학술논문
Utilidad de la resonancia magnética como marcador para el seguimiento de pacientes con enfermedad de pompe del adulto
Document Type
Dissertation/Thesis
Source
TDX (Tesis Doctorals en Xarxa)
Subject
616.8
Language
Spanish; Castilian
Abstract
En la enfermedad de Pompe, la acumulación progresiva de glucógeno en el músculo culmina con la pérdida progresiva de fibras musculares y la sustitución del tejido muscular por tejido fibro-adiposo. La terapia de reemplazo enzimático (TRE) ha mostrado que es capaz de estabilizar la sintomatología de los pacientes, a pesar de que todo parece indicar que el deterioro muscular continúa progresando lo que lleva a el empeoramiento de la fuerza muscular. Es evidente que necesitamos nuevos marcadores de seguimiento que sean capaces de identificar cambios en la estructura muscular que todavía no se traducen en un cambio en la debilidad muscular. La imagen de resonancia magnética se ha establecido en los últimos años como una herramienta útil en el seguimiento de las miopatías hereditarias, como la enfermedad de Pompe, ya que es capaz de mostrar cambios en la estructura muscular, especialmente acúmulo de grasa, antes de que se produzca un impacto en los síntomas de los pacientes. En la presente tesis doctoral, exploramos la utilidad de dos técnicas específicas de resonancia magnética (secuencia 2 punto-Dixon y la Transferencia de Magnetización) para caracterizar y cuantificar el daño en los músculos esquelético de pacientes con enfermedad de Pompe de inicio tardío. En nuestros estudios hemos observado que la resonancia muestra cambios antes de que éstos tengan un impacto en la función muscular, por lo que se plantea como una muy buena técnica para realizar el seguimiento de la respuesta a la TRE de los pacientes en la clínica diaria, pero también en ensayos clínico que analizan la eficacia de nuevas terapias. En el caso de los pacientes pre-sintomáticos, un aumento de grasa puede indicar que la enfermedad muscular ha empezado a afectar la capacidad de los músculos de los pacientes para regenerarse y éstos están degenerando, dando paso a la pérdida de fibras musculares y aumento de fracción grasa. Estos datos sugieren que la técnica de Dixon puede ser útil tanto en la clínica diaria como en los estudios de historia natural o en ensayos clínicos en pacientes con enfermedad de Pompe. La segunda técnica de resonancia magnética utilizada en esta tesis fue la transferencia de magnetización (TM) con el fin de estudiar los cambios estructurales que podrían estar relacionados con la acumulación de glucógeno en el musculo de estos pacientes. Hemos observado que existe una correlación negativa entre la fracción grasa y la TM, es decir a mayor contenido graso menor TM, lo que confirma que la masa grasa tiene un menor número de macromoléculas, a diferencia del músculo esquelético que tiene una gran cantidad de proteínas que forman parte de la estructura sarcomérica. Estos datos sugieren que la TM es útil para detectar pérdida de masa muscular en los pacientes con enfermedad de Pompe. Consecuentemente, hemos evidenciado una correlación significativa entre la TM y los resultados de las pruebas funcionales, demostrando que esta técnica podría ser útil en el seguimiento de los pacientes con esta enfermedad.
In Pompe disease, the progressive accumulation of glycogen in the muscle culminates in the progressive loss of muscle fibers and the replacement of muscle tissue with fibro-adipose tissue. Enzyme replacement therapy (ERT) is able to stabilize patients’ symptomatology, although it seems that muscle deterioration continues to progress leading to worsening muscle strength. We need new follow-up markers that can identify changes in muscle structure that do not yet translate into a change in muscle weakness. Magnetic resonance imaging has been established in recent years as a useful tool in the follow-up of hereditary myopathies, such as Pompe disease, as it can show changes in muscle structure, especially fat accumulation before there is an impact on patients’ symptoms. In the present dissertation, we explored the usefulness of two specific MRI techniques (2-point-Dixon sequence and Magnetization Transfer) to characterize and quantify skeletal muscle damage in patients with late-onset Pompe disease. In our studies we have observed that MRI shows changes before they have an impact on muscle function, making it a very good technique for monitoring the response to ERT of patients in daily clinical practice, but also in clinical trials analyzing the efficacy of new therapies. In the case of pre-symptomatic patients, an increase in fat may indicate that the muscle disease has started to affect the ability of the patient’s muscles to regenerate and they are degenerating, giving way to loss of muscle fibers and an increase in fat fraction. These data suggest that Dixon’s technique may be useful both in daily clinical practice and in natural history studies or clinical trials in patients with Pompe disease. The second MRI technique used in this thesis was magnetization transfer (MT) to study structural changes that could be related to glycogen accumulation in the muscle of these patients. We have observed that there is a negative correlation between fat fraction and MT, i.e. the higher the fat content the lower the MT, which confirms that fat mass has a lower number of macromolecules, unlike skeletal muscle which has a large amount of proteins that are part of the sarcomeric structure. These data suggest that MT is useful for detecting muscle mass loss in patients with Pompe disease. Consequently, we have evidenced a significant correlation between MT and functional test results, demonstrating that this technique could be useful in the follow-up of patients with this disease.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina
In Pompe disease, the progressive accumulation of glycogen in the muscle culminates in the progressive loss of muscle fibers and the replacement of muscle tissue with fibro-adipose tissue. Enzyme replacement therapy (ERT) is able to stabilize patients’ symptomatology, although it seems that muscle deterioration continues to progress leading to worsening muscle strength. We need new follow-up markers that can identify changes in muscle structure that do not yet translate into a change in muscle weakness. Magnetic resonance imaging has been established in recent years as a useful tool in the follow-up of hereditary myopathies, such as Pompe disease, as it can show changes in muscle structure, especially fat accumulation before there is an impact on patients’ symptoms. In the present dissertation, we explored the usefulness of two specific MRI techniques (2-point-Dixon sequence and Magnetization Transfer) to characterize and quantify skeletal muscle damage in patients with late-onset Pompe disease. In our studies we have observed that MRI shows changes before they have an impact on muscle function, making it a very good technique for monitoring the response to ERT of patients in daily clinical practice, but also in clinical trials analyzing the efficacy of new therapies. In the case of pre-symptomatic patients, an increase in fat may indicate that the muscle disease has started to affect the ability of the patient’s muscles to regenerate and they are degenerating, giving way to loss of muscle fibers and an increase in fat fraction. These data suggest that Dixon’s technique may be useful both in daily clinical practice and in natural history studies or clinical trials in patients with Pompe disease. The second MRI technique used in this thesis was magnetization transfer (MT) to study structural changes that could be related to glycogen accumulation in the muscle of these patients. We have observed that there is a negative correlation between fat fraction and MT, i.e. the higher the fat content the lower the MT, which confirms that fat mass has a lower number of macromolecules, unlike skeletal muscle which has a large amount of proteins that are part of the sarcomeric structure. These data suggest that MT is useful for detecting muscle mass loss in patients with Pompe disease. Consequently, we have evidenced a significant correlation between MT and functional test results, demonstrating that this technique could be useful in the follow-up of patients with this disease.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina