Assuntos
Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Doença dos Neurônios Motores/genética , Insuficiência Respiratória/genética , Paralisia Respiratória/genética , Atrofias Musculares Espinais da Infância/genética , Fatores de Transcrição/genética , Adulto , Idade de Início , Criança , Feminino , Testes Genéticos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico , Exame Neurológico , Fenótipo , Polimorfismo Genético/genética , Insuficiência Respiratória/diagnóstico , Paralisia Respiratória/diagnóstico , Atrofias Musculares Espinais da Infância/diagnósticoRESUMO
BACKGROUND: In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), CSF biomarkers are increasingly studied to evaluate their relevance for differential diagnosis, disease progression, and understanding of pathophysiologic processes. OBJECTIVE: To identify a biomarker profile of neuronal and glial CSF proteins to discriminate ALS from other motor neuron diseases (MND) and to assess whether baseline levels of CSF measures in ALS are associated with the course of the disease. METHODS: A total of 122 consecutive subjects with MND were included in this cross-sectional study (ALS, n = 75; lower motor neuron syndrome, n = 39; upper motor neuron diseases, n = 8). Clinical follow-up included 76 patients. We determined baseline levels of protein tau and astroglial S100beta in CSF and microglial sCD14 in CSF and serum in relation to diagnosis, duration of disease, and survival. RESULTS: CSF tau was significantly elevated in ALS and upper motor neuron diseases as compared to lower motor neuron diseases and controls. CSF S100beta levels were significantly lower in lower motor neuron diseases as compared to other MND. CSF concentrations of S100beta and sCD14 correlated with the survival time in patients with ALS. CONCLUSIONS: In motor neuron diseases, CSF tau elevation indicates the degeneration of upper motor neurons, while S100 beta and sCD14 may indicate the activation of CNS glial cells. Because S100beta and sCD14 concentrations correlate with survival in amyotrophic lateral sclerosis (ALS), we suppose that the combination of both markers may be useful to obtain prognostic information in patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica/líquido cefalorraquidiano , Fatores de Crescimento Neural/líquido cefalorraquidiano , Proteínas S100/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/mortalidade , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/sangue , Doença dos Neurônios Motores/líquido cefalorraquidiano , Fatores de Crescimento Neural/sangue , Prognóstico , Curva ROC , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/sangue , Taxa de Sobrevida , Proteínas tau/sangueRESUMO
OBJECTIVE: Myocardial involvement in motor neuron diseases (MND) is an uncommon feature. In amyotrophic lateral sclerosis (ALS) abnormalities of the autonomic nervous system affecting cardiac function have been described, for the hereditary spastic paraplegias (HSP) comparable manifestations are unknown. This study observed ALS and HSP patients with coexisting cardiomyopathy without major cardial risk factors. METHODS: Four patients with definite ALS and two pHSP patients. In all patients detailed clinical, cardiological, electrophysiological and laboratory data were analysed. In two ALS patients skeletal muscle biopsy was performed. RESULTS: In all investigated MND patients cardiomyopathy was present. Beside hyperlipoproteinaemia and mild hypertension in one case, none of the patients showed major cardiovascular risk factors. There was no evidence for a secondary cause of cardiomyopathy like coronary heart disease, myocarditis, or mitochondrial damage mimicking MND. CONCLUSION: This report could not conclude that the occurrence of cardiomyopathy is rare logically. Although an underlying pathophysiological cause was not obvious, it is proposed that in all MND patients a routine cardiological evaluation should be performed.