Cervical Artery Dysfunction (CAD): Implications for Physiotherapy Diagnosis and Management

Master Class Penticton, BC September 13, 2010 Peter Huijbregts

Presenter
    

Diploma Physiotherapy (1990) MSc Manual Therapy (1994) MHSc Physical Therapy (1997) Doctor of Physical Therapy (2001) Fellow Canadian Academy of Manipulative Therapy, American Academy of Orthopaedic Manual Therapy Board-certified Orthopaedic Specialist

Presenter
 Assistant

Professor, University of St. Augustine for Health Sciences  Advisory Faculty, NAIOMT  Editor-in-Chief, Consulting Editor JMMT  Clinical Consultant, Shelbourne Physiotherapy Clinic  Consulting Editor, Jones & Bartlett Publishers

Objectives
Upon completion of this session participants will be able to discuss:
 

Epidemiology of cervical (vertebral and internal carotid) artery dysfunction Anatomy, pathology, and physiology relevant to cervical artery dysfunction

Objectives
   

Research evidence on the use of manual therapy interventions Research linking cervical manual therapy interventions to cervical artery dysfunction Relevant clinical (differential) diagnosis Risk management and emergency procedures related to cervical artery dysfunction

High-profile cases in Canada
     

Laurie-Jean Mathiason 20-year old female Fell down stairs and hurt her back Boyfriend suggested seeing his chiropractor Over the next months 189 adjustments in 21 visits including upper cervical Note: initial complaint was low back pain…

High-profile cases in Canada
 Rotary

neck manipulation resulted in inability to turn head  That night she kept walking into things at work  Another visit to chiropractor next day

High-profile cases in Canada
 Neck

adjustment  Patient immediately began to cry  Left eye rolled up, right roamed randomly  Convulsions

High-profile cases in Canada
 Turned

blue, foaming at the mouth, did not recognize her mother  Coma  Died next day from a traumatic rupture left vertebral artery
Benedetti P, McPhail W. Spin Doctors 2002

High-profile cases in Canada
 Lana

Dale Lewis, age 45, Toronto, ON  Treated for migraine  Complained of intense pain after cervical manipulation  Stroke few days after visit  Second fatal stroke again a few days later on September 12, 1996

High-profile cases in Canada
 Inquest

2002-2004  Coroner’s jury verdict: Death by accident  Linked stroke causally to manipulation
Burdett J. Fatal chiropractic: The Lana Dale Lewis case. Association for Science & Reason 2007 Laeeque H, Boon H. Print media coverage on the Lana Dale Lewis Inquest verdict: Exaggerated claims or accurate reporting? Health Law Review 13(1):7-15.

High-profile cases in Canada
   

Mrs. Sandy Nette, Edmonton, AB Bilateral vertebral artery dissection Chiropractic neck manipulation $ 500-million class-action lawsuit against chiropractor, his clinic, Alberta College and Association of Chiropractors, and AB Ministry of Health and Wellness

Benedetti P, McPhail W. Twist and Shout. Globe and Mail, June 14, 2008

Relevance to Physiotherapy
 Now

wait a minute…

Relevance to Physiotherapy
 Now

wait a minute…  Why would we as physiotherapists be worried about the association between manipulation and stroke?

Relevance to Physiotherapy
 Now

wait a minute…  Why would we as physiotherapists be worried about the association between manipulation and stroke?  Isn’t this purely a chiropractic problem?

Clinical Vignette
 63-year

old male  Hypertensive  Right cerebral infarct five years earlier  Four months previously vertebrobasilar infarct

Clinical Vignette
 PHYSIOTHERAPIST

applied cervical

manipulation  Immediate dizziness post-manipulation  Over the next few hours dysarthria, dysphagia, and left-sided paralysis  Medullary infarct

Situation in the Netherlands
 In

2006, patients lodged 18 complaints with professional association  Of these 5 pertained to complaints resulting from manual therapy interventions to the neck
Vossen H. De Wijer A. Cervicale manipulaties: risico’s, neveneffecten en prognostische factoren. Waar liggen onze verantwoordelijkheden? Tijdschr Man Ther 2007;4:36-37.

Epidemiology CAD
   

1-2% of patients with blunt, non-penetrating headtrauma Includes facial and skull base fractures and traumatic brain injury Increased incidence of ICA dissection in patients with thoracic injuries Increased incidence of vertebral artery dissection in patients with cervical fractures and cord lesions

Debette S, Leys D. Cervical artery dissections: Predisposing factors, diagnosis, and outcome. Lancet Neurol 2009;8:668-678.

Epidemiology CAD
 North

American general population study: 1-year incidence 2.6 (95% CI 1.86-3.33) per 100,000 for CAD  Dijon, France: 1-year incidence 2.9 per 100,000 for ICA dissection
Lee VH, Brown RD, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006; 67:1809–1812. Debette S, Leys D. Cervical artery dissections: Predisposing factors, diagnosis, and outcome. Lancet Neurol 2009;8:668-678.

Epidemiology CAD
 1-year

incidence dissection vertebral artery 0.97 (95% CI 0.52-1.4)  Almost half of incidence ICA dissection: 1.72 (95% CI 1.13-2.32) per 100,000
Lee VH, Brown RD, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006; 67:1809–1812.

Epidemiology CAD
 Of

all CAD, 20% develop into CVA  CAD accounts for approximately 20% of all strokes in young versus 2.5% in older patients
Blunt SB, Galton C. Cervical carotid or vertebral artery dissection. BMJ 1997;314:243.

Epidemiology CAD
 Note

the extremely low incidence of CAD and even lower incidence of CADassociated CVA in the general population  Remember this when establishing pretest probability

Anatomy and physiology review
Time to review some material? 1. Arterial anatomy 2. Mechanisms of arterial injury 3. Anatomy and physiology of the cervical arteries

Anatomy: Artery
Three-layer structure artery
  

Intima Media Adventitia

Anatomy: Artery
INTIMA  Layer of endothelial cells lining vessel interior  Rests on basal lamina  Turnover rate 1% per day  Sub-endothelial layer: longitudinally arranged loose connective tissue and some smooth muscle cells  In arteries: Internal elastic lamina, fenestrated elastin allows diffusion to vessel wall

Anatomy: Artery
MEDIA  Concentric layers of helically arranged smooth muscle cells  Variable amounts of elastic fibers and lamellae, reticular fibers, and proteoglycans  In larger arteries: External elastic lamina separating media from adventitia

Anatomy: Artery
ADVENTITIA  Longitudinally oriented Type I collagen and elastic fibers  Gradually becomes continuous with enveloping connective tissue
Junqueira LC, et al. Basic Histology. 8th ed (1995)

Mechanisms of Arterial Trauma
      

Subintimal hematoma Intimal tear Intimal tear with thrombus formation Intimal tear with embolic formation Vessel wall dissection with subintimal hematoma Vessel wall dissection with pseudo-aneurysm False aneurysm

Subintimal Hematoma

Disruption vasa vasorum leads to subintimal bleeding and occlusion of VA lumen May also cause vasospasm

Intimal Tear

 

Intima is the least elastic layer and, therefore, most likely to tear Exposure subendothelial layer causes thrombosis Clot may propagate proximally or distally Vasospasm due to thrombin release

Intimal Tear with Embolization

 

Propagating clot extends into lumen and breaks off Embolus Distal arterial occlusion and infarction

Dissection and Subintimal Hematoma
 

 

Disruption intima and internal elastic lamina Blood dissects these layers from muscular media: dissecting aneurysm Compresses lumen Exposure subendothelial tissue and thrombosis

Dissection and Subintimal Hematoma: Reperfusion

Hemorrhage may again rupture through intima Reestablishes communication with true lumen Recanalization may occur

Dissection with PseudoAneurysm

 

Disruption of media, internal elastic lamina, and intima Pseudo-aneurysm under extending adventitia May propagate distally Frequent cause of occlusion PICA

False Aneurysm
 

 

Disruption total arterial wall Peri-arterial hemorrhage contained in fascia External compression lumen Turbulence in lumen may cause thrombus and embolus formation

Anatomy: Vertebral Artery

V1: Extra-Vertebral Segment

  

Branches off the subclavian artery and enters the transverse foramen of C6 in 89% of people Enters C7 in 3%, C5 in 6%, and C4 in 1% of population Anterior boundary formed by anterior scalene and longus colli muscles Posterior boundary transverse processes C7T1 and first rib

V2: Intra-Vertebral Segment
 Runs

through transverse foramina C7-

C2  Bordered anteromedially by uncovertebral joints  May be adherent to periosteum of the uncinate processes  Many anatomical variants have been described

V3: Atlanto-Axial Segment
 

 

Transverse foramen of C1 is far lateral as compared to that of C2 This causes a dorsolateral routing of the vertebral artery from the C2 to the C1 transverse foramen Tethered at C1 and C2 transverse foramina and atlanto-axial membrane Artery more prone to injury at this segment?

