William Salvatore, D.C.

DEFINITIONS

Scientific research articles use words that have important meanings in interpreting the value of a study. Such important words include:

Correlation / Association
Causation
Reverse Causation

We will use the words correlation and association as being synonymous, or as being the same.

Correlation (association) (1):

There is a relationship between two or more variables.

Correlations can be positive or negative. In a positive correlation, as one variable goes up, so does the other. As an example, as one increases marijuana smoking, relationship trouble increases.

In a negative correlation, as one variable goes up, another goes down. As an example, as one increases marijuana smoking, grade point average goes down.

Causation (1):

Causation means that the changes in one variable directly caused changes in the other. In biomedical research, this is often hard to show because of the difficulty in controlling all of the variables. Unless properly controlled for, there could be other variables affecting this relationship that the researchers don't know about. A simple example of causation would be that if one exercises vigorously, one’s heart rate increases.

It is impossible to establish 100% causality. Most research indicates a correlation between variables, not causation.

In biomedical research, the closest one can come to establishing causation is by dong a randomized clinical trial. In order to be able to claim causation, the researchers have to split the participants into different groups, and assign them the behavior they want to study. It's this random assignment to conditions that makes experiments suitable for the discovery of causality. Unlike in association studies, random assignment assures (if everything is designed correctly) that it’s the behavior being studied, and not some other random effect, that is causing the outcome.

The only study design involving humans that does rise to the level of demonstrating cause and effect is a randomized trial. In this design, study subjects are assigned an exposure (or a control condition) at random, irrespective of any other exposures in their lives, and all such other exposures are then assumed to even out between the treated group and the control group of subjects (and this can be demonstrated). As a result, the only difference between the groups is whether they receive the exposure under study or the control condition. This approach is a true experiment. Any difference in outcome seen between the control and the experimental group should be due to the one factor or variable that differs.

In 2014, Nina Teicholz states (2):

“To establish cause and effect with any reliability, investigators must almost always undertake a type of research called the clinical trial.”

It is much more difficult to prove causation than it is to prove a correlation. Under the best analysis circumstances, correlation is not the same as causation. “Association does not imply causation!” (3)

Reverse Causation

Reverse Causality is cause and effect in reverse. The effects precede the cause. In the example of positive correlation from above, if one increases marijuana smoking, relationship trouble increase. An example of reverse causality would be that people with relationship troubles smoke more marijuana.

Reverse causality refers to a direction of cause-and-effect contrary to a common presumption. Reverse causality is cause and effect in reverse. That is to say the effects precede the cause. The problem is when the assumption is A causes B when the truth may actually be that B causes A.

Another example of reverse causality is that when a whiplash injured patient seeks compensation (ask for compensation, hires a lawyer, etc.)(A), they have worse health outcomes and slower recovery rates (B). However, the concept of reverse causality is that slower recovery following a whiplash injury (B) leads individuals to fie a claim, seek legal advice, and litigate (A). (4)

As another example, there is a positive correlation between the number of firemen fighting a fire and the size of the fire. However, this doesn’t mean that bringing more firemen will cause the size of the fire to increase.

•••••

For decades, health care providers have noticed a correlation between certain cervical spine manipulations and dissections of either the internal carotid artery and/or the vertebral artery (cervical artery dissections). To date, the most extensive review of the literature pertaining to the relationship between cervical spine manipulation and cervical artery dissection was published in the journal Stroke, August 7, 2014 (5). Stroke is the official journal of the American Heart Association. The title of the article is:

Cervical Arterial Dissections and Association 
With Cervical Manipulative Therapy:
A Statement for Healthcare Professionals From the
American Heart Association/American Stroke Association

The American Heart Association Stroke Council’s Scientific

Statements Oversight Committee and the American Heart Association’s Manuscript Oversight Committee assigned thirteen experts to review the literature and write this paper. Their end product is endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons. “At the American Heart Association’s invitation, the American Chiropractic Association designated a representative to participate in the development of this paper but who elected not to be named.” This paper lists 236 references.

