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
36 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 36
- 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.
- Gait, posture and cognition in Parkinson's disease(2016) BARBOSA, Alessandra Ferreira; CHEN, Janini; FREITAG, Fernanda; VALENTE, Debora; SOUZA, Carolina de Oliveira; VOOS, Mariana Callil; CHIEN, Hsin FenABSTRACT Gait disorders and postural instability are the leading causes of falls and disability in Parkinson's disease (PD). Cognition plays an important role in postural control and may interfere with gait and posture assessment and treatment. It is important to recognize gait, posture and balance dysfunctions by choosing proper assessment tools for PD. Patients at higher risk of falling must be referred for rehabilitation as early as possible, because antiparkinsonian drugs and surgery do not improve gait and posture in PD.
- Rehabilitation in patients with cerebellar ataxias(2022) CHIEN, Hsin Fen; ZONTA, Marise Bueno; CHEN, Janini; DIAFERIA, Giovana; VIANA, Celiana Figueiredo; TEIVE, Helio Afonso Ghizoni; PEDROSO, Jose Luiz; BARSOTTINI, Orlando Graziani PovoasCerebellar ataxias comprise a heterogeneous group of diseases characterized by motor and non-motor symptoms, which can be acquired, degenerative, or have a genetic cause, such as spinocerebellar ataxias (SCA). Usually, the genetic and neurodegenerative forms of cerebellar ataxias present a progressive and inevitable worsening of the clinical picture so that rehabilitation treatment is fundamental. Rehabilitation treatment includes physical therapy, respiratory therapy, speech, voice and swallowing therapy, occupational therapy, and new technologies, such as the use of exergames. The current treatment of patients with cerebellar ataxias, especially neurodegenerative forms, genetic or not, should include these different forms of rehabilitation, with the main objective of improving the quality of life of patients.
- Effect of speech therapy on quality of life in patients with spinocerebelar ataxia type 3(2022) DIAFERIA, Giovana; BOMMARITO, Silvana; NETO, Pedro Braga; PARK, Sung Woo; PADOVANI, Marina; HADDAD, Fernanda; HADDAD, Leonardo; VOOS, Mariana Callil; CHIEN, Hsin Fen; PEDROSO, Jose Luiz; BARSOTTINI, OrlandoBackground Individuals with spinocerebellar ataxia type 3 (SCA3) present communication and swallowing disorders, and consequent deterioration in quality of life (QOL).Objective To evaluate the impact of a speech therapy rehabilitation program on the QOL of patients with SCA3.Methods All participants were randomly assigned to two groups, an intervention group receiving speech therapy (STG) and a control group (CG). The International Cooperative Ataxia Rating Scale scores were 32.4 1 20.2, and the Scale for the Assessment and Rating of Ataxia scores were 11.8 18.0. The intervention consisted of a 12-session speech therapy rehabilitation program with oral, pharyngeal, and laryngeal strengthening exercises & mdash;the so-called ATAXIA-Myofunctional Orofacial and Vocal Therapy (A-MOVT). They all were submitted to pre-and postintervention evaluations using the World Health Organization's Quality of Life (WHOQOL-BREF) assessment, as well as the Living with Dysarthria (LwD), Quality of Life in Swallowing Disorders (SWAL-QOL), and Food Assessment Tool (EAT-10).Results The study sample consisted of 48 patients with SCA3 (STG = 25; CG = 23), mean age was 47.1 111.4 years; mean age at symptom onset was 36.9 1 11.3 years; disease duration was 11.9 1 13.3 years. After the 3-month intervention, there were significant changes in the QOL in the STG compared with the CG, when assessed by the LwD (179.12 1 62.55 vs. 129.88 1 51.42, p < 0.001), SWAL-QOL (869.43 1153.63 vs. 911.60 1 130.90, p = 0.010), and EAT-10 (5.16 1 7.55 vs. 2.08 1 3.85, p = 0.018).Conclusions Patients with SCA3 should receive continuous speech therapy as part of the A-MOVT program, because therapy helps to improve difficulty swallowing and dysarthria.
- 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.
conferenceObject Classification and recommendation of nonpharmacological therapies for Parkinson's disease(2016) CAPATO, T. T. C.; FEN, C. H.; BARBOSA, E. R.- 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.