Atlanto-Axial Segment and Rotation

V3: Atlanto-Axial Segment

  

After exiting the C1 transverse foramen the artery runs medially in a sulcus in the lateral mass of the atlas Anatomical variant: Arcuate foramen and ponticulus posterior in posterior arch atlas Anterior boundary is formed by the C0-C1 joint Posterior boundary is formed by the obliquus capitis superior and rectus capitis posterior major muscles

V4: Subforaminal and IntraCranial Segment
 Pierces

the posterior atlanto-occipital membrane and dura and arachnoid mater  Courses on intra-cranially in subarachnoid space

Cervical Branches

 

Spinal rami branch off the vertebral artery and enter the intervertebral foramen where they split in anterior and posterior radicular arteries, anterior central artery, and anterior and posterior vertebral canal arteries Radicular arteries supply the anterior and posterior nerve roots and spinal ganglion The other branches supply epidural tissues

Cervical Branches

 

Muscular, cutaneous, and articular rami supply the local joints, intrinsic cervical muscles, and the skin innervated by the dorsal ramus of the cervical spinal nerves These branches also supply the flaval and interspinal ligaments The ascending axial arteries supply the body and odontoid process of C2 and the alar, transverse, and cruciform ligaments

Sub-Foraminal Branches
  

Subforaminal branches include the anterior, posterior, and lateral spinal arteries The posterior spinal artery also frequently branches off from the posterior inferior cerebellar artery Below C4 these spinal arteries form anastosmoses with the spinal rami of the vertebral arteries through the anterior radicular arteries This leaves the upper cervical cord vulnerable to vascular ischaemia: Implication?

Intra-Cranial Branches

The posterior inferior cerebellar artery (PICA) branches off before coalescence of the vertebral arteries into the basilar artery PICA supplies the dorsolateral medulla oblongata, the cerebellar vermis, and a number of cerebellar nuclei The basilar artery supplies the medulla oblongata, the pons, the mesencephalon, and parts of the cerebellum

Intra-Cranial Branches

The labyrinthine arteries branch off early from the basilar artery or the anterior inferior cerebellar arteries, which makes the vestibular nucleus and the inner ears very susceptible to ischaemic abnormalities The posterior cerebral arteries branch off the basilar artery and supply the thalamus and hypothalamus and the occipital and temporal lobes

Oostendorp R. Functionele Vertebrobasilaire Insufficientie. PhD Thesis. Nijmegen, The Netherlands: Katholieke Universiteit Nijmegen, 1988.

Anatomy: Internal carotid artery
Fig 2

C1 (atlas)

Vertebral Artery C6

Internal Carotid Artery

Anatomy: ICA
 Provides

80% of blood flow to the brain versus 20% supplied by the vertebrobasilar system  Traverses sternocleidomastoid, longus capitis, stylohyoid, omohyoid, and digastric muscles

Anatomy: ICA
 Fixed

to the anterior aspect of the C1 vertebral body and in the carotid canal in the petrous bone  Sustained rotation and extensionrotation tests have also been proposed as tests of ICA function

Relevance to Physiotherapy?
Physiotherapists routinely use cervical manual therapy in patients with:  Neck pain  Headache: Cervicogenic, tension-type, migraine  Dizziness: Cervicogenic  TMD  Subacromial impingement  Lateral epicondylalgia

Do these patients make up a big portion of our day-to-day clinical practice?

Epidemiology Neck Pain
• • • •

Point prevalence neck pain: 9% 6-month prevalence: 54% Lifetime prevalence: 66% Point prevalence chronic neck pain (>6 months): 18%

Douglass AB, Bope ET. Evaluation and treatment of posterior neck pain in family practice. J Am Board Fam Pract 2004;17:S13-S22. Guez M, et al. Chronic neck pain of traumatic and non-traumatic origin. Acta Orthop Scand 2003;74:576-579

Epidemiology Headache

Cervicogenic headache: 0.4-2.5% in the general population and up to 15-20% in those with chronic headaches Tension-type headache: Two-thirds of males and over 80% of females in developed countries Migraine headache: 1-year prevalence 6-8% in males and 15-18% of females in Europe and US

World Health Organization. Headache Fact Sheet. 2008. Haldeman S, Dagenais S. Cervicogenic headaches: A critical review. Spine J 2001;1:31-46

Epidemiology Dizziness
  

Dizziness accounts for 7% of physician visits for patients over the age of 45 For adults over 65, it is the number one reason to visit a physician Approximately 15 to 30% of people experiencing dizziness will seek medical attention
Huijbregts P, Vidal P. Dizziness in orthopaedic physical therapy practice: Classification and pathophysiology. J Man Manip Ther 2004; 12: 196-211

Epidemiology impingement
  

Point-prevalence in the Dutch general population of 20.9% 1-year incidence of 11.2 per 1,000 patients in Dutch general medical practice 41% of the patients seeking care for shoulder complaints diagnosed with impingement
Picavet HSJ, Van Gils HWV, Schouten JSAG. Klachten van het bewegingsapparaat in de Nederlandse bevolking: Prevalenties, consequenties en risicogroepen. Centraal Bureau voor Statistiek, Bilthoven: 2000 Van der Windt DA, Koes BW, De Jong BA, Bouter LM. Shoulder disorders in general practice: Incidence, patient characteristics and management. Ann Rheum Dis 1995;54:959964

Epidemiology lateral epicondylalgia
 Affects

1-2% of general population

Allander E. Prevalence, incidence, and remission rates of some common rheumatic diseases and syndromes. Scand J Rheumatol 1974;3(3):145-153.

Relevance to Physiotherapy?

Cervical spine diagnoses were the reason for referral in 16% of 1,258 outpatient PT patients, second only to lumbar spine-related diagnoses Headache reported as co-morbidity in 22% of 2,433 patients presenting for outpatient PT/OT

Boissonnault WG. Prevalence of comorbid conditions, surgeries, and medication use in a physical therapy outpatient population: A multi-centered study. J Orthop Sports Phys Ther 1999;29:506519

Relevance to Physiotherapy?
 11%

of 1,258 PT patients indicated the shoulder as their chief area of complaints
Boissonnault WG. Prevalence of comorbid conditions, surgeries, and medications in a physical therapy outpatient population: A multi-centered study. J Orthop Sports Phys Ther 1999;29:506-525

Relevance to Physiotherapy?
 All

member organizations IFOMT teach cervical segmental examination, manipulation, and mobilization techniques  19/20 member organizations teach upper cervical manipulation
Rivett D, Carlesso L. Safe Manipulative Practice in the Cervical Spine (2008)

So why use manual therapy?

Evidence-based practice  The process of integrating the best research evidence available with both clinical expertise and patients’ values
Sackett DL, et al. Evidence-Based Medicine. How to Practice & Teach EBM. New York, NY: Churchill Livingstone, 1997.

So why use manual therapy?
 

Evidence-informed not evidence-driven practice The clinician takes the evidence from research into account when making clinical decisions with regard to patient management but evidence does not dictate these decisions

Bohart A. Evidence-based psychotherapy means evidence-informed, not evidencedriven. Journal of Contemporary Psychotherapy 2005;35:39-53.

Research evidence
Systematic reviews on the effectiveness of manual therapy for patients with mechanical neck pain have indicated positive outcomes on pain and function for (non) thrust interventions but only when combined with exercise and only in subacute and chronic conditions
Gross AR, Hoving JLK, Haines TA, et al: A Cochrane Review of manipulation and mobilization for mechanical neck disorders. Spine 29:1541,2004. Sarigiovannis P, Hollins B: Effectiveness of manual therapy in the treatment of non-specific neck pain: A review. Phys Ther Rev 10:35,2005.

Research evidence
Hoving et al reported no significant between-group differences for pain, perceived recovery, and function in patients with neck pain managed by their family physician, exercise and stretching, or non-thrust techniques and stabilization exercises at 1 year But indicating relevant short-term effectiveness they noted significantly better results for the manual therapy group at 7 weeks
Hoving JL, De Vet HCW, Koes BW, et al: Manual therapy, physical therapy, or continued care by the general practitioner for patients with neck pain: Long-term results from a pragmatic randomized controlled clinical trial. Clin J Pain 22:370,2006.

Research evidence
Further indicating the cost-effectiveness of manual therapy management for patients with mechanical neck pain, an economic evaluation alongside this randomized trial (RCT) also showed significantly lower cost for the manual therapy intervention as compared to both others

Korthals-De Bos IBC, Hoving JL, Van Tulder MW: Cost effectiveness of physiotherapy, manual therapy, and general practitioner care for neck pain: Economic evaluation alongside a randomised controlled trial. BMJ 326:911,2003.

Research evidence
  

Multi-center RCT on patients with cervical radiculopathy True versus sham mechanical traction for cervical radiculopathy Both groups also received cervical and thoracic non-thrust techniques, thoracic thrust techniques, postural education, and cervical mobility and cervical and scapulothoracic strengthening exercises

Research evidence
 No

between-group differences  Within-group statistically and clinically significant improvements in pain and function
Young IA, Michener LA, Cleland JA, Aguilera AJ, Snyder AR: Manual therapy, exercise, and traction for patients with cervical radiculopathy: A randomized clinical trial. Phys Ther 89:632,2009.

