- Email: [email protected]
EARLY DIAGNOSIS OF COMPRESSION OF THE SPINAL CORD BY NEOPLASMS
1220 arthritis of the ankle-joint, in which the changes are limited to the articular margins only because of the nature of the trauma. In any first-class football team the ankle-joints of practically every player will show varying degrees of these changes ; the bony outgrowths will be more definite in the backs who must kick the ball long distances with great force. Despite these changes most players finish their careers free from ankle trouble, unless the joint is subjected to a more severe injury than usual, which serves to determine the onset of symptoms. If a radiograph is taken at the time, small areas of ossification in the ligaments attract attention and the player is said to be suffering from a chipped ankle bone.
Once a player gives up the game, the prognosis in this injury is excellent and no further deterioration occurs. I wish to thank Mr. J. these patients.
,
and we have found no evidence of any further deterioration thereafter. Operation is therefore only undertaken to enable a player to continue at his sport and such being the case is only advised when the individual is anxious to continue or stands to lose financially if he is unable to do so. At operation after opening the capsule of the joint, the bony outgrowth is removed together with any loose bony ossicles. The bony outgrowth in the posterior aspect of the joint is never so large as to require removal, but any loose bony fragments should be dealt with because they may give rise to pain in the back of the joint. A plaster cast is applied for four weeks after operation and this is followed by a period of physiotherapy and graduated exercises. Training is resumed at about the sixth week and the player should be fit to play in eight to ten weeks from the date of the operation. During the past five and a half years, 29 players with this lesion have been treated. Of these, 17 had conservative treatment only ; 12 were able to return to football, and 2 to rugby ; but 3 continued to have pain, and as their football was only a pastime they gave it up. 12 players were operated on, 7 immediately because of the acuteness of symptoms and size of the outgrowths and 5 after failure of conservative treatment. Of these, 11have returned to football; the twelfth continued to have discomfort, and as he was thirty-one years of age he decided to retire.
Summary A study of the condition known as athlete’s or footballer’s ankle indicates that the changes are a traumatic arthritis affecting only the marginal areas of the joint. Conservative treatment is successful provided the changes are not excessive ; in that case, operation is required.
was
in charge of
REFERENCES
Lloyd-Roberts, G. C. (1953) J. Bone Jt Surg. 35B, 627. McDougall, A. (1955) Ibid, 37B, 257. MoMurray, T. P. (1950) Ibid, 32B, 68. Morris, L. H. (1943) Ibid, 25, 220. The Practitioner (1950) 164, 289. Thorndike, A. (1950) Practitioner, 164, 306.
EARLY DIAGNOSIS OF COMPRESSION OF THE SPINAL CORD BY NEOPLASMS
G. F. ROWBOTHAM
Treatment
Thorndike (1950) states that it is possible by means of a modified figure-of-eight bandage to prevent jointligament sprains in all sports that require sudden twisting In these cases we advise such a bandage, or pivoting. or strapping, which undoubtedly supports the joint and diminishes the number of sprains. To be completely effective the bandage would have to be applied so as to interfere substantially with the function of the joint, and this is not practical. When a player first complains of pain in the ankle, conservative treatment should be given a trial ; McMurray (1950) found it ineffective, but with it a number of injuries settle down, and such a trial is justified. The symptoms subside when the patient stops playing, so a period away from the game is advised. If the ankle is swollen a plaster cast is applied for three to four weeks. This is followed by four weeks’ physiotherapy and ankle exercises ; if at the end of this time the joint is free from pain when it is moved passively through its full range, training begins and is graduated until the player has returned to the field. If this conservative regime fails operation must be considered. As I have said, symptoms disappear once the athlete gives up his sport
Patrick, who
B.Sc.
Manc., F.R.C.S.
REGIONAL CONSULTANT IN NEUROLOGICAL SURGERY, GENERAL HOSPITAL, NEWCASTLE UPON TYNE
EXPERIENCE has shown that the early diagnosis of the spinal cord, particularly by benign as meningiomata and neuromata, is one of the most difficult problems which confront a clinician. The classical syndromes are far too often those of the late stages of neural compression, when irreversible damage has already taken place. Between 1941 and 1948, 80 cases of compression of the spinal cord by neoplasms came under my care (table i).
compression of neoplasms such
TABLE
I-CASES OF COMPRESSION OF THE SPINAL CORD BY NEOPLASMS 1941-48
I have analysed thisgroup of cases to determine whether early diagnosis is possible without subjecting every patient suspected of spinal-cord compression to the dangers and discomforts of special investigations.
