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4.CervicalRadicularPain
ArticleinPainPractice·October2009
ImpactFactor:2.36·DOI:10.1111/j.1533-2500.2009.00319.x
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EVIDENCE BASED MEDICINEEvidence-based Interventional Pain Medicine
according to Clinical Diagnoses
4. Cervical Radicular Pain
Jan Van Zundert, MD, PhD, FIPP*†; Marc Huntoon, MD‡;Jacob Patijn, MD, PhD†; Arno Lataster, MSc§; Nagy Mekhail, MD, PhD, FIPP¶;
Maarten van Kleef, MD, PhD, FIPP†
*Department of Anesthesiology and Multidisciplinary Pain Centre, Ziekenhuis Oost-Limburg,Genk, Belgium; †Department of Anesthesiology and Pain Management, University MedicalCentre Maastricht, Maastricht, the Netherlands; §Department of Anatomy and Embryology,
Maastricht University, Maastricht, the Netherlands; ‡Division of Pain Medicine, Department ofAnesthesiology, Mayo Clinic, Rochester, Minnesota, U.S.A.; ¶Department of Pain Management,
Cleveland Clinic, Cleveland, Ohio, U.S.A.
� Abstract: Cervical radicular pain is defined as pain per-ceived as arising in the arm caused by irritation of a cervicalspinal nerve or its roots. Approximately 1 person in 1,000suffers from cervical radicular pain. In the absence of a goldstandard, the diagnosis is based on a combination of history,clinical examination, and (potentially) complementaryexamination. Medical imaging may show abnormalities, butthose findings may not correlate with the patient’s pain.Electrophysiologic testing may be requested when nervedamage is suspected but will not provide quantitative/qualitative information about the pain. The presumed caus-ative level may be confirmed by means of selective diagnosticblocks. Conservative treatment typically consists of medica-tion and physical therapy. There are no studies assessing theeffectiveness of different types of medication specifically inpatients suffering cervical radicular pain. Cochrane reviewsdid not find sufficient proof of efficacy for either educationor cervical traction. When conservative treatment fails, inter-ventional treatment may be considered. For subacute cervicalradicular pain, the available evidence on efficacy and safety
supports a recommendation (2B+) of interlaminar cervicalepidural corticosteroid administration. A recent negativerandomized controlled trial of transforaminal cervical epidu-ral corticosteroid administration, coupled with an increasingnumber of reports of serious adverse events, warrants anegative recommendation (2B-). Pulsed radiofrequencytreatment adjacent to the cervical dorsal root ganglion is arecommended treatment for chronic cervical radicular pain(1B+). When its effect is insufficient or of short duration,conventional radiofrequency treatment is recommended(2B+). In selected patients with cervical radicular pain, refrac-tory to other treatment options, spinal cord stimulation maybe considered. This treatment should be performed in spe-cialized centers, preferentially study related. �
Key Words: cervical pain, epidural analgesia,evidence-based medicine, neck pain, nerve block, pulsedradiofrequency, radiofrequency ablation
INTRODUCTIONThis article on cervical radicular pain is part of the series“Interventional practice guidelines based on clinicaldiagnosis”. Recommendations formulated in this articleare based on “Grading strength of recommendationsand quality of evidence in clinical guidelines” describedby Guyatt et al.1 and adapted by van Kleef et al. in the
Address correspondence and reprint requests to: Jan Van Zundert, MD,PhD, FIPP, Ziekenhuis Oost-Limburg, Genk, Multidisciplinary Pain Centre,Stalenstraat, 2, 3600 Genk, Belgium. E-mail: [email protected].
DOI. 10.1111/j.1533-2500.2009.00319.x
© 2009 World Institute of Pain, 1530-7085/10/$15.00Pain Practice, Volume 10, Issue 1, 2010 1–17
editorial accompanying the first article of this series2
(Table 1). The last literature update was performed inthe latter part of May 2009.
