Botulinum toxin and conservative treatment strategies in people with cervical dystonia: an online survey.

Isolated cervical dystonia is a focal, idiopathic dystonia affecting the neck muscles. Treatment usually consists of botulinum neurotoxin (BoNT) injections into the dystonic muscles. Our aim is to investigate the use of BoNT treatment and conservative treatments by people living with cervical dystonia. An online survey in English was conducted between June and August 2022. Participants were eligible to participate if they were living with cervical dystonia, were over 18 years old and could read and understand English. The survey consisted of demographic questions, characteristics of dystonia, questions relating to BoNT use and the perceived utility of conservative treatments. The data were analysed descriptively, and open-ended questions were grouped into similar topics represented by direct quotes. We received 128 responses from people with cervical dystonia, with an average age of 59 years and 77% women. Most participants (52%) described their cervical dystonia as mild to moderate with an average pain score of 5/10. Eighty-two (64%) participants were having regular BoNT injections, with overall positive perceived effects. Common activities reported to improve the symptoms were the use of heat packs, massage, relaxation, physiotherapy and participation in general exercise. Common coping strategies reported were getting sufficient rest, having the support of friends and family, and remaining engaged in enjoyable hobbies. We found that most participants received regular BoNT injections and that heat packs, exercise, massage, physiotherapy and relaxation were mostly perceived as effective in reducing the symptoms of cervical dystonia.

Development of a patient journey map for people living with cervical dystonia.

BACKGROUND: Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment. METHODS: The CDPJM was developed in 2 stages; a patient survey (open questions and multichoice) of 15 patients with CD was conducted to inform the design of the CDPJM, which was then refined and validated by an expert-patient focus group. RESULTS: Qualitative analysis of the patient survey supported five key stages of the patient journey: symptom onset, diagnosis and therapeutic relationship with healthcare professionals, initiation of care for CD, start of CD treatment, and living with treated CD. Following symptom onset, survey respondents described having multiple visits to their family doctor who prescribed strong pain killers and muscle relaxants and referred their patient to up to 10 different specialists for diagnosis. Over half (53.3%) of respondents had received ≥ 1 misdiagnosis. Respondents reported relief at having a diagnosis but a lack of understanding of the prognosis and treatment options; 46.7% said their neurologist did not spend enough time addressing their concerns. Survey respondents reported using a variety of alternative sources of information, including the internet (86.7%), self-help groups (66.7%) and information leaflets provided by health care professionals (60.0%). While botulinum toxin (BoNT) was consistently discussed as the main treatment option, some neurologists also mentioned physiotherapy, counselling, and other complementary approaches. However, patients were often left to seek complementary services themselves. Patients reported a 'rollercoaster' of relief with BoNT treatment with symptoms (and subsequent impact on daily life) returning towards the end of an injection cycle. "When BoNT works well I can return to an almost normal life … when the injections stop working so well, I have to rest more and avoid going to work and experience life restrictions." CONCLUSIONS: We present the first patient journey map for CD that can be used to guide local service mapping and to compare current provision with what patients say they want and need.

Study protocol: multimodal physiotherapy as an add-on treatment to botulinum neurotoxin type A therapy for patients with cervical dystonia: DysPT-multi-a prospective, multicentre, single-blind, randomized, controlled study.

BACKGROUND: Botulinum neurotoxin (BoNT) is currently the best therapeutic option in the treatment for cervical dystonia (CD). Additional treatments like physiotherapy (PT) may even improve the results of the BoNT injection with type A (BoNT-A), but there are no definite recommendations. In the last few years, some studies showed tendencies for PT as an adjuvant therapy to benefit. However, high-quality studies are required. METHODS: This study is a multicentre, randomized, single-blind, controlled trial to demonstrate the effectiveness of a multimodal PT program compared to a nonspecific cupping therapy, additionally to the BoNT-A therapy. Two hundred participants will be assigned into the multimodal PT plus BoNT intervention arm or the BoNT plus cupping arm using randomization. Primary endpoint is the total Score of Toronto Western Spasmodic Rating Scale (TWSTRS). Secondary endpoints are the mobility of the cervical spine (range of motion, ROM), the TWSTRS subscales, and the quality of life (measured by questionnaires: CDQ-24 and SF-36). Patients will be single-blind assessed every 3 months according to their BoNT injection treatment over a period of 9 months. DISCUSSION: The study aims to determine the effectiveness and therefore potential benefit of an additional multimodal physiotherapy for standardized treatment with BoNT-A in patients with CD, towards the BoNT-therapy alone. This largest randomized controlled trial in this field to date is intended to generate missing evidence for therapy guidelines. TRIAL REGISTRATION: The study was registered in the German Clinical Study Register before the start of the patient recruitment ( DRKS00020411 ; date: 21.01.2020).

Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment.

BACKGROUND: Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD. OBJECTIVES: We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function. METHODS: Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months). RESULTS: In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia. CONCLUSION: The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls.

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor.

OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We performed the first trial to investigate whether dystonic jerks/tremor in patients with CD respond to the selective serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was continued, and scores on rating scales regarding dystonia, psychiatric symptoms and quality of life (QoL) were compared. Primary endpoint was the proportion of patients that improved at least one point on the Clinical Global Impression Scale for jerks/tremor scored by independent physicians with experience in movement disorders. RESULTS: Fifty-threepatients were included. In the escitalopram period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48 patients (23%) in the placebo period (P=0.77). There were no significant differences between baseline and after treatment with escitalopram or placebo on severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved significantly in both periods compared with baseline. There were no significant differences between treatment with escitalopram and placebo for dystonia, psychiatric or QoL rating scales. During treatment with escitalopram, patients experienced slightly more adverse events, but no serious adverse events occurred. CONCLUSION: In this innovative trial, no add-on effect of escitalopram for treatment of CD with jerks was found on motor or psychiatric symptoms. However, we also did not find a reason to withhold patients treatment with SSRIs for depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER: NTR2178.

Cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia.

PURPOSE: A cost-utility analysis of botulinum toxin type A products for the treatment of cervical dystonia (CD) was conducted. METHODS: A cost-utility analysis of botulinum toxin type A products was conducted from the U.S. government perspective using a decision-analysis model with a one-year time horizon. Probabilities of the model were taken from several studies using the three botulinum type A products approved by the Food and Drug Administration for the treatment of CD: onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA (Xeomin). The main outcome measurement was successful treatment response with botulinum toxin type A, measured in quality-adjusted life years (QALYs). Response was defined as a patient who experienced improvement of CD symptoms without a severe adverse event. Probabilistic sensitivity analysis was conducted to test robustness of the base-case results. RESULTS: All three botulinum toxin type A agents were cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Xeomin was the most cost-effective with a cost-effectiveness ratio of $27,548 per QALY. Xeomin was dominant over the alternative agents with equivalent efficacy outcomes and lower costs. Dysport had the second lowest cost-effectiveness ratio ($36,678), followed by Botox ($49,337). The probabilistic sensitivity analysis supported the results of the base-case analysis. Dysport was associated with the lowest wastage (2.2%), followed by Xeomin (10%) and Botox (22.9%). CONCLUSION: A cost-utility analysis found that Xeomin was the more cost-effective botulinum toxin type A product compared with Botox and Dysport for the treatment of CD. Wastage associated with the respective products may have a large effect on the cost-effectiveness of the agents.

[Botulinum toxin therapy for spasmodic torticollis: medical and non-medical adjunct treatment]. / Botulinum-Toxin-Therapie bei Torticollis spasmodicus: Medizinische und nichtmedizinische Begleitbehandlungen.

BACKGROUND: Spasmodic torticollis patients were investigated with respect to the number of adjunct treatments used before and after the introduction of botulinum toxin therapy (Btx). The study was designed in a similar way to an earlier investigation by Birner et al. (Nervenarzt 70:903-908, 1999). MATERIAL AND METHODS: A total of 247 patients with idiopathic spasmodic torticollis were assessed at three time points for the diagnosis: before 1988 (n = 63), between 1989 and 1998 (n = 107) and after 1999 (n = 77). RESULTS: Independent of the year of diagnosis patients underwent a mean of 14.3 different treatments. In addition to Btx most of the patients were subjected to massage, physiotherapy, medication and a large number of non-medical treatments including praying. No associations to clinical or personal variables were found. Those patients with emotional disorders prior to onset of dystonia displayed a higher rate of medical and non-medical treatments in addition to Btx. CONCLUSIONS: The results confirmed those found by Birner et al.. In order to enhance compliance patients should undergo psychoeducation with respect to illness behaviour and specific history taking with respect to emotional disorders prior to dystonia.

