Discovering the Origin of Syrinx Fluid

Syringomyelia Fluid collection within the center of the spinal cord that expands the diameter of the spinal cord Causes spinal cord injury and dysfunction Weakness and loss of muscle Loss of pain and temperature sensation Stiffness and lack of control of the legs (lower extremity spasticity

Possible Origins of Syrinx Fluid in Chiari I malformation Increased fluid production in the spinal cord From filtered blood (serum) entering the spinal cord through abnormal, leaky small blood vessels (capillaries) Syrinx related to spinal cord tumors From filtered blood (serum) entering the spinal cord through capillaries that are under higher than normal pressure Mechanism in syrinx related to spinal cord arteriovenous malformations Decreased drainage of fluid from the spinal cord –Obstructed outflow of CSF from the central canal of the spinal cord –Decreased movement of CSF out of the spinal cord and into the subarachnoid space Obstructed outflow or decreased absorption of CSF from the brain results in hydrocephalus so why couldn’t decreased removal of fluid from the inside of the spinal cord result in syringomyelia? From CSF entering the spinal cord from the subarachnoid space outside the spinal cord due to increased CSF pressure (hydrostatic pressure)

Why Is This Research Important? Research addresses an unanswered medical or scientific question: What is the Origin of Syrinx Fluid? Research provides new knowledge, in this case knowledge of the process by which a syrinx develops. Knowledge could lead to new ways of thinking about the condition of syringomyelia and its treatment. Knowledge might lead to better treatments for dealing with syrinx formation and resolution. Knowledge might indicate ways to prevent a syrinx from developing in a patient with asymptomatic Chiari I malformation or in a patient who has experienced spinal trauma.

Does Chiari I Syrinx Fluid Originate from CSF (cerebrospinal fluid)? Historical Evidence: Chiari I patients with increased fluid diffusely (edema) within the spinal cord can later develop a syrinx Syrinx fluid in Chiari I-related syringomyelia is chemically identical to CSF, whereas syrinx fluid in syringomyelia associated with tumors and AVM’s have a higher protein concentration than CSF, reflecting its origin as a blood filtrate Myelogram dye enters the syrinx from the CSF in the spinal subarachnoid space on a delayed basis

Syrinx Development 3 Months Before Surgery1 Week Before Surgery

Stages of Fluid Accumulation and Syrinx Formation in Chiari I-Related Syringomyelia Chiari I without a syrinx Normal spinal cord Pre-syringomyelia Diffuse increase in s.c. fluid (Infrequently documented) SyringomyeliaExpanded fluid collection in the spinal cord Post-syringomyelia Narrow fluid collection

CT-Myelogram Study Eligibility: Patients with Chiari 1-syringomyelia, primarily spinal syringomyelia, or tumor-related syringomyelia Rationale: Because myelogram dye is in solution in the CSF, dye will acts as a marker of the movement of CSF (cerebrospinal fluid) Hypothesis: More dye (CSF) will enter the syrinx before compared to after surgery Procedure: CT-myelogram before and 1 week after surgery –Baseline CT image through the syrinx –Inject local anesthetic into the skin of the low back –Insert a 22 gauge (a small diameter) spinal needle –Measure CSF pressure –Remove 10 mL (2 teaspoons) of CSF –Inject 10 mL of myelogram dye (300 mg/mL of organically-bound iodine) into the CSF in the subarachnoid space –CT cut through the syrinx every 2 hours for 10 hours and then at 24 hours after the injection; make a graph of the result

CT-Myelogram Study Subjects Chiari I-related syringomyelia18 Primarily spinal syringomyelia10 Post-traumatic Focal arachnoiditis Spinal cord tumor 7 Hemangioblastoma

Entry of dye (CSF) into the Syrinx SyrinxSAS K(2,1) K(1,2) 1 2 Spinal Cord Wall

Hounsfield Units vs. Dye Concentration

Patients with Syrinx Shunts were Excluded from Analysis Concentration in SAS, mg/ml Concentration in Syrinx, mg/ml Concentration, mg/ml Time post-injection, hr

Syringomyelia from Chiari I Before Surgery Subarachnoid CSF Spinal cord tissue Syrinx fluid Concentration, mg/ml Time after injection, hr Subarachnoid CSF Spinal cord tissue Syrinx fluid Concentration, mg/ml Time after injection, hr After Surgery

Dye Movement, Chiari I Before and After Surgery Two compartment fit to background subtracted measurement in syrinx from PreOp CT-myelogram Measurement Simulation H. U. Time, hours k influx = hr k efflux = hr Measurement Simulation H. U. Time, hours k influx = hr k efflux = hr Two compartment fit to background subtracted measurement in syrinx from PostOp CT-Myelogram JW

Slow Decrease in Syrinx Size after Chiari I Surgery Mirrors Change in CSF Movement Into the Syrinx and Syrinx Fluid Movement Out of the Syrinx Figure 1. On T1-weighted sagittal MR images, a syrinx that is present before surgery (A) is little changed by 1 week after surgery (B), but then progressively becomes smaller by 3 months (C) and 1 year after surgery (D).

Chiari I Syrinx Resolution—A Slow Process Figure 3. On T1-weighted sagittal MR images, a syrinx (A) that is present before surgery becomes smaller by 1 week (B), and has nearly disappeared by 3 months after surgery that opens CSF pathways at the foramen magnum.

Primary Spinal Syringomyelia Before Surgery After Surgery

Primary Spinal Syringomyelia— More dye in the syrinx before, compared to after surgery

Primary Spinal Syringomyelia-- Less Dye Enters the Syrinx after Surgery

Primary Spinal Syringomyelia Before Surgery After Surgery Before Surgery3 Mos. After Surgery

More Myelogram Dye Enters the Syrinx in Syringomyelia Not Associated With Spinal Cord Tumors than in Patients with Spinal Cord Tumors

Chiari With Syrinx Primarily Spinal Syrinx Spinal Cord Tumor Number Mean Std Dev

Maximal Syrinx Intensity Hounsfield Units Pre-Op Post-Op Maximal syrinx intensity measurements for subjects with Primarily Spinal Syringomyelia before surgery (blue) and after surgery (red).

Average Change in Maximal Syrinx Intensity Hounsfield Units, normalized Pre-Op Post-Op Primary Spinal Syrinx (n=8), *p<0.05 * Chiari I Malformation with Syrinx (n=11) Combined Non- Tumor Syrinx (n=19), *<0.05 * Both Primary Spinal Syrinx group and Combined Non-Tumor Syrinx group had significant decrease in maximal syrinx dye concentration after surgery (p<0.05).

Unifying Theory of Syringomyelia Pathophysiology Chiari IPrimary Spinal