CAN I REALLY CAUSE A STROKE? Or, Cervical Manipulation and
Vertebrobasilar Ischemia Presented By: Joseph S. Ferezy, D.C.,
D.A.C.A.N., F.I.A.C.N.
Slide 3
SAFETY FIRST: PUTTING CVAs INTO THE PROPER PERSPECTIVE FOR
CHIROPRACTIC FCER Teleconference September 27, 2005 Anthony L.
Rosner, Ph.D., LL.D. [Hon.] Foundation for Chiropractic Education
and Research Brookline, Massachusetts, USA 02446
Slide 4
Without question, this is the most catastrophic iatrogenic
injury that can occur in the office of any practitioner of
manipulative therapy.
Slide 5
Terrett AGJ. Vascular accidents from cervical spinal
manipulation: report on 107 cases. J Aust Chiropractors' Assoc.
1987; 1 7:15-24. In 1987 Terrett reported on 107 cases that
appeared in the international literature.
Slide 6
Estimates of the incidence of cases of serious neural damage
from cervical manipulation range from as few as 1 in several tens
of millions to as many as 1 in 300,000 cervical manipulations. u
Maigne R. Orthopedic Medicine. A New Approach to Vertebral
Manipulations. Springfield, Ill: Charles C Thomas, Publisher;
1972:2, 169. u Gutmann G. Injuries to the vertebral artery caused
by manual therapy. Manuelle Medican. 1983;21:2-14.
Slide 7
Estimates of 1 in 20 million deaths from cervical manipulation
have been made, and it has been likened to the chances of dying
from a bee sting or from being hit by lightning. Chapman-Smith D.
Cervical adjustment the risk of vertebral artery injury. J
Chiropractic. 1987:12-15.
Slide 8
PROBABILITY OF STROKE FOLLOWING CERVICAL MANIPULATION
SourceMethodRisk Dvorak 1 Survey of 203 members of Swiss 1 ser
compl / 400,000 Society of Manual Medicine [all 0 deaths
non-chiropractors] Patijn 2 Review of computerized registration 1
compl / 518,000 system in Holland Haldeman 3 Extensive literature
review to formulate 1-2 str / 1,000,000 practice guidelines
Jaskoviak 4 Clinical files of National College 0 compl / 5,000,000
15 year period Henderson/ Canadian Memorial Chiropractic 0 compl /
5,000,000 Cassidy 5 College Clinic 9 year period Coulter 6 RAND
cervical study literature review 0.64 ser compl / 1,000,000 0.27
deaths / 1,000,000 Carey 7 Claim review: Canada's largest 1 CVA /
3,000,000 malpractice company 0 deaths 5 year period NCMIC 8 Claim
review: principal chiropractic1 CVA / 2,000,000 malpractice company
within U.S. 3 year period 1 Dvorak J, Orelli F. How dangerous is
manipulation of the cervical spine? Manual Med 1985; 2: 1-4. 2
Patijn J. Complications in manual medicine: A review of the
literature. Manual Med 1991; 6: 89-92. 3 Haldeman S, Chapman-Smith
D, Peterson DM. Guidelines for chiropractic quality assurance and
practice parameters. Gaithersburg, MD: Aspen Publishers, 1993,
170-172. 4 Jaskoviak PA. Complications arising from manipulation of
the cervical spine. J Man Physiol Ther 1980; 3: 213-219. 5
Henderson DJ, Cassidy JD. Vertebral artery syndrome: In Vernon H,
ed. Upper cervical syndrome: Chiropractic diagnosis and treatment.
Baltimore: Williams & Wilkins, 1988. 195-222. 6 Coulter I,
Hurwitz E, Adams A, Meeker W, Hansen D, Mootz R, Aker P, Genovese
B, Shekelle P. The appropriateness of spinal manipulation and
mobilization of the cervical spine: Literature review, indications
and ratings by a multidisciplinary panel. RAND: Santa Monica, CA,
1995. Monograph No. DRU-982-1-CCR. 7 Carey PF. A report on the
occurrence of cerebral vascular accidents in chiropractic practice.
J Canad Chiro Assoc 1993; 57(2): 104-106. 8 National Chiropractic
Mutual Insurance Company, unpublished case records 1991-1993.
Slide 9
CEREBROVASCULAR ANATOMY AND HEMODYNAMICS
Slide 10
n ascends through tightly binding myofascial tissues to
eventually pass through tendinous slips of the scalenus anterior
and medius muscles, as well as the longus collii, where it enters
the transverse foramen of the sixth, or sometimes the seventh,
cervical vertebra. ascends through the transverse foraminae of
cervical vertebrae C-6 to C-3; Between C-3 and C-2 it takes a
slightly posterior course. After passing through C-2, a very sharp
lateral course is taken, heading for the transverse foramina of C-
1. Anatomists discuss the vertebral artery as possessing four
parts.
Slide 11
Slide 12
u After passing through the lateral foramen of the atlas, the
third part of the artery takes another sharp deflection, as it must
travel almost directly posterior to run medially around the lateral
mass of C-1. Here, it lies in a groove along with the first
cervical nerve. u The fourth part of the vertebral artery passes
through the lower border of the posterior atlanto-occipital
membrane and through the arcuate foramen, piercing the dura mater
and moving upward through the foramen magnum.
Slide 13
Slide 14
The largest and most clinically significant branch, the
posterior inferior cerebellar artery takes its origin just prior to
the union of the two vertebral arteries. This irrigates the lateral
aspect of the medulla (hence the term "lateral medullary syndrome")
and the anterior portion of the cerebellum.
Slide 15
Slide 16
Hemodynamics
Slide 17
n choroid plexus of the fourth ventricle posterior cerebrum
(visual cortex) pons internal ear thalamus midbrain Brain
structures primarily receiving a vertebral artery blood supply
include: n bone and dura of the posterior cranial fossa facet joint
structures cervical nerve roots dorsal root ganglia spinal cord
much of the cerebellum medulla oblongata
Slide 18
When graphically depicted, the reason for the term "posterior
circulation" becomes obvious.
Slide 19
Slide 20
Studies on 20 cadavers who had cannulated major neck vessels
showed that water flow may be reduced by more than 90% by movements
well within the normal range of head motion. Toole JF, Tucker SH.
Influence of head position upon cerebral circulation. Studies on
blood flow in cadavers. Arch Neurol. 1960;2:616-623.
Slide 21
With rotation it was the vertebral artery contralateral to the
direction of chin deviation that was occluded (e.g., chin to left
caused right artery occlusion). When rotation was combined with
extension, the ipsilateral artery was affected about as frequently
as the contralateral.
Slide 22
Contralateral Artery Stretch
Slide 23
Rotation combined with flexion caused unpredictable results.
Lateral flexion had little effect in most cases, and extension did
not significantly alter flow in any case.
Slide 24
Rotation was the single most likely movement to cause
occlusion.
Slide 25
Slide 26
ROTATIONAL INJURY/VERTEBRAL ARTERY
Slide 27
Numerous other studies have corroborated contralateral and
ipsilateral vertebral artery occlusion with head movement. One
study used electromagnetic flow meters during radical neck surgery
in two patients, and another used retrograde brachial arteriography
on 43 asymptomatic volunteers. u Hardesty WH, Witacre WB, Toole JF,
Randall P, Royster HP. Studies on vertebral artery blood flow in
man. Surg Gynecol Obstel. 1963; 1 16:662-664. u Farris AA, Posner
CM, Wilmore DW, Agnew CH. Radiologic visualization of neck vessels
in healthy men. Neurology. 1963;13:386-396.
