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.     

A methodological approach for botulinum neurotoxin injections to the longus colli muscle in dystonic anterocollis: A case series of 4 patients and a literature review

We review the current approaches and their feasibility to treat dystonic anterocollis by injecting longus colli muscle (LCo) with botulinum neurotoxin (BoNT) as well as present our personal experiences in this field compared with the findings from previously published studies. First, we searched the PubMed database for the publications reporting patients who received LCo injections for anterocollis; we also thoroughly examined the references included in each of the found publications. Second, we present and analyze our own experiences in injecting LCo under EMG guidance in patients with dystonic anterocollis due to heredodegenerative disorders. We found 11 publications describing administration of LCo injections for the treatment of dystonic anterocollis in a total of 28 patients with primary dystonia aged between 21 and 80 years. The mean age of our patients was 44.8 years with the mean anterocollis duration being 15 months. OnabotulinumtoxinA in a dose of up to 35 U per LCo muscle was not associated with the development of transient dysphagia. The mean percentage of patient satisfaction was 36.3%, and the mean duration of the beneficial effect was 2.5 months. All patients agreed to receive a repeat injection. We provide a set of empirically based suggestions on the current use of BoNT injections to LCo for managing anterocollis in outpatient clinics, including pretreatment work-up, injection technique, and dose range.     

Clinical and polymyographic investigation of spasmodic torticollis

Summary Polymyographic recordings were used to identify the most dystonic muscles suitable for local injection with botulinum toxin in 100 patients with spasmodic torticollis (TS). Rotating TS (72% of the patients) was due to dystonic activity of the splenius muscle ipsilateral to and/or the sternocleidomastoid muscle contralateral to the side of chin deviation. One-third of these patients had also dystonic activation of the contralateral splenius muscle and, rarely, the contralateral trapezius muscle. Ten patients had laterocollis due to dystonic activation of all recorded muscles on one side of the neck. Nine patients had retrocollis due to activity of both splenius muscles and rarely additional activity in both trapezius muscles. The type of dystonic muscle activity was found to be tonic, phasic or tremulous. Besides the evaluation of spontaneous dystonic EMG activity further examination during the geste antagoniste or the muscle activity during rotating head movements can provide additional information. It is concluded that polymyography may provide a rationale for identifying the dystonic muscles underlying the different forms of TS. It may prove to be helpful for the successful therapy with botulinum toxin and may be useful in differentiating tremulous torticollis from other types of head tremor.     

Split‐screen video demonstration of sonography‐guided muscle identification and injection of botulinum toxin

A standardization of injection procedures for the various botulinum toxin (BoNT) indications has not been achieved to date. One established option to guide the therapist's needle is sonography guidance. It provides real‐time visualization of the injection process, which is quick, allows perfect precision, and the procedure as such is painless. To demonstrate these qualities, we have recorded six split‐screen video segments that show the handling of the probe and the needle during BoNT injections concurrently with the respective cross‐sectional sonography recordings. The video sequences show differentiation of the pollicis longus muscle and individual finger flexor fascicles, needle tracking, and real‐time sonography‐guided injection of the gastrocnemius, rectus femoris, and iliopsoas muscles. We hope this short presentation will help to encourage a more widespread use of the technique as well as further research on sonography guidance for precise delivery of BoNT injections to various target muscles. © 2010 Movement Disorder Society     

Treatment of dystonic clenched fist with botulinum toxin.

Fourteen patients with "dystonic clenched fist" (three with Corticobasal Ganglionic Degeneration, seven with Parkinson's disease, and four with Dystonic-Complex Regional Pain Syndrome) were treated with botulinum toxin A (BTXA, Dysport). The muscles involved were identified by the hand posture and EMG activity recorded at rest and during active and passive flexion/extension movements of the finger and wrist. EMG was useful in distinguishing between muscle contraction and underlying contractures and to determine the dosage of BTX. All patients had some degree of flexion at the proximal metacarpophalangeal joints and required injections into the lumbricals. The response in patients depended on the severity of the deformity and the degree of contracture. All patients had significant benefit to pain, with accompanying muscle relaxation, and palmar infection, when present, was eradicated. Four patients with Parkinson's disease and one patient with Dystonia-Complex Regional Pain Syndrome obtained functional benefit.     

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.     

Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm.

Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm.     

Computed tomographically-controlled injection of botulinum toxin into the longus colli muscle in severe anterocollis.

We report on a 44-year-old man who suffered from severe anterocollis. Repeated computed tomographically controlled injections of botulinum toxin into the right longus colli muscle allowed a precise location of the needle and injection of the toxin, leading to clear improvement of symptoms.     

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.     

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.     

Treatment of complex cervical dystonia with botulinum toxin: involvement of deep-cervical muscles may contribute to suboptimal responses

Complex cervical dystonia is a subgroup of cervical dystonia (CD) characterised by a combination of head deviations in more than one plane. In addition to superficial neck muscles, deep-cervical muscles contribute to a broad range of neck movements. These deep muscles include prevertebral muscles for primary neck flexion, lateral vertebral muscles for shoulder elevation and head tilt and a posterior group of muscles for neck extension. The authors describe three cases of complex deviations of the neck including anterocollis, retrocollis and lateral or sagittal shifts with involvement of deep-cervical muscles, which are not easily accessible by routine botulinum toxin (BoNT) therapy. Incomplete muscle selection may be one of the causes of treatment failures with BoNT in patients with complex CD, and targeting of deep-cervical muscles should be considered when patients exhibit complex deviations involving anterocollis, retrocollis, lateral or sagittal shifts.     

Prolonged vastus lateralis denervation after botulinum toxin type A injection

Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non‐injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT‐A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies. © 2010 Movement Disorder Society     

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.     

