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Exploring Anterior Circulation, Posterior Circulation, and Protopathic Bias

Exploring Anterior Circulation, Posterior Circulation, and Protopathic Bias
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Discussion

A disease is not a thing, but rather a process. A disease has a beginning, a middle, and an end.

A treatment intervention that is given in the middle of a disease process may be blamed for causing the disease itself. This is called protopathic bias.

Protopathic Bias is when a treatment for the symptoms of a disease or injury appears to cause the outcome, when in fact it did not.

Background

In 2017, the top-ranked orthopedic journal Spine published a study titled “The Prevalence, Patterns, and Predictors of Chiropractic Use Among US Adults.” (1) The findings were not surprising:

  • 63% of patients sought chiropractic care for low back pain
  • 30% of patients sought chiropractic care for neck pain

The subject of this writing is chiropractic care for neck pain, which is the second most common reason for people going to chiropractors.

It is unquestioned that chiropractic care (spinal manipulation) is effective for neck pain (2, 3, 4, 5, 6, 7). This includes neck pain with associated cervical intervertebral disk herniation resulting in proven compressive neuropathology (8).

It is also unquestioned that chiropractic care is exceptionally safe (8, 9, 10, 11). In some studies, the adverse events attributed to chiropractic spinal adjusting (specific line-of-drive manipulation) is zero (9, 10). This is a factor in chiropractic care being recommended in practice guidelines for the management of spinal pain syndromes (12, 13).

However, chiropractic care is not without some risks. This is why chiropractors, like all other health care providers, use Informed Consent. Typical Informed Consent language used by chiropractors would include:

Every type of health care is associated with some risk of a potential problem. This includes chiropractic health care. We want you to be informed about potential problems associated with chiropractic health care before consenting to treatment.

Chiropractic adjustments are the moving of bones with the doctor’s hands or with the use of a mechanical device or machine. Frequently adjustments create a “pop” or “click” sound/sensation in the area being treated.

Some states require the Informed Consent to be written. Even in states that do not require written a Informed Consent, it is generally a good idea to do so. Ideally, a written Informed Consent would be signed and dated by the patient, indicating that they understood the document and had any questions pertaining to it addressed by the chiropractor.

One’s Informed Consent often will include subjects such as:

  • Stroke
  • Disc Herniations
  • Cauda Equina Syndrome
  • Soft Tissue Injury
  • Rib and other Fractures
  • Physical Therapy Burns
  • Soreness

There is no need to inform about things that a particular chiropractor does not do. For example, if a chiropractor does not used thermal modalities (including ice packs), there is no need to include them in one’s Informed Consent.

Of the seven Informed Consent subjects listed above, the most serious is stroke. The stroke issue pertains only to the cervical spine adjustments. The remainder of this writing pertains to the stroke issue.

Definitions

Stroke means that a portion of the brain or spinal cord does not receive enough oxygen from the blood stream. The results can be temporary or permanent dysfunction of the brain, with a very rare complication of death.

Strokes are medical emergencies because the ultimate clinical outcome is often linked to the treatment given in the first three hours. Therefore, if a stroke is suspected before, during or after a chiropractic visit, a timely referral to the emergency department is important.

There are two primary forms of stroke:

  • Hemorrhagic (bleeding)
  • Embolic (clotting)

Chiropractic cervical adjustments are not associated with hemorrhagic strokes, and therefore they will not be discussed here other than to clarify this point: hemorrhagic strokes are medically managed very differently then embolic strokes. In fact, the most common medical management of an embolic stroke is contraindicated for a hemorrhagic stroke because it may make the patient worse. Therefore, a critical decision for the emergency department is to determine the type of stroke. The most common way to do this is via exposure of a CT scan. Many emergency departments will goal to have the CT scan exposed and read within thirty minutes of a patient’s arrival when a stroke is suspected. CT does not best document embolic stroke, but readily documents a hemorrhagic stroke. Therefore, if a CT rules out a hemorrhagic stroke, an embolic stroke is assumed and usually confirmed with MRI.

If the stroke is determined to be embolic, common medical intervention is the intravenous (IV) application of a clot-dissolving chemical, most commonly tPA (tissue plasminogen activator). Often emergency department personnel goal to have tPA administered within sixty minutes of a patient’s arrival. Again, the overall window for the administration of tPA is short, about 3 hours from first stroke symptoms. Evidence suggests that when administered after three hours of the initiation of stroke symptoms, much of the benefits of clot dissolving are lost.