Slide 28
Arteriograms performed with forced contralateral cervical
rotation revealed vertebral artery occlusion prior to the artery's
entrance into the transverse foramen of C-6. After surgical
division of "tendinous interdigitations", the occlusion was no
longer present. u Husni EA, BeII HS, Storer J. Mechanical occlusion
of the vertebral artery: a new concept. JAMA. 1966; 196:475-478. u
Husni EA, Storer J. The syndrome of mechanical occlusion of the
vertebral artery: further observations. Angiology. 1967; 1
8:106-116.
Slide 29
Ischemia also results from compression by spurs along its
course through the transverse foramen. Rotation and hyperextension
of the neck have been associated with increased compression of the
VA's adjacent to the spondylophyte. u Sheehan S, Bauer RB, Meyer
JS- Vertebral artery compression in cervical spondylosis:
arteriographic demonstration during life of vertebral artery
insufficiency due to rotation and extension of the neck. Neurology.
1960; 10:968-986.
Slide 30
Extra-luminal Compression Part II Vertebral Artery
Slide 31
n Bauer R, Sheehan S, Meyer JS. Arteriographic study of
cerebrovascular disease, cerebral symptoms due to kinking,
tortuosity, and compression of carotid and vertebral arteries in
the neck. Arch Neurol. 1961;4:ll6-131. The third portion is the
most susceptible to extraluminal occlusion, especially as it passes
over the lateral mass of the atlas. This finding is so common and
reproducible, that some authorities consider this extraluminal
occlusion a normal finding.
Slide 32
Slide 33
PATHOPHYSIOLOGICAL MECHANISMS IN VASCULAR INJURIES
Slide 34
CSMT may be responsible for neurovascular insufficiency via
indirect trauma to the arterial wall by causing vasospasm, a clot
or a tear.
Slide 35
Slide 36
Chen J, Smith R, Keller A, Kucharczyk W. Spontaneous dissection
of the vertebral artery: MR findings. J Computer Assist Tomogr.
1989; 13:326-329. Caplan LR. Zamis CK, Hemmati M. Spontaneous
dissection of the extracranial vertebral arteries. Stroke. 1985;
16:1030-1038. A syndrome of "Spontaneous Vertebral Artery
Occlusion" is now clearly recognized, and virtually
indistinguishable from arterial damage due to trauma.
Slide 37
Arterial Dissection
Slide 38
_________________________________________________________________________________________________________________________________________________________
1 Shievink WT, Mokri, B, O'Fallon WM. Recurrent spontaneous
cervical-artery dissection. New England Journal of Medicine 1994;
330: 393-397. 2 Shievink WT, Mokri B, Whisnant JP. Internal carotid
artery dissection in a community: Rochester, Minnesota, 1987-1992.
Stroke 1993; 24: 1678-1680. 3 Giroud M, Fayolle H, Andre N, Dumas
R, Becker F, Martin D, Baudoin N, Krause D. Incidence of internal
carotid artery dissection in the community of Dijon [Letter].
Journal of Neurology and Neurosurgical Psychiatry 1994;57: 1443.
1.The annual incidence of spontaneous vertebral artery dissection
in hospitals has been estimated at 1-1.5/100,000. 1 2.The annual
incidence of spontaneous vertebral artery dissection in
community-based studies has been estimated at 2.5-3/100,000. 2,3
SPONTANEOUS ARTERIAL DISSECTION RATES
Slide 39
RATES OF STROKE COMPARED TO INCIDENCE OF ARTERIAL DISSECTIONS
ATTRIBUTED CAUSERATE [PER MILLION] Spontaneous, hospital-based 1
10-15 Spontaneous, community-based 2,3 25-30 Cervical manipulation
4 2.5 Cervical manipulation 5 1-2 Cervical manipulation 6 0
Cervical manipulation 7 0.64 Cervical manipulation 8 0.17 1
Shievink WT, Mokri, B, O'Fallon WM. Recurrent spontaneous
cervical-artery dissection. New England Journal of Medicine 1994;
330(6): 393-397. 2 Shievink WT, Mokri B, Whisnant JP. Internal
carotid artery dissection in a community: Rochester, Minnesota,
1987-1992. Stroke 1993; 24(11): 1678-1680. 3 Giroud M, Fayolle H,
Andre N, Dumas R, Becker F, Martin D, Baudoin N, Krause D.
Incidence of internal carotid artery dissection in the community of
Dijon [Letter]. Journal of Neurology and Neurosurgical Psychiatry
1994; 57(11): 1443. 4 Dvorak J, Orelli F. How dangerous is
manipulation of the cervical spine? Manual Med 1985; 2: 1-4. 5
Haldeman S, Chapman-Smith D, Peterson DM. Guidelines for
chiropractic quality assurance and practice parameters.
Gaithersburg, MD: Aspen Publishers, 1993, 170-172. 6 Jaskoviak PA.
Complications arising from manipulation of the cervical spine. J
Man Physiol Ther 1980; 3: 213-219. 7 Hurwitz EL, Aker PD, Adams AH,
Meeker WC, Shekelle PG. Manipulation and mobilization of the
cervical spine: A systematic review of the literature. Spine
21(15): 1746-1760. 8 Haldeman S, Carey P, Townsend M, Papadopoulos
C. Arterial dissections following cervical manipulation:The
chiropractic experience. Canadian Medical Association Journal 2001;
165(7): 905-906.
Slide 40
PATIENT ASSESSMENT: PREDISPOSITION AND CLINICAL TESTING
Slide 41
The question of whether or not screening procedures to
adequately detect patients at increased risk of neural ischemia
related to CSMT are currently available is of paramount concern for
the practitioner of manual cervical spinal manipulation.
Slide 42
The unreliability of such tests has been pointed out in papers
dealing with vertebrobasilar insufficiency tests. Terrett AGJ.
Vascular accidents from cervical spinal manipulation: report on 107
cases. J Aust Chiropractors' Assoc. 1987; 1 7:15-24.
Slide 43
Bolton and associates discuss a patient who underwent four
separate provocative clinical tests, all of which failed to elicit
symptoms to help detect an angiographically proven vertebral artery
occlusion. u Bolton PS, Stick PE, Lord RSA. Failure of clinical
tests to predict cerebral ischemia before neck manipulation. J
Manipulative Physiol Ther. 1989; 12:304-307.
Slide 44
Case History:
Slide 45
A review of the major presenting complaints of patients who
subsequently suffered a manipulation- related vertebral-basilar
accident reveals little which could alert the astute practitioner
to an impending accident."
Slide 46
n headache, giddiness, and nausea neck pain and stiffness neck
stiffness strained shoulder, headache, and tension shoulder and
neck pain chest, arm, and head pain a "catch in the neck" Common
Complaints From Patients Who Subsequently Suffered VBI: n neck pain
n head and neck pain n neck and arm pain n headache, dizziness, and
neck stiffness n headache
Slide 47
Previously held beliefs that preexisting atherosclerosis,
cervical spondylosis, oral contraceptive use, and neck bruits may
be predisposing factors are simply not borne out by the evidence at
hand.