Cervical radicular pain is pain perceived in the upperlimb, shooting or electric in quality, caused by irritationand or injury of a cervical spinal nerve.3,4 In the classifica-tion of the International Association for the Study ofPain,5 cervical radicular pain is defined as pain perceivedas arising in the upper limb caused by ectopic activationof nociceptive afferent fibers in a spinal nerve or its rootsor other neuropathic mechanisms. This is, however, aproblematic definition, as the presence of ectopic activa-tion has rarely, if ever, been demonstrated in a clinicalsetting.6
Cervical radicular pain must be distinguished fromcervical radiculopathy. In the latter disorder there is anobjective loss of sensory and/or motor function.Radicular pain and radiculopathy are not synonymouseven though in the literature these terms are used inter-changeably. Radicular pain is a symptom that iscaused by ectopic impulse formation, while radicul-opathy also includes neurologic signs such as sensoryor motor changes. Still these two disorders may occursimultaneously. Moreover, they may be caused by thesame clinical entities; for example, narrowing of theintervertebral foramen, intervertebral disk herniation,and radiculitis due to arthritis, infection, or infl-ammatory exudates.5 Both syndromes can form a con-tinuum whereby radiculopathy may advance from
initial radicular pain when the underlying disorderprogresses.6
The natural history of cervical radicular pain orradiculopathy is not described in detail in the literature.Data on incidence and prevalence are scarce. The mostfrequently used epidemiologic data are from Rochester,MN, USA (1976 to 1990), where the incidence is cal-culated based on the information from the computerizedmedical record linkage system for the Mayo Clinic andits two affiliated hospitals. The authors claim that theirdatabase is essentially an enumeration of the Rochesterpopulation. They found in a population between 13 and91 years an annual incidence of cervical radiculopathyof 83 per 100,000.7 Although the authors classified thepatients as suffering from radiculopathy, the describedpopulation most probably included cervical radicularpain, because sensory changes were only reported in33% and weakness in 64%. The average age-adjustedincidence rates per 100,000 people were 107 for malesand 64 for females. The highest incidence was found inthe age group between 50 and 54 years with an averageof 203 per 100,000 people. In 15% of the patients, ahistory of physical exertion or trauma preceded theonset of symptoms, and 41% of the patients had aprevious history of lumbar radiculopathy. According tothis study, the most frequently involved level was C7 in45% to 60% of the cases. Level C6 represents approxi-mately 20% to 25% and levels C5 and C8 each repre-sent approximately 10% of the cases.8
Table 1. Summary of Evidence Scores and Implications for Recommendation
Score Description Implication
1 A+ Effectiveness demonstrated in various RCTs of good quality. The benefits clearly outweigh risk and burdens
Positive recommendation1 B+ One RCT or more RCTs with methodologic weaknesses, demonstrate effectiveness. The benefits clearly
outweigh risk and burdens2 B+ One or more RCTs with methodologic weaknesses, demonstrate effectiveness. Benefits closely balanced
with risk and burdens
2B� Multiple RCTs, with methodologic weaknesses, yield contradictory results better or worse than the controltreatment. Benefits closely balanced with risk and burdens, or uncertainty in the estimates of benefits,risk and burdens.
Considered, preferablystudy-related
2C+ Effectiveness only demonstrated in observational studies. Given that there is no conclusive evidence of theeffect, benefits closely balanced with risk and burdens
0 There is no literature or there are case reports available, but these are insufficient to suggest effectivenessand/or safety. These treatments should only be applied in relation to studies.
Only study-related
2C- Observational studies indicate no or too short-lived effectiveness. Given that there is no positive clinicaleffect, risk and burdens outweigh the benefit
Negative recommendation2B- One or more RCTs with methodologic weaknesses, or large observational studies that do not indicate any
superiority to the control treatment. Given that there is no positive clinical effect, risk and burdensoutweigh the benefit
2A- RCT of a good quality which does not exhibit any clinical effect. Given that there is no positive clinicaleffect, risk and burdens outweigh the benefit
RCT, randomized controlled trial.
2 • van zundert et al.
I. DIAGNOSIS
I.A HISTORY
Cervical radicular pain is characterized by pain in theneck that radiates over the posterior shoulder into thearm and sometimes into the hand. The radiation followsa segment-specific pattern. Pain originating from C4 isconfined to the neck and suprascapular region. Painoriginating from C5 radiates up to the upper arm, andpain from C6 and C7 radiates from the neck to theshoulder, the forearm, and the hand. The pain covers theposterolateral side of the upper arm, but the pain fromC7 extends more dorsally.4,9
Pain from various dermatomes can overlap and thereis no specific region of the arm, which is characteristicfor a particular segment. Radicular pain is not limited toa particular dermatome and can be perceived in allstructures that are innervated by the affected nerve rootssuch as muscles, joints, ligaments, and the skin.4
I.B PHYSICAL EXAMINATION
As with other types of spinal pain, there is no goldstandard for the diagnosis of cervical radicular pain. Forthis reason a diagnosis is made based on a combinationof history, clinical examination, and additional tests.6
Classical neurologic examination includes testingsensation, strength, and tendon reflexes.10 Specific clini-cal tests have been described for the diagnosis of cervicalradicular pain, including the neck compression test(Spurling test), the shoulder abduction test, and the
axial manual traction test.6 A description of these testscan be found in Table 2.
The validity of these three tests in the diagnosis ofroot compression in cervical disk disease was investi-gated regarding radicular pain, neurologic signs, androot compression signs in myelography. All of these testshave a high specificity (81% to 100%) but a low sensi-tivity. The Spurling test was similarly evaluated usingelectromyography as the reference test. The results werecomparable: sensitivity 30%, specificity 93%. Thesethree examinations are considered valuable aids in theclinical diagnosis of a patient with neck and arm pain.The neurologic characteristics of cervical radicularpain11 are given in Table 3.
I.C ADDITIONAL TESTS
The three most frequently requested types of additionaltests are medical imaging techniques, electrophysiologictests, and diagnostic selective nerve root blocks.
