Cranial-cervical Dystonia Research Articles

Cervico-facial dystonia as depicted in sculpture before its scientific description

The authors describe a sculpture from Daumier, called “Le Hargneux” (The peevish one), whose physiognomic study evokes hitherto unrecognized cranial-cervical dystonia. It is probably the first representation of dystonia in sculpture, before its scientific identification by Horatio Wood, in 1887.

Sensory trick in upper limb dystonia

IntroductionSensory trick is a specific maneuver that temporarily improves dystonia that is usually observed in 44%–89% of patients with cranial-cervical dystonia and in 20% of patients with upper limb dystonia. This study aimed to assess the prevalence of sensory trick in a cohort of 37 patients with idiopathic adult-onset upper limb dystonia and to determine whether sensory trick can be a useful tool to distinguish dystonic and non-dystonic tremor. MethodsThirty-seven right-handed patients with idiopathic upper limb dystonia and disturbed handwriting and 19 patients with non-dystonic action tremor in the upper limb causing writing disturbances participated into the study. Patients were asked to write a standard sentence twice, before and after applying a standardized sensory trick (gently grabbing right wrist with his left hand). Readability of the two sentences was assessed by three observers blinded to diagnosis. ResultsFive/37 patients (13%) self-discovered ST over disease history, while performing the standardized trick maneuver improved handwriting in 14/37 patients (38%). Interobserver agreement on the effectiveness of sensory trick among the three observers yielded a kappa value of 0.86 (p < 0.0001). The standardized trick was effective in 8/19 patients with dystonic tremor (42%) and in 0/19 patients with non-dystonic tremor (p = 0.003). ConclusionThe results of applying a standardized non-spontaneous trick demonstrated that, in upper limb dystonia, ST may be more frequent than usually observed. Effective sensory trick, when present, may be a hallmark of idiopathic dystonia. The lack of effective sensory trick may help to identify non dystonic upper limb tremor.

20. Habituation of somatosensory evoked potentials in dystonia

Dystonia is a disorder of both motor and sensory function, clinically characterized by involuntary movements, abnormal postures, and abnormal sensory discrimination. Whereas most data on the physiology of motor cortices are consistent with a general frame of reduced inhibition and maladaptative plasticity, electrophysiological data in sensory cortices are controversial. Habituation refers to response decrement with repeated stimulation, and reflects mechanisms that alter synaptic effectiveness in the stimulated cortex through LTD or LTP-like phenomena. We investigated somatosensory evoked potentials (SEPs) habituation in patients with dystonia and hemifacial spasm (HSF). We recorded median-nerve SEPs in 28 patients (8 cranial, 4 cervical, 1 cranial-cervical dystonia, 15 HSF) and 18 age-matched controls. We measured N20-P25 amplitudes from 3 blocks of 200 sweeps, and assessed amplitude of block 1, and habituation from amplitude changes between the 3 sequential blocks. ANOVA showed a main effect of factor group ( F =4.4 p =0.015). In patients with dystonia, SEP amplitudes were normal in block 1, but thereafter failed to habituate ( p =0.03). Patients with hemifacial spasm had normal SEP amplitudes and habituation ( p =0.98). SEP habituation is altered in dystonia indicating that somatosensory cortex becomes hyperresponsive. This abnormality is not the result of involuntary movements because in patients with HSF SEPs habituate normally.

Impaired cognitive functions in adult-onset primary cranial cervical dystonia

BackgroundAdult-onset primary dystonia is thought to be a purely motor disorder. Nevertheless, several studies provided evidence that sensory and psychiatric disturbances may contribute to the clinical spectrum of of dystonia, whereas evidence supporting cognitive impairment is still limited. MethodsA set of neuropsychological tests was administered to non depressed, non demented patients with cranial-cervical dystonia and healthy control subjects. The test battery included n-Back Task, Wechsler Memory Scale, Trail Making Test version A and B, and Wisconsin Card Sorting Test. ResultsAs compared with healthy control subjects of similar age, sex and socio-economic status, patients with cranial-cervical dystonia showed deficit on working memory functions revealed by n-Back task, impairment of mental control and visual reproduction subtests of Wechsler memory scale, deficit on information processing speed and set-shifting capacity revealed by Trail Making Test A and B. ConclusionPatients with cranial-cervical dystonia may have impairment in specific cognitive domains relative to working memory, processing speed, visual motor ability and short term memory. Probably, these deficits are not dependent on the clinical expression of dystonia but might rather reflect the cortical and subcortical changes highlighted by functional and VBM imaging studies in patients with different forms of dystonia.