Slide 48
Bilateral Blood Pressure and Auscultation
Slide 49
The taking of blood pressure bilaterally, does not appear to be
particularly useful, as the victims are usually young and neither
hypo- nor hypertension is consistently found; nor has a subclavian
steal syndrome ever been implicated.
Slide 50
Likewise, bruit in the neck have not been linked to post
manipulative VBI.
Slide 51
Vertebrobasilar Insufficiency Testing
Slide 52
Numerous authors have suggested that extension and rotation of
the cervical spine should be performed as a provocative test for
symptoms of ischemia. u George PE. Identification of high risk
prestroke patient. J Chiropractic. 1981; 15:26-28. u Smith RA,
Estridge MN. Neurologic complications of head and neck
manipulations: report of two cases. JAMA. 1962;192:528-531. u
Kleynhans AM, Teffett AGJ. Aspects of Manipulative Therapy. New
York: Churchill Livingston; 1985; 161-175. u Terrett AGJ.
Importance and interpretation of tests designed to predict
susceptibility to neurocirculatory accidents from manipulation. J
Am Chiropractic Assoc. 1983;13:29-34.
Slide 53
Three variations of the extension- rotation test are currently
in use; they differ in terms of patient position and what
constitutes a positive test. u Performed in the supine position,
with hyperextension and rotation. u Performed in the seated
position with both arms outstretched and hands supinated. u
Performed in the standing posture.
Slide 54
If positive findings occur, the test should be immediately
discontinued and no manipulations performed on that patient in that
direction. What is not agreed upon is exactly how long to perform
the test, and exactly what is a positive finding.
Slide 55
No evidence conclusively, or even preliminarily, exists to show
that this maneuver has any correlation whatever to impending neural
ischemia related to CSMT.
Slide 56
False-positive tests may occur due to stimulation of the
vestibular apparatus, cervical sympathetics, carotid sinus
receptors, and other vertebrogenic causes.
Slide 57
The clear possibility that the provocative test described by
some may be more dangerous than a skilled cervical adjustment, in
addition to the discomfort experienced by so many, and the sheer
impracticality of routinely administering the test, must lead one
to seriously question the utility of this test.
Slide 58
CURRENT VERTEBROBASILAR ARTERY RISK ASSESSMENT OPTIONS 1
_________________________________________________________________________________________________________________________________________________________
1 McGregor M, Haldeman S, Kohlbeck FJ. Vertebrobasilar compromise
associated with cervical manipulation. Topics in Clinical
Chiropractic 1995; 2(3): 63-73. OPTION Provocative Testing Doppler
ultrasound CT, MRI scan MRA Arteriography VALUE May provide some
medicolegal protection. Images vertebral arterial flow; may
document dissection in evolution. Images brain structure; of value
in documenting completed infarct. Visualizes vertebral arteries;
localizes the dissection and occlusion. Gold standard for
visualizing vertebral arteries; can document congenital
abnormalities. LIMITATION Little or no actual clinical value;
false- negative testing documented; false sense of security. Manual
compression and provocation testing does not appear to obstruct
flow in symptomatic individuals or controls; normal in unoccluded
arteries. Does not image vertebral arteries very well. High cost;
limited availability; never investigated as a screening tool.
Invasive test with known complication rate; expensive; not
demonstrated to show patients at risk.
Slide 59
RECOGNITION OF POSTADJUSTIVE VERTEBROBASILAR INSUFFICIENCY
Slide 60
In order for the competent doctor of chiropractic to properly
manage a patient who has suffered a vascular accident post-cervical
adjustment, it is obviously essential that he or she recognize it
at its earliest stages.
Slide 61
Lawsuits brought against chiropractors usually hinge not on the
cause-effect relationship, but on the doctor's apparent lack of
recognition, and/or on his or her apparently inappropriate
subsequent actions.
Slide 62
In view of the rarity of postadjustive VBI, it is no wonder
that many chiropractors do not have a sufficient plan of action to
deal with it.
Slide 63
Acceptable risk Versus Callousness or Ignorance.
Slide 64
RECOGNITION
Slide 65
Signs and symptoms of VBI usually occur immediately after the
first few cervical adjustments, although it is possible for
symptoms to begin minutes to days later, and after any number of
treatments.
Slide 66
Slide 67
Slide 68
Lateral Medulary Stndrome
Slide 69
Slide 70
Slide 71
Lateral Medulary Syndrome
Slide 72
Slide 73
Slide 74
Most postadjustive VBI result in almost complete recovery, or
at least minimal residual neurological deficit.
Slide 75
ACTION STEPS
Slide 76
Once your patient has reported adverse effects of a cervical
adjustment possibly consistent with the syndromes outlined above,
it may not be necessary to immediately call for an ambulance. Most
emergency room physicians are completely unfamiliar with
postadjustive VBI anyway, and are likely to misdiagnose.
Slide 77
Slide 78
Careful observation in the office is in order, as you should be
most familiar with the condition and capable of making a
preliminary diagnosis, and then initiating whatever follow-up may
be necessary.
Slide 79
As noted above, a myriad of disorders will produce
symptomatology identical to that of VBI. Many of these disorders
are not serious and will clear spontaneously.
Slide 80
If a vascular injury has occurred, little can be done at a
hospital to minimize the damage in the acute stage anyway.
Slide 81
Following these simple steps will enable you to provide the
best possible care for your patient: u Do not administer another
cervical adjustment. u Do not allow the patient to ambulate. u Keep
him or her comfortable. u Note all physical and vital signs
(pallor, sweating, vomiting, heart and respiratory rate, blood
pressure, body temperature, etc..) u Check the pupils for size,
shape, and equality.
Slide 82
Following these simple steps will enable you to provide the
best possible care for your patient: u Check eye light and
accommodation reflexes. u Test the lower cranial nerves, looking
for facial numbness or paresis, swallowing, gag reflex, slurred
speech, palatal elevation, etc.Test cerebellar function, looking
for dysmetria of extremities, nystagmus, tremor, etc. u Test the
strength and tone of the somatic musculature. u Test for somatic
sensation to pinprick.
Slide 83
Following these simple steps will enable you to provide the
best possible care for your patient: u Test the muscle stretch
reflexes and for the presence of pathological reflexes. u
Completely immobilize the neck. A soft cervical support may be
used. Take care not to cause excessive neck movements while placing
the device on the patient. u Any therapy involving neck movement,
including neck traction or flexion, is inappropriate, as it may
cause further injury.
Slide 84
Should any non- preexisting neurological abnormality exist,
make a prompt medical referral.
Slide 85
Should the symptoms be unaccompanied by any new neurological
abnormality, and clear quickly and spontaneously, then it is
unlikely that the patient has suffered any significant vascular
insult.
Slide 86
It is possible for all symptoms to clear and for a full-blown
stroke to occur at a later date.
Slide 87
Whether or not this patient is a candidate for future cervical
adjustments is often up to the confidence of the doctor as to his
or her diagnosis. I suggest that no additional manipulations be
performed on that visit.
Slide 88
The patient must be instructed to contact you immediately in
the event that any of these symptoms reappear.
