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 Surgery 1 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)
• Syringomyelia Expanded 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 syringomyelia 18

Primarily spinal syringomyelia 10
• Post-traumatic
• Focal arachnoiditis
Spinal cord tumor 7
• Hemangioblastoma
 Spinal
Entry Cord
Wall
of dye SAS Syrinx
(CSF) K(1,2)
into the 1 2
Syrinx K(2,1)
Hounsfield Units vs. Dye Concentration
Patients with Syrinx Shunts were
Excluded from Analysis
20
Concentration in SAS, mg/ml
Concentration, mg/ml

Concentration in Syrinx, mg/ml

15

10

0
0 5 10 15 20 25 30
Time post-injection, hr
 Syringomyelia from Chiari I
Before Surgery After Surgery

20 20

Subarachnoid CSF Subarachnoid CSF

Spinal cord tissue Spinal cord tissue
Syrinx fluid 15 Syrinx fluid
15

Concentration, mg/ml
Concentration, mg/ml

10 10

5 5

0 0
0 10 20 30 40 50 0 10 20 30 40 50
Time after injection, hr Time after injection, hr
 Dye Movement, Chiari I Before and After Surgery

Two compartment fit to background Two compartment fit to background

subtracted measurement in syrinx subtracted measurement in syrinx
from PreOp CT-myelogram from PostOp CT-Myelogram

100 100

k = 0.076 hr -1 k = 0.040 hr -1 k = 0.084 hr -1 k = 0.093 hr -1

influx efflux influx efflux
80 80

60 60

H. U.
H. U.

40 40

Measurement Measurement
20 Simulation 20 Simulation

0 0
0 5 10 15 20 25 30 35 0 5 10 15 20 25 30 35

Time, hours Time, hours

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
50
Before Surgery 50 After Surgery

H.U. SAS H.U. SAS

40 H.U. SC 40 H.U. SC
Iopamidol mg/ml

H.U. Syrinx H.U. Syrinx

30 30

20 20

10 10

0 0
0 10 20 30 40 50 60 0 10 20 30 40 50 60

time (hrs) time (hrs)

Primary Spinal Syringomyelia
Before Surgery After Surgery

Before Surgery 3 Mos. After Surgery

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

Number Mean Std Dev

Chiari With Syrinx 18 100 57

Primarily Spinal Syrinx 10 122 70
Spinal Cord Tumor 7 55 54
 Maximal Syrinx Intensity Pre-Op
300
Post-Op

250

200
Hounsfield Units

150

100

50

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 1.4

1.2 Pre-Op
Post-Op *
1

0.8

0.6 *

0.4

0.2

0 Primary Spinal Syrinx Chiari I Malformation Combined Non-

(n=8), *p<0.05 with Syrinx (n=11) 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 I Primary Spinal