Association of the Val66Met polymorphism of the BDNF gene with primary cranial–cervical dystonia patients from South-west China

BackgroundThe etiology of primary dystonia remains unclear. Recent genetic studies suggest that the Val66Met polymorphism of the BDNF gene is a genetic modifier in cranial–cervical dystonia in Caucasians. However, the finding is not consistent. Patients and MethodsA total of 193 patients with primary cranial–cervical dystonia from the Department of Neurology, West China Hospital of Sichuan University was included. From the same region, 216 healthy individuals were recruited as a control group. The Val66Met SNP was identified by polymerase chain reaction-restriction fragment length polymorphism. ResultsIn the present study, cervical dystonia (59.59%) was the most common type of primary cranial–cervical dystonia. No significant difference was found in the genotype and minor allele frequencies between all patients and controls, between cervical dystonia patients and controls, and between craniocervical dystonia patients and controls. However, significant differences were found in the genotype and minor allele frequencies of Val66Met SNP between blepharospasm (BSP) patients and controls (P=0.0080 and P=0.0042, respectively), and between BSP patients and patients with craniocervical derived from BSP (P=0.0010 and P=0.0002, respectively). ConclusionMinor allele “A” of BDNF Val66Met SNP may increase the risk for developing BSP and may be a protective factor for preventing BSP progressing to craniocervical dystonia. More association studies involving a larger number of participants are needed to confirm the present findings.

Dystonic Respiratory Dysregulation and Other Breathing Disorders Associated with Dystonia (P01.223)

Objective: To characterize respiratory complaints in dystonia. Background Respiratory difficulties are sometimes reported by patients with cranial-cervical dystonia (Mehanna R, Jankovic J. Respiratory problems in neurologic movement disorders. Parkinsonism Relat Disord. 2010;16: 628-38). This dystonia-related respiratory disorder, however, has not been well characterized. Design/Methods: We review 13 dystonic patients with various respiratory complaints and describe their symptoms and response to botulinum toxin injections. Results: The male to female ratio was 4/9 and the mean age 56.84. Cranial-cervical dystonia was the most frequent diagnosis affecting 9 (69%) patients. The cause of dyspnea was an upper airway dystonic obstruction in 9 (69%) patients, diaphragmatic dysfunction in one (8%) and a combination of both in the remaining 3 (23%) patients. Emergent tracheostomy was required in 2 (15%) patients. Among the 5 patients who underwent laryngoscopy, one had an adductor spasmodic dysphonia and 4 had normal vocal cord motion. Pulmonary function tests were performed in 5 patients and were normal. Videofluoroscopy was performed in 4 patients, showed decreased diaphragmatic movement in 2 and was normal in the 2 others. Among the 8 patient who received botulinum toxin injections and were not lost to follow up, 6 (75%) reported improvement in their respiratory distress and 2 (25%) reported no improvement. Conclusions: In some patients with dystonia, gasping, stridor, interrupted flow of speech, paradoxical breathing, dyspnea on exertion, and other respiratory symptoms suggest involvement of the upper airways, diaphragm, or both as a result of “dystonic respiratory dysregulation”. Botulinum toxin injections may be at least partially beneficial in some patients. This series of patients draws attention to respiratory distress as a potentially serious, even life-threatening, complication of dystonia. Disclosure: Dr. Mehanna has nothing to disclose. Dr. Jankovic has received personal compensation for activities with Allergan, Inc., Chelsea Therapeutics, Serono Inc., Merz Pharma, Lundbeck Research USA, Inc, Teva Neuroscience as a consultant. Dr. Jankovic has received personal compensation in an editorial capacity for Medlink: Neurology in Clinical Practice. Dr. Jankovic has received research support from Allergan, Inc, Allon Therapeutics, Ceregene, Inc., Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation, Serono Inc., Huntington9s Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Research USA, Inc.

