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Report on the project entitled:
The Effect Of Chiari I Malformations On CSF Flow In
Cavalier King Charles Spaniels
Funded by the American Cavalier King Charles
Spaniel Club Charitable Trust
Stated objectives
1. Compare CSF flow velocity and distribution at the
level of the foramen magnum between three
groups of CKCS: normal CKCS, symptomatic CKCS with Chiari malformations
and asymptomatic CKCS with Chiari malformations.
2. Estimate the incidence of asymptomatic Chiari I malformations in
a small group of American CKCS.
3. Collect pedigree information and DNA from all study participants
in collaboration with Dr. Rusbridge's study on the genetics of this
disorder.
Original Budget: $10,000. This was
increased to $20,000 in view of the excellent response to recruitment.
Summary of findings
There was an excellent response to the request for
participants and ultimately we imaged 59 dogs (rather than the 30-45
we had originally hoped for). Imaging studies took 30 minutes to perform
as long as everything went smoothly. The staff of the IAMS Pet Imaging
Center worked extremely hard to help us meet the target number of patients
to be imaged. We generated much more data than we expected, as the range
of skull morphologies (skull shape) present required full characterization.
The results of the study are therefore divided into firstly the morphological
findings and their correlation to the presence of clinical signs and/or
syringohydromyelia (SHM) and secondly the findings of the CSF flow measurements.
A) Morphological findings.
A set of definitions for the terms used has been added
to the end of this report for clarification. One of the major problems
we encountered was defining the limits of what is normal versus abnormal.
This has really not been done in a rigorous way previously and so we
hope that we have helped to increase the knowledge in this area. Some
of the parameters we evaluated we could measure and therefore document
in an objective manner (e.g. the distance of cerebellar herniation)
while others were more subjective. ·
Of the 59 dogs that were imaged, 13 had neurological
signs consistent with a Chiari Malformation (22%) and 46 were neurologically
normal (78%).
a) Cerebellar indentation and crowding (55 dogs: 93%
of cases).
b) Cerebellar herniation through the foramen magnum
(50 dogs: 85% of cases). This varied from mild (1mm) to severe (> 4mm).
c) Occipital dysplasia causing enlargement of the
foramen magnum (50 dogs: 85% of cases).
d) Syringohydromyelia (SHM) (22 dogs: 43% of cases).
It is important to note that 13 dogs with SHM did show any clinical
signs, they were neurologically normal.
e) Medullary kinking (33 dogs: 66% of cases).
f) A dorsal compressive lesion at the junction of
the first and second cervical vertebrae causing significant spinal cord
compression (12 dogs: 20% of cases). This was an unexpected finding
and was felt to playa role in the genesis of SHM in some dogs with apparently
mild indentation of the cerebellum. ·
The volume of the caudal fossa and of the total
cranial cavity were measured and the volume of the caudal fossa expressed
as a percentage of the total cranial cavity. The volume of the caudal
fossa is dictated by the occipital bone. a Both the absolute volume
of the caudal fossa and the ratio of the caudal fossa to the whole cranial
cavity were significantly smaller in dogs showing clinical signs. This
confirms that occipital hypoplasia plays an important role in this disease
syndrome in CKCS. ·
Statistical evaluation of all of the morphological
parameters was performed to determine the association of individual
abnormalities, and the abnormalities when considered together with the
presence of SHM and with the presence of clinical signs.
a The following single parameters were significantly
associated with the presence and severity of neurological signs:
· Cerebellar indentation · Syringohydromyelia · Volume
of the caudal fossa (absolute value and ratio). a When considered together,
the following parameters were highly predictive of neurological signs:
· Cerebellar indentation, medullary kinking and ratio of caudal fossa
volume/total cranial cavity volume. Conclusions from the morphological
study
1. The incidence of morphological abnormalities is
high.
2. The incidence of SHM is also relatively high and
is not always associated with clinical signs. In order to determine
whether SHM always ultimately causes clinical signs, we will have to
follow these dogs over time.
3. Occipital hypoplasia is present in dogs with clinical
signs.
4. This type of brain malformation is multifactorial
and includes abnormalities of the occipital bone (hypoplasia and dysplasia)
causing cerebellar crowding and herniation, and abnormalities of the
first and second cervical vertebrae and the articulation of Cl with
the occipital bone. Medullary kinking appeared to result from both the
occipital bone abnormalities and abnormalities of the craniocervical
junction.
B) CSF Flow Measurement Findings:
We were able to evaluate CSF flow in all of our study dogs using Phase
Velocity Contrast CINE MRI (PVC MRI), demonstrating the usefulness of
this imaging modality for analyzing cerebrospinal fluid flow in veterinary
patients. Peak velocities and CSF flow patterns were assessed in the
ventral and dorsal subarachnoid spaces and within syrinxes at the following
levels: just below the foramen magnum and within the cervical spinal
cord at the junction of the second and third cervical vertebrae (C2-C3
disc). Statistical evaluation of the observed flow characteristics was
then performed. Results were as follows: ·
CSF flow could be better visualized and more
effectively measured within the dorsal subarachnoid space if dogs were
positioned for imaging with their head and neck flexed, mimicking a
normal standing position, instead of the extended head and neck position
used routinely for MRI imaging.
