Dystonia gravidarum: A new entity?

We describe cervical dystonia occurring in a 31-year-old, previously well, primigravid, primiparous Chinese woman at 4 weeks' amenorrhea, which was ameliorated with low-dose clonazepam and disappeared completely by the end of the second trimester without recurring despite her being tapered off benzodiazepine therapy. Investigations were unremarkable for structural and biochemical causes of dystonia. Chorea, paraballismus, and restless legs syndrome are known to occur during pregnancy, attributable to high estrogen levels. Dystonia, on the other hand, has not been described to occur de novo in pregnancy. This association should be considered in women of reproductive age who present with cervical dystonia.     

Botulinum toxin type A therapy during pregnancy.

Injection with botulinum toxin type A (Botox) is a safe and efficacious treatment for idiopathic cervical dystonia. We present the first case report of clinical Botox treatment during pregnancy. This patient underwent four apparently uncomplicated full-term pregnancies while receiving regular Botox treatments.     

Secondary cervical dystonia associated with structural lesions of the central nervous system.

We tested the hypothesis that structural lesions of the central nervous system (CNS) associated with cervical dystonia more commonly involve the cerebellum and its primary afferent pathways than basal ganglia structures. Cervical dystonia is the most common focal dystonia, the majority of cases are idiopathic, and only a small percentage of patients have a family history of dystonia or other movement disorders. Pathophysiological mechanisms operative in solely or predominantly appendicular dystonias such as writer's cramp and Oppenheim's dystonia, respectively, may not be directly applicable to axial dystonias. The localization of structural lesions of the CNS associated with secondary cervical dystonia may provide some insight into the neural structures potentially involved in primary cervical dystonia. The National Library of Medicine Gateway (from 1960) and a clinical database maintained by the senior author (from 1999) were searched for cases of secondary cervical dystonia associated with structural lesions of the CNS. Search terms included one or more of the following: dystonia, torticollis, cervical, secondary, and symptomatic. Lesion localization and type, patient age, patient gender, head position, occurrence of sensory tricks, and associated neurological findings were tabulated for each case. Structural lesions associated with cervical dystonia were most commonly localized to the brainstem and cerebellum. The remaining cases were equally divided between the cervical spinal cord and basal ganglia. Although inconsistent, head rotation tended to be contralateral to lesion localization. Additional neurological abnormalities were present in the majority of patients with secondary cervical dystonia. The relative paucity of basal ganglia pathology and concentration of lesions in the brainstem, cerebellum, and cervical spinal cord in patients with secondary cervical dystonia suggests that dysfunction of cerebellar afferent pathways may be important to the pathophysiology of primary cervical dystonia.     

Paroxysmal dystonia due to a lesion of the cervical cord: Case report

A 48 year old woman complained of mild weakness and paresthesias of the left limbs, followed 15 days later by episodes of paroxysmal dystonia of the left limbs occurring several times daily over 10 day period. Magnetic resonance imaging (MRI) of head and neck revealed a small area of altered signal in the T2-weighted sequences in the left posterolateral quadrant of the cord at the second cervical vertebra. An MRI scan 18 months later showed no lesion. This is the second case of paroxysmal dystonia with a single MRI lesion in the cervical region on record.

---

Sommario Una donna di 48 anni accusò lieve ipostenia e parestesie agli arti di sinistra. A 15 giorni dall'esordio di questa sintomatologia si manifestarono molti episodi giornalieri di distonia parossistica agli arti di sinistra, per la durata di 10 giorni. Un esame di Risonanza Magnetica Nucleare cerebrale e cervicale evidenziò, come unica lesione, una piccola zona di alterato segnale, nelle sezioni pesate in T2, nel quadrante postero-laterale sinistro del midollo cervicale alla altezza della seconda vertebra cervicale; a un controllo RMN a 18 mesi la lesione non era più evidente. Questo descritto è il secondo caso noto in letteratura di Distonia Parossistica con lesione unica alla RMN in regione cervicale.

     

Assessment of D216H DYT1 polymorphism in a Chinese primary dystonia patient cohort

Background: The D216H single‐nucleotide polymorphism (SNP) (rs1801968) in DYT1 exon 4 has been suggested to be a genetic modifier in primary dystonia. Methods: To further explore this question, we assessed rs1801968 variations in a cohort of 210 Chinese patients with primary dystonia devoid of DYT1 mutations. Results: We found that focal dystonia, specifically cervical dystonia, was the most common form of dystonia, with 8.1% of all the patients having a positive family history of dystonia. No association of the D216H SNP with primary dystonia was identified. In a subsequent subgroup analysis, the 216H allele was found to occur more frequently in patients with writer’s cramp, but no correlation was found between the allele and other forms of dystonia or age of onset. Conclusions: Our findings do not confirm that the allele contributes to the risk of D216H SNP primary dystonia.     

