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

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], 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). 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.

[Grisel's syndrome : about two cases of a atlantoaxial (C1-C2) subluxation]. / Le syndrome de Grisel : à propos de deux cas de subluxation C1-C2.

Grisel's syndrome is a non-traumatic atlantoaxial (C1-C2) subluxation and one of the causes of torticollis in children. The subluxation occurs in the context of an infection in the ENT ("Ear Nose and Throat") region or following surgery. Diagnosis is based on clinical examination and radiological assessment. Treatment is typically medical and conservative, with surgical interventions reserved for recurrences and late presentations. We discuss here two cases of C1-C2 subluxation. The first case involves a 10-year-old child with subluxation following a rhinopharyngitis. This presentation is the classical manifestation of Grisel's syndrome. Prompt management led to correction of the subluxation using medical treatment and a soft Philadelphia collar. The second case involves a 34-year-old adult who developed posterior headaches after sphenoidotomy surgery. Grisel's syndrome is less common in adults, leading to clinical challenges and delayed diagnosis (> 1 month). Reduction combined with a halo vest treatment failed, and the patient required cervical arthrodesis.

Le syndrome de Grisel est une subluxation atlanto-axoïdienne (C1-C2) non traumatique et l'une des causes de torticolis chez l'enfant. La subluxation survient dans le cadre d'une infection de la sphère ORL ou à la suite d'une chirurgie. Le diagnostic est basé sur la clinique et l'examen radiologique. Le traitement est le plus souvent médical et conservateur. Les prises en charge chirurgicales sont limitées aux récidives et aux présentations tardives.Nous discutons ici deux cas de subluxation C1-C2. La première chez un enfant de 10 ans faisait suite à une rhinopharyngite. Cette présentation correspond à la présentation typique du syndrome de Grisel. Une prise en charge rapide a permis une correction de cette subluxation à l'aide d'un traitement médical et d'une minerve souple de type Philadelphia. Le second cas concerne une adulte de 34 ans qui a présenté des céphalées postérieures à la suite d'une chirurgie de sphénoïdotomie. Le syndrome Grisel est moins fréquent chez l'adulte, ce qui a engendré une errance clinique et un diagnostic retardé (> 1 mois). La réduction associée à un traitement par haloveste a échoué et la patiente a nécessité une arthrodèse cervicale.

Endoscopic minimally invasive treatment of congenital muscular torticollis in children.

BACKGROUND: This study aimed to investigate the clinical efficacy of minimally invasive endoscopic treatment of children with congenital muscular torticollis (CMT). METHODS: In total, 72 children (41 male, 31 female) with CMT who underwent endoscopic surgery at the Department of Orthopedics, Xi'an Children's Hospital, between January 2021 and January 2023 were included. Their mean age was 54 ± 36.1 (range, 12-141) months. Of these, 29 (40.3%) cases involved the left side while 43 (59.7%) involved the right side. Preoperative preparation involved precise body surface markings of the sternocleidomastoid muscle(SCM), clavicle, and important nerve and blood vessels, followed by the establishment of surgical channels through passive separation techniques. An arthroscope and a low-temperature plasma knife were utilized for accurate localization and surgical release of the clavicular and sternal heads of the SCM. The duration of surgery, blood loss, postoperative hospital stay, neck range of motion measurements, and any intraoperative or postoperative complications were analyzed using the rank sum test. Cervical and thoracic braces were applied for three months postoperatively, with follow-up assessments conducted using Cheng's scoring system. RESULTS: All patients successfully underwent endoscopic surgery, without the need for conversion to open surgery. No intra- or postoperative complications were observed. The average surgical duration was 56.4 ± 15.7 min, with minimal intraoperative bleeding (1-5 mL) and no need for blood transfusion. The mean postoperative hospital stay was 2.7 ± 0.8 days. Over a mean follow-up period of 22.2 ± 5.5 (range, 14-32) months, significant improvements were observed in neck rotation (from 20.2° [17.7° to 25°] to only 3.6° [2° to 6.7°]) and lateral flexion (from 19° [17° to 22.6°] to only 3° [2° to 7.8°]) restrictions (p < 0.05). According to Cheng's scoring system, 70 (97.2%) patients achieved excellent or good clinical outcomes, while 2 (2.8%) had average outcomes. The torticollis deformity was corrected during the follow-up period, and all surgical incisions healed without noticeable scarring. CONCLUSION: Endoscopic release is a safe, effective, and minimally invasive treatment option for CMT in children.

The Relationship Between Postural Torticollis Abnormalities and Plagiocephaly on the Early Motor Development Milestones of Lying and Rolling Activities in Infants: A Retrospective Study.

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).

Current use of neurotoxins for alleviating symptoms of cervical dystonia.

INTRODUCTION: Cervical dystonia (CD) causes involuntary movements and postures of the head, neck, and shoulders, as well as nonmotor symptoms including pain, mood, and sleep dysfunction, and impacts quality of life. The first-line treatment for CD is botulinum neurotoxin (BoNT) injections. AREAS COVERED: The clinical presentation and diagnosis of CD, as well as where BoNT resides in the treatment landscape, is reviewed first. Next, the mechanism of action and the pharmacological differences in the available preparations of BoNT products are explained. The evidence base for motor and nonmotor efficacy and safety of the available BoNT formulations is reviewed, with attention to duration of benefit as a driver of patient satisfaction. Practical determinants of BoNT efficacy are reviewed including muscle selection, accurate muscle injection, factors related to poor or deteriorating response, and immunogenicity. EXPERT OPINION: BoNT represents a significant advancement in the treatment of CD. More accurate diagnosis, muscle selection and targeting, and dosing can improve outcomes with existing BoNT formulations. Further refinement of BoNT potency, duration of action, safety, and immunogenicity will help reduce unmet needs in the magnitude and duration of benefit. Additional validation of DBS and MRI-guided focused ultrasound may expand options for patients with toxin nonresponse.

