The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Xiaojun Huang - One of the best experts on this subject based on the ideXlab platform.
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recommendations for the diagnosis and treatment of Paroxysmal Kinesigenic Dyskinesia an expert consensus in china
Translational neurodegeneration, 2021Co-Authors: Li Cao, Xiaojun Huang, Ning Wang, Cheng Zhang, Shuyan Cong, Ling Wei, Yanchun Deng, Qi Fang, Qi Niu, Jin WangAbstract:Paroxysmal Dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal Kinesigenic Dyskinesia (PKD) is the most common type of Paroxysmal Dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
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the phenotypic and genetic spectrum of Paroxysmal Kinesigenic Dyskinesia in china
Movement Disorders, 2020Co-Authors: Xiaojun Huang, Shige Wang, Xianan Guo, Wotu Tian, Feixia Zhan, Zeyu Zhu, Xiaomeng Yin, Qing Liu, Kaili YinAbstract:BACKGROUND Paroxysmal Kinesigenic Dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES We analyzed 600 Paroxysmal Kinesigenic Dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of Paroxysmal Kinesigenic Dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified Paroxysmal Kinesigenic Dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of Paroxysmal Kinesigenic Dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of Paroxysmal Kinesigenic Dyskinesia, family history, and more forms of Dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS We propose recommendations regarding diagnostic criteria for Paroxysmal Kinesigenic Dyskinesia based on this large clinical study of Paroxysmal Kinesigenic Dyskinesia. The findings offered some new insights into the diagnosis and treatment of Paroxysmal Kinesigenic Dyskinesia and might help in building standardized Paroxysmal Kinesigenic Dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.
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primary familial brain calcification presenting as Paroxysmal Kinesigenic Dyskinesia genetic and functional analyses
Neuroscience Letters, 2020Co-Authors: Feixia Zhan, Xiaojun Huang, Shige Wang, Wotu Tian, Zeyu Zhu, Chao Zhang, Li CaoAbstract:Abstract Background Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by calcium deposition in bilateral and symmetric brain. Evidence suggested that PFBC might be associated with Paroxysmal Kinesigenic Dyskinesia (PKD). We aim to investigate the genetic causes in PFBC patients manifested as PKD, and further to explore the pathogenic impact of the identified mutations. Methods 4 PKD-mimic PFBC patients were investigated in the study. Clinical assessment including laboratory tests, head computed tomography (CT) were conducted and followed by exome sequencing. Variants of PFBC genes were screened, and Sanger sequencing, segregation analysis were applied to confirm the findings. Functional assessment of the identified mutations was further analyzed. Results Among the 4 PKD-mimic PFBC patients, 3 presented with brain calcification, and 1 was identified carrying a PFBC mutation but without brain calcification. The clinical characteristics were summarized. Three heterozygous variants (2 novel, 1 documented) in PFBC genes were found. Further functional study showed abnormal accumulation and reduced uptake of Pi of the mutant protein, and the aggregated PDGFB failing to induce membrane ruffles compared with wild-type. Conclusions PKD can be a manifestation of PFBC, and brain calcification may be a cause of secondary PKD. So thoroughly evaluation including head CT or genetic screening for Paroxysmal Dyskinesia and PFBC should be applied before the diagnosis of PKD or PFBC. Moreover, negative brain calcification may not exclude the possibility of PFBC. The possible pathogenesis of primary calcification lie in the dysfunction of the protein or defective signal transduction caused by the mutations.
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the study of exercise tests in Paroxysmal Kinesigenic Dyskinesia
Clinical Neurophysiology, 2018Co-Authors: Haiyan Zhou, Xiaojun Huang, Wotu Tian, Feixia Zhan, Zeyu Zhu, Xiaoli Liu, Chao Zhang, Yan Wang, Xinghua Luan, Shengdi ChenAbstract:Abstract Objective To unravel if there was muscular ion channel dysfunction in Paroxysmal Kinesigenic Dyskinesia (PKD) patients using the exercises tests (ET). Methods Sixty PKD patients including 28 PRRT2 mutations carriers were enrolled in this study, as well as 19 hypokalaemic periodic paralysis (HypoPP) patients as the positive controls and 45 healthy subjects as the negative controls. ET including long exercise test (LET) and short exercise test (SET) was performed in the corresponding subjects. Results In the LET, both the overall PKD patients and HypoPP patients had greater CMAP amplitude and area increments during exercise than healthy controls. At most 25% of PKD patients were identified from the normality with greater amplitude increment than the area. On the contrary, 50% of HypoPP patients were differentiated with greater area increment than the amplitude. More percentage of PRRT2− patients than PRRT2+ patients had abnormal average amplitude increment. Unexpectedly, five PKD patients had abnormal maximum CMAP amplitude decrements after exercise in the LET, and one had abnormal maximum immediate amplitude decrement in the SET. Conclusions Distinct ET manifestations were found in PKD patients compared to normal controls and HypoPP patients. Significance Abnormal muscle membrane excitability might be involved in the mechanisms responsible for PKD.