Research evidence
A

systematic review of randomized and (non) controlled clinical trials found consistent significant improvements with soft tissue, non-thrust, and thrust interventions for patients with cervicogenic dizziness

Reid SA, Rivett DA: Manual therapy treatment of cervicogenic dizziness: A systematic review. Man Ther 10:4,2005

Research evidence

RCT in patients with cervicogenic dizziness treated with a Mulligan cervical SNAG intervention showed clinically and statistically significant reduced dizziness, neck pain, and dizziness-related disability over the group treated with detuned laser

Reid SA, Rivett DA, Katekar MG, Callister R: Sustained natural apophyseal glides are an effective treatment for cervicogenic dizziness. Man Ther 13:357,2008

Research evidence
A

systematic review noted moderate evidence for short-term efficacy of spinal manipulation similar to Amitryptiline in patients with migraine and chronic tension-type headache  No added benefit if manipulation was added to massage in patients with episodic tension-type headache

Research evidence
 Moderate

evidence that spinal manipulation was more efficacious for cervicogenic headache than massage

Bronfort G, Assendelft WJJ, Evenas R, Haas M, Bouter L: Efficacy of spinal manipulation for chronic headache: A systematic review. J Manipulative Physiol Ther 24:457,2001

Research evidence
A

systematic review yielded two RCTs that showed significant effects of spinal thrust interventions on headache intensity and duration and medication intake in patients with cervicogenic headache

Fernández-de-las-Peñas C, Alonso-Blanco C, Cuadrado ML, Pareja JA: Spinal manipulative therapy in the management of cervicogenic headache. Headache 45:1260,2005

Research evidence

RCT showed that twice weekly 45-minute massage and trigger point release sessions resulted in significant decreases in headache frequency, intensity, and duration and headache-related disability in patients with tension-type headache with these effects lasting into the 3-week follow-up period

Moraska A, Chandler C: Changes in clinical parameters in patients with tension-type headache following massage therapy: A pilot study. J Man Manip Ther 16:106,2008

Research evidence

Prospective cohort study in patients with migraine showed significant improvements in headache frequency, intensity, duration, and disability after 2 months of thrust interventions as deemed indicated by the clinician to the whole spine At 12 months there were still significant improvements as compared to baseline for headache frequency, intensity, and duration and medication use

Tuchin PJ: A twelve month clinical trial of chiropractic spinal manipulative therapy for migraine. Aust Chiro Ost 8:61,1999

Research evidence
 

RCT comparing spinal manipulation to interferential current in patients with migraine Significant between-group differences favoring manipulation for headache frequency, duration, disability, and medication use during the 2-month post-intervention follow-up

Tuchin PJ, Pollard H, Bonello R: A randomized controlled trial of chiropractic spinal manipulative therapy for migraine. J Manipulative Physiol Ther 23:91,2000

Research evidence
 Kalamir

et al reported that cervical manipulation might be beneficial for patients with temporomandibular disorders, although this recommendation was based solely on case studies

Kalamir A, Pollard H, Vitiello AL, Bonello R: Manual therapy for temporomandibular disorders: A review of the literature. J Bodywork Movement Ther 11:84,2007

Research evidence
 

Cohort studies on patients with subacromial impingement Medium and long-term (up to one year) benefits of thrust and non-thrust interventions to the cervical and thoracic spine, ribs, shoulder, and shoulder girdle Over or in addition to exercise, medical care, and steroid infiltration

Bang MD, Deyle GD: 2000 Comparison of supervised exercise with and without manual physical therapy for patients with shoulder impingement syndrome. J Orthop Sports Phys Ther 30:126,2000 Bergman GJD, Winters JC, Groenier KH, Pool JJM, Meyboom-De Jong B, Postema K, Van der Heijden GJMG: Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain. Ann Int Med 141:432,2004

Research evidence

Vicenzino et al have provided preliminary suggestions for a treatment-based classification system for patients with lateral epicondylalgia Perhaps patients presenting with greater pressure pain threshold deficits relative to pain-free grip force deficits should first be treated with manipulative therapy techniques directed at the cervical spine

Vicenzino B, Cleland JA, Bisset L: Joint manipulation in the management of lateral epicondylalgia: A clinical commentary. J Man Manip Ther 15:50,2007

Clinical decision-making
 Evidence

for effectiveness  Evidence for risk of harm  Risk-benefit analysis

Risk of harm research
 Standardization

of terminology only just

beginning  Minor adverse events: relatively short duration, less severe, occur immediately after treatment or with short latency period, minimal effect on function, fully reversible, require no adaptation of current treatment or additional treatment

Risk of harm research

Major adverse events: moderate to long duration, moderate to severe and unacceptable, require additional intervention
Carlesso L, MacDermid JC, Santaguida PL. Standardization of adverse event terminology and reporting in orthopaedic physical therapy: application to the cervical spine. J Orthop Sports Phys Ther 2010;40:455-463. Carnes D, Mullinger B, Underwood M. Defining adverse events in manual therapies: A modified Delphi consensus study. Man Ther 2010;15:2-6.

Risk of harm research
 

   

Research into risk of harm is wrought with methodological shortcomings Obvious ethical concerns with studies that would prospectively expose patients to a suspected risk factor Non-standardized terminology Non-adherence to CONSORT guideline Mostly based on case reports and case series Emphasizes serious adverse events

Minor adverse events
  

 

Survey South-African physiotherapists Mostly dizziness and headache Also nystagmus, vision disturbances, nausea and vomiting, acute wry neck, increased arm pain +/- neurological deficit, syncope Average duration 6.3 days 1 minor event per 3,020 manipulations

Michaeli A. Reported occurrence and nature of complications following manipulative physiotherapy in South Africa. Aust J Physiother 1993;39:309-315.

Minor adverse events
 

 

Survey Irish manual physiotherapists 26% respondents reported adverse events after cervical manipulation/mobilization in preceding 2 years Mostly dizziness, nausea, and temporary increase in complaints 1 case each of drop attack, syncope, and TIA post-mobilization

Sweeney A, Doody C. Manual therapy for the cervical spine and reported adverse effects: A survey of Irish manipulative physiotherapists. Man Ther 2010;15:3236.

Minor adverse events
  

 

Prospective study physiotherapists, osteopaths, chiropractors 60.9% of 283 patiënten reported at least one postmanipulation minor event Headache (19.8%), stiiffness (19.5%), local discomfort (15.2%), radiating discomfort (12.1%), and fatigue (12.1%) Muscle tension (5.8%), dizziness (4.3%) en nausea (2.7%) Majority of complaints occurred within 4 hours and had resolved fully within 24 hours
manipulation and can these side effects be predicted? Man Ther 2004;9:151-6.

Cagnie B, Vinck E, Beernaert A, Cambier D. How frequent are side effects of spinal

Minor adverse events
 RCT

comparing chiropractic cervical manipulation to mobilization  85 of 280 patients reported advesre event  Manipulation group: 48 patients with 120 complaints  Mobilization group: 37 patients with 92 complaints

Minor adverse events
  

 

25% increased neck pain and stiffness Headache (15.7%), fatigue (10%), radiating pain (6.1%) Dizziness, extremity weakness, tinnitus, depression or anxiety, nausea and vomiting, vision disturbances, confusion, or disorientation (1%) Majority occurred within 24 hours and fully resolved within 24 hours of onset Headache, dizziness, fatigue, and nausea in up to 75% general population in preceding three days

Hurwitz EL, Morgenstern H, Vassilaki M, Chiang LM. frequency and clinical predictors of adverse reactions to chiropractic care in the UCLA Neck Pain study. Spine 2005; 30:1477-1484.

Minor adverse events
 

Systematic review No increase in neck pain for cervical manipulation as compared to cervical mobilization (combined with thoracic manipulation): relative risk (RR) =1.25, 95% CI 0.84-1.87; P > 0.05) Small increase in incidence of mild neurological symptoms: RR = 1.96, 95% CI 1.09-3.54, P < 0.05).

Carlesso LC, Gross AR, Santaguida PL, Burnie S, Voth S, Sadie J. Adverse events associated with the use of cervical manipulation and mobilization for the treatment of neck pain in adults: A systematic review. Man Ther 2010;15(5):434-444.

Major adverse events
“…The temporal relationship between young healthy patients without osseous or vascular disease who attend an SMT practitioner and then suffer these rare strokes is so well documented as to be beyond reasonable doubt indicating a possible causal relationship…”
Terrett AGJ. Vertebrobasilar stroke following spinal manipulation therapy. In: Murphy R. Conservative Management of Cervical Spine Syndromes (2000)

Serious Manipulation-Related Adverse Events Two types of vertebral artery stroke: 1. Wallenberg syndrome 2. Locked-in syndrome

Wallenberg Syndrome
 Dorsolateral

medullary syndrome of

Wallenberg  Occlusion PICA  Other cause: Occlusion parent vertebral artery, a.k.a. syndrome of Babinski Nageotte  Due to destruction nuclei and pathways in dorsolateral medulla oblongata

Wallenberg Syndrome
 

Inferior cerebellar peduncle: ipsilateral ataxia and hypotonia Descending spinal tract and nucleus CN V: loss of pain and temperature sensation ipsilateral face and loss corneal reflex Ascending lateral spinothalamic tract: loss of pain and temperature sensation contralateral trunk and limbs (alternating analgesia)

Wallenberg Syndrome
 Descending

sympathetic tract: Ipsilateral Horner’s syndrome  Lower vestibular nuclei: Nystagmus, vertigo, nausea, and vomiting  Nucleus ambiguous of glossopharyngeal and vagus nerves: Hoarseness, dysphagia, or intractable hiccups

Locked-In Syndrome
 Cerebromedullospinal

disconnection

syndrome  Occlusion mid-basilar artery  Bilateral ventral pontine infraction  Effectively transects brain stem at midpons region  Patients are “conscious, paralyzed mutes”

