Automated assessment of cervical dystonia.

We developed an automated and objective method to measure posture and voluntary movements in patients with cervical dystonia using Fastrack, an electromagnetic system consisting of a stationary transmitter station and four sensors. The junction lines between the sensors attached to the head produced geometrical figures on which the corresponding aspects of the head were superimposed. The head position in the space was reconstructed and observed from axial, sagittal, and coronal planes. Four patients with cervical dystonia and 6 healthy subjects were studied. Each patient was representative of one of the typical patterns of cervical dystonia. The study allowed the authors to collect quantitative data on posture and range of motion of the head. This pilot study demonstrates the efficacy of the Fastrack system to objectively measure the head position in cervical dystonia patients.     

Treatment of cervical dystonia hand spasms and laryngeal dystonia with botulinum toxin

Summary One hundred and twenty-six patients with different forms of focal dystonia (89 with cervical dystonia, 12 with hand cramps and 25 with laryngeal dystonia) were treated with localised injections of botulinum toxin. Mean doses per muscle were 200 mouse units (m.u.) for treating cervical dystonia, 40–120 m.u. for forearm muscles in writers' cramp and 3.7 m. u. for the thyroarytenoid muscle in laryngeal dystonia. Responder rates have been above 80% in all patient groups and beneficial effects could be reproduced over follow-up periods of up to 4 years. The commonest side-effects were dysphagia after treatment of spasmodic torticollis, weakness of neighbouring muscles after injections for hand cramps and breathiness and hypophonia following laryngeal injections. All these were transient and generally well tolerated. It is concluded that botulinum toxin injections are a safe and effective treatment in all three types of focal dystonia.     

A metabolomic study of cervical dystonia

IntroductionCervical dystonia is the most common of the adult-onset focal dystonias. Most cases are idiopathic. The current view is that cervical dystonia may be caused by some combination of genetic and environmental factors. Genetic contributions have been studied extensively, but there are few studies of other factors. We conducted an exploratory metabolomics analysis of cervical dystonia to identify potentially abnormal metabolites or altered biological pathways.MethodsPlasma samples from 100 cases with idiopathic cervical dystonia and 100 controls were compared using liquid chromatography coupled with mass spectrometry-based metabolomics.ResultsA total of 7346 metabolic features remained after quality control, and up to 289 demonstrated significant differences between cases and controls, depending on statistical criteria chosen. Pathway analysis revealed 9 biological processes to be significantly associated at p < 0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism.ConclusionThis is the first large scale metabolomics study for any type of dystonia. The results may provide potential novel insights into the biology of cervical dystonia.     

Cortical inhibitory function in cervical dystonia

Objective

To assess the specificity of cortical inhibitory deficits in cervical dystonia patients.

Botulinum toxin in cervical dystonia: low dosage with electromyographic guidance

Sixty patients with idiopathic cervical dystonia were treated a total of 240 times with botulinum toxin type A (BTA). Selected muscles were injected with BTA under electromyographic (EMG) guidance. The clinical effect was measured on the Tsui scale and a 10-point anchored visual analogue scale. A dosage of 150–300 mouse units was used in 77% of the treatments (mean 204 mouse units). Based on the Tsui scale, 45% of 240 treatments were still effective at the moment of reinjection (median improvement 2 points). Based on the 10-point anchored visual analogue scale, 73% of treatments were successful (median improvement 3 points). Forty-eight patients (80%) responded favourably to the treatment. Side-effects were mild and transient. Dysphagia occurred in 9% of treatments. Antibody production was investigated in 41 patients and was negative in all. A striking difference from previous reports is the lower dosage used in this study. The clinical response, however, was similar to that of other studies. We conclude that a dosage of 200–400 mouse units BTA (Dysport) may also be effective in the treatment of cervical dystonia, but with fewer side effects. EMG guidance and application of BTA into deep cervical muscles may further improve the clinical effect.     

