Cervical Dystonia Research Articles

Wearable device to measure disease severity in cervical dystonia (P11-11.009)

Wearable device to measure disease severity in cervical dystonia (P11-11.009)

Clinical significance of indicators of energy metabolism in muscles involved in dystonic hyperkinesis in patients with idiopathic muscular dystonia

Introduction. Dystonia is a syndrome with location of pathological mechanisms in the central nervous system. The clinical manifestation of the syndrome is dystonic hyperkinesis with the formation of increased muscle tone, which may be associated with changes in cellular metabolism. Aim is to evaluate the indicators of energy metabolism in the muscles involved in dystonic hyperkinesis and compare with the severity of dystonia in patients with idiopathic muscular dystonia.
 Materials and methods. There were examined eighty four patients diagnosed with idiopathic muscular dystonia, including 17 men (20.2%) and 67 women (79.8%). In 38 cases there was cervical muscular dystonia, 36 and 10 cases showed segmental and generalized forms of dystonia with predominance of cervical dystonia syndrome, respectively. The average age of patients was 46 ± 11 among men and 52 ± 11 among women. The control group included 10 conditionally healthy individuals with an average age of 53.0 ± 13.4 years. The severity of cervical dystonia was assessed by the TWSTRS and Tsui scales. All participants of the study underwent biopsy sampling from the trapezius muscle, followed by determination of the level of ATP (adenosine triphosphoric acid), lactate and 2,3 DPH (2,3-diphosphoglyceric acid).
 Results. The results of the study revealed changes in the bioenergetics of muscle tissue in the form of a decrease in ATP and 2,3-DPH and an increase in lactate levels that did not correlate with the severity of dystonia on the TWSTRS and Tsui scales.
 Conclusion. Thus, bioenergetic changes in muscle tissue are not associated with the severity of dystonia and probably reflect general changes in the organization of intracellular energy metabolism in muscles in a hypertonic state.

Comparison of Oropharyngeal Dysphagia Before and After Botulinum Toxin Injection in Cervical Dystonia.

Cervical dystonia (CD) is the most common form of focal dystonia with Botulinum neurotoxin (BoNT) being a frequent method of treatment. Dysphagia is a common side effect of BoNT treatment for CD. Instrumental evaluation of swallowing in CD using standardized scoring for the videofluoroscopic swallowing study (VFSS) and validated and reliable patient-reported outcomes measures is lacking in the literature. (1) to determine if BoNT injections change instrumental findings of swallowing function using the Modified Barium Swallow Impairment Profile (MBSImP) in individuals with CD; (2) to determine if BoNT injections change self-perception of the psychosocial handicapping effects of dysphagia in individuals with CD, using the Dysphagia Handicap Index (DHI); (3) to determine the effect of BoNT dosage on instrumental swallowing evaluation and self-reported swallowing outcomes measures. 18 subjects with CD completed a VFSS and the DHI before and after BoNT injection. There was a significant increase in pharyngeal residue for pudding consistency after BoNT injection, p = 0.015. There were significant positive associations between BoNT dosage and self-perception of the physical attributes of the handicapping effect of dysphagia, the grand total score and patient self-reported severity of dysphagia on the DHI; p = 0.022; p = 0.037; p = 0.035 respectively. There were several significant associations between changes in MBSImP scores and BoNT dose. Pharyngeal efficiency of swallowing may be affected by BoNT for thicker consistencies. Individuals with CD perceive greater physical handicapping effects of dysphagia with increased amounts of BoNT units and have greater self-perceptions of dysphagia severity with increased amounts of BoNT units.

