Botulinum toxin A in patients with oromandibular dystonia: long-term follow-up

OBJECTIVE: To study the safety and efficacy of botulinum toxin A (BTX) in patients with oromandibular dystonia (OMD) and to compare the treatment results of the various subtypes of OMD. BACKGROUND: OMD is one of the most challenging forms of dystonia to treat. Pharmacologic therapies are generally not effective, and there are no surgical alternatives. METHODS: Of 202 patients diagnosed clinically to have OMD in a movement disorders clinic over a period of 10 years, 162 patients satisfied the study inclusion criteria. The masseters and submentalis complex were the only two muscle groups injected with BTX in this group of patients. RESULTS: The mean age was 57.9+/-15.3 years and the mean follow-up period was 4.4+/-3.8 years. More than half the patients had jaw-closing (JC) dystonia. A total of 2,529 BTX treatments were administered into the masseter muscles, submentalis complex, or both during a total of 1,213 treatment visits. The mean doses of BTX (per side) were 54.2+/-15.2 U for the masseters and 28.6+/-16.7 U for the submentalis complex. The mean total duration of response was 16.4+/-7.1 weeks. The mean global effect of BTX was 3.1+/-1.0 (range, 0 to 4, where 4 equals the complete abolition of the dystonia), with the JC dystonia patients responding best. Fifty-one patients (31.5%) reported adverse effects with BTX in at least one visit. Complications such as dysphagia and dysarthria were reported in 135 (11.1%) of all treatment visits. CONCLUSIONS: BTX is a safe and effective long-term treatment for OMD. JC dystonia responds better than jaw-opening or mixed dystonias, and the treatment of the latter types of OMD are more likely associated with dysphagia and dysarthria. Jaw-opening dystonia can be treated successfully by injecting the submentalis complex.     

Atypical phenotypes of DYT1 dystonia in three children

DYT-1 dystonia is the most common primary dystonia seen in childhood. It is an autosomal dominantly inherited disorder caused by deletion of a GAG triplet in exon 5 of the DYT1 gene. It characteristically starts in a distal limb during late childhood, subsequently spreads to involve other body regions sparing oromandibular muscles. However, clinical presentation can vary remarkably with respect to age, site of onset and progression. In this study we present three early-onset DYT-1 dystonia patients who are atypical according to age of onset and localization. Dystonia has started at 2, 3 and 7 years of age and generalized to involve other limbs in all patients and also oromandibular muscles in one patient. None of them have benefited from medical treatments including L-dopa. All had normal brain MRI scan, a history of normal birth without significant perinatal asphyxia, infection or trauma and all are neurodevelopmentally otherwise normal. Conclusion: In children with dystonia; if brain imaging is unremarkable and when there is no history of CNS disorders such as perinatal asphyxia, infections, drug exposure or trauma; genetic analysis for GAG deletion of DYT-1 gene may be performed even if dystonia starts at a very young age or it spreads to involve oromandibular muscles.     

Service-based survey of dystonia in munich

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000.     

Lower limb involvement in adult‐onset primary dystonia: frequency and clinical features

Background and purpose: Despite the growing number of reports describing adult‐onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult‐onset dystonia. Methods: From outpatients with adult‐onset primary dystonia attending nine Italian University centres for movement disorders we consecutively recruited 579 patients to undergo a standardized clinical evaluation. Results: Of the 579 patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone (n = 4, 0.7%) or as part of a segmental/multifocal dystonia (n = 7, 1.2%). The age at onset of LLD (47.9 ± 17 years) was significantly lower than the age at onset of cranial dystonias (57.9 ± 10.7 years for blepharospasm, and 58.9 ± 11.8 years for oromandibular dystonia) but similar to that of all the other adult‐onset primary dystonias. The lower limb was either the site of dystonia onset (36.4%) or the site of dystonia spread (63.6%). In patients in whom LLD was a site of spread, dystonia seemed to spread following a somatotopic distribution. Only one patient reported a recent trauma involving the lower limb whereas 36.4% of the patients reported pain at the site of LLD. Only 64% of our patients needed treatment for LLD, and similarly to previously reported cases, the most frequently tried treatments was botulinum toxin and trihexyphenidyl. Conclusion: The lower limb is an uncommon but possible topographical site of dystonia in adulthood that should be kept in consideration during clinical evaluation.     

Jaw-opening oromandibular dystonia secondary to Wilson's disease treated with botulinum toxin type A

We have reported a case series of five patients with jaw-opening oromandibular dystonia secondary to Wilson's disease (WD), in which the patients were treated with botulinum toxin type A (BTX-A). In all cases, dystonia score was partially reduced three weeks after injections. The most common side effect was transient mild dysphagia. This preliminary study showed that jaw-opening oromandibular dystonia in WD may be partially responsive to the use of BTX-A.     

Epidemiology of focal and generalized dystonia in Rochester, Minnesota

The epidemiology of generalized and focal dystonias was investigated in the Rochester, Minnesota, population over the period 1950-1982. The crude incidence of generalized dystonia was 2 per million persons per year, and for all focal dystonias combined, 24 per million per year. The crude prevalence rate was 34 per million persons for generalized dystonia and 295 per million persons for all focal dystonias. Torticollis was the most common focal dystonia; essential blepharospasm, oromandibular dystonia, spasmodic dysphonia, and writer's cramp were less common and had roughly equal incidence and prevalence rates.     

Sleep and cranial dystonia.

A nocturnal polygraphic study was performed on 10 patients with cranial dystonia (blepharospasm (BS) and oromandibular dystonia (OMD)). All patients showed impaired sleep efficiency and reduced slow and REM sleep, more marked in subjects with severe dystonia. Abnormal muscular activity decreased progressively with deeper sleep and during the first hours of the night, without disappearing. A disordered hypnic++ pattern and impaired motor control even during sleep are typical features in cranial dystonia.     

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.     

Pathological report of four patients presenting with cranial dystonias

Secondary dystonias and experimental models of dystonia suggest that mechanisms responsible for primary dystonias may lie in the basal ganglia or brainstem. A histological study has been done in three patients with cranial dystonia (blepharospasm with oromandibular dystonia in two, blepharospasm alone in one), and one patient with craniocervical dystonia (oromandibular dystonia with retrocollis). In the patient with blepharospasm alone, an angioma, 0.5 mm in diameter, was found in the dorsal pons at the site of the central tegmental tract, confirming that some patients presenting with primary dystonias may have longstanding lesions in the brainstem. In the three other cases, the striatum, pallidum, thalamus, and brainstem were examined and cell populations in the putamen, substantia nigra, and inferior olives were compared with age-matched controls, but no significant abnormality was found.     

A family with a hereditary form of torsion dystonia from Northern Sweden treated with bilateral pallidal deep brain stimulation

To evaluate pallidal DBS in a non‐DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non‐DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and “on” stimulation after a mean of 2.5 years (range 1–3) using the Burke‐Fahn‐Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 ± 24 to 9 ± 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia. © 2009 Movement Disorder Society     

Five-year experience in the treatment of focal movement disorders with low-dose dysportTM botulinum toxin

We report the results of botulinum toxin type A (Dysport^TM, Porton Products, UK) treatment over 5 years in 107 patients with blepharospasm, Meige's syndrome, oromandibular dystonia, hemifacial spasm, cervical dystonia, and writer's cramp. Electromyography was used to localize dystonic muscles and guide Dysport^TM injections in Meige's syndrome, oromandibular dystonia, cervical dystonia, and writer's cramp. All but 2 Meige's syndrome and 2 writer's cramp patients responded to treatment. Improvement was dramatic in blepharospasm (79%) and hemifacial spasm (90%); pronounced in cervical dystonia (74%); and moderate in Meige's syndrome (53%), oromandibular dystonia (57%), and writer's cramp (34%). Although Dysport^TM doses were 50–75% lower than usually reported, response and improvement rates as well as relapse intervals were similar to those of others. To treat cervical dystonia relapses, only 50% of the initial dose was required for continued optimal relief of symptoms. Low-dose Dysport^TM was associated with a very low incidence of dysphagia in cervical dystonia. © 1995 John Wiley & Sons, Inc.     

Prevalence of movement disorders in men and women aged 50-89 years (Bruneck Study cohort): a population-based study

BACKGROUND: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. METHODS: As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. FINDINGS: The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced. INTERPRETATION: There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.     

Development of Parkinson's disease in patients with blepharospasm.

The liability to develop parkinsonian symptoms was evaluated in 105 outpatients with idiopathic blepharospasm (IBS; 54 cases) or IBS associated to oromandibular dystonia (Meige's syndrome; 51 cases) mean age 70.3 +/- 9.6 years, and compared with an age- and sex-matched population. Eleven patients developed Parkinson's disease in the blepharospasm group, whereas only 2 of 105 patients were affected in the control group. Our results suggest that patients with IBS either isolated or associated with oromandibular dystonia are more prone to develop parkinsonian symptoms.     