Key points from this publication include:

• At least 38% of US adults and 12% of children use some form of alternative medicine, including chiropractic and osteopathic manipulations, mainly for back, neck, and joint pain.
•  “Chiropractic is the largest alternative medical profession in the United States and the third largest clinical profession granting doctorates behind medicine and dentistry.”
• Cervical artery “dissections can be either spontaneous or traumatic.”
• Patients with cervical artery dissection may present with unilateral headaches, posterior cervical pain, cranial nerve palsies, oculosympathetic palsy (Horner’s syndrome), or pulsatile tinnitus.
• Cervical artery dissection primarily occurs in young and middle-aged patients.
• Cervical artery dissection is most prevalent in the upper cervical spine and can involve the internal carotid artery or vertebral artery.
• “Current biomechanical evidence is insufficient to establish the claim that cervical manipulation causes cervical artery dissection.”
• “The underlying pathogenesis responsible for spontaneous cervical artery dissections is unknown.”
• Traumatic cervical artery dissections can range from the severe, such as that which might occur in a high-speed motor vehicle crash, to the more subtle, such as coughing, sneezing, or countless sporting activities such as heavy lifting, golf, tennis, and yoga.
• Other factors associated with cervical artery dissection include:
  
  • Major and minor cervical trauma
  • Arterial hypertension
  • Young age
  • Current use of oral contraceptives
  • Migraine
  • Fibromuscular dysplasia
  • Ultrastructural connective tissue abnormalities
  • Vascular subtype of Ehlers-Danlos syndrome
  • Marfan syndrome
  • Turner syndrome
  • Williams syndrome
  • Hereditary hemochromatosis
  • Osteogenesis imperfecta
  • Hyperhomocysteinemia
  • Long styloid process length
  • Autosomal-dominant polycystic kidney disease
  • Infections
  • Vessel redundancies (coils, kinks, loops), especially if bilateral
• It is “plausible that cervical manipulation could exacerbate the symptoms of the VAD and possibly increase the risk of stroke.”
• When a patient has neck pain or headache with focal neurological symptoms after any minor trauma, or following cervical manipulation, they should be evaluated immediately for possible cervical artery dissection.
• “Patients with neck pain and without neurological symptoms after any trauma should be informed about the potential risks and benefits of receiving cervical manipulation, and practitioners should carefully consider cervical artery dissection prior to performing cervical manipulation.”
• The vertebral artery (VA) between C1-C2, where most of cervical spine rotation occurs, “is most susceptible to injury.” “Dissections thought to be associated with cervical manipulation have a clear VA predominance.”
• “Current biomechanical evidence is insufficient to establish the claim that spinal manipulation causes cervical artery dissection, including data from a canine model showing no significant changes in VA lesions before and after cervical manipulation.”
• “The presence of high cervical osteophytic disease or other anatomic variations may predispose to or increase the likelihood of VA injury during extension and rotation of the head.”
• “With the increasing use of noninvasive imaging, cervical artery dissection is being diagnosed in many patients who present with subtle manifestations.” In fact, cervical artery dissection symptoms may remain asymptomatic. Asymptomatic cervical artery dissections are frequently encountered.
• The typical patient with internal carotid artery dissection presents with pain on one side of the head, face, or neck accompanied by a partial Horner syndrome. Although Horner’s syndrome has long been recognized as a manifestation of internal carotid artery dissection, it is found in fewer than half of the patients.
• Following the onset of pain of an internal carotid artery dissection, the median time to the appearance of neurological symptoms is on average 9 days with a range of 1–90 days.
• The typical patient with VAD presents with pain in the back of the neck or head, and these symptoms are usually initially interpreted as musculoskeletal in nature. The patient will usually have an occipital headache, but there have been cases of hemicranial or frontal headache, and the neck pain or headache can be bilateral. “The median interval between the onset of neck pain and the appearance of other symptoms is about 2 weeks.”
• “In the absence of prospective cohort or randomized studies, the current best available evidence suggests that cervical artery dissection, especially [vertebral artery dissection] VAD, may be of a low incidence but could be a serious complication of cervical manipulation. Although these studies suggest an association, it is very difficult to determine causation because patients with VAD commonly present with neck pain, which may not be diagnosed prior to any cervical manipulation. Because patients with VAD commonly present with neck pain, it is possible that they seek therapy for this symptom from providers, including cervical manipulation practitioners, and that the VAD occurs spontaneously, implying that the association between cervical manipulation and VAD/vertebrobasilar artery stroke is not causal.”
• Diagnostic tests for cervical artery dissection include:
  