Medical Imaging
Medical imaging is mainly used to exclude primarypathologies, the so-called “red flags” (e.g., tumor, infec-tion, and fractures). Computed tomography (CT) pro-vides good imaging of the cortical bone structures. CTscans are able to reproduce the changes in bone structuremore sensitively than nuclear magnetic resonance images(MRI), but they have limitations in detecting soft tissuelesions. MRI is better suited to demonstrating changes in
Table 2. Clinical tests for the Diagnosis of Cervical Radicular Pain
Test Description
Spurling test Neck extended with head rotated to affected shoulder while axially loaded. Reproduction of the patient’s shoulderor arm pain indicates possible cervical spinal nerve root compression
Shoulder abduction test The patient lifts a hand above his or her head. A positive result is the decrease or disappearance of the radicular symptom.Axial manual traction test In supine position an axial traction force corresponding to 10 to 15 kg is applied. A positive finding is the decrease
or disappearance of the radicular symptom.
From: Van Zundert et al.6 With permission of the publisher.
Table 3. Neurologic Characteristics of Cervical Radicular Pain
Disc level Root Pain Distribution Muscle Weakness Sensory Loss Reflex Loss
C4 to C5 C5 Medial scapular border, lateralupper arm to elbow
Deltoid, supraspinatus, infraspinatus Lateral upper arm Supinator reflex
C5 to C6 C6 Lateral forearm, thumb andindex finger
Biceps, brachioradialis, wrist extensors Thumb and index finger Biceps reflex
C6 to C7 C7 Medial scapula, posterior arm,dorsum of forearm, third finger
Triceps, wrist flexors, finger extensors Posterior forearm, third finger Triceps reflex
C7 to T1 C8 Shoulder, ulnar side of forearm,fifth finger
Thumb flexors, abductors, intrinsic handmuscles
Fifth finger —
From: Carette S. and Fehlings MG.11 with Permission of the Publisher.
4. Cervical Radicular Pain • 3
the intervertebral disks, the spinal cord, the nerve roots,and the surrounding soft tissue.
MRI is currently regarded as the most suitable medicalimaging technique for patients with cervical radicularpain. There are no data available regarding the sensitivityand specificity of the various imaging techniques, giventhat there is no “gold standard” for the diagnosis ofcervical radicular pain.6 A direct link between the painsyndrome and the results of medical imaging does notexist. Prospective studies have shown abnormal MRIimages in 19% to 28% of asymptomatic patients.12,13
Electrophysiologic Tests
Of the various electrodiagnostic studies, needle elec-tromyography and nerve conduction tests are consid-ered useful if the physical examination and case historydo not enable differentiation between cervical radicularpain and other neurologic causes of pain in the arm andneck. Approximately 3 weeks after nerve compression,one sees typical abnormal insertion activity, with posi-tive sharp wave potentials and vibration potentials inthe arm muscles.11
Electrophysiologic tests can be requested when nervedamage is suspected but will not provide any informa-tion about the pain. For this reason, in recent years,Quantitative Sensory Testing (QST) has been recom-mended in the literature as an electrophysiologic testthat can provide more specific information about pain.A QST study in patients with cervical radicular symp-toms showed an increased detection threshold for lighttouch and allodynia (touch-induced pain), which dif-fered significantly from that in healthy subjects. QSTconfirmed the level of involvement identified by meansof diagnostic selective nerve root blocks.14
Diagnostic Selective Nerve Root Blocks
Radiologic images depict the morphologic characteris-tics of the pathology. In patients with chronic pain ingeneral, and in particular cervical radicular pain, it isextremely difficult to determine with certainty whichintervertebral disk or nerve root is causing the pain. Forthis reason, one or more diagnostic selective nerve rootblocks are applied to determine the probable pain-generating nerve root level. The diagnostic blocks areapplied in separate sessions per level. Under X-ray visu-alization using a contrast dye (fluoroscopy), a smallamount of local anesthetic is injected (0.5 mL).15 Duringa period of 30 to 60 minutes after injection, the painscore is evaluated at regular time intervals. When there
is at least a 50% decrease in pain, further treatment atthis nerve root level is indicated.
I.D DIFFERENTIAL DIAGNOSIS
Given that there is no gold standard for the diagnosis ofcervical radicular pain, clinical practice relies uponextensive history and clinical examinations and, if indi-cated, medical imaging and/or electrophysiologic tests.Finally, there is confirmation of the likely pain-generating nerve root level using diagnostic selectivenerve root blocks.
The differential diagnosis will initially aim to excludeany “red flags” such as infections, vascular disorders,and tumors. One of the most frequently occurringtumors that need to be excluded is the Pancoast tumor:a tumor of the pulmonary apex that can cause compres-sion of the subclavian artery, the phrenic nerve, thebrachial plexus, and compression of the sympatheticganglion, resulting in a range of symptoms that areknown as Horner’s syndrome. If the radicular pain isassociated with strongly expressed spinal complaints,the differential diagnosis needs to exclude primaryspinal tumors as well as metastases. Other less frequenttumors of the spinal nerves include neurofibroma. Painresulting from carpal tunnel syndrome can also ascendto the neck and may be more intense at night.16
Clinical examination is very important in the differ-ential diagnosis of brachialgia based upon shoulderpathology or pain originating from the facet joints. Withshoulder pain there is usually limited movement of theshoulder joint, whereas with pain originating from thefacet joints, there is usually limited rotation of the cer-vical spinal column. There is a paravertebral pressurethat is not associated with a radicular distributionpattern but sometimes is associated with a pseudorad-icular distribution to include the occipital and/or shoul-der region. For detailed diagnostics, please refer to otherrelated articles in this series.
