Cervical dystonia: Improved treatment response to botulinum toxin after referral to a tertiary centre and the use of polymyography

RationaleCervical dystonia is the most common form of (primary) dystonia. The first line of treatment for cervical dystonia is intramuscular injections with botulinum toxin. To optimise the response to botulinum toxin proper muscles selection is required. Pre-treatment polymyographic EMG in addition to clinical evaluation is hypothesised to be a good tool to improve muscle selection and treatment outcome.ObjectiveTo determine the efficacy of botulinum toxin treatment after adjacent polymyographic EMG in cervical dystonia patients referred to our tertiary referral centre with an unsatisfactory response to botulinum toxin treatment elsewhere.MethodsWe performed a retrospective analysis of 40 consecutive second opinion cervical dystonia patients. Standard polymyographic EMG was performed before treatment. We retrieved the Tsui scores and subjective evaluations from the first visit, after 12 weeks and after one year of treatment. In addition, we assessed the final outcome of treatment in our centre based on the records and asked the patients for their personal opinion about the effect of referral to our centre on their treatment response.ResultsAfter one year of treatment there was a significant improvement on both the Tsui scores (p < 0.01) and the subjective treatment evaluation (p < 0.001.) On their last visit 60% of the patients still continued treatment with a reasonable to good response.ConclusionA substantial amount of CD patients with an unsatisfactory response to botulinum toxin improved after polymyography and subsequent treatment with botulinum toxin in a tertiary referral centre.     

Change in the pattern of cervical dystonia might be the cause of benefit loss during botulinum toxin treatment

The muscular patterns of cervical dystonia were identified by polymyographic recordings in 76 patients before botulinum toxin treatment. The leading muscles were considered to be those which started dystonic movement and which showed constant and maximal activity during all dystonic movements. The dystonic muscles were repeatedly treated by local Injections of botulinum toxin. Sixteen patients showed (after repeated injections) loss of the benefit of local applications of botulinum toxin after various periods of time. Repeated polymyographic recordings were performed in these patients during the loss of the benefit of injected botulinum toxin. In four patients repeated polymyographic recordings showed an Identical pattern of cervical dystonia, but the activity of previously injected muscles was apparently decreased. In 12 patients only minimum or no activity was recorded in muscles which had previously been treated with botulinum toxin, but the pattern of cervical dystonia was changed. Different patterns of cervical dystonia with different leading muscles, but with identical directions of head deviation, were observed in six patients. In another six patients, the head deviation direction was to the opposite side and was accompanied by a change of the leading muscle and a change of the muscular pattern of dystonia. These results suggest either that dystonic activity from the cerebral generator changes to new effectors during the peripheral blockade of primary dystonic muscles, or that a change of generators at different levels of the CNS occurs. It may be neccessary to carry out repeated polymyographic recordings throughout the period of loss of benefit of previously successful local botulinum toxin injections.     

Botulinum toxin treatment of dystonic anterocollis: What to inject

BackgroundAnterocollis (AC) is a rare form of cervical dystonia, which responds poorly to botulinum toxin treatment.ObjectivesTo recognise the different clinical phenotypes of AC and to detail the selection of muscles from the results of treating a cohort of 15 AC patients with Botulinum Toxin.MethodsThe study was performed using prospectively collected data. We included 15 patients with cervical dystonia and AC posture, treated between 2016 and 2019 in our joint Neuro-ENT clinic. We excluded patients with posterior cervical muscle weakness and patients with Parkinsonism. We characterised the primary dystonic posture of every AC patient as posterior sagittal shift, head flexion or neck flexion, or a combination of the three.ResultsAll AC patients had a more widespread dystonic picture with a majority having Meige syndrome, but AC was the most problematic feature. Treatment with botulinum toxin required the injection not only of the deep cervical flexor (DCF), but also the sterno-cleido-mastoid (SCM) and moreover the supra-hyoid (SH) muscles. The choice between the longus capiti and the longus colli depended on the AC posture. Half of the patients had a dramatic improvement with 90% satisfaction or above.ConclusionAC posture is a complex but treatable type of CD. A joint Neuro-ENT clinic is an ideal setting in which to target all the dystonic muscles. This allows the injection of the longus capiti (under nasal endoscopic approach) as well as the supra-hyoid and SCM muscles in the same session.     