Slide 89
Future manipulations should only be undertaken after the risks
are discussed with the patient. You may want him or her to sign a
consent form.
Slide 90
If similar symptomatology occurs a second time, I would not
continue with osseous cervical adjustments on that patient.
Slide 91
Many of the classic symptoms of neural ischemia (nausea,
tinnitus, lightheadedness, visual problems, etc.) are actually
relieved by cervical adjustment.
Slide 92
An Acceptable Risk
Slide 93
It has been said that "if you can cure it, you can cause it."
The RISK:BENEFIT ratio.
Slide 94
In light of the fact that the disastrous complication of
permanent neurological damage damage is such a rare event, is not
the term "acceptable risk" suitable in this instance?
Slide 95
No other health care profession can match the humanity shown by
chiropractic. The fact that vertebrobasilar ischemia has received
such great attention in the chiropractic literature, documents the
profession's unequaled concern for the welfare of the chiropractic
patient.
Slide 96
By "grasping at straws" in relation to testing, we may well
wind up depriving a significant number of those same patients of a
safe and effective way to relieve their suffering.
Slide 97
Recommendations
Slide 98
What needs to be clarified is the difference between
nontraumatic stroke and postmanipulative stroke. It is the
confusion between these two distinct entities has led to
over-reliance on warning signs and overutilization of virtually
useless testing procedures.
Slide 99
This author suggests the following procedure: u Always be
conscious of the gravity of the procedure which you are about to
undertake u Leave the lines of communication between you and your
patient wide open. u Talk to your patient prior to and during
palpation of the neck and ask them to immediately inform you of any
discomfort or nausea. u Hold the patient's head for about 5 seconds
in the preadjustive position prior to administering an
adjustment.
Slide 100
n Takes absolutely no additional time. May be repeated on every
patient, every visit. No additional financial expense. No increased
risk to the patient. Reminds the doctor of the magnitude of the
manipulation and allows the patient to play an active role in
helping stem a possible manipulative accident. While this appears
to be just another extension/rotation test, it has multiple
advantages:
Doctors or Guns? u (A) The number of physicians in the U.S. is
700,000. u (B) Accidental deaths caused by Physicians per year are
120,000. u (C) Accidental deaths per physician is 0.171. Statistics
courtesy of U.S. Dept of Health Human Services.
Slide 104
Doctors or Guns? u (A) The number of gun owners in the U.S. is
80,000,000. u (B) The number of accidental gun deaths per year, all
age groups, is 1,500. u (C) The number of accidental deaths per gun
owner is.000188. Statistics courtesy of FBI
Slide 105
Doctors or Guns? u So, statistically, doctors are approximately
9,000 times more dangerous than gun owners. Remember, "Guns don't
kill people, doctors do."
Slide 106
Perspectives u Talking Points Regarding Post- Manipulation VBI
u Compiled By: u Anthony Rosner, PhD - FCER
Slide 107
MOST COMMON CAUSES OF CHIROPRACTIC MALPRACTICE LAWSUITS 1 1
Type of loss study: Malpractice only for loss year 1995. Des
Moines, IA: National Chiropractic Mutual Insurance Company as
reported in Jagbandhansingh, MP. Most common causes of chiropractic
malpractice lawsuits. Journal of Manipulative and Physiological
Therapeutics 1997; 20(1): 60-64. 1.Disc problems. 2.Fractures.
3.Failure to diagnose. 4.Aggravation of a previous condition.
5.Cerebrovascular accidents. 6.Burns.
Slide 108
THE UCLA NECK PAIN STUDY 1 Synopsis: Outcomes of patients who
undergo cervical manipulation compared to those treated by
mobilization: a. Catalogued all adverse symptoms experienced by
both groups during trial. b. 280 participants polled, 30.4% had
adverse symptoms: 1] Most commonly increased neck pain or
stiffness, followed by headache or radiating pain. 2] Patients
randomized to manipulation more likely to report an adverse symptom
with odds ratio = 1.44. 3] No serious events reported.
_________________________________________________________________________________________________________
1 Hurwitz EL, Morgenstern H, Vassilaki M, Chiang L-M. Frequency and
clinical predictors of adverse reactions to chiropractic care in
the UCLA Neck Pain Study. Spine 2005; 30(13): 1477-1484.
Slide 109
RESPONSE TO UCLA NECK PAIN STUDY: 1 Rebuttal Arguments I 1.
Unconvincing time sequence: a. Odds ratio of 1.44 is the same
whether all times or 24 hours post-intervention is sampled. b.
Causality criteria of Bradford Hill 2 are violated. c. Contradicts
substantial body of literature which shows decline of number of
incidents as more time elapses between treatment and effect. 3,4 2.
Comparative odds ratios and frequencies: a. For patients
experiencing electromagnetic stimulation [EMS], odds ratio was
1.50, or greater than corresponding figure for manipulation. b. For
patients experiencing heat, frequencies of adverse events reported
to be similar.
___________________________________________________________________________________________________________________________________________________________
_ 1 Hurwitz EL, Morgenstern H, Vassilaki M, Chiang L-M. Frequency
and clinical predictors of adverse reactions to chiropractic care
in the UCLA Neck Pain Study. Spine 2005; 30(13): 1477-1484. 2 Hill
AB. The environment and disease: Association or causation?
Proceedings of the Royal Society of Medicine 1965; 58: 295-300. 3
Klougart N, LeBouef-Yde C, Rasmussen LR, Safety in chiropractic
practice, Part II: Treatment in the upper neck and the rate of
cerebrovascular incidents. Journal of Manipulative and
Physiological Therapeutics 1996; 19(9): 563-569. 4 Haldeman S,
Kohlbeck FJ, McGregor M. Unpredictability of cerebrovascular
ischemia associated with cervical spine manipulation therapy. Spine
2002; 27(1): 49-55.
Slide 110
RESPONSE TO UCLA NECK PAIN STUDY: 1 Rebuttal Arguments II 3.
Effect of preceding conditions: a. Predisposing conditions at
baseline significantly elevate the likelihood of reporting an
adverse event to treatment: 1] 5.18: Moderate or severe headache vs
mild. 2] 3.15: Elevated neck disability scores. b. No baseline data
exists to confirm that distribution of these patients was the same
in mobilization and manipulative groups. c. It has been shown
elsewhere that preexisting conditions may have considerable bearing
upon more serious events linked to cervical manipulation. 1,2 4.
Relativity to other interventions: a. Authors' own statement:
"Complication rates from surgical and pharmaceu- tical treatments
for neck pain are estimated to be much higher than those from
spinal manipulation or other chiropractic interventions. 1 b.
Relative risks outlined in detail elsewhere. 2
_________________________________________________________________________________________________________
1 Hurwitz EL, Morgenstern H, Vassilaki M, Chiang L-M. Frequency and
clinical predictors of adverse reactions to chiropractic care in
the UCLA Neck Pain Study. Spine 2005; 30(13): 1477-1484 2 Rosner A.
CVA risks in perspective. Manuelle Medizin 2003; 3: 1-9.
Slide 111
RESPONSE TO UCLA NECK PAIN STUDY: 1 Rebuttal Arguments III 5.
Lack of data regarding technique and number of adjustments: a.
Higher number of transient complications have been linked to rotary
maneuvers in the upper cervical region. 2 b. Specific regions
adjusted also influence rates of transient reactions reported. 2
CONCLUSION: Side-effects and complications which can be
unequivocally associated with manipulation need to be studied in
detail so that their frequency and severity can be diminished even
further, despite the fact that it has been demonstrated that it is
a far safer alternative than medical or surgical interventions for
the complaints studied.
_________________________________________________________________________________________________________
1 Hurwitz EL, Morgenstern H, Vassilaki M, Chiang L-M. Frequency and
clinical predictors of adverse reactions to chiropractic care in
the UCLA Neck Pain Study. Spine 2005; 30(13): 1477-1484. 2 Klougart
N, LeBouef-Yde C, Rasmussen LR. Safety in chiropractic practice,
Part II: Treatment in the upper neck and the rate of
cerebrovascular incidents. Journal of Manipulative and
Physiological Therapeutics 1996; 19(9): 563-569.
Slide 112
CERVICAL ADJUSTMENTS/SAFETY CHECK 1 Haymo Thiel, D.C., is
conducting a major prospective study on the safety of chiropractic
neck manipulation in the U.K., beginning in June 2004 involving 420
members of the British Chiropractic Association. To date, there
have been 50,214 consecutive neck manipulations without a single
serious incident of harm.
_________________________________________________________________________________________________________
1 Chapman-Smith D. The Chiropractic Report May 2005; 19(3): 4.
Slide 113
CERVICAL ADJUSMENTS: REALITY CHECK 1 Attacks against
chiropractic concerning perceived risks of cervical manipulation
are currently based upon co-incidence, anecdotal reports and junk
science. ---Adrian Upton Head, Division of Neurology McMaster
University School of Medicine
_______________________________________________________________________________________________________
1 Chiropractic Therapy as Seen by a Neurologist, lecture at 80th
Annual Spring Convention of the British Chiropractic Association in
conjunction with 40th anniversary celebration of the Anglo-European
College of Chiropractic, Bournemouth, UNITED KINGDOM, April 22,
2005 quoted in Chapman-Smith D. The Chiropractic Report May 2005;
19(3): 4.
Slide 114
CERVICAL ADJUSMENTS: OOPS 1 A recent incident noted by the
Canadian Chiropractic Protective Association involved a
chiropractic patient filing a claim for damages stating that a
stroke followed chiropractic treatment as the causative agent. The
claim was thrown out since the patient had only received
chiropractic treatment of the ankle.
__________________________________________________________________________________________________________
1 Chapman-Smith D. The Chiropractic Report May 2005; 19(3): 4.
Slide 115
Slide 116
MISUSE OF THE LITERATURE BY MEDICAL AUTHORS 1 A.Medical
misrepresentation by the literature [25]: Reverse [0] Original case
reports do not identify or clearly describe practitioner. But
medical author chooses to quote these as examples of "chiropractic
injury. EXAMPLES: blind masseur, Indian barber, medical/naturopath,
osteopath, heilpraktiker, physiotherapist, self. B.Inaccurate
reporting by medical authors [12]: Original literature does
attribute injury to chiropractor. Personal communication with the
author changes the story. EXAMPLES: medical, physiotherapist,
osteopath, Kung-fu practitioner, lay practitioner C.Inaccurate
reports by medicolegal journalists [4]: Bias [smear] in popular
press against chiropractors appears in some newspapers. EXAMPLES:
medical, osteopath
_________________________________________________________________________________________________
1 Terret AGJ. Current concepts in vertebrobasilar complications
following spinal manipulation. West Des Moines, IA: NCMIC Group
Inc., 2001.
Slide 117
CHIROPRACTORS UNJUSTLY MALIGNED IN MEDICAL LITERATURE 1 The
words chiropractic and chiropractor have been incorrectly used in
numerous publications dealing with SMT [spinal manipulation
therapy] injury by medical authors, respected medical journals and
medical organizations. In many cases this is not accidental; the
authors had access to original reports that identified the
practitioner involved as a nonchiropractor. The true incidence of
such reporting cannot be determined. Such reporting adversely
affects opinion of chiropractic and chiropractors.
____________________________________________________________________________________________________________________
_ 1 Terrett AGJ. Misuse of the literature by medical authors in
discussing spinal manipulative therapy injury. Journal of
Manipulative and Physiological Therapeutics 1995; 18(4):
203-210.
Slide 118
OVERSAMPLING OF CHIROPRACTORS IN CVA CALCULATIONS? 1 Terrett
AGL. Misuse of the literature by medical authors in discussing
spinal manipulative therapy injury. Journal of Manipulative and
Physiological Therapeutics 1995; 18(4): 203-210. 2 Shekelle PG,
Brook RH. A community based study of the use of chiropractic
services. American Journal of Public Health 1991; 81: 439-442. 3
Shekelle PG, Adams AH, Chassin MR, Hurwitz EL, Phillips RB, Brook
RH. The appropriateness of spinal manipulation for low back pain:
Project overview and literature review. RAND: Santa Monica, CA.
1991; CCR/FCER Monograph No. R-4025/1. 1.Cerebrovascular
manipulative "catastrophes" reported in the English language,
1934-1992 [excluding complete or almost complete recoveries,
unknown outcomes, and anecdotal cases]: 1
Chiropractor/chiropractic:All others*: 50 [64%]28 [36%] *Osteopath,
medical practitioner, physiotherapist, wife, self, barber, unnamed.
2.In U.S., the following percentages of manipulations are done by:
2,3 94%:chiropractors 4%:osteopaths 2%:medical practitioners
3.Based upon equal probability of occurrence, the chance of
encountering a serious CV event in a nonchiropractor's office
should be 6%. But the observed rate in Terrett's sample is 36%,
representing a disproportionate 6-fold increase. This speaks well
for the relative safety of chiropractic vs nonchiropractic
manipulation.
________________________________________________________________________________________________________
Slide 119
WHERE IS THE WEAKEST LINK? 1 1.Chiropractic spinal manipulation
is estimated to cause stroke in as many as one in 20,000 patients.
Jane Brody New York Times, April 3, 2001 1 2.As many as 1 in 20,000
spinal manipulations causes a stroke. Wouter Schievink New England
Journal of Medicine, March 22, 2001 2 3.Adverse events range from 1
in 20,000 patients undergoing cervical manipulation to 1 million
procedures. Andrew Vickers British Medical Journal, October 30,
1999 3
________________________________________________________________________________________________________________________________________________________
1 Brody J. When simple actions ravage arteries. New York Times,
April 3, 2001. 2 Schievink WI. Spontaneous dissection of the
carotid and vertebral arteries. NewEngland Journal of Medicine
2001; 344(12): 898-906. 3 Vickers A, Zollman C. ABC of
complementary medicine: The manipulative therapies: Osteopathy and
chiropractic. British Medical Journal 1999; 319: 1176-1179.
Slide 120
COMMON FALLACIES FROM CVA STUDIES 1.Failure to disclose that
the majority of VBAS are spontaneous, cumulative, or caused by
factors other than spinal manipulation. 2.Failure to disclose the
potential benefits of the procedure in the interest of reporting
true risk-benefit ratios. 3.Failure to place the risks of
manipulation in the context of those produced by other medical
treatments or lifestyle activities. 4.Failure to indicate the
actual frequency of the manipulations administered. 5.Failure to
account for the possibility that patients undergoing CVAs are
reported more than once. 6.Failure to report the rates of CVAs
following manipulation by parties other than licensed
chiropractors. 7.Incorrectly assuming that patients undergoing
adverse events following a manipulation would not report such
instances to either the attending chiropractor or appropriate
authority.
Slide 121
U.S. MORTALITY DATA FOR SEVEN DISORDERS, 1997 1
_______________________________________________________________________________________________
1 Wolfe MM, Lichenstein DR, Singh G. Gastrointestinal toxicity of
nonsteroidal antiinflammatory drugs. New England Journal of
Medicine 1999; 340(24): 1888-1899.
Slide 122
TAKING NSAIDS TOXICITY TO THE STREETS
Slide 123
VIOXX AND CARDIOVASCULAR EVENTS 1
_____________________________________________________________________________
__ 1 Couzin J. Withdrawal of Vioxx casts a shadow over COX-2
inhibitors. Science 2004; 306(5695): 384-385.
Slide 124
INTERNAL VERTEBRAL ARTERY FORCES DURING SMT 1 1.6 vertebral
arteries obtained from unembalmed postrigor cadavers, with distal
C0-C1 and proximal C6-subclavian loops exposed and fitted with pair
of piezoelectric ultra- sonographic crystals: a.Strains between
each crystal pair recorded during ROM testing, diagnostic tests,
and a variety of SMT procedures. b.Vertebral artery then dissected
free and strained on materials testing machine until mechanical
failure occurred. 2.Results: a.SMT values < those recorded
during diagnostic and ROM testing. b.SMT strains to VA 1/9 strains
needed to achieve failure. 1 Symons BP, Herzog W. Internal forces
sustained by the vertebral artery during spinal manipulative
therapy. Journal of Manipulative and Physiological Therapeutics
2002; 25(8): 504-510.
Slide 125
CAUTIONARY NOTES TO SYMONS 1 STUDY 2 1.The portion of the
artery most commonly involved in VA dissections associated with
spinal manipulation [C1-C2] was not measured; rather, the entire VA
was used to obtain mechanical failure points. 2.Stretch by tensile
forces rather than compression by combined forces [particularly at
the C2 foramen, proposed to be the actual force causing damage
during manipulation] was measured, which may not reflect the
suspected type of artery deformation occurring in patients. 3.The
strain caused to the thrust side VA when the neck is fully rotated
contralaterally was not evaluated, representing the most forceful
manipulation, was not measured. 4.The ranges of motion from the
80-99 year old cadavers would be expected to be more restricted
than those more typical of younger patients seen in chiropractic
offices, limiting the strains on the VAs that were measured by the
researchers and perhaps not representative of those seen in actual
practice. 5.There were wide variations in force ranges [4-18N] and
of strains [31%-75%]. 6.Preparing the arterial specimens in
ultrasound gel may have artificially increased their flexibility.
7.One may question whether the overall arterial failures observed
bear compelling resemblance to the intimal tearings experienced in
vivo during arterial dissections. Arterial dissections may occur
with considerably less arterial insult. 8.Since arterial
dissections may well represent the culmination of multiple arterial
insults, this experiment must be repeated to assess arterial
integrity after dozens and perhaps hundreds of applied stretches to
the VA.
____________________________________________________________________________________________________________________________________________________________________________
1 Symons BP, Herzog W. Internal forces sustained by the vertebral
artery during spinal manipulative therapy. Journal of Manipulative
and Physiological Therapeutics 2002; 25(8): 504-510. 2 Good C.
Letter to the editor. Journal of Manipulative and Physiological
Therapeutics 2003; 26(5): 338-339.
Slide 126
RISKS IN PERSPECTIVE: COMPARISONS OF DEATH RATES DUE TO VARIOUS
CAUSES 1 Hurwitz EL, Aker PD, Adams AH, Meeker WC, Shekelle PG.
Manipulation and mobilization of the cervical spine: A systematic
review of the literature. Spine 21(15): 1746-1760. 2 Deyo RA,
Cherkin DC, Loesser JD. Blgos SJ, Ciol MA. Morbidity and mortality
in association with operations on the lumbar spine: The influence
of age, diagnosis, and procedure. Journal of Bone and Joint Surgery
AM 1992; 74 (4): 536-543. 3 Seagroat V, Tan HS, Goldacre M.
Bulstrode C, Nugent I, Gill L. Effective total hip replacement:
Incidence, emergency, readmission rate, and post-operative
mortality. British Medical Journal 1991; 330: 1431-1435. 4 Stremple
JS, Boss DC, Davis CH, McDonald GO. Comparison of post-operative
mortality and morbidity in Veterans Affairs and nonfederal
hospitals. Journal of Surgical Research 1994; S6: 405-416. 5
Roebuck DJ. Diagnostic imaging: Reversing the focus [letter].
Medical Journal of Australia 1995: 162: 175. 6 Horowitz SH.
Peripheral nerve injury and causalgia secondary to routine
venipuncture. Neurology 1994: 44: 962-964. 7 Dabbs V, Lauretti W. A
risk assessment of cervical manipulation vs NSAIDS for the
treatment of neck pain. Journal of Manipulative Physiological
Therapeutics 1995: 18(8): 530-536. 8 Dinman BD. The reality of
acceptance of risk. Journal of the American Medial Association
1980; 244 (11): 1226-1228. RISKFREQUENCY [PER MILLION] Neurological
complications from cervical manipulation0.3 1 Spinal surgery700 2
Total hip replacement4900-15,300 3 Appendectomies13,500 4 Nuclear
bone scan333 5 Venipuncture40 6 GI bleeding due to NSAID use400 7
Smoking: 20 cigarettes per day5000 8 Drinking: 1 bottle of wine per
day75 8 Canoeing10 8 Motorcycling20,000 8 Automobile driving
[United Kingdom]169 8 Soccer, football39 8
Slide 127
MEDICAL TREATMENTS AND ACCIDENTS MEDICAL TREATMENTS AND
ACCIDENTS RISKFREQUENCY/2M Serious stroke/neurological complication
resulting from SMT1 1,2 Fatal air crash, flying 3 hrs on commercial
U.S. airline1 3 Death in motor vehicle accident, driving 35 miles1
4 Injury in motor vehicle accident, driving 0.5 miles1 4 Death per
year from GI bleeding due to NSAIDs use a 800 5 Overall mortality
from spinal surgery 1400 6 Death rate from cervical spine surgery
800-2000 7 Serious/life-threatening complications from spinal
stenosis surgery 100,000 6 Developing gastric ulcer visible on
endoscopic examination b 380,000 8 a For osteoarthritis and related
conditions. b After 1 week's treatment with naproxen @500 mg/2x
daily. 1 Klougart N, Leboeuf-Yde C, Rasmussen LR. Safety in
chiropractic practice part I: The occurrence of cerebrovascular
accidents after manipulation to the neck in Denmark from 1978-1988.
Journal of Manipulative and Physiological Therapeutics 1996; 19(6):
371-376. 2 Haldeman S, Carey P, Townsend M, Papadopoulos C.
