48
toxoid (158/861 [18%]) than were those who did not believe that immunisations could transmit AIDS (40/417 [10%],OR2-12,95% CI 1 44-3 12). Of the mothers who responded that injections can transmit AIDS 212 answered affirmatively when questioned about concern that immunisations could be transmitting AIDS. But once again children of mothers who were concerned about immunisation transmitting AIDS had rates of immunisation similar to those of mothers who were not concerned (60/212 [28%] vs 194/645 [30%]; OR 092, 95% CI 064-131). This was also true for tetanus immunisation in the mothers. Although we cannot rule out the occasional transmission of HIV via injections, neither epidemiological studies nor age-specific HIV infection rates suggest that this is a major route of infection. However, there is always a danger that a health message--eg, to avoid contaminated injection materials-will be misunderstood and that immunisation programmes will be adversely affected. Happily, there is no evidence from this study to suggest that fear of contracting AIDS is causing mothers to abandon immunisation in Uganda. Nonetheless, radio messages about AIDS in Uganda have been modified to ensure that parents are aware of the safety of immunisations. We thank the members of the AIDS control programme, especially those in the health education division for conducting the excellent AIDS health education programme. We also thank Dr Daan Mulder for reviewing the manuscript and Dr Artur Galaska for participating in the review. S. B. is seconded to the Ministry of Health from the Uganda project of the Task Force for Child Survival which is funded by the Rockefeller Foundation and Mark Weeks from the Save the Children Fund, United Kingdom.
Epidemiology Unit, Uganda Ministry of Health, Entebbe, Uganda; and Uganda National Expanded, Programme of Immunisations
SETH BERKLEY* MARK WEEKS JOHN BARENZI
*Correspondence address: Health Science Division, Rockefeller Foundation, New York, NY 10036, USA.
photomicrographs showing, top, root from cauda equina with patchy fibre loss (luxol fast-blue; bar = 1 00 flm); bottom, ependyma of filum terminale with CMV inclusion.
Case 1:
1. Hrdy DB. Cultural practices contributing to the transmission of human immunodeficiency virus in Africa. Rev Infect Dis 1987; 9: 1109-19. 2. Quinn TC, Mann JM, Curran JW, Piot P. AIDS in Africa: an epidemiologic paradigm. Science 1986; 234: 955-63. 3. Anon. Expanded programme on immunization. Programme review Uganda. Wkly Epidem Rec 1988; 16: 114-17. 4. Berkley SF, Widy-Wirski R, Okware SI, Downing RG, Linnan MJ, White KE, Sempala S. Risk factors associated with HIV infection in Uganda. J Infect Dis 1989; 160: 22-30. 5. Henderson RH, Sundaresan T. Cluster sampling to assess immunization coverage: a review of experience with a simplified sampling method. Bull WHO 1982; 60: 253-60.
Ganciclovir for lumbosacral polyradiculopathy in AIDS SIR,-Cytomegalovirus (CMV) can cause a polyradiculopathy in patients with AIDS.1-4 The clinical presentation is an acute severe cauda equina syndrome, which is fatal, usually within 2 months. Ganciclovir is effective against CMV, and CMV retinitis in AIDS responds. We therefore gave ganciclovir to four homosexual AIDS patients with a predominantly lumbosacral polyradiculopathy. Case l.-Presented with a 2 week history of weakness in his legs, low back pain, difficulty in micturition, and perianal numbness, and a 3-day history of neck stiffness and photophobia. He had active CMV retinitis in his right eye. The arms were normal ; he had urinary retention, a flaccid paraparesis (unable to walk); leg reflexes diminished or absent; right plantar response extensor, left flexor; perianal anaesthesia. CMV complement-fixation test (CFT) negative (table) but CMV was isolated 6 weeks later. He was treated with ganciclovir 10 mg/kg daily and the neck stiffness and back pain improved. After 3 weeks he could walk unaided, with normal hip flexion and restored knee reflexes. He died, 2 months after this presentation, with Pneumocystis carinii pneumonia. At necropsy CMV was seen and confirmed immunohistochemically in ependymal cells of the filum terminale. Numerous roots of cauda equina showed patchy axonal loss with Schwann cell proliferation (figure). Dorsal root ganglia and spinal motor cells were normal. Spinal cord showed mild diffuse gliosis.