Fluoroscopic, EMG-guided injection of botulinum toxin into the longus colli for the treatment of anterocollis

BackgroundAnterocollis is a form of cervical dystonia characterized by forward neck flexion. While botulinum toxin is the treatment of choice for cervical dystonia, patients with anterocollis, who receive injections into the sternocleidomastoid and anterior scalene muscles, represent a disproportionate number of treatment failures. Deep cervical muscles such as the longus colli likely play an important role in neck flexion but are not routinely injected.ObjectiveTo describe a technique for longus colli injection in cases of anterocollis and to report the clinical outcomes of 10 such injections of botulinum toxin.MethodsThree patients were referred for evaluation and treatment of anterocollis. All had previous treatment failures with sternocleidomastoid/anterior scalene injections or no activity noted on needle EMG investigation of these muscles. All patients received injections of botulinum toxin into the longus colli under fluoroscopic and EMG guidance.ResultsAll patients experienced symptomatic improvement (eight of 10 injections). Two patients reported mild dysphagia without serious complications after dose increases in botulinum toxin.ConclusionsIncomplete muscle selection may be one cause of treatment failures in anterocollis. Deep cervical flexors such as the longus colli represent an under-recognized potential target for symptomatic treatment of anterocollis.     

Electromyographic evaluation of cervical dystonia for planning of botulinum toxin therapy

The success of botulinum toxin (BT) injections for treatment of cervical dystonia depends on precise identification of dystonic muscles and on quantification of their dystonic involvement. Conventionally, this is attempted by clinical examination analysing the dystonic head position. In this presentation, a more systematic approach is sought by using an electromyography (EMG)-based evaluation procedure. In 10 consecutive patients with cervical dystonia not previously exposed to BT clinical examination, analysing the dystonic head position was performed to classify patients into four groups with similar dystonic head positions. Additionally, a 2-channel concentric needle EMG was used to measure the amplitudes of dystonic and maximal voluntary activities in sternocleidomastoid (SCM), splenius capitis (SC) and trapezius/semispinalis capitis (T/SS) muscles bilaterally. The ratio between both amplitudes, the dystonia ratio, was used to quantify dystonic muscle involvement. In all patients dystonia ratios could be calculated. In patients with similar head positions, EMG evaluation revealed different qualitative and quantitative dystonic involvement patterns. In six patients, there were discrepancies in identification of dystonic muscles between clinical examination and EMG evaluation. EMG evaluation excluded dystonic involvement in five patients. All excluded muscles were SCM. In one of these patients, additional T/SS involvement was detected by EMG evaluation. In one patient, SC involvement was revealed by EMG evaluation. All dystonic muscle involvement detected by EMG evaluation represented genuine dystonic muscle coactivation rather than compensatory muscle activity. The EMG evaluation presented allows quantitative and qualitative identification of dystonic muscle involvement which cannot be achieved by clinical examination. Both pieces of information may be helpful for optimization of BT therapy.     

Utility of an EMG mapping study in treating cervical dystonia

Intramuscular injections of botulinum toxin are the cornerstone of treatment for cervical dystonia. Controversy exists regarding the necessity for EMG-guided injections. We compared the clinical examination of four movement disorder specialists to an electromyographic (EMG) mapping study. Clinical predictions of individual muscle involvement were only 59% sensitive and 75% specific. Muscle hypertrophy, shoulder elevation, and dominant head vector did not bolster clinical accuracy. An EMG mapping study facilitates identification of dystonic muscles in cervical dystonia, which may enhance botulinum toxin therapy.     

