News Botulinum toxin treatment For many people botulinum toxin treatment makes a huge difference in helping to manage their dystonia. But what happens if botulinum toxin treatment is not working. Dr Marie-Helene Marion is one of the Society’s medical advisers, and also chair of the British Neurotoxin Network (BNN) – the network for medical professionals who work with botulinum toxin. We asked her for her views on what can be done for people with dystonia when this happens. The injections of botulinum toxin have been used for the last 30 years in the treatment of blepharospasm and cervical dystonia. It’s the most efficient treatment of focal dystonia, but about 20% of patients discontinue the treatment, most of them because they don’t feel they are achieving significant relief from the injections. Reasons for treatment failure Most poor responses are related to ‘suboptimal treatment’ – there is some more information below about what this can mean. A minority (about 2%) is due to immunoresistance, due to the development of neutralising antibodies, which can be seen like an unwanted vaccination against botulinum toxin! The underlying disease severity can also explain some long-term poor response. Dystonia can be a capricious condition and fluctuations in severity over days, weeks, months or years are well described. Side effects can become a limitation to optimal treatment, such as double vision and droopy eyelid in case of blepharospasm and dysphagia in case of cervical dystonia. Some patients may also have a perception of poor response attributable to unrealistic expectations, depressed mood or comparison of the current response with the initial treatment, which may have had the most noticeable benefit. What is suboptimal treatment with botulinum toxin? For the treatment of dystonia ‘sub optimal’ normally means that the dosage, the sites or the technique of the injections are not optimal for that patient’s dystonia. It is difficult to establish a standard protocol of injections due to individual variation in terms of posture, severity of spasm and individual sensitivity to the botulinum toxin. Dystonia is so unique to every individual that optimal treatment can vary significantly from person to person. 1. The dosage of botulinum injections per session can be too low to control a severe spasm. The initial injections are usually performed cautiously and the dosage is increased at subsequent injections, depending on the improvement and of the duration of benefit. The occurrence of side effects can be a limiting factor to an injector giving a higher dosage. You have to be patient. You may need more than 1 session to get the right dosage for you! 2. The sites of the injections are not targeting the dystonic spasms. The sites of the injections may need to be reviewed. In some types of blepharospasm, for example, the injections along the eyelashes into the eyelid (called the pretarsal part of the orbicularis oculi) are more efficient than injections at the vicinity of the eyes (around the orbit). Image source: Krack and Marion, Mov Disorders 1994 The picture on the left represents the orbicularis oculi muscle with its 3 parts, (1) orbital part, (2) preseptal part, (3) pretarsal part. The picture on the right represents the pretarsal sites of injections following the black arrows. For further details on different types of blepharospasm, read: https://infodystonia.com/2011/11/02/are-all-the-blepharospasms-the-same/ https://infodystonia.com/category/apraxia-of-eyelid-opening/ For some cases of cervical dystonia as well as muscles in the neck, there are also the shoulder muscles (trapezius, levator scapulae) associated in complex posture (double chin, goose neck, flexion of head and neck). The selection of the muscles to inject can be difficult and is based on the clinical examination of the patient sitting, standing, walking, turning their head and eyes closed. For more information visit: https://infodystonia.com/2011/11/23/what-makes-my-head-turn/ 3. Deep dystonic muscles can be difficult to access without electromyography (EMG) or ultrasound (US) guidance. For instance the longus colli, in case of flexion of the neck, requires EMG guidance. The anterior scalenius, in case of some lateral tilt of the neck, requires US guidance. Do people develop a resistance to botulinum toxin? It’s rare, about 2%, but very occasionally it is possible and this is the reason that doctors avoid injecting patients repetitively with too short intervals between injections. The main time when this can occur is when patients are being supported in two different toxin clinics, such as ophthalmology and neurology, or ENT and neurology, with no synchronisation between the injection times in the two speciality clinics. Joint multidisciplinary clinics avoid such a problem. Resistance to the main type of botulinum toxin used in treating dystonia (type A) may occur 2 to 3 years after initiation of therapy. Objective tests are used to diagnose whether there is resistance, either an injection on one side of the forehead or an injection of the back of either foot. If the resistance is confirmed, there are a couple of options. Sometimes the therapeutic strategy is a ‘botulinum toxin holiday’ (stopping the injections for 12 months if possible), after which treatment may become more effective. Sometimes using alternative brands of botulinum toxin such as botulinum toxin type B may be an option. The underlying severity of the dystonia Some forms of focal dystonia are more severe than others, in terms of severity of the spasms and spread of the dystonia on different parts of the body. This can have an impact on the effectiveness of treatment. The clinical spectrum of facial dystonia (also called cranial dystonia) can extend from an isolated blepharospasm to a craniocervical dystonia where the dystonia spread from the eyes to jaw, tongue, throat and neck. The clinical spectrum of neck dystonia can extend from a mild rotation of the head, well controlled by touching the chin with the fingers, to a severe painful spasm involving neck and shoulder muscles, with additional jerks, on which the patient has no controlled. Also, stress can account for recent worsening of a dystonia which was previously well controlled by treatment. For cases where the severity of the dystonia means that the botulinum toxin treatment is not working effectively enough a more holistic approach, including drug treatment with anticholinergic drugs, mindfulness, and sensory motor retraining is advisable. The expectations of patient Any individual’s view of the effectiveness of treatment will inevitably be coloured by their expectations of that treatment. One challenge with botulinum toxin treatment can be if there is a very dramatic benefit from the first treatment session. This can be explained by the increased action of the toxin when the muscles are over-activated. When the dystonia has improved over time, the patient feels that the injections are less effective as the benefit is less dramatic, and the patient may not be as aware that they are continuing to improve when looking back at previous video recording. There are also studies which show the importance of self-management of the patient to decrease impact of a condition on daily life, even beyond the primary motor impairment due to the dystonia. For example, it is often important for a patient try to focus as little as possible on the dystonia, to distract their mind from the spasms; for some people techniques such as mindfulness and /or hypnosis can be a helpful to achieve this, which can improve the overall management of the condition. Also, it’s important to detect any issues with emotional or mental well-being, as this can have a significant impact on a patient’s overall response to their condition, and can be treated specifically. Conclusions Achieving the optimal treatment for dystonia is complex and multi-faceted, and can take time. Issues with sub-optimal treatment, such as finding the right dose and right location for injections, are the most common reasons for botulinum toxin treatment not working as effectively as hoped. Developing an immunity can happen, but it is actually very rare. Many of these different factors can add up in the same patient. It justifies a systematic approach from the injector, beyond the syringe and needle, to discuss openly with the patient these different issues. Also, always be aware that dystonia needs time to get better.