Locked-In Syndrome
 Consciousness

retained because reticular formation midbrain and rostral pons is unaffected  Cerebrospinal tracts destroyed: Decerebrate rigidity  Nuclei CN V-XII destroyed: Also affects oculomotor nerve (CN III) due to descending neuronal connections

Locked-In Syndrome

 

Cutaneous sensation may be grossly intact because lateral spinothalamic tract located laterally in brain stem is spared Auditory nerves ascend brainstem lateral to infarct area: Patient still can hear CN IV spared: Eye convergence and upward gaze intact

Establishing causality
 Retrospectively

establishing cause-andeffect relationships?  In clinical medicine we cannot establish causal relationship beyond any doubt  But we can increase or decrease conviction of a causal effect  Bradford-Hill criteria: Sir Austin Bradford Hill (1965)

Bradford-Hill Criteria for Causation
    

Biologically plausible Proposed cause temporally related to occurrence Consistent across different samples and groups Positive correlation exposure and occurrence No other explanation

Bradford-Hill Criterion # 1: Biological Plausibility
It is certainly biologically plausible that excessive mechanical force imparted to the artery could cause arterial wall damage especially in case of pathologically weakened artery

Bradford-Hill Criterion # 1: Biological Plausibility
 Cadaver

study: 5 cadavers 80-99 y.o.  SMT contralateral C1-C2, C3-C4, C6C7  AROM and extension-rotation testing  6.2% +/-1.3% to the distal (C0-C1) loop of the VA and a 2.1% +/-0.4% strain to the proximal (C6-subclavian artery) loop

Bradford-Hill Criterion # 1: Biological Plausibility
   

Strain range AROM tests: 1.2+/-0.6% 12.5+/-10.1% Strain range extension-rotation tests: 3.2+/2.4% - 11.8+/-8.6% Failure testing: 139% to 162% Single thrust unlikely to mechanically disrupt VA

Symons B, Leonard TR, Herzog W. Internal forces sustained by the vertebral artery during spinal manipulative therapy. J Manipulative Physiol Ther 2002;25:504-10.

Bradford-Hill Criterion # 1: Biological Plausibility
   

24 test specimens from cadaveric rabbit ascending aorta Specimens were exposed to 1000 strain cycles of 0.06 and 0.30 of their in situ length Control and 0.06 strain tissues were statistically the same (P = .406) 0.30 strain group showed micro-structural damage beyond that seen in the control group (P = .024)

Bradford-Hill Criterion # 1: Biological Plausibility

Cadaveric rabbit arterial tissue similar in size and mechanical properties of that of the human VA can withstand repeat strains of magnitudes and rates similar to those measured in the cadaveric VA during cervical SMT without incurring micro-structural damage beyond control levels

Austin N, DiFrancesco LM, Herzog W. Micro-structural damage in arterial tissue exposed to repeated tensile strains. J Manipulative Physiol Ther 2010;33:14-19

Bradford-Hill Criterion # 1: Biological Plausibility

Eight piezoelectric ultrasound crystals of 0.5mm diameter were sutured into the lumen of the left and right VA of one cadaver Strains calculated during cervical spinal range of motion testing, chiropractic cervical spinal manipulation adjustments, and vertebrobasilar insufficiency testing Lateral flexion + rotation and lateral flexion SMT at C2-C3 and C4-C5 bilaterally

Bradford-Hill Criterion # 1: Biological Plausibility
 

Complex and non-intuitive strain patterns of the VA within the cervical transverse foramina Strains for cervical spinal manipulations were consistently lower than those obtained for cervical rotation Neck manipulations impart stretches on the VA that are well within the normal physiologic range of neck motion

Wuest S, Symons B, Leonard T, Herzog W. Preliminary report: biomechanics of vertebral artery segments C1-C6 during cervical spinal manipulation. J Manipulative Physiol Ther 2010;33:273-278.

Bradford-Hill Criteria #2 - #3
 Proposed

cause temporally related to occurrence  Consistent across different samples and groups

Evidence Linking Manipulation to Stroke
 Terrett

(1995): Narrative review of English, French, German, Scandinavian, and Asian literature 1934-2000: 185 cases reported, death in 30 cases

Evidence Linking Manipulation to Stroke
 Updated

in 2001: 236 cases reported  Triano and Kawchuk (2006) updated this review and found reports of 80 additional cases of post-manipulation complications
Triano JJ, Kawchuk G. Current Concepts in Spinal Manipulation and Cervical Arterial Incidents (2006)

Evidence Linking Manipulation to Stroke
 

 

DiFabio (1999): systematic review over period 1925-1997 177 cases with mostly arterial dissection or spasm, brain stem lesion, and Wallenberg syndrome Death resulted in 18% (n=32) Also visual defects, hearing loss, balance deficits, and phrenic nerve damage

Evidence Linking Manipulation to Stroke
  

Cervical manipulation NOT a new treatment in 41% of patients When described rotational thrust seemed most injurious (23%) However, technique described in only 54%

DiFabio RP. Manipulation of the cervical spine: Risks and benefits. Phys Ther 1999;79:50-65

Evidence Linking Manipulation to Stroke
  

Ernst (2002): Systematic review over 19952001 period 42 cases with serious adverse events: Mainly arterial dissection Also long thoracic nerve palsy, disk herniations, myelopathy, epidural hematoma

Evidence Linking Manipulation to Stroke
 

Insufficient data on type of manipulation used Underreporting bias?

Ernst E. Manipulation of the cervical spine: A systematic review of case reports of serious adverse events, 1995-2001. Med J Aust 2002;176:376-380

Evidence Linking Manipulation to Stroke
    

True risk remains unknown Estimated risks adjusted assuming a reporting rate of only 10% in literature All complications: 5-10 per 10 million Serious complications: 6 in 10 million Risk of death: 3 in 10 million

Hurwitz EL, et al. Manipulation and mobilization of the cervical spine: A systematic review of the literature. Spine 1996;21:1746-1759

Current Emphasis on ICA: Let’s Put This in Perspective
Terrett only found five cases (2.7%) of 185 reported cervical artery injuries associated with SMT involving the ICA

Terrett AGJ. Current Concepts: Vertebrobasilar Complications following Spinal Manipulation (2001)

Current Emphasis on ICA: Let’s Put This in Perspective
 Systematic

review Medline 1966-2000  13 reports of dissection ICA temporally associated with neck manipulation  Risk of ICA dissection with manipulation estimated at less than 1 in 601 million
Haneline MT, Croft AC, Frishberg BM. Association of internal carotid artery dissection and chiropractic manipulation. The Neurologist 2003;9:35-44

Bradford Hill criterion #4: Positive correlation exposure and occurrence
   

582 cases of vertebrobasilar accidents (VBA) in ON, 1993-1998 Age and sex-matched controls from provincial insurance database Exposure to chiropractic using provincial insurance data VBA< 45 years old 5 times more likely (95% CI 1.31-43.87) to have visited a chiropractor within 1 week before VBA

Bradford Hill criterion #4: Positive correlation exposure and occurrence

 

Also, in younger age group 5 times as likely to have had ≥ 3 visits with cervical diagnosis in month before VBA (95% CI 1.34-18.57) No significant associations for those over 45 years old Further prospective study indicated; sources of bias acknowledged

Rothwell DM, Bondy SJ, Williams JI. Chiropractic manipulation and stroke: A population-based case control study. Stroke 2001;32:1054-1060

Bradford Hill criterion #4: Positive correlation exposure and occurrence
  

Population-based study over period 19932001 818 subjects with VBA stroke Case crossover portion: 4 control periods randomly chosen from the year before the stroke Case control portion: 4 age and sex-matched controls from provincial insurance database

Bradford Hill criterion #4: Positive correlation exposure and occurrence
 Case

control study  Visiting chiropractor in month before stroke  > 45: OR 0.83 (95% CI: 0.52-1.32)  < 45: OR 3.13 (95% CI: 1.48-6.63)

Bradford Hill criterion #4: Positive correlation exposure and occurrence
 However,…  Case

control study  Visiting GP in month before stroke  > 45: OR 2.67 (95% CI: 2.25-3.17)  < 45: OR 3.57 (95% CI: 2.17-5.86)

Bradford Hill criterion #4: Positive correlation exposure and occurrence
“… [A similar association between chiropractic and GP visits in the month before the stroke event] suggests that patients with undiagnosed VA dissection are seeking clinical care for headache and neck pain before having a VBA stroke…”
Cassidy JD, et al. Risk of vertebrobasilar stroke and chiropractic care. Spine 2008;33:S176-S183.