Teaching Neuro Images : Facial grimacing and sensorineural hearing loss in a woman with cirrhosis of the liver

A 29-year-old woman presented with 5-year history of gait instability and hearing loss. Medical history disclosed cirrhosis of the liver and polycythemia. Examination showed bradykinesia, facial grimacing, cervical dystonia, and ataxia. Neuroimaging showed hyperintense signal in basal ganglia on T1-weighted images (figure). Blood tests showed 18.5 g/dL of hemoglobin and 1,500 nmol/L of serum manganese (reference <320 nmol/L). Genetic analysis revealed previously described pathogenic1,2 homozygous mutation c.266T>C(p.Leu89Pro) in the SLC30A10 gene.

What Are the Functions of the Superior Colliculus and Its Involvement in Neurologic Disorders?

The superior colliculus (SC) is an evolutionary conserved sensorimotor structure that is specialized for detecting, localizing, and orienting toward environmental events and has a critical role in orienting motor responses, visuospatial attention, and perceptual decision-making.1-8 The SC consists of a superficial layer that receives visual inputs and intermediate and deep motor layers that initiate saccades and other orienting movements toward the contralateral hemispace. Modern molecular and genetic methods combined with behavioral assessments have provided further understanding of the cell types, circuits, and functions of the SC (reviewed in ref. 9,10). The SC is affected by α-synuclein and tau neuropathology in Lewy body dementia (LBD),11 shows abnormal responses to visual stimuli in Parkinson disease (PD),12,13 may contribute to impaired saccades in progressive supranuclear palsy (PSP),14 and may be involved in the pathophysiology of cervical dystonia.15,16 This brief review will focus on recent concepts on the functional organization and connectivity of the SC that are relevant to understand the pathophysiology of these and other neurologic disorders.

Pallidal Recordings in Chronically Implanted Dystonic Patients: Mitigation of Tremor-Related Artifacts.

Low-frequency oscillatory patterns of pallidal local field potentials (LFPs) have been proposed as a physiomarker for dystonia and hold the promise for personalized adaptive deep brain stimulation. Head tremor, a low-frequency involuntary rhythmic movement typical of cervical dystonia, may cause movement artifacts in LFP signals, compromising the reliability of low-frequency oscillations as biomarkers for adaptive neurostimulation. We investigated chronic pallidal LFPs with the PerceptTM PC (Medtronic PLC) device in eight subjects with dystonia (five with head tremors). We applied a multiple regression approach to pallidal LFPs in patients with head tremors using kinematic information measured with an inertial measurement unit (IMU) and an electromyographic signal (EMG). With IMU regression, we found tremor contamination in all subjects, whereas EMG regression identified it in only three out of five. IMU regression was also superior to EMG regression in removing tremor-related artifacts and resulted in a significant power reduction, especially in the theta-alpha band. Pallido-muscular coherence was affected by a head tremor and disappeared after IMU regression. Our results show that the Percept PC can record low-frequency oscillations but also reveal spectral contamination due to movement artifacts. IMU regression can identify such artifact contamination and be a suitable tool for its removal.

Topological differences and confounders of mental rotation in cervical dystonia and blepharospasm

Mental rotation (mR) bases on imagination of actual movements. It remains unclear whether there is a specific pattern of mR impairment in focal dystonia. We aimed to investigate mR in patients with cervical dystonia (CD) and blepharospasm (BS) and to assess potential confounders. 23 CD patients and 23 healthy controls (HC) as well as 21 BS and 19 hemifacial spasm (HS) patients were matched for sex, age, and education level. Handedness, finger dexterity, general reaction time, and cognitive status were assessed. Disease severity was evaluated by clinical scales. During mR, photographs of body parts (head, hand, or foot) and a non-corporal object (car) were displayed at different angles rotated within their plane. Subjects were asked to judge laterality of the presented image by keystroke. Both speed and correctness were evaluated. Compared to HC, CD and HS patients performed worse in mR of hands, whereas BS group showed comparable performance. There was a significant association of prolonged mR reaction time (RT) with reduced MoCA scores and with increased RT in an unspecific reaction speed task. After exclusion of cognitively impaired patients, increased RT in the mR of hands was confined to CD group, but not HS. While the question of whether specific patterns of mR impairment reliably define a dystonic endophenotype remains elusive, our findings point to mR as a useful tool, when used carefully with control measures and tasks, which may be capable of identifying specific deficits that distinguish between subtypes of dystonia.