Muscle texture features on preoperative MRI for diagnosis and assessment of severity of congenital muscular torticollis.

OBJECTIVES: To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT). MATERIAL AND METHODS: The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed. RESULTS: There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868. CONCLUSION: The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT.

Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

OBJECTIVE: Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. METHODS: The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. RESULTS: The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. CONCLUSIONS: Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

Duration of botulinum toxin efficacy in cervical dystonia clinical trials: A scoping review.

INTRODUCTION: Botulinum toxin (BoNT) is first-line treatment for cervical dystonia (CD). Treatment of CD with BoNT usually requires injections every 3-4 months for as long as symptoms persist, which can be for the lifetime of the individual. Duration of BoNT effect can impact quality of life since it is important that efficacy is maintained throughout an injection cycle to avoid fluctuations of effect after each injection. There is currently no consensus on how to assess duration of BoNT effect in patients with CD. METHODS: A scoping review was conducted to summarize the available evidence from phase 3 clinical trials of BoNT in CD and on the interpretation of the reported duration of effect. The available evidence was analyzed in the context of clinical experience and real-world treatment practices of CD. RESULTS: Methods for estimating duration of effect varied across publications; most were based on artificial constructs developed for clinical trials (time until a pre-specified efficacy endpoint was reached) and are not appropriate to apply in clinical practice. Clinical trial outcomes in CD were not objectively evaluated, and did not prioritize patients' needs or focus on factors that impact patients' daily living activities and quality of life. CONCLUSION: Better evidence and consistency of reporting for duration of effect for BoNT in CD is needed to help guide clinicians on when reinjection is likely to be required. The goal should be to keep patients as symptom-free as possible with flexible reinjection intervals tailored to individual needs.

The Application of Goal Attainment Scaling in Cervical Dystonia - An Exploratory Observational Pilot Study.

BACKGROUND: Due to its heterogeneous manifestation an individualized approach to reach therapeutic goals in cervical dystonia (CD) is advantageous. OBJECTIVES: The aim of the current study was to adapt goal attainment scaling (GAS) to drive the management of CD. METHODS: 38 patients with CD, regularly treated with botulinum neurotoxin (BoNT), were involved in the current exploratory observational pilot study. GAS, including domains of motor, pain, disability, and psychiatric features, was applied to set up individualized goals with the calculation of initial GAS T-scores. Following at least 4 BoNT injection cycles, patients were reassessed whether they reached the pre-set goals. RESULTS: The initial GAS T-scores (median: 36.9, range: 22.8-40) significantly improved (P < 0.001) to the end of the study (the median of final GAS T-scores: 50, range: 25.5-63.6). CONCLUSIONS: The applicability of GAS in CD patients was confirmed, but further large-scale studies are needed refining this innovative approach.

Topological alterations in white matter anatomical networks in cervical dystonia.

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Understanding Anxiety in Cervical Dystonia: An Imaging Study.

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.

François Rabelais and his dystonic giants.

Spasmodic torticollis was an early designation used for cervical dystonia. The origin of this name is attributed to French physician and writer François Rabelais in the mid-sixteenth century. This early description of torticollis in the book Pantagruel was an inspiration for the understanding of cervical dystonia. The art expressed in Rabelais' literature ‒ which was immortalized by the drawings of Gustave Doré ‒ influenced poetry, art, and photography, and led to the adoption of the term torticollis in the neurological sciences.

Uma designação inicial usada para distonia cervical era torcicolo espasmódico. A origem desse termo é atribuída ao médico e escritor francês François Rabelais em meados do século XVI. Essa descrição inicial do torcicolo no livro Pantagruel foi uma inspiração para a compreensão da distonia cervical. A arte exibida na literatura de Rabelais ‒ imortalizada pelos desenhos de Gustave Doré ‒ influenciou a poesia, a arte e a fotografia, e levou à adoção do termo torcicolo nas ciências neurológicas.

Severity of Antipsychotic-Induced Cervical Dystonia Assessed by the Algorithm-Based Rating System.

Background: The severity of antipsychotic-induced cervical dystonia has traditionally been evaluated visually. However, recent advances in information technology made quantification possible in this field through the introduction of engineering methodologies like machine learning.Methods: This study was conducted from June 2021 to March 2023. Psychiatrists rated the severity of cervical dystonia into 4 levels (0: none, 1: minimal, 2: mild, and 3: moderate) for 101 videoclips, recorded from 87 psychiatric patients receiving antipsychotics. The Face Mesh function of the open-source framework MediaPipe was employed to calculate the tilt angles of anterocollis or retrocollis, laterocollis, and torticollis. These were calculated to examine the range of tilt angles for the 4 levels of severity of the different types of cervical dystonia.Results: The tilt angles calculated using Face Mesh for each level of dystonia were 0° ≤ θ < 6° for none, 6° ≤ θ < 11° for minimal, 11° ≤ θ < 25° for mild, and 25° ≤ θ for moderate laterocollis; 0° ≤ θ < 11° for none, 11° ≤ θ < 18° for minimal, 18° ≤ θ <25° for mild, and 25° ≤ θ for moderate anterocollis or retrocollis; and 0° ≤ θ < 9° for none, 9° ≤ θ < 17° for minimal, 17° ≤ θ < 32° for mild, and 32° ≤ θ for moderate torticollis.Conclusion: While further validation with new cases is needed, the range of tilt angles in this study could provide a standard for future artificial intelligence devices for cervical dystonia.