Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity.

OBJECTIVES: The therapeutic effects of botulinum neurotoxin (BoNT) are well documented in upper limb spasticity. However, several factors may influence treatment efficacy, including targeting of neuromuscular junctions (NMJs). We examined whether NMJ-targeted BoNT injections were non-inferior, in terms of efficacy, to current injection practices. DESIGN: Open-label prospective evaluator-blinded study. SETTING: Conducted across 20 medical centres in Denmark, Finland, Norway and Sweden (24 September 2012 to 11 March 2015). PARTICIPANTS: Aged ˃18 years with upper limb spasticity (Modified Ashworth Scale [MAS] score of 2 or 3) following stroke or traumatic brain injury, had received ≥2 consecutive BoNT-A treatment cycles (the latest of which was abobotulinumtoxinA [aboBoNT-A]) and needed BoNT-A retreatment (same modality as previous cycle). Patients requiring aboBoNT-A doses >800units were excluded. In total, 88 patients were randomised (intention-to-treat [ITT] population), most were male (n=58/88, 65.9%) and 54/88 (61.4%) completed the study (per protocol [PP] population). INTERVENTIONS: Randomisation (1:1) to receive a single dose of aboBoNT-A (≤800 U) according to either current clinical practice (300 U/mL) or as an NMJ-targeted injection (100 U/mL). PRIMARY OUTCOME MEASURE: Proportion of patients with a ≥1 level reduction from baseline in MAS score at week 4 post-injection (responders). RESULTS: In the ITT population, the proportion of responders at elbow flexors was 72.7% in the current practice group and 56.8% in the NMJ-targeted group (adjusted difference -0.1673 [95% CIs: -0.3630 to 0.0284]; p=0.0986). Similar results were observed in the PP population (69.0% vs 68.0%, respectively, adjusted difference 0.0707 [-0.1948 to 0.3362]; p=0.6052). CONCLUSIONS: Owing to the limited number of participants, non-inferiority of NMJ-targeted injections could not be determined. However, there was no statistical difference between groups. Larger studies are needed confirm whether the two techniques offer comparable efficacy. TRIAL REGISTRATION NUMBER: NCT01682148.

Oromandibular dystonia, mental distress and oro-facial dysfunction-A follow-up 8-10 years after start of treatment with botulinum toxin.

BACKGROUND: Oromandibular dystonia (OMD) with involuntary jaw and tongue movements may be misdiagnosed as temporomandibular disorders (TMD) and because of the complex muscle activity and involvement of several small muscles, OMD is also considered difficult to treat. OBJECTIVES: The aim was to evaluate OMD in patients 8-10 years after start of treatment with botulinum toxin (BoNT) by self-reported and standardised global scales and questionnaires. METHODS: Of 21 previously reported patients with OMD, 14 responded to a mail health questionnaire to describe the disease course and treatment effect as well as the overall impact of OMD by a visual analogue scale (VAS), the Patient Health Questionnaire (PHQ) for depression and anxiety, and the Jaw Functional Limitation Scale (JFLS). The results were analysed with non-parametric statistical analysis (Wilcoxon matched-pairs test and Spearman's rank-order correlations). RESULTS: The OMD was still present in 13 patients. In nine patients, the BoNT treatment had continued as monotherapy or combined with oral medication. VAS for OMD was significantly reduced (P < 0.04) over the years, and most patients felt improvement from the treatment. However, the patients had still some functional limitations, typically regarding jaw mobility and communication, and both JFLS and mental distress (PHQ) were significantly correlated with the OMD VAS (rS 0.77 and 0.74). CONCLUSION: The results showed marked reduction of the experienced OMD with treatment and over time, and also stressed similarities between OMD and TMD. Both dentists and neurologists should be aware of this overlap and reduce misdiagnosis by applying an interdisciplinary approach.

Interdisciplinary recognizing and managing of drug-induced tardive oromandibular dystonia: two case reports.

Tardive dystonia is a risk factor in medical antipsychotic treatment. It often begins with repetitive involuntary jaw and tongue movements resulting in impaired chewing and detrimental effect on the dentition. The orofacial dysfunction may go unrecognized in a neurological setting. The diagnosis may be difficult so we suggest interdisciplinary collaboration.

Oromandibular dystonia--functional and clinical characteristics: a report on 21 cases.

OBJECTIVES: The objectives of this study were to describe subtypes, characteristics, and orofacial function of patients with oromandibular dystonia and report results of special dental importance. STUDY DESIGN: Symptoms, signs, and function were evaluated by questionnaires, video, and clinical and physiological examinations in 21 patients with primary and secondary dystonia (13 focal, 7 segmental, 1 multifocal). RESULTS: A mixture of 2 or more subtypes of jaw movements was most common (43%), and the dystonic electromyographic activity was frequent in the anterior digastric (62%) and temporal and lateral pterygoid (48%) muscles. The impact from the oromandibular dystonia was marked. The prevalence of problems with mastication and swallowing was high, as well as with hyposalivation, dental attrition, and other dental problems. CONCLUSIONS: Patients with oromandibular dystonia may present to dentists with involuntary jaw movements and other severe functional problems. Care must be adapted to the neurological disorder and may be complicated by the condition itself.

Chewing in patients with severe neurological impairment.