Pan-American Consortium of Multiple System Atrophy. Preliminary Report (P06.079)

Objective: To describe the clinical and epidemiological characteristics of a series of patients diagnosed with MSA from 5 different centers from North America and Latin America. Background Multiple system atrophy (MSA) is a rare, sporadic and rapidly progressive neurodegenerative disorder that presents with parkinsonism, cerebellar ataxia and autonomic failure. Clinical, demographic and epidemiological data from different centers have provided valuable information concerning the natural history of MSA and have contributed to improved diagnostic criteria. Design/Methods: We retrospectively analyzed the clinical data of 78 patients with probable MSA from 5 different movement disorders centers from Argentina, Chile, Mexico and the United States. Evaluations were performed according to the clinical and imagenologic criteria recently established. No patients with probable MSA were confirmed by autopsy. Results: Forty women and 38 men were included, with a mean age of 65,5 ±10 years. Family history was negative in 64 patients and unknown in 14. Seventy five percent corresponded to MSA-P variant. Dysautonomic symptoms were observed in 90,8 % of individuals, including mictional urgency 84,6%, orthostatism 65,3%, “cold hands” 41,9%, and severe hypophonia 86%. Dysphagia, falls and cranial cervical dystonia were present in the majority of cases. Response to levodopa was poor and transitory. MR imaging showed putaminal atrophy in 16 patients and hyperintense putaminal rims in 13 and the “hot cross bun” sign in 6. The mean estimate survival was 6 years (range 1-14). Chile and Mexico were countries with greater “mestizo” populations. Conclusions: The present series presents preliminary data about MSA in centers from North America and Latin America. In spite of the great ancestry variability observed in this population, no differences were observed regarding the other Western series. Disclosure: Dr. Gatto has nothing to disclose. Dr. Chana has nothing to disclose. Dr. Etcheverry has nothing to disclose. Dr. Gallin has nothing to disclose. Dr. Miranda has nothing to disclose. Dr. Parisi has nothing to disclose. Dr. Sanguinetti has nothing to disclose. Dr. Rodriguez Violante has nothing to disclose. Dr. Litvan has nothing to disclose.

Meige Syndrome Relieved by Bilateral Pallidal Stimulation With Cycling Mode

Deep brain stimulation (DBS) of the bilateral globus pallidus internus (GPi) has been used effectively to treat dystonia. We report a patient with severe Meige syndrome who received bilateral GPi DBS with good improvement in symptoms during the first 24-month stimulation therapy. To decrease energy consumption and to prolong battery life, the stimulation parameters of the replaced programmable pulse generator were adjusted to the cyclic mode and the stimulator was turned off during nighttime sleep. The patient achieved similar good treatment effect with extended battery life in the following years. A 66-year-old woman with a 3-year history of severe cranial-cervical dystonia received stereotaxic surgery for bilateral GPi DBS therapy. The Burke-Fahn-Marsden dystonia score improved from 32 to 7.5. The effect lasted up to 24 months after therapy when the battery ran out of life. After careful evaluation, we adjusted the stimulation parameters of the second implantable pulse generator to the cyclic stimulation mode and programmed the stimulator to turn off automatically during nighttime sleep. The patient showed persistent good effect 36 months after starting use of the second implantable pulse generator. To treat dystonic symptoms effectively, stimulation parameters with higher energy consumption are usually required. For reducing the discomfort of repeated battery replacement within a short time and decreasing energy consumption in implantable pulse generator, cyclic mode stimulation could be considered in dystonic patients receiving bilateral GPi DBS.

Asian over-representation among patients with hemifacial spasm compared to patients with cranial–cervical dystonia

Background and purpose Hemifacial spasm (HFS) is a common movement disorder, but its prevalence in different populations has not been elucidated. Methods We reviewed all patients with HFS currently followed at the Baylor College of Medicine Movement Disorders Clinic and compared their demographic and clinical data with a control group of patients with cranial–cervical dystonia (CD). Results In contrast to patients with CD ( N = 145, mean age 48.64 ± 13.61 years), of whom 117 (80.69%) were Caucasians, 13 (8.97%) Hispanic, 10 (6.90%) African-American, and 5 (3.45%) were of Asian origin, there were 81 (61.36%) Caucasians, 24 (18.18%) Hispanic, 13 (9.85%) African-Americans, and 14 (10.61%) Asians in the HFS group ( N = 132, mean age 49.33 ± 13.25). Although there was no statistical difference in the age and gender distribution between the two groups, the frequency of Asians in HFS group was 3.1 times higher than that in CD group ( P < 0.01). Furthermore, the prevalence of Asians among patients with HFS was nearly twice the estimated prevalence of Asians in a general Houston population (5.48%). Conclusion Our results support the observation that HFS is much more common in the Asian population than in other populations. Further epidemiological, genetic, imaging and anatomic studies are needed to understand the apparent difference in the prevalence of this peripherally induced movement disorder.

