3. CCSVI stands for Chronic Cerebrospinal Venous
Insufficiency and has been a vital issue in scientific
discussions over the last few years.
Recently CCSVI was officially classified as belonging
to a group of venous malformations (Congres Union
Internationale de Phlebologie, Monte Carlo 2009),
and has had its symptoms and methods of
treatment described.
CCSVI procedure consists of different pathologies:
constrictions, stenosis, mostly located near internal
cervical veins (vena jugularis interna) and the
azygos vein (vena azygos).
This disease has a positive correlation to multiple
sclerosis patients.
4. Multiple sclerosis is a demyelinating disease of the central nervous system,
characterized by multifocal damage to the nervous tissue and the ever-changing course.
There are periods of remission and exacerbations (relapses) with progressive loss of
neurons and deterioration of the central nervous system tissue.
In MS, damage to the myelin sheath surrounding the nerve cells occurs, making it
impossible to properly transmit nerve impulses along the tracks in the brain and spinal
cord. A characteristic feature of the disease is the dissemination of CNS lesions in time
and space. There are several subtypes of multiple sclerosis. Primarily progressive form is
characterized by a steady neurologic decline, while relapsing-remitting subtype involves
unpredictable attacks (relapses) followed by periods of remissions. Initial relapsing-
remitting form that begins to have neurologic decline without periods of remission is
known as a secondary progressive subtype.
Multiple sclerosis was first described by Jean-Martin Charcot in 1868. The incidence
depends on the geographic region and ranges from 2 to 150 per 100 000 population in
different countries and specific populations. MS affects mostly young adults, with peak
incidence between 20 and 40 years of age. Women tend to get sick more often than
men.
Many theories have been proposed to determine the etiology of multiple sclerosis, but
so far there is no one underlying cause of multiple sclerosis found. Theory of
autoimmune etiology seems to be dominating, although viral, bacterial, and other
unknown environmental factors may also play an important role in the development of
disease.
5. Hypothesis assuming the relationship between vascular
abnormalities and MS are known for many years.
First observations in the 19th century – in 1863, Rindfleisch
noted cumulation of blood vessels in the center of MS
plaques and Charcot observed vascular blockages in MS
patients.
In 1934 T. Putnam suggested a major role of compromised
venous drainage of the brain in forming MS lesions as well as
inflammatory changes of the central nervous system.
In 1981 F. A. Schelling proposed venous refluxes as one of
the causes of MS.
All those studies led to the introduction of endovascular
procedures in MS patients – called Liberation Treatment,
as first proposed by professor Zamboni in 2009.
6. Professor Zamboni launched a study to define whether there
is a link between CCSVI and MS. With the use of a Doppler
ultrasound, he examined the necks of MS patients and
according to data included in his publication, over 80% of
patients with a RR (relapsing - remitting) type, more than 90%
patients with a SP (secondary - progressive) type, and 90%
patients with PP (primary - progressive) type meet the criteria
for CCSVI diagnosis and liberation treatment (term proposed by prof. Zamboni). The
majority of patients with MS evaluated by the team presented with stenosis, valve
malformations and refluxes.
Dr Paolo Zambonii
Drawing on previous experiences with standard coronary angiography procedures, in
which balloons were used to restore patency of blocked coronary arteries and with the
cooperation of experienced vascular surgeon Dr Galeotti, they proposed venous
angioplasty as a method of CCSVI treatment in MS patients.
Prof. Zamboni’s open labeled angioplasty study involved 65 participants and showed
significant improvement in neurologic outcome and patients’ quality of life.
It has opened doors for further research all over the world and the widespread use of
endovascular treatment of CCSVI.
The subject still remains open and even controversial, especially the theory that the
venous pathology could constitute the primary patomechanism of the autoimmune
process.
7. The real link between CCSVI and MS remains not fully understood;
therefore it is crucial that further studies are carried out to
determine the exact mechanism and the underlying association.
Not every MS patient has his veins blocked, but this correlation is
relatively more significant in MS patients group. Maybe
endovascular treatment does not cure MS, however it definitely
affects its course, improving the state of health and helping to
relieve aggravating symptoms.
Even in studies that were not supportive for CCSVI theory, a link
between CCSVI and MS duration and severity has been
demonstrated. Indeed, there is no certainty around CCSVI and MS
but we have proven efficacy and safety of venous angioplasty in
treating MS patients. What is more, there are a number of
ongoing studies and trials and there are positive statements,
recommendations and guidelines from international associations.
Vascular component does not play a major role in every case.