A new treatment for cervical vertigo with botulinum toxin

A new and unique treatment for cervical vertigo with botulinum toxin is presented for a woman who sustained neck trauma from being hit by a wave. A diagnosis of cervical vertigo and cervical dystonia was confirmed by history, physical exam, dystonia on EMG exam, and a negative test for benign paroxysmal positional vertigo.She experienced consistent resolution of her vertigo symptoms and pain after each treatment for a total of 5 treatments with botulinum toxin to the upper cervical muscles. This report appears to be the first to demonstrate the missing link between vertigo and cervical dystonia with pain. Chemodenervation was effective in treating cervical vertigo and is likely to have altered the cervical proprioceptive input by relaxing the overactive muscles and/or by decompression of cervical nerves.     

Temporal discrimination,a cervical dystonia endophenotype: Penetrance and functional correlates

The pathogenesis of adult‐onset primary dystonia remains poorly understood. There is variable age‐related and gender‐related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)—the shortest time interval at which two separate stimuli can be detected as being asynchronous—is abnormal both in patients with cervical dystonia and in their unaffected first‐degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age‐related and gender‐related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first‐degree relatives of 84 patients with cervical dystonia. In 24 unaffected first‐degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society     

Duloxetine-related tardive dystonia and tardive dyskinesia: a case report

Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers. Duloxetine-related tardive syndrome is rarely reported in the literature. We report one case of tardive dystonia and tardive dyskinesia occurring in a 58-year-old female with major depressive disorder, who developed distressing oral dyskinesia, mandibular dystonia with trismus and dystonia over left neck after treatment of duloxetine (30–60 mg per day) for 18 months. Despite discontinuation of duloxetine, she only obtained partial remission. Even though this association has been rarely reported, duloxetine may pose a potential risk of inducing tardive syndrome. Clinicians should cautiously detect early signs of movement abnormality when prescribing antidepressants.     

Orthopedic and neurological complications of cervical dystonia--review of the literature

Cervical dystonia is the most frequent form of focal dystonia. Further, cervical dystonia can occur as a feature of segmental or generalized dystonias and cerebral palsy. Treatment with botulinum toxin to relieve pain and improve functional and psychological outcome is effective, but expensive. However, pharmacoeconomic studies evaluating treatment and disease costs have not taken into consideration the long-term complications of cervical dystonia. Here we present a review of the medical literature on orthopedic and neurological complications arising from cervical dystonia, including cervical spine degeneration, spondylosis, disk herniation, vertebral subluxations and fractures, radiculopathies and myelopathies. In summary, complications are more often reported in generalized dystonia and cerebral palsy than in focal dystonia. The prevalence is not well established, published estimations go from 18 to 41% in selected populations. Awareness of the frequent occurrence of complications and screening for symptoms of radiculomyelopathy in patients with dystonia is essential to avoid irreversible spinal cord damage. Complications of cervical dystonia need to be taken into consideration when weighting risks and calculating costs of the disease and its treatment.     

Dystonia associated with atlantoaxial subluxation

A case of primary dystonia with atlantoaxial subluxation is reported. This 46-year-old man who was suffering from primary generalized dystonia since childhood presented with clinical features suggestive of recent onset of cervical myelopathy. Imaging studies confirmed presence of severe spondylotic changes in the cervical spine with cord compression along with atlantoaxial subluxation. It is important to identify this potentially dangerous complication, which may be surgically managed. This is the first case report in the literature about the association of atlantoaxial subluxation and primary dystonia.     

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.     

Mutation screening of GNAL gene in patients with primary dystonia from Northeast China

BackgroundMutations in GNAL have recently been identified as responsible for primary dystonia, however, GNAL mutations in Chinese patients with primary dystonia are not well characterized.Patients and methodsFifty-nine unrelated patients with cervical onset or cervical involved primary dystonia and 120 neurologically normal controls from Northeast China without mutations of TOR1A and THAP1 were all screened for mutation of GNAL gene.ResultsOne subject with adult-onset generalized dystonia was found have a novel nonsense GNAL mutation (c.284C>T, p.Ser95X). Another subject with adult-onset cervical dystonia was found harbor the c.932-7T>G tentative splice site mutation. Although another seventeen sequence variants were identified in both patients and controls, no disease association was found among these sequence variants.ConclusionsMutations in GNAL gene can cause adult-onset primary dystonia in Chinese patients, and the mutation frequency is 3.4% in cervical onset or cervical involved primary dystonia. This paper identifies the first case of GNAL dystonia in the Chinese population.     

