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Acute chemical meningitis after metrizamide-lumbar myelography
456
Surg Neurol 1983;19:456-8
Acute Chemical Meningitis After Metrizamide-Lumbar Myelography Michael Worthington, M.D., Natalie Callander, Robert Flynn, M.D., and Raymond Sullivan, M.D. Departments of Medicine and Orthopedic Surgery, St. Elizabeth's Hospital and Tufts University School of Medicine, Boston, Massachusetts
Worthington M, Callander N, Flynn R, Sullivan R. Acute chemical meningitis after metrizamide lumbar myelography. Surg Neurol 1983;19:456-8.
Severe acute meningitis developed after the use of metrizamide for lumbar myelography; cerebrospinal fluid findings included a white blood cell count of 2300, mostly polymorphonuclear cells, glucose level of 8 m g % and protein level of 253%. This apparent chemical meningitis could not be distinguished, either clinically or by cerebrospinal fluid examination, from acute bacterial meningitis. This case emphasizes that severe acute meningeal reactions, while very rare, can occur after the use of metrizamide for myelography. Such patients must be evaluated promptly to rule out bacterial meningitis and should be followed carefully for possible later sequelae. KEY WORDS:
Metrizamide meningitis; Chemical meningitis;
myelography
In 1972, metrizamide was introduced in Scandinavia for clinical use as a water-soluble contrast agent for myelography [6]. Because o f its high solubility and relatively rapid clearance f r o m the cerebrospinal fluid, aspiration of metrizamide from the thecal sac is unnecessary. In addition, metrizamide and other water-soluble contrast media provide much better visualization of the spinal cord and nerve roots than previous agents such as iophendylate. Finally, metrizamide has appeared to be relatively nontoxic in many careful studies. Acute meningitis is particularly rare; we could find only two welldocumented reports of this in the literature [5,7]. We report here a case o f acute chemical meningitis after metrizamide-lumbar myelography in which the clinical picture and cerebrospinal fluid formula mimicked acute bacterial meningitis. Address reprint requests to." Michael Worthington, M.D., Department of Medicine, St. Elizabeth's Hospital, 736 Cambridge Street, Brighton, Massachusetts 02135
© 1983 by Elsevier Science Publishing Co., Inc.
Case
Report
A healthy 3 l-year-old man was admitted to St. Elizabeth's Hospital in April of 1981 with a two-month history of low back pain radiating down his left leg. Previous to this, the patient had low back pain which was resolved with bed rest. His present pain did not improve after 3 weeks of complete bed rest and therefore he was admitted to the hospital for evaluation. Past history was otherwise unremarkable. On physical examination, he was afebrile and other vital signs were normal. Physical examination was significant for a slight decrease in the ankle jerk on the left. On straight-leg raising, he developed pain radiating down the left leg at 40 ° of elevation of the left leg, and left buttock and left thigh pain at 60 ° of elevation of the right leg. After 8 days of bed rest in the hospital, he continued to have severe pain in his back and left leg whenever he got out of bed. Lumbar myelography with metrizamide was performed on the ninth day in the hospital and a small defect was noted at the level of L 4 L5. T h e r e were no problems at the time of myelography. The cerebrospinal fluid obtained was clear and colorless with no cells noted and protein of 62 m g % . Twentyfour hours after the myelogram the patient developed a severe headache, temperature of 40°C, and several shaking chills. On examination at this time, he had a stiff neck and was lethargic and confused. Physical examination was otherwise unchanged. A lumbar puncture was performed with an opening pressure of 240 m m H 2 0 and a closing pressure of 200 m m H 2 0 . White blood cell count in the cerebrospinal fluid was 2300 with 9 4 % polymorphonuclear cells and 6 % lymphocytes; cerebrospinal fluid glucose was 8 m g % (blood glucose of 75 m g % ) and protein was 253 m g % . G r a m stain of the cerebrospinal fluid did not reveal any definite bacteria. The patient was begun on intravenous penicillin, nafcillin, and chloramphenicol. A peripheral white count at this time was 13,400 with a marked shift to immature granulocytes. The antibiotics were discontinued after cultures failed to grow any bacteria after 48 hours. Cul0090-3019/83/050456-0353.00
Chemical Meningitis
tures of the same lot number of metrizamide as used on this patient also were negative. T h r e e days later, the patient still had a complaint o f headache and a temperature of 39°C. By 4 days after development of these symptoms, the patient was afebrile and essentially symptom-free. In the 1.5 years of observation since that time, he has had no recurrences of symptoms.