Expanding the phenotypic landscape of Gaucher disease type 3c with a novel entity - Transient neonatal cholestasis

Gaucher disease (GD) is the most frequent lysosomal storage disorder due to biallelic pathogenic variants in GBA gene. Only homozygous D409H variant has been associated with the cardiovascular phenotype which is also known as Gaucher disease type 3c. In this descriptive study, we presented phenotypic heterogeneity and a novel clinical finding among 13 patients with GD type 3c. Patients presented with varying degrees of cardiac valve and/or aortic calcifications (84,6%) and corneal opacities (76,9%) in addition to visceral (100%), hematological (92,3%), neurological (92,3%), and skeletal (30%) manifestations. Also, cervical dystonia (38,4%) and psychiatric disorders (46,1%) were not infrequent entities with respect to neurological involvement in GD type 3c. In this report, we highlight transient neonatal cholestasis (38,4%) as a novel finding in GD type 3c. Neonatal cholestasis is a finding associated with Gaucher type 2, but transient neonatal cholestasis has not been reported in GD patients, so far. The clinical features of GD type 3c are highly heterogeneous, from disease severity or age of onset to disease progression. Also, we concluded that phenotypic spectrum may be associated with age at onset of clinical symptoms. As, patients presenting in infancy or childhood had mainly visceral and hematological involvement and patients presenting in adolescence and adulthood had mainly cardiac, neurological involvement, and psychiatric behavioral disorders. Identifying the heterogeneous clinical course of these patients in this fatal disease, may lead a sufficient understanding of the pathophysiology which will enable targeted therapeutic interventions.

Is There a Standard Rehabilitation Procedure in Cervical Dystonia?

Introduction: Idiopathic cervical dystonia, also known as spasmodic torticollis, is the most common form of focal dystonia in adults. Cervical dystonia usually appears between the ages of 30 and 50, twice as often in women, and is characterised by uncontrollable painful contractions of the sternocleidomastoid muscle, which results in misalignment of the head and shoulder. Over time, the disease becomes very burdensome for the patient and reduces his/her independence and quality of life; falls happen.Aim: The aim of the article is to present the current state of knowledge on comprehensive rehabilitation in cervical dystonia. Data on the prevalence, symptoms, diagnosis, clinical assessment, pharmacological treatment (including the most commonly used botulinum toxin), neurosurgical treatment and comprehensive rehabilitation are presented.Methods: The applied methods was a narrative critical review of scientific reports.Results: Out of several hundred publications, works worthy of particular attention were selected. In them, are described of conducting exercises, the main goal of which is to stretch and relax the dystonic muscles while strengthening the antagonistic muscles and correcting the position of the head. The selected authors used manual therapy, exercises at the patient's home, EMG biofeedback, magnetic stimulation of the cerebellum, vibration of the neck muscles, functional electrostimulation (FES) of antagonistic muscles, mobilisation of the cervical spine, postural exercises, isometric exercises, muscle relaxation, the PNF method, relaxation training, balance exercises, coordination, corrective exercises, massage, relaxation exercises, stretching and kinesiotaping.Conclusions: The variety of disease forms (10 head positioning patterns are described) and different severity of symptoms make it impossible to draw up a scheme of rehabilitation. In each case, rehabilitation must be tailored individually, and the physiotherapist taking care of the patient should have extensive experience. Physiotherapy can alleviate the disability caused by dystonia, however, due to the many non-motor symptoms, a holistic approach to the patient should also be kept in mind.

A novel compound heterozygous mutation of COL6A3 in Chinese patients with isolated cervical dystonia.

