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SPINAL CORD DEGENERATION IN DIVERS
1365 revealed
Preliminary Communication
a
neurological
history of DCS and there
were
no
documented
abnormalities.
Pathological Features SPINAL CORD DEGENERATION IN DIVERS
Necropsies were carried out as soon as possible after death, delays sometimes inevitable because of difficulty in recovering the bodies. Brains (except case 3) and spinal cords were removed and fixed in 10% formol saline. Results of the neuropathological examination of the brains will be reported separately. Whole cords were
A. C. PALMER1
I. M. CALDER2
J. T. HUGHES3
Summary
Spinal
cords from 8 professional and 3 divers who died accidentally were
amateur
examined histopathologically. Marchi-positive degeneration was found in the cords of 3 professional divers, the posterior, lateral, and to a lesser the anterior columns. In 1 there was degeneration of afferent fibres within the posterior columns.
made available from all 11
except case 1 (caudal to C7 11 (Tl to L4 only). Initially, transverse segments were taken from each level of cord, embedded in paraffin wax, sectioned, and stained with haematoxylin and eosin; special stains were used as necessary. As the investigation proceeded we decided to look additionally for tract degeneration by means of the Marchi method. For this purpose the tissue available was limited to four or five intersegmental levels from each cord which had not been processed for paraffin embedded sections. The Marchi method used was that modified by Swank and Davenport -5 both frozen and paraffin embedded sections were prepared.
were
Comparative Neurology, School of Veterinary Medicine, Cambridge;1 Department of Morbid Anatomy, London Hospital Medical College, and Medical Division of Health and Safety Executive, London;2 and Department of Neuropathology, Radcliffe Infirmary, Oxford3 Wellcome Laboratory for
cases
only), case 6 (C5 to T9 only), and case
variously affecting extent
INTRODUCTION
DAMAGE to the spinal cord as a result of decompression sickness ("spinal bends" or type II decompression sickness, DCS) and caisson disease has been documented by several workers including ourselves.l-4 We previously reported a male sports diver who had recovered almost completely from an episode of spinal DCS 4 years before death but who was found subsequently to have extensive morphological changes in the posterior and lateral columns of the spinal cord.4 We have now conducted a histological survey of the spinal cords taken from 8 professional and 3 amateur male divers who had died from diving or non-diving accidents, to ascertain whether some active divers have unrecognised cord degeneration, perhaps as a result of decompression exposures. METHODS
Clinical Records All professional divers in the United Kingdom undergo a comprehensive annual examination that includes a thorough neurological assessment. This examination is carried out by an approved doctor under the Diving at Work Regulations 1981, of the Health and Safety at Work Act 1974. The examination is accepted international basis by both diving companies and divers. Amateur divers also usually have an annual medical examination, which is less rigorous than that required for professionals. If a diver, in his opinion, has suffered from a minor incident of DCS, he may not feel constrained to declare it. All the subjects in this series had been examined within a period of 2 to 38 weeks before death (see accompanying table), except for case 3 who had retired from diving 18 months earlier. Records of the last medical examination were available for all other cases; none on an
5. McAllister RG Jr. Kinetics and dynamics of
nifedipine after oral and sublingual doses. Am J Med 1986, 81: (suppl 6A): 2-5. 6. Kleinbloesem CH, van Harten J, van Brummelen P, Breimer DD. Liquid chromatographic determination of mfedipine in plasma and of its main metabolite in unne.J Chromatog Biomed Appl 1984; 308: 209-16. 7. Van Harten J, Lodewijks MThM, Guyt-Scholten JW. van Brummelen P, Breimer DD. Gas chromatographic determination of nisoldipine and one of its metabolites in plasma. J Chromatog Biomed Appl 1987; 423: 327-33 8. Kleinbloesem CH, van Brummelen P, Danhof M, Faber H, Urquhart J, Breimer DD. Rate-of-increase of plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans. Clin Pharmacol Ther 1987; 41: 26-30.
