560
Foscamet 60
amoxycillin 3 g four times daily was given for 3 weeks. The patient
mg/kg three times a day was added intravenously, and his condition
afebrile on day 2 and the neurological deficits disappeared in a week. The patient was discharged after 16 days and she was well 1 month later. Patient 3 (M/59, 2 week history of headache and fluctuating consciousness; he also had maturity-onset diabetes mellitus, and cirrhosis associated with pancytopenia; he was alcoholic). On admission, the patient was lethargic and aphasic without fever. The liver was enlarged, and neurological examination revealed paralysis of the right third, the right seventh, and the left eighth cranial nerves. Peripheral leucocyte count was 3-8 x 109/1 (60% polymorphs). Because of traumatic lumbar puncture, CSF was bloody and not cultured. Intravenous ampicillin 3 g four times daily was started. A second lumbar puncture at 24 h revealed 30 x 106/1 white cells (100% mononuclear), glucose 3-20 mmol/1 (blood 640), and protein 1’20 g/l. CSF microscopy and culture were negative. Computed tomography was normal and syphilis (VDRL, TPHA) and B burgdorferi antibody tests were negative. 2 weeks after admission anti-LLO dot-blot gave a titre of 300; titre was 400 at 1 month, and 2 and 6 months later, 500. He developed paresis of the right arm and paralysis of the left third cranial nerve during the first 2 days. Magnetic resonance imaging (MRI) on day 30 revealed multiple lesions in the protuberantial, peduncular, and left parieto-temporal regions. The patient received parenteral ampicillin for 4 weeks. He was discharged after 30 days with paralysis of the right seventh cranial nerve. Repeat MRI at 1 and 7 months showed that the lesions were healing. Serum anti-LLO titres of 500 or more were reached in each patient. These values are similar to those reported for adults with CSF or blood cultures positive for L monocytogenes; titres in healthy persons or in patients with non-listeric infections do not exceed 100.3 Consistent with our previous reports,3anti-LLO was found soon after the clinical onset. In our patients, the first sample after admission showed high titres, which is not surprising given that neurological signs were present 10-15 days earlier. The titres fell slowly over several months. No anti-LLO IgM was detected in CSF or serum, which is consistent with cases of culture-proven CNS listeriosis.3 Thus, screening for anti-LLO for diagnosis of CNS listeriosis in adults is useful, since CSF and blood cultures may remain negative. Cases with sterile CSF and blood do not merely represent partly treated CNS infections because two of our patients had not received antibiotics before sampling. More probably, they are cerebral infections in which L monocytogenes is absent from CSF and blood or present at low counts. The CSF may even be normal, as in our patient 2. This pattern is supported by the finding that L monocytogenes first enters the cerebral parenchyma via brain capillaries and subsequently spreads into the subarachnoid space.6 Our suggestion is to give antibiotics active against L monocytogenes in encephalitis and meningoencephalitis of unknown origin.
obvious, and he became progressively obtunded.
improved substantially. He became alert, the headache disappeared, nausea and vomiting stopped, and fever gradually subsided. CT after 15 days of treatment showed decreased periventricular contrast enhancement. CSF examination after 22 days of treatment revealed a decrease in pleocytosis (14 V,7BC); total protein was 0-85 g/l. Neither immunohistochemistry nor in-situ hybridisation demonstrated CMV. Viral culture remained negative. After 6 weeks of stabilisation, the doses of foscarnet and ganciclovir were lowered. 10 days later his condition deteriorated. The patient and his family decided to stop medication and he died 2 weeks later of progressive brainstem involvement. In a patient with AIDS who presents with progressive mental deterioration and brain stem (oculomotor) signs, periventricular contrast enhancement on CT, and CMV early antigen (and pleocytosis and positive viral culture) in the CSF, CMV meningoencephalitis is the most likely diagnosis. Ganciclovir/ foscarnet in induction doses may be of some benefit: our patient had a clinical, radiological, and virological response to this treatment. ROELIEN ENTING Departments of Internal Medicine, Neurology, and Microbiology, Academic Medical Centre, Univesity of Amsterdam, 1105 Amsterdam, Netherlands
JAN DE GANS PETER REISS CASPER JANSEN PETER PORTEGIES
CK, Cho ES, Lemann W, et al. Neuropathology of AIDS: an autopsy review. J Neuropathol Exp Neurol 1986; 45: 635-46. Morgello S, Cho ES, Nielsen S, et al. CMV encephalitis in patients with AIDS: an autopsy study of 30 cases and a review of the literature. Hum Pathol 1987; 18:
1. Petito 2.
289-97. 3. Edwards RH, Messing R, McKendall RR. Cytomegalovirus meningoencephalitis in a homosexual man with Kaposi’s sarcoma: isolation of CMV from CSF cells. Neurology 1985; 35: 560-62. 4. Berman S, Kim R, Hook B, et al. CMV encephalitis in patients receiving ganciclovir for CMV retinitis. VII International Conference on AIDS, Florence, 1991: abstr WB 2366.
