Typical Movement Disorders Research Articles

Drug-induced parkinsonism

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Transmembrane Protein 230 Mediates a Poly(ADP-ribose) Polymerase-1-Linked Apoptosis.

Mutations in transmembrane protein 230 (TMEM230) gene are suggested to be associated with the autosomal dominant Parkinson’s disease (PD) with typical movement disorders and Lewy body pathology. However, the normal functions and the pathological roles of TMEM230 are not clear. In this study, we used TMEM230 isoform II constructs including wild-type (WT) and four reported PD-linked mutation constructs (Y92C, R141L, 184Wext*5, and 184PGext*5). Ectopic expression of WT and PD-linked mutant TMEM230 variants in cultured cells dramatically induced apoptotic cell death compared with that of vector control cells. Mutant TMEM230 caused cell toxicity at an increased severity than WT TMEM230. Moreover, expression of TMEM230 increased mitochondrial reactive oxygen species (ROS) levels, decreased cellular ATP, activated caspase 3/7, and increased poly(ADP-ribose) polymerase-1 (PARP1) cleavage. Treatment with N-acetylcysteine (NAC; an ROS scavenger) or Z-VAD-FMK (a caspase inhibitor) significantly attenuated TMEM230-induced apoptosis in both cultured cells and primary neurons. Our results indicated that TMEM230 mediated a PARP1-linked apoptotic cell death pathway. These findings not only provide the novel insight into the biological roles of TMEM230 in the PARP1-linked pathway but also provide a TMEM230-induced cell death mechanism underlying PD pathogenesis.

Clinical phenotype heterogeneity in a family with ε-sarcoglycan gene mutation

This paper describes six cases of patients with myoclonus-dystonia syndrome who are members of a family in which an SGCE gene mutation has been confirmed. Myoclonus-dystonia syndrome is a very rare disease, with an incidence in Europe of about 2 in every million. Due to the fact that only a few case reports of this illness are accessible in the literature, the material we collected seems to be valuable for clinical practice. A history was taken, and physical and genetic examinations of the patients were performed. Furthermore, the clinical examination of three patients was video-recorded. The clinical picture of the disease varied significantly between the described individuals, from a healthy carrier of the SGCE mutation to patients presenting mild to moderate symptoms. The differences concerned the age at onset of the disease, the initial symptoms, the intensity of involuntary movements, and the predominant symptoms. In addition to the typical movement disorders which are myoclonus and dystonia, in the described family there was also the coexistence of epilepsy, obsessive-compulsive behaviour, dyslexia, dysgraphia, non-harmonious development of cognitive processes, as well as mild phenotypic features of muscular dystrophy. The mutation (NM_001099401.2:c.806-809delACTG) found in the presented family has not been described elsewhere. Our description of six cases of patients demonstrates the heterogeneity of the natural course of the disease, even in patients with the same mutation. It seems reasonable to regularly examine relatives of patients with myoclonus-dystonia syndrome, who should be observed for involuntary movements as well as non-motor symptoms.

Regenerative Therapies for Parkinson's Disease: An Update.

Parkinson's disease is the second most common neurodegenerative disorder. It is characterised by a typical movement disorder that occurs in part because of the selective degeneration of the dopaminergic neurons of the substantia nigra pars compacta. Current treatment for the motor disorder of Parkinson's disease consists of dopaminergic medications, but these come with significant adverse effects, themselves an important part of the clinical course of Parkinson's disease, particularly in advanced stages. Therefore, treatment is needed that can restore dopaminergic tone in the striatum in a physiological and targeted manner to avert these side effects. A number of potential regenerative treatments have been developed with a view to achieving this. Following decades of optimisation and development of stem-cell-based treatments and viral gene delivery, clinical trials are on the horizon. For these treatments to be widely useful, they must be clinically effective, cost efficient and safe, and a number of practical aspects regarding storage and delivery of treatment must be optimised. Many barriers have been overcome, and the field of regenerative medicine for Parkinson's disease is now increasingly focussed on how these treatments will be delivered, demonstrating the significant progress that has been made and the optimism surrounding these approaches.

Pediatric NMDAR encephalitis: A single center observation study with a closer look at movement disorders.

Anti-N-Methyl-d-aspartate-receptor (NMDAR) encephalitis is the most frequent autoimmune encephalitis in pediatric age. This retrospective observational study was aimed at describing the clinical characteristics of the disease in a cohort of children and teenagers. Eighteen patients (10 females and 8 males), with a median age of 12.4years at symptom onset were enrolled. The clinical presentation of the disease was marked by neurological manifestations in 13 patients and by severe psychiatric and behavioral symptoms in 5. The symptoms at onset varied according to the age: all the children presented with prominent neurological symptoms, whereas psychiatric symptoms were prominent in teenagers. Regardless the age, movement disorders (MDs) were distinctive symptoms during the acute stage of the disease. Several MDs might coexist in a given patient, and persist during sleep. The complexity, and the oddness of MDs often challenged their definition and the differential diagnosis with psychiatric manifestations and epileptic seizures. Stereotyped motor phenomena were the most typical MDs, and were recorded in all patients. Among them, perseveration, reproduction of acquired complex motor activities, and orofacial dyskinesia were the most distinctive features. In children, hyperkinetic MDs dominate; in teenagers, by contrast, a constellation of symptoms consistent with catatonia was the most frequent syndrome observed. The management of the several symptoms requires their accurate recognition, definition and assessment, and the knowledge of the potential side effects of antiepileptic and psychotropic drugs which could either mimic or worsen symptoms of encephalitis.