Case 2.-This man had low back pain in mid-November, 1988, followed over about 4 weeks by pain in his buttocks, difficulty in walking, difficulty in micturition, constipation, and perianal numbness. Neurological examination on Dec 12 revealed urinary retention, normal cranial nerves and arms, and a flaccid asymmetric areflexic paraparesis (proximal power 3); left plantar response absent, right flexor; pinprick and light touch lost on thighs, calves, and perianal region; vibration sense and proprioception intact, myelogram normal. Sensory action potentials were reduced in the legs, motor conduction normal, F wave prolonged. He was started on ganciclovir 10 mg/kg. By Dec 22 he had severe shooting pains in both legs and was unable to walk. Treatment was changed to foscamet but the leg weakness worsened and his serum creatinine rose; foscamet was stopped. On Jan 19 ganciclovir was restarted at 5 mg/kg twice daily and the shooting pains stopped within a week; by Feb 20 he transferred from bed to chair; and by March 27 he was walking with a frame. While on maintenance ganciclovir in April CMV retinitis developed. He was neurologically stable until shortly before his death in August 1989. No necropsy. Case 3.-He had difficulty in micturition when admitted with CMV retinitis on Feb 27,1989.22 weeks later, while on foscarnet, he complained of weakness in both legs and urinary retention for 1 day. Examination on March 13 revealed, apart from CMV retinitis, a flaccid asymmetric areflexic paraparesis (unable to walk); plantar responses flexor; patchy sensory loss over both legs. Motor and sensory conduction in the arms normal. Sensory action potentials low or reduced in the legs; motor conduction slightly abnormal, F waves prolonged. His treatment was changed to ganciclovir and 2 weeks later he was able to walk using a frame. Power improved in both legs. His neurological state remained the same until August, 1989, when last seen. Case 4.-Presented with a 3-week history of low back pain radiating down both legs and 2 weeks of difficulty in micturition and increasing leg weakness with flank numbness. Reduced vision in
49
CSF
INVESTIGATIONS (AT TIME OF FIRST EXAMINATION)
4.
Jacobson MA, Mills J, Rush J, et al. Failure of antiviral therapy for acquired immunodeficiency syndrome related cytomegalovirus myelitis. Arch Neurol 1988;
45: 1090-92. 5. Cornblath DR, McArthur JC,
Kennedy PGE, Witte AS, Griffin JW. Inflammatory demyelinating peripheral neuropathies association with Human T cell lymphotrophic virus type III infections. Ann Neurol 1987; 21: 32-40. 6. Lanska MJ, Lanska DJ, Schmidley JW. Syphilitic polyradiculopathy in an HIV positive man. Neurology 1988; 38: 1297-301. 7. Woosley RM, Chambers TJ, Chung HD, McGarry JD. Mycobacterial meningomyelitis associated with human immunodeficiency virus infection. Arch
a week. Examination revealed CMV retinitis. Cranial and arms intact. He was able to walk; mild proximal weakness; absent leg reflexes; flexor right and equivocal left plantar responses; sensory examination was normal. On ganciclovir 10 mg/kg daily he improved, power and reflexes returning to normal. He died from cryptosporidial diarrhoea 5 months later, having had no further neurological problems. No necropsy. The similarity in presentation and in clinical evolution to pathologically confirmed cases of CMV polyradiculopathy led to the clinical diagnosis. That CMV was the cause is not absolutely certain. However, CMV was isolated in CSF in case 1 and confirmed pathologically and in the other three the diagnosis was strengthened by CMV retinitis. Normal cellularity in CSF in cases 3 and 4 may indicate an earlier sample or milder disease. Most other causes of polyradiculopathy and myeloradiculopathy seem unlikely. For example, no patient had anal or genital ulceration but this does not exclude Herpes simplex infection since this would also have responded to ganciclovir. Guillain-Barre syndrome is excluded because of neutrophil pleocytosis or prominent sphincter involvement or preserved reflexes in the arms. The onset and time course differs from the chronic inflammatory polyradiculopathy previously described in AIDS’ and HIV itself is not known to cause polyradiculopathy. Syphilitic6 and tuberculous7 myeloradiculopathy can be distinguished microbiologically or serologically and by our patients improvement without specific