Primary Neoplasms EXTRAMEDULLARY PRIMARY NEOPLASMS
In this series of 80 cases there were 46 extramedullary neoplasms arising from one of the tissues of the spinal cord (table II). Theoretically it should have been possible to excise the 36 meningiomata and neuromata without inflicting permanent damage on the spinal cord, but unfortunately many of these patients were referred only when serious damage had already occurred. Although complete removal of the neoplasm was possible in 36 cases, only 16 patients regained complete function of limbs, bladder, and rectum. Of the remaining patients 13, although able to carry on useful lives, were left with some locomotor or sphincTABLE II-PRIMARY NEOPLASMS OF THE SPINAL CORD
1221 teric disability, 3 were left with poor functional results, and 3 died from infections after operation. 1 patient was not operated on, because of deep and extensive bedsores.
Memm
cause considerable paraplegia without any accompanying signs or symptoms. Angiomata Angiomata of the spinal cord are often clinically indistinguishable from meningiomata and neuromata. In angiomata the cord may be considerably damaged without any rise in the C.S.F. proteins and without any blocks in the arachnoidal pathways, whereas in meningiomata or neuromata severe compression of the cord is nearly always associated with a positive Queckenstedt test and a raised level of C.S.F. protein. Angiomata elsewhere in the body may point to the correct diagnosis. Straight radiography rarely shows angiomatous changes in the vertebral bodies, and there were negative findings ’
and Neuromata
neoplasms are grouped together because, in stages, they present the same diagnostic and operative problems. Both types of tumour are essentially benign. In this group of cases 4 were situated in the These 2 their early
cervical, 24 in the thoracic, and In 20 cases, the first
8 in the lumbar
symptom
was
severe
area.
pain of
in segmental pain was situated deeply in or near the midline. When the pain was non-segmental there was rigidity of the spine and restriction of movement, and often in each of the 5 cases in this series. tenderness on deep palpation. Pain was always severe. Surgery has little to offer in the treatment of -these Sensory change in a segmental distribution is an in and neoplasms. posterior-root compression, important early sign it is misleading to look for complete loss. When pain Tumours of the Ccz4da Equina was the first symptom, it began many months before Almost all the benign tumours at this site give the limb weakness. Unfortunately, it is in these signless same clinical picture. months that a doctor may decide that there is nothing Since the lumbar-puncture needle may be introduced seriously wrong with his patient, or be tempted to defer above the block, protein values are apt to be low, and a further examination until too late. Should a root pain. Queckenstedt test may give misleading results. Sciatic or central back pain be followed many months later by pain, followed by sphincteric disturbance, weakness, weakness of a limb, the possibility of spinal-cord comand sensory loss in the perineum are indications for pression should be fully investigated, and patients should myelography. never be allowed to become bedridden before special In 2 of the 5 cases in this series, the lumbar-puncture diagnostic tests have been carried out. needle was introduced into the tumour itself and blood By the time paralysis is first noticed, lumbar puncture was withdrawn ; in each case this was dismissed as a will almost certainly show an increase in the proteins of lumbar-puncture failure." This pitfall should always the cerebrospinal fluid (c.s.F.). It is not neoessary be kept in mind when a giant-cell tumour of the cauda for the proteins to have risen to 100 mg. per 100 ml. equina is suspected clinically. to make a diagnosis ; given that the normal protein Spina bifida, associated with progressive spinal-cord content is 40 mg. per 100 ml., a rise to 60 mg. should at the corresponding level, should always compression not be overlooked if there is the slightest suggestion of an underlying embryoma. Such cases were suggest weakness of the legs. In this present group the figure excluded from this series on radiographic.evidence. was over 150 mg. per 100 ml. in all cases. Many tumours of the cauda equina can be successfully Absence of blockage of the c.s.F. pathways (negative removed (as in 3 of the 5 cases in this series) in the early Queckenstedt test) by no means excludes spinal com- stages of the disease. pression. If there is the slightest suspicion of this, INTRAMEDULLARY PRIMARY NEOPLASMS lumbar puncture and Queckenstedt tests should be The clinical picture here is indistinguishable from repeated after four weeks, or sooner if the patient’s that of syringomyelia. In this small group of 6 cases, the paralysis becomes worse. To wait for clear radiographic evidence of bony change common first symptom was a " peculiar feeling somewhere is usually to wait too long. Should a lumbar puncture or in the body " which later developed into sensory loss of Queckenstedt test become positive, or should paralysis the dissociated type. Lower-motor-neurone paralysis advance rapidly, detailed myelographic examination is and wasting of the muscles in the corresponding segments essential. followed the sensory changes. Although the onset of Differential diagnosis.