II. TREATMENT OPTIONS
II.A CONSERVATIVE MANAGEMENT
Nonsteroidal anti-inflammatory medications are prima-rily recommended for short-term treatment because ofthe balance between efficacy and side effects. The anti-convulsants, such as carbamazepine, oxcarbamazepine,gabapentin, and pregabalin, are frequently used to treatneuropathic pain but they have not been studied in thetreatment of cervical radicular pain.6
4 • van zundert et al.
A Cochrane review evaluating the evidence forpatient education for neck pain with or without radicu-lopathy concluded that the available evidence does notshow effectiveness for educational interventions forvarious disorders and time intervals, including recom-mendations to activate, use of stress coping skills, and“neck school.”17
Another Cochrane review assessed the potentialvalue of mechanical traction for neck pain with orwithout radiculopathy and found no evidence tosupport or refute the efficacy or effectiveness of con-tinuous or intermittent traction for pain reduction,improved function or global perceived effect whencompared to placebo traction, or heat or other
conservative treatments in patients with chronic neckdisorders.18
Multidisciplinary rehabilitation with physiotherapyis recommended.19
II.B INTERVENTIONAL MANAGEMENT
Epidural Corticosteroid Administration
The principle of epidural administration of corticoster-oids relies on the anti-inflammatory response induced byinhibition of the phospholipase A2-initiated arachidonicacid cascade. There are two possible administrationroutes: the interlaminar and transforaminal routes(Figure 1). There are no direct comparisons available
Figure 1. Interlaminar and transfo-raminal administration in the epiduralspace. Illustration: Rogier Trompert,Medical Art.
Interlaminar
Vertebral artery
Transforaminal
Dorsal root ganglion(DRG)
Dura mater
Ligamentum flavum
vertebralartery
vertebralartery costocervical
trunkcostocervical
trunk
C8C8
C7C7
subclavianartery
subclavianartery
in posterior aspect ofin posterior aspect ofintervertebral foramentintervertebral forament
deep cervical arterydeep cervical artery
Figure 2. The three branches from the subclavian artery areshown. Most medially (left lower) the vertebral artery is seen,then the thyrocervical trunk in the forceps, followed more later-ally by the costocervical trunk. One of the deep cervical arterybranches from the costocervical trunk passes posterior to the C8ventral ramus.
vertebralartery
vertebralartery
costocervical trunkcostocervical trunk
subclavianartery
subclavianartery
ascendingascendingcervicalcervicalarteryartery
Figure 3. In this figure, the detail of the deep cervical artery(arrowhead) continuing from the costocervical trunk can be seenas it enters the posterior aspect of the foramen posterior to theC8 ventral ramus. This is the area of ideal needle pathway fortransforaminal epidural injection.
4. Cervical Radicular Pain • 5
between interlaminar and transforaminal administra-tion at a cervical level.
Interlaminar Administration: Efficacy. A systematicreview20 found two controlled studies involving the cer-vical interlaminar administration of corticosteroids. Anearlier randomized study comparing interlaminar andintramuscular corticosteroid administration found that68% of the patients treated using the interlaminarmethod had significant pain relief lasting at least 1 yearcompared to 12% in the group treated intramuscularly.21
A second study examined the effect ofco-administration of epidural morphine with corticos-teroid and local anesthetic vs. corticosteroid and localanesthetic. Despite a better transient improvement thefirst day after the intervention in the group receivingadditional morphine, long-term results did not differbetween groups.22 The update from the Cochrane sys-tematic review only included the first study.23
A recently published systematic review24 on the effec-tiveness of cervical interlaminar epidural steroid injec-tions in the management of chronic neck pain included3 randomized control trials (RCTs): the two studiesmentioned above and a study comparing the efficacy ofsingle injections with continuous infusion.25 Patientswere divided into 4 groups based on the duration oftheir pain, within each group of 40 patients half wererandomized to receive up to 9 epidural injections with4 to 5 days interval or administration of localanesthetic + corticosteroid via an epidural catheterfollowed by administration of local anesthetic every 6,12, or 24 hours along with corticosteroid every 4 to 5days for a total period of 30 days. The continuousadministration provided better pain relief than the singleinjection in patients with cervical radicular pain lastinglonger than 6 months, but no difference was observed inpatients with complaints of shorter duration. The sys-tematic review also included 5 observational studies ofvariable quality.26–29 The global conclusion of this sys-tematic review is that interlaminar cervical epidural cor-ticosteroid injections provide a significant effect oncervical radicular pain.24
Interlaminar Administration: Complications. Inter-laminar cervical corticosteroid administration is de-scribed in one review as relatively safe.30 A systematicreview of the literature found only two studies thatspecifically looked at the complications of cervical cor-ticosteroid administration. One study showed a <1%complication rate while the other reported a rate of
16.8%. This difference is mainly due to the time whenthe complications were noted and the method by whichthey were registered. Minor complications that sponta-neously disappeared, often within 24 hours, include,among others: increasing axial neck pain, posture-independent headache, facial flushing, and vasovagalepisodes. Major complications mentioned included epi-dural hematoma and accidental subdural injection with,as a result, hypoventilation and hypotension. Accidentalsubdural injection-induced hypoventilation must be dis-tinguished from the apnea and acute cardiovascular col-lapse that may result from an intrathecal injection.Paresthesia has been described after root damage. Therewere two reports of permanent damage to the spinalcord in patients who were sedated and possibly unableto report warning symptoms during the procedure.Intravascular uptake of the contrast dye has also beenreported, although this occurs less frequently in inter-laminar administration compared to the transforaminalroute. When the interlaminar corticosteroid administra-tion is correctly carried out, in a cooperative patient,using fluoroscopy and contrast medium, the incidence ofcomplications is low.30
Transforaminal Administration: Efficacy. The trans-foraminal administration route rapidly gained in popu-larity because of the more accurate administration of theactive product at the level of the affected nerve root. Thefirst randomized, controlled study by Anderberg et al.31
studied 40 successive patients with cervical radicularpain. They were randomly given a transforaminal epi-dural injection of either corticosteroid with a local anes-thetic or saline with a local anesthetic. Three weekspostinjection there were no differences in the subjectiveeffects between the treatments. Earlier reports from pro-spective, noncontrolled studies, however, reported apositive outcome that could not be confirmed by theRCT.