A prospective, randomized, double-blind study comparing the efficacy and safety of type a botulinum toxins botox and prosigne in the treatment of cervical dystonia.

Botulinum toxin A (BTA) is considered an effective treatment of cervical dystonia. The aim of this prospective, randomized, double-blind study was to compare Botox and Prosigne, a BTA of Chinese origin, with a view to establish the safety, the efficacy, and the equivalence of doses of the 2 formulations in the treatment of cervical dystonia. Twenty-four patients were randomized to receive 300 U of Botox or Prosigne (12 patients in each group). The patients were assessed before the injection and after 4 and 16 weeks by the Toronto Western Spasmodic Torticollis Rating Scale and the Short-Form 36 for quality of life before and 16 weeks after the injection. All patients were comparable in age, time since onset, number of previous injections, and time since last BTA application. According to the Toronto Western Spasmodic Torticollis Rating Scale scores, the patients improved after injection and the scores increased after 16 weeks, without returning to baseline values. Both pain and burning during the injection and the treatment outcomes were similar in both groups. No systemic adverse events occurred, and the severity and frequency of local events were comparable in both groups. Average duration of effect was similar in both groups (11 weeks). The quality-of-life evaluations before and after the injections were comparable in both groups. Social aspects, pain, and vitality improved after 16 weeks in both groups. In conclusion, Botox and Prosigne were determined to have equivalent efficacy, safety, and tolerability profiles and dose equivalence for cervical dystonia treatment is 1:1.

The Canadian multicenter trial of pallidal deep brain stimulation for cervical dystonia: preliminary results in three patients.

OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is beneficial for generalized dystonia and has been proposed as a treatment for cervical dystonia. The Canadian Stereotactic/Functional and Movement Disorders Groups designed a pilot project to investigate the following hypothesis: that bilateral DBS of the GPi will reduce the severity of cervical dystonia at 1 year of follow up, as scored in a blinded fashion by two neurologists using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcome measures included pain and disability subscores of the TWSTRS, Short Form-36 quality of life index, and the Beck Depression Inventory. METHODS: Three patients have undergone surgery in Calgary with a follow-up duration of 7.4 +/- 5.9 months (mean +/- standard deviation). One patient underwent inadvertent ineffective stimulation for the first 3 months and did not experience a benefit until DBS programming was corrected. All three patients had rapid response to stimulation, with the muscles relaxing immediately and abnormal movements improving within days. Total TWSTRS scores improved by 79%, and severity subscores improved significantly, from 15.7 +/- 2.1 to 7.7 +/- 2.9 (paired t-test, p = 0.02). Pain and disability subscores improved from 25.5 +/- 4.1 to 3.3 +/- 3.1 (paired t-test, p = 0.002) and from 13.3 +/- 4.9 to 3.3 +/- 4.2 (paired t-test, p = 0.06), respectively. CONCLUSIONS: Although it is too early to reach broad conclusions, this report of preliminary results confirms the efficacy of DBS of the GPi for cervical dystonia.

Unilateral pallidal stimulation in cervical dystonia.

Cervical dystonia (spasmodic torticollis) is a focal dystonia of the cervical region. Various treatment modalities have been performed with variable success rates. We present a 42-year-old woman complaining of involuntary head rotation for the last 3 years. Different medical treatments had been used for 3 years. Botulinum toxin injections resulted in temporary and moderate improvement for periods of 3-4 months. Pallidal stimulation was performed using a quadripolar electrode and a battery-operated programmable pulse generator. We conclude that a unilateral pallidal lesion or stimulation is an effective method of treatment in focal dystonia. The target must be the pallidum contralateral to the contracted sternocloidomastoid muscle. Deep brain stimulation is superior to lesioning because of the capability of manipulating the stimulation parameters which can modify the pallidotomy effect.