Bradford Hill criterion #5: No other explanation
 Are

there other plausible causes or pathologies that might lead to CAD?  Risk factor identification: Role in clinical diagnosis

Risk Factors
Atherosclerosis Hypertension Hypercholesterolaemia Hyperlipidaemia Hyperhomocysteinaemia Diabetes mellitus Genetic clotting disorders Infections Smoking Free radicals Upper cervical instability Migraine Direct vessel trauma Autosomal polycystic kidney disease Iatrogenic causes Endothelial inflammatory disease (e.g., temporal arteriitis) Arteriopathies Age Female gender Thyroid disease Oral contraceptive use

Direct Vessel Trauma:

 Manipulation  Whiplash

Direct Vessel Trauma: Whiplash
In a retrospective analysis, Beaudry and Spence attributed 70 of 80 traumatically induced cases of vertebrobasilar ischaemia to motor-vehicle accidents
Beaudry M, Spence JD. Motor vehicle accidents: The most common cause of traumatic vertebrobasilar ischaemia. Can J Neurol Sci 2003;30:320-325

Whiplash and Dizziness
Dizziness, vertigo, and dysequilibrium are symptoms in 20-58% of individuals that have sustained a whiplash-type injury of the cervical spine or a closed head injury
Wrisley DM, et al. Cervicogenic dizziness: A review of diagnosis and treatment. J Orthop Sports Phys Ther 2000;30:755-766

Whiplash and Dizziness
  

Damaged peripheral labyrinth or cochlea in 90% and both in 69% of 227 post-whiplash patients at neurology evaluation 92% met the diagnostic criteria for inner ear contusion Of this subgroup, 63% was diagnosed with BPPV, 64% with secondary endolymphatic hydrops, and 21% with unilateral or bilateral perilymphatic fistulae 25% prevalence of BPPV in 273 consecutive patients with rear-end impact whiplash injury without head injury
Grimm RJ. Inner ear injuries in whiplash. J Whiplash Rel Disord 2002:1:65-75; Oostendorp RAB, et al. Dizziness following whiplash injury: A neuro-otological study in manual therapy practice and therapeutic implication. J Manual Manipulative Ther 1999;7:123-130

Not all Dizziness Implies CAD
 Benign

Paroxysmal Positional Vertigo  Cervicogenic dizziness  Vertebrobasilar insufficiency

Dizziness type Cervicogenic dizziness Positioning-type

Nystagmus and dizziness characteristics  No latency period  Brief duration  Fatigable with repeated motion

BPPV

Positioning-type

  

Cervical artery dysfunction

Positional-type

 



Short latency: 1-5 seconds Brief duration: <30 seconds Fatigable with repeated motion Long latency: 55+/18 seconds Increasing symptoms and signs with maintained head position Not fatigable with repeated motion

Associated signs and symptoms  Nystagmus  Neck pain  Suboccipital headaches  Cervical motion abnormality on examination  Nystagmus

Ischaemic and (depending on etiology) possibly non-ischaemic signs and symptoms as described in Table 10

Hallpike-Dix Maneuver

Positional nystagmus on this test has been shown to identify patients with posterior SCC BPPV with 78% sensitivity Specificity as high as 88% has been reported

Age: 30-45 year old?

Age
 Relevant

to the clinical diagnosis of spontaneous if not manipulationinduced CAD is that Lee et al (2006) reported a mean age of 45.8 years for North-American patients

Lee VH, Brown RD, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006; 67:1809–1812

Age
 In

Europe, Touzé et al (2003) reported a mean age of 44.0 and Arnold et al (2006) noted a mean age of 45.3 years for patients diagnosed with CAD

Touzé E, Gauvrit JY, Moulin T, Meder JF, Bracard S, Mas JL. Risk of stroke and recurrent dissection after a cervical artery dissection: a multi-center study. Neurol 2003;61:1347–1351. Arnold M, Kappeler L, Georgiadis D, et al. Gender differences in spontaneous cervical artery dissection. Neurol 2006; 67:1050–1052.

Gender: Female Predisposition?
    

Terrett (1995) literature review of 185 patients with severe CSMT complications Gender known for 180 77 males (42.8%) of whom 13 died (16.9%) 103 females (57.2%) of whom 17 died (16.5%) Reflects of male-female ratio in chiropractic office: 40.7-59.3% or 44.8-55.2%?

Gender
 In

three large studies (Beletsky et al 2003, Lee et al 2006, Schievink et al 1994) 50-52% of patients with CAD were women  In two European studies (Arnold et al 2006, Touzé et al 2003) 53-57% were men

Gender

ICA dissection seems to be more common in men and at an older age (47.0 versus 43.4 years) than is VA dissection (Dziewas et al 2003, Lee et al 2006)

Beletsky V, Nadareishvili Z, Lynch J, Shuaib A, Woolfenden A, Norris JW. Cervical arterial dissection: Time for a therapeutic trial? Stroke 2003;34:2856-2860. Schievink WI, Mokri B, O’Fallon WM. Recurrent spontaneous cervical-artery dissection. N Engl J Med 1994;330:393–397. Dziewas R, Konrad C, Drager B, et al. Cervical artery dissection: Clinical features, risk factors, therapy and outcome in 126 patients. J Neurol 2003;250:1179-1184.

Arteriopathies
       

Marfan syndrome Ehlers-Danlos syndrome Fibromuscular dysplasia Cystic medial necrosis Osteogenesis imperfecta Alpha-1-antitrypsin deficiency Autosomal dominant polycystic kidney disease Previous CAD

Marfan Syndrome
      

Higher reported incidence of CAD Typically show signs of impaired skeletal integrity resulting in joint hypermobility Extremely arched palate with crowded teeth Long limbs, spider-like fingers: Arachnodactyly Chest abnormalities: Pectus excavatum Kyphoscoliosis Sometimes only vascular defects with minimal or no outward clinical manifestations

Ehlers-Danlos Syndrome
    

Higher reported incidence of CAD Vascular Type IV variant may play a role in familial CAD History of easy bruising Thin skin with visible veins Characteristic facial features: Protruding eyes, small chin, thin nose and lips, and sunken cheeks

Martin JJ, et al. Familial cervical artery dissections: Clinical, morphologic, and genetic studies. Stroke 2006;37:2924-2929

Hypermobility: Beighton Score

Hypermobility: Brighton Criteria

Fibromuscular Dysplasia
 Rare

non-atherosclerotic and noninflammatory vascular condition  Primarily affects medium-sized arteries, in particular the ICA and renal arteries  Present in females 3 to 4 times more frequently than in males  Bilateral in 65% of patients

Fibromuscular Dysplasia

 

May be related to mechanical stress to the arterial wall, ischaemia within the vessel due to disturbance of the vasa vasorum, or hormonal activity that negatively affects the muscular wall Present in up to 23% of patients with ICA dissection Presenting complaint may vary from TIA to headache and dizziness

Cystic Medial Necrosis
 Focal

degeneration of the elastic tissue and muscle of the tunica media, with the development of mucoid material  Associated with a variety of systemic disorders  Typically occurs in patients > 40  Male: female ratio = 2:1

Cystic Medial Necrosis
 Typically

affects large arteries, chiefly

the aorta  Sometimes associated with the cervical arteries  Breakdown of collagen, elastin, and smooth muscle, along with an increase in the artery’s ground substance  Ehlers-Danlos and Marfan syndrome

Osteogenesis Imperfecta
 Bone

fragility  Also blue sclerae, diminished hearing, thinness of the skin, and joint hypermobility  Type 1 associated with CAD: Decreased or structurally defective type I collagen produced

Alpha-1-Antitrypsin Deficiency

Circulating serine proteinase inhibitor of proteolytic enzymes that contributes to maintenance of integrity of connective tissues Deficiency provides insufficient protection against effect collagenase and elastase and may damage vessel wall Genetic systemic disorder with lung and liver disease

Alpha-1-Antitrypsin Deficiency
• • •

22 consecutive patients with SCAD and 113 controls with non-CAD stroke Significantly lower levels in CAD (P=0.01) OR 17.7 (95% CI: 2.9-105.6) for A1-AT levels < 90 mg/dl

Alpha-1-Antitrypsin Deficiency
 

Findings were refuted by a more recent and methodologically sound study Another small study consisting of 12 spontaneous CAD patients found 3 cases with a deficiency of alpha-1-antitrypsin Overall, there is little evidence in support of this relationship

Vila N, et al. Levels of α1-antitrypsin in plasma and risk of spontaneous cervical artery dissections. Stroke 2003;34:e168-169 Haneline M, Lewkovich GN. A narrative review of pathophysiological mechanisms associated with cervical artery dissection. J Can Chiropr Assoc 2007; 51(3):146–157

Autosomal Dominant Polycystic Kidney Disease
  

Common heritable condition: Prevalence rate of 1 in 400 to 1 in 1000 Affecting the renal system May also lead to extra-renal complications, including connective tissues disorders

Haneline M, Lewkovich GN. A narrative review of pathophysiological mechanisms associated with cervical artery dissection. J Can Chiropr Assoc 2007; 51(3):146–157

Previous CAD
 

Incidence of new CAD in first year post-CAD: 1.7% (95% CI 0.3-3.6%) Cumulative 1-year incidence of 10.7% (95% CI 6.5-14.9%) and 3-year incidence of 14.0% (95% CI 8.9-19.1%) for new CVA post initial CAD diagnosis

Weimar C, Kraywinkel K, Hagemeister C, Haass A, Katsarava Z, Brunner F, et al. Recurrent stroke after cervical artery dissection. J Neurol Neurosurg Psychiatry 2010;81:869-873.

