Tardive and idiopathic oromandibular dystonia: a clinical comparison

OBJECTIVE: Most patients with tardive dystonia have a focal onset involving the cranial-cervical region. Because of its resemblance to idiopathic cranial dystonia, a common form of dystonia, it often poses a diagnostic problem. To compare clinical features and response to botulinum toxin (BTX) injections between patients with tardive and idiopathic oromandibular dystonia (OMD). METHODS: Patients seen in a movement disorder clinic who satisfied the inclusion criteria for tardive or idiopathic OMD were studied. The clinical variables and responses to BTX between the two groups of patients were compared. In the tardive group, we also compared the clinical variables between those with oro-facial-lingual stereotypies, and those without. RESULTS: Twenty four patients with tardive OMD and 92 with idiopathic OMD were studied. There were no differences in the demographic characteristics. Most were women, with duration of symptoms longer than 8 years. The mean duration of neuroleptic exposure was 7.1 (SD 7.9) years. Jaw closure was the most frequent subtype of OMD (tardive=41.7%, idiopathic=51.1%). Idiopathic patients were more likely to have coexistent cervical dystonia (p<0.05), whereas isolated OMD was significantly higher in tardive patients (p<0.05). Limb stereotypies, akathisia, and respiratory dyskinesia were seen only in the tardive OMD. Frequency of oro-facial-lingual stereotypy was significantly higher in the tardive than the idiopathic group (75.0% v 31.5%, p<0.0001). The peak effect of BTX was similar in both groups. CONCLUSIONS: Oro-facial-lingual stereotypies were significantly more frequent in the tardive than the idiopathic group. Presence of stereotypic movements in the limbs, akathisia, and respiratory dyskinesias in patients with OMD strongly suggests prior neuroleptic exposure. Dystonia in tardive OMD is more likely to be restricted to the oromandibular region, whereas in patients with idiopathic OMD, there is often coexistent cervical dystonia. BTX is equally effective in both groups of patients.     

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.     

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.     

Botulinum toxin in the treatment of tics

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin A (BTX) injections in the treatment of tics in patients with Tourette syndrome (TS). BACKGROUND: BTX is an effective treatment for an increasing number of conditions characterized by abnormal muscle contractions. BTX may improve not only the motor component of tics, but also premonitory sensations that precede tics. METHODS: Thirty-five patients (30 male, 5 female) were treated with BTX in the sites of their most problematic tics. Response to BTX was based on a 0 to 4 clinical rating scale (0, no improvement, to 4, marked improvement in both severity and function). Questionnaires were administered to evaluate patients' impressions of overall efficacy and degree of benefit with premonitory sensations. RESULTS: Mean duration of tics prior to initial injection was 15.3 years (range, 1-62 years) and mean duration of follow-up was 21.2 months (range, 1. 5-84 months). The mean peak effect response in 35 patients treated in 115 sessions was 2.8 (range, 0-4); the mean duration of benefit was 14.4 weeks (maximum, 45 weeks); and the mean latency to onset of benefit was 3.8 days (maximum, 10 days). Twenty-one (84%) of 25 patients with premonitory sensations derived marked relief of these symptoms (mean benefit, 70.6%). Total mean dose was 502.1 U (range, 15-3550 U); mean number of visits, 3.3 (range, 1-16); and mean dose per visit, 119.9 U (range, 15-273 U). Sites of injections were as follows: cervical or upper thoracic area (17), upper face (14), lower face (7), vocal cords (4), upper back and/or shoulder (3), scalp (1), forearm (1), leg (1) and rectus abdominis (1). Complications included neck weakness (4), dysphagia (2), ptosis (2), nausea (1), hypophonia (1), fatigue (1), and generalized weakness (1), which were all mild and transient. CONCLUSIONS: Botulinum toxin A injections are an effective and well-tolerated treatment of tics. In addition to improving the motor component of tics, BTX also provides relief of premonitory sensations. Arch Neurol. 2000;57:1190-1193     

