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Background: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals., Objectives: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD., Methods: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale., Results: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction., Conclusion: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects., (© 2024. The Author(s).)

Objective: The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG)., Methods: We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple-channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution., Results: ST induced a decrease in low gamma (30-50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory-sensorimotor cerebellum connection., Interpretation: The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: 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., Objective: To identify the presence of TrPs in patients with isolated idiopathic CD and their association with pain., Methods: 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)., Results: 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., Conclusion: 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., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Individuals with idiopathic adult-onset isolated cervical dystonia (CD) may have cognitive difficulties and increased mood challenges. Social cognition and executive functioning may be particularly affected., Objective: To explore social cognition and executive functioning performance in individuals with CD, using the Cambridge Neuropsychological Test Automated Battery (CANTAB), as previous research has used traditional, nondigital neuropsychological assessments. We sought to investigate the relationships between social cognition, executive functioning, mood, and disability in individuals with CD., Methods: We recruited 37 individuals with CD, including 26 women with an age range of 33 to 69 years (M = 56.64, SD = 8.31) from a dystonia clinic in a hospital neurology department. The individuals completed selected tasks from the CANTAB measuring social cognition and executive functioning. We compared the individuals' performance with CANTAB normative data. Depression, anxiety, disease severity, and disability were measured., Results: The individuals with CD had significantly lower scores than the CANTAB normative data in both social cognition and executive functioning tasks, with the largest differences evident in problem-solving, attention, and positive emotion bias tasks. Poorer emotion recognition was associated with increased difficulties in problem-solving tasks. The individuals demonstrated a bias toward identifying happiness in facial affect, which was related to a poorer recognition of emotions. Cognitive performance was not related to CD severity or disability or to current mood symptoms., Conclusion: Difficulties with both social cognition and executive functioning were identified in the individuals with CD, and are likely important targets for clinical interventions., Competing Interests: M.H. has received research grants from Dystonia Ireland, Merrion Neuroscience Foundation, and the Irish Institute of Clinical Neuroscience. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: 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., Methods: 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., Results: 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 ], p 2 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 p 2 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 p 2 , r = 0.94, p = 6.68 × 10 -20 )., Discussion: 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.

Background: Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate., Objective: To investigate brain networks associated with anxiety in CD., Methods: Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales., Results: Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05)., Conclusion: Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Cervical dystonia (CD) is a movement disorder which causes sustained muscle contractions in the neck leading to abnormal postures and repetitive movements. As it is a highly visible condition, people with CD can experience stigma, which may lead to unhelpful coping strategies and increased psychological distress. This study investigated whether adaptive and maladaptive coping strategies mediate the relationship between stigma and psychological outcomes in people with CD. A total of 114 adults with CD completed measures of stigma, coping, health-related quality of life (HRQOL), psychological distress (depression, anxiety, stress), and psychological wellbeing at one time point. Participants' levels of distress were high, compared to the general population. Correlational analyses showed increased stigma and maladaptive coping (e.g. substance use, behavioural disengagement) were both significantly related to increased distress, lower wellbeing and lower HRQOL, whereas higher adaptive coping (e.g. acceptance, humour) was only related to higher wellbeing. In a parallel mediation model, maladaptive coping strategies mediated the relationship between stigma and distress, HRQOL and wellbeing, but adaptive coping strategies did not. These findings suggest that maladaptive coping may play an important role in explaining the relationship between stigma and some aspects of distress and wellbeing in CD. Interventions which focus on reducing different aspects of maladaptive coping may be helpful to improve wellbeing as well as reducing stigma.

The study examined how neck muscle imbalance and plagiocephaly affect the lying and rolling activities in 118 infants aged 4 to 6 months with postural torticollis. Outcome measures included age, sex, cervical movement, and plagiocephaly severity. Neck muscle function was assessed with the Muscle Function Scale (MFS), and infant motor abilities in lying and rolling were evaluated through the corresponding dimensions of the Gross Motor Function Measure (GMFM). Multiple regression analysis showed that a better MFS score of the affected neck was significantly associated with improved lying and rolling activities in the GMFM ( p  < .01), and importantly, the interaction between the plagiocephaly and the MFS scores of the affected neck muscle in these activities was found to be significant ( p  < .05). These results highlight the need for early intervention in infants with torticollis to address muscle imbalance and plagiocephaly, crucial for early motor development (KCT0008367).

Introduction: Cervical dystonia is defined by excessive contraction of muscles that produce abnormal postures and movements of the head, neck, and sometimes the shoulders. Many affected individuals also have pain, local muscle hypertrophy, and/or abnormally increased EMG activity. However, abnormal movements are considered the defining feature., Cases: Three cases are described suggesting that some features of cervical dystonia may occur without abnormal movements. In these cases, the only clinical features are pain, local muscle hypertrophy, or abnormal EMG activity. These features may occur years before abnormal movements emerge, or they may occur coincidentally with dystonia affecting regions other than the neck. In some cases, some features associated with cervical dystonia may occur without any obvious abnormal movements., Conclusions: Some symptoms of cervical dystonia may occur without abnormal movements of the head or neck. The purpose of this report is not to question current diagnostic criteria for cervical dystonia, but to call attention to a phenomenon that deserves further attention. Such cases may be considered to have a pro-dromal form of cervical dystonia or a formes fruste of cervical dystonia. Whatever diagnostic label is applied, the phenomenon is important to recognize, because symptoms may be readily alleviated with botulinum toxin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions causing sustained twisting movements and abnormal postures of the neck and head. Assumed affected neuronal regions are the cortico-striatal-thalamo-cortical circuits, which are also involved in cognitive functioning. Indeed, impairments in different cognitive domains have been found in CD patients. However, to date studies have only investigated a limited range of cognitive functions within the same sample. In particular, social cognition (SC) is often missing from study designs. Hence, we aimed to evaluate a broad range of cognitive functions including SC in CD patients., Method: In the present study 20 idiopathic CD patients and 40 age-, gender-, and IQ-matched healthy controls (HCs) were assessed with tests for non-SC (verbal memory, psychomotor speed, and executive functions) as well as for SC (emotion recognition, Theory of Mind (ToM), and empathy)., Results: CD patients scored on average significantly lower than HC on tests for non-SC, but did not show impairments on any of the tests for SC., Conclusions: The current study showed impairments in non-SC in CD, but intact social cognitive functions. These results underline the importance of recognizing non-motor symptoms in idiopathic CD patients, but emphasize a focus on identifying strengths and weaknesses in cognitive functioning as these influence daily life activities.