Discussion Both bacterial meningitis and, more commonly, acute aseptic meningitis have been well-documented after iophendylate myelography [10,17]. The cerebrospinal formula and clinical presentation o f these two conditions may be identical. It has been suggested that there may be a relationship between this acute aseptic meningitis and the development of a more serious chronic adhesive arachnoiditis [ 13]. In fact, one of the other two patients reported in the literature with a well-documented acute aseptic meningitis after metrizamide developed arachnoiditis and communicating hydrocephalus, and required ventriculoperitoneal shunting [7]. It has also been suggested that both the acute meningeal reaction and the chronic reaction leading to adhesive arachnoiditis represented an allergic reaction to the contrast material [ 13]. It has thus been encouraging that acute meningitis has not been found to be a serious problem with metrizamide. Most large, carefully studied series of cases have reported no case of acute meningitis after metrizamide myelography. In contrast, a mental disorder characterized by organic psychosis or varying degrees o f perceptual disturbance has been more common. In one series of 75 consecutive patients who received metrizamide for myelography, no case of acute meningitis occurred while 10 patients had severe mental disorders [16]. In nine other series of from 117 to 380 consecutive metrizamide myelographies, no cases o f acute meningitis were reported [1,2,4,8,9,11,12,14,15]. One of these authors reported up to 1600 further metrizamide myelograms without acute severe meningitis [11]. N o serious meningeal reactions were reported in 4,500 lumbar myelograms carried out in initial clinical trials of metrizamide [6]. There have been to our knowledge two well-documented reports in the literature of acute aseptic meningitis after metrizamide myelography [5,7]. In an additional report 5 out of 439 patients developed some meningismus and fever after myelography and had repeat cerebrospinal fluid examinations [3]. Few details of the the cases were given, but apparently cerebrospinal fluid pressures and protein values of these patients were normal, while cerebrospinal fluid white cell counts ranged from 2000 to 8000/mm ~. N o information was given about
Surg Neurol 1983;19:456-8
457
the cerebrospinal fluid glucose or the percent of white cells which were polymorphonuclear cells [3]. The onset was somewhat earlier than our case, generally 4 - 6 hours after the procedure, and all patients were essentially asymptomatic within 24 hours. While these cases appeared earlier after myelography, were milder, and of shorter duration than our case, they may have represented the same process o f either chemical irritation or allergic reaction to the metrizamide. As our case illustrates, an acute meningeal reaction can occur after metrizamide which cannot be distinguished clinically or by cerebrospinal fluid examination from acute bacterial meningitis. Since acute bacterial meningitis can occur after myelography, the physician must retain a high index of suspicion in these cases. This acute meningeal reaction may also identify a person who is at risk for the development of clinically significant adhesive arachnoiditis. These patients must be evaluated promptly in the acute situation and carefully followed thereafter. References I. Baker RA, Hillman BJ, McLennan JE, Strand RD, Kaufman SM. Sequelae of metrizamide myelography in 200 examinations. J Roentgenol 1978; 130:499-502. 2. Carella A, Federico F, Dicuonzo F, Vmjau E, Lamberti P. Adverse side effects of metrizamide and iopamidolo in myelography. Neuroradiology 1982;22:247-9. 3. Gelmars HJ. Adverse side effect of metrizamide in myelography. Neuroradiology 1979;18:119-23. 4. Hansen EB, Praestholm J, Fahrenkrug A, Bjerrum J. A clinical trial of amipaque in lumbar myelography. Br J Rad 1976;49:3,18. 5. Hurd RE, Sieger BE. Chemical meningitis secondary to metrizamide myelography. Spine 1982;7:82-3. 6. lrstam L. Lumbar myelography with amipaque. Spine 1978;3:7()82. 7. Kelly RE, Daroff RB, Sheremata WA, McCormick JR. Unusual effects of metrizamide lumbar myelography--Constellation of aseptic meningitis, arachnoiditis, communicating hydrocephalus, and Guillain-Barre syndrome. Arch Neurol 1980;37:588-9. 8. Kieffer SA, Binet EF, Esquerra JV, Hantman RP, Gross CE. Contrast agents for myelography: Clinical and radiological evaluation of amipaque and pantopaque. Radiology 1978;129:695705. 9. Legre J, Lavieille J, Debaene A, Tapias PL, Vaillant J. Prevention of adverse reactions to amipaque in cervical myelography--Report of a homogeneous series of 380 patients., J Neuroradiol 1981;8:353-61. 10. Mayher WE, Daniel EF, Allen MB. Acute meningeal reaction following pantopaque myelography. J Neurosurg 1971 ;34:396404. 11. McCormick CC, Apsimon HT, ChakeraTMH. Myelography with metrizamide--An analysis of the complications encountered in cervical, thoracic, and lumbar myelography. Aust N Z J Med 1981;11:645-50. 12. Picard L, Vespignani H, Vieux-Rochat P, Motet C, L'Esperance G, Montaut J, Weber M, Roland J. Serious neurological complications of metrizamide myelography. J Neuroradiol I979;6:3 ld.
