Secondary nonresponsiveness to botulinum toxin type A in patients with oromandibular dystonia.

Intramuscular injection of botulinum toxin type A is the treatment of choice for most cases of oromandibular dystonia. We report on five patients with oromandibular dystonia that developed secondary nonresponsiveness to botulinum toxin type A following multiple injections over a 6-year period.     

Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations

Amongst all regions of the body, the craniocervical region is the one most frequently affected by dystonia. Whilst blepharospasm – involuntary bilateral eye closure – is produced by spasmodic contractions of the orbicularis oculi muscles, oromandibular dystonia may cause jaw closure with trismus and bruxism, or involuntary jaw opening or deviation, interfering with speaking and chewing. Both forms of dystonia can be effectively treated with botulinum toxin injection. This article summarizes injection techniques in both forms of dystonia and compares doses, potency and efficacy of different commercially available toxins, including Botox®, Dysport®, Xeomin® and Myobloc®/NeuroBloc®.     

Identification and treatment of cervical and oromandibular dystonia in acutely brain-injured patients

Introduction: Primary cervical and oromandibular dystonia (CD and OMD, respectively) are well-recognized movement disorders, often treated with botulinum toxin (BTx). In contrast, dystonia related to acute brain injuries is not well delineated. Our objective was to define in neurocritically ill patients the clinical characteristics of CD and OMD and to investigate the safety of BTx. Methods: All acutely brain-injured patients admitted to a neurocritical care unit over a 10-month period were prospectively screened for CD and OMD. Clinical characteristics, etiology of brain injury, and pattern of dystonia were analyzed. Patients with clinically significant CD and OMD were treated with BTx and followed for 12 weeks. Results: Of 165 patients screened, 33 had new-onset CD or OMD. Of 21 patients enrolled, 14 had CD, 5 had OMD, and 2 had both. The pattern of brain injury included 13 cerebral hemorrhages, 6 ischemic strokes, 1 status epilepticus, and 1 unclear etiology. Improvement after BTx was seen in four of seven patients with CD and two of four with OMD; no adverse effects occurred. Spontaneous improvement was recorded in 7 of 11 nontreated patients with CD or OMD. Conclusions: Acute secondary CD or OMD, associated with a variety of causes, was identified in 20% of acutely brain-injured patients. The temporal profile of dystonia onset and resolution in these patients was variable. Treatment with BTx in the neurocritical care setting seems to be safe. Future, larger scale randomized studies should evaluate the effectiveness of BTx treatment in this patient population.     

Smothering dystonia in a patient with oromandibular dystonia.

A case report is presented of a patient with pathologically confirmed striatonigral degeneration who experienced episodic syncope as a result of oromandibular dystonia obstructing inhalation through her mouth and nose.     

Movement-related cortical potentials before jaw excursions in oromandibular dystonia.

Oromandibular dystonia is a neurological disorder characterized by involuntary contraction of masticatory and/or tongue muscles. Cortical negative shifts preceding voluntary movements called "movement-related cortical potentials" (MRCPs) reflect a central motor control process. Reduced amplitude of MRCPs has been reported in other types of dystonia. To elucidate whether the abnormality is observed also in oromandibular dystonia, we compared MRCPs associated with mandibular movements in 6 patients with this condition and in 8 normal subjects. Electroencephalograms (EEGs) were recorded from 11 electrodes, and electromyograms (EMGs) were recorded from the masseter muscle and the suprahyoid muscles. The subjects were asked to repeat mouth opening, closing, and left and right lateral mandibular excursions. MRCPs were obtained by averaging the EEG using the EMG onset as the trigger signal. In the patient group, MRCP amplitudes over central and parietal areas for mouth opening and lateral movements were significantly reduced compared to normal subjects. In normal controls, the MRCPs at mouth opening and closing were symmetrically distributed, whereas those at lateral movements showed predominance over the hemisphere ipsilateral to the direction of the movement. This laterality was lost in the patient group. These results suggest impaired cortical preparatory process for jaw movements in oromandibular dystonia.     

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.     

A型肉毒毒素治疗口下颌肌张力障碍

目的观察A型肉毒毒素治疗口下颌肌张力障碍(OMD)患者的临床效果。方法对19例口下颌肌张力障碍患者进行临床分析,依据患者临床特点,将A型肉毒毒素注射到患者一侧或双侧咀嚼肌、颞肌及翼外肌,并根据肌肉收缩力量大小、肌肉体积及患者体重调整剂量。结果 68.4%的患者功能改善评分≥3分,疗效平均维持8～12周(有效范围2～28周)。4例患者注射后有轻度咀嚼无力,2～3周恢复。1例混合型患者注射后出现轻度鼻音,持续13天后症状消失。所有患者未出现其它严重副作用。结论 A型肉毒毒素对于口下颌肌张力障碍的治疗是有效、安全的。熟悉本病的临床特点及分型,选择正确的靶肌肉及注射适宜剂量的肉毒毒素是治疗本病的关键。     

Somatosensory temporal discrimination tested in patients receiving botulinum toxin injection for cervical dystonia

We designed this study to find out more about the relationship between the sensory effects of Botulinum toxin type A (BTX) and the clinical benefits of BTX therapy in patients with cervical dystonia (CD). In 24 patients with CD, we tested sensory temporal discrimination (STD) in the affected and two unaffected body regions (neck, hand, and eye) before and 1 month after BTX injection. In 8 out of the 24 patients with CD, STDT values were tested bilaterally in the three body regions before, 1 and 2 months after BTX injection. As expected, STD testing disclosed altered STD threshold values in all three body regions tested (affected and unaffected by dystonic spasms) in patients with CD. STD threshold values remained unchanged at all time points of the follow‐up in all CD patients. The lack of BTX‐induced effects on STD thresholds suggests that STD recruits neural structures uninvolved in muscle spindle afferent activation. © 2010 Movement Disorder Society     

A型肉毒毒素治疗头颈部肌张力障碍的临床观察

目的观察A型肉毒毒素(BTXA)治疗偏侧面肌痉孪、睑痉孪、Meige’s综合征、痉孪性斜颈的疗效。方法治疗组(A组)用BTXA对86例患者进行头颈部肌肉多点注射,对照组(B组)50例根据诊断选用不同的药物或/和针灸、理疗、中医药治疗。观察两组疗效及副作用。结果A组治疗后当日至3d内开始见效,7～15d达高峰,疗效维持2～6月。总有效率为100%,疗效明显高于B组(P<0.001)。BTXA重复注射疗效无下降,1例HFS患者第三次注射产生耐药性,少数患者有轻微的局部副反应,未见全身副作用。B组62%(31例)的患者疗效维持5～15月后减退,需逐渐增加剂量,少数患者出现白细胞减少、肝功能损害、皮疹、共济失调等不良反应。结论A型肉毒毒素局部注射是治疗头颈部肌张力障碍的一种安全、有效、简便的方法。     

An open trial of levetiracetam for segmental and generalized dystonia.

Local botulinum toxin injections represent the treatment of choice for most patients with focal dystonia. However, patients with segmental or generalized forms require additional pharmacologic treatment which is often ineffective or limited by intolerable side-effects. An animal study and three case reports suggested antidystonic effects of levetiracetam, a pyrrolidone derivate, whereas a recent open-label study found no improvement in 10 patients with primary idiopathic cervical dystonia. We studied the efficacy of levetiracetam in a daily dose of 3000 mg in 10 consecutive patients with otherwise therapy refractory segmental or generalized dystonia. At 4-week follow-up, none of the patients showed improvement of dystonia, mild side-effects were observed in 3 patients.     

Surgical treatment for secondary dystonia

Surgical therapy for the secondary dystonias is generally perceived to be less effective than for primary disease. However, a number of case reports and small open series have recently appeared describing quite favorable outcomes following surgery for some nonprimary dystonias. We discuss surgical treatment options for this group of diverse conditions, including tardive dystonia, dystonic cerebral palsy, and certain heredodegenerative diseases in which deep brain stimulation and ablative lesions of the posteroventral pallidum have been shown to be effective. Other types of secondary dystonia respond less well to pallidal surgery, particularly when anatomical lesions of the basal ganglia are prominent on preoperative imaging. For these conditions, central baclofen delivery and botulinum toxin denervation may be considered. With optimal medical and surgical care, some patients with secondary dystonia have achieved reductions in disability and pain that approach those documented for primary dystonia. © 2012 Movement Disorder Society     

Reduced jaw opening from paradoxical activity of mandibular elevator muscles treated with botulinum toxin