Cervical dystonia following peripheral trauma

Abstract. Post-traumatic cervical dystonia as a diagnostic entity remains a subject of debate. Patients with cervical dystonia (CD) were asked to identify any significant illness prior to the onset of their CD. Sixteen patients of 95 respondents reported a history of injury in the four-week period prior to onset of their dystonia. A retrospective study of the clinical characteristics of the 16 patients with early post-traumatic CD (CD-PT) in comparison with the 52 patients reporting no antecedent trauma (CD-NT) was performed. In this comparison the CD-PT group had a significantly increased frequency of laterocollis, significantly more reported pain and more reported depression. Non-significant trends were noted for less responsiveness to botulinum toxin and less use of gestes antagonistes in the CD-PT group. There were no group differences in the presence of a family history of dystonia. Eleven of the CD-PT group had been or were currently involved in litigation. A sub-group of seven CD-PT patients had laterocollis, six of whom conformed to a clinical pattern of persistent non-spasmodic laterocollis with marked pain; all seven had been involved in litigation. This form of CD-PT is a distinct clinical entity and has an onset within hours or a few days of the trauma. In contrast, no significant differences were noted between patients with CD-NT and the eight patients with later onset of CD between 4 weeks and one year after peripheral trauma.     

The entity of young onset primary cervical dystonia.

Primary cervical dystonia is typically an adult onset condition with symptom onset usually in the fifth and sixth decade. Young onset (<28 years) is uncommon. We report 76 patients with cervical dystonia as a presenting or predominant feature, with disease onset before the age of 28. Male to female ratio was 1.24:1 and the mean onset age was 21 (3-28) years. A family history of tremor and/or dystonia was noted in 26.3%. Depression and anxiety attacks were present in 23.7%.Prior injury or surgery involving the neck was noted in 17.1%. 23 (30.3%) experienced spontaneous partial or complete remissions within the first 5 years of onset, but all relapsed. Cervical dystonia was predominantly rotational torticollis. 30% developed extra-nuchal dystonia and tremor affecting contiguous parts but in only one there was spread to affect the legs. All 15 patients tested for the DYT1 gene were negative. 74% responded favorably to botulinum toxin injections, whereas none of the 13 patients treated with L-Dopa preparations had a beneficial response. The distinctive features of this entity are discussed.     

Eating-induced facial myoclonic dystonia probably due to a putaminal lesion.

Myoclonic dystonia is considered a form of dystonia. We present the unusual case of a 36-year-old woman with HIV infection, who developed left facial myoclonic dystonia, triggered by eating in the setting of probable progressive multifocal leukoencephalopathy involving the contralateral basal ganglia.     

Chronic high-frequency globus pallidus internus stimulation in different types of dystonia: a clinical, video, and MRI report of six patients presenting with segmental, cervical, and generalized dystonia.

The results of deep brain stimulation (DBS) of the globus pallidus internus (Gpi) in six patients with generalized, focal, and segmental dystonia are presented. Pre- and postoperative assessments are given for one patient with generalized inherited dystonia and for five patients with idiopathic segmental or cervical dystonia. Clinical symptoms were evaluated before and 3-12 months after surgery using the Burke-Fahn-Marsden (BFM) dystonia rating scale for primary torsion dystonia and the Tsui scale for cervical dystonia. The Short-Form Health Survey (SF-36) was completed by each patient to document preoperative and postoperative health status. Also, neurological status was documented by video before and during chronic stimulation. Magnetic resonance imaging studies were performed to show the anatomical localization of the electrode leads. Five patients showed a progressive improvement within 7 days. One patient with cervical dystonia and Meige's syndrome showed no improvement for 3 months, but beneficial effects were observed after 12 months. On average, the BFM movement scale scores decreased by 72.5% and Tsui scale scores by 63%. SF-36 showed an improvement in health status by an average of 36% according to eight different health categories. We conclude that chronic high-frequency Gpi stimulation in different types of dystonia is a very effective and safe treatment.     

