RESUMO
Central Core Disease (CCD) is a genetic neuromuscular disorder characterized by the presence of cores in muscle biopsy. The inheritance has been described as predominantly autosomal dominant (AD), and the disease may present as severe neonatal or mild adult forms. Here we report clinical and molecular data on a large cohort of Brazilian CCD patients, including a retrospective clinical analysis and molecular screening for RYR1 variants using Next-Generation Sequencing (NGS). We analyzed 27 patients from 19 unrelated families: four families (11 patients) with autosomal dominant inheritance (AD), two families (3 patients) with autosomal recessive (AR), and 13 sporadic cases. Biallelic RYR1 variants were found in six families (two AR and four sporadic cases) of the 14 molecularly analyzed families (~43%), suggesting a higher frequency of AR inheritance than expected. None of these cases presented a severe phenotype. Facial weakness was more common in biallelic than in monoallelic patients (p = 0.0043) and might be a marker for AR forms. NGS is highly effective for the identification of RYR1 variants in CCD patients, allowing the discovery of a higher proportion of AR cases with biallelic mutations. These data have important implications for the genetic counseling of the families.
Assuntos
Miopatia da Parte Central , Neuroblastoma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Miopatia da Parte Central/genética , Miopatia da Parte Central/patologia , Linhagem , Estudos Retrospectivos , Canal de Liberação de Cálcio do Receptor de Rianodina/genéticaRESUMO
BACKGROUND: Impulse control disorders and punding are common in Parkinson's disease patients. Cross-sectional studies suggest an association between dopamine replacement therapy, especially dopaminergic agonists, and impulse control and related disorders in Parkinson's disease. However, some surveys suggest that Parkinson's disease itself does not confer an altered risk for impulse control disorders and related behavior, although these disturbances are more frequently reported in Parkinsonian patients than in healthy controls. OBJECTIVE: To ascertain the frequency of impulse control disorders and punding symptoms in Parkinson's disease patients and healthy controls and to determine the influence of dopamine agonist treatment on the prevalence of these disturbances. METHODS: A case-control study was conducted on 207 Parkinson's disease patients (79 taking dopamine agonists) and 230 healthy controls. The outcome measures were the presence of current impulse control disorders and punding symptoms, based on clinical criteria after application of the Minnesota Impulsive Disorders Interview for screening. RESULTS: The frequency of impulse control disorders in Parkinson's disease patients vs. Healthy controls was 16.9% vs. 15.2% (pâ¯=â¯0.631). Punding was more frequent in Parkinson's disease patients (pâ¯=â¯0.028); however, impulse control disorders were more frequent in medicated Parkinson's disease patients taking dopamine agonists than in medicated patients not taking dopamine agonists (pâ¯=â¯0.001) and healthy controls (pâ¯=â¯0.014). CONCLUSIONS: Parkinson's disease itself does not lead to the development of impulse control disorders. Dopaminergic agonist treatment may trigger the disorder in susceptible individuals. Punding may be more prevalent in Parkinson's disease patients.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Agonistas de Dopamina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Comportamento Estereotipado/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicaçõesRESUMO
Neuropsychiatric disorders are common among patients with Parkinson's disease and may appear in any stage of the disease. However, these disorders often go undiagnosed and receive insufficient treatment. Observations in recent years have revealed that dopamine replacement therapy may lead to the development or worsening of conditions, such as gambling disorder, compulsive sexual behavior, compulsive buying and binge eating, in addition to punding and dopamine dysregulation syndrome. The pathophysiology of these disorders seems to be related to abnormal dopaminergic stimulation of the basal regions of the basal ganglia, especially via nigro-mesolimbic pathways. The aim of the present study was to perform a literature review on impulsivity, impulse control disorders and related conditions among patients with Parkinson's disease, with emphasis on their epidemiology, clinical characteristics and treatment.
Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Doença de Parkinson/complicações , Humanos , Prognóstico , Fatores de RiscoRESUMO
ABSTRACT Neuropsychiatric disorders are common among patients with Parkinson's disease and may appear in any stage of the disease. However, these disorders often go undiagnosed and receive insufficient treatment. Observations in recent years have revealed that dopamine replacement therapy may lead to the development or worsening of conditions, such as gambling disorder, compulsive sexual behavior, compulsive buying and binge eating, in addition to punding and dopamine dysregulation syndrome. The pathophysiology of these disorders seems to be related to abnormal dopaminergic stimulation of the basal regions of the basal ganglia, especially via nigro-mesolimbic pathways. The aim of the present study was to perform a literature review on impulsivity, impulse control disorders and related conditions among patients with Parkinson's disease, with emphasis on their epidemiology, clinical characteristics and treatment.
RESUMO Alterações neuropsiquiátricas são comuns na doença de Parkinson e estão presentes em todas as fases da enfermidade. No entanto, frequentemente não são reconhecidas e recebem tratamento insuficiente. Ao longo dos últimos anos, observou-se que a terapia de reposição dopaminérgica pode levar ao desenvolvimento ou piora de condições como transtorno do jogo, compulsão por sexo, compras, e comida, além da síndrome de desregulação dopaminérgica e punding. Sua fisiopatologia parece estar relacionada à estimulação dopaminérgica anormal das regiões basais dos núcleos da base, sobretudo pelas vias nigro-mesolímbicas. O presente artigo tem como objetivo fazer uma revisão da literatura a respeito de impulsividade, transtornos do controle de impulso e condições relacionadas na doença de Parkinson, com foco na epidemiologia, características clínicas e tratamento.
Assuntos
Humanos , Doença de Parkinson/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Prognóstico , Fatores de RiscoRESUMO
The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. OBJECTIVE: To report the relative frequency of common neuromuscular diagnoses in a reference center. METHODS: A 17-year chart review of patients with suspicion of myopathy. RESULTS: Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). CONCLUSION: Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.
Assuntos
Doenças Neuromusculares/diagnóstico , Biópsia , Feminino , Humanos , Masculino , Doenças Neuromusculares/genética , Doenças Neuromusculares/patologia , Estudos RetrospectivosRESUMO
ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Conclusion: Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.
RESUMO O procedimento diagnóstico neuromuscular é complexo. O conhecimento da frequência relativa das doenças neuromusculares em uma população é importante para utilização dos testes diagnósticos mais apropriados. Objetivo: Relatar a frequência relativa de doenças neuromusculares em um centro de referência. Métodos: Revisão de prontuários de pacientes com suspeita de miopatia em 17 anos. Resultados: Dentre 3412 exames, 1603 (46,98%) foram confirmatórios: 782 (48,78%) estudos moleculares e 821 (51,21%) biópsias musculares. Os diagnósticos mais frequentes foram: distrofinopatia 460 (28,70%), mitocondriopatia 330 (20.59%), atrofia muscular espinhal 158 (9,86%), distrofia muscular cintura-membros 157 (9,79%), distrofia miotônica de Steinert 138 (8,61%), distrofia muscular face-escápulo-umeral 99 (6,17%) e outros diagnósticos 261 (16,28%). Conclusão: Utilizando as técnicas diagnósticas atualmente disponíveis em nosso serviço, o diagnóstico específico do subtipo de distrofia muscular cintura-membros foi obtido em 61% dos pacientes. O diagnóstico neuromuscular apropriado é importante para o aconselhamento genético, orientações de reabilitação e tratamento precoce de complicações respiratórias e cardíacas.
Assuntos
Humanos , Masculino , Feminino , Doenças Neuromusculares/diagnóstico , Biópsia , Estudos Retrospectivos , Doenças Neuromusculares/genética , Doenças Neuromusculares/patologiaRESUMO
BACKGROUND: Dystrophinopathies are X-linked muscular dystrophies characterized by pathogenic mutations in the dystrophin gene. Symptomatic dystrophinopathy female carriers may present with limb-girdle weakness. The diagnosis may be challenging in the absence of affected male relatives. We aimed to describe the phenotypic variability in a series of molecular-confirmed female dystrophinopathy patients. METHODS: This is a retrospective analysis of medical records from 1997 to 2015. RESULTS: Ten female dystrophinopathy patients were selected, two with unusual phenotypes: one with early joint contractures muscular dystrophy and the other with very late onset myopathy. Muscle imaging studies demonstrated predominant asymmetric fat replacement. Muscle biopsy immunohistochemistry demonstrated clear mosaic pattern in two cases and only subtle reduction of dystrophin intensity in three. CONCLUSIONS: Adequate diagnosis is fundamental for genetic counseling and cardiologic follow-up. Female patients with dystrophinopathy may present unusual phenotypes such as early contractures and very late onset myopathy.
Assuntos
Distrofina/genética , Heterozigoto , Distrofias Musculares/diagnóstico por imagem , Distrofias Musculares/genética , Fenótipo , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.
Assuntos
Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Ilustração Médica , Músculos/diagnóstico por imagem , Músculos/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.
As distrofias musculares progressivas cintura-membros são desordens neuromusculares hereditárias autossômicas heterogêneas. Elas produzem alterações distróficas à biópsia muscular e estão associadas a mutações em diversos genes envolvidos na estrutura e função muscular. Fluxograma diagnóstico, fotos, tabelas e diagramas ilustrados dos aspectos clínicos, laboratoriais e de imagem são apresentados para o diagnóstico diferencial de distrofias musculares cintura-membros autossômicas recessivas comuns, diagnosticadas atualmente em um centro de referência no Brasil. Exames de imagem pré-operatórios direcionam o local da biópsia muscular. O padrão de envolvimento muscular difere de acordo com o subtipo de distrofia muscular cintura-membros. A substituição fibroadiposa do tecido muscular é mais acentuada no compartimento posterior da coxa na calpainopatia e proteinopatia relacionada à fukutina; anterior da coxa na sarcoglicanopatia; difusa na coxa na disferlinopatia e teletoninopatia. O diagnóstico diferencial preciso das distrofias musculares cintura-membros é importante para o aconselhamento genético, orientação prognóstica, tratamento cardíaco e respiratório. Além disso poderá, no futuro, provavelmente, propiciar terapias gênicas específicas para cada subtipo.
Assuntos
Feminino , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Biópsia , Diagnóstico Diferencial , Ilustração Médica , Músculos/patologia , Músculos , Distrofia Muscular do Cíngulo dos Membros/genética , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The knowledge about the natural history of stroke in Chagas disease is incomplete. METHODS: Vascular risk factors and stroke subtypes of asymptomatic Trypanosoma cruzi-infected patients with no clinical evidence of heart failure were assessed. They were compared with chronic chagasic cardiomyopathy patients who suffered a stroke and with a control group of 60 T. cruzi-noninfected stroke patients. Eighty-six consecutive chagasic stroke patients (mean age: 57.4 years; 64% females) were studied. RESULTS: 38.4% of chagasic stroke patients had asymptomatic T. cruzi infection. Smoking was more frequent in asymptomatic chagasic stroke patients (21.2 vs. 5.7%; p = 0.04). Prevalence of hypertension, diabetes and prior stroke was similar in both groups. Small-vessel infarction (15.6 vs. 3.8%) and large-vessel atherosclerosis (9.4 vs. 3.8%) were significantly more frequent in asymptomatic than in symptomatic T. cruzi-infected stroke patients (p = 0.001). Nevertheless, their frequency was even higher in T. cruzi-noninfected stroke patients (36.7 and 13.3%, respectively). Apical aneurysm (27.3%), left atrial dilatation (12.1%), left ventricle hypokinesia (9.4%) and right bundle branch block (36.4%) were also detected in asymptomatic T. cruzi-infected stroke patients. CONCLUSIONS: Ischemic stroke may be the first manifestation of Chagas disease in asymptomatic patients with mild left ventricle dysfunction. Other noncardioembolic stroke subtypes can occur in asymptomatic T. cruzi-infected patients.