The etiology and pathogenesis of idiopathic dystonia remain obscure. Recent studies revealed that compound heterozygous mutations in collagen type VI alpha-3 gene COL6A3 may cause recessive isolated dystonia (DYT)-27. However, whether COL6A3 mutations are associated with Chinese patients with isolated dystonia is not yet reported. In this study, 45 Chinese patients with isolated cervical dystonia were recruited, and their blood DNA samples were subjected to whole-exome sequencing. The potential causal variants of COL6A3 were identified based on the criteria of the American College of Medical Genetics and Genomics and by prediction software. Among 45 isolated cervical dystonia patients, 18 patients (10 female patients and eight male patients) were found to have seven potential causal variants in the COL6A3 gene. Among these variants, a compound heterozygous mutation was found in one patient. One allele had a c.1264G>A mutation in exon 4 that resulted in an amino acid substitution of methionine for valine at codon 422 (p.Val422Met) and the other a c.8965+9G>A mutation involving a splicing change in exon 40. In addition, other five missense variants, including c.958G>A (p.Ala320Thr), c.1478T>C (p.Val493Ala), c.1597C>T (p.Arg533Cys), c.1762G>A (p.Asp588Asn), and c.4912G>A (p.Ala1638Thr), were identified as well. We identified a novel deleterious compound heterozygous mutation as well as five missense variants in the COL6A3 gene of Chinese patients with cervical dystonia. These findings may expand the spectrum of the COL6A3 genotype in isolated dystonia.

Management of cervical dystonia through Ayurveda - A case report

Abstract Spasmodic torticollis is a rare condition characterized by involuntary movement of the head. The pain often becomes the primary reason for the patient to seek medical attention, with the patient almost indifferent to the dystonic movements. Prakupita Vata (aggravated Vata) causes various kinds of diseases of Vata called Vata Vyadhi (diseases of vitiated Vata) and treatments such as Snehana (oleation therapy), Swedana (sudation therapy), and Shodhana (internal detoxification) are advised. The patient complaining of pain, stiffness of the neck, and tremors gradually progressing to hyperextension of the neck was clinically diagnosed as Dhatu Kshaya Vata Vikara and treated on the lines of Vata Vyadhi (diseases of vitiated Vata). Shodhana (internal detoxification) such as Nasya and Basti, in combination with external Panchakarma procedures and internal medicines including Rasayana (rejuvenation), were administered. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was assessed for the outcome of the treatment. The patient showed good improvement in pain, stiffness, tremors, and neck retention time. TWSTRS score had reduced from 66.25 to 29 and is presented here as a case study.

Isolated Cervical Dystonia: Diagnosis and Classification.

This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to make it reproducible across centers and applicable by expert and non-expert clinicians. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations, which are incorporated into the current criteria. Three iCD presentations are described in some detail: idiopathic (focal or segmental) iCD, genetic iCD, and acquired iCD. The relationship between iCD and isolated head tremor is also reviewed. Recognition of idiopathic iCD has two levels of certainty, definite or probable, supported by specific diagnostic criteria. Although a probable diagnosis is appropriate for clinical practice, a higher diagnostic level may be required for specific research studies. The consensus retains elements proven valuable in previous criteria and omits aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of iCD expands, these criteria will need continuous revision to accommodate new advances. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Xeomin®, a Commercial Formulation of Botulinum Neurotoxin Type A, Promotes Regeneration in a Preclinical Model of Spinal Cord Injury.

Xeomin® is a commercial formulation of botulinum neurotoxin type A (BoNT/A) clinically authorized for treating neurological disorders, such as blepharospasm, cervical dystonia, limb spasticity, and sialorrhea. We have previously demonstrated that spinal injection of laboratory purified 150 kDa BoNT/A in paraplegic mice, after undergoing traumatic spinal cord injury (SCI), was able to reduce excitotoxic phenomena, glial scar, inflammation, and the development of neuropathic pain and facilitate regeneration and motor recovery. In the present study, as proof of concept in view of a possible clinical application, we studied the efficacy of Xeomin® in the same preclinical SCI model in which we highlighted the positive effects of lab-purified BoNT/A. Data comparison shows that Xeomin® induces similar pharmacological and therapeutic effects, albeit with less efficacy, to lab-purified BoNT/A. This difference, which can be improved by adjusting the dose, can be attributable to the different formulation and pharmacodynamics. Although the mechanism by which Xeomin® and laboratory purified BoNT/A induce functional improvement in paraplegic mice is still far from being understood, these results open a possible new scenario in treatment of SCI and are a stimulus for further research.