Still, it is worth trying to restore patency. Improving flow even in
insignificant stenosis often turns out to be beneficial in many
respects and can really change a patient’s life.
8. “The existence of CCSVI, its relation to MS and the legitimacy of
performing balloon angioplasty is the source of much controversy
among and is dismissed by many neurologists. This state of affairs
is the result of the unfamiliarity with CCSVI, the attachment to their
theory of immuno-inflammatory disease, as well as the conviction
that procedures using stents (which are rarely used) are dangerous.
Reports presented at two international symposia devoted to CCSVI in
Katowice and Bologna in March 2011 confirm the association of
CCSVI with MS. As a result of venous re-canalization after
angioplasty, it has been objectively confirmed that the levels of
venous oxygen saturation do improve. The reports emphasized the
positive influence balloon angioplasty has on the quality of life of
patients, on their fatigue levels, bladder disorders, balance
disorders, vision problems, sensory problems and, to a lesser
degree, mobility issues. Improvement was also noted in cognitive
abilities (memory, concentration, attention).”
Professor Jerzy Kotowicz, MD, PhD
9. Ultrasound (Doppler and transcranial)
The basic method used in the diagnosis of
patients with chronic cerebro-spinal venous
insufficiency (CCSVI) is a Doppler ultrasound.
It is a safe and completely non-invasive
diagnosis of the vascular system.
3D Doppler technology is used to determine
the hemodynamic severity of venous
insufficiency.
There were five criteria introduced for the diagnosis of
CCSVI in the Doppler examination. Fulfilling two out of
the five criteria confirms the diagnosis.
The following parameters are assessed during diagnosis:
The presence of venous stenosis
Circulatory disorders and reversed blood flow (reflux)
Flow change in extra-cranial veins dependent on body
position
The presence of valvular disease
10. MRI of the brain and neck has two main purposes:
The assessment of brain activity in the context of
determining the presence and location of
demyelinating lesions, as well as the possible presence
of other abnormalities.
Evaluation of venous outflow, in particular the jugular
and azygos veins. The analysis includes: symmetry of
venous outflow, width and patency of the veins, as well
as an assessment of any stenosis or vein modeling
caused by adjacent anatomical structures.
The examination of the venous system is made using modern techniques with the
use of a contrast agent (which allows for optimum picture clarity): Multi-phase MRI
venography as well as a T1-weighted 3D GRE sequence of very high resolution,
which guarantees very high quality images.
11. The final step in the diagnostic process
is a venography, which produces the
most reliable diagnosis of
abnormalities in the venous system. It
consists of the administration of a
contrast agent into the vein via
a catheter (inserted in either the
femoral or subclavian vein). This allows the
most accurate visualization of vascular
lesions. This procedure is invasive and
therefore entails a risk of complications.
Venography precedes any intra-vascular
operations. The venography procedure
allows for an exact examination and imaging of
the venous system, which provides an excellent
method of verifying and confirming the
presence of any abnormalities detected by
Doppler or MRV.
12. Venous angioplasty, also known as balloon angioplasty, is the basic method
of treatment applied to CCSVI patients.
Venous angioplasty is a procedure performed in order to widen the constricted
vein with the use of a special catheter placed in the vein via percutaneous
access (the catheter is introduced in the groin area, into the femoral vein). A
balloon is then inserted into the constricted vein and inflated with gas, which
enlarges the vessel and restores its patency.
Evidence showed that using cutting balloons may improve the effect of
treatment, decrease the risk of restenosis and reduce the intraoperative trauma
of healthy tissue. For best results balloon with cutting blades is used together
with standard balloon catheters during angioplasty. This technique can also be
beneficial in cases of hardened or calcified occlusion when standard balloons
alone may not be as effective in restoring patency.
In exceptional cases when the narrowing does not expand under the balloon
pressure, or a vein dissection occurs, the balloon angioplasty is supplemented
with the insertion of a stent.
13. Stenting procedure may require the insertion of one or two
stents, depending on whether the stenosis is unilateral or
bilateral.
However according to recent publications and recommendations
in CCSVI management, insertion of stents is not recommended
as a method of choice and should be used only when there is a
direct indication present.
Stents are difficult to deliver particularly in small and twisted
vessels. One should be aware that a stent is a metallic foreign
object placed in the human body, carrying the risk of
thrombosis, systemic reactions and restenosis (due to the
intimal hyperplasia), not to mention stent migration or major
hemorrhages. Once it has been inserted it cannot be removed
or repositioned.