Arterial dissections following cervical manipulation: The
chiropractic experience. Canadian Medical Association Journal 2001;
165(7): 905-906. 3 Based on 1997-2000 Transportation Statistics
showing an average of 1:57 deaths per 1,000,000 flight hours.
http://www.bts.gov/publications/nts/http://www.bts.gov/publications/nts/
4 Based on 1.5 deaths per 100 million vehicle miles and 116
injuries per 100 million miles traveled in 2000. Traffic Safety
Facts 2000. National Highway Safety Administration.
http://www.nhtsa.dot/gov/ 5 Gabriel SE, Jaakimainen L, Bombardier
C. Risk of serious gastrointestinal complications related to use of
nonsteroidal anti-inflammatory drugs: A meta-analysis. Annals of
Internal Medicine 1991; 115(10_: 787-796. 6 Bigos S, Bowyer O,
Braen G, et al. Acute Low Back Pain in Adults: Clinical Practice
Guideline No. 14. AHCPR Publication No. 95-0642. Rockville, 1994,
Agency for Health Care Policy and Research, Public Health Service,
U.S. Department of Health and Human Services. 7 The cervical spine
research society editorial committee: The Cervical Spine [2nd
edition]. New York, NY: JB Lippincott Company, 1989. 8 Simon LS,
Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, Isakson
PC, Geis GS. Preliminary study of the safety and efficacy of
SC-8635, a novel cyclooxygenase 2 inhibitor. Arthritis and
Rheumatism 1998; 41(9): 1591-1602.
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The ACC Position u Tests are not useful u Should no longer be
taught
Slide 147
IN ADDITION. IN ADDITION. u All chiropractic colleges will be
eliminating u the teaching of provocative testing from u their
curricula.
Slide 148
ADDITIONAL PERSPECTIVES The Genetic and Homocysteine Link
Slide 149
PREDISPOSING FACTORS TO SPONTANEOUS VA DISSECTION
1.Fibromuscular dysplasia [hyperplasia] found in 23-33% patients in
VAD studies. 1-3 2.Post-SMT stroke post mortem examinations display
mediolytic arteriopathy with widespread mucoid degeneration, cystic
transformation of the vessel wall caused by degeneration of smooth
muscle cells of tunica media. 4 3.Ultrastructural connective tissue
abnormalities found in 55% of cases in study of 11 patients with
acute non- traumatic dissections of cervicocerebral arteries: 5
a.Elastic fiber degeneration seen in collagen bundles. b.Skin
biopsies from patients suffering spontaneous VAD are aberrant. 6
4.Genetic disorders for collagen observed: a.Alanine for glycine
substitutions seen in half of alpha 1 chains of type I collagen in
a patient suffering multiple VA dissections. 7 b.Patients with
vascular Ehlers-Danlos syndrome are known risks for spontaneous
VAD, most carrying mutations in gene coding for pro-alpha 1 (III)
collagen. 6 5.Febrile respiratory tract infection [tonsillitis,
pharyngitis, sore throat, cough, rhinitis] may be triggering factor
in pathogenesis of cervical artery dissections. 8,9 1 Chiras J,
Marciano S, VegaMolina J, Touboul B, Poirier B et al. Spontaneous
dissecting aneurysm of the extracranial vertebral artery [20
cases]. Neuroradiology 1985; 27: 327-333. 2 DeBray JM,
Penison-Bresnier I, Dubas F, Emile J. Extracranial vertebrobasilar
dissections: Diagnosis and prognosis. Journal of Neurology and
Neurosurgical Psychiatry 1997; 63: 46-51. 3 Mas JL, Goeau C,
Bousser MG, Chiras J, Verret JM, Touboul PJ. Spontaneous dissecting
aneurysms of the internal carotid and vertebral arteries: Two case
reports. Stroke 1985; 16: 125-129. 4 Terrett AGJ. Did the SMT
practitioner cause the arterial injury? Chiropractic Journal of
Australia 2002; 32(3): 99-110. 5 Brandt T. Orberk E, Hausser I,
Muller-Kuppers M, Lamprecht IA et al. Ultrastructural aberrations
of connective tissue components in patients with spontaneous
cervicocerebral artery dissections. Neurology 1996; 46: A193,
PO2.086. 6 Brandt T, Grond-Ginsbach C. Spontaneous cervical artery
dissection. From risk factors toward pathogenesis. Stroke 2002; 33:
657-658. 7 Mayer SA, Rubin BS, Starman BJ, Byers PH. Spontaneous
multivessel cervical artery dissection in a patient with a
substitution of alanine for glycine [G13A] in the alpha 1 [I] chain
of type I collagen. Neurology 1996; 47: 552-556. 8 Grau AJ, Buggle
F, Steichen-Weihn C. Clinical and biochemical analysis in
infection-associated stroke. Stroke 1995; 26: 1520-1526. 9 Grau AJ,
Brandt T, Forsting M, Winter R, Hacke W. Infection-associated
cervical artery dissection. Stroke 1997; 28: 453-455.
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Slide 151
HOMOCYSTEINE: A RISK FACTOR FOR SPONTANEOUS CAD 1 1.Cervical
artery dissection [CAD] accounts for up to 1/5 of ischemic strokes
occurring in young and middle- aged patients. 2 2.Three groups of
patients compared: CharacteristicNumberTotal Plasma Homocysteine
[micromole/L] sCAD2513.2 [7-32.8] non-CAD isc str3110.9 [6-30.2]
Control36 8.9 [75-17.3] 3.Representation of cases with homocysteine
levels above 12 micromole/L cutoff: GroupRepresentation [%]
Controls13.9 non-CAD isc str29 sCAD64 4.Significant association
between MTHFR TT genotype and sCAD also observed; prevalence not
elevated in control patients or those with non-CAD ischemic stroke.
5.CONCLUSION: Significant risk factors for sCAD may be: a.Increased
plasma homocysteine levels. b.TT MTHFR genotype [thermolabile
variant of methylenetetrahydrofolate reductase with about half
normal activity].
______________________________________________________________________________________________________________________________________________________
1 Pezzini A, Del Zotto E, Archetti S, Negrini R, Bani P, Albertini
A, Grassi M, Assanelli D, Gasparotti R, Vignolo LA, Magoni M,
Padovani A. Plasma homocysteine concentration, C677T MTHFR
genotype, and 844ins68bp genotype in young adults with spontaneous
cervical artery dissection and atherothrombotic stroke. Stroke
2002; 33: 664-669. 2 Schievink WI. Spontaneous dissection of the
carotid and vertebral arteries. New England Journal of Medicine
2001; 344: 898- 906.
Slide 152
HYPERHOMOCYSTEINEMIA [HYPERH]: RISK FACTOR FOR CAD? 1 1.26
patients with CAD admitted to stroke unit compared with age-matched
control subjects: a.All patients underwent duplex ultrasound, MR
angiography, and/or conventional angiography. b.15 men, 11 women,
16 vertebral arteries, 10 internal carotid arteries studied. 2.
Plasma homocysteine measured by using high-performance liquid
chromatography [HPLC] coupled to fluorescence detection: 2 3.
Results: a.With CAD: 17.88 micromoles/L [5.95-40.0]. b.Controls:
6.0 micromoles/L [5.01-6.99].