Cervical dystonia is a non-degenerative movement disorder characterized by dysfunction of both motor and sensory cortico-basal ganglia networks. Deep brain stimulation targeted to the internal pallidum is an established treatment, but its specific mechanisms remain elusive, and response to therapy is highly variable. Modulation of key dysfunctional networks via axonal connections is likely important. Fifteen patients underwent preoperative diffusion-MRI acquisitions and then progressed to bilateral deep brain stimulation targeting the posterior internal pallidum. Severity of disease was assessed preoperatively and later at follow-up. Scans were used to generate tractography-derived connectivity estimates between the bilateral regions of stimulation and relevant structures. Connectivity to the putamen correlated with clinical improvement, and a series of cortical connectivity-based putaminal parcellations identified the primary motor putamen as the key node (r = 0.70, P = 0.004). A regression model with this connectivity and electrode coordinates explained 68% of the variance in outcomes (r = 0.83, P = 0.001), with both as significant explanatory variables. We conclude that modulation of the primary motor putamen-posterior internal pallidum limb of the cortico-basal ganglia loop is characteristic of successful deep brain stimulation treatment of cervical dystonia. Preoperative diffusion imaging contains additional information that predicts outcomes, implying utility for patient selection and/or individualized targeting., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: To examine interactions between cortical areas and between cortical areas and muscles during sensory tricks in cervical dystonia (CD)., Methods: Thirteen CD patients and thirteen age-matched healthy controls performed forewarned reaction time tasks, sensory tricks, and two tasks replicating aspects of the tricks (moving necks/arms). Control subjects mimicked sensory tricks. Corticocortical and corticomuscular coherence values were calculated from surface electrodes placed over motor, premotor, and sensory cortical areas and dystonic muscles., Results: During initial preparation (after the warning stimulus), the only between-task difference was found in the γ-band corticocortical coherence (higher during tricks than during voluntary neck movements). With movements (before/after the imperative stimulus), the γ-band coherence of CD patients significantly increased during tricks but decreased during voluntary movements, while opposite trends were observed in healthy subjects. Additionally, the α- and β-band coherence decreased in healthy subjects during movements. Between the two patient subgroups (typical vs. forcible tricks), only those with typical tricks showed significant decrease in corticomuscular coherence during tricks., Conclusions: Observed changes in the corticocortical coherence suggest that sensory tricks improve cortical function, which reduces corticomuscular connectivity and the dystonia., Significance: We demonstrated that sensory tricks fundamentally affect sensorimotor integration in CD, both in movement preparation and execution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY., (© 2020 Wiley Periodicals, Inc.)

Objective: In patients with cervical dystonia we sought for the differences in neuronal behavior of pallidal regions where deep brain stimulation resulted in favorable therapeutic response compared to those where the response was absent., Methods: We compared single-unit activity of 564 neurons recorded from deep brain stimulation sensitive and non-sensitive regions in 17 cervical dystonia patients., Results: Globus pallidus internus regions responsive to the deep brain stimulation had lower firing rates and bursting compared to non-responsive areas. The differences were robust in locations where neuronal responses correlated with neck movements. Per the effects of deep brain stimulation, the pallidal regions were classified in weak, intermediate, and excellent responsive. Pallidal regions with weak response to deep brain stimulation had fewer burst neurons and higher firing rate compared to neurons in areas with excellent response. The burst index was significantly decreased in excellent response regions. There was a significant decrease in the alpha band oscillation score but a substantial increase in the gamma band in excellent response neurons., Conclusion: The pallidal region that would be responsive to deep brain stimulation has distinct physiology compared to the non-responsive region., Significance: These results provide novel insights into globus pallidus interna neurons' physiology in cervical dystonia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Benign paroxysmal torticollis (BPT) is characterized by attacks of head tilt associated with vomiting, irritability, and/or ataxia in early childhood. BPT is associated with migraine but risk factors are unknown. Impact on quality of life is also unknown., Methods: Parents/caregivers of children with ongoing or resolved BPT participated in telephone interviews (n = 73). Those with ongoing BPT completed the Infant Toddler Quality of Life questionnaire (ITQoL)., Results: Median age of children at the time of interview was 2.9 years (range 0.25-23). BPT was ongoing in 52% (n = 38). Nineteen percent (n = 14) developed migraine (median age 9.25 years, range 2.5-23) and 63% (n = 46) developed another episodic syndrome associated with migraine. Proportion of patients who developed migraine was higher among those with certain migrainous symptoms during BPT attacks vs. those without: phonophobia (58 vs. 21%, p = 0.02), photophobia and phonophobia (55 vs. 23%, p = 0.05), and photophobia, phonophobia, and motion sensitivity (60 vs. 22%, p = 0.02). ITQoL results showed significant impact of BPT on quality of life., Conclusions: Children with BPT may develop migraine or other episodic syndromes associated with migraine. Presence of migrainous features during BPT episodes may increase likelihood of developing migraine. Though characterized as "benign," BPT can significantly impact children and families., Impact: Benign paroxysmal torticollis (BPT) is a rare condition of early childhood characterized by episodes of head tilt associated with vomiting, irritability, ataxia, pallor, and/or malaise. This cohort study describes the phenotypic spectrum of BPT, variable treatment, natural history and association with migraine, and impact on development and quality of life. Children with BPT may go on to develop migraine or episodic syndromes that may be associated with migraine; presence of migrainous features during attacks may increase odds of developing migraine. BPT can have significant impact on quality of life, demonstrated by findings from the Infant Toddler Quality of Life questionnaire., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity. We confirmed the presence of theta (3-7 Hz) oscillatory activity, which was coherent throughout the cortico-subthalamic circuit and specifically suppressed by high-frequency stimulation. Stimulation also reduced the duration, rate and height of theta bursts. These findings motivated a proof-of-principle trial of a new form of adaptive deep brain stimulation - triggered by theta-burst activity recorded from the motor cortex. This facilitated increased peak stimulation amplitudes without induction of dyskinesias and demonstrated improved blinded clinical ratings compared to continuous DBS, despite reduced total electrical energy delivered. These results further strengthen the pathophysiological role of low frequency (theta) oscillations in dystonia and demonstrate the potential for novel adaptive stimulation strategies linked to cortico-basal theta bursts., (Copyright © 2021. Published by Elsevier Inc.)