What is more, patient after stent insertion requires prolonged
time of receiving anticoagulants and antiplatelet agents, which
are associated with various side effects and increase the risk of
bleeding.
14. Approximately 2% of patients with implanted stents are prone to
formation of clots in the place of their location within the vessels.
Thrombus may be the cause of embolic complications including
pulmonary embolism and brain stroke.
The risk of forming clots is greatest during the first few months
after placing the stent in the vein. For this reason it is
recommended to use antiplatelet drugs such as aspirin or
clopidogrel, or other anticoagulants for a period of one month to
one year after stent implantation.
The period, during which patients are supposed to be on
anticoagulants, depends on the type of surgery performed, as
well as on the type of stent. Taking anticoagulants and
antiplatelet agents is linked to a number of side effects and
increases the risk of bleeding.
It is difficult to identify the direct cause of stent thrombosis, or to
predict its occurrence. It is suspected that in some patients
developing this serious problem is a result of the suboptimal
response to anticoagulants. Complex and unpredictable clinical
course of stent thrombosis can contribute to many difficulties
met in treating this condition.
15. pregnancy
lack of patient's voluntary consent for the surgery
a relapse occurring (active demyelinating changes
in the MRI)
16. Angioplasty is a very safe procedure with low rate of complications (1-2%)
and rather those of small significance. Most common complications (like
small hematomas or swelling at the puncture site or fever) occur in very low
percentage of patients. Nevertheless, this is an invasive procedure and as
one of such kind may bring some more serious risks like thrombosis,
pulmonary embolism or hemorrhage. Those happen extremely rare (and in
most cases do not put patient in danger) but need to be pointed out.
Worldwide, there have been reports on major complications like cerebral
hemorrhage (2 cases) and stent migration (2-3 cases) but it happened over
20 000 procedures done and involved only stent implantation cases.
Any method of medical treatment is an intrusion in the functioning of human
organism and therefore may be producing, apart from the therapeutic result,
also undesirable side effects. Surgical intervention is a unique form of
intrusion. It involves tissue incision, removal of organs or their parts,
anatomical structure alterations, etc. No matter how beneficial it could be for
regaining one’s health, it incurs a certain risk of complications occurring
either during or after the surgery.
17. Complications, which may occur during the surgery, include: bleeding that
leads to a significant loss of blood; pressure drop; disorder of blood supply
to vital organs and blood clotting disturbances; accidental injury to
anatomical organs and structures caused by their abnormal position or by
inflammatory or neoplastic infiltration; heart action disorder (arrhythmia,
cardiac infarction) and central nervous system disorder (apoplexy) in patients
suffering from cardiovascular system diseases.
Complications which may occur after the surgery include: bleeding from the
wound; intramural or internal hematoma; wound infection; intramural
purulence; arteriovenous fistulas; pulmonary complications / atelectasis;
inflammation; pleural exudates; thrombotic inflammation of veins;
pulmonary embolism; dysuria; urinary tract infection; renal insufficiency;
circulatory insufficiency; respiratory insufficiency; consciousness disorders
(mainly in elderly persons); dissection (rupture) of the vein undergoing
angioplasty; cardiac tamponade; perforation of a vessel.
Apart from "surgical" complications, complications related to anesthetization,
administered medications and to transfusion of blood and blood derivatives
(post-transfusion reactions, viral infections) may also occur.
The risk of occurrence any of the complications listed above is usually very
small, and depends on the type of surgical procedure carried out and on
general condition of the patient. Most complications can be effectively cured,
even if by means of another surgical procedure, and cases of fatal
complications. are extremely rare.
18. The positive effects of treatment of MS patients are
noticeable both in the objective assessment of the
patients’ quality of life as per the MSIS-29 system, as
well as in their own assessment.
AMEDS Centrum has treated more than
600 MS patients to 2011,
from Poland and abroad, MS type
38% of which have been men.
Average age of patients was 46 years. 24% Relapsing-
37% remitting
The statistical patient Secondary
progressive
has been diagnosed with MS 11 years ago. Primary
The majority of patients suffered 39% progressive
from secondary progressive MS.
19. In two thirds of patients with multiple
sclerosis, chronic fatigue is a typical
accompanying symptom of the disease and
always a big problem for the patient. The FSS
scale helps in assessing fatigue levels. The scale
is from 1 to 7, with higher scores reflecting
higher fatigue levels (scores above 5.5 signify
severe fatigue). Our patients have been observed
to experience a marked improvement in the
incidence of fatigue (a reduction of 35% on the
FSS scale!) and a dramatic increase in strength
and energy.
