INTRODUCTION:

Previously, controlled trials have demonstrated the efficacy and tolerability of fixed doses of incobotulinumtoxinA (Xeomin, NT 201, botulinum toxin type A free from complexing proteins) to treat cervical dystonia (CD). To explore the clinical relevance of these findings, this study evaluated long-term use of flexible dosing regimens of incobotulinumtoxinA in a setting close to real-life clinical practice.

METHODS:

Patients with CD received five injection sessions of incobotulinumtoxinA using flexible intervals (10-24 weeks) and dosing (≤300 Units) based on patients' needs. Outcome measures included Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), the Dystonia Discomfort Scale (DDS), Investigator Global Assessment of Efficacy (IGAE) and Patient Evaluation of Global Response (PEGR).

RESULTS:

Of 76 patients enrolled (men: 34%; naïve to botulinum toxin: 25%), 64 completed the study, receiving treatment over a duration of 49.3-114.1 weeks (total maximum duration: 121 weeks). Mean TWSTRS-Total and DDS scores significantly improved from study baseline to 4 weeks after each injection session (ranges of improvement: TWSTRS-Total: -11.7 to -14.3; DDS: -20.2 to -23.0). Up to 81.6% of investigators rated the efficacy as 'good' or 'very good' (IGAE) and up to 78.9% of patients rated the treatment response as 'improved' (PEGR). The most common adverse events were dysphagia, nasopharyngitis and headache.

CONCLUSIONS:

In this long-term study, incobotulinumtoxinA was administered using more flexible dosing regimens than those permitted in previous controlled trials. Repeated injections of highly purified incobotulinumtoxinA are effective and well tolerated for the treatment of CD in a setting close to real-life clinical practice.

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

Acute dyskinetic or dystonic reactions are a long-recognized complication of medications that alter dopamine signaling. Most reactions occur following exposure to agents that block dopamine receptors (e.g., neuroleptics). However, agents that increase dopaminergic transmission (such as methylphenidate) can also trigger acute dyskinesias. This has been previously reported only in patients also taking dopamine antagonists or, less commonly, in children with developmental abnormalities. The present report describes a previously healthy toddler who developed transient torticollis and orolingual dyskinesias following accidental exposure to methylphenidate. He had no preexisting movement disorder, central nervous system injury, or developmental abnormalities-in short, none of the previously reported risk factors for this side effect. The unique features of this case led to the hypothesis that developmental shifts in dopamine signaling were the basis for his particular sensitivity to methylphenidate. If confirmed, this hypothesis has implications for the treatment of common childhood attentional and behavioral disorders. The article includes a literature review of dyskinetic/dystonic reactions in children and the developmental regulation of dopamine metabolism.

INTRODUCTION:

Tongue protrusion dystonia can cause difficulty with speech, mastication, breathing, and swallowing. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a widespread therapeutic alternative for treating medically refractory dystonia. To our knowledge, detailed reports regarding DBS for tongue protrusion dystonia are rare. In this report, we describe two patients with "sticking out" tongue protrusion who had undergone bilateral GPi DBS.

METHODS:

Operations were performed with surface electromyographic (EMG) monitoring, microelectrode recording, and macrostimulation to identify the point at which tongue kinetic cells respond most effectively. The most effective location for active contacts was identified according to burst EMG response in the posteroventral GPi.

RESULTS:

Two years after DBS, total Burke, Fahn, and Marsden Dystonia Rating Scale scores of two patients were improved from 12.5 to 1 (92.0%) and from 13 to 1 (92.3%), respectively. One 58-year-old woman who lost 7 kg weight from not eating well improved enough to eat solid food and became free from choking. Another 54-year-old woman who had dysarthria and mumbled could speak more fluently and would not have complained difficulty in reading any more.

CONCLUSION:

Stimulation on posteroventral GPi for patients with idiopathic "sticking-out" tongue movement changes EMG pattern in orofacial muscles. This fact supports a reason for modulation of unknown circuit connecting tongue-specific area in motor cortex, and basal ganglia.

Mutations or exon deletions of the epsilon-sarcoglycan (SGCE) gene cause myoclonus-dystonia (M-D), but a subset of M-D patients are mutation-negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M-D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M-D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score ("new score"), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole-gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9-Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE-positive from SGCE-negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation-dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes. © 2013 Movement Disorder Society.

As Wilson's disease is both preventable and treatable, the diagnosis must not be missed. Despite this, it is usually misdiagnosed. Misdiagnosis and delay in treatment are clinically relevant because if left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability, and death. Those adequately treated have a normal life span. Wilson's disease is an autosomal recessive disease caused by mutations in the ATP7B gene. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, parkinsonism, ataxia, and choreoathetosis. Once the possibility of Wilson's disease is considered, diagnosis is straight forward. Currently available treatments, including zinc acetate and trientine, are generally well tolerated and effective.

Although tetrabenazine is widely used as an effective treatment for chorea and other hyperkinetic movement disorders, it has been associated with rare instances of parkinsonism and acute dystonic reactions. There have been no prior reports of tardive dyskinesia with this drug.Case report.Generalized choreiform dyskinesia developed after 10 months of conventional-dosage tetrabenazine treatment, persisting for several weeks after the drug was discontinued.As might be anticipated from its pharmacological profile, tetrabenazine has the potential to cause tardive dyskinesia. Such an occurrence may be difficult to detect in a clinical population already affected with involuntary movements.

Dystonia is a movement disorder characterized by sustained muscle contractions, causing twisting and repetitive movements or abnormal postures of affected body parts. Here, we present a novel case of focal dystonia of a 51 years old right-handed woman who had developed difficulty in writing and performing fine motor tasks. Due to a discomfort in her right hand at use, she started using her left hand instead and noticed inconsistent mirror movements in her right hand upon use of left hand. She was treated with trihexyphenidyl which allowed her right hand to function better, though writing still remained a problem.

We report on a case of a 65-year-old (CD) woman who sustained an atraumatic neck fracture. A combination of Parkinson's disease with motor fluctuations, chronic cervical dystonia and osteoporosis provided the basis for this interesting diagnosis. Mrs CD had progressed to complex phase idiopathic Parkinson's disease within 13 years of diagnosis. During this time she remained independent, only using a wheelchair when her motor fluctuations were bad. In 2011, she developed a sudden onset of neck spasm and occipital neuralgia, initially attributed to severe spasmodic cervical dystonia. Despite a titration regime of analgesics and weaning off of her Parkinson's disease medications, the pain persisted. An X-ray of her cervical spine showed degenerative discopathies from C4 to C7. Mrs CD underwent a trial of Botox injections to no avail and she was admitted acutely under the spinal team after an MRI of her spine showed abnormal oedema of the odontoid peg. Subsequent CT diagnosed a type II fracture of the odontoid peg on the background of severe osteoporotic bone (spinal T score -3.4 on subsequent DEXA scan) and she underwent a successful occipital cervical fusion of C1-C6. What makes this case interesting is the fact that this lady's profound powerful neck movements on a background of osteoporosis led to fracture of her neck. Post-operatively, she admitted to non-adherence to her bisphosphonates, prioritising levodopa in the morning with food rather than taking her alendronate on an empty stomach. She is now pain free and receives annual zolendronate infusions.