Botulinum toxin injections reduce associative plasticity in patients with primary dystonia

Botulinum toxin injections ameliorate dystonic symptoms by blocking the neuromuscular junction and weakening dystonic contractions. We asked if botulinum toxin injections in dystonia patients might also affect the integrity of sensorimotor cortical plasticity, one of the key pathophysiological features of dystonia. We applied a paired associative stimulation protocol, known to induce long‐term potentiation–like changes in the primary motor cortex hand area to 12 patients with cervical dystonia before and 1 and 3 months after botulinum toxin injections to the neck muscles. Primary motor cortex excitability was probed by measuring transcranial magnetic stimulation‐evoked motor evoked potentials before and after paired associative stimulation. We also measured the input–output curve, short‐interval intracortical inhibition, intracortical facilitation, short afferent inhibition, and long afferent inhibition in hand muscles and the clinical severity of dystonia. Before botulinum toxin injections, paired associative stimulation significantly facilitated motor evoked potentials in hand muscles. One month after injections, this effect was abolished, with partial recovery after 3 months. There were significant positive correlations between the facilitation produced by paired associative stimulation and (1) the time elapsed since botulinum toxin injections and (2) the clinical dystonia score. One effect of botulinum toxin injection treatment is to modulate afferent input from the neck. We propose that subsequent reorganization of the motor cortex representation of hand muscles may explain the effect of botulinum toxin on motor cortical plasticity. © The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

Trick maneuvers in cervical dystonia: investigation of movement- and touch-related changes in polymyographic activity.

Antagonistic gestures or trick maneuvers are well-known clinical features to reduce or abolish dystonic posturing in cervical dystonia (CD). The maneuvers typically consist of a finger touch to the facial skin but their physiology remains unknown. To determine the temporal profile of geste maneuver performance, 25 patients with idiopathic CD were studied by means of polymyography of six cervical muscles prior to any botulinum toxin treatment. Two piezoelectric elements fixed to a fingertip of the hand involved in the trick maneuver and to the facial target region, respectively, were used to relate the essential points of the trick maneuver time course (start of geste-arm movement, facial contact, end of contact, end of movement) to changes in polymyographic activity. Thirteen patients (52%) showed marked reductions of electromyographic (EMG) activity (> or =50% in at least one muscle) during arm movement, definitely prior to contact between fingers and facial target area; in the remaining 12 patients (48%), geste-related EMG effects were confined to facial-finger contact. These results might indicate different physiological mechanisms in clinically indistinguishable antagonistic gestures.     

Polymyography combined with time-locked video recording (video EMG) for presurgical assessment of patients with cervical dystonia

We assessed 26 patients with cervical dystonia, in whom botulinum toxin (BT) injections had failed, before selective peripheral denervation. We decided to base the decision which muscle should be denervated on both clinical information and EMG data and focussed on the following features: activity at onset or during 'dystonic spasms' (according to the concept of the 'leading' dystonic muscle), paradoxical activity during voluntary head movements causing restriction of head movements opposite the side of head turn or tilt and activity when symptoms deteriorated during walking. To identify these muscles we developed a new recording system that integrates simultaneous video-taping and polymyography (video EMG) by means of a digital counter, driven by the recording software (resolution 0.1 s), that was fixed in view of the video camera. This system time-locked clinical signs with relevant EMG activity thus allowing demonstration of the above features. These were found in 68% of dystonic muscles with each of them being present in approximately 40%. Video EMG allows an integrated approach to identify overactive neck muscles in patients with cervical dystonia taking into account both relevant clinical findings and EMG data.     

Descending control of muscles in patients with cervical dystonia.