20. The patients who underwent treatment report a significant
improvement of their psychological state and physical
condition. A reduction of points within MSIS-29 scale is
noted after treatment.
Multiple Sclerosis Impact Scale 29 (MSIS-29) is a proven
and reliable scale for measuring the quality of life in
patients with MS. The patient answers 29 questions (20
regarding physical state, coordination and mobility and 9
about mental state). After the score is calculated we obtain
a result on a scale of 0-100, where the higher the
score, the worse the state of health of the patient.
Patients who have undergone treatment display a noticeable
improvement in mental and physical health – shown below
– with a corresponding reduction of points on the MSIS-29
scale.
21. A total of 47 patients suffering from Multiple Sclerosis (MS) with confirmed
diagnosis of Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) who underwent
endovascular treatment were included in the second study.
The improvement group was dominated by females (69% vs. 31% – males). Three out
of four patients in the group with improvement were suffering from Relapsing-
Remitting type of MS.
However, it should be noted that CCSVI treatment is associated with positive results
in people suffering from other types of MS as well.
The study also showed that young patients (age below 30) with short disease
duration are probably benefiting the most from the treatment.
PREVALENCE OF
IMPROVEMENT PREVALENCE OF
IN RELATION TO AGE IMPROVEMENT IN RELATION
100 TO DISEASE DURATION
100
75%
80 80
63%
60 60
36% 25%
40 40
8% 22% 13% 21%
20 20
0 0
<30 30-40 40-50 >50 <5 5-10 10-15 >15
YEARS YEARS YEARS YEARS YEARS YEARS YEARS YEARS
22. Characteristics of patients who have had
positive results from CCSVI treatment indicate
that most beneficial groups are:
females
Relapsing-Remitting type of MS
at young age
with short disease duration
with lower baseline EDSS.
23. After an endovascular surgery and following the discharge from
hospital, patients will have to take anticoagulants on the daily
basis, according to doctor's orders. How long the patient must remain
under anticoagulant treatment depends on the type of surgical
procedure and the type of stent used.
A recommended control test should be carried out after 3 and 6 months
after the procedure. A control test should include: Doppler
ultrasound, magnetic resonance, neurological examination and
laboratory tests. Its objective is to test the flow in the previously treated
veins.
All patients should undergo Doppler control every 6 months. In case of
deterioration of neurological symptoms, a Doppler of the jugular veins
should be done ASAP.
Patients should try not to overload physically during the first month
after the procedure, but you can still do light exercises. At about four
weeks after the procedure you can begin with moderate exercise (i.e.
swimming) but it is advised to wait for 3 months with burdensome
exercise like jogging, tennis or weightlifting in the gym.
24. Slight elevation of the bed (head side) is recommended.
It is important for the patients to be well hydrated, they should drink at
least 1.5 liters of fluid daily.
In order to maximize the benefits from the treatment rehabilitation is
recommended strongly. Of course the best rehabilitation programs are
the ones especially conceived for MS patients. In case of lack of access
to this type of programs benefits can be drawn from swimming pool
exercises, if such possibility exists or at least exercises to be performed
at home developed for MS patients.
As it is the case with all types of conditions here also the appropriate
diet is very important. There are several nutrition programs developed
for MS patients, for instance low fat diet rich in vegetables. In light of
recent research the most important seems to be to restrict animal fat
and saturated fat in the diet. It is worth to use products rich in non-
saturated fat (found mainly in fish), fruit and vegetables (rich in vitamins
and antioxidants) and other diet components including vitamins E, D or
beta-carotene. Of course that quitting smoking and giving up on
alcoholic beverages is highly recommended.
25. We would like you to be aware of the fact that CCSVI treatment should not be perceived as a miracle
drug curing multiple sclerosis once and for all. It can solely be treated as
a complimentary therapy to other methods. The therapy is helpful in combating the condition and
wonderfully complements the treatment methods applied so far, while its effectiveness depends in
large degree from the attitude of the patient himself. The treatment brings the greatest benefits among
persons who support it with regular physical activity (rehabilitation, physiotherapy), healthy lifestyle
and adequate diet (balanced, rich in vitamins, non-saturated fats and omega-3 and omega-6
acids, drinking large amounts of water).
In the reality we are all still at the very beginning of the process of research and understanding of
CCSVI and its correlation to MS. We know however – that independent of the temporary lack of results
from the official clinical trials – the results achieved in many CCSVI treatment centers in the world and
thousands of opinions of individual patients, readily available in the modern world of immediate
communication (internet) – speak for themselves.