Background: Cervical dystonia (CD) is the most common form of focal dystonia with involuntary movements and postures of the head. The pathogenesis and neural mechanisms underlying CD have not been fully elucidated., Methods: Twenty-seven newly drug-naïve patients with CD and 21 healthy controls (HCs) were recruited with clinical assessment and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Severity of CD was measured by Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui scores. Whole-brain voxel-wise intrinsic connectivity (IC) and seed-based functional connectivity (FC) analyses were performed for detection of changes in the CD group relative to HCs, controlling for age, gender, and global time series correlation, followed by correlation analyses of IC, seed-based FC and clinically relevant features, respectively., Results: In comparison with HCs, CD patients showed significantly increased IC measurement in the anterior part of the left supramarginal gyrus and extended to the inferior left postcentral gyrus (AL-SMG/IL-PCG). With this cluster as a seed, decreased FC was found in the right precentral and postcentral gyrus. Moreover, the regional IC value in the AL-SMG/IL-PCG was significantly positively correlated with TWSTRS-1 (severity) score, and significantly negatively correlated with the associated seed-based FC strength., Conclusions: Our results showed signs of both hyper- and hypo-connectivity in bilateral regions of the sensorimotor network related to CD. The imbalance of functional connectivity (both hyper- and hypo-) may hint both overloading and disrupted somatosensory or sensorimotor integration dysfunction within the sensorimotor network underlying the pathophysiology of CD, thus providing a network target for future therapies., (Copyright © 2021. Published by Elsevier Ltd.)

Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on consecutive patients with idiopathic cervical dystonia (ICD), treated regularly with periodic BT injections between the years 2008-2020. All treatment visits were analyzed regarding type of toxin, dose injected, and clinical outcomes. The vast majority of patients were treated with abobotulinum toxin A. Sixty-four ICD patients (51 (79.7%) females, onset at age 45.8 ± 13.7 years) were treated over 17.1 ± 13.9 (range 3 to 49) visits per patient; BT treatment efficacy increased gradually from initial treatment sessions to visit 13, when it achieved a steady state. While the subjective report of percentage improvement and its duration were around 78.9 ± 17.1% for 2.8 ± 1.0 months, respectively, the dose of BT increased significantly over the years (p = 0.006). Side effects (SE) were not rare, and commonly recurred after subsequent sessions and were usually mild and short-lasting, with dysphagia being the most common (~17.5%), followed by neck/arm weakness (11.9%) and cervical pain (8.9%). Repeated injections of BT for ICD remain beneficial for patients over several years of therapy, and despite mild SE, patients tend to adhere to a 3-4 months interval schedule., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Cervical dystonia (CD) is a heterogeneous condition. However, while motor subtypes of CD have recently been identified, it is still unknown whether and how non-motor symptoms contribute to CD heterogeneity. In the present cross-sectional study, we aimed to identify clinical CD subtypes on the basis of motor and non-motor symptoms by using a hypothesis-free data-driven approach., Methods: Fifty-seven patients with CD participated in the study. Patients underwent a clinical evaluation that assessed motor and non-motor features of CD with standardized clinical scales. We investigated five clinical domains, including motor symptoms, psychiatric disturbances, sleep disorders, cognitive impairment and pain. These domains were used as variables in a k-means cluster analysis with two-, three-, and four-cluster solutions., Results: The two-cluster solution best fits our sample. Cluster I (n = 32) included patients who were younger and had less severe non-motor symptoms and a lower disability level than patients included in Cluster II (n = 25). The two clusters showed similar sex distribution and disease duration. Similarly, the type of motor pattern and the occurrence of tremor and sensory trick were equally distributed in the two subtypes., Conclusions: We identified two clinical subtypes of CD. The two subtypes shared similar motor features but were characterized by different non-motor symptom severity. These findings suggest that motor network dysfunction is a common pathophysiological feature of CD, whereas the extent of non-motor network involvement may differ in CD, with age acting as a possible modulating factor., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Adult-onset focal dystonia can spread to involve one, or less frequently, two additional body regions. Spread of focal dystonia to a third body site is not fully characterized., Materials and Methods: We retrospectively analyzed data from the Italian Dystonia Registry, enrolling patients with segmental/multifocal dystonia involving at least two parts of the body or more. Survival analysis estimated the relationship between dystonia features and spread to a third body part., Results: We identified 340 patients with segmental/multifocal dystonia involving at least two body parts. Spread of dystonia to a third body site occurred in 42/241 patients (17.4%) with focal onset and 10/99 patients (10.1%) with segmental/multifocal dystonia at onset. The former had a greater tendency to spread than patients with segmental/multifocal dystonia at onset. Gender, years of schooling, comorbidity, family history of dystonia/tremor, age at dystonia onset, and disease duration could not predict spread to a third body site. Among patients with focal onset in different body parts (cranial, cervical, and upper limb regions), there was no association between site of focal dystonia onset and risk of spread to a third body site., Discussion and Conclusion: Spread to a third body site occurs in a relative low percentage of patients with idiopathic adult-onset dystonia affecting two body parts. Regardless of the site of dystonia onset and of other demographic/clinical variables, focal onset seems to confer a greater risk of spread to a third body site in comparison to patients with segmental/multifocal dystonia at onset., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38-63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.