Transforaminal Administration: Complications.There have been various instances of serious complica-tions reported in the literature, and this is without doubtjust the tip of the iceberg. In a recently published anony-mous survey by pain specialists, members of theAmerican Pain Society, 287 respondents mentioned78 complications, mainly neurologic in character, ofwhich 15 were fatal.32
The reported complications following transforaminalcervical corticosteroid injections were summarized inthe comprehensive review of Malhotra et al.33, though
6 • van zundert et al.
this group already identified 14 case reports an addi-tional case was reported since their last literatureupdate.34 A summary of those complications is given inTable 4.
Except for the case reported by J.H. Lee et al. in2008, which concerns direct lesion of the spinal corddue to inadvertent air and contrast injection in the cer-vical cord,34 and the case reported by J.Y. Lee et al.,35
which is a spinal cord compression due to epiduralhematoma, the cases can be divided into lesions of thespinal cord caused by the anterior spinal arterysyndrome,36–38 and effects on the central nervous systeminvolving brain stem and cerebellum related to inadvert-ent injection of the vertebral artery.39–46
Though the mechanisms behind these seriouscomplications are not fully understood, two mainconsiderations must be highlighted: anatomic andpharmacologic.
Anatomic considerations. The normal vascular supplyto the cervical spinal cord has been described by Gillilanand others in the human fetus.47 Branches from thesubclavian artery include the vertebral artery, which isusually the first and largest branch. The second andthird branches from the subclavian artery (thyrocervicaltrunk and costocervical trunk) eventually give rise to theascending cervical artery, medially continuing as in-ferior thyroidal artery and the deep cervical artery,respectively.
The vertebral artery may be subdivided into V1, V2,and V3 segments. The V1 segment represents the distancefrom the origin on the subclavian artery to its entrance inthe transverse foramen. The V2 segment includes the areafrom entrance of the transverse foramen to C2, and theV3 segment includes its course through the C1 transverseforamen, after which it turns medially and dorsallythrough the groove on the upper surface of C1 to pen-etrate the posterior atlanto-occipital membrane and duraand pass through the foramen magnum into the cranialcavity. The vertebral arteries eventually come together toform the basilar artery on the ventral surface of themedulla, but prior to this each of them gives rise to abranch. These branches fuse to form the anterior spinalartery that runs in the ventral median fissure of the spinalcord. The longitudinal anterior spinal artery must bereinforced by segmental medullary arteries (radiculararteries) that are primarily from the V2 segment of thevertebral artery, but also come from the ascending anddeep cervical arteries.
The V2 and V3 segments of the vertebral artery areprone to significant variability in their course. A recentstudy of 500 vertebral arteries on 200 MRIs and 50contrast-enhanced CT scans is illustrative of thesevariations.48 The authors found that in only 93% ofcases did the vertebral artery enter the transverseforamen at C6. The vast majority of these anomaliessaw the V2 segment begin at C5, but the vertebralartery was noted to enter the transverse foramen atC3, C4, or C7 as well. When the vertebral arteryentered the transverse foramen at an aberrant level,the unfilled transverse foramina appeared muchsmaller on CT than the contralateral side. In addition,in 2% of all specimens the vertebral artery formed amedial loop, whose inside border was medial tothe uncovertebral joint or into the intervertebralforamen.
