Treatment of cervical dystonia with botulinum toxins

Botulinum toxin (BoNT) treatment has been used extensively for the treatment of cervical dystonia. In most studies, there is significant improvement following treatment for head posture and pain. The common side effects following treatment include dysphagia, dry mouth, and neck weakness. There are five brands and two serotypes of BoNT available. The dosing of each serotype and brand differs. Perhaps more importantly, each brand and serotype may differ in immunogenic potential and occurrence of secondary unresponsiveness, an issue that is currently under active investigation. Although many aspects of the technique of injection have not been adequately studied, general guidelines are available.     

The entity of young onset primary cervical dystonia.

Primary cervical dystonia is typically an adult onset condition with symptom onset usually in the fifth and sixth decade. Young onset (<28 years) is uncommon. We report 76 patients with cervical dystonia as a presenting or predominant feature, with disease onset before the age of 28. Male to female ratio was 1.24:1 and the mean onset age was 21 (3-28) years. A family history of tremor and/or dystonia was noted in 26.3%. Depression and anxiety attacks were present in 23.7%.Prior injury or surgery involving the neck was noted in 17.1%. 23 (30.3%) experienced spontaneous partial or complete remissions within the first 5 years of onset, but all relapsed. Cervical dystonia was predominantly rotational torticollis. 30% developed extra-nuchal dystonia and tremor affecting contiguous parts but in only one there was spread to affect the legs. All 15 patients tested for the DYT1 gene were negative. 74% responded favorably to botulinum toxin injections, whereas none of the 13 patients treated with L-Dopa preparations had a beneficial response. The distinctive features of this entity are discussed.     

Secondary cervical dystonia associated with structural lesions of the central nervous system.

We tested the hypothesis that structural lesions of the central nervous system (CNS) associated with cervical dystonia more commonly involve the cerebellum and its primary afferent pathways than basal ganglia structures. Cervical dystonia is the most common focal dystonia, the majority of cases are idiopathic, and only a small percentage of patients have a family history of dystonia or other movement disorders. Pathophysiological mechanisms operative in solely or predominantly appendicular dystonias such as writer's cramp and Oppenheim's dystonia, respectively, may not be directly applicable to axial dystonias. The localization of structural lesions of the CNS associated with secondary cervical dystonia may provide some insight into the neural structures potentially involved in primary cervical dystonia. The National Library of Medicine Gateway (from 1960) and a clinical database maintained by the senior author (from 1999) were searched for cases of secondary cervical dystonia associated with structural lesions of the CNS. Search terms included one or more of the following: dystonia, torticollis, cervical, secondary, and symptomatic. Lesion localization and type, patient age, patient gender, head position, occurrence of sensory tricks, and associated neurological findings were tabulated for each case. Structural lesions associated with cervical dystonia were most commonly localized to the brainstem and cerebellum. The remaining cases were equally divided between the cervical spinal cord and basal ganglia. Although inconsistent, head rotation tended to be contralateral to lesion localization. Additional neurological abnormalities were present in the majority of patients with secondary cervical dystonia. The relative paucity of basal ganglia pathology and concentration of lesions in the brainstem, cerebellum, and cervical spinal cord in patients with secondary cervical dystonia suggests that dysfunction of cerebellar afferent pathways may be important to the pathophysiology of primary cervical dystonia.     

Neck movement speed in cervical dystonia

Clinical scales of patients with cervical dystonia do not rate neck movement velocity. We prospectively measured range of neck movements and movement velocities in 35 consecutive patients with cervical dystonia (CD) and 29 normal controls. Reduction of peak velocities in patients with CD was the most robust abnormality and was correlated to TWSTRS. Coupled movements out of attempted movement plane were increased in the patient group. Movement range was moderately though significantly reduced. We conclude that slowing of voluntary neck movements is a frequent and hitherto unrecognized feature in CD. © 2009 Movement Disorder Society     

Complex mechanisms of sensory tricks in cervical dystonia.

Muscle activities in 26 patients with predominantly rotational torticollis were quantified using surface electromyography. In the subgroup of 19 patients with an effective sensory trick, different modes and bilateral locations of trick application led to significant (P < 0.002) reduction of electromyographic (EMG) activity. A strong correlation was found between the efficacy of trick manoeuvres and the starting head position. Trick application in a neutral or even contralateral position was most effective while no reduction of muscle activity during trick application at the maximum dystonic head position was found (P < 0.001). We propose a two-phase model: First, normalisation of head posture is obtained by counterpressure or volitional antagonistic muscle activity. In a second step, this position can be stabilised using sensory tricks challenging central adaption of distorted sensorimotor integration.     

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     

Social stigmatization in patients with cranial and cervical dystonia.