-In 4 cases of this group the paraplegia was late, its progress was rapid. Chemical first symptom was weakness of the legs, unassociated changes in the C.S.F. and spinal blocks were also late with pain, or with sensory or sphincteric disturbance. developments. Surgery was of no value in these cases. Indeed, the diagnosis of disseminated sclerosis was made PRIMARY NEOPLASMS ARISING FROM THE SPINAL COLUMN and sustained by clinicians for periods as long as eighteen In this group there were 3 osteoclastomata, 1 osteomonths. In all of these cases operation proved the and 3 chondrosarcomata. The first symptom in the so that to be chondroma, midline, anteriorly placed neoplasms in each case was severe, persistent pain in the back, and the spinal cord was kinked over the swelling ; the late in every instance there was clear radiographic evidence appearance of sensory disturbances can therefore be of pathological changes in the vertebral before paralysis when the Even was explained anatomically. neoplasm became advanced. Early diagnosis in these cases is made to the referable posteriorly placed, sensory changes by radiography. Operation and decompression should long tracts were often late in appearing. The c.s.F. proteins increase early in anteriorly placedbe carried out at the first sign of spinal-cord compression, neoplasms. In disseminated sclerosis the early changesi if the neoplasm is thought not to be highly malignant. are in the Lange curve, and not in the protein content. A satisfactory result was obtained with 1 osteoclastoma The prodromal signs and symptoms of disseminatedIin my group. sclerosis have been described by McAlpine (1955) ; but; Secondary Neoplasms when there is the slightest doubt about the diagnosis; In the 20 cases of compression of the spinal cord by repeated lumbar punctures and protein estimations areBsecondary deposits the primary growths were situated as follows : bronchus, 7 ; prostate, 6 ; breast, 5 ; kidney, necessary. In cases of progressive paralysis unassociated withL 1 ; and stomach, 1. other signs, the possibility of a parasaggital meningiomaIIn 18 cases the nature of the lesion was known before must be considered. When such a tumour is presentt the spinal cord became affected. In 12, bony deposits radiographs of the skull will show enostosis, or enlarge- or erosion were revealed by radiography, and in 4, ment or multiplication of the diploic channels and1 although there was no bony change, cancer was known meningeal grooves. A parasaggital meningioma can1 to be present somewhere in the body. In the remaining
obvious
or
posterior-root distribution, and
12 the
"
,
-
1222 2 cases, it
was impossible to establish the nature of the lesion before laminectomy. In these cases, biopsy established that the growths were of prostatic and renal origin. In the prostatic case the first symptom was a deep, boring pain between the shoulder-blades ; and in the renal case it was non-segmental pain on the left side of the body, with weakness of the legs. Root pain is commonly the first symptom of a neoplasm arising in the posterior abdominal or thoracic wall. The growth tends to enter the spinal canal through the intervertebral foramina and wrap itself round the spinal theca, not only crushing the cord, but also strangling its foraminal blood-supply. Ischaemia as much as constriction of the cord accounts for the neural changes, and this explains why decompression and removal of the growth so rarely relieves the symptoms. The purpose of operation is usually to relieve pain.
Discussion
malignant constriction of the spinal cord by a silent primary neoplasm the neurological signs are much the same as those caused by the compression of a primary benign neoplasm. But in cancerous cases the patient may be fully paralysed within a few days of the first signs of weakness ; whereas in cases of benign neoplasm the paralysis develops slowly over months or even years. It is impossible to identify the origin of spinal-cord compression by the first symptom. A persistent pain of root distribution suggests a physical origin, and aggravation by straining or coughing confirms this. At the other end of the scale is the picture of complete paralysis, of gross sensory loss, of sphincteric paralysis, of decubitus ulcers, and of ascending infection of the kidneys. A diagnosis should be made as soon as possible after the appearance of the first symptom. Neoplasms that are surgically curable nearly always progress slowly, and it is often possible to make a diagnosis on clinical evidence alone before irreversible damage has been done to the spinal cord. In
I thank Dr. Raymond Whitehead, of the department of pathology of Manchester University, for his helpful criticisms. The preparation of this work was assisted by a research grant from No. 1 Regional Hospital Board. REFERENCE
McAlpine,
D.
(1955) Lancet, i, 1033.
THE NON-ANTIGENICITY OF CHONDROITIN SULPHATE W. C. BOAKE B.Sc., M.B. Melb., M.R.C.P. ASSISTANT,
MEDICAL UNIT
H. MUIR M.A., D.Phil. Oxfd EMPIRE RHEUMATISM COUNCIL FELLOW
MARY’S HOSPITAL, LONDON IT has often been suggested that rheumatic fever and acute glomerulonephritis are due to the fact that the patient’s tissues have become antigenic. This concept has been largely based on the undoubted association between these diseases and antecedent p-hsemolytic streptococcal infection. It is thought that these streptococci react with a normally non-antigenic component of the host’s tissues (generally assumed to be a connectivetissue component in rheumatism), rendering it antigenic. The auto-antibodies thus formed are thought to react in situ with the changed or unchanged body component and so to produce the characteristic local lesions. This hypothesis has never definitely been proved or disproved, although it has been the subject of much experimental work : ST.
Cavelti and Cavelti
(1945) produced glomerulonephritis by repeated injection of dead streptococci together with rat-kidney tissue. At the same time, antibodies were formed against the rat kidney. This work, however, has not been confirmed (Humphrey 1948). McKee and Swineford (1951) injected guineapigs with a vaccine made from dead hsemolytie streptococci and guineapig-joint tissue. No joint or kidney lesions or precipitins
in
rats
were
found.
Glynn and Holborow (1952a) produced arthritis in rabbits by a somewhat similar technique. They injected rabbits with a vaccine prepared from p-hsemolytio streptococci and chondroitin sulphate, a polysaccharide derived from human cartilage. These rabbits developed swollen joints and synovitis. This work differed from similar studies, however, in that Glynn and Holborow prepared their vaccine by incubating chondroitin sulphate with live (-h2emolytic streptococci, because they had already shown that this process conferred antigenicity on normally non-antigenic polysaccharides of vegetable origin (Glynn and Holborow 1952b).
We thought that their technique might be valuable on rheumatism. We therefore repeated this work doing so, used rabbit protein-free chondroitin
in work but, in
and a larger number of rabbits. (Glynn and Holborow used only very few rabbits and prepared their vaccine from human chondroitin sulphate.) Although human and rabbit chondroitin sulphate may be identical, nothing is known about the immunological relations of these two substances. To demonstrate auto-antibody production it was clearly necessary to use a substance derived from an animal of the same species as that subjected to the experiment.
sulphate
.
Materials and Methods The methods described by Glynn and Holborow (1952a) were followed closely, and their paper should be consulted.
Potassium Chondroitin Sulphate Chondroitin sulphate was prepared by the method of Einbinder and Schubert (1950) from cartilage obtained from -ears, trachea, and ribs of ten rabbits. Connective tissue and muscle were removed. The cartilage was sliced and suspended in a solution containing 30% potassium chloride and 1% potassium carbonate, and macerated in a Waring blender. It was twice extracted for forty-eight hours with this solution. The product obtained was purified twice more by the method of Einbinder and Schubert (1950) and dried in vacuo over
phosphorus pentoxide. The resultant product contained hexosaminez7%, nitrogen 2 2-15%, and potassium 13.6%. The formula for chondroitin being C14 H19 014 NSK2 2H2O, one would expect to find hexosamine 31.5%, nitrogen 2-45%, and potassium 13-66%. Einbinder and Schubert (1950) found in their potassium chondroitin sulphate from ox trachea hexosamine 22-43-26-36%, nitrogen 207-2-18%, and potassium 10-95-11.3%. The low nitrogen content of the preparation and the fact that it gave a negative Biuret reaction suggest that it contained little, if any, protein. For use in the experiment the chondroitin sulphate dissolved in sterile water in a concentration of (1% zu/v). This was sterilised by Seitz filtration, which led to a loss of 30% of the material, determined by nitrogen estimations on the filtrate. The sterile solution was therefore considered to contain 0.7% 2u/v of chondroitin sulphate.was
10 mg. per ml.
Preparation of iaceiites A group-A type-4 strain of a p-haemolytic streptococcus was obtained from the National Collection of Type Cultures and cultured for eighteen hours in trypticdigest broth, centrifuged, washed twice with physioby a modification of the method of Elson and Morgan (1933) Determined by the method of Conway (1947).
1. Determined 2.
Once a player gives up the game, the prognosis in this injury is excellent and no further deterioration occurs. I wish to thank Mr. J. these patients.
,
and we have found no evidence of any further deterioration thereafter. Operation is therefore only undertaken to enable a player to continue at his sport and such being the case is only advised when the individual is anxious to continue or stands to lose financially if he is unable to do so. At operation after opening the capsule of the joint, the bony outgrowth is removed together with any loose bony ossicles. The bony outgrowth in the posterior aspect of the joint is never so large as to require removal, but any loose bony fragments should be dealt with because they may give rise to pain in the back of the joint. A plaster cast is applied for four weeks after operation and this is followed by a period of physiotherapy and graduated exercises. Training is resumed at about the sixth week and the player should be fit to play in eight to ten weeks from the date of the operation. During the past five and a half years, 29 players with this lesion have been treated. Of these, 17 had conservative treatment only ; 12 were able to return to football, and 2 to rugby ; but 3 continued to have pain, and as their football was only a pastime they gave it up. 12 players were operated on, 7 immediately because of the acuteness of symptoms and size of the outgrowths and 5 after failure of conservative treatment. Of these, 11have returned to football; the twelfth continued to have discomfort, and as he was thirty-one years of age he decided to retire.
Summary A study of the condition known as athlete’s or footballer’s ankle indicates that the changes are a traumatic arthritis affecting only the marginal areas of the joint. Conservative treatment is successful provided the changes are not excessive ; in that case, operation is required.
was
in charge of
REFERENCES
Lloyd-Roberts, G. C. (1953) J. Bone Jt Surg. 35B, 627. McDougall, A. (1955) Ibid, 37B, 257. MoMurray, T. P. (1950) Ibid, 32B, 68. Morris, L. H. (1943) Ibid, 25, 220. The Practitioner (1950) 164, 289. Thorndike, A. (1950) Practitioner, 164, 306.
EARLY DIAGNOSIS OF COMPRESSION OF THE SPINAL CORD BY NEOPLASMS
G. F. ROWBOTHAM
Treatment
Thorndike (1950) states that it is possible by means of a modified figure-of-eight bandage to prevent jointligament sprains in all sports that require sudden twisting In these cases we advise such a bandage, or pivoting. or strapping, which undoubtedly supports the joint and diminishes the number of sprains. To be completely effective the bandage would have to be applied so as to interfere substantially with the function of the joint, and this is not practical. When a player first complains of pain in the ankle, conservative treatment should be given a trial ; McMurray (1950) found it ineffective, but with it a number of injuries settle down, and such a trial is justified. The symptoms subside when the patient stops playing, so a period away from the game is advised. If the ankle is swollen a plaster cast is applied for three to four weeks. This is followed by four weeks’ physiotherapy and ankle exercises ; if at the end of this time the joint is free from pain when it is moved passively through its full range, training begins and is graduated until the player has returned to the field. If this conservative regime fails operation must be considered. As I have said, symptoms disappear once the athlete gives up his sport
Patrick, who
B.Sc.
Manc., F.R.C.S.
REGIONAL CONSULTANT IN NEUROLOGICAL SURGERY, GENERAL HOSPITAL, NEWCASTLE UPON TYNE
EXPERIENCE has shown that the early diagnosis of the spinal cord, particularly by benign as meningiomata and neuromata, is one of the most difficult problems which confront a clinician. The classical syndromes are far too often those of the late stages of neural compression, when irreversible damage has already taken place. Between 1941 and 1948, 80 cases of compression of the spinal cord by neoplasms came under my care (table i).
compression of neoplasms such
TABLE
I-CASES OF COMPRESSION OF THE SPINAL CORD BY NEOPLASMS 1941-48
I have analysed thisgroup of cases to determine whether early diagnosis is possible without subjecting every patient suspected of spinal-cord compression to the dangers and discomforts of special investigations.
Primary Neoplasms EXTRAMEDULLARY PRIMARY NEOPLASMS
In this series of 80 cases there were 46 extramedullary neoplasms arising from one of the tissues of the spinal cord (table II). Theoretically it should have been possible to excise the 36 meningiomata and neuromata without inflicting permanent damage on the spinal cord, but unfortunately many of these patients were referred only when serious damage had already occurred. Although complete removal of the neoplasm was possible in 36 cases, only 16 patients regained complete function of limbs, bladder, and rectum. Of the remaining patients 13, although able to carry on useful lives, were left with some locomotor or sphincTABLE II-PRIMARY NEOPLASMS OF THE SPINAL CORD
1221 teric disability, 3 were left with poor functional results, and 3 died from infections after operation. 1 patient was not operated on, because of deep and extensive bedsores.
Memm
cause considerable paraplegia without any accompanying signs or symptoms. Angiomata Angiomata of the spinal cord are often clinically indistinguishable from meningiomata and neuromata. In angiomata the cord may be considerably damaged without any rise in the C.S.F. proteins and without any blocks in the arachnoidal pathways, whereas in meningiomata or neuromata severe compression of the cord is nearly always associated with a positive Queckenstedt test and a raised level of C.S.F. protein. Angiomata elsewhere in the body may point to the correct diagnosis. Straight radiography rarely shows angiomatous changes in the vertebral bodies, and there were negative findings ’
and Neuromata
neoplasms are grouped together because, in stages, they present the same diagnostic and operative problems. Both types of tumour are essentially benign. In this group of cases 4 were situated in the These 2 their early
cervical, 24 in the thoracic, and In 20 cases, the first
8 in the lumbar
symptom
was
severe
area.
pain of
in segmental pain was situated deeply in or near the midline. When the pain was non-segmental there was rigidity of the spine and restriction of movement, and often in each of the 5 cases in this series. tenderness on deep palpation. Pain was always severe. Surgery has little to offer in the treatment of -these Sensory change in a segmental distribution is an in and neoplasms. posterior-root compression, important early sign it is misleading to look for complete loss. When pain Tumours of the Ccz4da Equina was the first symptom, it began many months before Almost all the benign tumours at this site give the limb weakness. Unfortunately, it is in these signless same clinical picture. months that a doctor may decide that there is nothing Since the lumbar-puncture needle may be introduced seriously wrong with his patient, or be tempted to defer above the block, protein values are apt to be low, and a further examination until too late. Should a root pain. Queckenstedt test may give misleading results. Sciatic or central back pain be followed many months later by pain, followed by sphincteric disturbance, weakness, weakness of a limb, the possibility of spinal-cord comand sensory loss in the perineum are indications for pression should be fully investigated, and patients should myelography. never be allowed to become bedridden before special In 2 of the 5 cases in this series, the lumbar-puncture diagnostic tests have been carried out. needle was introduced into the tumour itself and blood By the time paralysis is first noticed, lumbar puncture was withdrawn ; in each case this was dismissed as a will almost certainly show an increase in the proteins of lumbar-puncture failure." This pitfall should always the cerebrospinal fluid (c.s.F.). It is not neoessary be kept in mind when a giant-cell tumour of the cauda for the proteins to have risen to 100 mg. per 100 ml. equina is suspected clinically. to make a diagnosis ; given that the normal protein Spina bifida, associated with progressive spinal-cord content is 40 mg. per 100 ml., a rise to 60 mg. should at the corresponding level, should always compression not be overlooked if there is the slightest suggestion of an underlying embryoma. Such cases were suggest weakness of the legs. In this present group the figure excluded from this series on radiographic.evidence. was over 150 mg. per 100 ml. in all cases. Many tumours of the cauda equina can be successfully Absence of blockage of the c.s.F. pathways (negative removed (as in 3 of the 5 cases in this series) in the early Queckenstedt test) by no means excludes spinal com- stages of the disease. pression. If there is the slightest suspicion of this, INTRAMEDULLARY PRIMARY NEOPLASMS lumbar puncture and Queckenstedt tests should be The clinical picture here is indistinguishable from repeated after four weeks, or sooner if the patient’s that of syringomyelia. In this small group of 6 cases, the paralysis becomes worse. To wait for clear radiographic evidence of bony change common first symptom was a " peculiar feeling somewhere is usually to wait too long. Should a lumbar puncture or in the body " which later developed into sensory loss of Queckenstedt test become positive, or should paralysis the dissociated type. Lower-motor-neurone paralysis advance rapidly, detailed myelographic examination is and wasting of the muscles in the corresponding segments essential. followed the sensory changes. Although the onset of Differential diagnosis.