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proline rich transmembrane protein 2 negative Paroxysmal Kinesigenic Dyskinesia clinical and genetic analyses of 163 patients
Movement Disorders, 2018Co-Authors: Wotu Tian, Xiaojun Huang, Xianan Guo, Qing Liu, Xiao Mao, Xiaoli Liu, Sheng Zeng, Junyi Shen, Huidong Tang, Xiaomeng YinAbstract:Background Paroxysmal Kinesigenic Dyskinesia is the most common type of Paroxysmal Dyskinesia. Approximately half of the cases of Paroxysmal Kinesigenic Dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. Objective The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with Paroxysmal Kinesigenic Dyskinesia. Methods We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a Paroxysmal movement disorders gene panel. Sanger sequencing, segregation analysis, and phenotypic reevaluation were used to substantiate the findings. Results The clinical characteristics of the enrolled 163 probands were summarized. A total of 39 heterozygous variants were identified, of which 33 were classified as benign, likely benign, and uncertain significance. The remaining 6 variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these, 3 were de novo (potassium calcium-activated channel subfamily M alpha 1, c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The other 3 (Paroxysmal nonkinesiogenic Dyskinesia protein, c.956dupA; potassium voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6 cases presented with typical Paroxysmal Kinesigenic Dyskinesia characteristics, except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family, where the proband's mother had abnormal discharges in her temporal lobes in addition to Paroxysmal Kinesigenic Dyskinesia episodes. Conclusions Our findings extend the genotypic spectrum of Paroxysmal Kinesigenic Dyskinesia and establish the associations between Paroxysmal Kinesigenic Dyskinesia and genes classically related to other Paroxysmal movement disorders. De novo variants might be a cause of sporadic Paroxysmal Kinesigenic Dyskinesia. © 2018 International Parkinson and Movement Disorder Society.
Wanjin Chen - One of the best experts on this subject based on the ideXlab platform.
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associations between neuroanatomical abnormality and motor symptoms in Paroxysmal Kinesigenic Dyskinesia
Parkinsonism & Related Disorders, 2019Co-Authors: Liqin Yang, Wanjin Chen, Gonglu Liu, Ning Wang, Dazhi Yin, Zheng WangAbstract:Abstract Introduction The pathophysiologic mechanism of Paroxysmal Kinesigenic Dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation. Methods Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure. Results Six (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers. Conclusions We observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD.
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Paroxysmal Kinesigenic Dyskinesia and myotonia congenita in the same family coexistence of a prrt2 mutation and two clcn1 mutations
Neuroscience Bulletin, 2014Co-Authors: Wanjin Chen, Wang Ni, Zhiying Wu, Hongfu LiAbstract:Paroxysmal Kinesigenic Dyskinesia (PKD) and myotonia congenita (MC) are independent disorders that share some clinical features. We aimed to investigate the sequences of PRRT2 and CLCN1 in a proband diagnosed with PKD and suspected MC. Clinical evaluation and auxiliary examinations were performed. Direct sequencing of the entire coding regions of the PRRT2 and CLCN1 genes was conducted. Haplotype analysis confirmed the relationships among the family members. The proband suffered choreoathetosis attacks triggered by sudden movements, and lower-limb weakness and stiffness that worsened in cold weather. Carbamazepine monotherapy completely controlled his choreoathetosis and significantly relieved his limb weakness and stiffness. His father, when young, had similar limb stiffness, while his mother and brother were asymptomatic. Genetic analysis revealed that the proband and his father harbored a PRRT2 c.649dupC mutation, and CLCN1 c.1723C>T and c.2492A>G mutations. His brother carried only the two CLCN1 mutations. None of these mutations were identified in his mother and 150 unrelated controls. This is the first report showing the coexistence of PRRT2 and CLCN1 mutations. Our results also indicate that both the PRRT2 and CLCN1 genes need to be screened if we fail to identify PRRT2 mutations in PKD patients or CLCN1 mutations in MC patients.