It is not alleged that chiropractors directly cause strokes. Rather, the allegation is that certain chiropractic adjustments on some patients can cause a dissection of a cervical artery. An arterial dissection occurs when there is a loss of integrity of the inner lining of the arterial blood vessel. The dissection results in a vascular clot that can dislodge and float downstream into the brain, resulting in an embolic stroke.

A number of mechanical events can increase the risk of cervical artery dissection in some individuals, but by far the primary cause is “spontaneous” dissections. Suspected mechanical events that may increase the risk of dissections in some individuals include:

  • Whiplash trauma
  • Sports trauma
  • Head rotation to check traffic
  • Head extension during hair washing
  • Dentistry positions
  • Cervical spine manipulation (as discussed below)

Amino acids are the building blocks of protein. All of our proteins are built by twenty different amino acids. Our body can manufacture eleven of these amino acids, but the other nine (essential amino acids) must be supplied by the diet.

When a person has an adequate supply of all twenty amino acids, their assembly into a specific sequence to make a specific protein is done by our genetic material (DNA). Since everyone’s DNA is unique to them, there is a similar uniqueness to the assembly of proteins in each person.

In addition to one’s innate genetics, other environmental factors can alter the creation of one’s unique repertoire of proteins. Non-mechanical factors that may also increase the risk of dissections in some individuals include:

  • Genetic mutation from exposure to ionizing radiation, smoking, and/or chemicals
  • Birth control pills
  • Infections
  • Certain antibiotics (fluoroquinolones)
  • B-vitamin deficiencies that result in elevated levels of homocysteine
  • Hypertension
  • Chronic stress

Collagen is a protein. It is the most common protein in our bodies. It is the biological “glue” that holds us together. It is responsible for the toughness of our skin, ligaments, tendons and intervertebral disc. Also, the blood vessel owes its vascular integrity to the quality of one’s collagen protein. All factors that weaken or degrade one’s collagen protein will weaken arterial wall vascular integrity, increasing the risk of dissection.

In the neck (cervical spine), there are two arteries that have the potential to dissect. They are the internal carotid artery and the vertebral artery.

The internal carotid arteries give rise to the blood that supplies the anterior (front) portion of the brain. The internal carotid arteries exist anterior to the spinal column.

The vertebral arteries give rise to the blood that supplies the posterior (back) portion of the brain, including the cerebellum and the brain stem. The vertebral arteries exist in the spinal vertebrae, C6 through C1, in a foramen called the foramen transversarium.

In the discussion of mechanical risk to cervical artery dissection, the vertebral artery predominates because of its location in the vertebral foramen transversarium.

Evidence

Cervical artery dissection in proximity to chiropractic spinal adjusting is so rare that it is all but impossible to effectively study. Claimed incidences range from about one in 400,000 adjustments to about one in ten million adjustments (5). What complicates the understanding of these numbers is the proof that many cervical artery strokes that are attributed to chiropractors should actually be attributed to lay (not trained) manipulators (masseuse, barber, spouse, Kung-Fu practitioner, self manipulation, medical doctor, osteopath, naturopath, physical therapist). (14, 15, 16) Apparently, some authors consider “manipulation” and “chiropractic” to be synonymous, when they are not. Chiropractors are well trained in vascular anatomy and trained to avoid any manipulations that may increase the risk of vascular injury. Lay manipulators often lack this training.

There are no published studies showing a causal link between chiropractic spinal adjusting and cervical artery dissection. The majority of evidence suggesting that there is an association between cervical artery dissection and chiropractic adjustments is weak or very weak. This evidence is typically retrospective single case anecdotes. Yet, larger population assessments involving up to 109,000,000 patient years of observation and millions of patients/controls are available, and are briefly reviewed here:

A book (monograph) published by the American Academy of Orthopaedic Surgeons in 2004 notes (5):

“Major complications from manual therapies are extremely rare but, nonetheless, have been a source of much discussion.”

“Estimates of vertebral artery dissections or stroke rates associated with cervical manipulation have ranged from 1 per 400,000 to 1 per 10 million manipulations.”

“An estimate of 1 per 5.85 million manipulations, based on 1988 to 1997 medical record and chiropractic malpractice data from Canada, reflects the experience of practitioners of manipulation.”

“No serious complications from spinal manipulation or other chiropractic forms of manual treatment have been reported from any of the published clinical trials involving manipulation or mobilization for neck pain.”

In 2008, the largest population-based case-control analysis on manipulation/vertebral artery stroke risk ever completed was published in the journal Spine. It involved an incredible 100 million person-years of analysis over a 9-year period. The authors note that most cases of vertebral arterial dissection occur spontaneously.

The authors “conclude that chiropractic care does not appear to pose an excess risk of vertebral artery stroke and to suggest that headache or neck pain from vertebral artery dissection causes people to seek care from either chiropractic or medical physicians.”

“We found no evidence of excess risk of vertebral artery stroke associated with chiropractic care.”

“Neck pain and headache are common symptoms of vertebral artery dissection, which commonly precedes vertebral artery stroke.”

“The increased risks of vertebral artery stroke associated with chiropractic and primary care physician visits is likely due to patients with headache and neck pain from vertebral artery dissection seeking care before their stroke.”

“Because patients with vertebrobasilar artery dissection commonly present with headache and neck pain, it is possible that patients seek chiropractic care for these symptoms and that the subsequent vertebral artery stroke occurs spontaneously, implying that the association between chiropractic care and vertebral artery stroke is not causal.”

“Our results suggest that the association between chiropractic care and vertebral artery stroke found in previous studies is likely explained by presenting symptoms attributable to vertebral artery dissection.”

“There is no acceptable screening procedure to identify patients with neck pain at risk of vertebral artery stroke.”

A 2012 study from the University of Calgary concluded (18):

“The vertebral artery is never really strained during spinal manipulative treatments but that the vertebral artery is merely taking up slack as the neck and head are moved during spinal manipulative treatments, but that there is no stress and thus no possibility for microstructural damage.”

“The results from this study demonstrate that average and maximal vertebral artery strains during high-speed low-amplitude cervical spinal manipulation are substantially less than the strains that can be achieved during range of motion testing for all vertebral artery segments.”

“We conclude that cervical spinal manipulations, as tested here, are safe from a mechanical point of view for normal, healthy vertebral artery.”

“We conclude from this work that cervical SMT performed by trained clinicians does not appear to place undue strain on vertebral artery, and thus does not seem to be a factor in vertebro-basilar injuries.”

A 2015 study looked at approximately 39 million Medicare patients to evaluate chiropractic care and the risk of vertebrobasilar stroke, noting (19):

“There was no association between chiropractic visits and VBA stroke found for the overall sample, or for samples stratified by age.”

“We found no significant association between exposure to chiropractic care and the risk of VBA stroke. We conclude that manipulation is an unlikely cause of VBA stroke.”

“Our results increase confidence in the findings of a previous study, which concluded there was no excess risk of VBA stroke associated chiropractic care compared to primary care.”

“Our results add weight to the view that chiropractic care is an unlikely cause of VBA strokes.”

A 2016 study from Penn State Hershey Medical Center, and the Johns Hopkins University School of Medicine produced a systematic review and meta-analysis of chiropractic care and cervical artery dissection, noting (20):

“We found no evidence for a causal link between chiropractic care and cervical artery dissection (CAD). This is a significant finding because belief in a causal link is not uncommon, and such a belief may have significant adverse effects such as numerous episodes of litigation.”

“Excellent peer reviewed publications frequently contain statements asserting a causal relationship between cervical manipulation and CAD. We suggest that physicians should exercise caution in ascribing causation to associations in the absence of adequate and reliable data. Medical history offers many examples of relationships that were initially falsely assumed to be causal, and the relationship between CAD and chiropractic neck manipulation may need to be added to this list.”

“There is no convincing evidence to support a causal link, and unfounded belief in causation may have dire consequences.”

“The association between a chiropractor visit and dissection may be explained by understanding that “patients with cervical artery dissection more frequently have headache and neck pain” and understanding that “patients with headache and neck pain more frequently visit chiropractors.”

A 2019 study from Norway analyzed the risk-benefit issue pertaining to cervical artery injury and cervical spine manual therapy, noting (21):

“The vertebral artery is thought to be most susceptible to injury due to extreme rotatory head movements, especially in the transverse foramen in the first cervical vertebrae, as the vertebral artery abruptly transitions from a vertical path to a horizontal orientation.”

“Several extensive cohort studies and meta-analyses have found no excess risk of cervical artery dissection resulting in secondary ischaemic stroke for chiropractic spinal manipulative therapy compared to primary care follow-up.”

“There is no strong evidence in the literature that manual therapy provokes cervical artery dissection.”

“The assumption that the cervical manual-therapy intervention triggers cervical artery dissection in rare cases has been dominated by single-case reports and retrospective case series or surveys from neurologists who naturally lack substantial methodological quality to establish definitive causality.”

“There is no sufficient evidence to support cervical vertebral artery tests to identify patients with a higher risk, and the validity and reliability of these tests are low.”

Also in 2019, a study in the journal BMJ Open evaluated the effect of cervical manipulation on vertebral artery blood flow (cerebral hemodynamics), noting (22):

“We found no significant changes within the cerebral haemodynamics following cervical manipulation or maximal neck rotation.”

“The changes observed were found to not be clinically meaningful and suggests that cervical manipulation may not increase the risk of cerebrovascular events through a haemodynamic mechanism.”

“Our work is the first to show that cervical manipulation does not result in brain perfusion changes compared with a neutral neck position or maximal neck rotation.”

“None of the participants during any of the experimental procedures reported, or were observed by the investigators, to have any signs or symptoms of neurological compromise.”

“In conclusion, we found no significant change in blood flow in the posterior cerebrum or cerebellum in chronic neck pain participants after maximum head rotation and cervical manipulation.”

“Our study does not support the hypothesis that neck manipulation or neck rotation are associated with vasospasm of the vertebral artery.”

A third in 2019, published in the Journal of Orthopaedic & Sports Physical Therapy, also assessed neck position influence of vertebral and carotid blood flow, noting (23):

“The positions and movements utilized in high velocity thrust techniques do not seem to alter blood flow.”

“Based on these data it is unlikely that head and neck movement alone, even if forceful, could mechanistically explain the aetiology of adverse events which have conventionally been purported to be related to therapeutic interventions.”

“Conventional thought within the domain of manual therapy has been that rapid, forceful interventions such as high velocity thrust techniques are considered to constitute a higher risk for neuro-vascular events resulting from cervical arterial compromise. However, we found that studies which focused specially on high velocity thrust reported no hemodynamic changes.”

“A clinical implication from this review is that the relationship between cranio-cervical movement and alterations in blood flow does not seem to be as obvious as previous data suggested.”

This study “suggests that adverse events related to cervical spine interventions might be the result of something other than the therapeutic positioning or movement of the head and neck.”

“Conclusion: Our results suggest that in most people, healthy as well as patients with vascular pathologies, cranio-cervical positions do not alter cervical blood flow. This includes vascular test positions, pre-manipulative positions and manipulations.”

“A key clinical implication from this review is that the relationship between cranio-cervical movement and blood flow does not seem to be as previously suggested.”

Clinical Presentation

Cervical artery dissections occur spontaneously, and spontaneous cervical artery dissections cause neck pain and/or headache. There are no tests that show that a person’s neck pain/headache are being caused by a spontaneous dissection:

In 2002, Dr. Scott Haldeman (DC, MD, PhD) and colleagues from the University of California, Irvine, noted (24):

“Cervical artery dissection is a rare event, creating a significant challenge for those who wish to understand it.”

In 2017, a study published in the Journal of Stroke and Cerebrovascular Disease, noted (25):

“Headache and neck pain are common presenting symptoms in patients with cervical artery dissection, and in some cases are the only presenting symptoms.”

“In the absence of neurological signs and symptoms, there are no practical, clinically valid screening tests to identify underlying dissections in patients with head or neck pain.”

Protopathic Bias

The beginning of this review discussed Protopathic Bias. Protopathic Bias is when a treatment for the symptoms of a disease or injury appears to cause the outcome, when in fact it did not. Several studies have used protopathic bias to explain the occurrences of neck pain and/or headache, including:

Journal of Stroke and Cerebrovascular Disease, 2017:

“In case-control studies, protopathic bias can lead to the illusion that the exposure caused the outcome. Even though it is not on the causal pathway.”

