Ann. rheum. Dis. (1974), 33, 526

Atlanto-axial subluxation in rheumatoidarthritisA 5-year follow-up study

J. A. MATHEWSFrom the Department ofRheumatology, St. Thomas's Hospital, London SEI 7EH

In 1969 the results of a survey of atlanto-axialsubluxation in all seventy-six consecutive rheumatoidpatients attending a clinic were published (Mathews,1969). Abnormal separation of the odontoid processfrom the anterior arch of the atlas was found innineteen (25%) patients and was found to be morecommon in patients with more serious forms of thedisease. In addition, an abnormal vertical relationshipof the tip of the odontoid process to the base of theskull was found in six (8%) patients. A curiousdiscrepancy between the amount of subluxation andthe presence of neurological damage led to thesupposition that this finding could often be relativelyinnocuous and indicated the need for a follow-upstudy to clarify the natural history of rheumatoiddisease in this region.

Material

Originally patients were included if they satisfied theA.R.A. criteria for definite rheumatoid arthritis, andseventy of the 76 patients had at least one additionaldiagnostic feature. To establish the technique and itsnormal values, 28 control subjects matched for ageand sex were also examined. After 5 years an attemptwas made to review all patients. Fifty-four (74%Y.) werefound and re-examined radiologically and all but one ofthese clinically. Sixteen patients (21 Y) had died, but inno case was this thought to be related to cervical disease,and six patients (8 Y) were lost to follow-up, including onewho was examined clinically but declined to wait forradiological examination.

Fig. 1 shows the percentage of patients with eachamount of anteroposterior atlanto-axial separation in theoriginal study and the percentage follow-up achieved. Itshows that the 22 (29 %O) patients lost were not concen-trated into any particular group. The mean duration offollow-up was 5 years 5 months, the range being 4 years7 months to 6 years 1 month.

Method

This was identical to that of the original study. All patientswere again questioned about cervical and neurologicalsymptoms, the cervical spine and nervous system were

Accepted for publication May 2, 1974.

100 At start lost90

ElAyer

80 LJAtSyears dead70bO.0

0

00-30-20-100~

uptol 2 3 4 5 6 b+totalAtlanto-axial separation (mm)

FIG. 1 The total follow-up is shown with the percentageachieved in each category ofatlanto-axial separation

examined, and a midline lateral tomogram taken centredon the odontoid process with the upper cervical spine infull active flexion. The midline films were again traced andmeasurements compared with those at the start of thestudy. In practice it was found that errors could beminimized and more accurate assessment of change madeby direct comparison of the films and direct measurement.By this technique changes of 1 mm or more were thoughtto be significant.

Results

ANTEROPOSTERIOR SUBLUXATIONAlteration in the atlanto-axial separation is recordedin Fig. 2. The gap increased in nine patients by thefollowing amounts: 1 mm in 5; 2 5 mm in 2; 3 mmand 4 mm in I each. Fig. 3 illustrates an increase of2-5 mm. 'Clunking', the 'palate sign', and 'abnormallaxity' are all clinical signs thought to be specific foranteroposterior instability. They were again foundto be unreliable, only one sign being positive in eachof three patients. Thirty-eight patients had noalteration in the separation and seven actuallyshowed a decrease. It can be seen from Fig. 2 thatwhereas the patients with increased or unchangedmeasurements are scattered throughout the groups oforiginal measurements, those with decreased separa-tion all started the study with substantial subluxation.

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Atlanto-axial subluxation in rheumatoid arthritis 527

Original measurement (mm): up to 1

Alteration increase

in 5 unchanged

years decrease

Total

2 3 4 5 6 6+ total

O 0*o 0 ooO 0 o 0

0 000:.v0 0@0000 0 0 9

000 @0 0 38

0 0 0 000 00 0 @0 7

0 10 26 8 5 2 3 54

FIG. 2 Alteration in atlanto-axial separation over the period of study. All patientswhere vertical shift has occurred o. Measurements are in mm

FIG. 3 This shows an increase in anteroposterior separation from 2S5 to 5 0 mm. There is no vertical shift

V'ERTICAL SUBLUXATIONApparent vertical shifting of the odontoid process(really a descent of skull and atlas) actually occurredmore often than anteroposterior subluxation and wasfound in eighteen patients (Table I). This group canbe seen from Fig. 2 to include five patients whoseanteroposterior separation had increased, seven in

Table I Alteration in vertical subluxation ofodontoidprocess during study

Increased 18 Into foramen magnumUnchanged 36 Start 6Decreased 0 5 yrs 10

Total 54

Increase= apparent rise of tip of odontoid process in relation toforamen magnum.

