Assuntos
Transtornos Parkinsonianos/fisiopatologia , ATPases Translocadoras de Prótons/genética , Paraplegia Espástica Hereditária/fisiopatologia , Adolescente , Ataxia/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Doença dos Neurônios Motores/fisiopatologia , Espasticidade Muscular/fisiopatologia , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/psicologia , Fenótipo , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Irmãos , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/psicologia , Adulto JovemAssuntos
Ataxia Cerebelar/fisiopatologia , Polineuropatias/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Distúrbios Somatossensoriais/fisiopatologia , Adulto , Idoso , Ataxia/diagnóstico por imagem , Ataxia/etiologia , Ataxia/fisiopatologia , Atrofia , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/etiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Eletrodiagnóstico , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Polineuropatias/etiologia , Síndrome de Sjogren/complicações , Distúrbios Somatossensoriais/etiologiaRESUMO
Sensory neuronopathies (SN) result from dorsal root ganglia damage and manifest with a combination of sensory deficits and proprioceptive ataxia. Characterization of the natural history and development of therapeutic trials are hampered by the lack of clinical scales that capture the whole spectrum of SN-related manifestations. We propose and validate a rating instrument for SN. Three experienced neuromuscular specialists developed items to rate SN. The resultant instrument was later validated by the assessment of the intra-class correlation coefficient, for inter-rater validity in 48 SN patients, and later in a smaller subset of 16 patients to assess its intra-rater validity. Standardized Crombach's alpha and Oblimin rotation analysis were performed to verify internal consistency and items' relationship, respectively. Evaluation of Sensory Ataxia Rating Scale (SEARS)'s external validity was performed by comparison to: scale for the assessment and rating of ataxia (SARA), Beck balance scale (BBS), and INCAT sensory sum score (ISS). A 10-item scale with an intra-class correlation coefficient >0.95 for intra- and inter-rating measurements with a good internal consistency (standardized Cronbach's alpha of 0.83) were observed. There was a normal distribution of the scores without a floor or ceiling effect. A moderate to good correlation between SEARS and SARA, BBS, and ISS was observed. SEARS is a reliable, easy-to-perform and consistent instrument to rate SN. Larger cohorts and multicenter studies are needed to validate its usefulness towards possible treatment trials.
Assuntos
Ataxia/diagnóstico , Adulto , Idoso , Ataxia/fisiopatologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Avaliação de SintomasRESUMO
Abnormalities in cerebellar structure and function may cause ataxia, a neurological dysfunction of motor coordination. In the course of the present study, we characterized a mutant mouse lineage with an ataxia-like phenotype. We localized the mutation on chromosome 17 and mapped it to position 1534 of the Nox3 gene, resulting in p.Asn64Tyr change. The primary defect observed in Nox3eqlb mice was increased proliferation of cerebellar granule cell precursors (GCPs). cDNA microarray comparing Nox3eqlb and BALB/c neonatal cerebellum revealed changes in the expression of genes involved in the control of cell proliferation. Nox3eqlb GCPs and NSC produce higher amounts of reactive oxygen species (ROS) and upregulate the expression of SHH target genes, such as Gli1-3 and Ccnd1 (CyclinD1). We hypothesize that this new mutation is responsible for an increase in proliferation via stimulation of the SHH pathway. We suggest this mutant mouse lineage as a new model to investigate the role of ROS in neuronal precursor cell proliferation.
Assuntos
Ataxia/genética , Cerebelo/enzimologia , Proteínas Hedgehog/genética , NADPH Oxidases/genética , Células-Tronco Neurais/enzimologia , Transdução de Sinais/genética , Animais , Ataxia/enzimologia , Ataxia/fisiopatologia , Diferenciação Celular , Proliferação de Células , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Mapeamento Cromossômico , Cromossomos de Mamíferos , Ciclina D1/genética , Ciclina D1/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Atividade Motora/genética , Mutação , NADPH Oxidases/deficiência , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/patologia , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo , Proteína Gli3 com Dedos de Zinco/genética , Proteína Gli3 com Dedos de Zinco/metabolismoAssuntos
Ataxia/fisiopatologia , Discinesias/fisiopatologia , Hipertonia Muscular/fisiopatologia , Hipotonia Muscular/fisiopatologia , Postura/fisiologia , Infecção por Zika virus/congênito , Brasil , Feminino , Maternidades , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Infecção por Zika virus/fisiopatologiaRESUMO
Zika virus (ZIKV) is an emerging flavivirus which has been linked to a number of neurologic manifestations such as Guillain-Barré syndrome (GBS), transverse myelitis, and meningo-encephalitis. Ophthalmologic manifestations are increasingly being reported; however, ocular dyskinesias have not been described in this context to date. Herein, we report a case of a 22-year-old female who presented with ocular flutter and associated Guillain-Barré syndrome following acute ZIKV infection. We speculate that although such symptoms may have originated from a direct viral insult, a post-infectious autoimmune mechanism may not be excluded. Physicians should include ZIKV as well as other flaviviruses in their diagnostic workup for all patients with ocular flutter/opsoclonus, after excluding other non-infectious causes of central nervous system pathology. To the best of our knowledge, this is the first report on the association of ocular flutter, GBS, and ZIKV infection.