Brain‐derived neurotrophic factor and risk for primary adult‐onset cranial‐cervical dystonia

Adult-onset dystonia may be related, amongst other factors, to abnormal neuronal plasticity in cortical and subcortical structures. Brain-derived neurotrophic factor is a major modulator of synaptic efficiency and neuronal plasticity. Recent works documented that a single nucleotide polymorphism (SNP) of the BDNF gene, the Val66Met SNP, modulates short-term plastic changes within motor cortical circuits. In this study we aimed at exploring the effect of this SNP upon the risk of developing common forms of primary adult-onset dystonia. We explored the influence of the Val66Met SNP of the BDNF gene on the risk of cranial and cervical dystonia in a cohort of 156 Italian patients and 170 age- and gender-matched healthy control subjects drawn from the same population. The presence of the rare Met allele was not significantly associated with the diagnosis of dystonia (age- and gender-adjusted odds ratios of 1.22, P = 0.38). The study had a >90% power to detect a 50% change in the risk of developing cranial-cervical dystonia associated with the presence of the Met allele. Moreover, there was no relationship between Val66Met SNP and age at dystonia onset or type of dystonia. Our data do not support the common variant Val66Met of the BDNF gene as an etiologic factor shared by the various forms of primary adult-onset dystonia.

Induction of Bradykinesia with Pallidal Deep Brain Stimulation in Patients with Cranial-Cervical Dystonia

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an effective and well-tolerated treatment for idiopathic generalized dystonia. More recently, it has been applied as a treatment for focal and segmental dystonias. This patient population offers an opportunity to study the effects of alteration of pallidal outflow on previously normal limb function. Methods: We sought to retrospectively characterize the extent of novel GPi DBS-induced adverse motor effects in patients with adult-onset cervical and cranial-cervical dystonia using a questionnaire, and compared the findings to dystonia improvement as measured by standard scales. Results: Despite significant improvement in dystonia (65% in mean Burke-Fahn-MarsdenDystonia Rating Scale motor score, p < 0.005, and 59% in mean Toronto Western Spasmodic Torticollis Rating Scale score, p < 0.008), slowing and difficulty with normal motor function was reported in previously nondystonic extremities in 10 of 11 patients. Symptoms were common in both upper and lower extremities and included new difficulties with handwriting (82%), getting up from a chair or in/out of a car (73%), and walking (45%), and were not associated with aberrant lead placement near the internal capsule. Conclusion: Although GPi DBS was shown to be effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.

Pallidal deep brain stimulation in patients with cranial–cervical dystonia (Meige syndrome)

Idiopathic cranial-cervical dystonia (ICCD) is an adult-onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.

Risk factors for spread of primary adult onset blepharospasm: a multicentre investigation of the Italian movement disorders study group

OBJECTIVESLittle is known about factors influencing the spread of blepharospasm to other body parts. An investigation was carried out to deterrmine whether demographic features (sex, age at blepharospasm onset), putative...

Auditory brain-stem responses in blepharospasm

The auditory brain-stem response (ABR) has been reported to detect abnormalities in both the auditory pathways and in adjacent structures. Ten of 35 consecutive patients with blepharospasm were found to have abnormal ABRs involving poor form and delayed peak latency of positive components III or V. Abnormal ABRs in approximately 30% of patients with essential blepharospasm suggest pathology in the brain-stem of a substantial proportion of patients with this form of cranial-cervical dystonia.

Genetic Contribution to Idiopathic Adult-Onset Blepharospasm and Cranial-Cervical Dystonia

A family study in 29 patients with idiopathic adult-onset blepharospasm (n = 16) and cranial-cervical dystonia (n = 13) was undertaken by examining 189 first-degree relatives. Six relatives with dystonia were identified in 6 families. A further 3 affected relatives, now deceased, were from 2 other families. All the secondary cases were parents or siblings. There was a tendency for affected relatives to have the same type of dystonia of index patients. To assess the significance of secondary cases we compare the incidence of affected siblings between probands and their spouses. Dystonia was found in 5 out of 120 proband siblings whereas none of the 142 spouse siblings was affected (p < 0.05). Segregation analysis suggested an autosomal-dominant transmission and reduced penetrance or, alternatively, polygenic inheritance.

Acoustic reflex abnormalities in cranial-cervical dystonia.

Previous anatomic and physiologic studies suggest brainstem dysfunction in cranial-cervical dystonia. To further explore this, we studied suprathreshold acoustic reflex waveforms in 15 such patients. A unique feature of this technique is its ability to reject movement artifacts before averaging the acoustic reflex waveforms. Thirteen patients (87%) showed some abnormality in reflex waveform morphology. There were both amplitude and latency abnormalities. These findings support the hypothesis that cranial-cervical dystonia reflects dysfunction of the brainstem.

Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm.

In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm.