Research Review By Dr. Michael Haneline©

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Date Posted:

February 2023

Study Title:

Association between cervical artery dissection and spinal manipulative therapy – a Medicare claims analysis

Authors:

Whedon J, Petersen C, Li Z, et al.

Author's Affiliations:

Health Services Research, Southern California University of Health Sciences, Whittier, CA, USA; The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH, USA; Department of Neurology, University of California at Irvine, Irvine, CA, USA

Publication Information:

BMC Geriatrics 2022; 22: 917. doi: 10.1186/s12877-022-03495-5.

Background Information:

Patients with cervical artery dissection (CeAD) involving the carotid or vertebral arteries may be asymptomatic, although they frequently experience neck pain and/or headache (therefore they may seek chiropractic care!). A recent case-control study involving 165 patients < 50 years-of-age with ischemic strokes found that headache and neck pain were positively correlated with CeAD (1). CeAD may lead to a stroke if the blood filled and weakened arterial wall obstructs blood flow to the brain or if a thrombus becomes dislodged.

CeAD is the most serious safety concern associated with cervical manipulation, but it is considered a rare condition, accounting for approximately 2% of ischemic strokes overall (that 2% includes both carotid and vertebral artery dissections) (2). The reported annual incidence is approximately 3 per 100,000 persons for carotid artery dissection (CAD) and 1 per 100,000 for vertebral artery dissection (VAD) (3). Nevertheless, VADs have been reported to occur following cervical spinal manipulation (CSM) 3 times more often than CADs (4).

CSM has been shown to be effective in the treatment of chronic nonspecific neck pain (5) and several medical associations recommend its use for managing neck pain in older adults. However, a systematic review that evaluated 31 case control studies reported a strong association between CSM and CeAD-associated stroke, with an adjusted odds ratio of 3.8 (3). Due to the rarity of CeAD, it has been suggested that much larger sample sizes would be required to fully assess the safety of CSM in this regard (5). The American Heart Association (AHA) and the American Stroke Association (ASA) recommend that patients should be informed of the association between CSM and CeAD (6) and this is something chiropractors discuss with patients during a typical informed consent process prior to providing neck manipulation.

CeAD is typically considered to be a condition that mainly affects younger, middle-aged people, although recent studies have suggested that it may have been underdiagnosed in older patients (7). In fact, based on data from the National Inpatient Sample, the prevalence of CeAD related stroke hospitalizations increases with age. Accordingly, this study evaluated the relationship between CSM and CeAD among Medicare beneficiaries using claims data from Medicare enrollees aged 65–99. Several different control groups were included, and advanced statistical methods were used to control for possible confounding.

Pertinent Results:

The total number of CeAD cases was 9021, there were 89 892 population controls, and 2 964 073 ischemic stroke controls. The demographics of these populations were similar.

The odds of CSM compared to Evaluation and Management (E&M) did not differ significantly between VAD cases and controls at any of the time points. Although not statistically significant, the odds of CSM compared to E&M were 1.60 higher in VAD patients within the 7 days before the index date. The odds of having neither CSM nor E&M in the 14- and 30-day windows before the index date were significantly lower among VAD cases, which may be related to cases seeking care for early VAD symptoms.

The odds of CSM compared to E&M were also not significantly elevated in CAD cases compared to controls and there were no significant differences between CAD cases and controls for having neither CSM nor E&M at any of the time points.

When compared to the ischemic stroke controls, the odds of CSM in VAD cases versus non-CeAD ischemic stroke controls were not significantly different at any of the time points. The odds of cases having neither a CSM nor E&M visit were noticeably lower (ORs 0.36 and 0.39) in both the VAD and CAD groups at every time point.

The case-crossover analyses showed that CSM was not more likely than E&M in the 7 days, 14 days, or 30 days prior to a VAD. There was also no increased risk of receiving CSM compared to E&M in any of the time periods for CAD.

Clinical Application & Conclusions:

The results of this study showed that there was no increased risk of VAD or CAD associated with CSM in older patients. On the other hand, there was a strong relationship between those patients who were seen for head and/or neck complaints and an ensuing diagnosis of CeAD, whether they received either CSM or E&M versus neither. A likely explanation for this disparity is that neck pain and/or headache may represent symptoms of a dissection in progress, which causes a patient to seek care (8).

Given that CeAD patients may seek care for early symptoms, like neck pain, headache, dizziness and others, it is important for physicians to perform a suitable neurological examination on these patients to rule out any related cerebral ischemia. Patients with findings positive for cerebral ischemia should not receive CSM but should be referred to a neurologist for evaluation and possible treatment (9).

