ON THE OCCURRENCE OF NEUROPATHICARTHROPATHIES IN PERNICIOUS ANAEMIA

BY

PENTTI I. HALONEN and KLAUS A. J. JARVINEN

From the Third Medical Clinic of the University ofHelsinki* andfrom the Hospital of the Wihuri Research Institute

Among the admissions to our clinic there was acase of severe anaemia perniciosa myelosis (subacutecombined degeneration of the spinal cord) associatedwith painless joint disease. The tendon reflexes ofthe lower limbs were lost, there was considerabledecrease in pain sensibility and deep sensibility, andthe gait was markedly ataxic. The x-ray findingsrevealed alterations in the joints, and particularly inthe knee bone a close resemblance to neuropathicjoint changes. These alterations suggested to theradiologist that tabes dorsalis might be present inthis case. Since the possibility oftabes was excludedby thorough examination, the suspicion arose thatthe patient's joint changes, which so closely resembledneuropathic ones, might be attributed to myelosisfunicularis.As we have not been able to find in the literature

descriptions of joint deformation associated withanaemia perniciosa myelosis, we consider a pre-sentation of our investigation of this problem to bejustified.

Discussion on Anaemia Perniciosa MyelosisIt is known that pernicious anaemia often pre-

sents cfegenerative changes in the spinal cord, whichcondition is called myelosis funicularis. Datayielded by detailed histological examination andpresented in various textbooks give evidence ofpatho-anatomical alterations in the spinal cord inup fo 90 per cent. of cases of pernicious anaemia.Clinical evidence of myelosis is markedly lessfrequent, being present, according to variousauthors, in from 8 to 30 per cent. With regard totheir location and histological picture, these changes-which may be very pronounced-bear resemblanceto tabetic changes in the spinal cord. Also theclinical picture of perniciosa myelosis is similar to

* Director, Professor Osten Holsti, M.D.

that of tabes. The literature actually points outthe tabetiform manifestations of perniciosa myelosis.The fact being that the spinal alterations in perni-ciosa myelosis and the clinical picture of thiscondition bears such close resemblance to thecorresponding changes and signs in tabes, it seemsreasonable to assume that perniciosa myelosis alsomight present changes in the joints similar to thosein tabes. This belief is given additional supportby the observation that the lesion of the spinal corddoes not seem to be of necessity a strictly specificone in order to produce a neuropathic joint lesion.The literature describes cases in which spinal changes,due to a variety of causes, are responsible for thistype of joint lesion: for example, traumatic orsubacute myelitis, trauma from tumour, or constantcompression of the spinal cord resulting fromtuberculous spondylitis. It has been found thateven a peripheral nerve lesion or cerebral paralysishas led to such a joint lesion (Pribram, 1902).Neurogenic arthropathy has also been foundassociated with diabetic neuropathy (Forster andBassett, 1948). In addition to tabes, we maypossibly mention syringomyelia as the best knownof all the agents of neuropathic arthropathies.

Material of the Present InvestigationOur material consists of fifty-two established cases

of pernicious anaemia. Most of these patientshave received repeated hospital care. Clinicalsymptoms of myelosis were present in twelve. Allsyphilitic patients have been exclude4 from thematerial by careful histories and by repeatedblood analysis, as well as by liquor tests in cases ofmyelosis. All patients were subjected to systematicx-ray examinations of the knee and hip joints.The distribution of our material and the revealedjoint changes are shown in Tables 1 and 2.

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NEUROPATHIC ARTHROPATHIES IN ANAEMIA

TABLE 1CASES OF PERNICIOUS ANAEMIA WITHNO SIGNS OF MYELOSIS FUNICULARIS

Age Sex of p iraction X-ray changes in joints *anaermiainIyears Hips KneesIl_~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

78777776767573727171717170696968686867666666666565646363635957575555535150454136

FFFFFFM

FFFFF

FFM

FM

FFFFM

M

FFFF

FF

M

FM

M

M

FF

FM

F

39972375

20286

203219

201229

203

172S

18214813

1135269

0

+

+

0

0

0

0

0

0

0

+

0

0

0

+

+

0

0

0

0

0

0

0

0

+

0

0

0

0

0

+

0.