Cervical dystonia (CD) is a movement disorder characterized by a stereotyped pattern of involuntary turning or tilting of the head, often combined with jerky or tremulous movements. Hypotheses for the origin of CD have traditionally focused on the basal ganglia, but the contemporary discussion has considered the potential role of altered cerebellar function. As basal ganglia and the cerebellum largely project to the different thalamic nuclei, alterations in pallidal versus cerebellar output could be reflected in the activity of these thalamic regions. In this study, we analyzed a unique historic database where the single-unit activity of pallidal and cerebellar receiving thalamic nuclei was measured en route to the mesencephalon. We compared the single-unit activity of pallidal and cerebellar receiving thalamic neurons in three groups of CD patients manifesting as pure dystonia, pure jerky head oscillations, and dystonia plus jerky head oscillations. We found that among different CD manifestations, the characteristics of neuronal firing, such as burst versus a single-spike pattern, vary in cerebellar thalamic receiving nuclei. The cerebellar receiving region in patients with jerky oscillations had single-spikes neurons primarily. Wherein the manifestation of CD did not influence pattern distribution in the pallidal receiving thalamic area. We also found increased neuronal firing rate correlated with strength of theta-band neuronal oscillations during muscle contractions associated with dystonia. These results demonstrate that the manifestations of CD, such as pure dystonia, pure jerky head oscillations, or dystonia and jerky head oscillations, determine the thalamic neuronal properties.

Introduction: Although sensory tricks are well known as the maneuvers that temporarily relieve dystonic symptoms in patients with cervical dystonia (CD), the underlying neurophysiological mechanisms remain unclear. We aimed to investigate brain potentials related to sensory tricks in patients with CD., Methods: Thirteen patients with CD and 13 age-matched healthy volunteers participated. The experiment consisted of three conditions (moving the neck, moving an arm, and performing sensory tricks) presented in different blocks in random order in a contingent negative variation (CNV) paradigm. Warning and trigger stimuli (S1 and S2) were presented to the participants, who were instructed to prepare to perform the specific task for each condition after S1, and then to perform the task after S2. Early and late components of the CNV were measured., Results: The late CNVs in patients with CD were significantly larger than those in healthy participants in Fz, FCz, Cz, and C3 electrodes. Only in patients with CD, the late CNVs were significantly greater for the 'sensory tricks' condition compared to the 'move neck' condition in Fz and C3 electrodes., Conclusion: The late CNV is increased during sensory tricks in patients with CD, suggesting that sensory tricks may affect mechanisms related to the motor preparatory phase in the premotor and primary motor areas. Sensory tricks may normalize impaired motor preparation in dystonia, leading to improved dystonic symptoms., (Published by Elsevier Ltd.)

Objective: Atlantoaxial instability, although rarely reported in the literature, can be associated with cervical dystonia (CD) and may lead to compression of the cord at the craniovertebral junction. We present a case series of 4 patients of longstanding CD with neurologic complications. Treatment strategies and challenges are discussed., Methods: Retrospective analysis of 4 cases of longstanding CD with complications of myelopathy or radiculopathy., Results: The average age at onset of complications was 28 years (range, 17-37). The average duration of CD was 23.75 years. Narrowing of the craniovertebral junction was seen in 3 patients, of which 2 had os odontoideum, and 1 had rotational malalignment at the atlantoaxial joint. One patient had disc desiccation with bulge and intramedullary signal changes in the cord at C3-4 level. Medical treatment was not satisfactory, but botulinum toxin was partly useful in all. One patient had sequelae of myelopathy and did recover partially after deep brain stimulation. Of the 2 patients who underwent surgical fixation with a fusion of the spine, one improved, and the other had no improvement due to irreversible cord damage. The overall outcome was satisfactory only in 2 patients., Conclusions: Early-onset CD can lead to cord complications at a young age and at higher levels of the cervical spine and at the cervicovertebral junction. Comprehensive management by a multidisciplinary team is crucial to prevent complications early., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Tongue motility is an essential physiological component of human feeding from infancy through adulthood. At present, it is a challenge to distinguish among the many pathologies of swallowing due to the absence of quantitative tools. We objectively quantified tongue kinematics from ultrasound imaging during infant and adult feeding. The functional advantage of this method is presented in several subjects with swallowing difficulties. We demonstrated for the first time the differences in tongue kinematics during breast- and bottle-feeding, showing the arrhythmic sucking pattern during bottle-feeding as compared with breastfeeding in the same infant with torticollis. The method clearly displayed the improvement of tongue motility after frenotomy in infants with either tongue-tie or restrictive labial frenulum. The analysis also revealed the absence of posterior tongue peristalsis required for safe swallowing in an infant with dysphagia. We also analyzed for the first time the tongue kinematics in an adult during water bolus swallowing demonstrating tongue peristaltic-like movements in both anterior and posterior segments. First, the anterior segment undulates to close off the oral cavity and the posterior segment held the bolus, and then, the posterior tongue propelled the bolus to the pharynx. The present methodology of quantitative imaging revealed highly conserved patterns of tongue kinematics that can differentiate between swallowing pathologies and evaluate treatment interventions. The method is novel and objective and has the potential to advance knowledge about the normal swallowing and management of feeding disorders., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Deep brain stimulation (DBS) is an effective treatment in medically resistant cervical dystonia (CD) with a documented therapeutic effect. Long term outcome beyond a decade, however, has not been studied systematically., Methods: To investigate the impact of pallidal DBS beyond 10 years in CD we followed a series of five consecutive patients with severe medication-resistant CD. Severity of head and neck deviation, disability, and pain related to dystonia were assessed by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in the frame of a prospective study. The primary endpoint of this study was a change in the TWSTRS total score. Secondary endpoints were changes in the subscores of the TWSTRS., Results: The mean follow-up time was 11.5 years (range 10-12.8). Comparing baseline and the last follow-up, CD improved by 53% on the total TWSTRS score, by 54.1% on the severity score, and by 70.1% on the disability score, while pain did not improve significantly. Improvement was stable over time. Patients with a tonic pattern of CD responded less to DBS than patients with a phasic pattern. DBS had no significant effect on mood and cognition. Two patients underwent electrode revisions. One patient had an infection of the proximal cable two years after surgery., Conclusions: Chronic bilateral pallidal stimulation improves severity of dystonia and disability over more than a decade in treatment resistant CD. Results may vary among individual patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Patients with essential tremor, vocal tremor, torticollis, myoclonus-dystonia and posthypoxic myoclonus often benefit in a surprisingly rapid and robust manner from ingestion of a modest amount of alcohol (ethanol). Despite considerable investigation, the mechanism of ethanol's ability to produce this effect remains a mystery. In this paper, we review the pharmacology of ethanol and its analogue GHB (or sodium oxybate), summarize the published literature of alcohol-responsive hyperkinetic movement disorders, and demonstrate videos of patients we have treated over the last fifteen years with either an ethanol challenge or with chronic sodium oxybate therapy. We then propose a novel explanation for this phenomenon-namely, that ingestion of modest doses of ethanol (or sodium oxybate) normalizes the aberrant motor networks underling these disorders. We propose that alcohol and its analogues improve clinical symptoms and their physiologic correlate by restoring the normal firing pattern of the major outflow pathways of the cerebellum (the Purkinje cells and deep cerebellar nuclei), We present evidence to support this hypothesis in animal models and in affected patients, and suggest future investigations to test this model., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Chemodenervation of cervical musculature using botulinum neurotoxin (BoNT) is established as the gold standard or treatment of choice for management of Cervical Dystonia (CD). The success of BoNT procedures is measured by improved symptomology while minimizing side effects and is dependent upon many factors including: clinical pattern recognition, identifying contributory muscles, BoNT dosage, and locating and safely injecting target muscles. In patients with CD, treatment of anterocollis (forward flexion of the neck) and anterocaput (anterocapitis) (forward flexion of the head) are inarguably challenging. The longus Colli (LoCol) and longus capitis (LoCap) muscles, two deep cervical spine and head flexor muscles, frequently contribute to these patterns. Localizing and safely injecting these muscles is particularly challenging owing to their deep location and the complex regional anatomy which includes critical neurovascular and other structures. Ultrasound (US) guidance provides direct visualization of the LoCol, LoCap, other cervical muscles and adjacent structures reducing the risks and side effects while improving the clinical outcome of BoNT for these conditions. The addition of electromyography (EMG) provides confirmation of muscle activity within the target muscle. Within this manuscript, we present a technical description of a novel US guided approach (combined with EMG) for BoNT injection into the LoCol and LoCap muscles for the management of anterocollis and anterocaput in patients with CD.

