CHIEN HSIN FEN
Projetos de Pesquisa
Unidades Organizacionais
P IOT, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto de Ortopedia e Traumatologia, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto de Ortopedia e Traumatologia, Hospital das Clínicas, Faculdade de Medicina - Médico
19 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 19
- DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease(2016) OLGIATI, Simone; QUADRI, Marialuisa; FANG, Mingyan; ROOD, Janneke P. M. A.; SAUTE, Jonas A.; CHIEN, Hsin Fen; BOUWKAMP, Christian G.; GRAAFLAND, Josja; MINNEBOO, Michelle; BREEDVELD, Guido J.; ZHANG, Jianguo; VERHEIJEN, Frans W.; BOON, Agnita J. W.; KIEVIT, Anneke J. A.; JARDIM, Laura Bannach; MANDEMAKERS, Wim; BARBOSA, Egberto Reis; RIEDER, Carlos R. M.; LEENDERS, Klaus L.; WANG, Jun; BONIFATI, VincenzoObjectiveDNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age<11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within approximate to 10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disease (PD). MethodsThe DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole-exome sequencing, and protein studies. ResultsWe identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady-state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early-onset PD, had symptoms onset in the third-to-fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early-onset PD. InterpretationOur findings delineate a novel form of hereditary early-onset PD. Screening of DNAJC6 is warranted in all patients with early-onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis. Ann Neurol 2016;79:244-256
- Guidelines for Parkinson's disease treatment consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology- motor symptoms(2022) SABA, Roberta Arb; MAIA, Debora Palma; CARDOSO, Francisco Eduardo Costa; BORGES, Vanderci; ANDRADE, Luiz Augusto F.; FERRAZ, Henrique Ballalai; BARBOSA, Egberto Reis; RIEDER, Carlos Roberto de Mello; SILVA, Delson Jose da; CHIEN, Hsin Fen; CAPATO, Tamine; ROSSO, Ana Lucia; LIMA, Carlos Frederico Souza; BEZERRA, Jose Marcelo Ferreia; NICARETTA, Denise; BARSOTTINI, Orlando Graziani Povoas; GODEIRO-JUNIOR, Clecio; BARCELOS, Lorena Broseghini; CURY, Rubens Gisbert; SPITZ, Mariana; SILVA, Sonia Maria Cesar Azevedo; COLLETTA, Marcus Vinicius DellaThe treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.
- Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency(2016) OLGIATI, Simone; SKORVANEK, Matej; QUADRI, Marialuisa; MINNEBOO, Michelle; GRAAFLAND, Josja; BREEDVELD, Guido J.; BONTE, Ramon; OZGUR, Zeliha; HOUT, Mirjam C. G. N. van den; SCHOONDERWOERD, Kees; VERHEIJEN, Frans W.; IJCKEN, Wilfred F. J. van; CHIEN, Hsin Fen; BARBOSA, Egberto Reis; CHANG, Hsiu-Chen; LAI, Szu-Chia; YEH, Tu-Hsueh; LU, Chin-Song; WU-CHOU, Yah-Huei; KIEVIT, Anneke J. A.; HAN, Vladimir; GDOVINOVA, Zuzana; JECH, Robert; HOFSTRA, Robert M. W.; RUIJTER, George J. G.; MANDEMAKERS, Wim; BONIFATI, VincenzoBackgroundECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. MethodsClinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed. ResultsThe first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh-like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise-induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous ECHS1 mutations: c.232G>T (predicted protein effect: p.Glu78Ter) and c.518C>T (p.Ala173Val). Linkage analysis, exome sequencing, cosegregation, expression studies, and metabolite profiling support the pathogenicity of these mutations. Expression studies in patients' fibroblasts showed mitochondrial localization and severely reduced levels of ECHS1 protein. Increased urinary S-(2-carboxypropyl)cysteine and N-acetyl-S-(2-carboxypropyl)cysteine levels, proposed metabolic markers of this disorder, were documented in both siblings. Sequencing ECHS1 in 30 unrelated patients with paroxysmal dyskinesias revealed no further mutations. ConclusionsThe phenotype associated with ECHS1 mutations might be milder than reported earlier, compatible with prolonged survival, and also includes isolated paroxysmal exercise-induced dystonia. ECHS1 screening should be considered in patients with otherwise unexplained paroxysmal exercise-induced dystonia, in addition to those with Leigh and Leigh-like syndromes. Diet regimens and detoxifying agents represent potential therapeutic strategies. (c) 2016 International Parkinson and Movement Disorder Society
- Specificity and sensibility of 9-Itens Wearing-off Questionnaire in Brazilian Parkinson disease patient sample(2014) SANTOS, Jasper Guimaraes; CHIEN, Hsin Fen; BARBOSA, Egberto ReisObjective: (1) To evaluate whether the Nine Items Questionnaire (WOQ-9) for the detection of wearing-off (WO) in Parkinson Disease (PD), by means of its screening ability, is a helpful tool to assist neurologists in diagnosing WO; (2) To determine the sensitivity and the specificity of a free Brazilian Portuguese translation of WOQ-9. Method: A sample obtained by convenience included 60 patients. The WOQ-9 was answered by the patients themselves before their routine consultations. The detection of the WO by the WOQ-9 was compared with the neurologist assessment. Statistical significance was 5%. Results: The WOQ-9 showed sensitivity of 100%, specificity of 10.3%, positive and negative predictive values of 54.4% and 100% respectively. The identification of WO by the WOQ-9 was congruent in 54.5% of cases with neurological evaluation. Conclusion: The WOQ-9 is a convenient screening tool to aid physicians to detect WO in PD patients, and it is a quick and easy self-administered questionnaire.