  • Duplex Ultrasonography
  • Cat Scan (CT)
  • Cat Scan Angiography (CTA)
  • MRI
  • MRI Angiogram
  • Digital Subtraction Angiography
• There is no gold standard diagnostic test for cervical artery dissection.
• “The clear majority of patients with cervical artery dissections have good outcomes.”
• “Although the incidence of cervical artery dissections in cervical manipulation patients is probably low, and causality difficult to prove, practitioners should both strongly consider the possibility of cervical artery dissections and inform patients of the statistical association between cervical artery dissections and cervical manipulation, prior to performing manipulation of the cervical spine.”

These authors note that the majority of the literature associating cervical manipulation with vertebral artery stroke is from case reports/case series, surveys, or expert opinions. “Given the very low incidence of cervical artery dissection, the best study design that has been used to date to determine whether cervical manipulation may cause cervical artery dissection is the case-control study.” These authors could only find 4 acceptable case-control studies evaluating cervical artery dissection and cervical manipulation. They were clearly most impressed with the article by Cassidy et al., noting (6):

“Cassidy et al analyzed every case of vertebrobasilar artery territory distribution ischemic stroke in the province of Ontario, Canada, over a 9-year period in a population-based case-control and case-crossover design.

There were 818 cases in 100 million person-years of analysis. They evaluated the association between VA territory stroke and chiropractic visits, as well as seeing a primary care physician.

For those <45 years of age, 8 cases (7.8%) had consulted a chiropractor within 7 days of the index date compared with 14 of controls (3.4%).

They found an association between chiropractic visits and VA strokes. However, the risk was similar to the risk of VA stroke after seeing a primary care physician. This led the authors to conclude that chiropractic care does not appear to pose an excess risk of VA stroke and to suggest that headache or neck pain from VAD causes people to seek care from either chiropractic or medical physicians.”

This study by Dr. David Cassidy also made these points (6):

1. “Vertebrobasilar artery stroke is a rare event in the population.”
2. “We found no evidence of excess risk of vertebral artery stroke associated with chiropractic care.”
3. “Neck pain and headache are common symptoms of vertebral artery dissection, which commonly precedes vertebral artery stroke.”
4. “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.”
5. Most cases of vertebral arterial dissection occur spontaneously.
6. “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.”
7. Cervical manipulation “is unlikely to be a major cause” of these rare vertebral artery stroke events.
8. “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.”
9. “There is no acceptable screening procedure to identify patients with neck pain at risk of vertebral artery stroke.”

•••••

This article from the American Heart/Stroke Association and published in the journal Stroke suggests there is an association (correlation) between cervical manipulation and cervical artery dissection. The authors emphasize that the evidence suggests association only, NOT causation, and at the most, the incidence in quite low. The authors indicate that the artery at greatest risk for dissection is the vertebral artery, and it is most vulnerable to dissection between C1-C2, especially when subjected to the combination of extension-rotation-thrust maneuvers. Importantly, for decades, chiropractors have been taught not to perform such maneuvers on patients. The incidence of cervical artery dissection is so rare that the vast majority of chiropractors will never see a single case in their career.

The authors of the Stroke study also make a strong argument for reverse causality. Relying on the Cassidy study (6), they present evidence that since spontaneous cervical artery dissections cause neck and head symptoms, such individuals present to health care providers to evaluate and treat such symptoms. In other words, the cervical artery dissection is spontaneous, not being caused by cervical manipulation.

Another important issue in evaluating the literature pertaining to cervical artery dissection and cervical manipulation, is that much of the published literature on the topic considers “chiropractic” and “manipulation” to be synonymous. Chiropractors are extensively trained in the science and art of manipulation, while lay practitioners often are not. Alan Terrett has shown that often, in the literature, when an untrained person manipulates a patient and causes an injury, the literature inappropriately labels the manipulator as being a chiropractor (7). The list of discovered manipulators included:

• A Blind Masseur
• An Indian Barber
• A Wife
• A Kung-Fu Practitioner
• Self Manipulation
• A medical doctor
• An osteopath
• A naturopath
• A physical therapist

Dr. Terrett concluded:

“This study reveals that the words chiropractic and chiropractor commonly appear in the literature to describe spinal manipulative therapy, or practitioner of spinal manipulative therapy, in association with iatrogenic complications, regardless of the presence or absence of professional training of the practitioner involved.”

“The words chiropractic and chiropractor have been incorrectly used in numerous publications dealing with spinal manipulative 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 non-chiropractor. The true incidence of such reporting cannot be determined.”

“Such reporting adversely affects the reader's opinion of chiropractic and chiropractors.”

“It has been clearly demonstrated that the literature of medical organizations, medical authors and respected, peer-reviewed, indexed journals have, on numerous occasions, misrepresented the facts regarding the identity of a practitioner of manual therapy associated with patient injury.”

“Such biased reporting must influence the perception of chiropractic held by the reader, especially when cases of death, tetraplegia and neurological deficit are incorrectly reported as having been caused by chiropractic.”

“Because of the unwarranted negative opinion generated in medical readers and the lay public alike, erroneous reporting is likely to result in hesitancy to refer to and underutilization of a mode of health care delivery.”

With respects to risk associated with cervical manipulation, there is particular concern pertaining to vertebral artery dissection. All chiropractors are well aware of the issue. Vertebral artery dissection is extensively discussed in both chiropractic undergraduate and post graduate continuing educational programs. Entire books are written on the subject and are a part of core curriculum at chiropractic colleges (8). Chiropractors are well schooled on the pertinent anatomy, signs/symptoms, clinical presentations, examination findings, and procedures that may possibly be associated with increased risk.

In 2002, the Journal of Neurology (9) published a study titled:

“Hyperhomocysteinemia

A potential risk factor for cervical artery dissection following chiropractic manipulation of the cervical spine”

In this study, the authors note that the risk factors used by chiropractors to screen patients at risk for cervical artery dissection from manipulation are usually unrevealing. Therefore, “the population at risk cannot be identified a priori” using standard risk factor screening.

In 2002, Dr. Scott Haldeman from the Department of Neurology, University of California, Irvine, and colleagues, published a study titled (10):

“Unpredictability of cerebrovascular ischemia associated 
with cervical spine manipulation therapy: 
a review of sixty-four cases after cervical spine manipulation”

The study, published in Spine, was a retrospective review of 64 medicolegal records describing cerebrovascular ischemia after cervical spine manipulation. The authors note, that up to the publication of their article in 2002, only about 117 cases of post-manipulation cerebrovascular ischemia had been reported in the English language literature.

The authors further indicate that proposed risk factors for cerebrovascular ischemia secondary to spinal manipulation include age, gender, migraine headaches, hypertension, diabetes, birth control pills, cervical spondylosis, and smoking, and that it is often assumed that these complications may be avoided by clinically screening patients and by pre-manipulation positioning of the head and neck to evaluate the patency of the vertebral arteries.

After an extensive review, these authors conclude:

“This study was unable to identify factors from the clinical history and physical examination of the patient that would assist a physician attempting to isolate the patient at risk of cerebral ischemia after cervical manipulation.”

“Cerebrovascular accidents after manipulation appear to be unpredictable and should be considered an inherent, idiosyncratic, and rare complication of this treatment approach.”

In 2004, the American Academy of Orthopedic Surgeons published a monograph titled Neck Pain (11). The second to last chapter in the monograph, chapter 7, is titled:

“Manual Therapy Including Manipulation
For Acute and Chronic Neck Pain”

The editor of the monograph is Jeffery Fischgrund, MD, from the Department of Orthopaedic Surgery at William Beaumont Hospital in Royal Oaks, Michigan. With respect to the safety of spinal manipulation, the authors make the following comments:

“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.”

