Pathophysiology and Treatment of Syringomyelia

脊髓空洞症的病理生理学和治疗

• 批准号: 8342270
• 负责人: Russell Lonser
• 金额: $ 73.67万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8342270
• 关键词: Affect; Appearance; Brain; Caring; Cerebellar tonsil; Cerebellum; Cerebrospinal Fluid; Cerebrospinal Fluid Pressure; Characteristics; Clinical Research; Congenital Disorders; Cyst; DNA; Data; Development; Etiology; Family; Family member; Functional disorder; Future; Genetic; Genotype; Infection; Lead; Magnetic Resonance Imaging; Measures; Medulla Oblongata; Monitor; Natural History; Neurologic Dysfunctions; Neurologic Examination; Obstruction; Operative Surgical Procedures; Outcome; Pain; Paralysed; Pathway interactions; Patients; Phenotype; Posterior Fossa; Process; Publishing; Reporting; Shapes; Specimen; Spinal; Spinal Cord; Structure; Subarachnoid Space; Syringomyelia; Trauma; Vertebral column; foramen magnum; genetic linkage analysis; genome wide association study; malformation; member; relating to nervous system; skull base; trait; tumor

Genetics of Chiari I Malformation. Syringomyelia is most often associated with Chiari I malformation. The process by which the Chiari I malformation develops is unknown. Ectopia of the cerebellar tonsils (through the foramen magnum at the base of the skull), which is the defining characteristic of the Chiari I malformation, may result because the posterior fossa does not develop normally. In a clinical study of families with multiple members affected by the Chiari I malformation, we are using magnetic resonance imaging of the brain to evaluate for Chiari I malformation and to measure the size of the osseous structures and volume of the posterior fossa. After phenotyping family members as being affected or unaffected by these traits, we collect DNA specimens from them for genotyping. Genotyping and phenotyping have been completed and linkage analysis and genome-wide association studies (GWAS) are being performed. Finding one or more genetic loci that are associated with the Chiari I malformation would lead to a better understanding of the etiology of the Chiari I malformation. Treatment of Syringomyelia. A natural history study of patients with syringomyelia was initiated this year in which patients will be monitored annually for 5 years with neurological examinations, standard scales of pain and function, and MRI of the brain and spine. Patients receive specialized care for their condition, including surgery if necessary. This study will better define the outcome of patients with syringomyelia and will provide preliminary data to generate hypotheses for future hypothesis-driven studies. This year we reported a study that evaluated the morphologic features of the cerebellum and medulla oblongata before and 3-6 months after surgery in patients with Chiari I malformation and syringomyelia. After surgery that expands the posterior fossa, the abnormal shape of the cerebellum and medulla oblongata characteristic of the Chiari I malformation will change to a more normal appearance. These findings support the concept that the Chiari I malformation arises from lack of development of the posterior fossa rather than a primary neural abnormality. This year we published a clinical study of the pathophysiology of persistent syringomyelia after craniocervical decompression. In these subjects, we have found that previous surgery failed simply because it did not relieve the obstruction of the cerebrospinal pathways at the foramen magnum. This year we reported another clinical study studying primary spinal syringomyelia, a type of syringomyelia not associated with Chiari I malformation. A preliminary finding was that obstruction of the spinal subarachnoid space in primary spinal syringomyelia was associated with enlarged cerebrospinal fluid (CSF) pressure waves superior to the obstruction. Successful surgery for primary spinal syringomyelia opens CSF pathways, reduces CSF pressure waves to normal and resolves syringomyelia, as had successful surgery in our studies of Chiari I-type syringomyelia. This association suggests that primary spinal syringomyelia and Chiari I-type syringomyelia arise from a similar mechanism.

Chiari I畸形的遗传学。 色疗中心通常与Chiari I畸形有关。 Chiari I畸形发生的过程尚不清楚。小脑扁桃体（通过颅骨底部的孔的大量）的外生可能会导致Chiari I畸形的定义特征，因为后窝没有正常发育。在对受Chiari I畸形影响的多个成员家庭的临床研究中，我们使用大脑的磁共振成像来评估Chiari I畸形并测量骨结构的大小和后孔的体积。在将家族成员表现为受这些特征影响或不影响这些特征后，我们从中收集了DNA标本进行基因分型。基因分型和表型已经完成，并且正在进行连锁分析和全基因组关联研究（GWAS）。找到与Chiari I畸形相关的一个或多个遗传基因座将使人们更好地理解Chiari I畸形的病因。 脊髓瘤的治疗。 今年启动了对血管瘤患者的自然史研究，其中每年将通过神经系统检查，疼痛和功能标准尺度以及大脑和脊柱的MRI监测患者5年。 患者为自己的病情接受专门护理，包括需要手术。 这项研究将更好地定义血管瘤患者的结果，并将提供初步数据，以产生假设驱动的研究的假设。 今年，我们报道了一项研究，该研究评估了Chiari I畸形和色疗中心患者的小脑和髓质长肌的形态学特征和手术后3-6个月的形态特征。 在扩展后窝的手术后，小脑和髓质长方体的异常形状的chiari i畸形特征将变为更正常的外观。 这些发现支持以下概念：Chiari I畸形是由于缺乏后窝而不是主要神经异常而引起的。 今年，我们发表了一项临床研究，该研究对颅尾减压后持续性脊髓瘤的病理生理学。在这些受试者中，我们发现以前的手术仅仅是因为它没有缓解孔孔大脑处的脑脊髓途径的阻塞。今年，我们报道了另一项研究原发性脊柱脊髓念珠菌的临床研究，这是一种与Chiari I畸形无关的脊髓念珠菌。一个初步发现是，原发性脊髓脊髓脊髓脊髓脊髓脊髓脊髓杆菌的阻塞与脑脊液增大（CSF）压力波相对于障碍物。原发性脊髓脊髓瘤的成功手术开放了CSF途径，将CSF压力波降低到正常，并溶解了脊髓脊髓瘤，在我们对Chiari I-I-type Symyomyelia的研究中成功手术。该关联表明，原发性脊髓色疗中心和Chiari I型色疗中心是由类似的机制引起的。