Serological evidence for culture-negative listeriosis of central
nervous
system
and meningoencephalitis account for most of listeriosis in non-pregnant adults.1.2 A new methodsfor the serodiagnosis of listeriosis is based on the detection of antibodies against listeriolysin 0 (LLO), a toxin essential for intracellular growth of Listeria monocytogenes.4 We have diagnosed three adults with central nervous system (CNS) listeriosis with sterile cerebrospinal fluid (CSF) and blood. Patient 1 (M/62, alcoholic, admitted with 2 week history of headache and fever; temperature on admission 41 °C). He was oriented to person, place, and time, and had no focal neurological deficit, but his neck was stiff. Peripheral leucocyte count was 16-1 x 109/1 with 75% polymorphonuclear cells. Lumbar puncture revealed 240 x 106/1 white cells (82% mononuclear, 18% polymorphs), glucose 3 55 mmol/1 (blood 7-20), and protein 3 10 g/1. CSF microscopy and culture were negative as were blood cultures. Indirect immunofluorescence assay for antibodies to Borrelia burgdorferi was negative. Anti-LLO dot-blot gave a titre of 800, unchanged 1 month later. Intravenous amoxycillin 3 g four times daily and gentamicin 60 mg thrice daily were started. On the fourth day, fever abated and the patient had improved neurologically. Gentamicin was discontinued and amoxycillin was maintained for 18 days. Repeat lumbar puncture after 18 days of antibiotic therapy yielded 48 x 106/1 white cells (98% mononuclear) and protein 0-67 g/1. The patient was discharged after 22 days and he was well 2 weeks later. Patient 2 (F/50, 10 day history of dizziness, diplopia, and fever; receiving aluminium salts for oesophagitis). Neurological examination showed paralysis of the right fifth, the left sixth, and the eighth cranial nerves. CSF and blood cultures and assay for antibodies to B burgdorferi were negative. Herpes simplex virus antibody titre was not increased. Anti-LLO dot-blot 3 days after admission gave a titre of 300.2 weeks later the titres reached 500 and declined slowly (400 at 6 weeks and 200 at 1 year). Intravenous
SIR,-Meningitis
cases
was
We thank R. Fournier and A. Edelman for help with the manuscript.
Laboratory of Microbiology, Hôpital Necker-Enfants Malades, 75730 Paris, Cedex 15; Medicine Service, Centre Hospitalier Saint-Morand, Altkirch, Infectious Diseases Service, Hôpital de la Croix-Rousee, Lyon, and Neurology Service, Hôpital Armées Robert Picqué, Bordeaux, France
JEAN-LOUIS GAILLARD JEAN-LUC BERETTI MANETTE BOULOT-TOLLE
JEAN-MARIE WILHELM J. L. BERTRAND THIERRY HERBELLEAU
PATRICK BERCHE
1. Nieman RE, Lorber B. Listeriosis in adults: a changing pattern. Report of eight cases and review of the literature, 1968-1978. Rev Infect Dis 1980, 2: 207-27. 2 McLauchlin J. Human listeriosis in Britain, 1967-85, a summary of 722 cases 2
Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence. Epidemiol Infect 1990; 104: 191-201. 3. Berche P, Reich KA, Bonnichon M, et al. Detection of anti-listenolysin O for serodiagnosis of human listeriosis. Lancet 1990; 335: 624-27. 4. Gaillard JL, Berche P, Mounier J, Richard S, Sansonetti P. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect Immun 1987; 55: 2822-29. 5. Watson GW, Fuller TJ, Elms J, et al. Listeria cerebritis. Arch Intern Med 1975, 138: 83-87. 6. Cordy DR. Osebold JW. The neuropathogenesis of Listeria encephalomyelitis in sheep and mice. J Infect Dis 1959; 104: 164-73.