one
eye for
Neurol 1988; 45: 691-93. 8. Miller RG, Storey J, Greco C. Successful treatment of progressive polyradiculopathy in AIDS patients. Neurology 1989; 39 (suppl 1): 271. 9. Novak IS, Trujillo R, Rivera VM, et al. Ganciclovir in the treatment of CMV infections in AIDS patiens with neurologic complications. Neurology 1989; 39 (suppl 1): 379-80. 10. Graveleau Ph, Perol R, Chapman A. Regression of cauda equina sydrome in AIDS patient being treated with ganciclovir. Lancet 1989; i: 511-12. 11. Guiloff RJ, Fuller GN, Roberts A, et al. Nature, incidence and prognosis of neurological involvement in the acquired immunodeficiency syndrome in central London. Postgrad Med J 1988; 64: 919-25.
nerves
therapy. Previously reported cases ended fatally in 3-8 weeks. None of our patients died from the neurological illness, suggesting a response to ganciclovir. Preliminary reports support a response to earlier treattnent.8-lO The syndrome is rare, occurring in less than 1% of AIDS patients," but as in three of our cases there are often other sites of CMV infection that would merit treatment. Ganciclovir should be considered in AIDS patients with predominantly lumbosacral polyradiculopathy with prominent sphincter involvement and CSF neutrophil pleocytosis after other conditions have been excluded. We thank Dr B. Gazzard, Dr R. George, and Prof M. J. G. Harrison and Prof P. J. G. Semple for allowing us to report patients under their care, and Dr G. Patou for viral studies in case 1.
Departments of Genitourinary Medicine, Medicine, Neurology, and Histopathology, University College and Middlesex School of Medicine, London W1; Department of Neurology, Westminster Hospital, London SW1, and Department of Neuropathology, Institute of Neurology, London WC1, UK
G. N. FULLER S. K. GILL R. J. GUILOFF R. KAPOOR S. B. LUCAS E. SINCLAIR F. SCARAVILLI R. F. MILLER
Psychological response to breast cancer and 15-year outcome SIR,-In a prospective study of non-metastatic breast cancer (To,l
reported that patients’ psychological responses to significantly related to disease outcome 5 and 10 years later.1,2 Patients who responded with fighting spirit or with denial (positive avoidance) were significantly more likely to be alive and free of recurrence than were patients with fatalistic or helpless responses. We now report the final results after 15 years’ follow-up. All 62 patients whose psychological responses to cancer were originally assessed were followed up. The findings were the same as at 5 and 10 years. Women who responded with fighting spirit or denial were significantly more likely to be alive and free of recurrence (9/20, 45%) than were women showing other responses (7/42,17%) (X2test, p 0-037). Multivariate analyses with the Cox regression mode 13 were done with the following prognostic factors: age, menopausal status, clinical stage, type of operation, whether or not the patient received prophylactic postoperative radiotherapy, tumour size, histological grade, and psychological response. Analyses were done with the event of interest being death from any
No,1 Mo)
we
cancer were
=
cause, death from breast cancer, or first recurrence of disease. A step-upward approach was used. When the prognostic factors were examined individually, psychological response was the most important factor in each analysis (death from any cause, p 0-006; first recurrence, p=0-006). When death from cancer, p
toxoid (158/861 [18%]) than were those who did not believe that immunisations could transmit AIDS (40/417 [10%],OR2-12,95% CI 1 44-3 12). Of the mothers who responded that injections can transmit AIDS 212 answered affirmatively when questioned about concern that immunisations could be transmitting AIDS. But once again children of mothers who were concerned about immunisation transmitting AIDS had rates of immunisation similar to those of mothers who were not concerned (60/212 [28%] vs 194/645 [30%]; OR 092, 95% CI 064-131). This was also true for tetanus immunisation in the mothers. Although we cannot rule out the occasional transmission of HIV via injections, neither epidemiological studies nor age-specific HIV infection rates suggest that this is a major route of infection. However, there is always a danger that a health message--eg, to avoid contaminated injection materials-will be misunderstood and that immunisation programmes will be adversely affected. Happily, there is no evidence from this study to suggest that fear of contracting AIDS is causing mothers to abandon immunisation in Uganda. Nonetheless, radio messages about AIDS in Uganda have been modified to ensure that parents are aware of the safety of immunisations. We thank the members of the AIDS control programme, especially those in the health education division for conducting the excellent AIDS health education programme. We also thank Dr Daan Mulder for reviewing the manuscript and Dr Artur Galaska for participating in the review. S. B. is seconded to the Ministry of Health from the Uganda project of the Task Force for Child Survival which is funded by the Rockefeller Foundation and Mark Weeks from the Save the Children Fund, United Kingdom.
Epidemiology Unit, Uganda Ministry of Health, Entebbe, Uganda; and Uganda National Expanded, Programme of Immunisations
SETH BERKLEY* MARK WEEKS JOHN BARENZI
*Correspondence address: Health Science Division, Rockefeller Foundation, New York, NY 10036, USA.
photomicrographs showing, top, root from cauda equina with patchy fibre loss (luxol fast-blue; bar = 1 00 flm); bottom, ependyma of filum terminale with CMV inclusion.
Case 1:
1. Hrdy DB. Cultural practices contributing to the transmission of human immunodeficiency virus in Africa. Rev Infect Dis 1987; 9: 1109-19. 2. Quinn TC, Mann JM, Curran JW, Piot P. AIDS in Africa: an epidemiologic paradigm. Science 1986; 234: 955-63. 3. Anon. Expanded programme on immunization. Programme review Uganda. Wkly Epidem Rec 1988; 16: 114-17. 4. Berkley SF, Widy-Wirski R, Okware SI, Downing RG, Linnan MJ, White KE, Sempala S. Risk factors associated with HIV infection in Uganda. J Infect Dis 1989; 160: 22-30. 5. Henderson RH, Sundaresan T. Cluster sampling to assess immunization coverage: a review of experience with a simplified sampling method. Bull WHO 1982; 60: 253-60.
Ganciclovir for lumbosacral polyradiculopathy in AIDS SIR,-Cytomegalovirus (CMV) can cause a polyradiculopathy in patients with AIDS.1-4 The clinical presentation is an acute severe cauda equina syndrome, which is fatal, usually within 2 months. Ganciclovir is effective against CMV, and CMV retinitis in AIDS responds. We therefore gave ganciclovir to four homosexual AIDS patients with a predominantly lumbosacral polyradiculopathy. Case l.-Presented with a 2 week history of weakness in his legs, low back pain, difficulty in micturition, and perianal numbness, and a 3-day history of neck stiffness and photophobia. He had active CMV retinitis in his right eye. The arms were normal ; he had urinary retention, a flaccid paraparesis (unable to walk); leg reflexes diminished or absent; right plantar response extensor, left flexor; perianal anaesthesia. CMV complement-fixation test (CFT) negative (table) but CMV was isolated 6 weeks later. He was treated with ganciclovir 10 mg/kg daily and the neck stiffness and back pain improved. After 3 weeks he could walk unaided, with normal hip flexion and restored knee reflexes. He died, 2 months after this presentation, with Pneumocystis carinii pneumonia. At necropsy CMV was seen and confirmed immunohistochemically in ependymal cells of the filum terminale. Numerous roots of cauda equina showed patchy axonal loss with Schwann cell proliferation (figure). Dorsal root ganglia and spinal motor cells were normal. Spinal cord showed mild diffuse gliosis.
