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

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.

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

Without question, this is the most catastrophic iatrogenic injury that can occur in the office of any practitioner of manipulative therapy.

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.

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.

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.

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.

CEREBROVASCULAR ANATOMY AND HEMODYNAMICS

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.

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.

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.

Hemodynamics

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

When graphically depicted, the reason for the term "posterior circulation" becomes obvious.

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.

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.

Contralateral Artery Stretch

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.

Rotation was the single most likely movement to cause occlusion.

ROTATIONAL INJURY/VERTEBRAL ARTERY

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.

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.

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.

Extra-luminal Compression Part II Vertebral Artery

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.

PATHOPHYSIOLOGICAL MECHANISMS IN VASCULAR INJURIES

CSMT may be responsible for neurovascular insufficiency via indirect trauma to the arterial wall by causing vasospasm, a clot or a tear.

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.

Arterial Dissection

_________________________________________________________________________________________________________________________________________________________ 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

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.

PATIENT ASSESSMENT: PREDISPOSITION AND CLINICAL TESTING

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.

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.

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.

Case History:

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."

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

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.

Bilateral Blood Pressure and Auscultation

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.

Likewise, bruit in the neck have not been linked to post manipulative VBI.

Vertebrobasilar Insufficiency Testing

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.

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.

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.

No evidence conclusively, or even preliminarily, exists to show that this maneuver has any correlation whatever to impending neural ischemia related to CSMT.

False-positive tests may occur due to stimulation of the vestibular apparatus, cervical sympathetics, carotid sinus receptors, and other vertebrogenic causes.

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.

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.

RECOGNITION OF POSTADJUSTIVE VERTEBROBASILAR INSUFFICIENCY

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.

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.

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.

Acceptable risk Versus Callousness or Ignorance.

RECOGNITION

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.

Lateral Medulary Stndrome

Lateral Medulary Syndrome

Most postadjustive VBI result in almost complete recovery, or at least minimal residual neurological deficit.

ACTION STEPS

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.

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.

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.

If a vascular injury has occurred, little can be done at a hospital to minimize the damage in the acute stage anyway.

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.

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.

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.

Should any non- preexisting neurological abnormality exist, make a prompt medical referral.

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.

It is possible for all symptoms to clear and for a full-blown stroke to occur at a later date.

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.

The patient must be instructed to contact you immediately in the event that any of these symptoms reappear.

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.

If similar symptomatology occurs a second time, I would not continue with osseous cervical adjustments on that patient.

Many of the classic symptoms of neural ischemia (nausea, tinnitus, lightheadedness, visual problems, etc.) are actually relieved by cervical adjustment.

An Acceptable Risk

It has been said that "if you can cure it, you can cause it." The RISK:BENEFIT ratio.

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?

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.

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.

Recommendations

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.

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.

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:

u STROKE - (CVA) Anterior Circulation Vast Majority - Internal Carotid System Rare Posterior Circulation - Vertebrobasilar System Hemmorhagic Ischemic Vast Majority Anoxia or Hypoxia Intraluminal - *Vast Majority Dissection - ^Rare - Traumatic - chiropractors?? Dissection - Non-Traumatic - Spontaneous Vast Majority -Thrombo-emboli Fibrous Dysplasia Extraluminal Kinks and Compression Blood Dyscrasias Cardiac Origin

PERSPECTIVES

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.

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

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."

Perspectives u Talking Points Regarding Post- Manipulation VBI u Compiled By: u Anthony Rosner, PhD - FCER

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. ________________________________________________________________________________________________________

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.

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.

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.

TAKING NSAIDS TOXICITY TO THE STREETS

VIOXX AND CARDIOVASCULAR EVENTS 1 _____________________________________________________________________________ __ 1 Couzin J. Withdrawal of Vioxx casts a shadow over COX-2 inhibitors. Science 2004; 306(5695): 384-385.

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.

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.

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

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.

The ACC Position u Tests are not useful u Should no longer be taught

IN ADDITION. IN ADDITION. u All chiropractic colleges will be eliminating u the teaching of provocative testing from u their curricula.

ADDITIONAL PERSPECTIVES The Genetic and Homocysteine Link

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 nontraumatic 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.

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.

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.

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.

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.

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.

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.

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.

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

Documents

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