Interoceptive sensitivity in patients with cervical dystonia

IntroductionInteroceptive sensitivity (IS) is the ability to perceive sensations arising from the inner body. One method used to measure IS is the heartbeat detection task. The aim of this study was to investigate IS in patients with cervical dystonia (CD) and compare the results with those obtained in healthy controls (HC). We also sought possible correlations between IS and demographic, clinical and emotional features in CD. To evaluate the reliability of IS in a subgroup of CD patients and HC, we retested IS 4–6 months after the first evaluation. We also investigated whether dystonic posture affects IS values in HC.MethodsTwenty CD patients and 20 HC were investigated. The heartbeat detection task was performed according to a standardized protocol. All the participants underwent a clinical, emotional and psychiatric evaluation.ResultsIS was lower in CD patients than in HC. The ROC curve analysis showed that an IS value of 0.52 differentiates CD patients from healthy controls. No correlations emerged in CD patients between IS and the demographic, clinical and emotional features. No differences were observed in either CD patients or healthy subjects when IS was retested 4–6 months after the first evaluation. When IS was tested in HC mimicking a dystonic posture, the results were similar to those obtained when they held their heads in a neutral position.ConclusionsThe study shows that IS is reduced in CD patients possibly due to an altered functional connection between basal ganglia and limbic circuit, including the insula.     

A cognitive-behavioural approach to the management of idiopathic cervical dystonia

A case is described in which a patient with idiopathic cervical dystonia is treated successfully with cognitive-behavioural therapy. It was hypothesised that although the dystonia was organic in origin, it was exacerbated and perpetuated by catastrophic thoughts and abnormal illness beliefs, and that modification of maintaining cognitive and behavioural responses would lead to improvement. Self-report outcome measures were consistent with this hypothesis and improvements were maintained at 6-month follow-up.     

Identification and treatment of cervical and oromandibular dystonia in acutely brain-injured patients

Introduction: Primary cervical and oromandibular dystonia (CD and OMD, respectively) are well-recognized movement disorders, often treated with botulinum toxin (BTx). In contrast, dystonia related to acute brain injuries is not well delineated. Our objective was to define in neurocritically ill patients the clinical characteristics of CD and OMD and to investigate the safety of BTx. Methods: All acutely brain-injured patients admitted to a neurocritical care unit over a 10-month period were prospectively screened for CD and OMD. Clinical characteristics, etiology of brain injury, and pattern of dystonia were analyzed. Patients with clinically significant CD and OMD were treated with BTx and followed for 12 weeks. Results: Of 165 patients screened, 33 had new-onset CD or OMD. Of 21 patients enrolled, 14 had CD, 5 had OMD, and 2 had both. The pattern of brain injury included 13 cerebral hemorrhages, 6 ischemic strokes, 1 status epilepticus, and 1 unclear etiology. Improvement after BTx was seen in four of seven patients with CD and two of four with OMD; no adverse effects occurred. Spontaneous improvement was recorded in 7 of 11 nontreated patients with CD or OMD. Conclusions: Acute secondary CD or OMD, associated with a variety of causes, was identified in 20% of acutely brain-injured patients. The temporal profile of dystonia onset and resolution in these patients was variable. Treatment with BTx in the neurocritical care setting seems to be safe. Future, larger scale randomized studies should evaluate the effectiveness of BTx treatment in this patient population.     

Long-term follow-up by video of cervical dystonia treated with botulinum toxin

We have analysed video recordings of 21 patients with cervical dystonia treated with botulinum toxin. Fourteen patients have a record both of their response shortly after injections were commenced and between four years five months and six years seven months later. Our analysis shows that the long term outcome is often better than the initial response. We suggest that chronic treatment with botulinum toxin allows different muscles to those initially injected to be identified as contributors to the dystonia. Subsequent injection of these muscles leads to further improvement. It implies that cervical dystonia is a more widespread disorder of motor control, rather than simply limited to a few muscles.     