- Neuropathologic Findings in a Patient With Juvenile-Onset Levodopa-Responsive Parkinsonism Due to ATP13A2 Mutation(2021) CHIEN, Hsin Fen; RODRIGUEZ, Roberta Diehl; BONIFATI, Vincenzo; NITRINI, Ricardo; PASQUALUCCI, Carlos Augusto; GELPI, Ellen; BARBOSA, Egberto ReisObjective To describe the postmortem neuropathologic findings of a patient with Kufor Rakeb syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment. Methods A detailed neuropathologic analysis of the brain was performed. The patient had a genetically confirmed ATP13A2 homozygous missense mutation and died at age 38 years, which was 26 years after the onset of his symptoms. Results The main brain neuropathologic findings were widespread neuronal and glial lipofuscin accumulation with no Lewy body-type inclusions and absence of alpha-synuclein-positive, tau-positive, beta-amyloid-positive, and TDP-43 protein-positive pathologies. Sparse iron deposits were observed in several brain areas, but no obvious axonal spheroids were identified. Discussion This is to our knowledge the first KRS postmortem neuropathologic description. Iron deposits were found but not associated with increased axonal spheroids, as frequently observed in neurodegeneration with brain iron accumulation. ATP13A2 mutations have been described in patients with neuronal ceroid lipofuscinosis (CLN). Moreover, animal models with these mutations develop neurodegenerative disorders with CLN pathology. Therefore, our findings support that ATP13A2 mutations may be considered a genetic etiology of neuronal lipofuscinosis.
- Cognitive or Cognitive-Motor Executive Function Tasks? Evaluating Verbal Fluency Measures in People with Parkinson's Disease(2017) BARBOSA, Alessandra Ferreira; VOOS, Mariana Callil; CHEN, Janini; FRANCATO, Debora Cristina Valente; SOUZA, Carolina de Oliveira; BARBOSA, Egberto Reis; CHIEN, Hsin Fen; MANSUR, Leticia LessaIntroduction. Executive function deficits are observed in people with Parkinson's disease (PD) from early stages and have great impact on daily living activities. Verbal fluency and oral diadochokinesia involve phonarticulatory coordination, response inhibition, and phonological processing and may also be affected in people with PD. This study aimed to describe the performance of PD patients and an age-and education-matched control group on executive function, verbal fluency, and oral diadochokinesia tests and to investigate possible relationships between them. Methods. Forty people with PD and forty controls were evaluated with Trail Making Test (TMT, executive function) and phonemic/semantic verbal fluency and oral diadochokinesia (/pataka/) tests. Groups were compared by ANOVA and relationships were investigated by Pearson tests. Results. People with PD showed longer times in parts A and B of TMT. They also said fewer words in phonemic/semantic verbal fluency tests and less syllables in the diadochokinesia test. Oral diadochokinesia strongly correlated to parts A and B of TMT and to phonemic verbal fluency. Conclusion. Oral diadochokinesia was correlated to executive function and verbal fluency. The cognitive-motor interaction in verbal fluency and oral diadochokinesia must be considered not to overestimate the cognitive or motor impairments in people with PD.
