Pathophysiology and Treatment of Syringomyelia

脊髓空洞症的病理生理学和治疗

• 批准号: 8158233
• 负责人: Russell Lonser
• 金额: $ 66.06万
• 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/8158233
• 关键词: Affect; Cerebellar tonsil; Characteristics; Congenital Disorders; Cyst; DNA; Development; Etiology; Family; Functional disorder; Genotype; Infection; Invaded; Lead; Magnetic Resonance Imaging; Nervous system structure; Pathway interactions; Posterior Fossa; Procedures; Process; Resolution; Syringomyelia; base; foramen magnum; skull base

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 phenotyping have been completed this year and linkage analysis is being performed. 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 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. 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。 脊髓空洞症可能与 Chiari I 畸形有关。 Chiari I 畸形的发展过程尚不清楚。 小脑扁桃体异位（通过颅骨底部的枕骨大孔）是 Chiari I 型畸形的典型特征，可能是由于后颅窝发育不正常而导致的。 在一项针对多个成员受 Chiari I 畸形影响的家庭的临床研究中，我们使用大脑磁共振成像来评估 Chiari I 畸形并测量骨结构的大小和后颅窝的体积。 在对家庭成员进行表型分析后，我们会收集他们的 DNA 样本进行基因分型。 今年已完成基因分型和表型分析，正在进行连锁分析。找到 Chiari I 畸形的遗传位点将有助于更好地了解 Chiari I 畸形的病因。 治疗脊髓空洞症。 一项阐明与 Chiari I 畸形相关的脊髓空洞症基础的临床研究已经完成，其中矛盾的是，该机制显示在脊髓外部，而不是内部。通过不侵入神经系统的手术（颅颈减压），成功的手术消除了压力波过大的解剖原因，并一致解决了脊髓空洞症。 这种机制的证明应该可以为这种形式的脊髓空洞症提供更有效的治疗。 今年我们报道了一项颅颈减压术后持续性脊髓空洞症病理生理学的临床研究。在这些受试者中，我们发现之前的手术失败仅仅是因为它没有缓解枕骨大孔处脑脊髓通路的阻塞。在另一项临床研究中，我们正在研究原发性脊髓空洞症，这是一种与 Chiari I 畸形无关的脊髓空洞症类型。初步发现，原发性脊髓空洞症中脊髓蛛网膜下腔的阻塞与大于阻塞的脑脊液（CSF）压力波增大有关。原发性脊髓空洞症的成功手术可打开脑脊液通路，将脑脊液压力波降至正常并解决脊髓空洞症，正如我们在 Chiari I 型脊髓空洞症研究中的成功手术一样。这种关联表明原发性脊髓空洞症和 Chiari I 型脊髓空洞症源于相似的机制。