RESUMO
BACKGROUND: Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia associated with oculomotor apraxia. AOA1, AOA2, AOA3, and AOA4 subtypes may present pathogenic variants in APTX, SETX, PIK3R5, and PNKP genes, respectively. Mutations in XRCC1 have been found to cause autosomal recessive spinocerebellar ataxia-26 (SCAR26) now considered AOA5. OBJECTIVES: To examine a cohort of Brazilians with autosomal recessive cerebellar ataxia plus oculomotor apraxia and determine the frequencies of AOA subtypes through genetic investigation. METHODS: We evaluated clinical, biomarkers, electrophysiological, and radiological findings of 52 patients with AOA phenotype and performed a genetic panel including APTX, SETX, PIK3R5, PNKP, and XRCC1. RESULTS: We found pathogenic variants in SETX (15 patients), PNKP (12), and APTX (5). No mutations in PIK3R5 or XRCC1 were identified. CONCLUSIONS: AOA2 and AOA4 were the most common forms of AOA in Brazil. Mutations in PIK3R5 and XRCC1 were not part of this genetic spectrum. © 2022 International Parkinson and Movement Disorder Society.
Assuntos
Apraxias , Ataxia Cerebelar , Apraxias/congênito , Apraxias/genética , Ataxia/genética , Brasil , Ataxia Cerebelar/complicações , Ataxia Cerebelar/genética , Síndrome de Cogan , DNA Helicases/genética , Enzimas Reparadoras do DNA/genética , Humanos , Enzimas Multifuncionais/genética , Mutação/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , RNA Helicases/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genéticaRESUMO
The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases.
Assuntos
Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/etiologia , Adolescente , Adulto , Idade de Início , Alelos , Brasil/epidemiologia , Criança , Estudos de Coortes , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imageamento por Ressonância Magnética , Masculino , Fenótipo , Vigilância da População , Paraplegia Espástica Hereditária/epidemiologia , Espastina/genética , Avaliação de Sintomas , Adulto JovemRESUMO
BACKGROUND: Gait and balance disturbance are challenging symptoms in advanced Parkinson's disease (PD). Anatomic and clinical data suggest that the fields of Forel may be a potential surgical target to treat these symptoms. OBJECTIVE: To test whether bilateral stimulation centered at the fields of Forel improves levodopa unresponsive freezing of gait (FOG), balance problems, postural instability, and falls in PD. METHODS: A total of 13 patients with levodopa-unresponsive gait disturbance (Hoehn and Yahr stage ≥3) were included. Patients were evaluated before (on-medication condition) and 1 yr after surgery (on-medication-on-stimulation condition). Motor symptoms and quality of life were assessed with the Unified Parkinson's Disease Rating scale (UPDRS III) and Quality of Life scale (PDQ-39). Clinical and instrumented analyses assessed gait, balance, postural instability, and falls. RESULTS: Surgery improved balance by 43% (95% confidence interval [CI]: 21.2-36.4 to 35.2-47.1; P = .0012), reduced FOG by 35% (95% CI: 15.1-20.3 to 8.1-15.3; P = .0021), and the monthly number of falls by 82.2% (95% CI: 2.2-6.9 to -0.2-1.7; P = .0039). Anticipatory postural adjustments, velocity to turn, and postural sway measurements also improved 1 yr after deep brain stimulation (DBS). UPDRS III motor scores were reduced by 27.2% postoperatively (95% CI: 42.6-54.3 to 30.2-40.5; P < .0001). Quality of life improved 27.5% (95% CI: 34.6-48.8 to 22.4-37.9; P = .0100). CONCLUSION: Our results suggest that DBS of the fields of Forel improved motor symptoms in PD, as well as the FOG, falls, balance, postural instability, and quality of life.