Assuntos
Ataxia/diagnóstico , Síndrome de Guillain-Barré/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Infecção por Zika virus/diagnóstico , Aciclovir/uso terapêutico , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , Ataxia/tratamento farmacológico , Ataxia/fisiopatologia , Ataxia/virologia , Feminino , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Guillain-Barré/virologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Transtornos da Motilidade Ocular/tratamento farmacológico , Transtornos da Motilidade Ocular/fisiopatologia , Transtornos da Motilidade Ocular/virologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologiaRESUMO
Fatigue has been described in several neurodegenerative diseases, reducing quality of life. A systematic evaluation of this clinical feature is lacking in SCA3/MJD. The aim of this study was to evaluate the frequency and the factors associated with fatigue in SCA3/MJD. Patients with SCA3/MJD and matched healthy controls answered the Modified Fatigue Impact Scale (MFIS), Beck Inventory Depression (BDI) and Epworth Sleepiness Scale (ESS). Scale for the assessment and rating of ataxia (SARA) was used to determine ataxia severity. We used Mann-Whitney and Fisher exact tests to compare mean scores and proportions between groups. Linear regression analyses were employed to investigate factors associated with fatigue in SCA3/MJD. Seventy-four patients were included with a mean age and disease duration of 47.2 ± 12.8 and 9.5 ± 6.37 years, respectively. There were 38 men and 36 women. Mean (CAG)n was 72.2 ± 3.8. Mean MFIS score was higher in patients with SCA3/MJD (41.4 ± 16.2 vs 18.4 ± 12.9, p < 0.001). According to BDI scores, relevant depressive symptoms were found in 69.4 % of patients but only in 10.4 % of controls (p < 0.001). The proportion of patients with ESS scores indicating excessive daytime somnolence was also higher than controls (37.5 vs 22.3 %, p = 0.05). In the multiple regression analysis, both BDI and ESS scores were associated with fatigue (r = 0.67, p < 0.001 and p = 0.01). Fatigue is frequent and strongly associated with depression and excessive daytime somnolence in SCA3/MJD.
Assuntos
Fadiga/complicações , Fadiga/fisiopatologia , Doença de Machado-Joseph/complicações , Doença de Machado-Joseph/fisiopatologia , Ataxia/complicações , Ataxia/fisiopatologia , Depressão/complicações , Depressão/fisiopatologia , Fadiga/psicologia , Feminino , Humanos , Modelos Lineares , Doença de Machado-Joseph/psicologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaAssuntos
Ataxia/diagnóstico , Ataxia/genética , Cerebelo/metabolismo , Predisposição Genética para Doença , Mutação , Semântica , Ubiquitina-Proteína Ligases/genética , Adulto , Ataxia/fisiopatologia , Atrofia , Cerebelo/patologia , Cerebelo/fisiopatologia , Cognição , Estudos de Associação Genética , Humanos , Masculino , Atividade Motora , NeuroimagemRESUMO
Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the conversion of glutamic acid to the neurotransmitter gamma-amino butyric acid. Antibodies against GAD (anti-GAD-Ab) are associated with an array of autoimmune-related neurological conditions, such as stiff-person syndrome, cerebellar ataxia, epilepsy and limbic encephalitis. The clinical spectrum of ataxia associated with anti-GAD-Ab comprises slowly progressive cerebellar ataxia syndrome evolving in months or years, associated with cerebellar atrophy on brain MRI. There are few reports of patients with ataxia associated with anti-GAD-Ab presenting with abnormal ocular movements, such as downbeat nystagmus (DBN).We present two patients with ataxia associated with anti-GAD-Ab from a large series of ataxic subjects who presented with cerebellar ataxia combined with spontaneous DBN. All patients underwent a thorough neurological evaluation with the use of ataxia scales, brain MRI scans, cerebrospinal fluid examination, 18FDG-PET/CT scans, laboratory work-up with on coneural and immune encephalitis antibodies, serum and cerebrospinal fluid levels of anti-GAD-Ab, and the antibody specificity index to measure the intrathecal synthesis of anti-GAD-Ab. All patients were treated with cycles of intravenous immunoglobulin and had mild/partial ataxia improvement and no improvement of DBN. The finding of DBN may work as a diagnostic clue in the context of adult-onset non-hereditary ataxias.