Pain processing in functional and idiopathic dystonia: An exploratory study

Background : Pain is often experienced by patients with functional dystonia and idiopathic cervical dystonia and is likely to be determined by different neural mechanisms. Objective : In this exploratory study, we tested the sensory‐discriminative and cognitive‐emotional component of pain in patients with functional and idiopathic dystonia. Methods : Ten patients with idiopathic cervical dystonia, 12 patients with functional dystonia, and 16 age‐ and sex‐matched healthy controls underwent psychophysical testing of tactile and pain thresholds and pain tolerance. We delivered electrical pulses of increasing intensity to the index finger of each hand and the halluces of each foot. Pain threshold and pain tolerance were respectively defined as the (1) intensity at which sensation changed from unpainful to faintly painful and (2) intensity at which painful sensation was intolerable. Results : No differences were found between the three groups for tactile and pain thresholds assessed in hands and feet. Pain tolerance was significantly increased in all body regions only in functional dystonia. Patients with continuous functional dystonia had higher pain tolerance compared to subjects with paroxysmal functional dystonia and idiopathic cervical dystonia. There was no correlation between pain tolerance and pain scores, depression, anxiety, disease duration, and motor disability in both groups. Conclusions : Patients with functional dystonia have a dissociation between the sensory‐discriminative and cognitive‐emotional components of pain, as revealed by normal pain thresholds and increased pain tolerance. Abnormal connectivity between the motor and limbic systems might account for abnormal pain processing in functional dystonia. © 2018 International Parkinson and Movement Disorder Society     

Treatment of cervical dystonia hand spasms and laryngeal dystonia with botulinum toxin

Summary One hundred and twenty-six patients with different forms of focal dystonia (89 with cervical dystonia, 12 with hand cramps and 25 with laryngeal dystonia) were treated with localised injections of botulinum toxin. Mean doses per muscle were 200 mouse units (m.u.) for treating cervical dystonia, 40–120 m.u. for forearm muscles in writers' cramp and 3.7 m. u. for the thyroarytenoid muscle in laryngeal dystonia. Responder rates have been above 80% in all patient groups and beneficial effects could be reproduced over follow-up periods of up to 4 years. The commonest side-effects were dysphagia after treatment of spasmodic torticollis, weakness of neighbouring muscles after injections for hand cramps and breathiness and hypophonia following laryngeal injections. All these were transient and generally well tolerated. It is concluded that botulinum toxin injections are a safe and effective treatment in all three types of focal dystonia.     

Modification of cervical dystonia by selective sensory stimulation

Cervical dystonia is often refractory to all forms of therapy. Many patients, however, are able to transiently abolish their spasms following a specific gesture that presumably enhances sensory input. Such observations prompted us to develop a protocol to determine if various forms of sensory stimulation could modify the motor control patterns in cervical dystonia. Surface EMG recordings of multiple neck and trunk muscles were obtained in 11 consecutive cervical dystonia patients. Baseline patterns of voluntary and involuntary muscle activation were established during a series of motor and non-motor tasks. The tasks were repeated during the application of vibratory or electrical stimulation to select muscle groups or to cutaneous and mixed nerves. Analysis of the results was made on the basis of paper and computer recordings of the data. Sensory stimulation decreased involuntary muscle activity and reduced spasms in 5 subjects. However, objective or subjective improvement usually occured only after specific stimuli were applied to specific anatomical sites. In these cases, the protocol identified the site at which a specific sensory stimulus could be applied to control the dystonia. we conclude that selective sensory stimulation can beneficially modify cervical dystonia in some patients. Such findings warrant further investigation of the use of sensory stimulation for control of cervical dystonia.     

Slowly progressive cerebellar ataxia and cervical dystonia: Clinical presentation of a new form of spinocerebellar ataxia?

We describe 5 cases with a rare combination of young-onset, slowly progressive cerebellar ataxia and cervical dystonia. Two were sporadic, whereas the other 3 were familial, including 2 from one family. The age of onset of these cases was between 16 and 37 years. The presenting symptom was cervical dystonia and/or dystonic head tremor in 3 patients and hand or lower limb tremor in 2. In 2 cases, cervical dystonia and/or dystonic head tremor developed approximately 6 to 10 years before cerebellar dysfunction, and in three they developed at the same time. Apart from cervical dystonia, there was mild dystonic limb involvement in 2 cases, but generalized dystonia was not seen. Cerebellar ataxia was slowly progressive. A literature search showed 10 cases of cervical dystonia associated with genetically undetermined (n = 5) or genetically proven (n = 5) spinocerebellar ataxia (SCA). When the genotype was known, these patients had either SCA3, 6, 7, or 12. However, our 5 cases (or their first-degree relatives) tested negative for SCA1, 2, 3, 6, and 7, and in the 4 cases (or their first-degree relatives) tested for SCA12, the result was negative. We propose that this rare phenotype manifesting as a combination of cerebellar ataxia and cervical dystonia may represent one or more new, as yet uncharacterized, genotypes of inherited young-onset spinocerebellar ataxia. Copyright Movement Disorder Society