Conclusions: Memory-guided saccades, depression, and anxiety improve after BoNT/A in CD.

The role of tsui scale in the treatment of primary cervical dystonia

Objective: To evaluate the severity of patients with primary cervical dystonia and the effectiveness of treatment with botulinum toxin A (Dysport based on the Tsui scale Methods: We conducted a cross-sectional descriptive study of all patients with primary cervical dystonia treated with botulinum toxin A injections at Tam Anh General Hospital from November 2022 to April 2024. Patients were assessed in detail on the Tsui scale before and after treatment 4-6 weeks. Patients were considered to have improvement when the Tsui score after treatment decreased by at least 30% compared to before treatment. Results: There were 17 patients (12 men and 5 women) who met the criteria in our study. The Tsui score before treatment in the male patient group, complex disease, with tremor was higher than that in the female patient group, simple disease, without tremor (p&lt; 0.001). 100% of patients responded to treatment with an average improvement rate of 0.56. The Tsui score after 4-6 weeks of injection (4.59 ± 2.87) improved significantly compared to before treatment (9.71 ± 4.34) (p&lt; 0.001). Conclusion: Our research has demonstrated an enhancement in Tsui score following treatment with BoNT among patients with cervical dystonia. The Tsui score is an objective measure for evaluating treatment effectiveness and should be more widely used in clinical practice.

Predictive modelling of Immunogenicity to Botulinumtoxin A Treatments for Glabellar Lines.

Botulinum toxin A (BoNT-A), derived from Clostridium botulinum, is widely used in medical and aesthetic treatments. Its clinical application extends from managing chronic conditions like cervical dystonia and migraine to reducing facial wrinkles. Despite its efficacy, a significant challenge associated with BoNT-A therapy is immunogenicity, where the immune system produces neutralising antibodies (NAbs) against BoNT-A, reducing its effectiveness over time. This issue is critical for patients requiring repeated treatments. The study aims to compare FDA-approved BoNT-A products, examining the factors influencing NAbs development using advanced machine learning techniques. This research analysed data from randomised controlled trials (RCTs) involving five main BoNT-A products. The study selected trials based on detailed immunogenic responses to these treatments, particularly for glabellar lines. Machine learning models, including logistic regression, random forest classifiers, and Bayesian logistic regression, were employed to assess how treatment specifics and BoNT-A product types affect the development of NAbs. Analysis of 14 studies with 8,190 participants revealed that dosage and treatment frequency are key factors influencing the risk of NAbs development. Among BoNT-A products, IncobotulinumtoxinA shows the lowest, and AbobotulinumtoxinA the highest likelihood of inducing NAbs. The study's machine learning and logistic regression findings indicated that treatment planning must consider these variables to minimise immunogenicity. The study underscores the importance of understanding BoNT-A immunogenicity in clinical practice. By identifying the main predictors of NAbs development and differentiating the immunogenic potential of BoNT-A products, the research provides insights for clinicians in optimising treatment strategies. It highlights the need for careful treatment customisation to reduce immunogenic risks, advocating for further research into the mechanisms of BoNT-A immunogenicity.

Amelioration of Focal Hand Dystonia via Low-Frequency Repetitive Somatosensory Stimulation.

Dystonia presents a growing concern based on evolving prevalence insights. Previous research found that, in cervical dystonia, high-frequency repetitive somatosensory stimulation (RSS; HF-RSS) applied on digital nerves paradoxically diminishes sensorimotor inhibitory mechanisms, whereas low-frequency RSS (LF-RSS) increases them. However, direct testing on affected body parts was not conducted. This study aims to investigate whether RSS applied directly to forearm muscles involved in focal hand dystonia can modulate cortical inhibitory mechanisms and clinical symptoms. We applied HF-RSS and LF-RSS, the latter either synchronously or asynchronously, on forearm muscles involved in dystonia. Outcome measures included paired-pulse somatosensory evoked potentials, spatial lateral inhibition measured by double-pulse somatosensory evoked potentials, short intracortical inhibition tested with transcranial magnetic stimulation, electromyographic activity from dystonic muscles, and behavioral measures of hand function. Both synchronous and asynchronous low-frequency somatosensory stimulation improved cortical inhibitory interactions, indicated by increased short intracortical inhibition and lateral spatial inhibition, as well as decreased amplitude of paired-pulse somatosensory evoked potentials. Opposite effects were observed with high-frequency stimulation. Changes in electrophysiological markers were paralleled by behavioral outcomes: although low-frequency stimulations improved hand function tests and reduced activation of dystonic muscles, high-frequency stimulation operated in an opposite direction. Our findings confirm the presence of abnormal homeostatic plasticity in response to RSS in the sensorimotor system of patients with dystonia, specifically in inhibitory circuits. Importantly, this aberrant response can be harnessed for therapeutic purposes through the application of low-frequency electrical stimulation directly over dystonic muscles. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prevalence of Myofascial Trigger Points in Isolated Idiopathic Cervical Dystonia: A Possible Contributor to Pain, Movement and Disability.

Myofascial trigger points (TrPs) are hypersensitive points located in a tight band of muscle that, when palpated, produce not only local pain but also referred (distant) pain. The role of TrPs in patients with cervical dystonia (CD) has not been investigated. To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain. Thirty-one patients (74.2% women; age: 61.2 years, SD: 10.1 years) participated. TrPs were explored in the sternocleidomastoid, upper trapezius, splenius capitis, levator scapulae, anterior scalene, suboccipital, and infraspinatus muscles. Clinical features of CD were documented as well as the presence of pain. The severity of dystonia and its consequences were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The mean number of TrPs for each patient was 12 (SD:3), with no differences between patients with pain (n = 20) and those without pain (n = 11). Active TrPs were only found in patients with pain (mean: 7.5, SD:4). Latent TrPs were found in both groups but were more prevalent (P < 0.001) in patients without pain (mean: 11, SD:3.5) than in those with pain (mean: 5, SD:3.5). The number of active TrPs or latent TrPs was positively associated with the TWSTRS disability subscale and the TWSTRS total score. The number of active, but not latent, TrPs was associated with worse scores on the TWSTRS pain subscale. Active TrPs were present in patients with CD reporting pain, while latent TrPs were present in all CD patients, irrespective of their pain status. The numbers of active/latent TrPs were associated with disability. TrPs could act as pain generators in CD and also contribute to the involuntary muscle contractions characteristic of dystonia.

Cost-Utility Analysis of Deep Brain Stimulation for Generalized and Cervical Dystonia: A Perspective from Brazilian Healthcare

ObjectiveIn the Brazilian public national healthcare system, botulinum toxin type A has traditionally been the sole treatment option for patients with dystonia. However, as of October 2022, Deep Brain Stimulation (DBS) garnered positive recommendations for the condition. This study aims to assess the cost-effectiveness of DBS in treating adults with generalized and cervical dystonia within the Brazilian healthcare context, considering its recent inclusion. MethodsA systematic review identified randomized controlled trials (RCTs) assessing DBS efficacy in treating adults with generalized and cervical dystonia. Two cost-utility analyses compared the cost-effectiveness of DBS plus the Best Clinical Practice (BCP) to BCP alone. Markov models, which included three health states (no clinical improvement, clinical improvement, and death), employed a one-year cycle and a lifetime horizon. The study utilized both one-way and probabilistic sensitivity analyses. ResultsTwo RCTs, one for each condition, revealed superior clinical improvement with DBS when compared to sham simulation. The Incremental Cost-Utility Ratio (ICUR) was $ 1,121.66 for generalized dystonia and $4,556.50 for cervical dystonia. Effectiveness discount rates and age at surgery were identified as influential parameters. In 1,000 Monte Carlo simulations, 99.9% of the ICUR values for generalized dystonia and 74.2 % for cervical dystonia fell below the cost-effectiveness threshold in Brazil ($8,146.64 per QALY). ConclusionsFrom the perspective of the Brazilian public health system, the combination of DBS and BCP appears to be cost-effective for the treatment of both generalized and cervical dystonia when compared to BCP alone.

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.

White Matter Microstructural Changes Using Ultra-Strong Diffusion Gradient MRI in Adult-Onset Idiopathic Focal Cervical Dystonia.

Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves abnormal posturing of the cervical musculature and, in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity toward underlying pathophysiologic differences. We aim to assess white matter motor pathways for localized, microstructural differences, which may aid in understanding underlying mechanisms. Individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited through the Welsh Movement Disorders Research Network. All participants underwent in-depth clinical phenotyping and MRI (structural and diffusion sequences) using ultra-strong diffusion gradients. Tractography (whole-tract median values) and tractometry (along tract profiling) were performed for key white matter motor pathways assessing diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and standard model parameters. Groups were compared using linear model analysis with Bonferroni multiple comparison correction. Fifty participants with AOIFCD and 30 healthy control participants were recruited, with 46 with AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid-tract fractional anisotropy [estimate = -0.046, p = 3.07 × 10-3], radial kurtosis [estimate = -0.165, p = 1.42 × 10-4], f-intra-axonal signal fraction [estimate = -0.044, p = 2.78 × 10-3], p2 orientation coherence [estimate = -0.043, p = 1.64 × 10-3], higher Orientation Dispersion Index [ODI, estimate = 0.023, p = 2.22 × 10-3]) and thalamopremotor tracts (higher mid-tract mean kurtosis [estimate = 0.064, p = 7.56 × 10-4], lower Neurite Density Index [estimate = 0.062, p = 2.1 × 10-3], higher distal tract ODI [estimate = 0.062, p = 3.1 × 10-3], lower f [estimate = -0.1, p = 2.3 × 10-3], and striatopremotor tracts [proximal lower f: estimate = -0.075, p = 1.06 × 10-3]). These measures correlated with clinical measures: dystonia duration (right thalamopremotor distal ODI: r = -0.9, p = 1.29 × 10-14), psychiatric symptoms (obsessive compulsive symptoms: left anterior thalamic radiation p2 r = 0.92, p = 2.797 × 10-11), sleep quality (Sleep Disorders Questionnaire Score: left anterior thalamic radiation ODI: r = -0.84, p = 4.84 × 10-11), pain (left anterior thalamic radiation ODI: r = -0.89, p = 1.4 × 10-13), and cognitive functioning (paired associated learning task p2, r = 0.94, p = 6.68 × 10-20). Overall, localized microstructural differences were identified within tracts linking the prefrontal and premotor cortices with thalamic and basal ganglia regions, suggesting pathophysiologic processes involve microstructural aberrances of motor system modulatory pathways, particularly involving intra-axonal and fiber orientation dispersion measures.

Prevalence and clinical features of cervical dystonia in Parkinson's disease

ObjectiveTo study the prevalence and clinical features of cervical dystonia in Parkinson's disease (CD-PD). BackgroundPD features various forms of dystonia, including CD. Yet, the prevalence and clinical features of CD in PD patients are not well-characterized. MethodsWe conducted a single site, prospective study where consecutively evaluated PD patients were examined for the presence of CD to ascertain its prevalence. For each case of CD-PD, a standardized questionnaire assessing demographic and clinical features was completed. Statistical analysis was performed to compare CD-PD characteristics to those of a previously published large idiopathic CD cohort. ResultsOf 301 consecutive PD patients evaluated, 28 (9.3 %) had CD, far surpassing estimates of CD prevalence in the general population. This CD-PD cohort was predominantly male (71 %) with a mean age of 70.9 ± 8.1 years. The mean duration of PD was 10.4 ± 6.7 years. In most cases (n = 19, 68 %), CD developed after the onset of PD. Five patients reported dystonia improvements in response to levodopa, while none reported medication-induced worsening. In contrast to CD-PD, those with ICD (n = 209) were on average younger (59.7 ± 10.1) and mostly female (74 %, p < 0.001). In addition, CD-PD was overall less severe as measured by the Global Dystonia Rating Scale (GDRS) (p = 0.002) and featured less head tremor and pain. ConclusionOur findings indicate CD is overrepresented in PD compared to the general population and has clinical features distinct from those of ICD. These results justify larger, more comprehensive studies of CD-PD to better understand its frequency, pathophysiology, clinical characteristics, and associated risk factors.