1342
EFFECT OF DESFERRIOXAMINE ON HIV-1 REPLICATION AND
Continuous
CELL NUM BER/VIABILITY IN H9CELLS7 DAYSAFTER INFECTION
haemoperfusion for fulminant hepatic failure
SIR,-We have developed a new protocol for the treatment of hepatic failure, this being a combination of plasma and continuous haemofiltration (CHF). The daily exchange strategy of our protocol is simple. Patients usually die as a result of bleeding or brain oedema. Plasma exchange is a well-known technique of giving a large volume of fresh frozen plasma (FFP) to treat a bleeding tendency without causing volume overload. Methods for preventing brain oedema have aimed to remove middle sized molecular substances that are strongly associated with hepatic encephalopathy,’ but they can keep such patients conscious for only several hours in the face of progression of brain oedema. extensive haemodiafiltration with (HDF) Repeated fulminant
Triplicate cultures of H9 (105 cells/0 2 ml RPMI medium 1640 plus 10% fetal calf serum) were mfected wrth 2 x 10’ mfectious units of HIV-1, strain I I Ig m the presence of various concentrations of substance Cultures were split (1 2) on day 3 On day 7, viral production (mean supernatant RT on untreated culture, 1531 [SD 261 ] counts per minute/il) in infected cells was measured. With umnfected cells, membrane Integrity (FDA), cellular DNA content (DAPI), and metabolic actIvity (XTT) were measured absolute values (SD) for these mdices in these cultures were: 1 7 (0 1 ), 56 (2), and 1 4 (0 1 ), respectively
MT-2, CEM-SS, U-937, and H9 cell lines were obtained from the American Type Culture Collection cell repository. Human lymphocytes and in-vitro differentiated monocytes were prepared and infected with HIV-1, strain HTLV-IIIB, and the monocytotropic isolate HIV-12 Virus replication was assessed by measurement of reverse transcriptase activity (RT) in cell supernatants and morphologically by formation of giant cells.2 Cell metabolic activity was assessed with the XTT methodand cell numbers were counted directly after staining with trypan blue, or by use of DAPI (intracellular DNA content) or of FDA (intracellular esterase activity.3 H9 cells were infected as described by Tabor et al in the presence of desferrioxamine (0-5-60 µmol/1) or zidovudine (5 ug/ml). Cell number, cell viability, and virus production were measured on days 3 and 7 after infection. The table shows the results of a representative experiment. Similar results were obtained with U937, CEM-SS, and MT-2 cell lines. In all instances concentrations of desferrioxamine higher than 16 umol/1 were toxic, and reduction of RT production was seen only at these concentrations. With human lymphocytes or macrophages, inhibition of HIV-1 replication was seen only at cytotoxic concentrations of desferrioxamine. In all the acute models of infection zidovudine had a clear inhibitory effect without
cytotoxicity. We
investigated the effect of desferrioxamine in macrophages undergoing chronic infection.2 On day 11 after infection, after medium change, desferrioxamine (25 and 50 lunol/1) was added to the cultures. RT production was monitored thereafter. Cytotoxicity was not noted; however, virus production was indistinguishable from that in untreated cultures, indicating no effect on late events in the virus cycle. These experiments clearly demonstrate that in vitro also
desferrioxamine does not have an anti-HIV effect, whatever the cell virus type used. Tabor and colleagues’ results probably reflect the lack of evaluation of cell number and viability in their experiments. Providing the percentage of viable cells at the end of an experiment is meaningless, unless accompanied by absolute cell numbers. On the basis of our results we do not see any reason to recommend further in-vivo evaluation. or
JANIS K. LAZDINS
Pharma Research, CIBA-GEIGY Ltd, CH-4002, Basel,
Switzerland
ENRICA ALTERI THOMAS KLIMKAIT KATHIE WOODS-COOK MAJA R. WALKER GERARD GOUTTE BERNARD PONCIONI
E, Epstein JS, Hewlett IK, Lee SF. Inhibition by desferrioxamine of in-vitro replication of HIV-1 Lancet 1991, 337: 795 2 Lazdins JK, Klimkait T, Woods-Cook K, et al In vitro effect of transforming growth factor-&bgr; on progression of HIV- 1 infection in primary mononuclear phagocytes. J Immunol 1991, 147: 1201-07. 3. Gulakowski RJ, McMahon JB, Staley PG, Moran RA, Boyd MR A semiautomated multiparameter approach for anti-HIV drug screening J Virol Methods 1991; 33: 1. Tabor
87-100.