458
Surg N e u r o l 1983;19:456-8
13. Quencer RM, Tenner M, Rothman L. The postoperative myelogram--Radiographic evaluation of arachnoiditis and dural/arachnoidal tears. Radiology. 1977;123:667-9. 14. Rolfe EB, Maguire PD. The incidence of headache following various techniques of metrizamide myelography. Br J Rad 1980;53:840-4. 15. Sage MR, Benness GT, Perrett LV, Mansfield J. Lumbar mye-
Worthington et al
lography today--Experience with metrizamide, a water-soluble, nonionic contrast medium. Med J Aust 1981 ; 1: 1"75-6. 16. Schmidt RC. Mental disorders after myelography with metrizamide and other water-soluble contrast media. Neuroradiology 1980;19:153-7. 17. Worthington M, Hills J, Tally F, Flynn R. Bacterial meningitis after myelography. Surg Neurol 1980; 14:318-2(L
Surg Neurol 1983;19:456-8
Acute Chemical Meningitis After Metrizamide-Lumbar Myelography Michael Worthington, M.D., Natalie Callander, Robert Flynn, M.D., and Raymond Sullivan, M.D. Departments of Medicine and Orthopedic Surgery, St. Elizabeth's Hospital and Tufts University School of Medicine, Boston, Massachusetts
Worthington M, Callander N, Flynn R, Sullivan R. Acute chemical meningitis after metrizamide lumbar myelography. Surg Neurol 1983;19:456-8.
Severe acute meningitis developed after the use of metrizamide for lumbar myelography; cerebrospinal fluid findings included a white blood cell count of 2300, mostly polymorphonuclear cells, glucose level of 8 m g % and protein level of 253%. This apparent chemical meningitis could not be distinguished, either clinically or by cerebrospinal fluid examination, from acute bacterial meningitis. This case emphasizes that severe acute meningeal reactions, while very rare, can occur after the use of metrizamide for myelography. Such patients must be evaluated promptly to rule out bacterial meningitis and should be followed carefully for possible later sequelae. KEY WORDS:
Metrizamide meningitis; Chemical meningitis;
myelography
In 1972, metrizamide was introduced in Scandinavia for clinical use as a water-soluble contrast agent for myelography [6]. Because o f its high solubility and relatively rapid clearance f r o m the cerebrospinal fluid, aspiration of metrizamide from the thecal sac is unnecessary. In addition, metrizamide and other water-soluble contrast media provide much better visualization of the spinal cord and nerve roots than previous agents such as iophendylate. Finally, metrizamide has appeared to be relatively nontoxic in many careful studies. Acute meningitis is particularly rare; we could find only two welldocumented reports of this in the literature [5,7]. We report here a case o f acute chemical meningitis after metrizamide-lumbar myelography in which the clinical picture and cerebrospinal fluid formula mimicked acute bacterial meningitis. Address reprint requests to." Michael Worthington, M.D., Department of Medicine, St. Elizabeth's Hospital, 736 Cambridge Street, Brighton, Massachusetts 02135
© 1983 by Elsevier Science Publishing Co., Inc.