Mutation screening of AOPEP variants in a large dystonia cohort.

Recently, AOPEP has been identified to be a novel causative gene of autosomal-recessive dystonia. However, no large cohort study has been conducted to confirm the association. We aimed to systematically evaluate the genetic associations of AOPEP with dystonia in a large Chinese dystonia cohort. We analyzed rare variants of AOPEP in 878 dystonia patients with whole-exome sequencing. The over-representation of rare variants in patients was examined with Fisher's exact test at allele and gene levels. Among the 878 patients with dystonia, we found two patients with biallelic likely pathogenic variants in the AOPEP gene. One patient carried putative compound heterozygous variants (p.A212D and p.G216R) and presented with childhood-onset segmental dystonia involving the upper limbs and craniocervical muscles accompanied by myoclonus of the dystonia affected areas. One patient carried homozygote of p.M291Nfs*68 and presented with adult-onset isolated cervical dystonia. Another 15 patients were identified to carry heterozygous rare variants in AOPEP, including 2 loss-of-function variants (p.M291Nfs*68 and p.R493X) and 6 missense variants. One loss-of-function variant (p.R493X) was the same as previously reported. Nearly, all of the 15 patients carrying heterozygous variants in AOPEP presented with isolated dystonia with only craniocervical muscles affected, except for one patient who carried the p.R493X variant presented with segmental dystonia affecting the neck and right upper limb combined with parkinsonism. Gene-based burden analysis detected enrichment of rare variants and rare damaging variants of AOPEP in dystonia. Our study supplemented the evidence on the role of AOPEP in autosomal-recessive dystonia in Chinese population, and expanded the genotypic and phenotypic spectrum of AOPEP.

Iron accumulation and axonal damage of cerebellum in idiopathic cervical dystonia.

Postmortem brain study indicated that cerebellar Purkinje cell (PC) loss might be a pathological finding in patients with inherited and idiopathic cervical dystonia (ICD). The analysis of conventional magnetic resonance imaging brain scans failed to yield support for this finding. Previous studies have identified that iron overload can be the consequence of neuron death. The objectives of this study were to investigate iron distribution and demonstrate changes in axons in the cerebellum, providing evidence for PC loss in patients with ICD. Twenty-eight patients with ICD (20 females) and 28 age- and sex-matched healthy controls were recruited. A spatially unbiased infratentorial template was applied to perform cerebellum optimized quantitative susceptibility mapping and diffusion tensor analysis based on magnetic resonance imaging. Voxel-wise analysis was performed to assess cerebellar tissue magnetic susceptibility and fractional anisotropy (FA) alterations, and the clinical relevance of these findings was investigated in the patients with ICD. Increased susceptibility values revealed by quantitative susceptibility mapping in the right lobule CrusI, CrusII, VIIb, VIIIa, VIIIb and IX were found in the patients with ICD. A reduced FA value was found across almost all the cerebellum; an FA value of the significant clusters within the right lobule VIIIa significantly correlated with the motor severity of patients with ICD (r=-0.575, p=0.002). Our study provided evidence for cerebellar iron overload and axonal damage in patients with ICD, which may indicate PC loss and related axonal changes. These results provide evidence for the neuropathological findings in patients with ICD and further highlight the cerebellar involvement in the pathophysiology of dystonia.