A recent anatomic study of human cadavers49 notedseveral other potential variations in normal anatomy:(1) there were instances of several deep cervical arter-ies arising from the subclavian artery directly, or froma very short costocervical trunk (Figure 2). These deepcervical arteries often enter the intervertebral foramenin its posterior aspect near sites of recommended trans-foraminal needle placement (Figure 3); (2) a singleascending cervical artery was noted to enter the pos-terior foramen at C4 and eventually supply the ante-rior spinal artery; (3) a large segmental medullarycontributing artery was noted to be the main supplierto the anterior spinal artery when the ipsilateral sidevertebral artery entered the spine at C5 instead of C6;(4) several anastomoses were noted between all threemain supply arteries in several cadavers, suggesting agreat potential for communication; and (5) in general,if the deep cervical artery tended to enter the interver-tebral foramina it was at either C7/T1 or C6/C7, andthe ascending cervical artery tended to enter theforamina at C5/C6 or higher. A recent study utilizingultrasound guidance for cervical transforaminal injec-tions50 noted a remarkably similar percentage of arte-rial vessels in the posterior aspect of the foramina(20%) as the cadaver study noted above. Cumula-tively, these anatomic features suggest that there is nospecific “safe zone” for needle placements in the pos-terior cervical foramina. It is unclear whether hypo-plastic or aberrant vertebral arteries or other arterialvariants described above absolutely increase the risksof transforaminal epidural injections, but certainlyvessel vulnerability warrants greater care in the perfor-mance of these procedures.
4. Cervical Radicular Pain • 7
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4. Cervical Radicular Pain • 9
Pharmacologic considerations. The case report ofKarasek and Bogduk51 reporting transient quadriplegiaafter injection of local anesthetic, suggest inadvertentpuncture of a cervical radicular artery and transientanesthesia of the spinal cord. However, when a spinalcord infarction is demonstrated, only partial recovery ofthe motor function occurs37,38 and one case had a fataloutcome due to complications.36
It has been postulated that upon inadvertent injectioninto the cervical radicular artery, the particulate steroidsmay act as an embolus and cause spinal cord infarctionand permanent impairment. Particle size of differentcorticosteroid preparations were studied undiluted anddiluted in saline or local anesthetic. The results of thisin-depth research illustrated that differences in the per-centage of large particles exist between compoundedand commercially available preparations. Because thespecifications of corticosteroid preparations commer-cially available in different countries may be different, itis difficult to draw conclusions for clinical practice.52
A recent study in a swine model underscores thepotential for catastrophic outcomes from particulatesteroids injected intra-arterially. Okubadejo and col-leagues53 instrumented the vertebral arteries in 11 pigsand intentionally injected them with either particulate(methylprednisolone) or nonparticulate steroid (dexam-ethasone). Interestingly, the animals that received par-ticulate steroid could not be removed from life support.Each of these 4 particulate steroid-receiving animals hadevidence on histologic examination of severe tissueedema, ischemic changes, and other pathologies. Noneof the animals receiving nonparticulate steroid had anyissues. These animal cases appear to be functionallysimilar to the case described by Beckman et al.42 Thestudy by Dreyfuss et al.54 comparing triamcinolone todexamethasone (nonparticulate) for cervical epiduralinjections was quite small, but certainly their efficacydata combined with the animal study described aboveseem to suggest that nonparticulate steroid may be agood alternative for those physicians who continue toperform transforaminal injections.
When patients demonstrate central symptoms such asnystagmus, confusion, and coma, it is less obvious toindicate an embolus caused by particulate steroids. Inthe McMillan and Crumpton39 case, no steroid wasinjected. Moreover, there are two cases where thepatient developed symptoms of brain stem infarctionseveral hours after the injection as opposed to thealmost immediate effect seen in others.42,43 In his com-ments on the case reported by Beckman et al.,42 de Leon-
Casasola remarks that the late onset of symptomsindicates that steroid embolism was not responsible forthe complication. It clearly depicts the clinical course ofvertebral artery dissection.55 Dissection of the vertebralartery and disruption of the blood brain barrier causesischemia and brain death due to acute intracranialhypertension. This mechanism is probably involved inthe case described by Rosenkranz et al.37
These serious and up till now inexplicable complica-tions provide good reason to be extremely cautiousabout performing transforaminal cervical epidural injec-tions with depot corticosteroids. In a letter to the editorfollowing the review of the complications,33 we stronglyrecommended curtailing use of transforaminal cervicalepidural corticosteroid administration until the mecha-nisms of those serious complications and the methods toprevent them have been better elucidated.56
Practical Recommendations. Direct comparisons be-tween interlaminar and transforaminal corticosteroidinjections in the cervical epidural space are not avail-able. The positive RCT for interlaminar administrationand, moreover, the quick succession of reports of seriouscomplications after transforaminal cervical epidural cor-ticosteroid injections supports the preference for inter-laminar administration.
There are no studies which have investigated theeffectiveness of the various depot corticosteroids, so nodistinction can be confirmed between them. The particlesize of the depot corticosteroid is possibly related to thereported neurologic complications, but also on thistopic the literature is inconclusive.52 Currently there isno evidence that a higher dose of corticosteroids willresult in a better clinical effect.57 On the other hand therisk of endocrine side effects is notably higher.58
In the randomized clinical trial, 1 to 3 epidural dosesadministered at intervals of 2 weeks were described.21
Shortening the interval between two corticosteroidadministrations may result in higher plasma levels andthus increase the risk for endocrine and other systemicside effects.