Background: Tremor is an important phenotypic feature of dystonia. Using the new concept (Col-Cap) of classification we examined the frequency of tremor in cervical dystonia (CD) patients, their main subtypes and muscles injected., Methods: In this large study conducted at multiple movement disorder centres in Europe and India, between January and June 2019, we examined 293 patients with idiopathic CD who were all treated with botulinum toxin (BTX)., Results: The dystonic head tremor (DHT+) was present in 57.6 % of CD patients and they had a significantly longer duration of symptoms than patients without head tremor (DHT-). In DHT+ patients torticaput was the most common subtype and the majority (63.3%) had one or two subtypes only. There was no significant difference between the number of unilateral injections for any of the muscles in the DHT+ and DHT- groups, while the number of patients receiving bilateral injections in splenius capitis (78 vs 25; p = 0.00001), sternocleidomastoid (31 vs 6; p = 0.0005), trapezius (28 vs 9; p = 0.01), and obliquus capitis inferior (15 vs 2; p = 0.008) were significantly more in the DHT+ group. The mean doses of all three types of BTX/A were not significantly different between the two groups., Conclusions: The frequency of head tremor was 57.6% in our CD patients and torticaput was the most common dystonic subtype associated with tremor. Simple forms of CD seemed more likely associated with head tremor, than complex forms of CD. Most of the DHT+ patients received bilateral injections. The use of 'Col-Cap' classification was helpful in the identification of muscles likely to be involved in tremor in CD patients., Competing Interests: Dr. Sanjay Pandey and Dr. Christian Altmann have no conflict of interest. All other authors were speakers and consultants for Allergan, Merz/Desitin and Ipsen, but none relevant to this study (and had no financial or other support)., (Copyright: © 2020 The Author(s).)

Deep brain stimulation of the globus pallidus pars interna (GPi-DBS) is an effective treatment for primary dystonia; however, its therapeutic mechanism is poorly understood. Because improvement is gradual, GPi-DBS treatment likely involves short- and long-term mechanisms. Abnormal plasticity resulting in somatotopic reorganization is involved in the development of dystonia and has been proposed as a possible mechanism for this gradual improvement, yet it has not been directly investigated. We hypothesized that GPi-DBS will lead to progressive changes in the cortical representations (motor maps) of upper limb muscles. Neuronavigated robotic transcranial magnetic stimulation was used to map the cortical representation of five upper limb muscles in six healthy controls and a 45-yr-old female cervical dystonia patient before (Pre) and at four time points (Post5 to Post314), 5 to 314 days after GPi-DBS. Motor map area and volume decreased in all muscles following GPi-DBS, while changes in overlap and center of gravity distance between muscles were variable. Despite these motor map changes, only dystonic tremor improved after a year of DBS; neck position worsened slightly. These preliminary findings suggest that GPi-DBS may reduce the cortical representation and excitability of upper limb muscles in dystonia and that these changes can occur without clinical improvement. NEW & NOTEWORTHY Neuronavigated robotic transcranial magnetic stimulation was used to investigate changes in upper limb muscle representation in a cervical dystonia patient before and at four time points up to 314 days after globus pallidus pars interna deep brain stimulation (GPi-DBS). GPi-DBS altered excitability and motor cortical representation of upper limb muscles; however, these changes were not associated with clinical improvement.