polymethylmetacrylate or cellulose triacetate membrane filters has prevented the progression of brain oedema even if there is severe liver failure.2 Surprisingly, this method has not been accepted world wide. We chose CHF rather than instead of HDF because of our familiarity with this technique. CHF can remove substances of molecular weight less than 10 000 Da with polyacrylnitrile or polymethylmetacrylate membrane filters for body fluid control in severe cardiac or pulmonary failure. We report a patient whom we treated with this new technique. A 55-year-old Japanese woman with fulminant hepatitis felt fatigued on July 15, 1991, and visited her family doctor, who diagnosed mild liver disorder. She had slightly raised serum alanine aminotransferase (ALT 192 IU/1), signs of jaundice were noted 42 days later, on Aug 25, and she was admitted to hospital. Despite conservative treatment she became confused on Aug 30. She was transferred to our hospital for intensive care, with grade III consciousness level (excitation to pain and unresponsive to calling). All hepatitis virus markers were negative, and she had no history of recent halothane anaesthesia or paracetamol (acetaminophen) ingestion. Subacute non-A, non-B viral hepatitis was thought to be indicated by the clinical course. On arrival she received our new treatment, along with the usual bowel clearance, correction of electrolyte balance, and control of blood glucose concentration. 2-5-301 of FFP was given in each session. CHF was continuously applied, with PAN membrane filters (’PANFIL APF-05’, effective filtration square 0-5 m2, Asahi Medical, Tokyo, Japan). The target filtration volume was equivalent to one body water volume per day (30-35 I) and was replaced with acetate Ringer’s solution (’Sublood’, Fuso Pharmacy, Tokyo). A double-lumen catheter was placed in a femoral vein. Blood flow rate was 120-200 ml per minute, and 5-10 mg per hour of nafamostat mesilate (’Fusan’, Torii Pharmacy, Tokyo) was given as anticoagulant. The membrane had to be changed once or twice daily. Just before the patient was put on this protocol her consicousness level dropped to grade IV. From day 3 (Sept 1) she was conscious and alert (coma grade II), even though computed tomography indicated ther her liver volume was only a third of normal (464 ml). This striking improvement was confirmed by electroencephalography: abnormally slow waves were dominant on the first and second days, but disappeared on day 3 when a waves predominated. Her level of consciousness was dependent on filtration volume. Because of technical difficulties we could not achieve sufficient filtration (22 1 per day) on day 11, and her consciousness level fell to grade III. It took two days for her to recover to grade II consciousness despite return to the correct filtration volume on day 12. Platelet count fell to 30 x 109/1 by day 15, and platelet transfusions were needed every day thereafter. Because we could not control the coagulation defect she had severe intestinal bleeding on Sept 19 (day 21): cost prevented us from obtaining sufficient FFP to maintain ’Hepaplastin’ test at over 20%. CHF could not be continued because of the severe hypotension resulting from the haemorrhage, and she died on Sept 20 (day 22 after admission) from respiratory arrest due to cerebral herniation only 8 h after CHF was stopped. Chapman et aP pointed out the controversy about the effectiveness of liver transplantation versus intensive supportive therapy and the need for large-scale controlled comparisons. Fundamentally, there is no difference between our new protocol
1343
and other intensive-care regimens, apart from the use of CHF, with which we at least double survival time. This protocol therefore increases the chance of spontaneous recovery and helps to correctly whether liver transplantation is needed. CHF should be seriously considered in intensive care of fulminant hepatitis. FFP for plasma exchange, and filters for plasma exchange and CHF are, however, very expensive. Our protocol costs about 500 000 Japanese Yen ([2000) per day and cannot be continued
judge
indefinitely. Blood Transfusion Service,
Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku,
Fukuoka 812, Japan, Emergency Service, Kyushu University Hospital, First Department of Internal Medicine, Kyushu University, and Internal Medicine,
Fujigaoka Hospital, Yokohama
SHOICHI INABA TOSHISUKE KISHIKAWA AKINORI ZAITSU HIROMI ISHIBASHI JIRO KUDO RYUJI OGAWA MAKOTO YOSHIBA
1. Opolon P. Significance of middle molecules in the pathogenesis of hepatic encephalopathy. In: Kleinberger G, Ferenci P, Riederer P, Thuler H, eds. Advances in hepatic encephalopathy and urea cycle diseases Basel. Karger, 1984. 310-14. 2. Yoshiba M, Yamada
hepatic
coma
H, Yoshikawa Y, et al. Hemodiafiltration treatment of deep by protein passing membrane. case report. Artif Organs 1986; 10:
417-19. 3.