Electromyographic guidance of botulinum toxin treatment in cervical dystonia

We report the results of electromyographic (EMG) guidance in the treatment of cervical dystonia with botulinum toxin. Eight-four patients received a total of 225 injection sessions. Overall there was moderate objective improvement in 78.7%. The mean dose of toxin was 269 +/- 39 mouse lethal units and the mean duration of maximum effect was 107 +/- 49 days. Complications included excessive neck weakness in 16.0% and dysphagia in 11.1% of the injection sessions. We conclude that EMG guidance is a safe and effective method of administering botulinum toxin in the treatment of cervical dystonia.     

Peripherally induced oromandibular dystonia

OBJECTIVES—Oromandibular dystonia (OMD) is afocal dystonia manifested by involuntary muscle contractions producingrepetitive, patterned mouth, jaw, and tongue movements. Dystonia isusually idiopathic (primary), but in some cases it follows peripheralinjury. Peripherally induced cervical and limb dystonia is wellrecognised, and the aim of this study was to characterise peripherallyinduced OMD.
METHODS—The following inclusion criteria were usedfor peripherally induced OMD: (1) the onset of the dystonia was withina few days or months (up to 1 year) after the injury; (2) the traumawas well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral).
RESULTS—Twenty seven patients wereidentified in the database with OMD, temporally and anatomicallyrelated to prior injury or surgery. No additional precipitant otherthan trauma could be detected. None of the patients had any litigationpending. The mean age at onset was 50.11 (SD 14.15) (range 23-74)years and there was a 2:1 female preponderance. Mean latency betweenthe initial trauma and the onset of OMD was 65 days (range 1 day-1year). Ten (37%) patients had some evidence of predisposing factorssuch as family history of movement disorders, prior exposure toneuroleptic drugs, and associated dystonia affecting other regions oressential tremor. When compared with 21 patients with primary OMD,there was no difference for age at onset, female preponderance, andphenomenology. The frequency of dystonic writer's cramp, spasmodicdysphonia, bruxism, essential tremor, and family history of movementdisorder, however, was lower in the post-traumatic group (p<0.05). Inboth groups the response to botulinum toxin treatment was superior tomedical therapy (p<0.005). Surgical intervention fortemporomandibular disorders was more frequent in the post-traumaticgroup and was associated with worsening of dystonia.
CONCLUSION—The study indicates thatoromandibular-facial trauma, including dental procedures, mayprecipitate the onset of OMD, especially in predisposed people. Promptrecognition and treatment may prevent further complications.

     

Long-term botulinum toxin efficacy, safety, and immunogenicity.

To determine the long-term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow-up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 +/- 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0-to-4 scale (0 = no effect; 4 = marked improvement) was 3.7 +/- 0.6 and the mean total duration of response was 15.4 +/- 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab-negative patients, 16 resumed responsiveness after dose adjustments and 2 persisted as nonrespondents. Except for 1 patient, the 4 Ab-positive and the 2 clinical nonresponders are being treated with BTX-B. This longest reported follow-up of BTX injections confirms the long-term efficacy and safety of this treatment.     

Treatment of upper limb dystonia with botulinum toxin

The use of botulinum toxin A (BTX A) in upper limb dystonia is gaining increasing acceptance and it has recently been suggested that it be considered as first line treatment.(1) We have reviewed our experience since 1991 of treating 20 cases of upper limb dystonia. 14 patients had task-specific dystonias (6 simple writer's cramp, 5 dystonic writer's cramp, 3 musician's cramp) and 6 had secondary focal or segmental dystonias (4 with early cortico-basal degeneration). All patients had electromyography to both determine and guide muscle selection. Pre- and post-treatment video as well as questionnaires formed the basis for outcome assessment. Botulinum toxin therapy was clearly beneficial in about two-thirds of those with primary upper limb dystonia, a condition affecting young adults (mean onset 32.9 years). In contrast, BTX A was far less effective in secondary upper limb dystonias which occurred in the elderly (mean onset 71.7 years). Optimal treatment strategies are discussed. In conclusion, botulinum toxin is an effective form of treatment for primary upper limb dystonia; its role in late onset secondary dystonia is mainly palliative.     