Case
Report
A healthy 3 l-year-old man was admitted to St. Elizabeth's Hospital in April of 1981 with a two-month history of low back pain radiating down his left leg. Previous to this, the patient had low back pain which was resolved with bed rest. His present pain did not improve after 3 weeks of complete bed rest and therefore he was admitted to the hospital for evaluation. Past history was otherwise unremarkable. On physical examination, he was afebrile and other vital signs were normal. Physical examination was significant for a slight decrease in the ankle jerk on the left. On straight-leg raising, he developed pain radiating down the left leg at 40 ° of elevation of the left leg, and left buttock and left thigh pain at 60 ° of elevation of the right leg. After 8 days of bed rest in the hospital, he continued to have severe pain in his back and left leg whenever he got out of bed. Lumbar myelography with metrizamide was performed on the ninth day in the hospital and a small defect was noted at the level of L 4 L5. T h e r e were no problems at the time of myelography. The cerebrospinal fluid obtained was clear and colorless with no cells noted and protein of 62 m g % . Twentyfour hours after the myelogram the patient developed a severe headache, temperature of 40°C, and several shaking chills. On examination at this time, he had a stiff neck and was lethargic and confused. Physical examination was otherwise unchanged. A lumbar puncture was performed with an opening pressure of 240 m m H 2 0 and a closing pressure of 200 m m H 2 0 . White blood cell count in the cerebrospinal fluid was 2300 with 9 4 % polymorphonuclear cells and 6 % lymphocytes; cerebrospinal fluid glucose was 8 m g % (blood glucose of 75 m g % ) and protein was 253 m g % . G r a m stain of the cerebrospinal fluid did not reveal any definite bacteria. The patient was begun on intravenous penicillin, nafcillin, and chloramphenicol. A peripheral white count at this time was 13,400 with a marked shift to immature granulocytes. The antibiotics were discontinued after cultures failed to grow any bacteria after 48 hours. Cul0090-3019/83/050456-0353.00
Chemical Meningitis
tures of the same lot number of metrizamide as used on this patient also were negative. T h r e e days later, the patient still had a complaint o f headache and a temperature of 39°C. By 4 days after development of these symptoms, the patient was afebrile and essentially symptom-free. In the 1.5 years of observation since that time, he has had no recurrences of symptoms.
Discussion Both bacterial meningitis and, more commonly, acute aseptic meningitis have been well-documented after iophendylate myelography [10,17]. The cerebrospinal formula and clinical presentation o f these two conditions may be identical. It has been suggested that there may be a relationship between this acute aseptic meningitis and the development of a more serious chronic adhesive arachnoiditis [ 13]. In fact, one of the other two patients reported in the literature with a well-documented acute aseptic meningitis after metrizamide developed arachnoiditis and communicating hydrocephalus, and required ventriculoperitoneal shunting [7]. It has also been suggested that both the acute meningeal reaction and the chronic reaction leading to adhesive arachnoiditis represented an allergic reaction to the contrast material [ 13]. It has thus been encouraging that acute meningitis has not been found to be a serious problem with metrizamide. Most large, carefully studied series of cases have reported no case of acute meningitis after metrizamide myelography. In contrast, a mental disorder characterized by organic psychosis or varying degrees o f perceptual disturbance has been more common. In one series of 75 consecutive patients who received metrizamide for myelography, no case of acute meningitis occurred while 10 patients had severe mental disorders [16]. In nine other series of from 117 to 380 consecutive metrizamide myelographies, no cases o f acute meningitis were reported [1,2,4,8,9,11,12,14,15]. One of these authors reported up to 1600 further metrizamide myelograms without acute severe meningitis [11]. N o serious meningeal reactions were reported in 4,500 lumbar myelograms carried out in initial clinical trials of metrizamide [6]. There have been to our knowledge two well-documented reports in the literature of acute aseptic meningitis after metrizamide myelography [5,7]. In an additional report 5 out of 439 patients developed some meningismus and fever after myelography and had repeat cerebrospinal fluid examinations [3]. Few details of the the cases were given, but apparently cerebrospinal fluid pressures and protein values of these patients were normal, while cerebrospinal fluid white cell counts ranged from 2000 to 8000/mm ~. N o information was given about