The relationship between two common movement disorders, dystonia and tremor, is controversial. Both deficits have correlates in the network that includes connections between the cerebellum and the basal ganglia. In order to assess the physiological relationship between tremor and dystonia, we measured the activity of 727 pallidal single-neurons during deep brain stimulation surgery in patients with cervical dystonia without head oscillations, cervical dystonia plus jerky oscillations, and cervical dystonia with sinusoidal oscillations. Cluster analyses of spike-train recordings allowed classification of the pallidal activity into burst, pause, and tonic. Burst neurons were more common, and number of spikes within spike and inter-burst intervals was shorter in pure dystonia and jerky oscillation groups compared to the sinusoidal oscillation group. Pause neurons were more common and irregular in pure tremor group compared to pure dystonia and jerky oscillation groups. There was bihemispheric asymmetry in spontaneous firing discharge in pure dystonia and jerky oscillation groups, but not in sinusoidal oscillation group. These results demonstrate that the physiology of pallidal neurons in patients with pure cervical dystonia is similar to those who have cervical dystonia combined with jerky oscillations, but different from those who have cervical dystonia combined with sinusoidal oscillations. These results imply distinct mechanistic underpinnings for different types of head oscillations in cervical dystonia.

Objective: Dystonia is associated with reduced intracortical inhibition as measured by the cortical silent period (cSP); however, this may be due to abnormal cSP threshold or input-output properties. This study evaluated cSP recruitment properties in people with cervical dystonia (CD)., Methods: Bilateral electromyographic recordings were collected in the upper trapezius muscle in response to transcranial magnetic stimulation of the left and right primary motor cortex in a group with CD (n = 19) and controls (n = 21). cSP threshold, cSP input-output properties at stimulation intensities from 1 to 1.4x the cSP threshold, ipsilateral silent period duration (iSP) and timing and magnitude of the contralateral and ipsilateral motor evoked potential (MEP) were assessed., Results: The cSP threshold, input-output properties, and contralateral MEP magnitude were not significantly different between groups (all p > 0.07). Hemispheric symmetry was present in the control group while the CD group had reduced iSP (p < 0.01) and a trend for reduced ipsilateral MEP response (p = 0.053) in the left hemisphere., Conclusions: Recruitment properties of intracortical inhibition are similar between control and CD groups. Transcallosal inhibition is asymmetric between hemispheres in people with CD., Significance: Evidence of normal intracortical inhibition recruitment properties challenge the commonly held view that cortical inhibition is reduced in dystonia., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Primary cervical dystonia (CD) is characterized by abnormal contractions of neck muscles. Globus pallidus internus deep brain stimulation (GPi-DBS) is recognized as an effective therapy for patients with refractory CD, but the prognostic factors need further research. Our study investigated the predictive factors of clinical outcomes in CD patients who underwent GPi-DBS., Patients and Methods: Patients (n = 23) who underwent GPi-DBS at Chinese PLA General Hospital from March 2012 to April 2018 were included in our analysis. Their scores of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui were acquired at baseline and at the last follow-up visit. Percent improvement in these scores were compared between the categorical variables. Correlations between outcomes and continuous demographic and clinical variables were calculated., Results: Patients showed significant improvement in TWSTRS total (55.71 %), severity (48.75 %), disability (57.05 %), pain (63.67 %) scores and total Tsui score (46.07 %, all P ﹤0.001). Follow-up duration was positively correlated with percent improvement in TWSTRS total (rho = 0.594, P =  0.003), severity (rho = 0.581, P =  0.004) and disability (rho = 0.470, P =  0.023) scores. No significant differences in the outcomes were found between any pair of the categorical variables., Conclusions: Follow-up duration was the only independent factor correlated to the outcomes of GPi-DBS for CD patients. However, follow-up duration is an indefinite factor prior to surgery, thus further studies are needed before the final conclusions of prognostic factors are established., Competing Interests: Declaration of Competing Interest We do not have any conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD); and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus.

Sensory trick may relieve dystonic symptoms in patients with idiopathic cervical dystonia (CD). We investigated the patterns of brain functional MRI (fMRI) during resting state, sensory trick simulation and sensory trick imagination in CD patients both with and without an effective sensory trick. We recruited 17 CD patients and 15 healthy controls. Nine patients (CD-trick) had an effective sensory trick, while 8 patients (CD-no-trick) did not. Cervical range of motion validated instrument assessed dystonic posture and sensory trick effect. Participants underwent resting state fMRI, which was repeated by patients while executing the sensory trick. Patients also performed an fMRI task in which they were asked to imagine a sensory trick execution. CD-trick and CD-no-trick patients were comparable in terms of CD severity. Applying the sensory trick, CD-trick patients significantly improved dystonic posture. CD-no-trick patients showed an increased functional connectivity of sensorimotor network relative to controls during classic resting state fMRI. During resting state fMRI with sensory trick, CD-trick patients showed a decrease of sensorimotor network connectivity. During the sensory trick imagination fMRI task, CD-trick relative to CD-no-trick patients increased the recruitment of cerebellum bilaterally. This study suggests a hyper-connectivity of sensorimotor areas during resting state in CD-no-trick subjects. In CD-trick patients, the sensory trick performance was associated with a decreased connectivity of the sensorimotor network. The increased activation of cerebellum in CD-trick patients during the sensory trick imagination suggests a possible role of this area in modulating cortical activity.