“Our results suggest that the association between chiropractic care and carotid artery stroke is explained by protopathic bias.”

“Younger patients with impending carotid artery stroke could be seeking care for dissection-related pain in the head and neck prior to developing stroke. Under this scenario, any care provided by chiropractors or primary care providers is coincidental to the stroke and not the causal pathway.”

BMJ Open, 2019 (22):

“Together with previous work, our results support the position that the association between cervical manipulation and stroke is due to protopathic bias.”

Recommendations

If a patient’s symptoms include more than neck pain and/or headache, and include the 5 Ds And the 3 Ns (below), additional investigations and/or referral may be prudent.

  • Dizziness/vertigo/giddiness/light headedness
  • Drop attacks/loss of consciousness
  • Diplopia (or other visual problems)
  • Dysarthria (speech difficulties)
  • Dysphagia (discomfort or difficulty in swallowing)
  • Ataxia of gait (walking difficulties/ incoordination)
  • Nausea (with possible vomiting)
  • Numbness on one side of the face and/or body
  • Nystagmus

References:

  1. Adams J, Peng W, Cramer H, Sundberg T, Moore C; The Prevalence, Patterns, and Predictors of Chiropractic Use Among US Adults; Results From the 2012 National Health Interview Survey; Spine; December 1, 2017; Vol. 42; No. 23; pp. 1810–1816.
  2. Woodward MN, Cook JCH, Gargan MF, Bannister GC; Chiropractic treatment of chronic ‘whiplash’ injuries; Injury; November 1996; Vol. 27; No. 9; pp. 643-645.
  3. Khan S, Cook J, Gargan M, Bannister G; A symptomatic classification of whiplash injury and the implications for treatment; The Journal of Orthopaedic Medicine; Vol. 21; No. 1; 1999; pp. 22-25.
  4. Hoving JC, Koes BW, de Vet HCW, van der Windt DAWM, Assendelft WJJ, Mameren H, Devillé WLJM; Manual Therapy, Physical Therapy, or Continued Care by a General Practitioner for Patients with Neck Pain; A Randomized Controlled Trial; Annals of Internal Medicine; May 21, 2002; Vol. 136; No. 10; pp. 713-722.
  5. Fischgrund JS; Neck Pain, Monograph 27, American Academy of Orthopaedic Surgeons; 2004.
  6. César Fernández-de-las-Peñas; J. Fernández-Carnero; L. Palomeque del Cerro; Manipulative Treatment vs. Conventional Physiotherapy Treatment in Whiplash Injury: A Randomized Controlled Trial; Journal of Whiplash & Related Disorders; 2004; Vol. 3; No. 2.
  7. Langenfeld A, Humphreys K, Swanenburg J, Peterson CK; Prognostic Factors for Recurrences in Neck Pain Patients Up to 1 Year After Chiropractic Care; Journal of Manipulative and Physiological Therapeutics; September 2015; Vol. 38; No. 7; pp. 458-464.
  8. Peterson CK; Schmid C; Leemann S; Anklin B; Humphreys BK; Outcomes From Magnetic Resonance Imaging: Confirmed Symptomatic Cervical Disk Herniation Patients Treated With High-Velocity, Low-Amplitude Spinal Manipulation Therapy: A Prospective Cohort Study With 3-Month Follow-Up; Journal of Manipulative and Therapeutics; October 2013; Vol. 36; pp. 461-467.
  9. Giles LGF; Muller R; Chronic Spinal Pain: A Randomized Clinical Trial Comparing Medication, Acupuncture, and Spinal Manipulation; Spine July 15, 2003; Vol. 28; No. 14; pp. 1490-1502.
  10. Muller R, Giles LGF; Long-Term Follow-up of a Randomized Clinical Trial Assessing the Efficacy of Medication, Acupuncture, and Spinal Manipulation for Chronic Mechanical Spinal Pain Syndromes; Journal of Manipulative and Physiological Therapeutics; January 2005; Vol. 28; No. 1; pp. 3-11.