Neurological manifestations in Wilson's disease: Report of 119 cases.

We describe the neurological manifestations of 119 patients with WD (93 index cases and 26 affected family members) seen between 1963 and 2004. The mean age at symptoms onset was 19.6 years (range, 7-37 years). Medical records were reviewed for the patient's first neurological examination. The most frequent neurological manifestations observed were dysarthria (91%), gait disturbance (75%), risus sardonicus (72%), dystonia (69%), rigidity (66%), tremor (60%), and dysphagia (50%). Less frequent manifestations were chorea (16%) and athetosis (14%). Rare neurological presentations were seizures (4.2%), and pyramidal signs (3%).     

Low-dose botulinum toxin-a treatment of cervical dystonia - a double-blind,randomized pilot study

The purpose of the study was to evaluate the clinical efficacy of low-dose botulinum toxin (BTX) treatment of cervical dystonia in a double-blind, randomized pilot study. Thirty-one patients with cervical dystonia and a minimum of 2 previous Dysport treatments received either a mean total target dose of 547 +/- 113 mouse units (MU) (group A, 500 MU Dysport/ml) or a 4-times-diluted preparation 130 +/- 32 MU (group B, 125 MU Dysport/ml). Assessment was made before and 4 weeks after the injection using Toronto Western Spasmodic Torticollis Rating Scales (TWSTRS). Additionally, a self-response scale evaluated the patients' subjective condition for 12 weeks after injection. TWST rating before and after injection revealed comparable clinical improvement in both groups. The severity of cervical dystonia at study entry had no effects on therapeutic effects of either preparation. Self-rating revealed comparable subjective improvement in both groups; however, 3 patients of group B received reinjections due to insufficient effects of the injection. Our findings suggest that low-dose treatment of cervical dystonia with Dysport may be clinically effective during maintenance therapy, at least for a limited period of time. Long-lasting effects of previous Dysport treatments at conventional doses and possibly improved diffusion of a highly diluted toxin preparation may have contributed to the effects of the low-dose regimen. Our data emphasize the need for further studies in order to clearly identify optimal toxin preparations for therapeutic uses of BTX-A in neurologic disorders.     

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.     

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.     

Evidence-based medicine in botulinum toxin therapy for cervical dystonia

Early controlled studies of botulinum toxin (BTX) in cervical dystonia were unblinded and indicated that BTX injections are more successful than medication. In this article, the use of botulinum toxin (BTX) in cervical dystonia is reviewed according to evidence-based medicine. To document the efficacy of BTX, there have been a number of prospective, placebo-controlled studies of the use of BTX in cervical dystonia. Most were double-blind, some included videotapes to provide blinded objective assessments. The more recent studies of BTX in cervical dystonia focused on particular issues such as utility of EMG guidance, comparison to anti-cholinergic treatment, BTX serotype B in BTX type A resistant and non-resistant patients and different dosages. Despite the wealth of data generated with prospective placebo-controlled studies on the effectiveness of BTX in cervical dystonia, there is uncertainty on which outcome measures to use to express the efficacy of treatments for cervical dystonia. Disease specific instruments to measure quality of life in cervical dystonia have not been used so far. Data on the use of BTX for cervical dystonia have long been restricted to small series of patients reflecting exclusively the experience of individual specialized centers.     