- Relationship Between Posturography, Clinical Balance and Executive Function in Parkinson ' s Disease(2019) SOUZA, Carolina de Oliveira; VOOS, Mariana Callil; BARBOSA, Alessandra Ferreira; CHEN, Janini; FRANCATO, Debora Cristina Valente; MILOSEVIC, Matija; POPOVIC, Milos; FONOFF, Erich Talamoni; CHIEN, Hsin Fen; BARBOSA, Egberto ReisThis study aimed to evaluate the relationship between posturography, clinical balance, and executive function tests in Parkinson ' s disease (PD). Seventy-one people participated in the study. Static posturography evaluated the center of pressure fluctuations in quiet standing and dynamic posturography assessed sit-to-stand, tandem walk, and step over an obstacle. Functional balance was evaluated by Berg Balance Scale, MiniBESTest, and Timed Up and Go test. Executive function was assessed by Trail Making Test (TMT) and semantic verbal fluency test. Step over obstacle measures (percentage of body weight transfer and movement time) were moderately correlated to Timed Up and Go, part B of TMT and semantic verbal fluency (r > 0.40; p < 0.05 in all relationships). Stepping over an obstacle assesses the responses to internal perturbations. Participants with shorter movement times and higher percentage of body weight transfer (higher lift up index) on this task were also faster in Timed Up and Go, part B of TMT, and semantic verbal fluency. All these tasks require executive function (problem solving, sequencing, shifting attention), which is affected by PD and contribute to postural assessment.
- Frequency of the LRRK2 G2019S mutation in late-onset sporadic patients with Parkinson's disease(2014) CHIEN, Hsin Fen; FIGUEIREDO, Tamires Rocha; HOLLAENDER, Marianna Almeida; TOFOLI, Fabiano; TAKADA, Leonel Tadao; PEREIRA, Lygia do Veiga; BARBOSA, Egberto ReisMutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson's disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients. Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR). Results: No G2019S mutations were found in both patients with sporadic PD and controls. Conclusions: Our results may be explained by the relatively small sample size.
- Effects of resistance training on postural control in Parkinson's disease: a randomized controlled trial(2021) CHEN, Janini; CHIEN, Hsin Fen; FRANCATO, Debora Cristina Valente; BARBOSA, Alessandra Ferreira; SOUZA, Carolina de Oliveira; VOOS, Mariana Callil; GREVE, Julia Maria D'Andrea; BARBOSA, Egberto ReisBackground: Postural instability affects Parkinson's disease (PD) patients' postural control right from the early stages of the disease. The benefits of resistance training (RT) for balance and functional capacity have been described in the literature, but few studies have been conducted showing its effects on PD patients' postural control. Objective: To investigate the effects of a three-month RT intervention on static posturography (SP) measurements and clinical functional balance assessment among PD patients. Methods: Seventy-four patients were randomly assigned to a three-month RT intervention consisting of using weightlifting machines at a gym (gym group) or RT consisting of using free weights and elastic bands (freew group), or to a control group. The participants were evaluated at baseline, three months and six months. We evaluated changes of SP measurements under eyes-open, eyes-closed and dual-task conditions (primary endpoint), along with motor performance and balance effects by means of clinical scales, dynamic posturography and perceptions of quality of life (secondary endpoints). Results: There were no significant interactions in SP measurements among the groups. Unified Parkinson Disease Rating Scale (UPDRS-III) motor scores decreased in both RT groups (p<0.05). Better perceived quality of life for the mobility domain was reported in the gym group while functional balance scores improved in the freew group, which were maintained at the six-month follow-up (p<0.05). Conclusions: This study was not able to detect changes in SP measurements following a three-month RT intervention. Both RT groups of PD patients showed improved motor performance, with positive balance effects in the freew group and better perceived quality of life in the gym group.
article 36 Citação(ões) na Scopus Physical therapy program for cervical dystonia: a study of 20 cases(2012) RIBEIRO QUEIROZ, Mariana Araujo; CHIEN, Hsin Fen; SEKEFF-SALLEM, Flavio Augusto; BARBOSA, Egberto ReisBotulinum toxin (BTX) is the best therapeutic option in patients with cervical dystonia (CD), but physical therapy (PT) can be added to the treatment to achieve better results. Forty of our 70 patients with CD were enrolled in a controlled open study. Subjects were divided into two groups: G1 (intervention group comprising patients receiving BTX and PT) and G2 (control group comprising patients receiving BTX only). Both groups were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the 36-Item Short-Form Health Survey (SF-36). On the TWSTRS, significant improvements in disease severity were seen in G1 and G2 but significant improvements on the pain and disability subscales were seen only in G1 patients. There was a significant difference only on the pain subscale between G2 and G1 following treatment. An analysis of the physical aspects of SF-36 showed significant improvement in G1 on three subscales. An intergroup difference was also seen on two subscales. Regarding emotional aspects, G1 showed a significant improvement on three subscales. A significant difference on two subscales was also seen between G2 and G1 following treatment. BTX plus PT treatment achieved symptom relief in patients with CD and improved their quality of life.