FV 10 Cerebellar modulation of associative plasticity is impaired in cervical dystonia

FV 10 Cerebellar modulation of associative plasticity is impaired in cervical dystonia

Isolated Dystonia as an Initial Presentation of GDAP2-Related Disorder.

Isolated Dystonia as an Initial Presentation of GDAP2-Related Disorder.

METHODS OF BRAIN RESEARCH IN THE CERVICAL DYSTONIA

The review is based on 149 foreign and Russian articles. The features of the brain functioning in cervical dystonia (CD) through the prism of modern technologies are reviewed. CD is hard to diagnose currently. CD is one of the promising areas not only in the clinical paradigm. In the future, CD can become an interesting model for studying the features of the balance of excitation/inhibition in brain neurons with the use of modern technologies. Using CD as a model of specific changes in function connections of brain regions, it would be possible to extrapolate the results to a healthy population and to the patients with other neurological or mental diseases.

Cortico-Subcortical White Matter Bundle Changes in Cervical Dystonia and Blepharospasm

Dystonia is thought to be a network disorder due to abnormalities in the basal ganglia-thalamo-cortical circuit. We aimed to investigate the white matter (WM) microstructural damage of bundles connecting pre-defined subcortical and cortical regions in cervical dystonia (CD) and blepharospasm (BSP). Thirty-five patients (17 with CD and 18 with BSP) and 17 healthy subjects underwent MRI, including diffusion tensor imaging (DTI). Probabilistic tractography (BedpostX) was performed to reconstruct WM tracts connecting the globus pallidus, putamen and thalamus with the primary motor, primary sensory and supplementary motor cortices. WM tract integrity was evaluated by deriving their DTI metrics. Significant differences in mean, radial and axial diffusivity between CD and HS and between BSP and HS were found in the majority of the reconstructed WM tracts, while no differences were found between the two groups of patients. The observation of abnormalities in DTI metrics of specific WM tracts suggests a diffuse and extensive loss of WM integrity as a common feature of CD and BSP, aligning with the increasing evidence of microstructural damage of several brain regions belonging to specific circuits, such as the basal ganglia-thalamo-cortical circuit, which likely reflects a common pathophysiological mechanism of focal dystonia.

Conversion to AbobotulinumtoxinA Increases Waning Time and Efficacy for Cervical Dystonia.

Symptom re-emergence before re-injection negatively impacts cervical dystonia (CD) patients receiving botulinum toxin type A (BoNT-A) therapy. Longer waning time is associated with abobotulinumtoxinA (abo-BoNT-A) as compared to onabotulinumtoxinA (ona-BoNT-A)/incobotulinumtoxinA (inco-BoNT-A) formulations. To compare waning time and treatment outcomes when chronically injected CD patients experiencing early waning despite being optimized on BoNT-A (ona-BoNT-A/inco-BoNT-A) were converted to abo-BoNT-A. Thirty-three chronically injected CD participants with a waning time of ≤8 weeks were converted to abo-BoNT-A (1:2.5 dose ratio) for three injections every 12-weeks. The second and third injection patterns were kinematically optimized. Participants were converted back to their original BoNT-A for the fourth injection (1:2.5) using the same third abo-BoNT-A pattern. Participant-perceived waning times were collected post-injections. Clinical scales (Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)) and kinematic measures were collected 12-weeks post-injection and at three peak effect time-points. Compared to baseline, waning time (12-22 days) significantly increased following all abo-BoNT-A treatments (P < 0.005) but was not significantly different at the fourth injection (original BoNT-A reconversion). TWSTRS sub-scores significantly reduced following all abo-BoNT-A treatments (P < 0.0001) and at peak effect following the third injection compared to original BoNT-A. Dysphagia and muscle weakness were reported and comparable to safety of original BoNT-A formulations. Optimized patients experiencing waning had significant improvement in the peak benefit as well as the duration of effect when converted to abo-BoNT-A. This effect was toxin dependent as reconversion to the original BoNT-A using the kinematically optimized pattern failed to produce an improvement in waning.