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prrt2 mutation correlated with phenotype of Paroxysmal Kinesigenic Dyskinesia and drug response
Neurology, 2013Co-Authors: Wanjin Chen, Kaiyan Wang, Gonglu Liu, Ning Wang, Zhiqi XiongAbstract:The Bruno et al.1 criteria are commonly used to diagnose Paroxysmal Kinesigenic Dyskinesia (PKD), listed as follows: The authors thank the participants for taking part in this study.
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exome sequencing identifies truncating mutations in prrt2 that cause Paroxysmal Kinesigenic Dyskinesia
Nature Genetics, 2011Co-Authors: Wanjin Chen, Yu Lin, Zhiqi Xiong, Wei Wei, Guohe Tan, Shunling Guo, Yafang Chen, Qijie Zhang, Yi LinAbstract:Paroxysmal Kinesigenic Dyskinesia is the most common type of Paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. Using whole-exome sequencing followed by Sanger sequencing, we identified three truncating mutations within PRRT2 (NM_145239.2) in eight Han Chinese families with histories of Paroxysmal Kinesigenic Dyskinesia: c.514_517delTCTG (p.Ser172Argfs*3) in one family, c.649dupC (p.Arg217Profs*8) in six families and c.972delA (p.Val325Serfs*12) in one family. These truncating mutations co-segregated exactly with the disease in these families and were not observed in 1,000 control subjects of matched ancestry. PRRT2 is a newly discovered gene consisting of four exons encoding the proline-rich transmembrane protein 2, which encompasses 340 amino acids and contains two predicted transmembrane domains. PRRT2 is highly expressed in the developing nervous system, and a truncating mutation alters the subcellular localization of the PRRT2 protein. The function of PRRT2 and its role in Paroxysmal Kinesigenic Dyskinesia should be further investigated.
Li Cao - One of the best experts on this subject based on the ideXlab platform.
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recommendations for the diagnosis and treatment of Paroxysmal Kinesigenic Dyskinesia an expert consensus in china
Translational neurodegeneration, 2021Co-Authors: Li Cao, Xiaojun Huang, Ning Wang, Cheng Zhang, Shuyan Cong, Ling Wei, Yanchun Deng, Qi Fang, Qi Niu, Jin WangAbstract:Paroxysmal Dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal Kinesigenic Dyskinesia (PKD) is the most common type of Paroxysmal Dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
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novel mutation of the prrt2 gene in two cases of Paroxysmal Kinesigenic Dyskinesia two case reports
Biomedical Reports, 2020Co-Authors: Jiajia Fang, Guo-hua Zhao, Shige Wang, Li CaoAbstract:Paroxysmal Kinesigenic Dyskinesia (PKD) is a rare condition characterized by recurrent brief episodes of dystonia, chorea, athetosis or any combination of these, without alterations of consciousness. The proline-rich transmembrane protein 2 (PRRT2) gene has been widely investigated as a causative gene of PKD. To date, a cluster of pathogenic variants associated with PKD have been identified in the PRRT2 gene. In the present case report, two Chinese patients with sporadic PKD are discussed. Genetic analysis revealed a de novo heterozygous missense mutation, c.955G>T (p.Val319Leu) in exon 3 of the PRRT2 gene. Compared with the commonly reported clinical manifestation of PRRT2-associated PKD, the patients in this report showed several primary distinctive features. The mutations identified in the present analysis expand upon the mutation spectrum of the PRRT2 gene, and this newly found variant further reinforces the importance of the PRR2 gene in PKD.