Phenotype of the DYT1 mutation in the TOR1A gene in a Polish population of patients with dystonia. A preliminary report

BACKGROUND AND PURPOSE: DYT1 dystonia is the most common form of inherited primary dystonia. The aim of the study was: 1) to evaluate the prevalence of the DYT1 mutation in a population of Polish patients with early-onset generalized dystonia and with other forms of familial dystonia, 2) to evaluate the frequency of the DYT1 mutation in patients with writer's cramp, 3) to characterize the phenotype of the DYT1 mutation in the Polish population, and 4) to define the group of patients in whom genetic testing is recommended. MATERIAL AND METHODS: The following groups of patients were included in the study: 1) patients with early-onset (<30 years) generalized dystonia and those patients with onset after age 30 years who have relatives with early-onset dystonia, 2) patients with writer's cramp (focal or as part of segmental dystonia) independently of age of onset, 3) asymptomatic (adult only) relatives of the diagnosed DYT1 carriers. Genetic tests were performed in 63 subjects---28 sporadic cases of dystonia, 20 patients with familial dystonia, and 15 asymptomatic relatives of patients with confirmed DYT1 mutation. RESULTS: The DYT1 mutation was found in 17 subjects--10 patients with dystonia and 7 asymptomatic relatives (from 6 families). In all mutation carriers dystonia occurred in one limb before age 26 years. In 8 patients, generalization of dystonia was observed and in 2 cases it remained in a focal form. CONCLUSIONS: 1. The prevalence of DYT1 mutation among patients with early-onset (相似文献   

The prevalence of primary dystonia: A systematic review and meta‐analysis

Dystonia is a hyperkinetic movement disorder characterized by sustained muscle contractions that produce repetitive movements and abnormal postures. Specific information on the prevalence of dystonia has been difficult to establish because the existing epidemiological studies of the condition have adopted different methodologies for case ascertainment, resulting in widely differing reported prevalence. Medline and Embase databases were searched using terms specific to dystonia for studies of incidence, prevalence, and epidemiology. All population‐based studies reporting an incidence and/or prevalence of primary dystonia were included. Sixteen original studies were included in our systematic review. Fifteen studies reported the prevalence of dystonia, including 12 service‐based and three population‐based studies. We performed a meta‐analysis on the results of the service‐based studies, and were able to combine data on the prevalence of several dystonia subtypes. From these studies, we calculated an overall prevalence of primary dystonia of 16.43 per 100,000 (95% confidence interval [CI]: 12.09–22.32). The prevalence of dystonia reported in the three population‐based studies appears higher than that reported in the service‐based studies. Only 1 of the 16 studies reported an incidence of cervical dystonia. This corresponded to a corrected incidence estimate of 1.07 per 100,000 person‐years (95% CI: 0.86–1.32). Despite numerous studies on the epidemiology of dystonia, attempting to determine an accurate prevalence of the condition for health services planning remains a significant challenge. Given the methodological limitations of the existing studies, our own prevalence estimate of primary dystonia likely underestimates the true prevalence of the condition. © 2012 Movement Disorder Society     

Community survey of primary dystonia in the city of Kolkata, India.

An epidemiological study on dystonia has not been reported from India. As part of a major study to find out the prevalence of major neurological disorders in the large urban city of Kolkata, Eastern India, we planned to determine the prevalence of primary dystonia. The study design was a cross-sectional study of a sample population obtained through stratified random selection and conducted in a two-stage procedure of screening by a nonprofessional team followed by confirmation of screened positive cases by the study neurologist. A total population of 52,377 was screened, and 29 subjects with dystonia were diagnosed. Out of them 23 subjects had primary dystonias [crude prevalence rate (CPR), 43.91/100,000; 95% confidence interval (CI), 28.41-64.81; age-standardized rates to world standard population, 49.06 (95% CI,31.74-72.41)] and all cases were focal type and predominantly of limb dystonia variety. Mean onset of dystonias were earlier in women (43.5 years) as compared to men (46.6 years). Thus our study on primary dystonia shows higher prevalence when compared with that of many studies globally, predominantly of focal type, earlier onset among women, and more cases of limb dystonias when compared with more prominent blepharospasm and cervical dystonias in western reports.     

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.     

