Special Issue "Pathophysiology and Genetics of Movement Disorders"

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (31 May 2017).

Special Issue Editors

Guest Editor
Prof. Dr. Steven Frucht

Department of Neurology, Mount Sinai Medical Center, New York, New York, USA
Website | E-Mail
Interests: movement disorders; dystonia; myoclonus; chorea; parkinsonism; ataxia; phenomenology; musician’s dystonia
Guest Editor
Dr. Pichet Termsarasab

Division of Neurology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Website | E-Mail
Interests: movement disorders; dystonia; myoclonus, chorea; parkinsonism; ataxia; phenomenology; genetics

Special Issue Information

Dear Colleagues,

Movement disorders is one of the most clinically-oriented fields in Neurology. Clinical phenomenology remains an important aspect in diagnosis and treatment. Nevertheless, it is impossible to advance clinical sciences without progress in the basic sciences, particularly understanding in pathophysiology. Advances in the genomic era especially massively parallel sequencing provides tremendous insights to pathophysiology and clinical heterogeneity of movement disorders. The pathophysiology, genetics and clinical phenomenology are in fact the main three foundations that have provided positively feedforward advance of one another.

In this Special Issue on the “Pathophysiology and Genetics of Movement Disorders”, we would like to invite manuscripts on variety of topics related to these three main foundations of movement disorders: Pathophysiology, genetics, and clinical phenomenology. Thus, the coverage in this issue is broad. Works in either basic or clinical sciences are welcome. We hope that this Special Issue will be of interest for both basic scientists and clinicians working in the field of movement disorders. Bridging the gap between basic and clinical sciences by application of knowledge from bench to bedside to mitigate patients’ suffer is our primary common aim.

Prof. Dr. Steven Frucht
Dr. Pichet Termsarasab
Guest Editors

Manuscript Submission Information

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Keywords

  • movement disorders
  • pathophysiology
  • genetics
  • parkinsonism
  • dystonia
  • chorea
  • myoclonus
  • chorea
  • ataxia
  • tics
  • neuroimaging

Published Papers (8 papers)