whom it was unchanged, and six out of seven inwhom it had actually decreased. In ten patients thetip of the odontoid process was actually at or throughthe foramen magnum compared with six at the startof the study, a situation which is always abnormaland was not found in control subjects. Fig. 4 is anexample of a patient whose odontoid process shifted7 mm passing through the foramen magnum.A total of 22 patients had radiological alter-

ation in the upper cervical region during the courseof the study shown by shift in an anteropos-terior, vertical, or both directions. The relevantfeatures of these patients are shown in Table II, andas might be expected, there is a positive relationshipto neck pain, seropositivity, rheumatoid nodules, andthe administration of steroids. In particular, sevenout of eight patients with mutilating changes inperipheral x-rays showed an alteration.

are represented by 0 except

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52.8 Annals ofthe Rheumatic Diseases

j. ,.=I

FIG. 4 In this patient there is vertical shift of 7 mm-from 3 mm below to 4 mm above the foramen magnum. At thesame time the anteroposterior separation has increasedfrom 3*0 to 6*0 mm

Table HI Various features related to increase ofanteroposterior and vertical subluxation

Finding Pain Serology Erosions Nodules Steroids

+ + ++H + + _ + _

No. of patients 32 22 39 15 8 43 13 41 11 43Increased subluxation

no. 16 6 18 4 7 18 8 14 6 16% 50 27 46 27 88 42 61 34 55 37

NEUROLOGICAL SIGNSMany patients had minor and apparently trivialneurological signs and in practice the presence of anextensor plantar response was necessary to provideconvincing evidence of long tract damage. At thestart of the study, five of the 76 patients had suchsigns and of these three had anteroposterior sub-luxation and one vertical subluxation in addition.By the time of follow-up, two of these had died butsix more had developed long tract signs, making a

total of eleven. Of the nine patients available atfollow-up, seven had abnormal anteroposteriorseparation, five vertical subluxation, only one beingnormal in both respects (Table III). When thenumbers of patients with pyramidal signs are

expressed as a proportion of those with a radiologicalabnormality it can be seen (Table IV) to vary fromthree out ofnineteen with anteroposterior subluxationat the start, to five out of ten with vertical subluxationat follow-up.

Discussion

The high incidence of atlanto-axial subluxationreported by Conlon, Isdale, and Rose (1966),Mathews (1969), and Meikle and Wilkinson (1971)emphasized the need for further knowledge about thenatural history of this condition so that unnecessarytreatment for this apparently alarming conditioncould be avoided and treatment concentrated whereneeded.A 6-year follow-up report was published by

Isdale and Conlon (1971), who traced 171 of theiroriginal 333 patients. The incidence of antero-posterior subluxation in this radiological follow-upmore than doubled from 38 to 79 cases. Verticalsubluxation was not mentioned and neurologicalfollow-up was incomplete, but no patient showedevidence of gross neurological damage. Smith, Benn,and Sharp (1972), in a large study, examined 962inpatients of whom 150 had cervical subluxation

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Atlanto-axial subluxation in rheumatoid arthritis 529

Table IH Radiological measurements ofallpatients with long tract signs

Patients with pyramidal signs

Atlanto-axial separation

Before After

Signs at startCase 1

2345

Signs at 5 yrsCase 6

7891011

4.51*03-05-02*0

2*03.54.56-03-04.5

Total 11Anteroposterior subluxationVertical subluxation

3*05*01.5

2-04*03.56-06-05*0

85

Vertical subluxation

Change Before After

0

0

-05

0

0-5-10

+3+0-5

-3-3-10

0

-1*5

-24.5

-3-6-3-2

-10+20

-2-3+3+5*+4-2

4-both2-neither

* Spurious underestimate due to bony destruction.

Table IV Number of patients with subluxationshowing long tract signs

At start

Total Proportion with long tract signs

73/19 with anteroposterior1/6 with vertical

5-year follow-up 547/21 with anteroposterior

< 5/10 with vertical

and twenty evidence of cord damage. Taking the130 without cord damage at the outset, they dis-covered 91 patients with anteroposterior atlanto-axial subluxation, nine with vertical subluxation, and85 with subluxations at other cervical levels. Unfor-tunately this study only made use of subjectivemethods for assessing vertical subluxation. Eighty-four of these patients survived an average follow-uptime of 7-8 years. Of these, 55 patients started withanteroposterior subluxation and their radiologicalprogress over this period was recorded. They notedthat nineteen deteriorated, 28 were unchanged, andeight 'improved or recovered', including five inwhom no residual subluxation was visible. Nine oftheir original 130 patients showed vertical subluxationand this increased to nineteen of those completingthe study. Four patients with anteroposteriorsubluxation developed cord signs and one of thesewho died tetraplegic also had vertical subluxation.''The authors commented that vertical subluxationusually follows anteroposterior subluxation.Although their study differs from that reported in

this paper, both in selection and methods ofexamina-tion of patients, it gives an idea of the likelihood ofcord damage developing-and incidentally theuselessness of collars (types not specified) in prevent-ing it. It draws attention to diminishing antero-posterior atlanto-axial subluxation which is attri-buted to 'spontaneous recovery'.