Cervical dystonia (CD) is the most common form of focal dystonia characterized by involuntary contractions of the neck muscles, causing abnormal rotation of the head into specific directions. Studies report that idiopathic dystonia is a developmental disorder of the sensorimotor circuits, involving both the cortico-striatal and thalamo-cortical pathways. It is also suggested that enhanced cortical plasticity extends beyond the clinically affected region and may also be detected in the unaffected upper limbs of the patient with CD. In the present study, we aimed at exploring if patients with CD had hand motor dysfunctions. Forty patients with idiopathic CD and 40 healthy controls were included in this study. Dystonic symptoms were assessed by means of The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Stanford Health Assessment Questionnaire (HAQ) was used to assess functional status. Quality of life (QoL) was assessed by using the Medical Outcomes Study Short Form 36-Item Health Survey (SF 36). Grip strength was assessed by using hand dynamometers. Tip pinch, lateral pinch and chuck pinch of the hand were assessed by using a pinchmeter. Fingertip dexterity and hand coordination was assessed using Purdue Pegboard. Duruoz Hand Index (DHI) was used for the assessment of hand functions. There were no significant differences between the groups in grip and pinch strengths of hands and fingers. As to the fingertip dexterity, patients with CD had a mean Pin 1 and Pin 2 test score of 10.6 ± 2.8 and 10.8 ± 3.2 respectively and a mean assembling test score of 5.2 ± 2.0. These results were significantly worse than those of the healthy controls. As to the SF 36 sub-scores, there were significant differences between the groups in all SF 36 sub-scores (p < .001). This study indicates that patients with CD suffer a deteriorated fine motor coordination of hands without dystonic involvement of upper extremities. Furthermore, lower SF 36 scores in patients with CD suggest poorer health-related quality of life., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neuroimaging studies using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting the changes in blood oxygenation levels, are advancing our understanding of the pathophysiology of dystonia. Neurobiological disturbances in dystonia, however, may affect neurovascular coupling and impact the interpretability of fMRI studies. We evaluated here whether the hemodynamic response patterns during a behaviorally matched motor task are altered in isolated cervical dystonia (CD). Twenty-five CD patients and 25 healthy controls (HCs) underwent fMRI scanning during a paced finger tapping task (nondystonic task in patients). Imaging data were analyzed using a constrained principal component analysis-a statistical method that combines regression analysis and principal component analysis and enables the extraction of task-related functional networks and determination of the spatial and temporal hemodynamic response patterns associated with the task performance. Data from three patients and two controls were removed due to excessive movement. No significant differences in demographics or motor performance were observed. Three task-associated functional brain networks were identified. During task performance, reduced hemodynamic responses were seen in a sensorimotor network and in a network that included key nodes of the default mode, executive control and visual networks. During rest, reductions in hemodynamic responses were seen in the cognitive/visual network. Lower hemodynamic responses within the primary sensorimotor network in patients were correlated with the increased dystonia severity. Pathophysiological disturbances in isolated CD, such as alterations in inhibitory signaling and dopaminergic neurotransmission, may impact neurovascular coupling. Not accounting for hemodynamic response differences in fMRI studies of dystonia could lead to inaccurate results and interpretations., (© 2019 Wiley Periodicals, Inc.)

Background. Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary contractions of the cervical musculature and is known to be associated with proprioceptive dysfunction in dystonic/nondystonic limbs. Objectives. We examined how neck botulinum neurotoxin (BoNT) injection affects wrist proprioception and the corresponding sensorimotor cortical activity in CD. Method. Wrist position sense acuity of the dominant (right) hand was evaluated in 15 CD and 15 control participants. Acuity measures were a psychophysical position sense discrimination threshold (DT; based on passive joint displacement) and joint position matching error (based on active movement). Cortical activity during the motor preparation period of the active joint position matching was examined using electroencephalography. Results. In their symptomatic state, patients demonstrated a significantly higher wrist proprioceptive DT, indicating an abnormal passive wrist position sense. Yet BoNT injections had no significant effect on this threshold. During active joint position matching, errors were significantly larger in patients, but this difference vanished after the administration of BoNT. Motor preparation of active wrist position matching was associated with a significantly higher rise of β-band (13-30 Hz) power over contralateral somatosensory-motor cortical areas in patients. This excessive cortical activity significantly declined post-BoNT. Conclusion . Wrist proprioceptive perception during passive/active movements is abnormal in CD. An excessive rise of premotor/motor cortical β-oscillations during motor planning is associated with this proprioceptive dysfunction. Neck BoNT injections normalized the cortical processing of proprioceptive information from nonsymptomatic limbs, indicating that local injections may affect the central mechanisms of proprioceptive function in CD.

The pathophysiology of cervical dystonia is not completely understood. Current concepts of the pathophysiology propose that it is a network disorder involving the basal ganglia, cerebellum and sensorimotor cortex. These structures are primarily concerned with sensorimotor control but are also involved in non-motor functioning such as the processing of information related to the chemical senses. This overlap lets us hypothesize a link between cervical dystonia and altered sense of smell and taste. To prove this hypothesis and to contribute to the better understanding of cervical dystonia, we assessed olfactory and gustatory functioning in 40 adults with idiopathic cervical dystonia and 40 healthy controls. The Sniffin Sticks were used to assess odor threshold, discrimination and identification. Furthermore, the Taste Strips were applied to assess the combined taste score. Motor and non-motor deficits of cervical dystonia including neuropsychological and psychiatric alterations were assessed as cofactors for regression analyses. We found that cervical dystonia subjects had lower scores than healthy controls for odor threshold (5.8 ± 2.4 versus 8.0 ± 3.2; p = 0.001), odor identification (11.7 ± 2.3 versus 13.1 ± 1.3; p = 0.001) and the combined taste score (9.5 ± 2.2 versus 11.7 ± 2.7; p < 0.001), while no difference was found in odor discrimination (12.0 ± 2.5 versus 12.9 ± 1.8; p = 0.097). Regression analysis suggests that age is the main predictor for olfactory decline in subjects with cervical dystonia. Moreover, performance in the Montreal Cognitive Assessment is a predictor for gustatory decline in cervical dystonia subjects. Findings propose that cervical dystonia is associated with diminished olfactory and gustatory functioning.

Objective: To determine whether different phenotypes of cervical dystonia (CD) express different types and levels of somatosensory impairment., Methods: We assessed somatosensory function in patients with CD with and without tremor (n = 12 each) and in healthy age-matched controls (n = 22) by measuring tactile temporal discrimination thresholds of the nondystonic forearm and proprioceptive acuity in both the dystonic (head/neck) and nondystonic body segments (forearm/hand) using a joint position-matching task. The head or the wrist was passively displaced along different axes to distinct joint positions by the experimenter or through a robotic exoskeleton. Participants actively reproduced the experienced joint position, and the absolute joint position-matching error between the target and the reproduced positions served as a marker of proprioceptive acuity., Results: Tactile temporal discrimination thresholds were significantly elevated in both CD subgroups compared to controls. Proprioceptive acuity of both the dystonic and nondystonic body segments was elevated in patients with CD and tremor with respect to both healthy controls and patients with CD without tremor. That is, tactile abnormalities were a shared dysfunction of both CD phenotypes, while proprioceptive dysfunction was observed in patients with CD with tremor., Conclusions: Our findings suggest that the pathophysiology in CD can be characterized by 2 abnormal neural processes: a dysfunctional somatosensory gating mechanism involving the basal ganglia that triggers involuntary muscle spasms and abnormal processing of proprioceptive information within a defective corticocerebellar loop, likely affecting the feedback and feedforward control of head positioning. This dysfunction is expressed mainly in CD with tremor., (© 2020 American Academy of Neurology.)

Background: Although abnormal head and neck postures are defining features of cervical dystonia (CD), head tremor (HT) is also common. However, little is known about the relationship between abnormal postures and HT in CD., Methods: We analyzed clinical data and video recordings from 185 patients enrolled by the Dystonia Coalition. We calculated the likelihood of their HT and HT type ("regular" vs. "jerky") given directionality of abnormal head postures, disease duration, sex, and age., Results: Patients with retrocollis were more likely to have HT than patients with anterocollis (X 2 (1, N = 121) = 7.98, p = 0.005). There was no difference in HT likelihood given left or right turning in laterocollis and rotation. Patients with HT had longer disease duration ( t (183) = 2.27, p = 0.024). There was no difference in age between patients with and without HT. In a logistic regression model, anterocollis/retrocollis direction (X 2 (1, N = 121) = 6.04, p = 0.014), disease duration (X 2 (1, N = 121) = 7.28, p = 0.007), and the interaction term between age and disease duration (X 2 (1, N = 121) = 7.77, p = 0.005) collectively contributed to HT likelihood. None of the postural directionality or demographic variables were associated with differential likelihood of having regular versus jerky HT., Discussion: We found that HT is more likely for CD patients with a specific directionality in their predominant posture. Our finding that CD patients with longer disease duration have a higher likelihood of HT also raises the question of whether HT becomes more likely over time in individual patients., Competing Interests: Funding: This research was conducted by the Dystonia Coalition, which is part of the Rare Diseases Clinical Research Network, an initiative funded by the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences (U54 TR001456) in collaboration with the National Institute of Neurological Disorders and Stroke (U54 NS065701) at the National Institutes of Health (NIH). This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer-Reviewed Medical Research Program under Award No. W81XWH-17-1-0393. Opinions, interpretations, conclusions, and recommendations made in this article are those of the author and are not necessarily endorsed by the Department of Defense. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent., (© 2020 Chen et al.)

Patients with cervical dystonia (CD) may present with head and/or neck movements in the coronal, sagittal or transverse plane. According to the Col-Cap concept, CD postures are classified in torti-, latero-, ante- and retrocollis/caput patterns. The frequency of these different subtypes has to be evaluated. Between January and June 2019, we examined 306 patients (55.5 ± 13.1 years, 67% female) with CD according to the Col-Cap concept. They were all treated with botulinum toxin. This prospective study took place in seven different movement disorder centers. The most common primary form was torticaput (49%), the second most common was laterocaput (16.7%). All other subtypes were less than 10% of the study population. Pure forms were observed in 16.3% of patients only. Torticaput was combined in 46% with laterocaput, and in 20.7% with retrocaput. Laterocaput was combined mainly with torticaput (45.1%), laterocollis (33.2%) or retrocaput (23.5%). Shift forms were found in 14.7%, but diagnosed only in 3.9%. On average, the patients had 2.51 (± SD 1.09) subtypes each. Tremor was observed in 55.6%. The mean number of injected muscles was 4.4 (SD 1.6). The most often injected muscles were splenius capitis (83%), sternocleidomatoideus (79.1%), and upper trapezius (58.5%). This is the first multicenter study to examine the frequency of different subtypes of CD according to the Col-Cap concept. The caput subforms are more common than the cervical types, with torticaput as the most common one. Shift forms were diagnosed less often than described. Pure forms are very rare, combinations of 2-6 subtypes are common (83.7%). Sternocleidomatoideus, splenius capitis and trapezius muscles were still injected most often, but the muscles rarely injected in the past such as levator scapulae (48.7%), obliquus capitis inferior (35.3%) and longissimus (16.7%) were considered quite often. Since optimal therapy results depend on the injection of the right muscles, the correct classification should optimize the treatment outcome.

Background: Idiopathic cervical dystonia (ICD) is a focal dystonia affecting neck muscles. Botulinum neurotoxin (BoNT) is the first-line treatment of ICD and different physical therapies (including exercise) are often proposed as adjunct treatments. However, the actual effectiveness of exercise in ICD is unclear. The aim of the current work is to assess the potential effectiveness of the Sensorimotor Perceptive Rehabilitation Integrated (SPRInt) exercise program as adjunct therapy for ICD., Methods: Fifteen ICD patients received BoNT injections in the neck muscles and, 12 weeks later, received BoNT a second time and SPRInt started. SPRInt consists in 18 exercise sessions in which augmented feedback of movement (including visual and acoustic feedback) is extensively used. Dystonia burden was measured by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patients were evaluated immediately before, 6 and 12 weeks after each BoNT injection., Results: Six weeks after the first BoNT injection (i.e., at BoNT peak effect), TWSTRS total score was better than baseline and remained improved at 12 weeks. TWSTRS disability domain slightly improved 6 weeks after the first BoNT injection, but after 6 more weeks returned to its baseline level. Disability improved more at SPRInt end (i.e., 6 weeks after the second BoNT injection), being even lower than after toxin alone. With a single-subject analysis, 4/10 patients who did not improve disability after BoNT improved after SPRInt plus BoNT., Conclusions: SPRInt plus BoNT can be more effective than BoNT alone in improving cervical dystonia patients' difficulties in the activities of daily living., Trial Registration: www.ClinicalTrials.gov, identifier NCT03247868 (https://register.clinicaltrials.gov).

Background: Physical examination findings of dystonia are often underrecognized, especially in the setting of other movement disorders such as essential tremor (ET)., Phenomenology Shown: A patient with ET exhibited numerous textbook features of cervical dystonia, which were misattributed to ET by a primary care physician and two neurologists., Educational Value: To provide a clear and unmistakable visual example of the clinically significant characteristics of cervical dystonia in the setting of concomitant ET., Competing Interests: Funding: This research was supported by the National Institutes of Health Grant R01 NS094607. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent. All patients who appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided., (© 2019 Hale et al.)