Study Methods:

Three different types of controls were used to analyze the relationship between CSM and CeAD:
  1. a case-control design comprised of cases with CeAD and controls from the population of Medicare beneficiaries matched by sex, age and calendar year of the CeAD;
  2. a case-control design with the same cases and controls with ischemic stroke from the population of Medicare beneficiaries; and
  3. a case-crossover design, in which exposures prior to the CeAD were compared to exposures in the period 6 months earlier in the same patient.
The study’s primary outcome was the occurrence of a CeAD, which was sub-divided into vertebral artery (VAD) and carotid artery (CAD) dissections. Cases were Medicare beneficiaries with a new (none in the prior year) primary diagnosis of International Classification of Disease (ICD-9) code 443.24 (VAD) or 443.21 (CAD) on at least 1 inpatient hospital claim or a primary/secondary diagnosis for outpatient hospital claims on at least 2 separate days. Most (73%) of CeAD cases had a diagnosis of stroke within 30 days of the CeAD diagnosis.

Control Populations & Case-Crossover:
  • Population controls were Medicare beneficiaries without CeAD matched to the CeAD cases in a 10:1 ratio. Controls were excluded if they ever had a diagnosis of CeAD.
  • The ischemic stroke controls had a diagnosis code for a non-CeAD-associated ischemic stroke on at least one inpatient hospital claim or a primary/secondary diagnosis for outpatient hospital and Part B claims on at least 2 separate days.
  • For the case-crossover study, claims for the CeAD cases were evaluated in the 6–7 months period immediately before the date of diagnosis of their CeAD.
In addition to the primary exposure, which was CSM as identified by Current Procedural Terminology (CPT) codes indicating spinal manipulation by a Doctor of Chiropractic, a secondary exposure that was included in the analysis was an encounter for certain E&M codes (E&M = evaluation and management). The primary and secondary exposure were then categorized as 1) CSM, 2) E&M but no CSM and 3) neither CSM nor E&M. Only the cases with both a CSM and an E&M visit in the required time period were analyzed in the CSM group. These exposures were analyzed for 3 timeframes, up to 7, 14 and 30 days prior to the index event. All diagnoses 14 to 365 days preceding the index date were considered to factor comorbidities into the analysis.

Study Strengths / Weaknesses:

This was a well-done study on the association between CSM and CeAD which resolved some of the limitations of previous research on this topic. The sample size was more than 9 times larger than the biggest previous study on this topic which gave it a considerable statistical advantage.

Advanced statistical techniques were used to control for potential confounding variables, including comorbidities. Three different kinds of control groups were used, and the exposure (CSM) was analyzed at 3 different points in time (7, 14 and 30 days). Patients receiving CSM were compared to patients receiving a similar E&M visit to take into consideration care-seeking behavior prior to any CeAD which found no significant relationship between CSM and CeAD.

This study involved a retrospective analysis of health claims data which has several limitations, including inconsistent billing practices and coding procedures, as well as non-randomization of the subjects leading to possible systematic differences between the groups.

Another study limitation is the large confidence interval for “Any CSM Visit” suggesting a degree of uncertainty about the results. Patients were all aged 65 and older, making generalization to other (younger) populations problematic. With that said, this paper certainly helped fill a gap in the literature pertaining to this potential relationship in older patients.

Additional References:

  1. Cheng W, Wang Y, Lian Y, et al. A case-control study of the determinants for cervicocerebral artery dissection. J Neurol 2019; 266: 119–23.
  2. Schievink W, Mokri B, O’Fallon W. Recurrent spontaneous cervical artery dissection. N Engl J Med 1994; 330: 393–7.
  3. Rubinstein S, Peerdeman S, van Tulder M, Riphagen I, Haldeman S. A systematic review of the risk factors for cervical artery dissection. Stroke. 2005; 36: 1575–80.
  4. Haneline M, Lewkovich G. An analysis of the etiology of cervical artery dissections: 1994 to 2003. J Manip Physiol Ther 2005; 28: 617–22.
  5. Coulter I, Crawford C, Vernon H, et al. Manipulation and Mobilization for Treating Chronic Nonspecific Neck Pain: A Systematic Review and Meta-Analysis for an Appropriateness Panel. Pain Physician 2019; 22: E55–70.
  6. Biller J, Sacco R, Albuquerque F, et al. Cervical arterial dissections and association with cervical manipulative therapy: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45: 3155–74.
  7. Riou-Comte N, Mione G, Humbertjean L, Ottenin M, Lacour J, Richard S. Spontaneous cervical artery dissection in patients aged over 70 years: two cases and systematic literature review. Clin Interv Aging 2017; 12: 1355–62.
  8. Haldeman S, Kohlbeck FJ, McGregor M. Stroke, cerebral artery dissection, and cervical spine manipulation therapy. J Neurol 2002; 249: 1098–104.
  9. Haneline M, Lewkovich G. Chiropractic manipulation and cervical artery dissection. J Amer Chiropr Assoc 2007 Jan-Feb; 44(1): 20-26.

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