Up until now far more about 30 000 CCSVI procedures among patients with multiple sclerosis have
been performed worldwide. According to reliable sources there have been only 3 cases of
complications resulting in patient’s death. This means a mortality level of 1/7000, therefore much
lower than with similar procedures performed for different reasons and considered statistically
acceptable. It should be mentioned that the complications in all
3 cases were linked to some other underlying conditions.
Ultimately, it is the patient who takes the decision to undergo the treatment. Patients make that
decision being aware that in a big majority of cases angioplasty procedure helps and brings a lot of
positive changes such as the decrease of disease symptoms.
26. improvement of blood circulation,
greater warmth felt in the upper and lower limbs,
reduced muscle spasticity and improvement of muscle function,
decreased limb tremors,
full recovery from or significant decrease of fatigue,
sight improvement,
improvement of sphincter function (digestive and urinary tract),
increased endurance during physical effort,
greater psychological strength and better mood,
significant change in the overall quality of life.
27. Angiograph – standard equipment of catheterization laboratory (Cat Lab).
Modern radiologic device dedicated to vascular diagnostics and intravascular
treatment.
Balloon Angioplasty – surgical widening of a narrowed blood vessel by means
of a balloon catheter. Balloon Angioplasty is performed by incising the
femoral vein in the groin and inserting a catheter (a narrow tube). Next, a
balloon is passed through the catheter and into the narrowed location, and
then inflated to a required size and kept in place for several minutes.
Balloon Catheter – thin, flexible tube with a balloon at its tips inserted into
the vessel during angioplasty and used to restore patency of stenotic vessels.
CCSVI - Chronic Cerebro-Spinal Venous Insufficiency, a recently isolated
disease which is a venous pathology (Congres Union Internationale de
Phlebologie, Monte Carlo 2009), officially classified among vascular venous
malformations. CCSVI is a malfunction caused by the narrowing of veins
which collect blood from the brain and the spinal cord. The criteria for
diagnosing CCSVI have been put forth by Prof. Paolo Zamboni.
28. Cutting balloon - is an angioplasty balloon catheter equipped with small blades
attached to its surface. It is a new device developed for use in endovascular treatment of
stenotic vessels. It acts by cutting the stenosis or occlusion when balloon is being
inflated. Evidence showed that using cutting balloons may improve the effect of
treatment, decrease the risk of restenosis and reduce intraoperative trauma of healthy
tissue. For best results balloon with cutting blades is used together with standard
balloon catheters during angioplasty. This technique can also be beneficial in cases of
hardened or calcified occlusion when standard balloons alone may not be as effective in
restoring patency.
Guidewire - very thin wire with a flexible tip inserted into the vessel during angioplasty
before insertion of balloon catheter. Guidewire is passed to the blockage and then is
used as a pathway to stenosis.
High-pressure balloon – these balloons are usually used during high pressure
angioplasty since they are resistant to deformation at high pressure, allowing very
effective dilatation of the narrowing.
Mitoxantrone - is an anti-neoplastic agent also used to treat multiple sclerosis (MS). It is
not an absolute contraindication for the liberation procedure, however it may increase
the risk of complications during and after surgery. There is a possibility of
disqualification from the procedure, due to abnormal blood tests results
(leucopenia, thrombocytopenia) as Mitoxantrone may affect the composition of the
blood.
29. Restenosis – the recurrence of abnormal narrowing of a vessel (vein), which sometimes
occurs after corrective surgery such as vascular Angioplasty.
Stent – a synthetic, elastic tube or a spiral, usually made of 316 LVM steel or
a chromium-cobalt alloy, placed inside the vein to restore its patency. Stents
implantation is used in angioplasty. Stents used in this procedure are not of the drug-
eluting type. Once inserted into patient's body stents are irremovable.
Stenting –inserting one or more stents in the patient's venous vessels.
Valves – in cases of impaired blood flow through the valves the treatment might be
performed. This treatment involves placement of the deflated angioplasty balloon in the
exact area of venous valve and precise inflation in order to swing valve to the right
position. In general one can benefit from this procedure but it is not always possible to
proceed with and certainly not equally effective for all patients.
Venography (also called phlebography) – a procedure where a venogram of the veins is
taken after a special dye (the so called contrast) and injected into the veins via a catheter
inserted into the femoral vein in the groin, thus visualizing them as an X-ray image. This
procedure makes it possible to assess the appearance of all venous vessels, exposing
clogs and malformations.
