Upper Cervical Vertebral Subluxation in Multiple Sclerosis Subjects with Chronic Cerebrospinal Venous Insufficiency: A Pilot Study

Abstract

Objective: The purpose of this study is to evaluate the relationship between Atlas vertebra misalignments identified via radiographs and patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI). Clinical Features: Four patients with MS and CCVSI, three women and one man were evaluated according to revised McDonald criteria. These four patients were compared to a control group of four patients of similar age but with no neuro-degenerative diseases. Intervention and Outcomes: This is the first report on Atlas (C1) misalignment in MS patients with CCVSI. Four patients were evaluated using the Zamboni's criteria using the following: Echo Color Doppler (ECD) MyLab Vinco System Esaote, Upper cervical x-ray examination, Myofunctional Map, and Tytron thermal scanning instrumentation. In this study we found different alterations of C1 alignment in the MS patients versus the control group. Analysis of the x-ray examination permits us to identify a severe rotation and anterior intrusion of C1 in the MS patients with CCVSI. Conclusion: We found not only endovenous congenital malformations, but also external venous compression that blocks drainage flow. This confirms the validity of our Mechanical Posture Vascular Compressive Block. We hypothesize that extracranial venous compression is linked to severe misalignment of C1. We can also catalogue misalignments into two types of degrees: moderate and severe. This staging permits us to begin to distinguish paraphysiological misalignments from true pathological misalignments.

Full text

Upper Cervical Vertebral Subluxation in Multiple Sclerosis Subjects
with Chronic Cerebrospinal Venous Insufficiency: A Pilot Study
Sandro Mandolesi, MD,1Giuseppe Marceca, MD,2Stephen Conicello, DC,3Eriece Harris, DC4
ABSTRACT
Objective: The purpose of this study is to evaluate the relationship between Atlas vertebra misalignments identified via
radiographs and patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI).
Clinical Features: Four patients with MS and CCVSI, three women and one man were evaluated according to revised
McDonald criteria. These four patients were compared to a control group of four patients of similar age but with no
neuro-degenerative diseases.
Intervention and Outcomes: This is the first report on Atlas (C1) misalignment in MS patients with CCVSI. Four
patients were evaluated using the Zamboni’s criteria using the following: Echo Color Doppler (ECD) MyLab Vinco
System Esaote, Upper cervical x-ray examination, Myofunctional Map, and Tytron thermal scanning instrumentation. In
this study we found different alterations of C1 alignment in the MS patients versus the control group. Analysis of the x -
ray examination permits us to identify a severe rotation and ant erior intrusion of C1 in the MS patients with CCVSI.
Conclusion: We found not only endovenous congenital malformations, but also external venous compression that blocks
drainage flow. This confirms the validity of our Mechanical Posture Vascular Compressive Block. We hypothesize that
extracranial venous compression is linked to severe misalignment of C1. We can also catalogue misalignments into two
types of degrees: moderate and severe. This staging permits us to begin to distinguish paraphysiologic al misalignments
from true pathological misalignments.
Keywords: Multiple sclerosis, chronic cerebrospinal venous insufficiency, upper cervical, subluxation
Introduction
Multiple sclerosis (MS) is considered a chronic disease of the
brain and spinal cord characterized by inflammatory-
demyelinating and neurodegenerative features that coexist
from early stages.1It is estimated that it currently affects
400,000 individuals in the United States, with 12,000 being
new cases annually, with more people being diagnosed now
than in the past.2MS affects twice as many women as it does
men, mimicking the unexplained bias found in other
ORIGINAL RESEARCH
1. Professor –Cardiovascular and Respiratory Science
Department, Sapienza University of Rome, Rome, Italy
2. Professor –School of Medicine, Sapienza University of
Rome, Rome, Italy
3. Private Practice of Chiropractic, Rome, Italy
4. Private Practice of Chiropractic, Naples, FL
J. Upper Cervical Chiropractic Research –September 23, 2013 65
Multiple Sclerosis

autoimmune disorders.3This autoimmune disorder usually
begins in subjects around the ages of 20-40.2The majority of
MS patients (80%) present with the relapsing/remitting form
of the disease.3This form is characterized by relapsing of
symptoms followed by full recovery, relapse with persistent
deficit, and finally secondary progression.3In about a quarter
of the patients, MS never affects activities of daily living;
conversely 15% become severely disabled in a short period of
time.3Recognized and described over 150 years ago by a
French neurologist Charcot, the exact cause of the disease
remains unknown.4
In general, we consider MS to be caused by an autoimmune
mechanism with multiple etiological factors such as genetic,
infectious, and environmental.4Recently, chronic
cerebrospinal venous insufficiency (CCSVI) has been
described as a condition that may possibly contribute to the
symptoms often experienced by patients with MS.4CCSVI
has been described as a vascular condition characterized by
anomalies of the main extra-cranial cerebrospinal venous
routes that interfere with normal venous flow.1These
anomalies have been reported to affect the internal, vertebral
and azygous veins.1
The origin of CCSVI related venous anomalies has not been
determined.5It has been suggested that the origin of these
abnormalities could be physiological, age-dependent,
congenital, and a possible consequence of an inflammatory
process or environmental factors.5It has been hypothesized
that cerebrospinal venous anomalies may cause alterations to
blood flow that result in iron deposition, decreased brain
parenchyma metabolism, degeneration of neurons and
characteristic brain injury patterns found in MS.1This
hypothesis is referred to as “The Big Idea”.6
The Big Idea hypothesis was created by Paolo Zamboni. In
2006 Zamboni researched and published a paper in the Journal
of the Royal Society of Medicine entitled “The Big Idea:
Iron-dependent inflammation in venous disease and proposed
parallels in multiple sclerosis”.6His paper outlines the
mechanism of pathology in CCSVI and MS. This paper also
suggests that there is a connection due to similarities in tissue
response. To summarize the findings of the paper, the
correlation begins with increased iron stores in areas of the
body - mainly the legs, due to extravasation of red blood cells
(RBC) in conditions of significant venous stasis in CCSVI.
The RBC’s are degraded by interstitial macrophages and the
released iron is converted into ferritin. Eventually the ferritin
is transformed into haemosiderin and then deposited into
venous tissue. This increase of iron storage in the body as
well as interstitial proteins attracts potent chemicals that
represent the initial chronic inflammatory signal response for
white blood cell recruitment and migration in the matrix.6The
predominate cells migrating into the extra cellular matrix are
macrophages and T-lymphocytes.
Similarly, the inflammation in MS is characterized by
expression of adhesion molecules followed by the migration
of macrophages and T-lymphocytes across the blood brain
barrier. In both scenarios there is an over expression of matrix
metallo-proteases (MMPs) that are not substantially balanced
by their physiological tissue inhibitors (TIMPs). If MMP is
unrestricted it leads to matrix break down and ulcer onset.10
Ajay has proposed the use of susceptibility weighted
neuroimaging techniques to confirm the hypothesis of iron
playing a role in the formation of MS.14 This imaging is able
to detect the iron deposits in the brain tissue.14
The proposed correlation in the two diseases comes from the
similar altered venous haemodynamics. The altered venous
haemodynamics are considered the trigger mechanism that
caused the inflammatory process in CVD. This has to be
studied further in relation to MS.18
Methods
Eight patients were selected to participate. Four of the
patients were diagnosed with MS according to the revised
McDonald criteria and CCSVI. The median age for the
patients is 33 with a maximum age of 36 and minimum of 30.
The gender of the patients consisted of three women and one
man. Disease duration for the patient group did not exceed 15
years. The other four patients were the control sample group
composed of subjects of the same age, without any neuo-
degenerative diseases.
Each patient was examined using the following: ECD,
Doppler Ultrasonography dynamic test, total body
myofunctional map, upper cervical radiography, and Tytron
C-5000 thermal scanning.
Results
Echo Color Doppler
According to Menegatti ECD demonstrated to be an ideal non
invasive tool for screening patients.7There was a question of
the reproducibility of the instrumentation based on the training
of the individual performing the exam.7The conclusion of the
36 subject study showed ECD is a powerful non-invasive and
reproducible tool for screening CCSVI and MS but the
individual needs special training.7ECD was used to measure
outflow in veins and inflow in arteries. In the MS sample the
venous outflow assessment showed: jugular vein stenosis in
50%, not visible vertebral veins in 25%, reflux in 50%,
blockage in 50%, and compression block in 25% of the
sample. The control sample assessment revealed ectasia of the
jugular vein only in 50% of the sample. The ECD arterial
inflow assessment of MS sample showed thoracic outlet
syndrome on the left side in 100%, kinking in vertebral
arteries in 75% of the sample. The control sample showed
kinking of the carotid arteries only in 25% of sample.
Myo-functional Map
Myo-functional assessment is an objective hand examination
of the skeletal muscle system that allows us to find, in an
objective way, the muscular contractures perceived
(spontaneous painful) from those not perceived
(spontaneously not painful). We then draw specific symbols
on an accurate Myo-functional Map. In the MS sample we
found muscular contractures of the total body examination:
Median 47±21, 9, Points min: 22 and Points max: 28. In the
control sample we found muscular contracture of the total
body examination: Median 15, Points min: 2, Points max: 28
Multiple Sclerosis
66 J. Upper Cervical Chiropractic Res. –September 23, 2013

Cervical Radiographic Examination
Each patient received a series of cervical radiographs. The
following projections were taken and measured for each
sample group: APOM (anterior posterior open mouth), lateral
cervical and base posterior.
APOM
This projection is used to measure left or right laterality of C1.
To measure this a horizontal line was drawn through the upper
½ to 1/3 portion of the foramen magnum. The foramen
magnum is then bisected with a vertical line. A line is then
drawn from the vertical line to the edge of the lateral mass on
the right and left side. Measure both sides and the longer side
is the side of laterality of C1.
Base Posterior
This projection is used to measure the rotational component of
C1. To measure the anterior or posterior rotation first a dot
must be placed in the center of each transverse process. Then
a line is drawn connecting the two dots. The is called the atlas
line. A dot is then placed in the middle of the nasal septum.
Draw a line through the dot in the middle of the nasal septum
through the middle of the basilar process. This line should
intersect the atlas line. The angle is measured on the side of
laterality to check for posterior or anterior rotation.
Lateral Cervical
This projection is used to measure anterior intrusion of C1.
This is measured by drawing a line from the posterior foramen
magnum to the posterior neural canal of axis. This will be
labeled as line A. Another line is then drawn from the
posterior portion of the neural canal of the posterior arch of
atlas to the posterior of foramen magnum. This line will be
labeled line B. Another line is then drawn from the posterior
of the neural canal of the posterior arch of the atlas to the
posterior neural canal of axis. This line will be labeled line C.
Measure the distance from the point where B and C meet at
posterior neural canal at the posterior arch of atlas to line A at
a perpendicular angle.
The normal values for these radiographs are as follows: tilt of
18-22 degrees, no laterality, no rotation, and no intrusion into
the spinal laminar line (neural canal). The moderate categorey
values are as follows: inferior tilt of 16-18 degrees, superior
tilt of 22-24 degress, laterality of < 1.5mm, rotation of < 1
degree, and anterior intrusion of < 1.8mm. The severe
categorey values are as follows: inferior tilt of <16 degrees,
superior tilt of > 24, laterality > 1.5mm, rotation of > 1 degree,
and anterior intrusion of > 1.8 mm.
The radiographic results of the study are displayed in Figure 1.
J. Upper Cervical Chiropractic Research –September 23, 2013 67
Multiple Sclerosis