Chapman RW, Forman D, Peto R, Smallwood hepatic failure? Lancet 1990; 335: 32-35.
Neck
R. Liver
transplantation for
acute
injuries
SIR,-Your timely editorial (Sept 21, p 728) on neck injury brings some sanity into the whiplash controversy; too often patients are consigned to the abnormal illness behaviour category. Many doctors refuse to accept, in the absence of radiographic signs, that unhealed soft tissue injuries can cause chronic pain. Evidence is accumulating that soft tissue damage in cervical motion segments is common after neck trauma." This damage is not visible on radiography and disc injuries do not heal in two months, as is traditionally expected, because these injuries are in avascular tissues. Jonsson et aP examined 22 cervical spines from victims of road traffic accidents and found injuries in all spines, with over 200 lesions, most of which were not visible on plain radiographs. In our series of 43 deaths in trauma patients cervical spines were frozen at 70°C and sectioned in 2 mm thick sagittal slices, and almost all showed signs of injury-disc injuries in 96% and soft tissue injuries of the facet joints in 72%. Only 28% had fractures, some of which were not visible on radiographs.4 In a much larger survey of 385 -
in this motion segments were much more common than fractures of the cervical vertebrae. This cervical pattern differs from thoracolumbar injuries in which the more vertical facet orientation gives the discs greater mechanical protection from shearing forces. Osti et al5 showed in sheep that small transverse incised disc lesions close to the vertebral end-plate do not heal in 18 months, except in the outer vascular part of the anterior annulus. In magnetic resonance imaging (MRI) studies of patients with extension injuries to the neck, Davies et al6 also showed that disc tears and avulsions heal slowly. We report features of two young adult male survivors of neck injury who later died and in whom we could relate necropsy findings to clinical records. Both show a good correlation between the sites of disc injuries and the segmental distribution of pain. A 30-year-old man had an extension injury after a rear-end car accident and died 14 months later. He had had chronic right arm and shoulder pain after the injury up to the time of death. Transverse clefts were found in four discs (C4-5 to C7-Tl), adjacent to the anterior vertebral rims, all on the right side of the midline. These clefts were similar in appearance and site to the cleft consistently found in the discs of victims of trauma (figure) and their position differed from that of age-related fissures. The patient’s limb and shoulder pain had consistently been at the C5 to Tl level on the right side. In two discs there was also calcification of the injured anterior annulus, adjacent to the clefts. This change was not present initially but appeared in radiographs obtained between 7 and 14 months after injury. A 43-year-old man died 3-5 years after an extension injury to the neck, having had chronic severe pain in the neck and upper back with tingling and weakness in both arms. Examination in the months after injury showed tenderness which was greatest at the C4-5 disc; there was some sensory loss in the C6 dermatomes on both sides with decreased power in muscle groups of both upper limbs supplied by C5, 6, and 7; reflexes and muscle tone were normal. He had paraesthesia in the arms and hands, which was brought on by extension of his neck. On lumbar puncture he was thought to have a block to cerebrospinal fluid circulation when the neck was extended; traction improved his symptoms. He had no radiologically evident neck pathology, other than slight narrowing of the C4-5 disc space; an orthopaedic surgeon stated that there was "a very strong functional element in his symptoms". Findings at
spines from trauma patients, examined at necropsy department, injuries to the soft tissues of the cervical
were partial fusion across the posterior C4-5 disc space, and vascularisation of the upper part of the C5-6 disc, with an old posterior disc prolapse. The C5-6 disc had no abnormalities on radiography. There was cord damage in the form of demyelination and gliosis of the left lateral column with overlying dural fibrous thickening. It seems likely in hindsight that he had traumatic posterior prolapses of the C5-6 disc and possibly of the C4-5 disc. Traumatic disc prolapse was common in extension injuries, in both the MRI study of Davis et al6 and in our necropsy study.2 It is unreasonable to assume that chronic pain in such cases has a psychosomatic basis. Clefts in trauma patients persist for a year or more in the innervated parts of the anterior annulus, with adjacent scarring and possible calcification. Other injured parts of the disc, which have no innervation to start with, may acquire it by vascular and neural ingrowth into disc clefts.The accelerated degenerative change in the whole injured motion segment may also give rise to recurrent mechanical pain, which can sometimes be eliminated by a disc or facet block.