RESULTS
Pathological changes in the spinal cord were of two types-those associated with acute decompression (in subjects who died suddenly from diving accidents) and those associated with chronic injury. The acute changes consisted firstly of grossly distended empty blood vessels in the meninges, nerve roots, and white matter of the cord and were found in all diving accidents except cases 3, 6, 9, and 10. Occasionally there was associated perivascular haemorrhage. Secondly, perivascular proteinaceous globules, indicating vasogenic oedema (also seen in experimental type II DCS),9 occurred in cases, 1, 2, and 7. The chronic changes were in most cases minor, as judged in sections stained by haematoxylin and eosin. There was a small focus of gliosis in the gracile funiculi of case 2 at C7 and C8. In 1 case only (case 7) there was some fibrosis in a posterior nerve root at Cl. Hyalinisation of blood vessels in the white matter was present in several cords, especially in cases 2, 6, 9, and 10. Corpora amylacea were a common feature and were especially numerous in cases 3, 5, and 10; they were absent in cases 1,8, and 9. The features of chronic degenerative change were judged to be small but relevant in view of the age group being studied. In sections stained by the sensitive Marchi method, 3 cases showed positive staining. At C7 in case 5 there was degeneration in the posterior columns and the neuroanatomical distribution suggested that the long ascending fibres were affected. In case 7 there was a similar distribution of recent degeneration in the posterior columns in the cervical region together with Marchi-positive fibres in the anterior and lateral columns. In the third case (case 6) there was recent Marchi-positive degeneration with a distribution affecting the afferent fibres from the posterior roots (within the cord) as well as bilateral degeneration of the tract of Lissauer (see accompanying figure); there was also some degeneration of a few fibres in the anterior columns. In all instances Marchi-positive material was extracellular (not within macrophages) and the staining took on a beaded appearance, described as true degeneration by Smith.6 DISCUSSION
Our results document important tract degeneration in the spinal cord of some professional divers. These features were difficult to recognise in haematoxylin,and eosin sections but
1366 DIVING EXPERIENCE OF THE
8 PROFESSIONAL AND 3 AMATEUR SUBJECTS
DA diving accident; RTA road traffic accident. + denotes positive staining; - denotes negative staining. =
=
shown by the sensitive Marchi technique, which should be adopted in future studies. It is generally accepted that Marchi-positive material does not appear in degenerating myelinated fibres until 7-10 days after the initiating lesion.7 Moreover, it does not appear intracellularly until some 10 weeks after the lesion.8 The Marchi-positive material we describe appears, therefore, to have occurred between 1 and 10 weeks before the final accidents. Assuming that these tract degenerations arose from a previous incident of DCS, the distribution of the degeneration suggests that there may be two separate pathogenic mechanisms. Lesions in the lateral and ventral columns may arise from focal infarcts as suggested from experience with experimental DCS in the goat.9 In case 6, however, afferent fibres from the dorsal roots were especially affected, as well as branch fibres in the tract of Lissauer. These findings suggest that dorsal nerve roots themselves may be compromised or that these afferent fibres are damaged within the cord by a process of infarction. Injury to these afferent fibres might explain the transient sensory phenomena that are characteristic of type I DCS (temporary sensory and cutaneous changes). In our series Marchi-positive degeneration was identified in the spinal cords of 3 of 8 professional divers; the cords from 3 amateur divers were unaffected. 2 of the professionals had dived to depths of 100 m (on helium/gas mixtures) and
were
clearly
they were also saturation divers. Saturation divers are kept at the pressure of their diving depth for periods of up to 1 month in order to reduce the amount of time which would otherwise be engaged in repeated long decompression schedules. When not diving, the men are kept in large compression chambers on the surface. These 2 professionals were in the middle age group of the series (see table) and had been diving for 8 and 13 years, respectively. The third affected diver had not worked at a depth greater than 50 m (on air), was also of the middle age group, and had been diving for 8 years. Could the lesions that we describe have arisen from causes other than diving, such as alcohol toxicity, subacute degeneration of the cord, or multiple sclerosis? In all these conditions degenerative changes are readily recognisable in paraffin sections stained with haematoxylin and eosin-in our cases this was not so. The possibility arises that the lesions may have contributed to the patients’ difficulties in their final diving accidents. The tract degeneration may have been detectable had a full neurological examination been carried out before their final dives. Our results also indicate that some professional divers appear to be unwittingly working with tract degeneration in the spinal cord. This work was carried out with the aid of a grant from the Medical Research Council. We thank all the clinicians who made available their case-material and the medicolegal authorities in various countries for their cooperation. We are especially grateful for the advice given to us by Dr Marion C. Smith and for the technical assistance of Mrs P. Deacon, Mrs I. S. Lloyd, and Mr J. E. Payne. Mrs E. Williams prepared the typescript.