Foscamet 60
amoxycillin 3 g four times daily was given for 3 weeks. The patient
mg/kg three times a day was added intravenously, and his condition
afebrile on day 2 and the neurological deficits disappeared in a week. The patient was discharged after 16 days and she was well 1 month later. Patient 3 (M/59, 2 week history of headache and fluctuating consciousness; he also had maturity-onset diabetes mellitus, and cirrhosis associated with pancytopenia; he was alcoholic). On admission, the patient was lethargic and aphasic without fever. The liver was enlarged, and neurological examination revealed paralysis of the right third, the right seventh, and the left eighth cranial nerves. Peripheral leucocyte count was 3-8 x 109/1 (60% polymorphs). Because of traumatic lumbar puncture, CSF was bloody and not cultured. Intravenous ampicillin 3 g four times daily was started. A second lumbar puncture at 24 h revealed 30 x 106/1 white cells (100% mononuclear), glucose 3-20 mmol/1 (blood 640), and protein 1’20 g/l. CSF microscopy and culture were negative. Computed tomography was normal and syphilis (VDRL, TPHA) and B burgdorferi antibody tests were negative. 2 weeks after admission anti-LLO dot-blot gave a titre of 300; titre was 400 at 1 month, and 2 and 6 months later, 500. He developed paresis of the right arm and paralysis of the left third cranial nerve during the first 2 days. Magnetic resonance imaging (MRI) on day 30 revealed multiple lesions in the protuberantial, peduncular, and left parieto-temporal regions. The patient received parenteral ampicillin for 4 weeks. He was discharged after 30 days with paralysis of the right seventh cranial nerve. Repeat MRI at 1 and 7 months showed that the lesions were healing. Serum anti-LLO titres of 500 or more were reached in each patient. These values are similar to those reported for adults with CSF or blood cultures positive for L monocytogenes; titres in healthy persons or in patients with non-listeric infections do not exceed 100.3 Consistent with our previous reports,3anti-LLO was found soon after the clinical onset. In our patients, the first sample after admission showed high titres, which is not surprising given that neurological signs were present 10-15 days earlier. The titres fell slowly over several months. No anti-LLO IgM was detected in CSF or serum, which is consistent with cases of culture-proven CNS listeriosis.3 Thus, screening for anti-LLO for diagnosis of CNS listeriosis in adults is useful, since CSF and blood cultures may remain negative. Cases with sterile CSF and blood do not merely represent partly treated CNS infections because two of our patients had not received antibiotics before sampling. More probably, they are cerebral infections in which L monocytogenes is absent from CSF and blood or present at low counts. The CSF may even be normal, as in our patient 2. This pattern is supported by the finding that L monocytogenes first enters the cerebral parenchyma via brain capillaries and subsequently spreads into the subarachnoid space.6 Our suggestion is to give antibiotics active against L monocytogenes in encephalitis and meningoencephalitis of unknown origin.
obvious, and he became progressively obtunded.
improved substantially. He became alert, the headache disappeared, nausea and vomiting stopped, and fever gradually subsided. CT after 15 days of treatment showed decreased periventricular contrast enhancement. CSF examination after 22 days of treatment revealed a decrease in pleocytosis (14 V,7BC); total protein was 0-85 g/l. Neither immunohistochemistry nor in-situ hybridisation demonstrated CMV. Viral culture remained negative. After 6 weeks of stabilisation, the doses of foscarnet and ganciclovir were lowered. 10 days later his condition deteriorated. The patient and his family decided to stop medication and he died 2 weeks later of progressive brainstem involvement. In a patient with AIDS who presents with progressive mental deterioration and brain stem (oculomotor) signs, periventricular contrast enhancement on CT, and CMV early antigen (and pleocytosis and positive viral culture) in the CSF, CMV meningoencephalitis is the most likely diagnosis. Ganciclovir/ foscarnet in induction doses may be of some benefit: our patient had a clinical, radiological, and virological response to this treatment. ROELIEN ENTING Departments of Internal Medicine, Neurology, and Microbiology, Academic Medical Centre, Univesity of Amsterdam, 1105 Amsterdam, Netherlands
JAN DE GANS PETER REISS CASPER JANSEN PETER PORTEGIES
CK, Cho ES, Lemann W, et al. Neuropathology of AIDS: an autopsy review. J Neuropathol Exp Neurol 1986; 45: 635-46. Morgello S, Cho ES, Nielsen S, et al. CMV encephalitis in patients with AIDS: an autopsy study of 30 cases and a review of the literature. Hum Pathol 1987; 18:
1. Petito 2.
289-97. 3. Edwards RH, Messing R, McKendall RR. Cytomegalovirus meningoencephalitis in a homosexual man with Kaposi’s sarcoma: isolation of CMV from CSF cells. Neurology 1985; 35: 560-62. 4. Berman S, Kim R, Hook B, et al. CMV encephalitis in patients receiving ganciclovir for CMV retinitis. VII International Conference on AIDS, Florence, 1991: abstr WB 2366.
Serological evidence for culture-negative listeriosis of central
nervous
system
and meningoencephalitis account for most of listeriosis in non-pregnant adults.1.2 A new methodsfor the serodiagnosis of listeriosis is based on the detection of antibodies against listeriolysin 0 (LLO), a toxin essential for intracellular growth of Listeria monocytogenes.4 We have diagnosed three adults with central nervous system (CNS) listeriosis with sterile cerebrospinal fluid (CSF) and blood. Patient 1 (M/62, alcoholic, admitted with 2 week history of headache and fever; temperature on admission 41 °C). He was oriented to person, place, and time, and had no focal neurological deficit, but his neck was stiff. Peripheral leucocyte count was 16-1 x 109/1 with 75% polymorphonuclear cells. Lumbar puncture revealed 240 x 106/1 white cells (82% mononuclear, 18% polymorphs), glucose 3 55 mmol/1 (blood 7-20), and protein 3 10 g/1. CSF microscopy and culture were negative as were blood cultures. Indirect immunofluorescence assay for antibodies to Borrelia burgdorferi was negative. Anti-LLO dot-blot gave a titre of 800, unchanged 1 month later. Intravenous amoxycillin 3 g four times daily and gentamicin 60 mg thrice daily were started. On the fourth day, fever abated and the patient had improved neurologically. Gentamicin was discontinued and amoxycillin was maintained for 18 days. Repeat lumbar puncture after 18 days of antibiotic therapy yielded 48 x 106/1 white cells (98% mononuclear) and protein 0-67 g/1. The patient was discharged after 22 days and he was well 2 weeks later. Patient 2 (F/50, 10 day history of dizziness, diplopia, and fever; receiving aluminium salts for oesophagitis). Neurological examination showed paralysis of the right fifth, the left sixth, and the eighth cranial nerves. CSF and blood cultures and assay for antibodies to B burgdorferi were negative. Herpes simplex virus antibody titre was not increased. Anti-LLO dot-blot 3 days after admission gave a titre of 300.2 weeks later the titres reached 500 and declined slowly (400 at 6 weeks and 200 at 1 year). Intravenous
SIR,-Meningitis
cases
was
We thank R. Fournier and A. Edelman for help with the manuscript.
Laboratory of Microbiology, Hôpital Necker-Enfants Malades, 75730 Paris, Cedex 15; Medicine Service, Centre Hospitalier Saint-Morand, Altkirch, Infectious Diseases Service, Hôpital de la Croix-Rousee, Lyon, and Neurology Service, Hôpital Armées Robert Picqué, Bordeaux, France
JEAN-LOUIS GAILLARD JEAN-LUC BERETTI MANETTE BOULOT-TOLLE
JEAN-MARIE WILHELM J. L. BERTRAND THIERRY HERBELLEAU
PATRICK BERCHE
1. Nieman RE, Lorber B. Listeriosis in adults: a changing pattern. Report of eight cases and review of the literature, 1968-1978. Rev Infect Dis 1980, 2: 207-27. 2 McLauchlin J. Human listeriosis in Britain, 1967-85, a summary of 722 cases 2
Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence. Epidemiol Infect 1990; 104: 191-201. 3. Berche P, Reich KA, Bonnichon M, et al. Detection of anti-listenolysin O for serodiagnosis of human listeriosis. Lancet 1990; 335: 624-27. 4. Gaillard JL, Berche P, Mounier J, Richard S, Sansonetti P. In vitro model of penetration and intracellular growth of Listeria monocytogenes in the human enterocyte-like cell line Caco-2. Infect Immun 1987; 55: 2822-29. 5. Watson GW, Fuller TJ, Elms J, et al. Listeria cerebritis. Arch Intern Med 1975, 138: 83-87. 6. Cordy DR. Osebold JW. The neuropathogenesis of Listeria encephalomyelitis in sheep and mice. J Infect Dis 1959; 104: 164-73.
![[Listeriosis of the central nervous system].](/assets/img/hold.png)
