Pub Date: Thursday, Aug 07, 2014
Author: Steven R. Levine, MD, FAHA, FAAN, FANA
Affiliation: The State University of New York (SUNY) Downstate Medical Center
There are many causes of stroke in the young.1 Aspects of our understanding of risk factors in young patients with stroke come from well-documented case reports/series that raise suspicion and subsequent epidemiological studies that reveal potential associations. It is well established that pre-cerebral and cerebral arterial dissections can cause ischemic stroke and that dissection has been invoked as one of the more common causes of strokes under age 50. However, cerebral arterial dissections are unusual to rare in a given primary care clinician's practice. This stroke mechanism can have a myriad of clinician presentations, depending on which pre-cerebral or cerebral artery, the location of the artery, and which area(s) of the brain are affected.
This AHA/ASA statement2 on cervical arterial dissections (CD) has brought together the collective wisdom of a multi-disciplinary expert panel to provide an updated, current state of scientific information on diagnosis and management, as well as the relationship (including a statistical approach) of health care professional cervical manipulative therapy (CMT) causing or contributing to cervical arterial dissection.
The expert panel performed a comprehensive literature review, critiqued a broad range of article types in both the medical and chiropractic peer-reviewed, published literature, and developed consensus. They also tackled the critical issue of whether the force exerted on the local structures including the artery during manipulation with rapid neck movement (that may include lateral and hyperextension) can initiate a tear in the vessel that can manifest either immediately or on a delayed basis. This has public health importance given that approximately 10% of Americans visit a chiropractor, albeit more commonly for low back pain.
Key diagnostic conclusions include:
- Diagnosis of CD should be suspected in patients with an appropriate clinical syndrome, especially when patients are young and without conventional cerebrovascular risk factors.
- Diagnosis of CD is supported by absence of radiological findings typical for other cerebral arteriopathies (e.g. atherosclerotic cerebrovascular disease).
- No single test must be viewed as a gold standard.
- Imaging of the arterial wall is advisable.
- Repeat imaging studies over time are often required.
Evidence for the strengths and limitations of various diagnostic approaches are carefully outlined for both non-invasive (CTA, MRI/MRA, Doppler) and invasive arterial imaging (conventional angiography). Advances in MRI imaging with "dissection protocols" that involve fast spin echo, axial T1-weighted, fat suppression sequences has allowed non-invasive imaging of blood within the vessel wall to facilitate the diagnosis of CD.
Approximately half the patients with "spontaneous" CD have ultrastructural aberrations of dermal collagen fibrils and elastic fibers.
Key therapeutic conclusions include:
- Thrombolysis with IV tPA is reasonably safe in the treatment of patients with acute ischemic stroke due to CD within 4.5 hours.
- For patients with TIA or ischemic stroke due to CD, antiplatelets or anticoagulant therapy for 3-6 months is reasonable.
- ndovascular therapy may be considered for patients with CD who experience definite recurrent cerebral ischemic events while on appropriate antithrombotic therapy.
Caveats include that there are no published results of a randomized clinical trial informing the medical community of which treatment is superior to any other treatment. Retrospective comparisons have failed to show one form of therapy to be superior to another. An ongoing randomized trial in Europe is comparing anticoagulation to antiplatelet therapy. There is also no evidence to support use of endovascular therapy for CD over any other treatment approach. The language of the conclusions reflects our current uncertainty (i.e. "reasonable", "appropriate").
One recent study compared the evolution of the mural hematoma in CD during the first week after treatment initiation (antiplatelet therapy or anticoagulation therapy), using dedicated cervical MRI of the arterial wall.3 A dissection protocol MRI was performed on admission and during the first week after initiation of the treatment. Two readers measured volumes, craniocaudal length of the mural hematoma and lumen patency, and searched for early recurrent CD. They also searched for extension or recurrence of ischemic brain lesions and for hemorrhagic transformation on MRI. Of 44 patients (31 in group AC, 13 in group AP) with 49 CAD (35 carotid, 14 vertebral), there was no recurrent CD, and reduction of the lumen did not occur in either group. Mean volumes and length of the mural hematoma decreased after treatment in both groups (no difference between groups), and approximately one third of patients in each group had some growth of the mural hematoma as well as an increase in length. The authors found that neither treatment approach promoted reduction of the lumen or recurrent dissection.
- CD follow-up studies have shown that the risk of recurrent stroke is low and that there may be a higher risk of early recurrent stroke (often from the initially symptomatic dissection) as opposed to late recurrence.
- Asymptomatic recurrent CDs seen on MRI are likely more common than symptomatic recurrences
- Certain groups (especially those with a family history or fibromuscular dysplasia) may be at higher risk of recurrence.