Surg Neurol 1983;19:456-8
457
the cerebrospinal fluid glucose or the percent of white cells which were polymorphonuclear cells [3]. The onset was somewhat earlier than our case, generally 4 - 6 hours after the procedure, and all patients were essentially asymptomatic within 24 hours. While these cases appeared earlier after myelography, were milder, and of shorter duration than our case, they may have represented the same process o f either chemical irritation or allergic reaction to the metrizamide. As our case illustrates, an acute meningeal reaction can occur after metrizamide which cannot be distinguished clinically or by cerebrospinal fluid examination from acute bacterial meningitis. Since acute bacterial meningitis can occur after myelography, the physician must retain a high index of suspicion in these cases. This acute meningeal reaction may also identify a person who is at risk for the development of clinically significant adhesive arachnoiditis. These patients must be evaluated promptly in the acute situation and carefully followed thereafter. References I. Baker RA, Hillman BJ, McLennan JE, Strand RD, Kaufman SM. Sequelae of metrizamide myelography in 200 examinations. J Roentgenol 1978; 130:499-502. 2. Carella A, Federico F, Dicuonzo F, Vmjau E, Lamberti P. Adverse side effects of metrizamide and iopamidolo in myelography. Neuroradiology 1982;22:247-9. 3. Gelmars HJ. Adverse side effect of metrizamide in myelography. Neuroradiology 1979;18:119-23. 4. Hansen EB, Praestholm J, Fahrenkrug A, Bjerrum J. A clinical trial of amipaque in lumbar myelography. Br J Rad 1976;49:3,18. 5. Hurd RE, Sieger BE. Chemical meningitis secondary to metrizamide myelography. Spine 1982;7:82-3. 6. lrstam L. Lumbar myelography with amipaque. Spine 1978;3:7()82. 7. Kelly RE, Daroff RB, Sheremata WA, McCormick JR. Unusual effects of metrizamide lumbar myelography--Constellation of aseptic meningitis, arachnoiditis, communicating hydrocephalus, and Guillain-Barre syndrome. Arch Neurol 1980;37:588-9. 8. Kieffer SA, Binet EF, Esquerra JV, Hantman RP, Gross CE. Contrast agents for myelography: Clinical and radiological evaluation of amipaque and pantopaque. Radiology 1978;129:695705. 9. Legre J, Lavieille J, Debaene A, Tapias PL, Vaillant J. Prevention of adverse reactions to amipaque in cervical myelography--Report of a homogeneous series of 380 patients., J Neuroradiol 1981;8:353-61. 10. Mayher WE, Daniel EF, Allen MB. Acute meningeal reaction following pantopaque myelography. J Neurosurg 1971 ;34:396404. 11. McCormick CC, Apsimon HT, ChakeraTMH. Myelography with metrizamide--An analysis of the complications encountered in cervical, thoracic, and lumbar myelography. Aust N Z J Med 1981;11:645-50. 12. Picard L, Vespignani H, Vieux-Rochat P, Motet C, L'Esperance G, Montaut J, Weber M, Roland J. Serious neurological complications of metrizamide myelography. J Neuroradiol I979;6:3 ld.
458
Surg N e u r o l 1983;19:456-8
13. Quencer RM, Tenner M, Rothman L. The postoperative myelogram--Radiographic evaluation of arachnoiditis and dural/arachnoidal tears. Radiology. 1977;123:667-9. 14. Rolfe EB, Maguire PD. The incidence of headache following various techniques of metrizamide myelography. Br J Rad 1980;53:840-4. 15. Sage MR, Benness GT, Perrett LV, Mansfield J. Lumbar mye-
Worthington et al
lography today--Experience with metrizamide, a water-soluble, nonionic contrast medium. Med J Aust 1981 ; 1: 1"75-6. 16. Schmidt RC. Mental disorders after myelography with metrizamide and other water-soluble contrast media. Neuroradiology 1980;19:153-7. 17. Worthington M, Hills J, Tally F, Flynn R. Bacterial meningitis after myelography. Surg Neurol 1980; 14:318-2(L