The aim of the study was the effect of injections with botulinum toxin A (BTX-A) on reduced jaw opening, caused by paradoxical, antagonistic activity of jaw elevator muscles after brain stem lesions. The study included a male (51 years) and a female (69 years) patient. Subjective assessment, clinical recordings, muscle blocks and electromyography (EMG) were used to diagnose paradoxical activity, and to plan, guide and evaluate the treatment. The paradoxical innervation pattern was unilateral in the male and bilateral in the female. The paradoxical activity during jaw opening amounted to 24-109% of the level during maximum biting, and bursts of paradoxical activity were also present during chewing. EMG-guided blocks and later BTX-A injections of the affected muscles increased the opening by 9-23 mm from pre-treatment values of 15-18 mm, and normalized chewing. The study proved BTX-A to be an effective treatment for reduced jaw opening caused by paradoxical activity. Treatment was optimized by EMG evaluation of the current activity of the jaw elevator muscles, permitting individual treatment plans with longer intervals between BTX-A injections and lower doses than with conventional treatment for oromandibular dystonia. Thus the treatment only had to be repeated one to two times per year to maintain acceptable jaw mobility.     

Effect of cervical dystonia on employment: A retrospective analysis of the ability of treatment to restore premorbid employment status

Using a structured interview method, we sought to address the following questions regarding cervical dystonia (CD) and employment: (1) what is the frequency and severity of job impairment in CD; (2) what are the clinical features that contribute to job impairment; (3) how does the effectiveness of botulinum toxin (BTx) compare to oral medications in restoring employment status. In our population of 155 CD patients, employment was affected by CD in 53.3% (31.2% reduced hours or responsibilities, 3.3% changed to different job, 18.9% loss of employment) and 68.9% of patients reported reduced overall productivity. The likelihood of altered employment (P < 0.0006), reduced productivity (P < 0.0001), and seeking disability benefits (P < 0.003) was significantly associated with the presence of neck pain, but not type of employment, spasmodic head motions, or duration of CD symptoms before treatment with BTx. Treatment with BTx was more likely to improve employment status than oral medications (66.1 vs. 18.5%) and much more likely to restore full employment with normal productivity (12.9 vs. 0.0%). These findings suggest that employment status is frequently affected by CD, particularly in patients withneck pain. BTx is significantly more effective than oral medications in restoring premorbid employment status. © 2009 Movement Disorder Society     

Long-term follow-up of cervical dystonia patients treated with botulinum toxin A.

We followed the course in 100 consecutive patients with cervical dystonia (CD) after they were initially treated with botulinum toxin (BTX) in the form of Dysport 10 to 12 years ago. A total of 4 patients had died, and 6 were lost to follow-up. Of the remaining 90 patients, 57 (63%) were still treated with BTX. In the patients treated at one centre over the whole period with Dysport, mean dose used during each treatment session was 833 (SD +/- 339) units Dysport with a cumulative dose of 20,943 (SD +/- 9462) units Dysport over a mean of 26.8 (SD +/- 8.6) treatment cycles. Secondary nonresponse was detected in 3 of the 90 patients. During follow-up, 12 patients developed blepharospasm, 13 oromandibular dystonia, and 17 patients writer's cramp. We conclude that BTX remains effective and safe for approximately 60% of CD patients for more than 10 years.     

Long-term botulinum toxin treatment increases employment rate in patients with cervical dystonia.

We examined the impact of cervical dystonia (CD) and long-term botulinum toxin (BTX) treatment on employment status. Data on employment status at onset of CD, at initiation of BTX treatment, and at evaluation of long-term treatment were obtained from 62 CD patients aged 31-66 years (median, 53 years; 61% females) who had been treated for a median of 5 years (range, 1.5-10 years). The employment rate fell from 84% at the onset of CD to 47% before initiation of BTX treatment. With long-term BTX treatment, 72% of those who worked at the initiation of treatment stayed employed, and 67% of those on sick leave returned to work. A younger age and a higher level of education increased the probability of being employed and avoiding disability benefits. Among those who were younger than 55 years at evaluation of BTX treatment (n = 40), the employment rate increased from 47% to 65% with treatment, and among the male patients, it reached the level of the general population (86%). About half of the 34% who received disability benefits did so already before the BTX treatment was initiated.     

Asynchronous blepharospasm, facial and cervical dystonia, and bilateral asynchronous hemifacial spasm.

We present a patient with a facial movement disorder that has characteristics of both blepharospasm and bilateral asynchronous hemifacial spasm. Because of the increased incidence of blepharospasm in patients with hemifacial spasm, our patient's clinical presentation is probably not a chance occurrence, but rather a manifestation of some predisposition for these two movement disorders. This unusual constellation of signs and symptoms challenges the current diagnostic criteria and suggests that some of these facial movement disorders may lie on a spectrum, rather than represent distinct entities.     

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.