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Research

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Open AccessArticle
Multifaceted Communication Problems in Everyday Conversations Involving People with Parkinson’s Disease
Brain Sci. 2017, 7(10), 123; https://doi.org/10.3390/brainsci7100123
Received: 23 August 2017 / Revised: 18 September 2017 / Accepted: 22 September 2017 / Published: 25 September 2017
Cited by 2 | PDF Full-text (228 KB) | HTML Full-text | XML Full-text
Abstract
It is known that Parkinson’s disease is often accompanied by a motor speech disorder, which results in impaired communication. However, people with Parkinson’s disease may also have impaired word retrieval (anomia) and other communicative problems, which have a negative impact on their ability [...] Read more.
It is known that Parkinson’s disease is often accompanied by a motor speech disorder, which results in impaired communication. However, people with Parkinson’s disease may also have impaired word retrieval (anomia) and other communicative problems, which have a negative impact on their ability to participate in conversations with family as well as healthcare staff. The aim of the present study was to explore effects of impaired speech and language on communication and how this is managed by people with Parkinson’s disease and their spouses. Using a qualitative method based on Conversation Analysis, in-depth analyses were performed on natural conversational interaction in five dyads including elderly men who were at different stages of Parkinson’s disease. The findings showed that the motor speech disorder in combination with word retrieval difficulties and adaptations, such as using communication strategies, may result in atypical utterances that are difficult for communication partners to understand. The coexistence of several communication problems compounds the difficulties faced in conversations and individuals with Parkinson’s disease are often dependent on cooperation with their communication partner to make themselves understood. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
Open AccessArticle
Hypermethylation of Synphilin-1, Alpha-Synuclein-Interacting Protein (SNCAIP) Gene in the Cerebral Cortex of Patients with Sporadic Parkinson’s Disease
Brain Sci. 2017, 7(7), 74; https://doi.org/10.3390/brainsci7070074
Received: 20 May 2017 / Revised: 22 June 2017 / Accepted: 23 June 2017 / Published: 27 June 2017
Cited by 3 | PDF Full-text (1938 KB) | HTML Full-text | XML Full-text
Abstract
Objective: To determine and compare DNA methylation patterns between patients with Parkinson’s disease (PD) and age- and sex-similar matched non-PD controls. Background: Epigenetic regulation is one of the major mechanisms for an organism to respond to the environment through changes in gene expression [...] Read more.
Objective: To determine and compare DNA methylation patterns between patients with Parkinson’s disease (PD) and age- and sex-similar matched non-PD controls. Background: Epigenetic regulation is one of the major mechanisms for an organism to respond to the environment through changes in gene expression and has been implicated in numerous disease processes. We would like to examine epigenetic modification patterns that may predispose or protect against PD. Methods: Frozen tissue samples of the human cerebral cortex from 12 PD patients and 12 subjects without PD pathology were obtained. Genome-wide DNA methylation profiling was performed using the Illumina HumanMethylation450 BeadChip array. Differential methylation was defined as a mean methylation level difference (delta β) of at least 0.20 (Δβ ≥ 0.20). Methylation regions with an absolute delta β value ≥ 0.20 were selected for further gene function studies. Results: We identified 2795 differentially methylated CpG sites in the frontal cortex of PD cases with a detection p-value of ≤ 0.01 and 328 differentially methylated CpG sites with a detection p-value of ≤ 0.001. A pattern of robust hypermethylation of synphilin-1, α-synuclein-interacting protein (SNCAIP) gene was found in the brain of PD cases (p = 4.93 × 10−7 and delta β = 0.60). Conclusion: Our findings support a link between SNCAIP methylation and PD risk. Hypomethylation of SNCAIP may function to protect against PD. The current results may suggest that the methylation status of SNCAIP could be useful as a marker in PD diagnosis and treatment and warrants further investigation. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
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Open AccessArticle
Astrocytic Expression of GSTA4 Is Associated to Dopaminergic Neuroprotection in a Rat 6-OHDA Model of Parkinson’s Disease
Brain Sci. 2017, 7(7), 73; https://doi.org/10.3390/brainsci7070073
Received: 29 May 2017 / Revised: 20 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
Cited by 3 | PDF Full-text (3579 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Idiopathic Parkinson’s disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been [...] Read more.
Idiopathic Parkinson’s disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD. We therefore investigated whether PVG alleles in Vra1 are neuroprotective in a toxin-induced model of PD and if this effect is coupled to Gsta4. We performed unilateral 6-hydroxydopamine (6-OHDA) partial lesions in the striatum and compared the extent of neurodegeration in parental (DA) and congenic (DA.VRA1) rats. At 8 weeks after 6-OHDA lesion, DA.VRA1 rats displayed a higher density of remaining dopaminergic fibers in the dorsolateral striatum compared to DA rats (44% vs. 23%, p < 0.01), indicating that Vra1 alleles derived from the PVG strain protect dopaminergic neurons from 6-OHDA toxicity. Gsta4 gene expression levels in the striatum and midbrain were higher in DA.VRA1 congenic rats compared to DA at 2 days post-lesion (p < 0.05). The GSTA4 protein co-localized with astrocytic marker GFAP, but not with neuronal marker NeuN or microglial marker IBA1, suggesting astrocyte-specific expression. This is the first report on Vra1 protective effects on dopaminergic neurodegeneration and encourages further studies on Gsta4 in relation to PD susceptibility. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
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Review