In the study reported here a 71 % follow-up wasachieved. Deterioration in the anteroposterior re-lationship of atlas to axis was found in nine of the 54patients (one-sixth) and in the vertical relationship ineighteen patients (one-third)-although by no meansall of these patients either became radiologically ab-normal or, more important, developed long tract signs.The majority of patients with long tract signs did haveradiological abnormalities in the cervical spine but itcannot be claimed that these were always causally re-lated. In most patients the amount of disabilitydid notjustifymore extensive neuroradiological investigation,although one patient (Case 9, Table III) developedsevere and progressive quadriparesis and was foundalso to have a compressive midcervical subluxation.Foramen magnum decompression and midcervicalfusion were performed with considerable relief. Itwould be useful clinically if the patients at highestrisk could be detected. and in this respect it seems thatmutilating peripheral joint disease is closelyrelated; bycontrast, theabsence ofpain attributable to the cervicalspine by no means excluded radiological deterior-ation. This study also strongly suggests that the 'spon-taneous recovery' referred to above is an illusionand really represents vertical deterioration in ajoint already the site of marked anteroposterior

Change

0+2+1-5

0+1.5+6+25*+70

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530 Annals ofthe Rheumatic Diseases

subluxation. Evidence of this is provided by thefinding that six out of seven apparent anteroposteriorimprovements were accompanied by vertical shiftof the odontoid process, and it may well be that moresuch patients are included in the group whoseanteroposterior measurement remained unchanged,i.e. the effects of anteroposterior and vertical shifthave 'cancelled out'. One of the six patients withlessening anteroposterior subluxation is illustrated inFig. 5 where clearly the effect is that of pushing aconical peg into a round hole.

Cervical myelopathy has been reported by Stevens,Cartlidge, Saunders, Appleby, Hall, and Shaw(1971) to occur in two-thirds of patients with atlanto-axial subluxation, but assessment of subjective signsmakes comparison between different studies difficult.Certainly this report indicates a similar risk (evenusing stricter neurological criteria) in anteroposterioratlanto-axial subluxation and an even higher risk invertical subluxation-whose mechanism, possiblesevere sequelae, and management were reported inthree cases by Swinson, Hamilton, Mathews, andYates (1972).The variable and not universally poor prognosis of

patients with atlanto-axial subluxation makes itunnecessary and unkind to subject all to uncomfort-able and restricting collars. My view is that thesepatients should be kept under review, the neckimmobilized as best possible if signs of cord damagedevelop, and surgery as described by Crellin, Mac-cabe, and Hamilton (1970) be undertaken if controlis not achieved.

Summary

A 5-year follow-up study of the clinical and radio-logical changes relating to the atlanto-axial joint ina group of 76 rheumatoid patients is discussed. Of the54 patients completing the 5-year study, one-third ofthose with anteroposterior and half of those withvertical subluxation had long tract signs, often arisingin patients with severe disease. A policy for avoidingunnecessarily restrictive treatment of the remainderis suggested. An original explanation for apparentimprovement is anteroposterior subluxation isadvanced.

I am grateful to Dr. J. W. Pierce and the Department ofRadiology for their co-operation, and Mr. T. Brandonand the Photographic Department for the illustrations.

DISCUSSION

DR. D. R. SWINSON (King's) There is some anecdotalevidence and you presented some more evidence to suggestthat patients with vertical atlanto-axial subluxation farebadly compared with ordinary forward subluxation of theatlas. Have you any more figures to confirm or refute thisimpression?

DR. MATHEWS I hope these are the sort of figures youmeant (Table IV). Remember there were 76 patients at thebeginning of the study and five of these had pyramidalsigns. There were nineteen with anteroposterior sub-luxation and three of those had pyramidal signs. Therewere six with vertical subluxation and one of the six hadpyramidal signs. By the time you get to the end of the

FIG. 5 This pair ofx-rays demonstrates that the lessening ofanteroposterior separation is due to dramatic deteriorationof vertical subluxation (peg-in-hole effect)

I

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Atlanto-axial subluxation in rheumatoid arthritis 531

study the situation really looks quite a bit worse in patientswith radiological abnormalities. We have nine withpyramidal signs out of 54, that is one-sixth. Five out often with vertical and seven out of 21 with anteroposteriorsubluxation have extensor plantars; so a third of theanteroposterior and half of the vertical subluxers haveextensor plantars.