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complicated Paroxysmal Kinesigenic Dyskinesia associated with sacs mutations
Annals of Translational Medicine, 2020Co-Authors: Liang Shang, Wotu Tian, Qing Liu, Li Cao, Xue ZhangAbstract:Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by pathogenic variants in the SACS gene and is characterized by ataxia, peripheral neuropathy, pyramidal impairment and episodic conditions such as epilepsy. Paroxysmal Kinesigenic Dyskinesia (PKD) had not been previously described in ARSACS. Methods: We analyzed clinical manifestations and performed whole-exome sequencing (WES) in two independent patients with ARSACS and PKD. Both patients’ parents were unaffected. Genetic data were filtered for potential pathogenic variants, searching for de novo mutations suggestive of a dominant disease model or homozygous and compound heterozygous variants of a recessive model. Potential mutations that existed in both patients were generated and subjected to Sanger sequencing. The WES results of 163 PKD patients without additional symptoms from previous experiments were also reviewed. Results: Novel compound heterozygous mutations in the SACS gene were identified in Patient 1 (p.P3007S and p.H3392fs), and a novel homozygous truncating mutation (p.W1376X) was identified in Patient 2. In both patients, each mutant allele was inherited from one of his or her unaffected parents. All 3 mutations were absent in 196 ethnic-matched control chromosomes or in data from the 1000 Genomes Project. No pathogenic variants associated with Paroxysmal diseases, especially PKD and episodic ataxia, were identified. In PKD patients without additional symptoms, no homozygous or compound heterozygous variants in the SACS gene were detected. Conclusions: This study expands the clinical phenotype of ARSACS and suggests the inclusion of SACS screening in patients with PKD plus ARSACS.
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primary familial brain calcification presenting as Paroxysmal Kinesigenic Dyskinesia genetic and functional analyses
Neuroscience Letters, 2020Co-Authors: Feixia Zhan, Xiaojun Huang, Shige Wang, Wotu Tian, Zeyu Zhu, Chao Zhang, Li CaoAbstract:Abstract Background Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by calcium deposition in bilateral and symmetric brain. Evidence suggested that PFBC might be associated with Paroxysmal Kinesigenic Dyskinesia (PKD). We aim to investigate the genetic causes in PFBC patients manifested as PKD, and further to explore the pathogenic impact of the identified mutations. Methods 4 PKD-mimic PFBC patients were investigated in the study. Clinical assessment including laboratory tests, head computed tomography (CT) were conducted and followed by exome sequencing. Variants of PFBC genes were screened, and Sanger sequencing, segregation analysis were applied to confirm the findings. Functional assessment of the identified mutations was further analyzed. Results Among the 4 PKD-mimic PFBC patients, 3 presented with brain calcification, and 1 was identified carrying a PFBC mutation but without brain calcification. The clinical characteristics were summarized. Three heterozygous variants (2 novel, 1 documented) in PFBC genes were found. Further functional study showed abnormal accumulation and reduced uptake of Pi of the mutant protein, and the aggregated PDGFB failing to induce membrane ruffles compared with wild-type. Conclusions PKD can be a manifestation of PFBC, and brain calcification may be a cause of secondary PKD. So thoroughly evaluation including head CT or genetic screening for Paroxysmal Dyskinesia and PFBC should be applied before the diagnosis of PKD or PFBC. Moreover, negative brain calcification may not exclude the possibility of PFBC. The possible pathogenesis of primary calcification lie in the dysfunction of the protein or defective signal transduction caused by the mutations.
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familial Paroxysmal Kinesigenic Dyskinesia is associated with mutations in the kcna1 gene
Human Molecular Genetics, 2018Co-Authors: Xiaomeng Yin, Wotu Tian, Sheng Zeng, Li Cao, Junling Wang, Jinghan Lin, Tongmei Zhang, Kailin Zhang, Jifeng Guo, Ruoxi WangAbstract:Paroxysmal Kinesigenic Dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent Dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other loci are most likely involved in the etiology of this disorder. To explore the underlying causative gene of PRRT2-negative PKD, we used a combination strategy including linkage analysis, whole-exome sequencing and copy number variations analysis to detect the genetic variants within a family with PKD. We identified a linkage locus on chromosome 12 (12p13.32-12p12.3) and detected a novel heterozygous mutation c.956 T>G (p.319 L>R) in the potassium voltage-gated channel subfamily A member 1, KCNA1. Whole-exome sequencing in another 58 Chinese patients with PKD who lacked mutations in PRRT2 revealed another novel mutation in the KCNA1 gene [c.765 C>A (p.255 N>K)] within another family. Biochemical analysis revealed that the L319R mutant accelerated protein degradation via the proteasome pathway and disrupted membrane expression of the Kv1.1 channel. Electrophysiological examinations in transfected HEK293 cells showed that both the L319R and N255K mutants resulted in reduced potassium currents and respective altered gating properties, with a dominant negative effect on the Kv1.1 wild-type channel. Our study suggests that these mutations in KCNA1 cause the Kv1.1 channel dysfunction, which leads to familial PKD. The current study further extended the genotypic spectrum of this disorder, indicating that Kv1.1 channel dysfunction maybe one of the underlying defects in PKD.