Patients with cranial and cervical dystonia (CCD) suffer from visible involuntary facial, head, and neck movements. Therefore, the social appearance of patients with CCD may be seriously affected and self-perceived stigma can be a major source of disability. The present study investigated enacted social stigmatization of patients with CCD. In a pilot study, a semantic differential scale for assessment of stigma was constructed and validated. The final scale contained eight items representing personality traits to be rated on a seven-point scale (-3 negative extreme to 3 positive extreme). Short video sequences (15 seconds) of patients with various types of CCD and age- and sex-matched healthy controls were presented to a sample of 80 biology students (mean age, 19.8 +/- 2.3 years). Immediately after presentation of each video sequence, the students were asked to perform stigma ratings. Significant differences between CCD patients and controls were found on all eight items (P < 0.001 for each). CCD patients were rated as less accountable for their actions, less likeable, less trustworthy, less attractive, less self-confident, more odd and different, more reserved, and more piteous than controls. CCD patients are subject to serious prejudice and enacted stigmatization. There is a need for informing the public about the nature and symptoms of this disorder and a need to support patients to cope with stigmatization.     

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.     

Cervical dystonia in dentatorubral-pallidoluysian atrophy

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disease characterized by variable clinical phenotypes. Its characteristic clinical manifestations include ataxia, choreoathetotic movements, seizures, myoclonus and dementia, but cervical dystonia has been rarely reported. Here we report a family with DRPLA who presented with cervical dystonia. The proband was a 66-year-old woman. Cervical dystonia was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed. DNA analysis revealed expanded trinucleotide repeats within the DRPLA gene. The daughter of the proband, a 29-year-old woman, also had cervical dystonia for 3 years. Cranial magnetic resonance imaging showed a mild atrophy of the brainstem and the cerebellum in both of these patients. DRPLA should be considered in the differential diagnosis of patients presenting with cervical dystonia.     

Cervical dystonia following peripheral trauma

Abstract. Post-traumatic cervical dystonia as a diagnostic entity remains a subject of debate. Patients with cervical dystonia (CD) were asked to identify any significant illness prior to the onset of their CD. Sixteen patients of 95 respondents reported a history of injury in the four-week period prior to onset of their dystonia. A retrospective study of the clinical characteristics of the 16 patients with early post-traumatic CD (CD-PT) in comparison with the 52 patients reporting no antecedent trauma (CD-NT) was performed. In this comparison the CD-PT group had a significantly increased frequency of laterocollis, significantly more reported pain and more reported depression. Non-significant trends were noted for less responsiveness to botulinum toxin and less use of gestes antagonistes in the CD-PT group. There were no group differences in the presence of a family history of dystonia. Eleven of the CD-PT group had been or were currently involved in litigation. A sub-group of seven CD-PT patients had laterocollis, six of whom conformed to a clinical pattern of persistent non-spasmodic laterocollis with marked pain; all seven had been involved in litigation. This form of CD-PT is a distinct clinical entity and has an onset within hours or a few days of the trauma. In contrast, no significant differences were noted between patients with CD-NT and the eight patients with later onset of CD between 4 weeks and one year after peripheral trauma.     

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.     

Patterns of EMG-EMG coherence in limb dystonia.

Dystonia of the limbs may be due to a wide range of aetiologies and may cause major functional limitation. We investigated whether the previously described pathological 4 to 7 Hz drive to muscles in cervical dystonia is present in patients with aetiologically different types of dystonia of the upper and lower limbs. To this end, we studied 12 symptomatic and 4 asymptomatic carriers of the DYT1 gene, 6 patients with symptomatic dystonia due to focal basal ganglia lesions, and 11 patients with fixed dystonia, a condition assumed to be mostly psychogenic in aetiology. We evaluated EMG-EMG coherence in the tibialis anterior (TA) of these and 15 healthy control subjects. Ten of 12 (83%) of symptomatic DYT1 patients had an excessive 4 to 7 Hz common drive to TA, evident as an inflated coherence in this band. This drive also involved the gastrocnemius, leading to co-contracting electromyographic bursts. In contrast, asymptomatic DYT1 carriers, patients with symptomatic dystonia, patients with fixed dystonia, and healthy subjects showed no evidence of such a drive or any other distinguishing electrophysiological feature. Moreover, the pathological 4 to 7 Hz drive in symptomatic DYT1 patients was much less common in the upper limb, where it was only present in 2 of 6 (33%) patients with clinical involvement of the arms. We conclude that the nature of the abnormal drive to dystonic muscles may vary according to the muscles under consideration and, particularly, with aetiology.     

Neuronal globus pallidus activity in patients with generalised dystonia.

We studied 516 globus pallidus neurons in dystonic patients. The firing rate was analysed. We classified the burst activity into tonic, burst, and pause patterns. Mean +/- SD firing rates and tonicity score for internal globus pallidus (GPi) and external globus pallidus (GPe) were 54.6 +/- 28.6; 58.01 +/- 39.1 and 1.18 +/- 0.55; 0.95 +/- 0.43, respectively. Differences in percentage appearance of tonic, burst, or paused neurons were not statistically significant for GPi versus GPe. GPi firing features in dystonic patients were closely similar to those of GPe. This could suggest that the abnormally patterned output from GPi would not result from increased differential inhibitory/excitatory input arising from the direct/indirect pathway but rather be transmitted from GPe, striatum, or either centromedian nucleus.     

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.     

Impairment of individual finger movements in patients with hand dystonia.