Cardiovascular Risk Factors
 Hypertension  Tobacco

use  Hypercholesterolaemia  Diabetes  Atherosclerosis

Hypertension
 Risk

factors studied: tobacco use, hypertension, diabetes, and hypercholesterolaemia  Compared a group of 153 consecutive patients with CAD, a group of patients with ischaemic stroke unrelated to CAD, and a group of controls

Hypertension
 Hypertension

was the only one of 4 variables significantly associated with CAD, but only in the subgroup of CAD patients who developed cerebral infarction  Overall OR 1.94 (95% CI: 1.01-3.70)  For VA dissection OR 2.69 (95% CI:1.20-6.04)

Atherosclerosis
    

362 cadaver vertebral arteries Grade 0 (0% occlusion) to grade 5 (75% occlusion) atherosclerosis Highest incidence of grade of atherosclerosis: Grade 3 Mainly in atlanto-occipital portion of VA: 4.0% Also in intra-cranial portion of VA: 35.2%

Atherosclerosis
 Blood

flow proportional to fourth power of diameter  Population at risk for developing VBI?  Note: Only basic science extrapolation!
Mitchell J. Vertebral artery atherosclerosis: A risk factor in the use of manipulative therapy? Physiother Res Int 2002;7:122-13

Hypercholesterolaemia
  

Prospective study on infection as risk factor for CAD 47 consecutive patients with spontaneous CAD and 52 with ischemic stroke Significantly higher hypercholesterolaemia in controls (42.6%) versus subjects (12.9%)

Guillon B, et al. Infection and the risk of spontaneous cervical artery dissection. Stroke 2003;34:e79-e81

Hypercholesterolaemia
 72

CAD patients compared with 72 nonCAD stroke control patients  Diabetes, current smoking, hypercholesterolaemia, and oral contraceptive use not associated with CAD
Pezzini A, et al. History of migraine and the risk of spontaneous cervical artery dissection. Cephalagia 2005;25:575-580

Hypercholesterolaemia
 So:

Hypercholesterolaemia is protective?  Comparing apples and oranges…  Hypercholesterolaemia more frequent in subgroup of CAD patients with ischaemic events
Arnold M, et al. Vertebral artery dissection: Presenting findings and predictors of outcome. Stroke 2006;37:2499-2503

Thyroid disease
 

 

Case-control study involving 58 subjects Present in 31.0% of CAD patients (9/29), compared with 6.9% of non-CAD stroke patients (2/29) (P=0.041) Immunologic mechanisms contributing to the vascular damage? Reports of ICA dissection in patients with Graves disease: Effects of thyroid hormones on the smooth muscle cells and endothelium of the vascular system

Clinical Vignette
 39-year

old male  Felt dizzy and clammy  Consulted osteopath and received traction manipulation  Semi-comatose state and vomiting  Died in hospital 19 hours later  Cerebellopontine infarction following bilateral vertebral artery dissection

Infection
 

Seasonal variation incidence of CAD: related to the higher incidence of upper respiratory infections during the winter? 31.3% (95% CI: 26.5-36.4) of cohort of 352 CAD patients developed dissection in the winter Statistically significantly more than in the spring, 25.5% (95% CI: 21.1-30.3), the summer 23.5% (95% CI: 19.3-28.3), and the autumn 19.7% (95% CI: 15.7-24.1)

Paciaroni M, et al. Seasonal variability in spontaneous cervical artery dissection. J Neurol Neurosurg Psychiatry 2006;77:677-679

Infection
• • •

• •

Prospective study on infection as risk factor for CAD 47 consecutive patients with spontaneous CAD and 52 with ischemic stroke Acute infection present within 4 weeks preceding vascular event more common in SCAD (31.9%) than control subjects (13.5%) Crude OR 3.0 (95% CI: 1.1-8.2, P= 0.032) Adjusted OR 3.1 (95% CI: 1.1-9.2)

Guillon B, et al. Infection and the risk of spontaneous cervical artery dissection. Stroke 2003;34:e79-e81

Oral Contraceptive Use
 One

retrospective case-control study (17subjects, 24 controls) investigating CAD risk factors generated statistically significant findings  Current (but not past) use of oral contraceptives associated with CAD

Oral Contraceptive Use

Another case-control study that explored CAD risk factors found that 58.3% of CAD cases were using oral contraceptives (27 of 47), as compared with 40.0% of the controls who had ischemic stroke from another cause (21 of 52): non-significant difference No consensus

Haneline M, Lewkovich GN. A narrative review of pathophysiological mechanisms associated with cervical artery dissection. J Can Chiropr Assoc 2007; 51(3):146–157

Other Risk Factors
  

Mechanical stress of coughing, sneezing, or vomiting: OR 1.6 (95% CI: 0.67-3.80) Vascular risk factors OR 0.14 (95% CI: 0.340.65) Current smoking habit OR 0.49 (95% CI: 0.18-1.05)

Triano JJ, Kawchuk G. Current Concepts in Spinal Manipulation and Cervical Arterial Incidents (2006)

Systematic Review of Risk Factors CAD
 Systematic

review risk factors cervical artery dissection  Two computerized databases, 19662005  31 case control studies

Systematic Review of Risk Factors CAD
 Aortic

root diameter > 34 (mm): OR=14.2 (95% CI: 3.2-63.6)  Homocysteine levels (may cause endothelial damage): OR=1.3 (95% CI: 1.05-1.52)  Little relevance to PT clinical practice…

Systematic Review of Risk Factors CAD
More relevant to PT clinical practice:  Migraine: OR=3.6 (95% CI: 1.5-8.6)  Trivial trauma (neck manipulation): OR=3.8 (95% CI: 1.3-11)  Recent infection: OR=1.6 (95% CI: 0.67-3.80) However, most studies had major sources of bias
Rubinstein SM, et al. A systematic review of the risk factors for cervical artery dissection. Stroke 2005;36:1575-1580

Bradford Hill criteria

Although opinions certainly and justifiably differ, case reports and narrative reviews of such case reports provided by authors in diverse geographical locations temporally linking possible mechanical trauma of the cervical arteries due to manipulation to CAD would seem to qualify as supporting the first three criteria However, we can argue criteria 4 and 5 are not satisfied…

Clinical Diagnosis
 Two

relevant questions…

First Relevant Question

How do we identify patients at risk for cervical artery dysfunction?

Identify patients at risk for CAD

Clinically relevant risk factors: Previous medical history of treatment with cervical manual therapy interventions, hypertension, previous infection, previous CAD, and migraine headache Questionable risk factors: Atherosclerosis, thyroid disease, and arteriopathies…

Second Relevant Question

How do we identify patients with cervical artery dysfunction in progress?

They are not all this easy…

Presenting Complaint?
 Major

presenting complaint of 137 patients who subsequently had an SMTinduced vertebrobasilar vascular incident

Presenting Complaint
         

47.4%: Neck pain and stiffness 19.7%: Neck pain, stiffness, and headache 16.8%: Torticollis 2.2%: Low back pain 2.2%: Abdominal complaint 1.5%: (Kypho) scoliosis 1.5%: Head cold 1.5%: Upper thoracic pain 0.7%: Upper limb numbness 0.7%: Hay fever

Terrett AGJ. Vertebrobasilar stroke following spinal manipulation therapy. In: Murphy R. Conservative Management of Cervical Spine Syndromes (2000)

So Where Does This Leave Us?

 Presenting

complaint provides no relevant information

Physical Examination?

De Kleyn-Nieuwenhuyse Test
 In

1927, De Kleyn and Nieuwenhuyse reported decreased or even absent vertebral artery blood flow based on cadaver perfusion studies in different head and neck positions

De Kleyn-Nieuwenhuyse Test

Based on these anatomical observations and these early perfusion studies, the sustained extension-rotation and the sustained rotation tests have been proposed and widely instructed and used as tests to determine the presence of vertebrobasilar artery dysfunction

De Kleyn A, Nieuwenhuyse AC. Schwindelanfälle und Nystagmus bei einer bestimmten Stellung des Kopfes. Acta Otolaryngologica 1927;11:155-157

Sustained Extension-Rotation Test and VA
 

 

Extensively studied with equivocal results Some authors have reported significant decreases in VA blood flow, whereas other studies found no changes Case reports have noted false negative results Case series have reported 75-100% false positive results

Sustained Rotation Test and VA
 Research

findings for the sustained cervical rotation test are equally equivocal  Significant decreases or no effect noted on vertebral artery blood flow or volume

Sustained Extension-Rotation Test and VA
  

Meta-analysis of Doppler studies of VA blood flow velocity Effect size: Cohen’s d VA blood flow velocity compromised more in patients than asymptomatic subjects, on contralateral rotation, in sitting more than lying, intra-cranial more than cervical

Mitchell J. Vertebral artery blood flow velocity changes with cervical spine rotation: A metaanalysis of the evidence with implications for professional practice. J Manual Manipulative Ther 2009;17:46-57.

Sustained (Extension) Rotation Test and ICA
 Refshauge

noted an increase in right ICA blood flow velocity with sustained contralateral rotation in healthy volunteers

Sustained (Extension) Rotation Test and ICA

In contrast, Licht et al found no change in peak flow or time-averaged mean flow velocity in the ICA during sustained extension-rotation test Patients nonetheless experienced symptoms (vertigo, visual blurring, nausea, hemicranial paraesthesiae) classically considered a positive response on this test
Licht PB, Christensen HW, Høilund-Carlsen PF. Carotid artery blood flow during premanipulative testing. J Manipulative Physiol Ther 2002;25:568-572.