___________________________________________________________________________________________________________________________________________________
1 Gallai V, Caso V, Paciaroni M, Cardaioli G, Arning E, Bottiglieri
T, Pernetti L. Mild hyperhomosyct(e)inemia: A possible risk factor
for cervical artery dissection. Stroke 2001; 32: 714-718. 2 Vester
B, Rasmussen K. High performance liquid chromatography method for
rapid and accurate determination of homocysteine in plasma and
serum. European Journal of Clinical Chemistry and Clinical
Biochemistry 1991; 29: 549-554.
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PROCESSES LEADING TO SPONTANEOUS CAD 1 1.In majority of skin
biopsies taken from CAD patients, irregular collagen fibrils and
elastic fiber fragmentations found: 2 a.Strengthens relationship
between sCAD and connective tissue disorders. b.Potential defects
in extracellular matrix of vessel wall may play a role in
pathogenesis of arterial dissection. 2.Link between
hyperhomocysteinemia and abnormalities in elastic components of
arterial wall have been reported: a.Find in vitro a decrease in
elastin content of arterial wall as a direct or indirect
consequence of homocysteine activation of metalloproteinases 2 and
serine elastases. 3 b.Increased elastolytic activity may result in
opening and/or enlargement of fenestrae in medial elastic laminae,
leading to premature fragmentation of arterial elastic fibers and
degradation of extracellular matrix. 2,3 3.Homocysteine shown to
block aldehydic groups in elastin, inhibiting the cross-linking
needed to stabilize elastin. 4 4.Cross-linking of collagen may also
be impaired. 5 1 Pezzini A, Del Zotto E, Archetti S, Negrini R,
Bani P, Albertini A, Grassi M, Assanelli D, Gasparotti R, Vignolo
LA, Magoni M, Padovani A. Plasma homocysteine concentration, C677T
MTHFR genotype, and 844ins68bp genotype in young adults with
spontaneous cervical artery dissection and atherothrombotic stroke.
Stroke 2002; 33: 664-669. 2 Charplot P, Bescond A, Augler T,
Chereyre C, Fratermo M, Rolland PH, Garcon D. Hyperhomocysteinemia
induces elastolysis in minipig arteries: Structural consequences,
arterial site specificity and effect of
captoprilhydrochlorothiazide. Matrix Biology 1998; 17: 559-574. 3
Rahmani DJ, Rolland PH, Rosset E, Branchereau A, Garcon D.
Homocysteine induces synthesis of a serine elastase in arterial
smooth muscle cells from multiorgan donors. Cardiovascular Research
1997; 34: 597-602. 4 Jackson SH. The reaction of homocysteine with
aldehyde: An explanation of the collagen defects in homocystinuria.
Clinica Chimica Acta 1973; 45: 215-217. 5 Kang AH, Trelstad RL. A
collagen defect in homocystinuria. Journal of Clinical
Investigation 1973; 52: 2571-2578.
Slide 155
CLINICAL ASSAYS FOR HOMOCYSTEINE 1.High-pressure liquid
chromatography + gas chromatography/mass spectrometry. 2.Enzyme
conversion immunoassay [EIA] 4 can be automated on the Abbot IMx,
which can operates on the principle of fluorescence polarization. 5
3.A second automated assay method using the Immunlite 2000 analyzer
which operates on the principle of chemiluminescence correlates
extremely well with the Abbott Imx. 6
__________________________________________________________________________________________________________________________________________
1 Ueland P, Refsum H, Stabler SP, Mainow MR, Anderson A, Allen RH.
Total homocysteine in plasma and serum: Methods and clinical
applications. Clinical Chemistry 1993; 39: 1764-1779. 2 Stabler SP,
Marcell PD, Podell ER, Allen RH. Quantitation of total
homocysteine, total cysteine, and methionine in normal serum and
urine using capillary gas chromatography-mass spectrometry.
Analytical Biochemistry 1987; 162: 185-196. 3 Pietzsch J, Julius U,
Hanefeld M. Rapid determination of total homocysteine in human
plasma by using N(O,S)-ethoxycarbonyl ethyl ester derivatives and
gas chromatography-mass spectrometry. Clinical Chemistry 1997; 43:
2001-2004. 4 Frantzen F, Faaren AL, Alfheim I, Nordehi AK. Enzyme
conversion immunoassay for determining total homocysteine in plasma
or serum. Clinical Chemistry 1998; 344: 311-316. 5 Shipchandler MT,
Moore EG. Rapid, fully automated measurement of plasma
homocyst(e)ine with the Abbott IMx analyzer. Clinical Chemistry
1995; 41: 991-994. 6 Quillard M, Berthe M.-C, Sauger F, Lavoinne A.
Dosage plasmatique de lhomocysteine sur lImmulite 2000 DPC:
Comparison avec le dosage sur lIMX Abbott. Annals de Biologie
Clinique 2003; 61: 699-704.
Slide 156
SERUM FOLATE: RELATIONSHIP TO HOMOCYSTEINE AND NITRATE 1
1.Folate may contribute in prevention of coronary heart disease
because folate seems to restore impaired nitric oxide [NO]
metabolism. 2 NO relaxes vascular smooth muscle cells, causes
vasodilation, inhibits platelet aggregation. 2.Proposed metabolic
relationships: Folate and NO 3 and folate and homocysteine:
______________________________________________________________________________________________________
1Mansoor MA, Kristensen O, Hervig T. Stakkestad JA, Berge T,
Drablos PA, Rolfsen S, Wentzel-Larsen T. Relationship between serum
folate and plasma nitrate concentrations: Possible clinical
implications. Clinical Chemistry 2005; 51(7): 1266-1268.
Slide 157
DIETARY FOLATE INTAKE 1 1.In a population of 9764
non-institutionalized men and women in the U.S. aged 25-75 years,
dietary intake of folate from food sources in independently and
inversely related to the risk of stroke and cardiovascular disease.
1 2. National average of folate intake is 224 micrograms/day; 2 an
additional intake of 95 micrograms/day in the diet of middle-aged
and older adults has been proposed to be consistent with
approximately a 12% reduction in stroke over 20 years. 2 1 Bazzano
LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L., Shelton PK.
Dietary intake of folate and risk of stroke in US men and women:
NHANES I epidemiologic I follow-up study. Stroke 2002; 33(5):
1183-1189. 2 Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA,
Manson JE, Hennekens C, Stampher Mj. Folate and vitamin B6 from
diet and supplements in relation to the risk of coronary heart
disease among women. Journal of the American Medication Association
1998; 279: 359-364.
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LOWERING SERUM HOMOCYSTEINE 1 In a placebo-controlled RCT with
530 men and post- menopausal women with homocysteine levels at 13
micromoles/ L [1.8 mg/L] or higher, folate supplement of 0.8 mg/d
for 1 year: a. Increased serum folate 400% [362-436%]. b. Decreased
serum homocysteine 28% [24-36%]:
________________________________________________________________________________________________
_____ 1 Durga J, van Tits LJH, Schouten EG, Kok FJ, Verhoef P.
Effect of lowering homocysteine levels on inflammatory markers.
Archives of Internal Medicine 2005; 165: 1388-1394.
Slide 159
CHIROPRACTIC RESEARCH CHALLENGE? u Remember, Ginger Rogers did
everything Fred Astaire did, but she did it back- wards and in high
heels. u -Faith Whittlesey