DR. M. THOMPSON (Newcastle) The distance from theposterior aspect of the odontoid to the anterior aspect ofthe vertebral arch seems to be a very important measure-ment. I think you have performed a great service in con-sidering these correlations between anteroposteriorsubluxation and vertical movement. Have you anyinformation on the spinal canal depth?

DR. MATHEWS I did publish in the original survey(Mathews, 1969) the vital statistics of the five patients whohad long tract signs and I didn't find any relationshipexcept possibly in one patient whose canal depth posteriorto the odontoid process was 19 mm. Thus I didn't find anycorrelation between the remaining space for the spinalcord and the development of long tract signs.

DR. D. R. HENDERSON (Guy's) When we looked at agroup of patients with vertical subluxation in Bath wefound that there was a high incidence ofsevere subluxationin the lower part of the cervical spine and that where wefound severe and definite pyramidal signs these seemed tobe almost certainly due to the lower cervical subluxation.We also found cranial nerve palsies and I would like toask if you found these as well and what the lower part ofthe cervical spine in these patients looked like on x-ray?

D R. MATHEWS Thank you for giving me the chance topoint out some of the defects in this study. I cannot reallyconclude that any of these patients developed their

neurological signs because of the x-ray changes. Only afew of them had progressive neurological signs whichwould demand thorough neurological examinationincluding cervical mnyelograms, but I do agree that Ishould really have x-rayed the whole length of the cervicalspine and would do so if starting again. I did a limitedneurological examination and it seemed that the mostrelevant signs might be the absence of a corneal reflex.I examined the corneal reflex in every patient and I didn'tfind that it was absent very often; it certainly did notrelate to any of the x-ray changes.

DR. K. N. LLOYD (Cardiff) In view of the figures thatyou have just shown, the inference is that the longer anyform of subluxation has been present, the more likelythere are to be long tract signs. Further, how were youcertain that these patients were x-rayed in the same degreeof flexion after this 5-year interval?

DR. MATHEWS In the original survey I took great careabout this. I checked reproducibility by x-raying twentyof the patients on a second occasion and, except in twopatients in whom the disease was obviously getting worse,I found that the measured gap didn't alter by more than0-5 mm between one x-ray examination and another. Ialways put the patient's cervical spine into the maximumamount of active flexion until pain or stiffness brought therange to an end. I think it is fortunate that this turnsout to give reproducibility of 0 5 mm. Now when it comesto the 5-year follow-up study, I found that owing to theappearance of erosions the anatomy was often quitealtered so that I could not make the direct tracing com-parison which I would have liked, but I could still put thex-rays side by side and measure gaps of a mm, whichwere incidentally visually obvious. If they were less thana mm I haven't included them as changes in this study.

References

CONLON, P. W., ISDALE, I. C., AND ROSE, B. S. (1966) Ann. rheum. Dis., 25, 120 (Rheurnatoid arthritis of the cervicalspine)

CRELLIN, R. Q., MACCABE, J. J., AND HAMILTON, E. B. D. (1970) J. Bone Jt Surg., 52B, 244 (Severe subluxation ofthe cervical spine in rheumatoid arthritis)

ISDALE, I. C., AND CONLON, P. W. (1971) Ann. rheum. Dis., 30, 387 (Atlanto-axial subluxation: a six year follow-upreport)

MATHEWS, J. A. (1969) Ibid., 28, 260 (Atlanto-axial subluxation in rheumatoid arthritis)MEIKLE, J. A. K., AND WILKINSON, M. (1971) Ibid., 30, 154 (Rheumatoid involvement of the cervical spine:

radiological assessment)SMITH, P. H., BENN, R. T., AND SHARP, J. (1972) Ibid., 31, 431 (Natural history of rheumatoid cervical luxations)STEVENS, J. C., CARTLIDGE, N. E. F., SAUNDERS, M., APPLEBY, A., HALL, M., AND SHAW, D. A. (1971) Quart. J. Med.,

40, 391 (Atlanto-axial subluxation and cervical myelopathy in rheumatoid arthritis)SWINSON, D. R., HAMILTON, E. B. D., MATHEWS, J. A., AND YATES, D. A. H. (1972) Ann. rheum. Dis., 31, 359

(Vertical subluxation of the axis in rheumatoid arthritis)

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