necropsy
Department of Neuropathology, Royal Perth Hospital, Perth, Western Australia
J. R. TAYLOR B. A. KAKULAS
JR, Twomey LT. Disc injuries in cervical trauma. Lancet 1990; 336: 1318. JR, Twomey LT Acute injuries to cervical joints an autopsy study of neck sprain. Spine (in press). 3. Jonsson H, Bring G, Rauchning W, Sahlstedt B. Hidden cervical spine injuries in traffic accident victims with skull fractures. J Spinal Disorders 1991; 4: 251-63. 4. Taylor JR. "Whiplash": the cause and the lesion. 1991 proceedings of the Australian Association of Musculo-skeletal Medicine, pl. 5 Osti OL, Vemon-Roberts B, Fraser RD. Annulus tears and invertebral disc degeneration. an experimental study using an animal model. Spine 1990; 15: 1. Taylor 2. Taylor
Sagittal section (100 pm) near midline of C6-7 disc from a 32-year-old man who died from head injuries after a car accident. Small transverse cleft containing blood (short arrow) at attachment of anterior annulus to vertebral rim and disc prolapse (long arrow) through the posterior annulus are seen. Anterior and posterior longitudinal
ligaments are not avulsed
762-67. SJ, Teresi
LM, Bradley WG, et al. Cervical spine hyperextension injuries: MR findings. Radiology 1991; 180: 245-51.
6. Davis
EFFECT OF DESFERRIOXAMINE ON HIV-1 REPLICATION AND
Continuous
CELL NUM BER/VIABILITY IN H9CELLS7 DAYSAFTER INFECTION
haemoperfusion for fulminant hepatic failure
SIR,-We have developed a new protocol for the treatment of hepatic failure, this being a combination of plasma and continuous haemofiltration (CHF). The daily exchange strategy of our protocol is simple. Patients usually die as a result of bleeding or brain oedema. Plasma exchange is a well-known technique of giving a large volume of fresh frozen plasma (FFP) to treat a bleeding tendency without causing volume overload. Methods for preventing brain oedema have aimed to remove middle sized molecular substances that are strongly associated with hepatic encephalopathy,’ but they can keep such patients conscious for only several hours in the face of progression of brain oedema. extensive haemodiafiltration with (HDF) Repeated fulminant
Triplicate cultures of H9 (105 cells/0 2 ml RPMI medium 1640 plus 10% fetal calf serum) were mfected wrth 2 x 10’ mfectious units of HIV-1, strain I I Ig m the presence of various concentrations of substance Cultures were split (1 2) on day 3 On day 7, viral production (mean supernatant RT on untreated culture, 1531 [SD 261 ] counts per minute/il) in infected cells was measured. With umnfected cells, membrane Integrity (FDA), cellular DNA content (DAPI), and metabolic actIvity (XTT) were measured absolute values (SD) for these mdices in these cultures were: 1 7 (0 1 ), 56 (2), and 1 4 (0 1 ), respectively
MT-2, CEM-SS, U-937, and H9 cell lines were obtained from the American Type Culture Collection cell repository. Human lymphocytes and in-vitro differentiated monocytes were prepared and infected with HIV-1, strain HTLV-IIIB, and the monocytotropic isolate HIV-12 Virus replication was assessed by measurement of reverse transcriptase activity (RT) in cell supernatants and morphologically by formation of giant cells.2 Cell metabolic activity was assessed with the XTT methodand cell numbers were counted directly after staining with trypan blue, or by use of DAPI (intracellular DNA content) or of FDA (intracellular esterase activity.3 H9 cells were infected as described by Tabor et al in the presence of desferrioxamine (0-5-60 µmol/1) or zidovudine (5 ug/ml). Cell number, cell viability, and virus production were measured on days 3 and 7 after infection. The table shows the results of a representative experiment. Similar results were obtained with U937, CEM-SS, and MT-2 cell lines. In all instances concentrations of desferrioxamine higher than 16 umol/1 were toxic, and reduction of RT production was seen only at these concentrations. With human lymphocytes or macrophages, inhibition of HIV-1 replication was seen only at cytotoxic concentrations of desferrioxamine. In all the acute models of infection zidovudine had a clear inhibitory effect without
cytotoxicity. We