+

0

+

++

0

0

0

0

0

+

0

0

0

0

+

0

0

0

++

0

0

0

0

0

+

++

+

* The joint changes have been assessed as follows:O No pathological changes in the joints.+ Changes considered to be manifestations of mild osteo-

arthritis.++ Marked changes of osteo-arthritis.

+++ Excessive joint changes. Severe manifestations of osteo-arthritis with additional presence of loose fragments in thevicinity of the articular surfaces. The interarticular spaceis, as a rule, markedly narrowed or entirely lost. Theremay be a tendency toward subluxation of the joints.

We have attempted to make the classification ofthe x-ray findings showing the various degrees ofalteration as objective as possible by letting theradiologist carry out the grouping only on the basisof the radiographs presented to him, withoutany information whatever about the clinicalexaminations.

Discussion of our FindingsAs will be seen from the two Tables, it is in

cases of myelosis funicularis that joint changesmost frequently occur, and indeed all the mostserious changes in the knee joint fall into the groupof severe myelosis. Quite naturally our patients,most of whom were old people (the average ageof those without myelosis being 64 years, thosewith mild myelosis 63, and those with severemyelosis 66 years) also presented changes in thejoints attributable to other causes, particularly tosimple osteo-arthritis of old age. The frequency ofthe joint changes and the severity of the alterationsin the knee joints being appreciably greater in thegroup with myelosis than in those with other typesof pernicious anaemia (according to the controlmaterial), we find it reasonable to assume that thecondition of myelosis funicularis and the presenceofjoint changes bear a causal relation to each other.For the reasons offered above the theory of aneuropathic aetiology for these changes seemsjustified. This view is supported by the frequencyof joint changes in perniciosa myelosis, by theirscarcity in other types of pernicious anaemia, andparticularly by the x-ray picture of the extremechanges concerned, which is similar to those ofother known cases of neuropathic arthropathies:severe changes of osteo-arthritic type, the appearanceof osteoplaytes, marked narrowing of the inter-itrticular space, loose fragments found in the vicinityof the joint surfaces, and a tendency to developsubluxation (Figs. 1 and 2). We do not considerthat the fact that the joint changes described do notappear in every single instance of myelosis con-tradicts our view (in two serious cases of myelosisthere were no recognizable changes in the joints).Tabes and syringomyelia, for instance, as far as weknow, present simultaneous severe neuropathicjoint changes relatively seldom.A view generally held, and confirmed particularly

by animal tests (Katsuki, 1936), is actually that alesion of the nerve fibres alone cannot be respon-sible for neuropathic arthropathies. Additionalagents, such as local trauma, metabolic disorder,etc., are needed to produce them. We think ithas not been possible to carry out an analysis ofsuch additional factors on account of the scantymaterial available.The clinical picture of extensive joint changes

appearing in the knees in the more severe instancesof myelosis is one of marked thickening of the kneejoints and, on flexion, crepitation louder than usual.More pronounced motor disturbances have not

been encountered. In one of the cases of this groupoccasional locking of the kneee joints occurred

- i..

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ANNALS OF THE RHEUMATIC DISEASES

TABLE 2CASES OF PERNICIOUS ANAEMIA WITH SIGNS OF MYELOSIS FUNICULARIS-

Duration of the signs RadiographicAge Sex Duration of pernicious of myelosis funicularis changes in jointsanaemia in years in years Hp ne

GroupA 71 F 8 2 0 070 M 1 1 ++ +68 M 6 >2 +* ±61 F 13 >1 ++ +43 F 19 7 + 0

Group B 71 F >1 >1 +±+69 F 17 >2 + +67 F 23 2 + +66 F 10 >5 + +++64 M >3 >3 ++ +64 F 10 >1 + +++62 F >1 >1 0 0