OBJECTIVE AND DESIGN: As degenerative disease, infarction and hemorrhage in the CNS may compromise chewing, the aim was to classify and analyse such chewing disturbances. The case series included clinical and electromyographic recordings from 10 patients (ages 12-78 years) with neurological disorders. RESULTS: Classifications were involuntary munching (two women with dystonia which was abolished during mastication), ceased chewing function (three men with impaired volitional motor control and spasticity from locked-in syndrome, restricted chewing range (two men and one woman with reduced jaw opening due to paradoxical activity after brainstem lesions), and distorted chewing pattern (two men with dystonia resulting in blockings during chewing). CONCLUSION: The effect of the neurological impairment illustrated the complex control of mastication and the interaction between central and peripheral mechanisms, and the variation of the chewing disturbances was surprisingly great, even with similar diagnosis.

Oromandibular dystonia involving the lateral pterygoid muscles: four cases with different complexity.

The report describes oromandibular dystonia (OMD) in four women with involuntary activity of the lateral pterygoid muscles (LP), causing incapacitating protrusive and lateral jaw movements and displacements, and treatment with botulinum toxin type A (BTX). For initial survey and treatment control, OMD was analyzed with several, independent, and standardized methods. OMD severity and functional difficulties were evaluated subjectively and scored from videotapes. Jaw movements were assessed graphically with a magnetic tracking system, and electromyographical activity (EMG) of LP was recorded with needle electrodes using an intraoral approach, whereas activity of masseter muscles was recorded with surface electrodes. EMG-guided BTX injections (25-40 units Botox per muscle) into the muscles were performed with cannula electrodes. Compared with reference values for LP, OMD was associated with a markedly increased level of spontaneous activity, but almost normal level of maximum voluntary activity. The central pattern generator for mastication seemed to override the dystonic activity, as all patients were able to chew despite some distortion. BTX reduced both the spontaneous and the maximum activity for 3-9 months. Concomitantly, a marked reduction of the OMD severity, mandibular movements and functional disturbances were also present with the best effect in localized OMD with late onset.

Treatment of gustatory sweating with low-dose botulinum toxin A: a case report.

UNLABELLED: Frey's syndrome, gustatory sweating in the preauricular area, is an unpleasant phenomenon occurring during meals after surgery on the parotid gland. Recently, botulinum toxin A (BTX) has been shown to reduce the symptoms, but the variation in the reported doses is large. OBJECTIVE: To quantify the effect of treatment with low-dose BTX in a case of Frey's syndrome over a period of 6 months. MATERIAL AND METHODS: A 56-year-old woman was treated with 10 U Botox given as 20 single, intracutaneous injections of 0.5 U, one for each cm(2), 3 years after resection of the parotid gland. Before treatment and repeatedly during the 6-month period, the sweating was rated subjectively on a 100-mm visual analog scale (VAS) and by a severity index, and objectively by assessment of the extent of the involved skin area using Minor's iodine-starch test, staining the area of sweating dark. RESULTS: The treatment decreased the involved area from 20 to 5 cm(2) and the VAS ratings from 98 to 8 mm. The index showed that treatment affected the sweating intensity, not the frequency. After the 6-month period the patient was still satisfied, but the involved skin area had increased; however, not entirely to pretreatment values. CONCLUSIONS: The effect of BTX injections for gustatory sweating obtained in this case was comparable to results reported using higher doses. Low doses of BTX can therefore be used in the treatment of Frey's syndrome, but studies to clarify the dose-response relationship, in terms of both time-course and obtained effect, are needed.

Treatment of severe temporomandibular joint clicking with botulinum toxin in the lateral pterygoid muscle in two cases of anterior disc displacement.

A novel treatment procedure is introduced for severe clicking of the temporomandibular joint (TMJ) associated with anterior disc displacement (ADD), using injections with botulinum toxin (BTX-A) in the lateral pterygoid muscle (LP). It has been suggested that ADD may be caused, precipitated, or maintained by LP activity, but the role of the LP in the dynamics of the TMJ clicking is uncertain. The case report includes 2 women, followed with clinical examinations, TMJ imaging, and electromyography (EMG), in whom local anesthetics in the LP could abolish the clicking for several days. BTX-A block of the LP (30 U Botox, given twice under EMG guidance with 6-month interval) temporarily reduced the action of the muscle, but the clicking was permanently eliminated and did not return during the observation period of 1 year, and a small but distinctive positional improvement in the disc-condyle relationship was obtained. However, the precise mechanisms behind the favourable treatment outcome are unclear.

Treatment of perioral dystonia with botulinum toxin in 4 cases of Meige's syndrome.

OBJECTIVE: We describe the treatment of 4 patients (median age, 53.5 years) with incapacitating perioral dystonia and insufficient response to peroral medication. Their general treatment with clonazepam and anticholinergics was supplemented by intramuscular injections with botulinum toxin A (20-40 U) in the orbicularis oris muscle, guided by electromyography (EMG). STUDY DESIGN: Perioral dystonia and treatment effect were assessed by using subjective global and visual analog scales, examiner-based video movement counts and rating scales, and quantitative EMG. t Tests were used for statistical analysis. RESULTS: The result of the intramuscular botulinum toxin A injections was characterized by the patients as "much improved"; correspondingly, dystonia was significantly reduced in visual analog scale scores, on examiner-based assessments, and in recordings of EMG. The side effects were few and short-lasting. CONCLUSION: Incapacitating perioral dystonia in Meige's syndrome may be safely controlled by recurrent EMG-guided botulinum toxin A injections in the orbicularis oris muscle, in combination with general medication.