investigated the effect of desferrioxamine in macrophages undergoing chronic infection.2 On day 11 after infection, after medium change, desferrioxamine (25 and 50 lunol/1) was added to the cultures. RT production was monitored thereafter. Cytotoxicity was not noted; however, virus production was indistinguishable from that in untreated cultures, indicating no effect on late events in the virus cycle. These experiments clearly demonstrate that in vitro also
desferrioxamine does not have an anti-HIV effect, whatever the cell virus type used. Tabor and colleagues’ results probably reflect the lack of evaluation of cell number and viability in their experiments. Providing the percentage of viable cells at the end of an experiment is meaningless, unless accompanied by absolute cell numbers. On the basis of our results we do not see any reason to recommend further in-vivo evaluation. or
JANIS K. LAZDINS
Pharma Research, CIBA-GEIGY Ltd, CH-4002, Basel,
Switzerland
ENRICA ALTERI THOMAS KLIMKAIT KATHIE WOODS-COOK MAJA R. WALKER GERARD GOUTTE BERNARD PONCIONI
E, Epstein JS, Hewlett IK, Lee SF. Inhibition by desferrioxamine of in-vitro replication of HIV-1 Lancet 1991, 337: 795 2 Lazdins JK, Klimkait T, Woods-Cook K, et al In vitro effect of transforming growth factor-&bgr; on progression of HIV- 1 infection in primary mononuclear phagocytes. J Immunol 1991, 147: 1201-07. 3. Gulakowski RJ, McMahon JB, Staley PG, Moran RA, Boyd MR A semiautomated multiparameter approach for anti-HIV drug screening J Virol Methods 1991; 33: 1. Tabor
87-100.
polymethylmetacrylate or cellulose triacetate membrane filters has prevented the progression of brain oedema even if there is severe liver failure.2 Surprisingly, this method has not been accepted world wide. We chose CHF rather than instead of HDF because of our familiarity with this technique. CHF can remove substances of molecular weight less than 10 000 Da with polyacrylnitrile or polymethylmetacrylate membrane filters for body fluid control in severe cardiac or pulmonary failure. We report a patient whom we treated with this new technique. A 55-year-old Japanese woman with fulminant hepatitis felt fatigued on July 15, 1991, and visited her family doctor, who diagnosed mild liver disorder. She had slightly raised serum alanine aminotransferase (ALT 192 IU/1), signs of jaundice were noted 42 days later, on Aug 25, and she was admitted to hospital. Despite conservative treatment she became confused on Aug 30. She was transferred to our hospital for intensive care, with grade III consciousness level (excitation to pain and unresponsive to calling). All hepatitis virus markers were negative, and she had no history of recent halothane anaesthesia or paracetamol (acetaminophen) ingestion. Subacute non-A, non-B viral hepatitis was thought to be indicated by the clinical course. On arrival she received our new treatment, along with the usual bowel clearance, correction of electrolyte balance, and control of blood glucose concentration. 2-5-301 of FFP was given in each session. CHF was continuously applied, with PAN membrane filters (’PANFIL APF-05’, effective filtration square 0-5 m2, Asahi Medical, Tokyo, Japan). The target filtration volume was equivalent to one body water volume per day (30-35 I) and was replaced with acetate Ringer’s solution (’Sublood’, Fuso Pharmacy, Tokyo). A double-lumen catheter was placed in a femoral vein. Blood flow rate was 120-200 ml per minute, and 5-10 mg per hour of nafamostat mesilate (’Fusan’, Torii Pharmacy, Tokyo) was given as anticoagulant. The membrane had to be changed once or twice daily. Just before the patient was put on this protocol her consicousness level dropped to grade IV. From day 3 (Sept 1) she was conscious and alert (coma grade II), even though computed tomography indicated ther her liver volume was only a third of normal (464 ml). This striking improvement was confirmed by electroencephalography: abnormally slow waves were dominant on the first and second days, but disappeared on day 3 when a waves predominated. Her level of consciousness was dependent on filtration volume. Because of technical difficulties we could not achieve sufficient filtration (22 1 per day) on day 11, and her consciousness level fell to grade III. It took two days for her to recover to grade