It was reported recently that specific features in the frequency analysis of electromyographic (EMG) activity in the sternocleidomastoid (SCM) and splenius (SPL) muscles were able to distinguish between rotational idiopathic cervical dystonia (CD) and voluntary torticollis in individual subjects. Those with CD showed an abnormal drive to muscles at 5 to 7 Hz and an absence of the normal 10 to 12 Hz peak in the autospectrum of SPL. We sought to determine whether the same abnormalities in the frequency domain are found in complex CD, in which the head is displaced in more than two planes. EMG activity was recorded in the SCM, SPL, trapezius, and levator scapulae muscles bilaterally in 10 patients with complex CD. Frequency analysis of EMG was compared with conventional clinical and polymyographic assessment. The autospectrum of SPL during free dystonic contraction showed an absence of a significant peak at 10 to 12 Hz in 8 of the 10 patients. The presence of a 5 to 7 Hz frequency drive showed a significant association with muscle pairs determined as dystonic by means of polymyography (P < 0.005). The neck posture predicted blindly, based on the low-frequency drive, correlated significantly with the clinical assessment of posture (P < 0.01). Conventional assessment and the results of frequency analysis correlated, suggesting that a low-frequency drive to neck muscle may be a general feature of simple rotational and more complex cervical dystonia. The pattern of coherence between the EMG in different neck muscles may provide a means of identifying leading dystonic muscles, especially in patients with complex cervical dystonia.     

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.     

Treatment of upper limb dystonia with botulinum toxin

The use of botulinum toxin A (BTX A) in upper limb dystonia is gaining increasing acceptance and it has recently been suggested that it be considered as first line treatment.(1) We have reviewed our experience since 1991 of treating 20 cases of upper limb dystonia. 14 patients had task-specific dystonias (6 simple writer's cramp, 5 dystonic writer's cramp, 3 musician's cramp) and 6 had secondary focal or segmental dystonias (4 with early cortico-basal degeneration). All patients had electromyography to both determine and guide muscle selection. Pre- and post-treatment video as well as questionnaires formed the basis for outcome assessment. Botulinum toxin therapy was clearly beneficial in about two-thirds of those with primary upper limb dystonia, a condition affecting young adults (mean onset 32.9 years). In contrast, BTX A was far less effective in secondary upper limb dystonias which occurred in the elderly (mean onset 71.7 years). Optimal treatment strategies are discussed. In conclusion, botulinum toxin is an effective form of treatment for primary upper limb dystonia; its role in late onset secondary dystonia is mainly palliative.     

Tiefe Hirnstimulation bei zervikaler Dystonie

BACKGROUND: Cervical dystonia results in severe disability and cannot be effectively treated with medication. Repeat injections of botulinum toxin into the dystonic neck muscles can relieve the symptoms in most patients. When this treatment fails (mostly due to antibody formation), deep brain stimulation can be considered. PATIENTS AND METHODS: We report our experiences with eight patients who were treated with bilateral deep brain stimulation of the globus pallidus interna for cervical dystonia. The mean observation period was 31 months. RESULTS: Six of eight patients experienced relief from symptoms a few days after the implantation. Improvement of symptoms was a mean of 60% during the 1st year. There were no complications. CONCLUSION: In this and in other studies with small numbers of patients, deep brain stimulation has shown a good effect on cervical dystonia. According to our results, the patients who benefit most are those with no dystonic shoulder involvement and who have a tonic rather than clonic symptomatology. It seems probable that deep brain stimulation will become the therapy of choice for otherwise intractable cervical dystonia.     

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.     

A new treatment for cervical vertigo with botulinum toxin

A new and unique treatment for cervical vertigo with botulinum toxin is presented for a woman who sustained neck trauma from being hit by a wave. A diagnosis of cervical vertigo and cervical dystonia was confirmed by history, physical exam, dystonia on EMG exam, and a negative test for benign paroxysmal positional vertigo.She experienced consistent resolution of her vertigo symptoms and pain after each treatment for a total of 5 treatments with botulinum toxin to the upper cervical muscles. This report appears to be the first to demonstrate the missing link between vertigo and cervical dystonia with pain. Chemodenervation was effective in treating cervical vertigo and is likely to have altered the cervical proprioceptive input by relaxing the overactive muscles and/or by decompression of cervical nerves.     

