Severe Meningoencephalitis: An Unusual Manifestation of Chlamydia pneumoniae Infection
Jean Guglielminotti, Nicolas Lellouche, Eric Maury, Marc Alzieu, Bertrand Guidet, and Georges Offenstadt
Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Paris, France
Reprints or correspondence: Dr. J. Guglielminotti, Service de Réanimation Médicale, Hôpital Saint-Antoine, APHP, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France.
Chlamydia pneumoniae is a frequent respiratory pathogen. However, severe CNS involvement is very uncommon . We report a case of meningoencephalitis caused by C. pneumoniae that followed acute bronchitis. It suggests that C. pneumoniae infection should be included in the differential diagnosis of meningoencephalitis, especially if there are associated respiratory symptoms.
A 95-year-old man was admitted to the hospital on 18 March 1999 for impaired consciousness. He had been well until 6 days earlier, when he began to complain of fever, myalgia, headache, and nonproductive cough. He received treatment with amoxicillin (1 g t.i.d.) from 13 to 15 March followed by ofloxacin (200 mg b.i.d.) from 15 to 18 March.
Physical examination revealed a drowsy man with a rigid neck; there were no other neurological abnormalities. The core temperature was 37.4°C. Initial laboratory investigation disclosed a leukocyte count of 8.7 × 109/L (70% neutrophils) and normal RBC and platelet counts. The C-reactive protein concentration was 27 mg/L (normal value, <9 mg/L). Sodium and potassium concentrations were normal. Creatinine clearance was 38 mL/min.
Chest radiography was unremarkable. Brain CT demonstrated mild cortical atrophy. An electroencephalogram displayed slow wave activity without asymmetry or seizures. Analysis of CSF obtained by lumbar puncture revealed the following values: protein, 1.06 g/L; glucose, 3.9 mmol/L (blood glucose, 6.5 mmol/L); leukocytes, 64 × 106/L; lymphocytes, 59 × 106/L; and RBCs, 19 × 106/L. No tumoral cells were observed. Gram and auramine stains of CSF were negative.
Treatment with iv acyclovir (750 mg b.i.d.) and amoxicillin (2 g 6 times daily) was started. Acyclovir therapy was stopped on 23 March because PCR analysis of CSF was negative for herpes simplex virus. All sets of standard blood cultures remained sterile, as did CSF cultures.
His neurological status worsened, and the patient was intubated and mechanically ventilated on 24 March. Analysis of CSF from another lumbar puncture revealed the following values: protein, 0.82 g/L; glucose, 13.1 mmol/L (blood glucose, 25.4 mmol/L); leukocytes, 82 × 106/L; lymphocytes, 66 × 106/L; and no RBCs. Brain MRI was unremarkable. Microimmunofluorescence for C. pneumoniae of a blood sample obtained on 23 March revealed an IgG titer of 2048 and an IgA titer of 515. Treatment with intravenous erythromycin (500 mg t.i.d.) was started on 25 March. Amoxicillin therapy was stopped on 28 March.
Serological tests for Legionella pneumophila, Mycoplasma pneumoniae, influenza and parainfluenza viruses, adenovirus, respiratory syncytial virus, and HIV were negative. L. pneumophila antigen was not detected in urine. The patient remained comatose, and erythromycin was replaced by ofloxacin (200 mg once a day) on 28 March. Microimmunofluorescence for C. pneumoniae of a blood sample obtained on 1 April revealed an IgG titer of 1024 and an IgA titer of 128. On the same day, analysis of CSF showed an IgG titer of 32.
His neurological status improved slowly, allowing weaning from mechanical ventilation on 14 April. However, the patient remained drowsy with slurred speech. Ofloxacin treatment was stopped on 17 April. The patient was transferred to the general ward on 20 April, but he died of aspiration pneumonia on 25 April.
On 1 April, 20 days after the beginning of clinical symptoms, the concentration of intrathecal synthesis of total IgG was 20.1 mg/L (40% of the concentration of total IgG in CSF), the blood specific antibody activity (SAA) of IgG antibody to C. pneumoniae was 100 × 10-3 units, and the intrathecal SAA of IgG antibody to C. pneumoniae was 1442 × 10-3 units; these findings strongly support the intrathecal presence of C. pneumoniae [2, 3].
Several elements of this case support that C. pneumoniae was the causative agent of meningoencephalitis. First, the titer of IgG antibody to C. pneumoniae was above the threshold (titer, 512) proposed by Grayston  to define acute infection. The high titer of IgA suggests reinfection. Second, no other pathogens causing lymphocytic meningoencephalitis were isolated. Third, intrathecal synthesis of IgG antibody to C. pneumoniae was demonstrated.
Only 4 cases of central neurological disease related to C. pneumoniae infection have been reported: meningitis, 1; encephalitis, 1; and meningoencephalitis, 2 [4 7]. Preceding respiratory symptoms were present in only 2 cases. Three patients required mechanical ventilation, but in only 1 case, mechanical ventilation was required for neurological symptoms. All patients survived, and all received treatment with an antibiotic active against C. pneumoniae. In these cases, the diagnosis relied on a 4-fold increase of the IgG titer in blood or on the presence of IgM, but no specific antibody to C. pneumoniae could be demonstrated in CSF. At our institution, the presence of IgM antibody to C. pneumoniae is not used to diagnose C. pneumoniae infection. Indeed, these antibodies are detected only during the first infection and do not reappear during reinfections, which are the most frequent type of C. pneumoniae infection .
In our case, intrathecal synthesis of IgG was demonstrated on 1 April . Moreover, IgG antibody to C. pneumoniae was detected in CSF. Transudation from blood is unlikely, because the intrathecal SAA of IgG antibody to C. pneumoniae was 14 times higher than the blood SAA. A ratio of intrathecal SAA to blood SAA that is >2 supports the hypothesis that the immune reaction is more important within the CNS and strongly suggests the intrathecal presence of the microorganism .
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