Chunquan Cai - One of the best experts on this subject based on the ideXlab platform.
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missense mutations of the proline rich transmembrane protein 2 gene cosegregate with mild Paroxysmal Kinesigenic Dyskinesia and infantile convulsions in a chinese pedigree
Parkinsonism & Related Disorders, 2013Co-Authors: Chunquan Cai, Ouyan ShiAbstract:Abstract Paroxysmal Kinesigenic Dyskinesia is an autosomal dominant dystonia induced by sudden voluntary movements. Recently, proline-rich transmembrane protein 2 (PRRT2) gene mutations, especially frameshift mutations, were described for PKD. In our study, we have collected a three-generation Paroxysmal Kinesigenic Dyskinesia-infantile convulsions pedigree in Tianjin, North China. The symptoms of six patients varied; age of onset decreased in each generation. Mutations in the PRRT2 gene in nine PKD family members were screened by PCR sequencing of genomic DNA samples. Missense mutations of the PRRT2 gene were found in all four PKD patients and two children with infantile convulsions. All six individuals carried heterozygous codon 138 (Pro/Ala) and codon 306 (Ala/Asp) mutations. Missense mutations of the PRRT2 gene other than truncate and frameshift mutations were account for PKD and/or infantile convulsions. Age of onset and symptoms were not necessarily associated with PRRT2 mutations.
Dong Zhou - One of the best experts on this subject based on the ideXlab platform.
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disruption of gray matter morphological networks in patients with Paroxysmal Kinesigenic Dyskinesia
Human Brain Mapping, 2021Co-Authors: Du Lei, Running Niu, Xueling Suo, Chen Yang, Tianhua Yang, Jiechuan Ren, Walter H L Pinaya, Dong ZhouAbstract:This study explores the topological properties of brain gray matter (GM) networks in patients with Paroxysmal Kinesigenic Dyskinesia (PKD) and asks whether GM network features have potential diagnostic value. We used 3D T1-weighted magnetic resonance imaging and graph theoretical approaches to investigate the topological organization of GM morphological networks in 87 PKD patients and 115 age- and sex-matched healthy controls. We applied a support vector machine to GM morphological network matrices to classify PKD patients versus healthy controls. Compared with the HC group, the GM morphological networks of PKD patients showed significant abnormalities at the global level, including an increase in characteristic path length (Lp) and decreases in local efficiency (Eloc ), clustering coefficient (Cp), normalized clustering coefficient (γ), and small-worldness (σ). The decrease in Cp was significantly correlated with disease duration and age of onset. The GM morphological networks of PKD patients also showed significant changes in nodal topological characteristics, mainly in the basal ganglia-thalamus circuitry, default-mode network and central executive network. Finally, we used the GM morphological network matrices to classify individuals as PKD patients versus healthy controls, achieving 87.8% accuracy. Overall, this study demonstrated disruption of GM morphological networks in PKD, which might extend our understanding of the pathophysiology of PKD; further, GM morphological network matrices might have the potential to serve as network neuroimaging biomarkers for the diagnosis of PKD.
