Pathophysiology and Treatment of Syringomyelia

脊髓空洞症的病理生理学和治疗

• 批准号: 7735337
• 负责人: Russell Lonser
• 金额: $ 51.7万
• 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/7735337
• 关键词: Affect; Anatomy; Brain; Cerebellar tonsil; Cerebrospinal Fluid; Cerebrospinal Fluid Pressure; Characteristics; Clinical Research; Condition; Congenital Disorders; Cyst; DNA; Decompressive incision; Development; Etiology; Family; Family member; Functional disorder; Genetic; Genotype; Infection; Invaded; Invasive; Lead; Magnetic Resonance Imaging; Measures; Nervous system structure; Neurologic Dysfunctions; Obstruction; Operative Surgical Procedures; Paralysed; Pathway interactions; Patients; Phenotype; Posterior Fossa; Procedures; Process; Purpose; Reporting; Resolution; Specimen; Spinal; Spinal Cord; Structure; Subarachnoid Space; Symptoms; Syringes; Syringomyelia; Time; Trauma; base; external Decompression; foramen magnum; genetic linkage analysis; malformation; member; painful neuropathy; pressure; size; skull base; trait; tumor

Genetics Chiari I Malformation. Syringomyelia can be 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 linkage analysis will be performed after all family members in the study have been phenotyped. Finding a genetic locus for the Chiari I malformation would lead to a better understanding of the etiology of the Chiari I malformation. Treatment of Syringomyelia. A clinical study elucidating the basis of syringomyelia associated with the Chiari I malformation was completed in which the mechanism was shown, paradoxically, to be outside, not inside, the spinal cord. Successful surgery, by a procedure that does not invade the nervous system (craniocervical decompression), eliminated the anatomic cause of the excess pressure waves and resulted in consistent resolution of syringomyelia. The demonstration of this mechanism should result in more effective treatment for this form of syringomyelia. This year we reported the time course for changes in syrinx size after craniocervical decompression for Chiari I malformation and syringomyelia. Decrease in syrinx size after this surgery is a slow process that takes several months to years to complete. Radiographic resolution of the syrinx is associated with stabilization or mild improvement in most symptoms, but neuropathic pain of some degree remains a persistent problem in most patients. In a related study, we are continuing to evaluate and treat subjects with Chiari I-type syringomyelia but who have had unsuccessful surgery elsewhere. 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. In another clinical study we are studying primary spinal syringomyelia, a type of syringomyelia not associated with Chiari I malformation. A preliminary finding is that obstruction of the spinal subarachnoid space in primary spinal syringomyelia is 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.

遗传学Chiari I畸形。 脊椎队可能与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。 在研究了所有家庭成员之后，将进行基因分型和连锁分析。找到Chiari I畸形的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。 一项阐明了与Chiari I畸形相关的脊椎动物基础的临床研究完成，在该研究中，矛盾地显示了该机制，即在外面而不是内部，而不是脊髓。通过不侵入神经系统（颅尾解减压）的手术，成功的手术消除了过量压力波的解剖原因，并导致了脊椎队的一致分辨率。 这种机制的证明应导致对这种形式的色疗形式的更有效的治疗。 今年，我们报道了Craniocervical Decompressions Chiari I畸形和脊椎队的颅骨减压后Syrinx大小变化的时间课程。 该手术后的Syrinx大小的减小是一个缓慢的过程，需要几个月到几年才能完成。 在大多数症状中，Syrinx的放射学分辨率与稳定或轻度改善有关，但是在大多数患者中，神经性疼痛在某种程度上仍然是一个持续的问题。 在一项相关研究中，我们正在继续评估和治疗Chiari I型色疗中心的受试者，但在其他地方的手术失败。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。在另一项临床研究中，我们正在研究原发性脊髓色瘤，这是一种与Chiari I畸形无关的脊髓瘤。初步发现是，原发性脊柱脊髓脊髓脊髓脊髓蛛网膜下腔的阻塞与脑脊液肿大（CSF）压力波相比，高于障碍物。 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。