Correspondence should be addressed to A. C. P., School of Veterinary Medicine, Madingley Road, Cambridge CB3 OES. REFERENCES
Histological features in case 6. Marchi-positive degeneration in afferent fibres of the posterior columns, in fibres of Lissauer’s tract, and also scattered in the anterior and lateral columns. Marchi x 10 (original magnification).
1. Rensselaer H. The pathology of caisson disease. Med Rec 1891; 40: 141-50, 178-82. 2. Sharples CW. A contribution to the pathology of the spinal cord in diver’s palsy. J Nerv Dis 1894; 19: 636-40. 3. Lichtenstein BW, Zeitlin H. Caisson disease a histologic study of late lesions Arch Path 1936; 22: 86-98. 4. Palmer AC, Calder IM, McCallum RI, Mastaglia FL Spinal cord degeneration in a case of "recovered" spinal decompression sickness. Br Med J 1981; 283: 888 5. Swank RL, Davenport HA. Marchi’s staining method. Studies of some of the underlying mechanisms involved. Stain Tech 1934; 9: 11-19. 6. Smith MC. The recognition and prevennon of artefacts of the Marchi method J Neurol Neurosurg Psychiatry 1956; 19: 74-83. 7. Smith MC. The use of Marchi staining in the later stages of human tract degeneration. J Neurol Neurosurg Psychiatry 1951; 14: 222-25. 8. Smith MC. Observations on the extended use of the Marchi method J Neurol Neurosurg Psychiatry 1956; 19: 67-73. 9. Palmer AC, Blakemore WF, Greenwood AG. Neuropathology of experimental decompression (dysbarism) in the goat. Neuropathol Appl Neurobiol 1976, 2: 145-56.
Preliminary Communication
a
neurological
history of DCS and there
were
no
documented
abnormalities.
Pathological Features SPINAL CORD DEGENERATION IN DIVERS
Necropsies were carried out as soon as possible after death, delays sometimes inevitable because of difficulty in recovering the bodies. Brains (except case 3) and spinal cords were removed and fixed in 10% formol saline. Results of the neuropathological examination of the brains will be reported separately. Whole cords were
A. C. PALMER1
I. M. CALDER2
J. T. HUGHES3
Summary
Spinal
cords from 8 professional and 3 divers who died accidentally were
amateur
examined histopathologically. Marchi-positive degeneration was found in the cords of 3 professional divers, the posterior, lateral, and to a lesser the anterior columns. In 1 there was degeneration of afferent fibres within the posterior columns.
made available from all 11
except case 1 (caudal to C7 11 (Tl to L4 only). Initially, transverse segments were taken from each level of cord, embedded in paraffin wax, sectioned, and stained with haematoxylin and eosin; special stains were used as necessary. As the investigation proceeded we decided to look additionally for tract degeneration by means of the Marchi method. For this purpose the tissue available was limited to four or five intersegmental levels from each cord which had not been processed for paraffin embedded sections. The Marchi method used was that modified by Swank and Davenport -5 both frozen and paraffin embedded sections were prepared.