Lingual protrusion dystonia: Frequency,etiology and botulinum toxin therapy

The purpose of this study was to examine lingual protrusion dystonia (LPD); its frequency, etiology and response to botulinum toxin therapy. Previous literature suggests that LPD is more frequently the result of heredodegenerative disease and that the use of botulinum toxin therapy in LPD is associated with significant adverse effects. This is a retrospective database and record review from a movement disorder clinic. Of 421 dystonia patients, we identified 17 with LPD (4%). Of these cases, the diagnoses were: primary cranial dystonia (5), primary generalized dystonia (2), tardive dystonia (7), heredodegenerative disease (1), multifactorial (1) and post-infectious (1). All primary cases had concomitant oromandibular dystonia. In some secondary cases the LPD was the only cranial feature. Nine received botulinum toxin injections and 55.6% sustained moderate or marked improvement. Of 89 total botulinum toxin sessions, 66.3% had an excellent response, and 92.1% had some response. 97.8% of the sessions resulted in no significant adverse effects. On one occasion one patient developed severe dysphagia requiring placement of a percutaneous gastrostomy (PEG) tube. We conclude that LPD is rare, most commonly the result of tardive and primary dystonia. Botulinum toxin therapy may be very effective but needs to be utilized with care because of the possibility for the development of dysphagia.     

The broadening application of chemodenervation in X-linked dystonia-parkinsonism (Part II): an open-label experience with botulinum toxin-A (Dysport®) injections for oromandibular, lingual, and truncal-axial dystonias

While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. BoNT-A (Dysport?) was injected in a total 109 dystonias of XDP. Our cohort included: 50 cases in the oromandibular area (jaw opening: 32 cases, jaw closing: 12 cases, and jaw deviation: 6 cases); 35 cases in the lingual area (tongue protrusion: 27 cases and tongue curling: 8 cases); and, 24 cases in the truncal-axial area (flexor: 12 cases, extensor: 7 cases, and lateral-extensor: 5 cases). Interestingly, pain, often a nonprominent symptom of dystonias, was frequently reported in 40/50 XDP cases with oromandibular dystonia and 18/24 XDP cases with truncal-axial dystonia. All BoNT-A procedures were performed under electromyography guidance. A "high potency, low dilution" BoNT-A protocol was applied for oromandibular, lingual, cranial, cervical, and distal limb dystonias; whereas for dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol was applied. Outcomes measures included: the global dystonia rating scale (DRS) and pain visual analog scale (VAS) reduction at week 4; duration of BoNT-A effects; and, side effect profile. The median DRS score after 4 weeks was 3 ("substantial improvement") for oromandibular and lingual dystonias and 2 ("moderate improvement") for truncal-axial dystonias. Pain reduction was significantly reduced (75%-80% in oromandibular; 30%-80% in truncal-axial dystonias). The median duration of BoNT-A effect was 16 weeks for oromandibular, 12 weeks for lingual, and 11 weeks for truncal-axial dystonias. Compared to a generally safe and well-tolerated BoNT-A injections for truncal-axial dystonias, the oromandibular-lingual dystonias had the following frequency of adverse events: oromandibular--19% in jaw opening and 17% in jaw closing dystonias; lingual--19% in tongue protrusion and 13% in tongue curling dystonias. The most frequent adverse events were mouth dryness and dysphagia. Thus, BoNT-A injection working protocols may be adopted in XDP dystonia that adheres to cost minimization (e.g., lower dose end per selected muscle), while achieving some benefit, and potentially reduce the adverse event profile.     

Prevalence and diagnostic challenge of dystonia in Thailand: a service-based study in a tertiary university referral centre

Although the subspeciality of movement disorders was established in neurology more than 20 years ago, it is relatively new in Thailand, and while most physicians are generally aware of Parkinson's disease, they often are not familiar with dystonia. As one of the common movement disorders seen in general practice, a number of family and population studies have suggested that as many as two-thirds of patients with dystonia may be underdiagnosed and it is likely that misdiagnosis occurs frequently. Moreover, there is little information on the prevalence of dystonia in Thailand. The purpose of this study was to determine the prevalence and clinical profile of dystonia among Thai patients who came from the southern part of Bangkok, which is in the catchment area of Chulalongkorn University Hospital. In addition, the diagnostic accuracy of dystonia among referred patients was assessed. The medical records of 207 patients were reviewed and it was determined that a large proportion of them (71.9%) had focal dystonia with cervical dystonia being the most common form. Primary dystonia (68.1%) accounted for the majority of the cases. The prevalence of all forms of dystonia, primary dystonia and focal dystonia was 19.9, 13.6 and 14.3 per 100,000 persons, respectively. The diagnostic accuracy of dystonia among referred patients was 85.5%. The most common misdiagnosis was cervical spondylosis, followed by myofascial pain syndrome. Most patients had an average disease duration of 4 years before dystonia was finally diagnosed. Most patients with focal dystonia responded well to botulinum toxin therapy, with 13.3% suffering only mild transient adverse events. In spite of the limitations of this study, this data will initiate a process of increasing both patient and professional awareness of dystonia in Thailand.