-In 4 cases of this group the paraplegia was late, its progress was rapid. Chemical first symptom was weakness of the legs, unassociated changes in the C.S.F. and spinal blocks were also late with pain, or with sensory or sphincteric disturbance. developments. Surgery was of no value in these cases. Indeed, the diagnosis of disseminated sclerosis was made PRIMARY NEOPLASMS ARISING FROM THE SPINAL COLUMN and sustained by clinicians for periods as long as eighteen In this group there were 3 osteoclastomata, 1 osteomonths. In all of these cases operation proved the and 3 chondrosarcomata. The first symptom in the so that to be chondroma, midline, anteriorly placed neoplasms in each case was severe, persistent pain in the back, and the spinal cord was kinked over the swelling ; the late in every instance there was clear radiographic evidence appearance of sensory disturbances can therefore be of pathological changes in the vertebral before paralysis when the Even was explained anatomically. neoplasm became advanced. Early diagnosis in these cases is made to the referable posteriorly placed, sensory changes by radiography. Operation and decompression should long tracts were often late in appearing. The c.s.F. proteins increase early in anteriorly placedbe carried out at the first sign of spinal-cord compression, neoplasms. In disseminated sclerosis the early changesi if the neoplasm is thought not to be highly malignant. are in the Lange curve, and not in the protein content. A satisfactory result was obtained with 1 osteoclastoma The prodromal signs and symptoms of disseminatedIin my group. sclerosis have been described by McAlpine (1955) ; but; Secondary Neoplasms when there is the slightest doubt about the diagnosis; In the 20 cases of compression of the spinal cord by repeated lumbar punctures and protein estimations areBsecondary deposits the primary growths were situated as follows : bronchus, 7 ; prostate, 6 ; breast, 5 ; kidney, necessary. In cases of progressive paralysis unassociated withL 1 ; and stomach, 1. other signs, the possibility of a parasaggital meningiomaIIn 18 cases the nature of the lesion was known before must be considered. When such a tumour is presentt the spinal cord became affected. In 12, bony deposits radiographs of the skull will show enostosis, or enlarge- or erosion were revealed by radiography, and in 4, ment or multiplication of the diploic channels and1 although there was no bony change, cancer was known meningeal grooves. A parasaggital meningioma can1 to be present somewhere in the body. In the remaining
obvious
or
posterior-root distribution, and
12 the
"
,
-
1222 2 cases, it
was impossible to establish the nature of the lesion before laminectomy. In these cases, biopsy established that the growths were of prostatic and renal origin. In the prostatic case the first symptom was a deep, boring pain between the shoulder-blades ; and in the renal case it was non-segmental pain on the left side of the body, with weakness of the legs. Root pain is commonly the first symptom of a neoplasm arising in the posterior abdominal or thoracic wall. The growth tends to enter the spinal canal through the intervertebral foramina and wrap itself round the spinal theca, not only crushing the cord, but also strangling its foraminal blood-supply. Ischaemia as much as constriction of the cord accounts for the neural changes, and this explains why decompression and removal of the growth so rarely relieves the symptoms. The purpose of operation is usually to relieve pain.
Discussion
malignant constriction of the spinal cord by a silent primary neoplasm the neurological signs are much the same as those caused by the compression of a primary benign neoplasm. But in cancerous cases the patient may be fully paralysed within a few days of the first signs of weakness ; whereas in cases of benign neoplasm the paralysis develops slowly over months or even years. It is impossible to identify the origin of spinal-cord compression by the first symptom. A persistent pain of root distribution suggests a physical origin, and aggravation by straining or coughing confirms this. At the other end of the scale is the picture of complete paralysis, of gross sensory loss, of sphincteric paralysis, of decubitus ulcers, and of ascending infection of the kidneys. A diagnosis should be made as soon as possible after the appearance of the first symptom. Neoplasms that are surgically curable nearly always progress slowly, and it is often possible to make a diagnosis on clinical evidence alone before irreversible damage has been done to the spinal cord. In
I thank Dr. Raymond Whitehead, of the department of pathology of Manchester University, for his helpful criticisms. The preparation of this work was assisted by a research grant from No. 1 Regional Hospital Board. REFERENCE
McAlpine,
D.