II consciousness despite return to the correct filtration volume on day 12. Platelet count fell to 30 x 109/1 by day 15, and platelet transfusions were needed every day thereafter. Because we could not control the coagulation defect she had severe intestinal bleeding on Sept 19 (day 21): cost prevented us from obtaining sufficient FFP to maintain ’Hepaplastin’ test at over 20%. CHF could not be continued because of the severe hypotension resulting from the haemorrhage, and she died on Sept 20 (day 22 after admission) from respiratory arrest due to cerebral herniation only 8 h after CHF was stopped. Chapman et aP pointed out the controversy about the effectiveness of liver transplantation versus intensive supportive therapy and the need for large-scale controlled comparisons. Fundamentally, there is no difference between our new protocol
1343
and other intensive-care regimens, apart from the use of CHF, with which we at least double survival time. This protocol therefore increases the chance of spontaneous recovery and helps to correctly whether liver transplantation is needed. CHF should be seriously considered in intensive care of fulminant hepatitis. FFP for plasma exchange, and filters for plasma exchange and CHF are, however, very expensive. Our protocol costs about 500 000 Japanese Yen ([2000) per day and cannot be continued
judge
indefinitely. Blood Transfusion Service,
Kyushu University Hospital, 3-1-1, Maidashi, Higashi-ku,
Fukuoka 812, Japan, Emergency Service, Kyushu University Hospital, First Department of Internal Medicine, Kyushu University, and Internal Medicine,
Fujigaoka Hospital, Yokohama
SHOICHI INABA TOSHISUKE KISHIKAWA AKINORI ZAITSU HIROMI ISHIBASHI JIRO KUDO RYUJI OGAWA MAKOTO YOSHIBA
1. Opolon P. Significance of middle molecules in the pathogenesis of hepatic encephalopathy. In: Kleinberger G, Ferenci P, Riederer P, Thuler H, eds. Advances in hepatic encephalopathy and urea cycle diseases Basel. Karger, 1984. 310-14. 2. Yoshiba M, Yamada
hepatic
coma
H, Yoshikawa Y, et al. Hemodiafiltration treatment of deep by protein passing membrane. case report. Artif Organs 1986; 10:
417-19. 3.
Chapman RW, Forman D, Peto R, Smallwood hepatic failure? Lancet 1990; 335: 32-35.
Neck
R. Liver
transplantation for
acute
injuries
SIR,-Your timely editorial (Sept 21, p 728) on neck injury brings some sanity into the whiplash controversy; too often patients are consigned to the abnormal illness behaviour category. Many doctors refuse to accept, in the absence of radiographic signs, that unhealed soft tissue injuries can cause chronic pain. Evidence is accumulating that soft tissue damage in cervical motion segments is common after neck trauma." This damage is not visible on radiography and disc injuries do not heal in two months, as is traditionally expected, because these injuries are in avascular tissues. Jonsson et aP examined 22 cervical spines from victims of road traffic accidents and found injuries in all spines, with over 200 lesions, most of which were not visible on plain radiographs. In our series of 43 deaths in trauma patients cervical spines were frozen at 70°C and sectioned in 2 mm thick sagittal slices, and almost all showed signs of injury-disc injuries in 96% and soft tissue injuries of the facet joints in 72%. Only 28% had fractures, some of which were not visible on radiographs.4 In a much larger survey of 385 -
in this motion segments were much more common than fractures of the cervical vertebrae. This cervical pattern differs from thoracolumbar injuries in which the more vertical facet orientation gives the discs greater mechanical protection from shearing forces. Osti et al5 showed in sheep that small transverse incised disc lesions close to the vertebral end-plate do not heal in 18 months, except in the outer vascular part of the anterior annulus. In magnetic resonance imaging (MRI) studies of patients with extension injuries to the neck, Davies et al6 also showed that disc tears and avulsions heal slowly. We report features of two young adult male survivors of neck injury who later died and in whom we could relate necropsy findings to clinical records. Both show a good correlation between the sites of disc injuries and the segmental