Assuntos
Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Encéfalo , Marcha , Transtornos Neurológicos da Marcha/tratamento farmacológico , Transtornos Neurológicos da Marcha/etiologia , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Equilíbrio Postural , Qualidade de VidaRESUMO
INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficient treatment of primary dystonia. Few studies have reported the effect of STN-DBS on secondary or acquired dystonia. METHODS: We reported 2 patients with acquired dystonia treated by subthalamic DBS and followed up for 24 months, besides providing a systematic review and meta-analysis of published series. RESULTS/CONCLUSIONS: Both patients had thalamic vascular or autoimmune lesions within the ventral and the pulvinar nuclei. A reduction of 67.2% on the Burke-Fahn-Marsden Dystonia Rating Scale and 90% improvement in disability scores were shown in the first patient, while the second patient showed a lower reduction in both dystonia symptoms (28.6%) and disability scores (44%). Both patients had a significant mean improvement in the quality of life (62.5% in the first and 57.9% in the second) and were free of drugs postoperatively. A systematic review showed a mean follow-up of 13 months in 19 patients, including our 2 patients. The review showed a significant Burke-Fahn-Marsden Dystonia Scale (BFMDRS) score median reduction of 19 points (52.4%; confidence interval [CI]: 11.0-25.0) and a significant median reduction of 6 points in disability scores (44.5%; 95% CI: 4.0-14.0), thereby improving quality of life. Age at surgery was inversely correlated with postoperative improvement (r = 0.63; p = 0.039). Hemidystonia had a nonsignificant better improvement than generalized dystonia (55.3 vs. 43.5%; p = 0.4433). No association between etiology and postoperative improvement and no serious complications were found. Although few data reported so far, subthalamic DBS is likely efficient for acquired dystonia.
Assuntos
Estimulação Encefálica Profunda , Distonia , Distúrbios Distônicos , Núcleo Subtalâmico , Distonia/terapia , Distúrbios Distônicos/terapia , Humanos , Qualidade de Vida , Resultado do TratamentoAssuntos
COVID-19/complicações , COVID-19/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , COVID-19/diagnóstico , Feminino , Seguimentos , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Ophthalmological abnormalities may occur in specific subtypes of hereditary spastic paraplegia (HSP) and in genetic diseases that present with spastic paraplegia mimicking HSP. These ophthalmological changes may precede the motor symptoms and include pigmentary retinal degeneration, ophthalmoplegia, optic atrophy, cataracts and nystagmus. Some ophthalmological abnormalities are more prevalent in specific forms of HSP. Considering that the diagnosis of HSP is usually difficult and complex, specific ophthalmological changes may guide the genetic testing. There are other genetic diseases such as autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), X-linked adrenoleukodystrophy and spastic paraplegia, optic atrophy and neuropathy (SPOAN) that may mimic HSP and also may present with specific ophthalmological changes. In this article, we review the main ophthalmological changes observed in patients with HSP and HSP-like disorders.
Assuntos
Técnicas de Diagnóstico Oftalmológico , Oftalmopatias/diagnóstico por imagem , Oftalmopatias/genética , Paraplegia Espástica Hereditária/diagnóstico por imagem , Paraplegia Espástica Hereditária/genética , Oftalmopatias/epidemiologia , Humanos , Espasticidade Muscular/diagnóstico por imagem , Espasticidade Muscular/epidemiologia , Espasticidade Muscular/genética , Atrofia Óptica/diagnóstico por imagem , Atrofia Óptica/epidemiologia , Atrofia Óptica/genética , Paraplegia/diagnóstico por imagem , Paraplegia/epidemiologia , Paraplegia/genética , Paraplegia Espástica Hereditária/epidemiologia , Ataxias Espinocerebelares/congênito , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genéticaRESUMO
People sometimes explain behavior by appealing to an essentialist concept of the self, often referred to as the true self. Existing studies suggest that people tend to believe that the true self is morally virtuous; that is deep inside, every person is motivated to behave in morally good ways. Is this belief particular to individuals with optimistic beliefs or people from Western cultures, or does it reflect a widely held cognitive bias in how people understand the self? To address this question, we tested the good true self theory against two potential boundary conditions that are known to elicit different beliefs about the self as a whole. Study 1 tested whether individual differences in misanthropy-the tendency to view humans negatively-predict beliefs about the good true self in an American sample. The results indicate a consistent belief in a good true self, even among individuals who have an explicitly pessimistic view of others. Study 2 compared true self-attributions across cultural groups, by comparing samples from an independent country (USA) and a diverse set of interdependent countries (Russia, Singapore, and Colombia). Results indicated that the direction and magnitude of the effect are comparable across all groups we tested. The belief in a good true self appears robust across groups varying in cultural orientation or misanthropy, suggesting a consistent psychological tendency to view the true self as morally good.