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.     

The utility of EMG interference pattern analysis in botulinum toxin treatment of torticollis: A randomised, controlled and blinded study

Objective

The significance of electromyography (EMG) guidance in botulinum toxin (BT) treatment has been much debated. The aim of this study was to evaluate if EMG guidance in the treatment of torticollis in BT-naive patients had a better outcome than treatment after clinical evaluation alone.

Methods

Twenty-six patients with torticollis were included and treated for 1 year in this prospective, blinded study. Quantitative EMG was performed simultaneously in the four most frequently affected muscles: the sternocleidomastoid muscles and the posterior neck muscles on both sides. EMGs were analysed for turns per second. Clinical ratings were performed by an experienced neurologist (A). Injections were given by another neurologist (B), who was blinded to the ratings. In group 1, the results of the EMG were available to the treating neurologist B, whereas in group 2, neurologist B was blinded. In group 1, treatment with BT was given when turns per second were higher than 100.

Results

In patients treated guided by EMG, clinical outcome, evaluated by objective ratings, was better than in patients treated based on clinical judgement alone (p = 0.05). In group 2, 105 muscles were treated with BT. Of these, 37 did not show dystonic EMG activity.

Conclusions

Treatment with BT guided by EMG results in better clinical outcome than treatment without EMG and reduces the amount of BT used.

Significance

EMG guidance by interference pattern analysis may optimise BT treatment in torticollis by a more precise injection and may reduce side effects and the risk of development of antibodies to BT.     

Abnormal spinal interactions from hand afferents to forearm muscles in writer's cramp.

OBJECTIVE: Spinal reflexes from hand to wrist muscles were investigated in writer's cramp. METHODS: Stimulus-triggered rectified EMG averages after ulnar nerve and cutaneous stimulation, in wrist flexors and extensors during tonic contraction, were compared in 18 controls and 19 patients. RESULTS: On the patient dystonic side, ulnar-induced EMG suppression was decreased in wrist extensors, and facilitation in wrist flexors modified dependent on the dystonic wrist posture during writing. No change was found on the patient non-dystonic side. Cutaneous stimulation increased wrist flexor EMG on both sides of the patients with normal wrist posture during writing, but had no effect in controls and patients with abnormal wrist posture. CONCLUSIONS: Comparison between cutaneous and mixed nerve stimuli suggests that spindle afferents from intrinsic hand muscles may mediate patients' ulnar-induced EMG modulations. Abnormal proprioceptive control was only observed on dystonic side, while bilateral unusual cutaneous control was found in patients. Changes in spinal transmission were partly related to the dystonic wrist posture, suggesting that systems involved in sensory processing can be differentially altered in writer's cramp. SIGNIFICANCE: Changes in spinal transmission, probably related to peripheral and/or cortical inputs, might either take part in primary or adaptive mechanisms underlying writer's cramp.     

Botulinum toxin treatment of children with cerebral palsy — a short review of different injection techniques

The intramuscular application of botulinum toxin type A (BoNT/A) has emerged to be an established treatment option to reduce muscular hyperactivity due to spasticity in children with cerebral palsy. Accurate injection is a prerequisite for efficient and safe treatment with BoNT/A. So far, treatment procedures have not been standardized. This paper is a short review of different injection techniques, i.e., manual needle placement as well as guidance by electromyography, electrical stimulation, and ultrasound. Advantages and disadvantages of the different injection techniques are discussed with a focus on needle positioning within the targeted muscle, injection close to the neuromuscular junction and diffusion of BoNT/A within the target muscles and through fascia. The additional information gained by each injection technique is weighed in terms of the clinical impact for children with cerebral palsy.     

Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C

Botulinum neurotoxin type A (BoNT/A) is commonly used in human therapy. This treatment may induce immunoresistance and preliminary evaluation of other botulinum neurotoxin serotypes suggested botulinum neurotoxin type C (BoNT/C) to be a good alternative to BoNT/A. Here, we have further characterized the biological activities of BoNT/C using a variety of experimental approaches. Muscle paralysis and time of recovery of mouse hind limb injected with BoNT/A or BoNT/C were assayed with the Digit Abduction Scoring assay. The extent and duration of paralysis were similar with the two toxin serotypes. Extensor digitorum longus or tibialis anterior muscles were dissected at times of complete paralysis and of complete recovery. Muscle weight and force were significantly reduced in mice injected with BoNT/A and BoNT/C, and some atrophy persisted for a long time. In BoNT/C-treated junctions, nerve terminal sprouting was prominent, indicating that the capacity to extend the field of innervation is not hampered by BoNT/C. BoNT/C induced a marked decrease in the frequency of miniature endplate potentials and in the amplitude of endplate potentials. 3,4-diaminopyridine reversed the effect of BoNT/C by increasing the amplitude of synchronized endplate potentials. The present study shows an extensive similarity in the biological activities of BoNT/A and BoNT/C, further supporting the suggestion that BoNT/C is a valid alternative to BoNT/A.     

Botulinum toxin therapy of writer's cramp

The pathophysiology and management of writer's cramp is one of the most challenging amongst the various forms of focal dystonias. Frequently, the dystonic postures are confounded by compensatory muscle activity. Correct identification of target muscles for botulinum toxin (BT) injections determines the treatment success. The dosages of different preparations vary, with 1 unit of Botox® roughly equalling 3.5 units of Dysport®. Electromyographic guided injections yield better results and may also decrease the amount of toxin required. Weakness of target muscles interfering with other non‐writing activities is a frequently encountered adverse effect. Studies have shown that BT is a safe long‐term therapy option.