distribution of pain. A 30-year-old man had an extension injury after a rear-end car accident and died 14 months later. He had had chronic right arm and shoulder pain after the injury up to the time of death. Transverse clefts were found in four discs (C4-5 to C7-Tl), adjacent to the anterior vertebral rims, all on the right side of the midline. These clefts were similar in appearance and site to the cleft consistently found in the discs of victims of trauma (figure) and their position differed from that of age-related fissures. The patient’s limb and shoulder pain had consistently been at the C5 to Tl level on the right side. In two discs there was also calcification of the injured anterior annulus, adjacent to the clefts. This change was not present initially but appeared in radiographs obtained between 7 and 14 months after injury. A 43-year-old man died 3-5 years after an extension injury to the neck, having had chronic severe pain in the neck and upper back with tingling and weakness in both arms. Examination in the months after injury showed tenderness which was greatest at the C4-5 disc; there was some sensory loss in the C6 dermatomes on both sides with decreased power in muscle groups of both upper limbs supplied by C5, 6, and 7; reflexes and muscle tone were normal. He had paraesthesia in the arms and hands, which was brought on by extension of his neck. On lumbar puncture he was thought to have a block to cerebrospinal fluid circulation when the neck was extended; traction improved his symptoms. He had no radiologically evident neck pathology, other than slight narrowing of the C4-5 disc space; an orthopaedic surgeon stated that there was "a very strong functional element in his symptoms". Findings at
spines from trauma patients, examined at necropsy department, injuries to the soft tissues of the cervical
were partial fusion across the posterior C4-5 disc space, and vascularisation of the upper part of the C5-6 disc, with an old posterior disc prolapse. The C5-6 disc had no abnormalities on radiography. There was cord damage in the form of demyelination and gliosis of the left lateral column with overlying dural fibrous thickening. It seems likely in hindsight that he had traumatic posterior prolapses of the C5-6 disc and possibly of the C4-5 disc. Traumatic disc prolapse was common in extension injuries, in both the MRI study of Davis et al6 and in our necropsy study.2 It is unreasonable to assume that chronic pain in such cases has a psychosomatic basis. Clefts in trauma patients persist for a year or more in the innervated parts of the anterior annulus, with adjacent scarring and possible calcification. Other injured parts of the disc, which have no innervation to start with, may acquire it by vascular and neural ingrowth into disc clefts.The accelerated degenerative change in the whole injured motion segment may also give rise to recurrent mechanical pain, which can sometimes be eliminated by a disc or facet block.
necropsy
Department of Neuropathology, Royal Perth Hospital, Perth, Western Australia
J. R. TAYLOR B. A. KAKULAS
JR, Twomey LT. Disc injuries in cervical trauma. Lancet 1990; 336: 1318. JR, Twomey LT Acute injuries to cervical joints an autopsy study of neck sprain. Spine (in press). 3. Jonsson H, Bring G, Rauchning W, Sahlstedt B. Hidden cervical spine injuries in traffic accident victims with skull fractures. J Spinal Disorders 1991; 4: 251-63. 4. Taylor JR. "Whiplash": the cause and the lesion. 1991 proceedings of the Australian Association of Musculo-skeletal Medicine, pl. 5 Osti OL, Vemon-Roberts B, Fraser RD. Annulus tears and invertebral disc degeneration. an experimental study using an animal model. Spine 1990; 15: 1. Taylor 2. Taylor
Sagittal section (100 pm) near midline of C6-7 disc from a 32-year-old man who died from head injuries after a car accident. Small transverse cleft containing blood (short arrow) at attachment of anterior annulus to vertebral rim and disc prolapse (long arrow) through the posterior annulus are seen. Anterior and posterior longitudinal
ligaments are not avulsed
762-67. SJ, Teresi
LM, Bradley WG, et al. Cervical spine hyperextension injuries: MR findings. Radiology 1991; 180: 245-51.
6. Davis