Sustained (Extension) Rotation Test and ICA

Rivett et al reported increase in ICA blood flow velocity with cervical extension due to narrowing in the ICA? Decrease in peak systolic and end-diastolic blood flow velocity in both ICA during sustained rotation Found no between-group differences for subjects that were positive or negative on this test
Rivett DA, Sharpless KJ, Milburn PD. Effect of premanipulative tests on vertebral artery and internal carotid artery blood flow: A pilot study. J Manipulative Physiol Ther 1999;22:368-375.

Psychometric Data
    

Duplex Doppler ultrasonography Measured blood flow and vessel diameter Subjects 1,108 consecutive subjects referred for neurovascular evaluation 136 (12.3%) had unexplained vertebrobasilar distribution symptoms Extension-rotation position held for at least 10 seconds

Sakaguchi M, et al. Mechanical compression of the extracranial vertebral artery during neck rotation. Neurol 2003;61:845-847

Psychometric Data
 Richter

and Reinking calculated diagnostic accuracy statistics  Comparing signs and symptoms with extension rotation as clinical test and US findings as reference test
Richter RR, Reinking MF. Evidence in Practice. Phys Ther 2005;85:589-599

Psychometric Data

Psychometric Data
 Sensitivity

9.3% (95% CI: 4-19.9%)  Specificity 97.8% (95% CI: 96.7-98.5%)  LR+ 4.243 (95% CI: 1.678-10.729)  LR- 0.928 (95% CI: 0.851-1.011)  Interpretation in light of extremely low pretest probability?

Psychometric Data
 

12 experimental and 30 control subjects recruited from chiropractic clinics Experimental group had history of symptoms related to head and neck movement and positive Wallenberg test (head and neck extension-rotation for 30 seconds) Non-vascular causes excluded by radiography and neurologist examination

Côté P, et al. The validity of the extension-rotation test as a clinical screening procedure before neck manipulation: A secondary analysis. J Manipulative Physiol Ther 1996;19:159-164

Psychometric Data
  

Extension-rotation test held for 30 seconds Doppler ultrasound at C3-C5: Systolic peak velocity to end-diastolic minimum velocity Positive index test: Vertigo, nausea, tinnitus, lightheadedness, visual problems, numbness of the face or one side of the body, nystagmus, vomiting, or loss of consciousness

Psychometric Data

Predictive Validity
 How

can positional testing of haemodynamics in a still patent vessel be expected to produce clinically useful information regarding the risk of injury with manipulative interventions?

Predictive Validity

With an already pathologically weakened vessel wall, performing the test itself might put the patient at greater risk due to the potential stretching forces exerted At least in cadaver studies, strain values produced during the test exceeded those produced with manipulation

Thiel H, Rix G. Is it time to stop functional pre-manipulation testing of the cervical spine? Man Ther 2005;10:154-158

Predictive Validity

 

Haldeman et al did a retrospective analysis of 64 medicolegal records describing cerebrovascular ischaemia after cervical SMT The clinicians involved described doing the sustained extension-rotation test in 27 cases None of these patients had adverse responses

Haldeman S, et al. Unpredictability of cerebrovascular ischaemia associated with cervical spine manipulation therapy: A review of sixty-four cases after cervical spine manipulation. Spine 2002;27:49-55

Again, Where Does This Leave Us?
We talked about the limited value of:  Presenting complaint  Clinically relevant risk factors  Questionable risk factors Sustained extension-rotation test would at the very most only seem relevant when positive

Teaching Provocative Tests
 17/20

member organizations IFOMT teach provocative tests involving rotation +/- extension  In March 2004, clinic directors of all US chiropractic colleges agreed to abandon teaching provocative tests
Rivett D, Carlesso L. Safe Manipulative Practice in the Cervical Spine (2008) Clum G. Cervical Spine Adjusting and the Vertebral Artery (2006)

Remember the Two Relevant Questions?
Goals of history and examination  Screen patients at risk for adverse effect with intervention  Identify patients with cervical artery dysfunction in progress?

Five Ds And Three Ns
        

Dizziness Drop attacks Diplopia (including amaurosis fugax and corneal reflux) Dysarthria Dysphagia (including hoarseness and hiccups) Ataxia of gait Nausea Numbness (in ipsilateral face and/or contralateral body) Nystagmus

Nystagmus
 Repetitive,

back-and-forth, involuntary eye movements initiated by slow drifts away from the visual target  Pendular nystagmus consists of slow sinusoidal oscillations  Jerk nystagmus is characterized by an alternating slow drift and a quick corrective phase

Nystagmus
 Spontaneous

nystagmus may imply an acute peripheral vestibular lesion and may occur in the symptom-free interval in patients with vestibular migraine  Jerk nystagmus with the quick phase indicating the unaffected side

Nystagmus
 Purely

vertical (upbeat or downbeat) or torsional spontaneous nystagmus is indicative of a central vestibular lesion  Nystagmus due to a central lesion usually cannot be suppressed with visual fixation

Nystagmus
 Positional

downbeat vertical or skew nystagmus: Posterior fossa lesions (Arnold-Chiari malformation or another compressive lesion at the foramen magnum)

Nystagmus
 Pendular

nystagmus occurs most commonly in patients with multiple sclerosis and brain stem stroke

Cervical Artery Dysfunction
 Non-ischaemic

signs and symptoms  Ischaemic signs and symptoms  Vertebrobasilar system  Internal carotid artery

Non-Ischaemic Signs and Symptoms VA
   

 

Ipsilateral posterior neck pain Ipsilateral occipital headache Sudden-onset and severe Described as stabbing, pulsating, aching, “thunderclap”, sharp, or of an unusual character “A headache unlike any ever experienced before…” Rarely C5-C6 nerve root impairment due to local neural ischaemia

Ischaemic Signs and Symptoms VA
       

Five Ds And 3 Ns Vomiting Loss of short-term memory Vagueness Hypotonia and limb weakness affecting arm or leg Anhydrosis: lack of facial sweating Hearing disturbances Horner syndrome

Ischaemic Signs and Symptoms VA
      

Malaise Perioral dysaesthesia Photophobia Clumsiness Agitation Cranial nerve palsies Hindbrain stroke: Wallenberg or locked-in syndrome

Non-Ischaemic Signs and Symptoms ICA
 Ipsilateral

upper and mid-cervical pain  Ipsilateral fronto-temporal or peri-orbital headache  Sudden onset, severe, uncommon character  Horner syndrome  Pulsatile tinnitus  Cranial nerve palsies

Non-Ischaemic Signs and Symptoms ICA
 Ipsilateral

carotid bruit  Neck swelling  Scalp tenderness  Anhydrosis face

Ischaemic Signs and Symptoms ICA
        

TIA Middle cerebral artery distribution stroke Retinal infarction Amaurosis fugax: Temporary blindness Local patchy blurring of vision: Scintillating scotomata Weakness extra-ocular muscles Protrusion eye Swelling eye or conjunctiva Horner syndrome

Carotid Bruit

56% sensitivity and 91% specificity for detection of a 70-99% carotid stenosis when compared with color duplex ultrasound Implication: Maybe this is a test we need to do more often when the index of suspicion is raised?

Magyar MT, et al. Carotid artery auscultation: Anachronism or useful screening procedure? Neurol Res 2002;24:705-708

Cranial Nerve Palsies

Relevant to the physical examination are the cranial nerve palsies that may occur with cervical artery dissection Dissection of the ICA mainly causes CN IXXII dysfunction with the hypoglossal nerve initially affected and then the other three nerves; eventually all cranial nerves except the olfactory can be affected Cranial nerve palsies are part of the ischaemic presentation of a vertebral artery dissection

Cranial Nerve Palsies
 Large

study of hospitalized patients with CAD  Only 7% had cranial nerve palsies
Debette S, Leys D. Cervical artery dissections: Predisposing factors, diagnosis, and outcome. Lancet Neurol 2009;8:668-678.

Cranial Nerve Palsies
Cranial nerve I. Olfactory II. Optic III. Oculomotor IV. Trochlear V. Trigeminal VI. Abducens VII. Facial VIII. Vestibulo-cochlear IX. Glossopharyngeal X. Vagus XI. Accessory XII. Hypoglossal Test Identify different odors Test visual fields (Confrontation method) Upward, downward, and medial gaze Downward and lateral gaze Corneal reflex, face sensation, clench teeth Lateral gaze Close eyes tight, smile, whistle, puff cheeks Hear watch ticking, hearing tests, balance tests Gag reflex, ability to swallow Gag reflex, ability to swallow, say “Ahhh” Resisted shoulder shrug Tongue protrusion (Observe for deviation) L/R + + + + + + + + + + + + -

Horner Syndrome
 Four

physical signs: miosis, ptosis, enophthalmos, and anhydrosis  Miosis or inability to dilate a pupil  Paralysis of the dilatator pupillae muscle

Horner Syndrome
  

Incomplete ptosis or droopy upper eyelid Weakness tarsalis superior muscle Ptosis can occur due to weakness in the levator palpebrae, a voluntary muscle innervated by the oculomotor nerve or as a result of weakness in the sympathetically innervated tarsalis superior muscle Ptosis can also occur congenitally, and it can occur as a familial condition, with increasing age, fatigue, depression, and drowsiness

Horner Syndrome
      

Enophthalmus or deeper-seated eye Weakness orbitalis muscle Anhydrosis or decreased sweating Affects ipsilateral head and shoulders Syndrome often incomplete Especially the enophthalmus and the anhydrosis are frequently absent Miosis is often only noticeable in a dark environment when the unaffected pupil dilates and the affected pupil does not