Group A.-Slight cases of myelosis funicularis with distinct reflex disturbances. As a rule, a marked uncertainty or loss of tendon reflexes inthe lower extremities, and a distinct decrease of pain and deep sensibility. Walking fairly normal.Group B.-The more serious forms of myelosis funicularis. Tendon reflexes of the lower extremities completely lacking. Walking distinctlyataxic. Pain and deep sensibility markedly decreased.

very late in the patient's history. Alterations inthe hip joints in the presence of myelosis have, as arule, produced no manifest cinical symptoms. Nopainful joints have been seen in the presence ofarthropathies associated with perniciosa myelosisand this is true ofneuropathic joint lesions in general.It is the absence of pain symptoms that presumablyexplains the fact that, as far as we know, no attentionhas formerly been paid to these marked alterationsin the joints.

Since, according to what has been said above, itseems reasonable to believe that neuropathic changesin the joints may develop pernicious anaemiaassociated with myelosis funicularis, we think itmore justified than ever before to call attention tothe prevention and treatment of myelosis funi-cularis.

SummaryOur investigations comprised fifty-two cases of

pernicious anaemia, five of which showed mildmyelosis funicularis and seven a severe type of thedisease. Joint changes, particularly in the knees,were seen in the presence of myelosis, and the mostextensive changes were found in the cases of severemyelosis. In two cases, however, no-or onlyslight-joint changes were seen. In cases withoutmyelosis there were comparatively few and onlymild joint lesions. In the opinion of the writers the

joint changes detected are both clinically and radio-logically of the type of neuropathic arthropathies.

REFERENCESEhrlich, P., and Lazarus, A. (1898). " Die Anaemie."

Nothnagels spez. Path. Ther., vol. 8, Vienna.Forster, D. B., and Bassett, R. C. (1947). Arch. Neurol.

Psychiat., Chicago, 57, 173.Katsuki, S. (1936). Z. klin. Med., 130, 567.Pribram, A. (1902). " Chronische Gelenkrheimtismus

und Osteoarthritis deformans." Nothnagels spez.Path. Ther., vol. 7, Vienna.

Sur la Frequence des Arthropathies Nerveusesdans lAn6mie Pernicieuse

RSSUMÆNos recherches ont port6 sur cinquante-deux cas d'an6

mie pernicieuse dont cinq presentaient une l6g6re scl6rosesyst6matis6e et sept une forme plus grave de la maladie.On a observe des lesions articulaires, particulierementdans les genoux, chez les malades atteints de scl6rosem6dullaire, et ce sont les sujets les plus gravementatteints qui presentaient les l6sions les plus etendues.Deux malades ne presentaient cependant que des l6sionsarticulaires tr6s l6g6res ou pas de lesions. Les autres casd'an6mie pernicieuse ne pr6sentaient que des lesionsarticulaires relativement peu nombreuses et peu marqu6es.Les auteurs considerent que les l6sions articulairesobserv6es appartiennent cliniquement et radiologique-ment a la cat6gorie des arthropathies nerveuses.

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NEUROPATHIC ARTHROPATHIES IN ANAEMIA

FIG. 1 and 2.-Radiographs of a patient, aged 66, who has been suffering from anaemia perniciosa for tenyears and has had a strong myelosis funicularis for the last five years. There are severe changes of osteo-arthritic type, especially in the right knee. Note also the appearance of osteophytes, marked narrowingat the interarticular spaces, and loose fragments in the vicinity of joint surfaces.

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ILLUSTRATIONS TO ARTICLE BY WOLFSON AND ALTER

FIG. l.-Electrocardiogram taken on July 3, 1947, showing left axis shift and aQRS duration of 0 11 second in lead II, but considered normal.

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ILLUSTRATIONS TO ARTICLE BY WOLFSON AND ALTER 157

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158 ILLUSTRATlONS TO ARTICLE BY WOLFSON AND ALTER

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