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brain structural connectome in relation to prrt2 mutations in Paroxysmal Kinesigenic Dyskinesia
Human Brain Mapping, 2020Co-Authors: Du Lei, Xueling Suo, Chen Yang, Tianhua Yang, Jiechuan Ren, Dong Zhou, Guangxiang Chen, Graham J KempAbstract:This study explored the topological characteristics of brain white matter structural networks in patients with Paroxysmal Kinesigenic Dyskinesia (PKD), and the potential influence of the brain network stability gene PRRT2 on the structural connectome in PKD. Thirty-five PKD patients with PRRT2 mutations (PKD-M), 43 PKD patients without PRRT2 mutations (PKD-N), and 40 demographically-matched healthy control (HC) subjects underwent diffusion tensor imaging. Graph theory and network-based statistic (NBS) approaches were performed; the topological properties of the white matter structural connectome were compared across the groups, and their relationships with the clinical variables were assessed. Both disease groups PKD-M and PKD-N showed lower local efficiency (implying decreased segregation ability) compared to the HC group; PKD-M had longer characteristic path length and lower global efficiency (implying decreased integration ability) compared to PKD-N and HC, independently of the potential effects of medication. Both PKD-M and PKD-N had decreased nodal characteristics in the left thalamus and left inferior frontal gyrus, the alterations being more pronounced in PKD-M patients, who also showed abnormalities in the left fusiform and bilateral middle temporal gyrus. In the connectivity characteristics assessed by NBS, the alterations were more pronounced in the PKD-M group versus HC than in PKD-N versus HC. As well as the white matter alterations in the basal ganglia-thalamo-cortical circuit related to PKD with or without PRRT2 mutations, findings in the PKD-M group of weaker small-worldness and more pronounced regional disturbance show the adverse effects of PRRT2 gene mutations on brain structural connectome.
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altered topological organization of functional brain networks in drug naive patients with Paroxysmal Kinesigenic Dyskinesia
Journal of the Neurological Sciences, 2020Co-Authors: Yingying Zhang, Tianhua Yang, Jiechuan Ren, Qiyong Gong, Yingjie Qin, Cheng Yang, Tianyu Zhang, Dong ZhouAbstract:Abstract Background Previous neuroimaging studies have revealed aberrant basal ganglia-thalamocortical circuit in patients with Paroxysmal Kinesigenic Dyskinesia (PKD) with drug treatment. This study aims to investigate the topological organization of functional networks in drug-naive PKD. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 24 drug-naive PKD patients and 24 age, gender and mean framewise displacement (FD)-matched healthy controls (HCs). The network topological properties (including global and nodal measures) were analyzed between two groups by using graph-based theoretical approaches. Pearson's correlation analysis was performed between significant metrics and duration of disease and the age of onset of patients with PKD. Results Compare to HCs, the drug-naive PKD patients showed increased nodal centralities mainly in left precentral gyrus, basal ganglia and limbic regions and decreased nodal centralities in the temporal pole. Our results showed that drug-naive PKD patients presented the small-world topology and at the global level no significant differences were found between PKD and HCs. In the correlation analysis, the increased nodal efficiency in the left pallidum was positively correlated with the onset of age. Conclusions Our findings supported the previous observation of the disruptive cortical-basal ganglia circuitry in PKD patients, but difference in that the prominent change of precentral area and temporal pole were also observed in our study when the potential impact of drug was excluded. These findings may provide a novel insight into further delineation of the pathophysiological genesis and possible target for PKD.
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increased interhemispheric resting state functional connectivity in Paroxysmal Kinesigenic Dyskinesia a resting state fmri study
Journal of the Neurological Sciences, 2015Co-Authors: Jiechuan Ren, Du Lei, Tianhua Yang, Fenglai Xiao, Xiaoqi Huang, Qiyong Gong, Dong ZhouAbstract:Abstract Purpose Paroxysmal Kinesigenic Dyskinesia (PKD) is a rare movement disorder. The underlying neural mechanisms have not been fully understood. This study aimed to examine the alteration of resting-state functional connectivity (RSFC) between interhemispheric homotopic regions in PKD using a technique called “voxel-mirrored homotopic connectivity” (VMHC). Methods The VMHC analysis was performed on resting-state functional MRI data from 11 PKD patients and 17 age and gender matched healthy subjects. Comparison between the two groups was conducted. The correlation relationship between VMHC and illness duration was analyzed. Results Compared with healthy subjects, PKD patients showed increased interhemispheric RSFC in bilateral putamen, primary motor cortex, supplementary motor area, dorsal lateral prefrontal cortex, primary somatosensory cortex, superior and middle occipital gyri, as well as cerebellar tonsil. Besides, negative correlation was detected between illness duration and VMHC in bilateral putamen and the insular cortex. Conclusion The present study provided preliminary evidence of increased interhemispheric RSFC in PKD mainly in the basal ganglia-thalamo-cortical circuitry and cerebellum. A negative correlation between VMHC and illness duration was also detected. These findings could further enhance our understandings of the pathophysiology of PKD.