  11. Whedon JM, Mackenzie TA, Phillips RB, Lurie JD; Risk of Traumatic Injury Associated with Chiropractic Spinal Manipulation in Medicare Part B Beneficiaries Aged 66-99; Spine; February 15, 2015; Vol. 40; No. 4; pp. 264-270.
  12. Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians; Annals of Intern Medicine; 2017; Vol. 166; No. 7; pp. 514-530.
  13. Chou R, Deyo R, Friedly J, et al; Non-pharmacologic therapies for low back pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline; Annals of Intern Medicine; 2017; Vol. 166; No. 7; pp. 493-505.
  14. Terrett AG; Misuse of the literature by medical authors in discussing spinal manipulative therapy injury; Journal of Manipulative and Physiological Therapeutics; May 1995; Vol. 18; No. 4; pp. 203-210.
  15. Weban A, Beck J, Raabe A, Dettmann E. Seifert V; Misuse of the terms chiropractic and chiropractor; J Neurol Neurosurg Psychiatry; May 2004; Vol. 75; No. 5; p. 794.
  16. Weban A; Inappropriate use of the title ‘chiropractor’ and term ‘chiropractic manipulation’ in the peer-reviewed biomedical literature; Chiropractic and Osteopathy; August 2006; Vol. 22; Vol. 14; p. 16.
  17. Cassidy JD; Boyle E, Côté P, Yaohua H, Hogg-Johnson S, Bondy SJ; Risk of Vertebrobasilar Stroke and Chiropractic Care: Results of a Population-Based Case-Control and Case-Crossover Study; Spine; Vol. 33; No. 4S; February 15, 2008; pp. S176-S183.
  18. Herzog W, Leonard TR, Symons B, Tang C, Wuest S; Vertebral artery strains during high-speed, low amplitude cervical spinal manipulation; Journal of Electromyography and Kinesiology; October 2012; Vol. 22; No. 5; pp. 740-746.
  19. Kosloff TM, Elton D, Tao J, Wade M Bannister WM; Chiropractic Care and the Risk of Vertebrobasilar Stroke: Results of a Case–control Study in U.S. Commercial and Medicare Advantage Populations; Chiropractic & Manual Therapies 2015; Vol. 23; No. 19; pp. 1-10.
  20. Church EW, Sieg EP, Zalatimo O, Hussain NS, Glantz M, Harbaugh RE; Systematic Review and Meta-analysis of Chiropractic Care and Cervical Artery Dissection: No Evidence for Causation; Cureus; February 16, 2016; Vol. 8; No. 2; e498.
  21. Chaibi A, Russell MJ; A Risk–benefit Assessment Strategy to Exclude Cervical Artery Dissection in Spinal Manual Therapy: A Comprehensive Review; Annals of Medicine; March, 2019; Vol. 19; pp. 1-10.
  22. Moser N, Mior S, Noseworthy M, Cote P, Wells G, Behr M, Triano J; Effect of Cervical Manipulation on Vertebral Artery and Cerebral Haemodynamics in Patients with Chronic Neck Pain: A Crossover Randomised Controlled Trial; BMJ Open; May 28, 2019; Vol. 9; No. 5; pp. e025219.
  23. Kranenburg R, Tyer R, Schmitt M, Luijckx GJ, van der Schans C, Hutting N, Kerry R; Effects of Head and Neck Positions on Blood Flow in the Vertebral, Internal Carotid and Intracranial Arteries: A Systematic Review; Journal of Orthopaedic & Sports Physical Therapy; July 2019 [epub].
  24. Haldeman S, Kohlbeck FJ, McGregor M; Unpredictability of Cerebrovascular Ischemia Associated with Cervical Spine Manipulation Therapy: A Review of Sixty-four Cases After Cervical Spine Manipulation; Spine; January 1, 2002; Vol. 27; No. 1; pp. 49-55.
  25. Cassidy JD, Boyle E, Côté P, Hogg-Johnson S, Bondy SJ, Haldeman S; Risk of Carotid Stroke after Chiropractic Care: A Population-Based Case-Crossover Study; Journal of Stroke and Cerebrovascular Disease; April 2017; Vol. 26; No. 4; pp. 842-850.

“Authored by Dan Murphy, D.C.. Published by ChiroTrust® – This publication is not meant to offer treatment advice or protocols. Cited material is not necessarily the opinion of the author or publisher.”