Transcript spinal cord tumors

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
• Pre-syringomyelia
• Syringomyelia
• Post-syringomyelia
Normal spinal cord
Diffuse increase in s.c. fluid
(Infrequently documented)
Expanded fluid collection in the
spinal cord
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
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–
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–
–
–
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
Primarily spinal syringomyelia
• Post-traumatic
• Focal arachnoiditis
Spinal cord tumor
• Hemangioblastoma
18
10
7
Entry
of dye
(CSF)
into the
Syrinx
Spinal
Cord
Wall
SAS
Syrinx
K(1,2)
1
2
K(2,1)
Hounsfield Units vs. Dye Concentration
Patients with Syrinx Shunts were
Excluded from Analysis
20
Concentration, mg/ml
Concentration in SAS, mg/ml
Concentration in Syrinx, mg/ml
15
10
5
0
0
5
10
15
20
Time post-injection, hr
25
30
Syringomyelia from Chiari I
Before Surgery
After Surgery
20
20
Subarachnoid CSF
Spinal cord tissue
Syrinx fluid
15
Concentration, mg/ml
Concentration, mg/ml
15
10
5
0
10
5
0
0
10
20
30
40
Time after injection, hr
Subarachnoid CSF
Spinal cord tissue
Syrinx fluid
50
0
10
20
30
Time after injection, hr
40
50
Dye Movement, Chiari I Before and After Surgery
Two compartment fit to background
subtracted measurement in syrinx
from PreOp CT-myelogram
Two compartment fit to background
subtracted measurement in syrinx
from PostOp CT-Myelogram
100
100
k
80
= 0.076 hr -1 k
= 0.040 hr -1
influx
efflux
k
80
= 0.093 hr -1
= 0.084 hr -1 k
efflux
influx
60
H. U.
H. U.
60
40
40
Measurement
Simulation
20
0
0
5
10
15
20
Time, hours
25
Measurement
Simulation
20
30
35
0
0
5
10
15
20
25
30
35
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
Before Surgery
50
After Surgery
50
H.U. SAS
Iopamidol mg/ml
40
H.U. SAS
40
H.U. SC
H.U. SC
H.U. Syrinx
H.U. Syrinx
30
30
20
20
10
10
0
0
0
10
20
30
40
time (hrs)
50
60
0
10
20
30
40
time (hrs)
50
60
Primary Spinal Syringomyelia
Before Surgery
Before Surgery
After 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
Chiari With Syrinx
18
Primarily Spinal Syrinx 10
Spinal Cord Tumor
7
Mean
100
122
55
Std Dev
57
70
54
300
Maximal Syrinx Intensity
Pre-Op
Post-Op
250
Hounsfield Units
200
150
100
50
0
Maximal syrinx intensity measurements for subjects
with Primarily Spinal Syringomyelia before surgery
(blue) and after surgery (red).
Hounsfield Units, normalized
1.4
1.2
Average Change in Maximal Syrinx Intensity
Pre-Op
Post-Op
*
1
0.8
0.6
*
0.4
0.2
0
Primary Spinal Syrinx
(n=8), *p<0.05
Chiari I Malformation
with Syrinx (n=11)
Combined NonTumor 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