Symptomatic and functional outcome of surgical treatment of cervical dystonia

OBJECTIVES—Previous studies of surgical treatmentfor cervical dystonia have reported highly variable rates ofpostoperative symptomatic benefit and morbidity. Little is known aboutfunctional improvement and long term results. This study evaluates thesymptomatic and functional outcome of surgical treatment of cervicaldystonia in a consecutive series of 46patients.
METHODS—The most affected muscles were selectedfor denervation after clinical examination and confirmation by fourchannel EMG studies. Surgical treatment, aiming at selectiveelimination of pathological activity while preserving normal motorfunction and avoiding side effects, was achieved by using a broad scopeof techniques including intradural denervation, extradural denervation,and myotomy. Rather than carrying out standard operations, thetreatment was tailored to the needs of the patient according to theindividual pattern of dystonic activity. Long term benefit was assessedwith a global outcome score, and a modified Toronto western spasmodictorticollis rating scale (TWSTRS) in those 34 patients who wereavailable for a recent follow up evaluation.
RESULTS—The 46 patients underwent a total of 70 procedures with intradural approaches in 33 instances, extraduralapproaches in 21,and muscle sections (singly or combined) in 22 instances. Transient mild postoperative side effects occurred in 10%of the procedures. The mean duration of long term follow up was 6.5 years. The global outcome was rated as excellent in nine patients(21%), as marked in 12 (27%), as moderate in nine (21%), as mild innine (21%), and as no improvement in five (11%). A persistent sideeffect consisting of mild difficulty with balance was noted in onecase. There were highly significant changes of the preoperative and postoperative mean values for almost all TWSTRS subscores for severityof cervical dystonia, functional disability, and pain. Patients withexcellent outcome underwent a higher number of surgical procedures onaverage than those patients who achieved no benefit.
CONCLUSIONS—Surgical treatment tailored to thespecific pattern of dystonic activity in the individual patient is avaluable alternative in the long term management of cervical dystonia.

     

Efficacy of single-photon emission computed tomography aided botulinum toxin injection in cervical dystonia: A double-blind,randomized study

BackgroundAlthough single-photon emission computed tomography (SPECT/CT) could help to predetermine dystonic muscles in patients with cervical dystonia (CD), its efficacy in aiding botulinum toxin injection is undetermined. This randomized, double-blinded study aimed to assess the efficacy of SPECT/CT aided botulinum toxin injection in CD.MethodsPatients were randomized into study group (candidate muscles selected by SPECT/CT and clinical evaluation) or control group (clinical evaluation). Follow-ups were done at two weeks (T1), one (T2), three (T3) and six months (T4). The primary outcomes included symptom improvement assessed using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and Tsui score at T2.ResultsA total of 122 patients were enrolled and 108 patients accomplished the study. For primary outcomes, the study group had significantly better symptom improvement at T2 (TWSTRS: β, −4.86 [95%CI -9.40 to −0.32; P = 0.036]; Tsui: β, −1.65 [95%CI -2.77 to −0.54; P = 0.004]). For secondary outcomes, the study group also showed better outcomes at T1 (TWSTRS: β, −6.33 [95%CI -10.17 to −2.49; P = 0.001]; Tsui: β, −1.42 [95%CI -2.48 to −0.37; P = 0.008]) and T3 (TWSTRS: β, −6.05 [95%CI -11.09 to −1.01; P = 0.019]; Tsui: β, −1.24 [95%CI -2.40 to −0.08; P = 0.037]). The interval of re-injection was significantly longer in the study group than the control group (159.1 ± 28.6 versus 141.8 ± 51.0 days, P = 0.032).ConclusionsSPECT/CT could improve the efficacy of botulinum toxin in CD. It could become a useful tool to aid botulinum toxin injection.     