Autoimmune Movement Disorders in Children

Over the last decade, there have been significant advances in the identification, characterization, and treatment of autoimmune neurologic disorders in children. Many of these diseases include a typical movement disorder that can be a powerful aid to diagnosis. Frequently, movement disorders in autoimmune conditions are the sole or among a few presenting symptoms, allowing for earlier diagnosis of an underlying malignancy or systemic autoimmune disease. Given that early detection and treatment with immunotherapy may confer improved outcomes, recognizing these patterns of abnormal movements is essential for child neurologists. The purpose of this review is to summarize the clinical characteristics, diagnosis, and treatment of movement disorders that occur in pediatric autoimmune disorders.

Recognizing Parkinsonian Gait Pattern by Exploiting Fine-Grained Movement Function Features

Parkinson's disease (PD) is one of the typical movement disorder diseases among elderly people, which has a serious impact on their daily lives. In this article, we propose a novel computation framework to recognize gait patterns in patients with PD. The key idea of our approach is to distinguish gait patterns in PD patients from healthy individuals by accurately extracting gait features that capture all three aspects of movement functions, that is, stability, symmetry, and harmony. The proposed framework contains three steps: gait phase discrimination, feature extraction and selection, and pattern classification. In the first step, we put forward a sliding window--based method to discriminate four gait phases from plantar pressure data. Based on the gait phases, we extract and select gait features that characterize stability, symmetry, and harmony of movement functions. Finally, we recognize PD gait patterns by applying a hybrid classification model. We evaluate the framework using an open dataset that contains real plantar pressure data of 93 PD patients and 72 healthy individuals. Experimental results demonstrate that our framework significantly outperforms the four baseline approaches.

Juvenile Huntington disease in Argentina.

We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

Classic neuroimaging findings of nonketotic hyperglycemia on computed tomography and magnetic resonance imaging with absence of typical movement disorder symptoms (hemichorea-hemiballism)

While there are broad differential diagnoses for either the clinical finding of hemichorea-hemiballism or the imaging finding of lateralizing/asymmetric basal ganglia lesions (hyperdense on computed tomography, hyperintense on T1 magnetic resonance imaging), the presence of both findings is highly suggestive of nonketotic hyperglycemia. We present an unusual case of a patient with vague stroke-like complaints and imaging findings notable for lateralizing basal ganglia lesions. Laboratory analysis revealed nonketotic hyperglycemia and neurologic exam failed to elicit any findings of movement disorder. As far as we know, this is the first published case of a patient with typical neuroimaging manifestations of nonketotic hyperglycemia without associated hemichorea-hemiballism (a disorder of abnormal movements comprised of more proximal, higher amplitude movements-ballismus and lower amplitude, more distal movements-chorea). This finding suggests that radiologists should be alert to the possibility of nonketotic hyperglycemia in patients with asymmetric/lateralizing basal ganglia lesions even in the absence of a movement disorder.

Validity and Utility of a LRRK2 G2019S Mutation Test for the Diagnosis of Parkinson's Disease

The G2019S mutation in the LRRK2 gene, the most common known cause of Parkinson's disease (PD), will soon be widely available as a molecular clinical test for PD. The objective of this study was to assess performance characteristics of G2019S as a clinical test for PD in the setting of typical movement disorder clinics in the United States. Subjects included 1,518 sequentially recruited PD patients from seven movement disorder clinics in the United States, and 1,733 unaffected subjects. All 3,251 subjects were genotyped for the G2019S mutation using a TaqMan assay, and mutations were verified by direct sequencing. Test validity estimates were calculated using standard methods. A total of 20/1518 patients and 1/1733 controls carried the G2019S mutation. Specificity was 99.9% (95% CI, 99.6-100%), sensitivity was 1.3% (0.8-2.1%), and the positive likelihood ratio was 22.8. A positive family history of PD increased the positive likelihood ratio to 82.5. Information on gender, age at disease onset, or age at testing did not improve test performance. The gene test was highly accurate in classifying mutation carriers as PD, but it performed poorly in predicting the phenotype of non-mutation carriers. A G2019S molecular test for PD would be highly specific, technically simple, and inexpensive. Test interpretation is straightforward when used for diagnosis of symptomatic individuals, but is more complex for risk assessment and predictive testing in asymptomatic individuals. Test results can have psychological, social, and economical ramifications; thus, proper counseling is essential.

A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa

Presented is a pedigree with infancy-onset benign hereditary chorea (BHC) caused by a novel nonsense mutation in exon 3 (523G-->T, E175X) of the TITF-1 (Nkx2.1) gene. Four confirmed mutation carriers showed the typical movement disorder of BHC and congenital hypothyroidism. Surprisingly, treatment with levodopa improved gait dramatically and reduced chorea in two patients. Dopaminergic drugs should be considered a useful therapeutic option in BHC.

Spinal cord pattern generators for locomotion.

It is generally accepted that locomotion in mammals, including humans, is based on the activity of neuronal circuits within the spinal cord (the central pattern generator, CPG). Afferent information from the periphery (i.e. the limbs) influences the central pattern and, conversely, the CPG selects appropriate afferent information according to the external requirement. Both the CPG and the reflexes that mediate afferent input to the spinal cord are under the control of the brainstem. There is increasing evidence that in central motor diseases, a defective utilization of afferent input, in combination with secondary compensatory processes, is involved in typical movement disorders, such as spasticity and Parkinson's disease. Recent studies indicate a plastic behavior of the spinal neuronal circuits following a central motor lesion. This has implications for any rehabilitative therapy that should be directed to take advantage of the plasticity of the central nervous system. The significance of this research is in a better understanding of the pathophysiology underlying movement disorders and the consequences for an appropriate treatment.