Horner Syndrome

Horner Syndrome
Three possible locations for the lesion:  The central neuron runs from the hypothalamus to the ciliospinal center and is located in the cervical spinal cord (C8-T2)  This may occur as a result of ischaemic processes affecting the medulla (i.e., vertebrobasilar ischaemia) or as a result of insult to the spinal cord

Horner Syndrome
 The

secondary neurons run from the ciliospinal center by way of the nerve roots C8-T2 to the sympathetic ganglia and through these ganglia to the superior cervical or stellate ganglion  This may occur as a result of, e.g., syringomyelia or a tumor of the apex of the lung

Horner Syndrome

  

The tertiary neuron runs from the stellate ganglion to the dilatator pupillae and the vascular supply to the iris This may occur due to carotid ischaemia Clinical implications? Note: A congenital form of Horner’s syndrome exists and can be recognized by unequal coloring of both irises

Thunderclap Headache

Headache: Differential Diagnostic Options
 Cervicogenic

headache  Tension-type headache  Migraine headache

Cervicogenic Headache
Pain, referred from a source in the neck and perceived in one or more regions of the head and/or face, fulfilling criteria C and D Clinical, laboratory and/or imaging evidence of a disorder or lesion within the cervical spine or soft tissues of the neck known to be, or generally accepted as, a valid cause of headache

Cervicogenic Headache
Evidence that the pain can be attributed to the neck disorder or lesion based on at least one of the following: 1. Demonstration of clinical signs that implicate a source of pain in the neck 2. Abolition of headache following diagnostic blockade of a cervical structure or its nerve supply using placebo- or other adequate controls Pain resolves within 3 months after successful treatment of the causative disorder or lesion

Referral Pattern Upper Trapezius Muscle

Referral Pattern Levator Scapulae Muscle

Referral Pattern Sternocleidomastoid Muscle

Referral Pattern Temporalis Muscle

Referral Patterns Splenius Capitis (Left) and Cervicis (Right) Muscles

Referral Patterns Semispinalis Cervicis (Left) and Capitis (Right) Muscles

Tension-Type Headache
  

Hypothesized to be related to myofascial trigger points Prolonged nociceptive input may lead to central sensitization Amplification of receptiveness of central painsignaling neurons to input from low-threshold mechanoreceptors Clinically characterized by the presence of hyperalgesia and/or allodynia

Tension-Type Headache
Headache has at least two of the following characteristics: 1. Bilateral location 2. Pressing/tightening (non-pulsating) quality 3. Mild to moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing stairs Both of the following: 1. No more than one of photophobia, phonophobia or mild nausea 2. Neither moderate or severe nausea nor vomiting Not attributed to another disorder

Migraine with Aura
  

At least 2 attacks fulfilling criteria 2-4 Aura consisting of at least one of the following, but no motor weakness: 1. Fully reversible visual symptoms including positive features (e.g., flickering lights, spots or lines) and/or negative features (i.e., loss of vision) 2. Fully reversible sensory symptoms including positive features (i.e., pins and needles, peri-oral paraesthesiae) and/or negative features (i.e., numbness) 3. Fully reversible dysphasic speech disturbance

Migraine with Aura
  

 

At least two of the following: 1. Homonymous visual symptoms and/or unilateral sensory symptoms 2. At least one aura symptom develops gradually over ≥5 minutes and/or different aura symptoms occur in succession over ≥5 minutes 3. Each symptom lasts ≥5 and ≤60 minutes Headache fulfilling criteria Migraine without aura begins during the aura or follows aura within 60 minutes Not attributed to another disorder

CPR Migraine Headache Diagnosis
Five questions: 1. Is it a pulsating headache 2. Does it last between 4 and 72 hours without medication? 3. Is it unilateral? 4. Is there nausea 5. Is the headache disabling (disrupting daily activities)?

CPR Migraine Headache Diagnosis
    

≥ 4 questions yes: LR+ 24 (95% CI: 1.5-388) 3 questions yes: LR+ 3.5 (95% CI: 1.3-9.2) 1 or 2 questions yes: LR+ 0.41 (95% CI: 0.320.52) Mnemonic POUNDing: Pulsating, Duration of 4-72 hours, Unilateral, Nausea, Disabling But note similarity to neurological deficits noted in cervical artery dysfunction!

Relevance thunderclap headache
In 27 cases of non-CSMT VAD this headache preceded the neurological symptoms:  By less than 1 day in < 30% of cases  By 1-3 days in 15%  By 1-2 weeks in 30%  By > 3 weeks in 25%
Terrett AGJ. Vertebrobasilar stroke following spinal manipulation therapy. In: Murphy R. Conservative Management of Cervical Spine Syndromes (2000)

Risk Management
 Manipulation

or mobilization  Type of manipulative technique  Upper versus lower cervical techniques

Mobilization or Manipulation?
 Michaeli

(1993): Questionnaire sent to manipulative physiotherapists in South Africa  228,050 procedures  Only minor adverse effects reported for manipulation  29 patients receiving cervical spinal manipulation reported 52 complications

Mobilization or Manipulation?
   

However: 58 patients receiving spinal mobilization to the cervical spine reported 129 complications One mobilization patient suffered a CVA Implication for risk reduction?

Michaeli A. Reported occurrence and nature of complications following manipulative physiotherapy in South Africa. Aust J Physiother 1993;39:309-315

Mobilization or Manipulation?
 Survey

Irish manual physiotherapists  Only three major adverse events all associated with cervical manipulation  Drop attack, syncope, TIA
Sweeney A, Doody C. Manual therapy for the cervical spine and reported adverse effects: A survey of Irish manipulative physiotherapists. Man Ther 2010;15:32-36.

Manipulation: Effect of Technique?
   

Rotation appears to place the greatest stress on arterial structures, especially in the upper cervical spine However, Haldeman et al (2002): review 64 medicolegal reports Strokes noted after any type of manipulation Including rotation, extension, side bending, non-force, and neutral position manipulation

Haldeman S, et al. Stroke, cervical artery dissection, and cervical spine manipulation therapy. J Neurol 2002;249:1098-1104

Manipulation: Effect of Level?
 Most

reported site of VA damage is at C1-C2  Includes traumatic and spontaneous dissections
Mas JL, et al. Extracranial vertebral artery dissections: A review of 13 cases. Stroke 1987;18:1037-1047 Mokri B, et al. Spontaneous dissections of the vertebral arteries. Neurology 1988;38:880-885 Saeed AB, et al. Vertebral artery dissection: Warning symptoms, clinical features, and prognosis in 26 patients. Can J Neurol Sci 2000;27:292-296.

Manipulation: Effect of Level?
 

Cervical manipulation definable event with evidence of a mechanical effect Provided and recorded by third parties unlike etiologic mechanisms such as shoulder checking, hair washing, etc. “Not to say less recordable mechanical events are less related to dissection”

Kawchuk GN, et al. The relationship between the spatial distribution of vertebral artery compromise and exposure to cervical manipulation. J Neurol 2008;255:371-377.

Manipulation: Effect of Level?
 

Populations studied 5-year retrospective review yielding a cohort of 25 patients with VA dissection not related to major trauma or CSMT from Foothills Hospital, Calgary, AB 26 of 64 cases reported by Haldeman et al from retrospective case review article associated with manipulation Diagnostic imaging or reports had to be available to determine location of VA dissection

Manipulation: Effect of Level?
 V3

segment most commonly dissected  Prevalence ratio (PR) V3 versus V1 prevalence in CSMT group = 8.46 (95% CI: 3.53-20.24)  PR V3 versus V1 in non-CSMT group = 4.00 (95% CI: 1.43-11.15)

Manipulation: Effect of Level?
 

 

Note: Higher prevalence irrespective of exposure to CSMT “Demonstrates the impact of everyday movements and postures [on this mechanically more vulnerable segment]” Age and gender not found to be significant factors But: V3 vulnerability augmented by CSMT exposure

Manipulation: Effect of Level?
 However,

multiple site lesions also significantly more common in both groups  CSMT: PR = 2.67 (95% CI: 1.98-3.58)  No CSMT: PR = 2.44 (95% CI: 1.813.29)  Interpretation?

Manipulation: Effect of Level?
 Report

of compression at C6 secondary to osteophyte arising from superior facet C6

Citow JS, Macdonald RL. Posterior decompression of the vertebral artery narrowed by cervical osteophyte: Case report. Surg Neurol 1999;51:495-498.

Emergency Procedures: What if the Unthinkable Happens…?
Onset of symptoms indicated in 138 of 185 cases:  69%: during CSMT  3%: within minutes of CSMT  8.5%: within 1 hour of CSMT  8.5%: 1-6 hours post-CSMT  5%: 7-24 hours post-CSMT  6%: >24 hours post-CSMT

Emergency Procedures: What if the Unthinkable happens…?
 Do

not re-manipulate the patient’s neck  Observe the patient: Transient signs and symptoms or cervicogenic proprioceptive dizziness?  Refer the patient: rescue and recovery position, do not give the patient anything to eat or drink (dysphagia), note the time, call 911

Conclusion
 Manipulation

is but one factor in the multi-factorial etiology of CAD  There may be no dangerous techniques but rather dangerous patients  Identification of risk factors or signs and symptoms indicating CAD in progress clearly pose contraindication to manual therapy

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