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.

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Pan, Kristen S; Heiss, John D; Brown, Sydney M et al. (2018) Chiari I Malformation and Basilar Invagination in Fibrous Dysplasia: Prevalence, Mechanisms, and Clinical Implications. J Bone Miner Res 33:1990-1998
Heiss, John D; Jarvis, Katie; Smith, René K et al. (2018) Origin of Syrinx Fluid in Syringomyelia: A Physiological Study. Neurosurgery :
Bogdanov, Enver I; Faizutdinova, Aisylu T; Mendelevich, Elena G et al. (2018) Epidemiology of Symptomatic Chiari Malformation in Tatarstan: Regional and Ethnic Differences in Prevalence. Neurosurgery :
Shepard, Matthew J; Padmanaban, Varun; Edwards, Nancy A et al. (2017) Discovery of Aquaporin-1 and Aquaporin-4 Expression in an Intramedullary Spinal Cord Ependymal Cyst: Case Report. World Neurosurg 107:1046.e1-1046.e7
Buell, Thomas J; Heiss, John D; Oldfield, Edward H (2015) Pathogenesis and Cerebrospinal Fluid Hydrodynamics of the Chiari I Malformation. Neurosurg Clin N Am 26:495-9
Heiss, John D; Oldfield, Edward H (2014) Response. J Neurosurg Spine 21:315-6
Linge, Svein O; Mardal, Kent-A; Helgeland, Anders et al. (2014) Effect of craniovertebral decompression on CSF dynamics in Chiari malformation type I studied with computational fluid dynamics: Laboratory investigation. J Neurosurg Spine 21:559-64
Oishi, Masahiro; Hayashi, Yasuhiko; Kita, Daisuke et al. (2013) Rapidly progressing monoparesis caused by Chiari malformation type I without syringomyelia. Surg Neurol Int 4:79
Heiss, John D; Suffredini, Giancarlo; Bakhtian, Kamran D et al. (2012) Normalization of hindbrain morphology after decompression of Chiari malformation Type I. J Neurosurg 117:942-6
Heiss, John D; Snyder, Kendall; Peterson, Matthew M et al. (2012) Pathophysiology of primary spinal syringomyelia. J Neurosurg Spine 17:367-80

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