Modification of cervical dystonia by selective sensory stimulation

Cervical dystonia is often refractory to all forms of therapy. Many patients, however, are able to transiently abolish their spasms following a specific gesture that presumably enhances sensory input. Such observations prompted us to develop a protocol to determine if various forms of sensory stimulation could modify the motor control patterns in cervical dystonia. Surface EMG recordings of multiple neck and trunk muscles were obtained in 11 consecutive cervical dystonia patients. Baseline patterns of voluntary and involuntary muscle activation were established during a series of motor and non-motor tasks. The tasks were repeated during the application of vibratory or electrical stimulation to select muscle groups or to cutaneous and mixed nerves. Analysis of the results was made on the basis of paper and computer recordings of the data. Sensory stimulation decreased involuntary muscle activity and reduced spasms in 5 subjects. However, objective or subjective improvement usually occured only after specific stimuli were applied to specific anatomical sites. In these cases, the protocol identified the site at which a specific sensory stimulus could be applied to control the dystonia. we conclude that selective sensory stimulation can beneficially modify cervical dystonia in some patients. Such findings warrant further investigation of the use of sensory stimulation for control of cervical dystonia.     

Pain incidence in cervical dystonia is determined by the disease phenotype

BackgroundCervical dystonia (CD) is a movement disorder caused by prolonged contractions of the head and neck muscles resulting in abnormal postures and repetitive movements. Depending on the direction of the head and neck deviation, CD phenotypes are divided into torti-, latero-, antero-, and retro- impairments assessed in commonly used TWSTRS classification, or -caput and -collis according to the novel Col-Cap concept. Cervical pain, which pathophysiology has not been fully elucidated, affects more than 60% of CD patients. To date, none of the studies have investigated the risk of pain associated with the particular disease phenotype.MethodsIn this observational study data collection was based on the survey completion by the participants, analysis of the medical records, and physical examination with the use of proper scales (TWSTRS, Col-Cap, Tsui). Extended pain profile questionnaire included detailed questions about pain localization, character, and intensity.ResultsWe examined 60 patients suffered from CD; 66,7% of them reported cervical pain. Latero- as the only TWSTRS phenotype was associated with increased risk of pain occurrence (OR = 3,95; p < 0,05). Interestingly, each of two Col-Cap phenotypes correlated with cervical pain: -caput positively (OR = 3,78; p < 0,05) and -collis negatively (OR = 0,29; p < 0,05).ConclusionsThe risk of dystonic pain was highly differentiated within the particular CD phenotypes. The enhanced risk of cervical pain was observed in latero- (TWSTRS) and -caput (Col-Cap) phenotypes; conversely, -collis type (Col-Cap) was characterized by the lowest risk of cervical pain.     

Motor and non-motor subtypes of cervical dystonia

IntroductionCervical 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.MethodsFifty-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.ResultsThe 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.ConclusionsWe 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.     

Beyond a motor disorder: A prospective evaluation of sleep quality in cervical dystonia

BackgroundLittle is known about sleep disturbances in cervical dystonia (CD), particularly the relationship to motoric symptoms. It is critical to clarify these points given the impact on quality of life.MethodsPrimary CD patients receiving botulinum toxin (BoNT) injections and age- and gender- matched healthy controls were included. In both groups, sleep quality and daytime sleepiness were assessed. In CD, these assessments were repeated following BoNT injections. CD severity, mood symptoms, and health impact of CD were also assessed.Results54 CD patients and 55 controls were included. Impaired sleep quality was more frequent in CD compared to controls (t = 4.82, p < 0.0005), even when controlling for the effects of depression, anxiety, and benzodiazepineuse (F = 5.62, p = 0.020). Excessive daytime sleepiness was not significantly different between groups (t = 1.67, p = 0.1). 48 patients received BoNT and returned for follow-up. There was no improvement in sleep quality (t = 0.834, p = 0.41) or daytime somnolence (t = 1.77, p = 0.083) despite improvement in CD severity (t = 4.77, p < 0.0005) with BoNT. There was a small improvement in health impact (t = 2.10, p = 0.04).ConclusionSleep quality was more impaired in CD patients, compared to healthy subjects, and did not improve following BoNT treatment, despite a robust improvement in CD severity. This dichotomy suggests that sleep aberrations in CD require separate focus for effective treatment and cannot be viewed as secondary complications of the motor elements of this condition.     

The treatment of cervical dystonia with botulinum toxins

Summary Botulinum neurotoxin (BoNT) treatment has been used extensively for the treatment of cervical dystonia. There are three established brands and two serotypes of BoNT commercially available in most of the world, and several additional brands are available in selected geographic regions. In most controlled studies, there is significant improvement following treatment for head posture, pain and disability. The common side effects of treatment include dysphagia, dry mouth, and neck weakness. Each brand and serotype is pharmacologically distinct. The dosing of each type differs, and no simple dose equivalency has been established. With repeated treatment, the development of immunoresistance is observed in a percentage of patients. However, it is likely that each brand and serotype may differ in immunogenic potential and occurrence of secondary unresponsiveness, an issue that is currently under active investigation. Correspondence: Cynthia L. Comella, Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA     

Sensory tricks modulate corticocortical and corticomuscular connectivity in cervical dystonia

ObjectiveTo examine interactions between cortical areas and between cortical areas and muscles during sensory tricks in cervical dystonia (CD).MethodsThirteen 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.ResultsDuring 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.ConclusionsObserved changes in the corticocortical coherence suggest that sensory tricks improve cortical function, which reduces corticomuscular connectivity and the dystonia.SignificanceWe demonstrated that sensory tricks fundamentally affect sensorimotor integration in CD, both in movement preparation and execution.     

Prepulse inhibition and recovery of trigemino-cervical reflex in patients with cervical dystonia

ObjectiveWe aimed to analyze the prepulse inhibition (PPI) and recovery rate (R) of the trigeminocervical reflex (TCR) in patients with cervical dystonia (CD).MethodsWe enrolled 15 patients with CD and 16 healthy subjects. TCR was recorded over splenius capitis after infraorbital nerve stimulation. For TCR-PPI, we applied a prepulse stimulus to the left second finger 100 ms prior to the test stimulus and the percentage of change of response to test stimulus was calculated. For TCR-R, we applied paired infraorbital stimuli at interstimulus interval (ISIs) of 300 ms and the percentage of change of the second compared to the first response was calculated.ResultsTCR-PPI and TCR-R values were higher (less inhibition and greater recovery) on both sides in the patient group compared to healthy subjects. There was high correlation between TCR-PPI and TCR-R on both sides in patients with dystonia (p < 0.005). We did not find any significant relationship between TCR-R or TCR-PPI and side of dystonic posture.ConclusionsWe showed disturbed modulation of TCR in CD patients. In CD, a general inhibition of the inhibitory pathways and facilitation of the excitatory pathways occur. Although TCR was recorded directly on the affected muscles in CD, symmetric abnormal TCR findings in CD suggest that these findings are probably secondary to altered function of higher order centers rather than being directly related to the pathophysiological process.     

Changed patterns of cerebral activation related to clinically normal hand movement in cervical dystonia

OBJECTIVES: The relief of cervical dystonia by sensory tricks points at complex sensorimotor interaction. The relation between such stimulus-induced normalization of posture and parietal activation [Naumann M, Magyar-Lehmann S, Reiners K, Erbguth F, Leenders KL. Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming. Ann Neurol 2000;47:322-8] further supports the idea of disturbed higher-order motor control and suggests that the organization of movement is affected beyond the level of a local output channel. Dysbalance beyond a restricted output channel is also supported by the spread of focal dystonia to adjacent body parts. In this fMRI study, we aimed to determine whether cervical dystonia patients have indeed different patterns of cerebral activation during clinically normal hand performance. PATIENTS AND METHODS: By means of statistical parametric mapping (SPM) of 3T fMRI results, task-related cerebral activations measured in eight cervical dystonia patients were compared to data of nine healthy volunteers. RESULTS: Compared to controls, the patient group showed a relative reduction of activations in bilateral parietal, left premotor and cingulate cortex regions during imagining of movement, while activation of right (ipsilateral) putamen, insula and cingulate cortex was impaired during movement execution. CONCLUSION: Cervical dystonia appears to concern a general disorganization of cerebral motor control, which indicates a pre-dystonic state of clinically normal hand movements. The latter may imply an increased vulnerability for deteriorating triggers such as minor accidents.