· Flow patterns could be visualized in both the sagittal
(in-plane) and transverse (through-plane) views at all levels.
. Flow pattern observations included:
a) Obstruction to CSF flow was evident at the level
of the foramen magnum in the majority of CKCS when compared with control
dogs. This included clinically affected and unaffected Cavaliers, and
varied from mild obstructions to a complete absence of observable flow
at this level.
b) Obstruction to flow was also noted at the
level of the CI-C2 dorsal compression if this lesion was present.
b) CSF flow was present within syrinxes, and peak
flow velocities within syrinxes were often higher than within the corresponding
subarachnoid space.
c) Turbulent flow and high-velocity jets were seen
equally at the level of the foramen magnum, at the level of the cervical
spinal cord, and within syrinxes. They were also seen most frequently
in dogs with syringohydromyelia. . Peak velocities of CSF flow were
determined using transverse views. Velocity measurements demonstrated
the following:
a) Peak velocities within the ventral and dorsal subarachnoid
spaces were not significantly different between clinically affected
and unaffected CKCS. However, affected dogs demonstrated a trend towards
higher peak velocities within the dorsal subarachnoid space at the level
of the foramen magnum.
b) Peak velocities were not significantly associated
with the presence of syringohydromyelia at the level of the foramen
magnum. However, peak velocities of CSF flow in the dorsal subarachnoid
space were significantly lower at the level of the C2-C3 junction in
dogs with syringohydromyelia.
c) Additionally, when considered together, peak velocities
within the dorsal subarachnoid space at the level of the foramen magnum
and at the level of the cervical spinal cord were highly predictive
of the presence of a syrinx, such that:
i) Higher peak velocities at the foramen magnum correlated
with higher incidence of syringohydromyelia
ii) Lower peak velocities at the cervical spinal cord
correlated with higher incidence of syringohydromyelia.
d) We propose that this velocity gradient could be
the result of obstruction to flow at the level of the foramen magnum
and a relative post-obstructive expansion of the subarachnoid space
and subsequent slowing of flow at the level of the cervical spine.
e) Importantly, it was difficult to obtain measurements
at the point of maximum obstruction at the foramen magnum, so measurements
were obtained immediately caudal to this point in all CKCS. This limitation
may have affected our ability to fully evaluate changes in peak velocities
at the foramen magnum of CKCS.
Conclusions from the CSF flow study:
1. CSF flow patterns and velocities can be evaluated
in dogs using PVC MR!.
2. Head position is important when performing these
studies. A flexed head and neck imitating normal standing posture leads
to a better determination of flow characteristics.
3. Obstruction to CSF flow at the foramen magnum is
a component of Chiari malformations in CKCS.
4. In affected dogs, CSF flow velocity is high
at the level of the FM and decreases over the C2-3 disc space, demonstrating
a gradient of flow.
5. Quantitative assessment of CSF flow velocities
may require more sophisticated software that is better able to measure
flow within small regions of interest by taking measurements on a pixel
- by - pixel basis, in order to allow evaluation at the point of maximal
obstruction (at the foramen magnum). Clinical relevance of CSF flow
findings:
1. PVC MRI could be used pre-operatively to determine
if obstruction(s) to CSF flow, turbulence, and/or high-velocity jets
are present in CKCS with morphologic changes suggestive of a Chiari
Malformation. This information could help neurologists and owners when
deciding whether the observed clinical signs are due to the Chiari Malformation
or if these morphologic findings are non-clinical. Such information
could prove very useful in deciding the best course of treatment of
such a patient.
2. Post-operatively, PVC MRI could be used to
determine if obstruction(s) to CSF flow have been relieved by surgery
or if additional surgery is warranted in patients with residual clinical
signs.
3. The clinical progress of the study participants
will be followed annually for 3 years and CSF flow velocities will be
re-correlated with the development of clinical signs. This will be used
to pursue a better understanding of velocity ranges that are predictive
of clinically apparent disease.
Budget
The initial budget was $10,000. This was increased
to $20,000 in view of the excellent response of breeders and owners
to the request for cases. The total outlay of the project was $16,777.55:
$15,000 on rental of MRI, anesthesia and MRI technician. $1,777.55 was
expended on supplies for DNA extraction and shipping of samples to Dr
Rusbridge's collaborators. $3,222.45 will be returned to the sponsoring
agency.
Dr. Sofia Cerda-Gonzalez, Neurology Clinical Studies,
College of Veterinary Medicine, NCSU
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