Case 2.-This man had low back pain in mid-November, 1988, followed over about 4 weeks by pain in his buttocks, difficulty in walking, difficulty in micturition, constipation, and perianal numbness. Neurological examination on Dec 12 revealed urinary retention, normal cranial nerves and arms, and a flaccid asymmetric areflexic paraparesis (proximal power 3); left plantar response absent, right flexor; pinprick and light touch lost on thighs, calves, and perianal region; vibration sense and proprioception intact, myelogram normal. Sensory action potentials were reduced in the legs, motor conduction normal, F wave prolonged. He was started on ganciclovir 10 mg/kg. By Dec 22 he had severe shooting pains in both legs and was unable to walk. Treatment was changed to foscamet but the leg weakness worsened and his serum creatinine rose; foscamet was stopped. On Jan 19 ganciclovir was restarted at 5 mg/kg twice daily and the shooting pains stopped within a week; by Feb 20 he transferred from bed to chair; and by March 27 he was walking with a frame. While on maintenance ganciclovir in April CMV retinitis developed. He was neurologically stable until shortly before his death in August 1989. No necropsy. Case 3.-He had difficulty in micturition when admitted with CMV retinitis on Feb 27,1989.22 weeks later, while on foscarnet, he complained of weakness in both legs and urinary retention for 1 day. Examination on March 13 revealed, apart from CMV retinitis, a flaccid asymmetric areflexic paraparesis (unable to walk); plantar responses flexor; patchy sensory loss over both legs. Motor and sensory conduction in the arms normal. Sensory action potentials low or reduced in the legs; motor conduction slightly abnormal, F waves prolonged. His treatment was changed to ganciclovir and 2 weeks later he was able to walk using a frame. Power improved in both legs. His neurological state remained the same until August, 1989, when last seen. Case 4.-Presented with a 3-week history of low back pain radiating down both legs and 2 weeks of difficulty in micturition and increasing leg weakness with flank numbness. Reduced vision in
49
CSF
INVESTIGATIONS (AT TIME OF FIRST EXAMINATION)
4.
Jacobson MA, Mills J, Rush J, et al. Failure of antiviral therapy for acquired immunodeficiency syndrome related cytomegalovirus myelitis. Arch Neurol 1988;
45: 1090-92. 5. Cornblath DR, McArthur JC,
Kennedy PGE, Witte AS, Griffin JW. Inflammatory demyelinating peripheral neuropathies association with Human T cell lymphotrophic virus type III infections. Ann Neurol 1987; 21: 32-40. 6. Lanska MJ, Lanska DJ, Schmidley JW. Syphilitic polyradiculopathy in an HIV positive man. Neurology 1988; 38: 1297-301. 7. Woosley RM, Chambers TJ, Chung HD, McGarry JD. Mycobacterial meningomyelitis associated with human immunodeficiency virus infection. Arch
a week. Examination revealed CMV retinitis. Cranial and arms intact. He was able to walk; mild proximal weakness; absent leg reflexes; flexor right and equivocal left plantar responses; sensory examination was normal. On ganciclovir 10 mg/kg daily he improved, power and reflexes returning to normal. He died from cryptosporidial diarrhoea 5 months later, having had no further neurological problems. No necropsy. The similarity in presentation and in clinical evolution to pathologically confirmed cases of CMV polyradiculopathy led to the clinical diagnosis. That CMV was the cause is not absolutely certain. However, CMV was isolated in CSF in case 1 and confirmed pathologically and in the other three the diagnosis was strengthened by CMV retinitis. Normal cellularity in CSF in cases 3 and 4 may indicate an earlier sample or milder disease. Most other causes of polyradiculopathy and myeloradiculopathy seem unlikely. For example, no patient had anal or genital ulceration but this does not exclude Herpes simplex infection since this would also have responded to ganciclovir. Guillain-Barre syndrome is excluded because of neutrophil pleocytosis or prominent sphincter involvement or preserved reflexes in the arms. The onset and time course differs from the chronic inflammatory polyradiculopathy previously described in AIDS’ and HIV itself is not known to cause polyradiculopathy. Syphilitic6 and tuberculous7 myeloradiculopathy can be distinguished microbiologically or serologically and by our patients improvement without specific