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Open AccessReview
Myoclonic Disorders
Brain Sci. 2017, 7(8), 103; https://doi.org/10.3390/brainsci7080103
Received: 30 May 2017 / Revised: 6 August 2017 / Accepted: 8 August 2017 / Published: 14 August 2017
Cited by 5 | PDF Full-text (288 KB) | HTML Full-text | XML Full-text
Abstract
Few movement disorders seem to make a straightforward approach to diagnosis and treatment more difficult and frustrating than myoclonus, due to its plethora of causes and its variable classifications. Nevertheless, in recent years, exciting advances have been made in the elucidation of the [...] Read more.
Few movement disorders seem to make a straightforward approach to diagnosis and treatment more difficult and frustrating than myoclonus, due to its plethora of causes and its variable classifications. Nevertheless, in recent years, exciting advances have been made in the elucidation of the pathophysiology and genetic basis of many disorders presenting with myoclonus. Here, we provide a review of all of the important types of myoclonus encountered in pediatric and adult neurology, with an emphasis on the recent developments that have led to a deeper understanding of this intriguing phenomenon. An up-to-date list of the genetic basis of all major myoclonic disorders is presented. Randomized studies are scarce in myoclonus therapy, but helpful pragmatic approaches at diagnosis as well as treatment have been recently suggested. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
Open AccessReview
Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review
Brain Sci. 2017, 7(7), 84; https://doi.org/10.3390/brainsci7070084
Received: 31 May 2017 / Revised: 27 June 2017 / Accepted: 9 July 2017 / Published: 15 July 2017
Cited by 8 | PDF Full-text (544 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural [...] Read more.
Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
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Open AccessReview
Clinicopathological Phenotype and Genetics of X-Linked Dystonia–Parkinsonism (XDP; DYT3; Lubag)
Brain Sci. 2017, 7(7), 72; https://doi.org/10.3390/brainsci7070072
Received: 31 May 2017 / Revised: 22 June 2017 / Accepted: 23 June 2017 / Published: 26 June 2017
Cited by 3 | PDF Full-text (1345 KB) | HTML Full-text | XML Full-text
Abstract
X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in [...] Read more.
X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in the later years of life. Among the primary monogenic dystonias, XDP has been identified as a transcriptional dysregulation syndrome with impaired expression of the TAF1 (TATA box-binding protein associated factor 1) gene, which is a critical component of the cellular transcription machinery. The major neuropathology of XDP is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen). XDP may be used as a human disease model to elucidate the pathomechanisms by which striatal neurodegeneration leads to dystonia symptoms. In this article, we introduce recent advances in the understanding of the interplay between pathophysiology and genetics in XDP. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
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Open AccessReview
Brain Magnetic Resonance Imaging (MRI) as a Potential Biomarker for Parkinson’s Disease (PD)
Brain Sci. 2017, 7(6), 68; https://doi.org/10.3390/brainsci7060068
Received: 28 April 2017 / Revised: 9 June 2017 / Accepted: 13 June 2017 / Published: 16 June 2017
Cited by 5 | PDF Full-text (232 KB) | HTML Full-text | XML Full-text
Abstract
Magnetic resonance imaging (MRI) has the potential to serve as a biomarker for Parkinson’s disease (PD). However, the type or types of biomarker it could provide remain to be determined. At this time there is not sufficient sensitivity or specificity for MRI to [...] Read more.
Magnetic resonance imaging (MRI) has the potential to serve as a biomarker for Parkinson’s disease (PD). However, the type or types of biomarker it could provide remain to be determined. At this time there is not sufficient sensitivity or specificity for MRI to serve as an early diagnostic biomarker, i.e., it is unproven in its ability to determine if a single individual is normal, has mild PD, or has some other forms of degenerative parkinsonism. However there is accumulating evidence that MRI may be useful in staging and monitoring disease progression (staging biomarker), and also possibly as a means to monitor pathophysiological aspects of disease and associated response to treatments, i.e., theranostic marker. As there are increasing numbers of manuscripts that are dedicated to diffusion- and neuromelanin-based imaging methods, this review will focus on these topics cursorily and will delve into pharmacodynamic imaging as a means to get at theranostic aspects of PD. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

Other

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Open AccessCase Report
Phenotypic Discordance in Siblings with Identical Compound Heterozygous PARK2 Mutations
Brain Sci. 2017, 7(7), 71; https://doi.org/10.3390/brainsci7070071
Received: 31 May 2017 / Revised: 18 June 2017 / Accepted: 21 June 2017 / Published: 24 June 2017
Cited by 1 | PDF Full-text (2810 KB) | HTML Full-text | XML Full-text
Abstract
PARK2 mutations are the most common cause of early-onset Parkinson’s disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the PARK2 gene manifesting strikingly different phenotypes. The older brother demonstrated [...] Read more.
PARK2 mutations are the most common cause of early-onset Parkinson’s disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the PARK2 gene manifesting strikingly different phenotypes. The older brother demonstrated marked parkinsonism by his mid-20’s, whereas the younger brother developed exercise-induced dystonia in his mid-30’s with no subsequent clinical progression, highlighting the clinical heterogeneity of the disease and implying the role of other genetic and/or environmental factors in disease progression. The younger sibling, despite his mild symptoms, had a clearly abnormal dopamine transporter (DaT)-SPECT scan. To our knowledge, this is the first such reported case of an abnormal DaT-SPECT scan in a patient with biallelic PARK2 mutations who does not meet the clinical criteria for Parkinson’s disease. Full article
(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)
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