“It should be noted that complications rates from medications, surgery, and most other neck pain treatments for which data are available are estimated to be higher than those from manual and manipulative therapies.”

In 2012, Walter Herzog and colleagues from the University of Calgary, Canada, published a study titled (12):

Vertebral artery strains during high-speed,  low amplitude cervical spinal manipulation

These authors subjected 12 human cadavers (2 embalmed and 10 fresh) to rotational manipulations performed by 3 licensed chiropractors, while measuring the strain on the cadaver’s vertebral arteries. The study is extensive, performing a total of 3,034 segment strains. Their results include:

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

“The results from this study demonstrate that average and maximal VA strains during high-speed low-amplitude cervical spinal manipulation are substantially less than the strains that can be achieved during ROM 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 VA.”

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

•••••

All therapeutic interventions have risk. The risk of cervical artery dissection from cervical manipulation is extremely low, and may be nonexistent. Associations between cervical artery dissection and cervical manipulation may in fact be an example of reverse causality, meaning the patient with neck/head symptoms my be presenting themselves to a chiropractic office already in spontaneous dissection. Direct causation between cervical manipulation and cervical artery dissection cannot be established because a randomized clinical trial of the risk has never been done and will never be done.

If there is a risk of cervical artery dissection from cervical manipulation, it is clear that such risk is greatest when the manipulation is performed by an untrained individual. Those well trained in the science and art of spinal manipulation, like chiropractors, know to avoid the supposed most risky maneuvers, specifically extension-rotation-thrust of the upper cervical spine. In addition, chiropractors are well schooled in the signs and symptoms of spontaneous cervical artery dissection and the need for an appropriate referral. They are also aware of the genetic, biochemical, congenital and life-style factors that may increase the risk of a cervical artery dissection. Should a suspected vascular event occur following a spinal manipulation, chiropractors are aware of the need for an immediate emergency intervention.

Despite the uncertainty of the relationship between cervical manipulation and cervical artery dissection, informing each patient of the potential risk is prudent.

REFERENCES 

1. Jaffe, A; All About Addiction: Correlation, causation, and association - What does it all mean???; Psychology Today; March 30, 2010.
2. Teicholz N; The Big Fat Surprise, Why Butter, Meat, and Cheese Belong in a Healthy Diet; SIMON & SCHUSTER, 2014, pg. 72.
3. Dallal GE; Little Handbook of Statistics: An Overview of Statistical Methods; Published Online, 2012.
4. Spearing NM, Connelly LB; Is compensation “bad for health”? A systematic meta-review; Injury; January 8, 2010.
5. Biller J, Sacco RL, Albuquerque FC, Demaerschalk BM, Fayad P, Long PH, Noorollah LD, Panagos PD, Schievink WI, Schwartz NE, Shuaib A, Thaler DE, Tirschwell DL; on behalf of the American Heart Association Stroke Council; Cervical Arterial Dissections and Association With Cervical Manipulative Therapy: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association; Stroke; August 7, 2014. [epub]
6. Cassidy JD, Boyle E, Cote P, He Y, Hogg-Johnson S, Silver FL, Bondy SJ. Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study. Spine (Phila Pa 1976). 2008;33:S176–S183.
7. Terrett AG; Misuse of the literature by medical authors in discussing spinal manipulative therapy injury; Journal of Manipulative and Physiological Therapeutics; 1995 May;18(4):203-10.
8. Terrett AGJ; Current Concepts in Vertebrobasilar Complications Following Spinal Manipulation; Second Edition, NCMIC Group, 2001.
9. Pezzini A, Del Zotto E, Padovani A; Hyperhomocysteinemia: A potential risk factor for cervical artery dissection following chiropractic manipulation of the cervical spine; Journal of Neurology, October 2002, Vol. 249, Issue 10, pp. 1401-1403.
10. 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; 2002 Jan 1;27(1):49-55.
11. Fischgrund, JS; Neck Pain, 2004.
12. 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.