one
eye for
Neurol 1988; 45: 691-93. 8. Miller RG, Storey J, Greco C. Successful treatment of progressive polyradiculopathy in AIDS patients. Neurology 1989; 39 (suppl 1): 271. 9. Novak IS, Trujillo R, Rivera VM, et al. Ganciclovir in the treatment of CMV infections in AIDS patiens with neurologic complications. Neurology 1989; 39 (suppl 1): 379-80. 10. Graveleau Ph, Perol R, Chapman A. Regression of cauda equina sydrome in AIDS patient being treated with ganciclovir. Lancet 1989; i: 511-12. 11. Guiloff RJ, Fuller GN, Roberts A, et al. Nature, incidence and prognosis of neurological involvement in the acquired immunodeficiency syndrome in central London. Postgrad Med J 1988; 64: 919-25.
nerves
therapy. Previously reported cases ended fatally in 3-8 weeks. None of our patients died from the neurological illness, suggesting a response to ganciclovir. Preliminary reports support a response to earlier treattnent.8-lO The syndrome is rare, occurring in less than 1% of AIDS patients," but as in three of our cases there are often other sites of CMV infection that would merit treatment. Ganciclovir should be considered in AIDS patients with predominantly lumbosacral polyradiculopathy with prominent sphincter involvement and CSF neutrophil pleocytosis after other conditions have been excluded. We thank Dr B. Gazzard, Dr R. George, and Prof M. J. G. Harrison and Prof P. J. G. Semple for allowing us to report patients under their care, and Dr G. Patou for viral studies in case 1.
Departments of Genitourinary Medicine, Medicine, Neurology, and Histopathology, University College and Middlesex School of Medicine, London W1; Department of Neurology, Westminster Hospital, London SW1, and Department of Neuropathology, Institute of Neurology, London WC1, UK
G. N. FULLER S. K. GILL R. J. GUILOFF R. KAPOOR S. B. LUCAS E. SINCLAIR F. SCARAVILLI R. F. MILLER
Psychological response to breast cancer and 15-year outcome SIR,-In a prospective study of non-metastatic breast cancer (To,l
reported that patients’ psychological responses to significantly related to disease outcome 5 and 10 years later.1,2 Patients who responded with fighting spirit or with denial (positive avoidance) were significantly more likely to be alive and free of recurrence than were patients with fatalistic or helpless responses. We now report the final results after 15 years’ follow-up. All 62 patients whose psychological responses to cancer were originally assessed were followed up. The findings were the same as at 5 and 10 years. Women who responded with fighting spirit or denial were significantly more likely to be alive and free of recurrence (9/20, 45%) than were women showing other responses (7/42,17%) (X2test, p 0-037). Multivariate analyses with the Cox regression mode 13 were done with the following prognostic factors: age, menopausal status, clinical stage, type of operation, whether or not the patient received prophylactic postoperative radiotherapy, tumour size, histological grade, and psychological response. Analyses were done with the event of interest being death from any
No,1 Mo)
we
cancer were
=
cause, death from breast cancer, or first recurrence of disease. A step-upward approach was used. When the prognostic factors were examined individually, psychological response was the most important factor in each analysis (death from any cause, p 0-006; first recurrence, p=0-006). When death from cancer, p