Click-evoked vestibulocollic reflexes in torticollis.

A total of 26 patients with torticollis were studied using a recently developed technique for recording vestibulocollic reflexes from the sternocleidomastoid muscles in addition to conventional caloric tests of vestibular function. Previous reports of abnormalities of vestibulo-ocular reflexes in these patients were confirmed with just fewer than half having significant canal pareses or directional preponderances (nine of 20 tested). In addition, there was a high incidence of abnormal click-evoked vestibulocollic reflexes (17 of 26 tested), which were not simply the result of prior treatment with botulinum toxin, nor due to unequal levels of muscle activation. In patients never previously treated with botulinum toxin (14 patients), the effect almost always consisted of suppressed responses in the sternocleidomastoid muscle ipsilateral to the direction of head turning. Because responses were not abnormal in all patients tested, and more commonly so in those with a history of torticollis of > or = 5 years (eight of nine patients) than in de novo patients, we suggest that the changes are more likely to be compensatory than causal.

Open label evaluation of cannabidiol in dystonic movement disorders.

Cannabidiol (CBD), a nonpsychoactive cannabinoid of Cannabis, was given to 5 patients with dystonic movement disorders in a preliminary open pilot study. Oral doses of CBD rising from 100 to 600 mg/day over a 6 week period were administered along with standard medication. Dose-related improvement in dystonia was observed in all patients and ranged from 20 to 50%. Side-effects of CBD were mild and included hypotension, dry mouth, psychomotor slowing, lightheadedness, and sedation. In 2 patients with coexisting Parkinsonian features, CBD at doses over 300 mg/day exacerbated the hypokinesia and resting tremor. CBD appears to have antidystonic and Parkinsonism-aggravating effects in humans.

Management of spasmodic torticollis.

Based on a review of the literature, the management of spasmodic torticollis may begin with the conservative measures of pharmacotherapy, sensory feedback, or percutaneous dorsal column stimulation. Approximately 50% of patients will benefit from an adequate trial of these modalities. With particularly resistant and disabling torticollis, the ablative procedures of microsurgical cervical rhizotomy or stereotaxic thalamotomy have offered significant relief in about 74% and 56%, respectively, of properly selected cases. Nevertheless, the variability in the duration of response to all forms of therapy has made the treatment of spasmodic torticollis a difficult and often frustrating undertaking.

[Effect of DOPA and haloperidol on experimental torticollis originating in the mesencephalon and its modulation by stimulation of the caudate nucleus]. / Vliianie DOFA i galoperidola na éksperimental'nyi tortikollis mezéntsefalicheskogo proiskhozhdeniia i ego moduliatsiiu razdrazheniem khvostatogo iadra.

Electrolytic injury to dopaminergic neurons of the mesencephalic tegmentum in cats produced a steady experimental torticollis (ET) with contralateral turning of the head and body. DOPA potentiated and haloperidol mostly reduced ET. Analogous changes were induced by electrical stimulation of the ipsi- and contralateral caudate nucleus, respectively. Stimulation of the contralateral nucleus coupled with haloperidol administration led to a more pronounced restriction of ET. Unexpectedly, the same result was obtained after DOPA administration coupled with stimulation of the ipsi-lateral caudate nucleus. It is suggested that pharmacological treatment of torsion diseases should be combined with physical treatment methods.

Effect of L-glutamine and isoniazid on torticollis and segmental dystonia.

Fourteen patients with spasmodic torticollis and other segmental dystonic syndromes, who were refractory to previous forms of therapy, were selected for treatment with drugs intended to elevate brain gamma-aminobutyric acid (GABA) levels. These patients were simultaneously given diazepam, isoniazid, pyridoxine, and large doses of L-glutamine. Involuntary spasmodic activity improved to varying degrees in 7 patients; in 2 the dyskinesia became worse. Transient alteration of renal or hepatic function occurred in 6 patients and mild euphoria unrelated to neurological improvement in 8. Two patients are still being treated. Deficiency of GABA may be a factor in some patients with these disorders.