(Pulsed) Radiofrequency Treatment
Radiofrequency Treatment: Efficacy. The efficacy ofradiofrequency (RF) treatment adjacent to the dorsalroot ganglion (DRG) was reported in two randomizedclinical studies.59,60
The first study compared RF adjacent to the cervicalDRG with a sham intervention. In the actively treated
10 • van zundert et al.
group, 8 weeks postintervention the Number Needed toTreat, ie, the number of patients that need to be treatedin order to have at least one patient who has at least a50% reduction in pain, was 1.4.59
The second study compared RF with an electrode tiptemperature of 40°C with RF at 67°C.60 At 6 weeks andat 3 months after treatment there was a significantdecrease in the visual analog scale pain score in bothgroups. There was no significant difference in outcomebetween the two groups.
Radiofrequency Treatment: Complications. In theabove-mentioned studies, transient neuritis and/or aburning sensation in the treated spinal nerve werereported. Additionally, a slight loss of muscular strengthin the hand and arm of the treated side was reported.
Pulsed Radiofrequency Treatment: Efficacy. Cur-rently preference is given to pulsed radiofrequency treat-ment (PRF) where the tip temperature of the electrodedoes not exceed the critical threshold of 42°C and con-sequently there is minimal neuro-destruction. In anRCT, PRF appeared to be more effective than placebo 3months post-treatment. Also 6 months post-treatmentthere was a positive trend in the PRF treatmentbut in this study the outcome fell short of statisticalsignificance.61
Pulsed Radiofrequency Treatment: Complications.Up until now there have been no reported complicationsassociated with PRF.62
Surgical Treatment
Surgical treatment can provide pain relief in patientswhose symptoms seem to be refractory to all othertreatments. Surgical treatment is indicated in cervicalradiculopathy with spinal cord compression (myeloma-lacia) because of the risk for possibly irreversible neu-rologic deficiency.
In a randomized study where surgical treatment wascompared with conservative treatment a significantimprovement in pain relief was noted 3 months after theintervention. A year post-treatment however there wasno difference between the two groups.63 A small, ran-domized study indicated no differences in neurologicoutcome between patients who were surgically or con-servatively treated.64
Spinal Cord Stimulation
Spinal cord stimulation (SCS) consists of percutaneouslyapplying an electrode at the level of the involvedsegment of the spinal cord. These are then connected toa generator that delivers electric shocks in order tostimulate the painful dermatome and introduce analtered pain pathway. The mechanism behind SCS restson the gate control theory of pain.65
Up until now there is no literature on the outcome ofSCS in the treatment of cervical radicular pain.
SCS can be considered in clinical practice for chroniccervical radicular pain in well-selected patients whenother types of treatment have failed, given that the effi-cacy has been demonstrated in other comparable neu-ropathic pain syndromes.
The techniques and complications of implantationare presented in other articles in this series.
II.D EVIDENCE FOR INTERVENTIONALMANAGEMENT
A summary of the available evidence is given in Table 5.
III. RECOMMENDATIONSBased on the available evidence regarding efficacy andcomplications, the following treatments are recom-mended for cervical radicular pain:
1. In the subacute phase, an interlaminar epiduraladministration of local anesthetic and corticos-teroids is recommended. The cervical transfo-raminal epidural corticosteroid retained anegative recommendation.
2. For chronic cervical radicular pain, PRF adjacentto the cervical DRG is the first line recommendedinterventional pain management technique,because there are up till now no reports of neu-rologic complications with PRF. In the event that
Table 5. Evidence for The Treatment Options ForCervical Radicular Pain
Technique Score
Interlaminar corticosteroid administration 2B+Transforaminal corticosteroid administration 2B-Radiofrequency treatment adjacent to the dorsal
root ganglion (DRG)2B+
Pulsed radiofrequency treatment adjacent to the DRG 1B+*Spinal cord stimulation 0
* The score 1B+ is established according to the methodology described in theeditorial2. The authors want to stress the fact that more studies are needed tocontinue supporting this score.
4. Cervical Radicular Pain • 11
this has a poor or short-term effect an RF treat-ment adjacent to the cervical DRG is recom-mended.
3. If the symptoms persist then study-related SCScan be considered after extensive multidisci-plinary evaluation. Spinal cord stimulationshould be performed in specialized centers.
A suggested clinical practice algorithm is shown inFigure 4.
III.B TECHNIQUE(S)
Interlaminar Cervical Epidural Steroid Administration
During the planning of cervical epidural infiltrations,review of a preprocedural MRI should be strongly con-sidered. The procedure should be performed under fluo-roscopy. Correlation of fluoroscopic images with theMRI may avert potential complications in cases of largedisk protrusions mechanically deforming the posteriorepidural space.66
Cervical radicular pain
III.A CLINICAL PRACTICE ALGORITHM
Red flags excluded?
Yes
Conservative treatment was adequately carried out without satisfactory results (VAS>4)
Subacute pain
Yes
Chronic pain
Interlaminar corticosteroid administration
Confirmation of the presumed causative level with a selective diagnostic block
Pulsed radiofrequency treatment adjacent to the cervical dorsal root ganglion (DRG)
Poor or short lasting result
Conventional radiofrequency adjacent to the cervical DRG
Poor result
Consider study-related SCS
Figure 4. Practice algorithm for the treatment of cervical radicular pain.
12 • van zundert et al.