Evidence-based medicine in botulinum toxin therapy for cervical dystonia

Early controlled studies of botulinum toxin (BTX) in cervical dystonia were unblinded and indicated that BTX injections are more successful than medication. In this article, the use of botulinum toxin (BTX) in cervical dystonia is reviewed according to evidence-based medicine. To document the efficacy of BTX, there have been a number of prospective, placebo-controlled studies of the use of BTX in cervical dystonia. Most were double-blind, some included videotapes to provide blinded objective assessments. The more recent studies of BTX in cervical dystonia focused on particular issues such as utility of EMG guidance, comparison to anticholinergic treatment, BTX serotype B in BTX type A resistant and non-resistant patients and different dosages. Despite the wealth of data generated with prospective placebo-controlled studies on the effectiveness of BTX in cervical dystonia, there is uncertainty on which outcome measures to use to express the efficacy of treatments for cervical dystonia. Disease specific instruments to measure quality of life in cervical dystonia have not been used so far. Data on the use of BTX for cervical dystonia have long been restricted to small series of patients reflecting exclusively the experience of individual specialized centers.

     

The characteristics of side-effects of bromperidol in schizophrenic patients

The characteristics of the side-effects of bromperidol was investigated in 33 acutely exacerbated schizophrenic patients. The most frequently observed side-effects were extrapyramidal symptoms. Acute dystonia developed in 10 of 33 patients, and the mean age was significantly lower (P < 0.05) in patients with dystonia (27.3 +/- 6.2 years) than that in patients without dystonia (41.5 +/- 12.9 years). Plasma drug concentrations were not associated with side-effects. These findings suggest that acute dystonia is affected by age factor, and that daily dosage or monitoring of drug concentration is unlikely to be a useful marker for the prediction of side-effects during bromperidol treatment.     

Continuous subcutaneous lisuride infusion in OPCA

Summary Four patients with sporadic olivopontocerebellar atrophy (OPCA) and severe signs of Parkinsonism received continuous subcutaneous lisuride infusion via a small external pump. All 4 patients benefitted from this treatment: 3 showed an overall improvement in motor performance, in 1 patient mainly dysphagia and dysarthria improved. Therapeutic benefit lasted for at least 6 months of follow up. With a daily dose of 1.0 mg of subcutaneous lisuride, treatment limitations were reached in the form of dysphagia, probably due to oropharyngeal dystonia. Subcutaneous lisuride infusion should be taken into consideration in OPCA patients with signs of Parkinsonism if oral dopaminergic treatment has failed earlier on.     

Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period.

Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long-term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10-year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty-eight percent of patients discontinued treatment during the follow-up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction.     

Severe dysphagia after botulinum toxin injection for cervical dystonia in multiple system atrophy.

A 71-year-old woman was treated by botulinum toxin (BTX) type A injections for cervical dystonia related to a multiple system atrophy (MSA). A few days later and persisting for the next 4 months, she developed a severe dysphagia, requiring nasogastric feeding. This implicates cautious use of BTX in a case of MSA.     

Clozapine treatment in oromandibular dystonia

Oromandibular dystonia (OMD) is a form of focal dystonias, which can be associated with substantial disability and is frequently refractory to all antidystonic therapies. Clozapine is a dibenzodiazepin derivative atypical neuroleptic that has been reported to be effective in the treatment of primary or symptomatic dystonia. We report here two patients with severe OMD refractory to other antidystonic therapies, who had substantial improvement with clozapine. We suggest that clozapine should be considered in patients with OMD who fail to response to other treatments.     

Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes

We used single fiber electromyography (SFEMG) to study 42 patients who had enrolled in a double-blind, placebo-controlled trial undertaken to assess the efficacy of botulinum toxin (BTX) injection of neck muscles to treat torticollis. SFEMG in a limb muscle was performed before treatment, 2, and 12 weeks after injection of placebo or BTX. Before treatment, the mean jitter was 26.8 microsec in patients who were to receive BTX, and 25.7 microsec in the placebo group. Two weeks after injection, mean jitter in the group receiving BTX was 43.6 microsec. In the placebo group, it was 26.5 microsec (P = less than .05). Twelve weeks after injection, mean jitter in the BTX group was 35.5; for the placebo group it was 24.5. Fiber density did not change in any patient during the study. There were no remote clinical effects of BTX. Injection of BTX into muscles affected with focal dystonia is a promising and safe treatment, but there are subclinical effects on uninjected muscles.