(1955) Lancet, i, 1033.
THE NON-ANTIGENICITY OF CHONDROITIN SULPHATE W. C. BOAKE B.Sc., M.B. Melb., M.R.C.P. ASSISTANT,
MEDICAL UNIT
H. MUIR M.A., D.Phil. Oxfd EMPIRE RHEUMATISM COUNCIL FELLOW
MARY’S HOSPITAL, LONDON IT has often been suggested that rheumatic fever and acute glomerulonephritis are due to the fact that the patient’s tissues have become antigenic. This concept has been largely based on the undoubted association between these diseases and antecedent p-hsemolytic streptococcal infection. It is thought that these streptococci react with a normally non-antigenic component of the host’s tissues (generally assumed to be a connectivetissue component in rheumatism), rendering it antigenic. The auto-antibodies thus formed are thought to react in situ with the changed or unchanged body component and so to produce the characteristic local lesions. This hypothesis has never definitely been proved or disproved, although it has been the subject of much experimental work : ST.
Cavelti and Cavelti
(1945) produced glomerulonephritis by repeated injection of dead streptococci together with rat-kidney tissue. At the same time, antibodies were formed against the rat kidney. This work, however, has not been confirmed (Humphrey 1948). McKee and Swineford (1951) injected guineapigs with a vaccine made from dead hsemolytie streptococci and guineapig-joint tissue. No joint or kidney lesions or precipitins
in
rats
were
found.
Glynn and Holborow (1952a) produced arthritis in rabbits by a somewhat similar technique. They injected rabbits with a vaccine prepared from p-hsemolytio streptococci and chondroitin sulphate, a polysaccharide derived from human cartilage. These rabbits developed swollen joints and synovitis. This work differed from similar studies, however, in that Glynn and Holborow prepared their vaccine by incubating chondroitin sulphate with live (-h2emolytic streptococci, because they had already shown that this process conferred antigenicity on normally non-antigenic polysaccharides of vegetable origin (Glynn and Holborow 1952b).
We thought that their technique might be valuable on rheumatism. We therefore repeated this work doing so, used rabbit protein-free chondroitin
in work but, in
and a larger number of rabbits. (Glynn and Holborow used only very few rabbits and prepared their vaccine from human chondroitin sulphate.) Although human and rabbit chondroitin sulphate may be identical, nothing is known about the immunological relations of these two substances. To demonstrate auto-antibody production it was clearly necessary to use a substance derived from an animal of the same species as that subjected to the experiment.
sulphate
.
Materials and Methods The methods described by Glynn and Holborow (1952a) were followed closely, and their paper should be consulted.
Potassium Chondroitin Sulphate Chondroitin sulphate was prepared by the method of Einbinder and Schubert (1950) from cartilage obtained from -ears, trachea, and ribs of ten rabbits. Connective tissue and muscle were removed. The cartilage was sliced and suspended in a solution containing 30% potassium chloride and 1% potassium carbonate, and macerated in a Waring blender. It was twice extracted for forty-eight hours with this solution. The product obtained was purified twice more by the method of Einbinder and Schubert (1950) and dried in vacuo over
phosphorus pentoxide. The resultant product contained hexosaminez7%, nitrogen 2 2-15%, and potassium 13.6%. The formula for chondroitin being C14 H19 014 NSK2 2H2O, one would expect to find hexosamine 31.5%, nitrogen 2-45%, and potassium 13-66%. Einbinder and Schubert (1950) found in their potassium chondroitin sulphate from ox trachea hexosamine 22-43-26-36%, nitrogen 207-2-18%, and potassium 10-95-11.3%. The low nitrogen content of the preparation and the fact that it gave a negative Biuret reaction suggest that it contained little, if any, protein. For use in the experiment the chondroitin sulphate dissolved in sterile water in a concentration of (1% zu/v). This was sterilised by Seitz filtration, which led to a loss of 30% of the material, determined by nitrogen estimations on the filtrate. The sterile solution was therefore considered to contain 0.7% 2u/v of chondroitin sulphate.was
10 mg. per ml.
Preparation of iaceiites A group-A type-4 strain of a p-haemolytic streptococcus was obtained from the National Collection of Type Cultures and cultured for eighteen hours in trypticdigest broth, centrifuged, washed twice with physioby a modification of the method of Elson and Morgan (1933) Determined by the method of Conway (1947).
1. Determined 2.