Evidence-based medicine in botulinum toxin therapy for cervical dystonia

Early controlled studies of botulinum toxin (BTX) in cervical dystonia were unblinded and indicated that BTX injections are more successful than medication. In this article, the use of botulinum toxin (BTX) in cervical dystonia is reviewed according to evidence-based medicine. To document the efficacy of BTX, there have been a number of prospective, placebo-controlled studies of the use of BTX in cervical dystonia. Most were double-blind, some included videotapes to provide blinded objective assessments. The more recent studies of BTX in cervical dystonia focused on particular issues such as utility of EMG guidance, comparison to anticholinergic treatment, BTX serotype B in BTX type A resistant and non-resistant patients and different dosages. Despite the wealth of data generated with prospective placebo-controlled studies on the effectiveness of BTX in cervical dystonia, there is uncertainty on which outcome measures to use to express the efficacy of treatments for cervical dystonia. Disease specific instruments to measure quality of life in cervical dystonia have not been used so far. Data on the use of BTX for cervical dystonia have long been restricted to small series of patients reflecting exclusively the experience of individual specialized centers.

     

Botulinum toxin as treatment for focal dystonia: a systematic review of the pharmaco-therapeutic and pharmaco-economic value

Focal dystonia is a common, invalidating neurologic condition characterized by involuntary, sustained muscle contractions causing twisting movements and abnormal postures in one body part. Currently, botulinum toxin is the treatment of first choice. We performed a systematic review towards the pharmaco-therapeutic and pharmaco-economic value of botulinum toxin as treatment for focal dystonia, which yielded the following results. Botulinum toxin is the most effective treatment for reducing dystonic symptoms measured with dystonia-specific and general questionnaires, and pain in patients with focal dystonia. Seventy-one percent of patients with cervical dystonia had a reduction in neck pain compared to 12?% in placebo groups. Adverse events occur in 58?% of patients during treatment with botulinum toxin compared to 46?% treated with placebo. Especially dry mouth, neck weakness, dysphagia, and voice changes are common. Adverse events are usually mild and self-limiting. Health-related quality of life, measured with the SF-36 is 20?C50 points lower in patients with focal dystonia compared to controls and the effect of botulinum toxin on health-related quality of life is unclear. Botulinum toxin treatment is expensive because the drug itself is expensive. Yearly costs for treating a patient with focal dystonia with botulinum toxin range from EUR 347 to EUR 3,633 and the gain in QALYs with BTX treatment is small. Focal dystonia impairs the productivity and the ability to work. At start of botulinum toxin treatment only 47?C50?% was working. Botulinum toxin partly improves this. Overall, we conclude that botulinum toxin is an expensive drug with good effects. From a societal perspective, the costs may well weigh up to the regained quality of life. However, the available literature concerning costs, health-related quality of life and labor participation is very limited. An extensive cost-effectiveness study should be performed incorporating all these aspects.     

Clinical characteristics of the geste antagoniste in cervical dystonia

The geste antagoniste (moving an arm to the face or head) is a well-known clinical feature in cervical dystonia (CD) to alleviate the abnormal posture. The clinical phenomenology of these manoeuvres has not so far been assessed systematically. Fifty patients with idiopathic CD aware of at least one geste antagoniste (60 % women, mean age at onset 44.1 years, mean disease duration 7.5 years) were subjected to a standardized investigation including a semiquantitative clinical rating scale and polymyographic recordings of six cervical muscles. Twenty-seven patients (54 %) demonstrated more than one geste antagoniste (range 2–5). A clinically significant (≥ 30 %) reduction of head deviation was observed in 41 patients (82 %). Dystonic head posture improved by a mean of 60 % along all planes by the geste manoeuvre with a complete cessation of head oscillations in nine of 33 patients (27 %) with phasic CD. No significant laterality of the “geste-arm” or the facial target area was found. The duration of geste-effects depended significantly on disease duration and determined the patient's self-rating of the benefit of the manoeuvre. EMG-polygraphy revealed two types of geste-induced polymyographic changes: a decrease in recruitment density and amplitude in at least one dystonic muscle (66 %), and an increased tonic muscle activation in the remaining patients. The remarkable efficacy of the geste antagoniste and the considerable variety in performance, duration, and EMG-pattern of these manoeuvres warrant further investigation of the therapeutic use of sensorimotor stimulation, in particular for those CD patients who experience limited or no effect from botulinum toxin therapy. Received: 23 August 2000, Received in revised form: 7 December 2000, Accepted: 27 December 2000