were
Comparative Neurology, School of Veterinary Medicine, Cambridge;1 Department of Morbid Anatomy, London Hospital Medical College, and Medical Division of Health and Safety Executive, London;2 and Department of Neuropathology, Radcliffe Infirmary, Oxford3 Wellcome Laboratory for
cases
only), case 6 (C5 to T9 only), and case
variously affecting extent
INTRODUCTION
DAMAGE to the spinal cord as a result of decompression sickness ("spinal bends" or type II decompression sickness, DCS) and caisson disease has been documented by several workers including ourselves.l-4 We previously reported a male sports diver who had recovered almost completely from an episode of spinal DCS 4 years before death but who was found subsequently to have extensive morphological changes in the posterior and lateral columns of the spinal cord.4 We have now conducted a histological survey of the spinal cords taken from 8 professional and 3 amateur male divers who had died from diving or non-diving accidents, to ascertain whether some active divers have unrecognised cord degeneration, perhaps as a result of decompression exposures. METHODS
Clinical Records All professional divers in the United Kingdom undergo a comprehensive annual examination that includes a thorough neurological assessment. This examination is carried out by an approved doctor under the Diving at Work Regulations 1981, of the Health and Safety at Work Act 1974. The examination is accepted international basis by both diving companies and divers. Amateur divers also usually have an annual medical examination, which is less rigorous than that required for professionals. If a diver, in his opinion, has suffered from a minor incident of DCS, he may not feel constrained to declare it. All the subjects in this series had been examined within a period of 2 to 38 weeks before death (see accompanying table), except for case 3 who had retired from diving 18 months earlier. Records of the last medical examination were available for all other cases; none on an
5. McAllister RG Jr. Kinetics and dynamics of
nifedipine after oral and sublingual doses. Am J Med 1986, 81: (suppl 6A): 2-5. 6. Kleinbloesem CH, van Harten J, van Brummelen P, Breimer DD. Liquid chromatographic determination of mfedipine in plasma and of its main metabolite in unne.J Chromatog Biomed Appl 1984; 308: 209-16. 7. Van Harten J, Lodewijks MThM, Guyt-Scholten JW. van Brummelen P, Breimer DD. Gas chromatographic determination of nisoldipine and one of its metabolites in plasma. J Chromatog Biomed Appl 1987; 423: 327-33 8. Kleinbloesem CH, van Brummelen P, Danhof M, Faber H, Urquhart J, Breimer DD. Rate-of-increase of plasma concentration of nifedipine as a major determinant of its hemodynamic effects in humans. Clin Pharmacol Ther 1987; 41: 26-30.
RESULTS
Pathological changes in the spinal cord were of two types-those associated with acute decompression (in subjects who died suddenly from diving accidents) and those associated with chronic injury. The acute changes consisted firstly of grossly distended empty blood vessels in the meninges, nerve roots, and white matter of the cord and were found in all diving accidents except cases 3, 6, 9, and 10. Occasionally there was associated perivascular haemorrhage. Secondly, perivascular proteinaceous globules, indicating vasogenic oedema (also seen in experimental type II DCS),9 occurred in cases, 1, 2, and 7. The chronic changes were in most cases minor, as judged in sections stained by haematoxylin and eosin. There was a small focus of gliosis in the gracile funiculi of case 2 at C7 and C8. In 1 case only (case 7) there was some fibrosis in a posterior nerve root at Cl. Hyalinisation of blood vessels in the white matter was present in several cords, especially in cases 2, 6, 9, and 10. Corpora amylacea were a common feature and were especially numerous in cases 3, 5, and 10; they were absent in cases 1,8, and 9. The features of chronic degenerative change were judged to be small but relevant in view of the age group being studied. In sections stained by the sensitive Marchi method, 3 cases showed positive staining. At C7 in case 5 there was degeneration in the posterior columns and the neuroanatomical distribution suggested that the long ascending fibres were affected. In case 7 there was a similar distribution of recent degeneration in the posterior columns in the cervical region together with Marchi-positive fibres in the anterior and lateral columns. In the third case (case 6) there was recent Marchi-positive degeneration with a distribution affecting the afferent fibres from the posterior roots (within the cord) as well as bilateral degeneration of the tract of Lissauer (see accompanying figure); there was also some degeneration of a few fibres in the anterior columns. In all instances Marchi-positive material was extracellular (not within macrophages) and the staining took on a beaded appearance, described as true degeneration by Smith.6 DISCUSSION
Our results document important tract degeneration in the spinal cord of some professional divers. These features were difficult to recognise in haematoxylin,and eosin sections but
1366 DIVING EXPERIENCE OF THE
8 PROFESSIONAL AND 3 AMATEUR SUBJECTS
DA diving accident; RTA road traffic accident. + denotes positive staining; - denotes negative staining. =
=
shown by the sensitive Marchi technique, which should be adopted in future studies. It is generally accepted that Marchi-positive material does not appear in degenerating myelinated fibres until 7-10 days after the initiating lesion.7 Moreover, it does not appear intracellularly until some 10 weeks after the lesion.8 The Marchi-positive material we describe appears, therefore, to have occurred between 1 and 10 weeks before the final accidents. Assuming that these tract degenerations arose from a previous incident of DCS, the distribution of the degeneration suggests that there may be two separate pathogenic mechanisms. Lesions in the lateral and ventral columns may arise from focal infarcts as suggested from experience with experimental DCS in the goat.9 In case 6, however, afferent fibres from the dorsal roots were especially affected, as well as branch fibres in the tract of Lissauer. These findings suggest that dorsal nerve roots themselves may be compromised or that these afferent fibres are damaged within the cord by a process of infarction. Injury to these afferent fibres might explain the transient sensory phenomena that are characteristic of type I DCS (temporary sensory and cutaneous changes). In our series Marchi-positive degeneration was identified in the spinal cords of 3 of 8 professional divers; the cords from 3 amateur divers were unaffected. 2 of the professionals had dived to depths of 100 m (on helium/gas mixtures) and
were
clearly
they were also saturation divers. Saturation divers are kept at the pressure of their diving depth for periods of up to 1 month in order to reduce the amount of time which would otherwise be engaged in repeated long decompression schedules. When not diving, the men are kept in large compression chambers on the surface. These 2 professionals were in the middle age group of the series (see table) and had been diving for 8 and 13 years, respectively. The third affected diver had not worked at a depth greater than 50 m (on air), was also of the middle age group, and had been diving for 8 years. Could the lesions that we describe have arisen from causes other than diving, such as alcohol toxicity, subacute degeneration of the cord, or multiple sclerosis? In all these conditions degenerative changes are readily recognisable in paraffin sections stained with haematoxylin and eosin-in our cases this was not so. The possibility arises that the lesions may have contributed to the patients’ difficulties in their final diving accidents. The tract degeneration may have been detectable had a full neurological examination been carried out before their final dives. Our results also indicate that some professional divers appear to be unwittingly working with tract degeneration in the spinal cord. This work was carried out with the aid of a grant from the Medical Research Council. We thank all the clinicians who made available their case-material and the medicolegal authorities in various countries for their cooperation. We are especially grateful for the advice given to us by Dr Marion C. Smith and for the technical assistance of Mrs P. Deacon, Mrs I. S. Lloyd, and Mr J. E. Payne. Mrs E. Williams prepared the typescript.
Correspondence should be addressed to A. C. P., School of Veterinary Medicine, Madingley Road, Cambridge CB3 OES. REFERENCES
Histological features in case 6. Marchi-positive degeneration in afferent fibres of the posterior columns, in fibres of Lissauer’s tract, and also scattered in the anterior and lateral columns. Marchi x 10 (original magnification).
1. Rensselaer H. The pathology of caisson disease. Med Rec 1891; 40: 141-50, 178-82. 2. Sharples CW. A contribution to the pathology of the spinal cord in diver’s palsy. J Nerv Dis 1894; 19: 636-40. 3. Lichtenstein BW, Zeitlin H. Caisson disease a histologic study of late lesions Arch Path 1936; 22: 86-98. 4. Palmer AC, Calder IM, McCallum RI, Mastaglia FL Spinal cord degeneration in a case of "recovered" spinal decompression sickness. Br Med J 1981; 283: 888 5. Swank RL, Davenport HA. Marchi’s staining method. Studies of some of the underlying mechanisms involved. Stain Tech 1934; 9: 11-19. 6. Smith MC. The recognition and prevennon of artefacts of the Marchi method J Neurol Neurosurg Psychiatry 1956; 19: 74-83. 7. Smith MC. The use of Marchi staining in the later stages of human tract degeneration. J Neurol Neurosurg Psychiatry 1951; 14: 222-25. 8. Smith MC. Observations on the extended use of the Marchi method J Neurol Neurosurg Psychiatry 1956; 19: 67-73. 9. Palmer AC, Blakemore WF, Greenwood AG. Neuropathology of experimental decompression (dysbarism) in the goat. Neuropathol Appl Neurobiol 1976, 2: 145-56.