The MS sample group results show that 25% of participants
presented with severe inferior tilt, severe left laterality,
moderate right laterality, severe right lateraltiy, moderate
anterior right rotation, severe anterior right rotation, severe
posterior right rotation, and severe posterior left rotation.
Normal superior tilt was found in 75% of the MS sample
group and no left rotation was found in any paticipants. The
major finding is that 100% of sample group presented with
severe anterior instrusion into the neural canal with the
maximum being 4.07mm.
The control sample group results show 25% of the participants
presented with normal tilt values and no anterior intrusion.
Fifty percent of the sample group presented with moderate left
laterality, moderate right laterality, moderate impairment on
left and right in anterior rotation. The control group also
presented with moderate superior tilt and moderate
impairment in anterior intrusion in 75% of participants. The
major finding in this group is 100% of sample group presented
with anterior rotation.
Tytron Thermal Scanning
Thermocouple devices have been used in chiropractic as early
as 1924 to measure side-to-side skin temperature
differentials.8According to Owens the Tytron shows very
high intraexaminar and interexaminer reliability with
intraclass correlation coefficient values between .91 and .98.8
When scanned using the tytron the MS sample group had
greater temperature alterations than the control group.
Discussion
CCVSI as a potential etiopathic entity in MS has recently been
suggested and gained significant attention.9It is widely
accepted that MS is an autoimmune disease but now we are
faced with a new model of it being possibly vascular or
degenerative. There is also a possiblility of there being a
mechanical component involving the C1 vertebra. To begin to
adress these concerns we must first look at the current
literature.
Williams created a study to evalute the hypothesis of Zamboni
in the Big Idea. In order to evaluate this hypothesis she
developed an animal model. The conclusion of her study
showed that MS caused the vascular abnormalities, not the
other way around.10
There is also controversy about the frequency and the role of
CCVSI in patients with MS.12-13 Laupacis performed a
systematic review and meta-analysis of all the peer review
studies that compared the frequency of CCVSI among patients
with MS.11 The meta-analysis published in 2011 included 8
studies and the article concluded that there was a strong and
statistically significant association between CCVSI and MS.11
The article did have a limitation of a small sample size but
found a strong association between CCVSI and MS.11 The
study concluded that more high quality studies using identical
ultrasound protocols are needed.11
Awad published a critical review on the subject. He states the
controversy of the subject is due to the inability of any other
researchers to reproduce the results published by Zamboni.9
Awad goes on to list six different recent studies that have been
done to recreate Zamboni’s results but have been
unsuccessful.9Awad goes on to discuss the plausibility of
CCVSI being biologically linked to MS and states the gold
standard to confirm would be a tissue diagnosis.9
One common theme that seems to reoccur is the use of ECD in
evaluating CCVSI. The instrumentation has been deemded
reliable but only if the ultrasonographer is trained properly.
More and better quality reasearch needs to be done on the
subject in order to determine causality.
The presence of substitute circles in Zamboni type
hemodynamic classification, when joined to external
compression of the jugular veins, suggests to us that a venous
vertebral and/or jugular postural venous compression block
may be caused by misalignment of C1.19
This intermittent compression block of vertebral and jugular
veins may be one of the multi-factorial causes of the worst
clinical conditions in MS patients with CCSVI, the
Mechanical Postural Vascular Block (MPVB) (Mandolesi-
Marceca, 2010 hypothesis).20 These patients frequently had
head and neck trauma.
There is a proposed relationship between MS and upper
cervical subluxation. Elster conducted a study on upper
cervical subluxation and it’s connection to MS and Parkinsons
disease.15
The retrospective study consisted of 81 patients. Of the 81
patients 44 had MS and all were diagnosed with upper cervical
subluxations. These patients were diagnosed using paraspinal
digital infrared imaging and laser-aligned radiography.
After the instrumentation and radiograph anaylsis were done,
the patients were adjusted using Knee Chest technique. The
result of this study showed 91% of the participants responded
to care with improved or reversed symptoms, and no further
progression of symptoms. The results suggested a link
between trauma, upper cervical injury, and disease onset for
both MS and Parkinsons.15 In addition to this study Stude
presented a case study showing conservative spinal
manipulations had positive effects in an MS patient. The
patient presented in the case did not have any upper cervival
subluxations but did have significant reduction in symptoms
posttreament.16
There seems to be some similarities in this study and the study
done by Elster. Two of the same examinations were used,
Tytron and upper cervical radiographs. They both also show a
relationship between C1 subluxation and the presence of MS.
The differences are Elster’s paper was focused on trauma as a
possible cause of MS while this paper is focused the
relationship between misalignment and CCVSI in patients
with MS.
Conclusion
As far as we know, this is the first report on C1 misalignment
in MS patients with CCSVI. In this study we found a
significant parameter of C1 misalignment (anterior intrusion)
in patients with MS with CCVSI versus control subjects.
Multiple Sclerosis
68 J. Upper Cervical Chiropractic Res. –September 23, 2013

We postulate that the severe rotation and anterior intrusion
should be an important radiological marker for MS patients
with CCSVI. Further study with a larger sample size of these
CCSVI patients is recommended.
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J. Upper Cervical Chiropractic Research –September 23, 2013 69
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Figure 1. Results from Radiographic Study
Multiple Sclerosis
70 J. Upper Cervical Chiropractic Res. –September 23, 2013