Cervical epidural infiltrations are preferably carriedout with the patient in a sitting position. The cervicalspinal column is bent forwards. The skin is disinfected.For positions C5 to C6 or C6 to C7, the anesthetistplaces his middle and index fingers on both sides of thespinous processes.67 After a midline needle placement“down the barrel,” with the needle firmly fixed, theoperator can switch to a lateral view and very slowlyadvance the needle as it approaches the base of thespinous processes, while concomitantly using a glasssyringe loss of resistance or alternatively using hangingdrop technique under fluoroscopic guidance.66
A small amount of contrast dye can be injected inorder to ensure the correct epidural placement of theneedle using fluoroscopy. When the needle is correctlyinserted, a syringe containing the administration solu-tion is attached. Aspiration is carefully carried out inorder to identify cerebrospinal fluid or blood.
Larkin et al.68 described another technique, using astyletted catheter that is placed in the potentially saferarea of the T2 to T4 epidural space and advancedtoward the desired cervical root with continuousfluoroscopy.
An important warning was recently published byRacz and Heavner about the risks of generating highpressure in the epidural space if the flow is obstructed.They stress the need for ensuring transforaminal outletflow and recommend immediately flexing and rotatingthe patient’s head upon the first signs of spinal cordischemia.69
(Pulsed) Radiofrequency Treatment61
Diagnostic Blocks. After the clinical diagnosis of cer-vical radicular pain is made, confirmation of the mostaffected segment is carried out using diagnostic selectivenerve root blocks. The patient is placed in supine posi-tion on a translucent operation table. The C-arm of thefluoroscope is placed such that the beam is parallel tothe axis of the intervertebral foramen. The axis points25 to 35° oblique and 10° caudally. In this way, theentry point is determined by the projection of a metalruler over the caudal part of the intervertebral foramen.A 60-mm 24G neuroradiography needle is introducedparallel to the beam (tunnel view). Then the beam direc-tion is changed to the anteroposterior position and theintroducer needle is further introduced until the tip isprojected just laterally to the facet column. When thesegmental nerve is identified using 0.4 mL iohexol con-trast dye, 0.5 to 1.0 mL lidocaine is slowly injected
around the nerve. Overflow into the epidural space isavoided by “real time” observation of the radio-opaquemixture (Figure 5). The pain relief is observed for 30minutes after the infiltration. A positive diagnostic blockprovides at least 50% pain relief.
PRF Technique—Placement of the Electrode. Theentry point is determined in the same way as for diag-nostic blocks, by projecting a metal ruler over the caudaland posterior part of the intervertebral foramen. Thecannula (22G SMK-C5 needle 51 mm with 4 mm activetip. Cotop International B.V., Amsterdam, the Nether-lands) is introduced parallel to the beam and if requiredthe direction is corrected while the cannula is still in theuppermost subcutaneous layers. The correct position isreached when the cannula is projected as a point on thescreen (Figure 6). This point must lie just above thedorsal part of the intervertebral foramen. This is thetransition between the middle and most caudal thirdpart of the neural foramen. This position is chosen inorder to avoid possible damage to the vertebral arterythat runs anterior to the intervertebral foramen. Thedirection of the beam is then changed to anteroposteriorposition and the cannula is moved up further until thetip is projected over the middle of the facetal column(Figures 7 and 8).
Figure 5. Interlaminar epidural corticosteroid administrationC6-C7, lateral view.
4. Cervical Radicular Pain • 13
The stylet is then exchanged for an RF electrode. Theimpedance is measured in order to check if a closedelectrical circuit is present. Then stimulation is started at50 Hz in order to determine the sensory stimulation
threshold. The patient must feel a tingling at less than0.5 V. This indicates that the tip is in close proximity tothe DRG.
Pulsed Radiofrequency Treatment. The RF current isdelivered in small bursts at 45 V; this output can alwaysbe adjusted if the temperature rises above 42°C. Forty-two degrees is the maximum temperature, but not theobligatory temperature to be reached. The pulsedcurrent is delivered for 120 seconds.
IV. SUMMARY1. There is no gold standard for the diagnosis of
cervical radicular pain.2. Case history and clinical examination form the
cornerstones of the diagnostic process.3. Medical imaging, with a slight preference for
MRI, is indicated when specific pathologiesand/or abnormal neurologic symptoms aresuspected.
4. The suspected level can also be confirmed usingdiagnostic selective nerve root blocks.
5. Whenever conservative treatments fail:• With (sub)acute cervical radicular pain,
interlaminar corticosteroid administration isrecommended
Figure 8. Cervical DRG procedure: needle is in the middle of thefacetal column in AP view.
Figure 6. Anteroposterior uptake after injection with contrastdye. The needle and the spread of the contrast dye.
Figure 7. X-ray detection with the C-arm in the lateral obliqueposition. The needle in the posterior caudal quadrant of theneuroforamen.
14 • van zundert et al.
• With chronic cervical radicular pain,PRF adjacent to the DRG is recommended.
6. If these therapies fail, study-related spinal cordstimulation can be considered.
ACKNOWLEDGEMENT
The authors thank N. Van den Hecke for literaturesearch and coordination. This review was initially basedon practice guidelines written by Dutch and Flemish(Belgian) experts that are assembled in a handbook forthe Dutch speaking pain physicians. After translation,the manuscript was updated and edited in cooperationwith U.S./international pain specialists.
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