We investigated finger movements in patients with hand dystonia to compare the kinematics of repetitive individual and non-individual finger oppositions. We used an optoelectronic motion analysis system to record movements in 3-D space, and recorded three 5-second trials for each task, counting how many finger oppositions subjects carried out during each trial, and measured the duration and amplitude of flexions, extensions, and pauses. During tasks, normal subjects and patients carried out finger flexions faster than extensions, and invariably they paused longer before extension than before flexion. Patients were slower and paused longer than controls during both individual and non-individual oppositions. During individual finger movements, patients were disproportionately slow during extension and pause before extension. Patients with hand dystonia perform finger movements abnormally; they are affected predominantly during individual oppositions. This finding reflects the finer cortical control needed to promote and sustain this highly fractionated type of motor output, and points toward underactivity of the primary motor cortex in dystonia.     

Abnormal low frequency drive in myoclonus‐dystonia patients correlates with presence of dystonia

The pathophysiology of Myoclonus‐Dystonia (M‐D), an autosomal dominantly inherited movement disorder is largely unknown. In different forms of dystonia abnormal intermuscular coherence is present. The objective of this stufy was to investigate whether the myoclonic and dystonic features are the result of an abnormal common drive to the muscles in M‐D. Coherence analysis was performed in 20 DYT11 mutation carriers (MC) and 13 healthy controls during resting condition and during weak isometric contraction of the arm and neck. The EMG‐EMG coherence analysis showed significantly increased intermuscular 3 to 10 Hz coherence in 4 DYT11 MC with clinical pronounced (mobile and static) dystonia. This coherence was not present in DYT11 MC with mild (static) dystonia and/or predominating myoclonus. The EEG‐EMG analysis showed significant 15 to 30 Hz coherence during weak isometric contraction of the arm in five healthy controls, but in none of the DYT11 MC. The intermuscular coherence in the low frequency band in DYT11 MC with predominant dystonia is concordant with the previously described coherence in dystonia and suggests that the pathophysiology of M‐D shares common pathophysiological features with dystonia. The absence of 15 to 30 Hz EEG‐EMG coherence in DYT11 MC may reflect abnormal motor activation caused by an altered cortical drive because of the basal ganglia dysfunction. © 2007 Movement Disorder Society     

Long-term follow-up of cervical dystonia patients treated with botulinum toxin A.

We followed the course in 100 consecutive patients with cervical dystonia (CD) after they were initially treated with botulinum toxin (BTX) in the form of Dysport 10 to 12 years ago. A total of 4 patients had died, and 6 were lost to follow-up. Of the remaining 90 patients, 57 (63%) were still treated with BTX. In the patients treated at one centre over the whole period with Dysport, mean dose used during each treatment session was 833 (SD +/- 339) units Dysport with a cumulative dose of 20,943 (SD +/- 9462) units Dysport over a mean of 26.8 (SD +/- 8.6) treatment cycles. Secondary nonresponse was detected in 3 of the 90 patients. During follow-up, 12 patients developed blepharospasm, 13 oromandibular dystonia, and 17 patients writer's cramp. We conclude that BTX remains effective and safe for approximately 60% of CD patients for more than 10 years.     

Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia.

The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in six patients with generalized, focal, and segmental dystonia are presented. Pre- and postoperative assessments are given for one patient with generalized inherited dystonia and for five patients with idiopathic segmental or cervical dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey (SF-36) was completed by each patient to document preoperative and postoperative health status. Also, neurological status was documented by video before and during chronic stimulation. Magnetic resonance imaging studies were performed to show the anatomical localization of the electrode leads. Five patients showed a progressive improvement within 7 days. One patient with cervical dystonia and Meige's syndrome showed no improvement for 3 months, but beneficial effects were observed after 12 months. On average, the BFM movement scale scores decreased by 72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status by an average of 36% according to eight different health categories. We conclude that chronic high-frequency Gpi stimulation in different types of dystonia is a very effective and safe treatment.     

Morphometric changes of sensorimotor structures in focal dystonia.

Idiopathic cervical dystonia (CD) and benign essential blepharospasm (BEB) are the most common forms of focal dystonia. Previous autopsy and imaging studies suggested that these disorders are not accompanied by structural brain abnormalities. However, recent brain voxel-based morphometry (VBM) studies of these conditions suggest that there actually may be changes in gray matter. The objective of this stdy was to detect possible gray matter abnormalities in patients with CD and BEB using VBM and to compare the results between the two conditions and with age- and gender-matched controls. High-resolution MRI was employed to evaluate healthy controls and individuals with BEB and CD. Eleven BEB, 9 CD, and 14 healthy control subjects were imaged. VBM revealed alterations of gray matter structures involved in sensorimotor processing in the individuals with focal dystonia. In CD subjects there was increased gray matter in the thalamus, caudate head bilaterally, superior temporal lobe, and left cerebellum, while gray matter was decreased in the putamen bilaterally. BEB subjects had increased gray matter in the caudate head and cerebellum bilaterally as well as decrease in the putamen and thalamus bilaterally. These findings strongly underline the recent notion that idiopathic focal dystonias might have a detectable structural correlate. They also demonstrate structural similarities of the investigated focal dystonias, possibly reflecting a shared common pathophysiological origin.