CD and CMT: Rigorous analyses
What has been somewhat controversial and at times contentious is whether neck manipulation – CMT by a chiropractor could trigger a CD and subsequent stroke. Miley et al4 previously performed a structured evidence-based clinical neurologic practice and literature review. Using causation criteria, 5 of the applicable 7 criteria were satisfactorily met, supporting weak to moderate strength of evidence for causation between CMT and vertebral artery dissection (VAD) and associated stroke, especially in young adults. They found that young vertebrobasilar artery territory stroke patients were 5 times more likely than controls to have had CMT within 1 week of the event date (OR 5.03, 95% CI, 1.32-43.87) with the caveat that the confidence intervals were quite wide. They did not find any significant associations for those 45 years of age or older. They estimated the incidence as ~ 1.3 cases of VAD or occlusion attributable to CMT for every 100,000 persons < 45 years of age receiving CMT within 1 week of manipulative therapy. As these authors noted, the acceptable level of risk associated with a therapeutic intervention like CMT must be balanced against evidence of therapeutic efficacy.
A more recent PRISMA guidelines-based systematic review5 aimed to determine whether conclusive evidence of a strong association exists. Two case-control studies were assessed to be the most robustly designed. One supported a strong association between stroke and various intensities of neck movement, including manipulation, and the other suggested a much reduced relative association. While biases and confounders render the results inconclusive, Thaler et al6 recently adjusted (re-performed the calculations) for specific aspects of bias and found a statistically significant link between CMT and CD. While definitive evidence is lacking for a strong association between neck manipulation and stroke, there also a lack of evidence for no association. The truth is probably closer to some link than no link with a need to better understand the magnitude of the effect. Hence, the statement includes the recommendation to warn patients prior to undergoing CMT. Future epidemiological studies will need to minimize potential biases and confounders.
Digging deeper into the quality of the case report descriptions, Wynd et al7 systematically reviewed the quality of the reports describing CD with CMT. Studies were screened by two independent reviewers for the presence/absence of 11 factors considered to be important in understanding the relation between CD and CMT. No single case included all 11 factors. The authors concluded that improving the quality, completeness, and consistency of reporting adverse events may improve our understanding of this important relation.
Main Conclusions from the AHA/ASA Statement:
- CD is an important cause of ischemic stroke in young and middle-aged patients.
- CD is most prevalent in the upper cervical spine and can involve the internal carotid artery or vertebral artery.
- Although current biomechanical evidence is insufficient to establish the claim that CMT causes CD, clinical reports suggest that mechanical forces play a role in a considerable number of CDs.
- Most controlled studies have found an association between CMT and CD of the vertebral artery causing stroke in young patients.
- Disability levels vary among CD patients with many having good outcomes, but serious neurologic injury can occur.
- Although the incidence of CMT-associated CD is not well established, and is probably low, patients should be informed of the association between CD and CMT prior to undergoing manipulation of the cervical spine.
While this AHA/ASA Statement provides clinicians with the current state of the science and art of CD and CMT, it also importantly presents multiple areas of knowledge gaps, ongoing areas of controversy, and directions for improving our clarity of this important topic.
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 [published online ahead of print August 7, 2014]. Stroke. doi: 10.1161/STR.0000000000000016.
- Singhal AB, Biller J, Elkind MS, Fullerton HJ, Jauch EC, Kittner SJ, Levine DA, Levine SR: Recognition and management of stroke in young adults and adolescents. Neurology. 2013; 81:1089-1097.
- 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 [published online ahead of print August 7, 2014]. Stroke. doi: 10.1161/STR.0000000000000016.
- Machet A, Fonseca AC, Oppenheim C, Touze E, Meder JF, Mas JL, Naggara O. Does anticoagulation promote mural hematoma growth or delayed occlusion in spontaneous cervical artery dissections? Cerebrovasc Dis. 2013;35:175-81.
- Miley ML, Wellik KE, Wingerchuk DM, Demaerschalk BM. Does cervical manipulative therapy cause vertebral artery dissection and stroke? Neurologist. 2008;14:66-73.
- Haynes MJ, Vincent K, Fischhoff C, Bremner AP, Lanlo O, Hankey GJ. Assessing the risk of stroke from neck manipulation: a systematic review. Int J Clin Pract. 2012;66:940-7.
- Thaler DE, et al. Case Misclassification in Studies of Spinal Manipulation and Arterial Dissection. J Stroke Cerebrovasc Dis. In press.
- Wynd S, Westaway M, Vohra S, Kawchuk G. The quality of reports on cervical arterial dissection following cervical spinal manipulation. PLoS One. 2013;8(3):e59170.
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