of the central nervous
Kevin RostasyMD, Department of Paediatrics and Paediatric
Neurology, Georg August University Göttingen;
Jens GieffersMD, Institute of Medical Microbiology and
Hygiene, University of Lübeck, Germany.
Matthias MaassMD, Institute of Medical Microbiology,
Hygiene and Infectious Diseases, Salzburg University
Folker Hanefeld*MD, Department of Paediatrics and
Paediatric Neurology, Georg August University Göttingen,
*Correspondence to last author atDepartment of
Paediatrics and Paediatric Neurology, Georg-August-Universität
Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
It has been suggested that Chlamydia pneumoniae
(C. pneumoniae) is involved in the pathogenesis of diverse
diseases of the central nervous system (CNS), including multiple
sclerosis. We report the case of a 12-year-old male with isolated
recurrent optic neuritis and an associated CNS infection with C.
pneumoniae. The patient presented with three attacks of optic
neuritis within 5 months. A positive polymerase chain reaction
for C. pneumoniae in the cerebrospinal fluid led to the
diagnosis of a CNS infection with C. pneumoniae. After
treatment with the antibiotic rifampicin, he experienced no
further attacks during the follow-up period of 6 years. These
findings suggest the possibility of a C. pneumoniae infection
as a contributing factor or even causative event for the
development of optic neuritis.
Optic neuritis is an acute demyelinating inflammatory dis-
ease of the optic nerve, leading to a reversible loss of vision.
Childhood optic neuritis is believed to have a lower risk of
recurrence and progression to multiple sclerosis (MS) com-
pared with optic neuritis in adults (Lucchinetti et al. 1997). It
can be associated with infections such as measles, varicella,
rubella, mumps, and infectious mononucleosis as well as with
immunizations (Selbst et al. 1983, Riikonen et al. 1988,
Lucchinetti et al. 1997).
Chlamydia pneumoniae (C. pneumoniae)is an intracellu-
lar pathogen responsible for a number of different acute and
chronic infections. It has been reported as a possible cause of
encephalitis, central nervous system(CNS) vasculitis, and acute
disseminated encephalomyelitis (ADEM; Stratton and Sriram
2003). A correlation between C. pneumoniae infection and
MS has also been suggested (Sriram et al. 1999, Buljevac
et al. 2003, Munger et al. 2003, Contini et al. 2004, Dong-Si
et al. 2004), but is conflicting (Kaufman et al. 2002,
Chatzipanagiotou et al. 2003, Furrows et al. 2004, Munger
et al. 2004). There is rising evidence that C. pneumoniae is
found in the CNS in a variety of neurological diseases
(Gieffers et al. 2001).
We present the first case, to our knowledge, of a CNS infec-
tion with C. pneumoniaein a patient with recurrent opticneu-
ritis. Thus, in view of the potential benefits of antibiotic
therapy, paediatricians, neurologists, and ophthalmologists
Developmental Medicine & Child Neurology 2006, 48: 770–772
See end of paper for list of abbreviations.
should consider C. pneumoniae as a possible causative or
aggravating agent in inflammatory CNS diseases including
In July 1998, a male aged 12 years 2 months presented with
blurred vision accompanied by painful eye movements, verti-
go, headache, nausea, and repetitive vomiting. Ophthalm-
ologic examination revealed papilledema and reduced visual
acuity to less than 0.1 on both eyes. Visual evoked potentials
showed bilateral prolongation of latencies and lowering of
amplitudes. Cerebral magnetic resonance imaging (MRI)
demonstrated diffuse thickening of both optic nerves in the
absence of other intracerebral lesions. Cerebral spinal fluid
(CSF) leukocyte count (36/µl) and protein content (0.59g/l)
were moderately elevated in the absence of oligoclonal
immunoglobulin (Ig)G. A positive IgG and negative IgM titre
for C. pneumoniae, as determined by microimmunofluores-
cence test (Labsystems, Helsinki, Finland), was noted in the
serum (Table I). Serological findings were unremarkable for
human immunodeficiency virus types 1 and 2, herpes simplex
virus types 1 and 2, human herpes virus 6, varicella zoster virus,
Epstein-Barr virus, cytomegalovirus, tick-borne encephalitis
virus, measles, mumps, rubella, Borrelia burgdorferi, and
Mycoplasma pneumoniae. Clinical and paraclinical findings
led to the diagnosis of bilateral optic neuritis. A 3-day course of
prednisolone was followed by marked improvement of symp-
toms and full recovery of visual acuity 3 weeks later.
In October 1998, the patient presented with left-sided optic
neuritis. CSF analysis showed a normal cell count and protein
content. A nested polymerase chain reaction (PCR) for C. pneu-
moniae was performed as previously described (Gieffers et al.
2001), and revealed a positive signal in the CSF, but not in
peripheral blood monocytes. The patient was subsequently
treated with erythromycin (500mg tid) and trimethoprim/sul-
famethoxazole (160mg/800mg bid) for 5 weeks.
A repeat lumbar puncture in November 1998 after 3 weeks
of antibiotic treatment still showed a positive PCR for C.
pneumoniae. In December 1998, the patient had a third attack
of optic neuritis, this time right-sided. Antibiotic treatment
was changed to rifampicin (300mg bid for 5wks), and a fast
and complete recovery occurred. After 4 weeks of rifampicin
treatment, CSF analysis showed normal cell count and pro-
tein content, no oligoclonal IgG, and a negative PCR result
for C. pneumoniae. Rifampicin treatment was discontinued.
In the following years the patient’s neurological and visual
status remained normal. Follow-up visits 1, 2, and 5 years later
showed normal cerebral MRI findings, visual evoked poten-
tials, and visual acuity.
To our knowledge, this is the first report of an association of
optic neuritis with C. pneumoniaeinfection of the CNS, sup-
ported by a positive PCR signal for C. pneumoniaein the CSF.
No such signal could be detected in peripheral blood mono-
cytes, thereby ruling out a secondary contamination in the
course of lumbar puncture.
Optic neuritis is an acute inflammation of the optic nerve,
leading to reversible loss of vision. The inflammatory lesion in
the optic nerve resembles the plaques found in MS. Childhood
optic neuritis is believed to progress to MS in a lower frequency
than adult onset optic neuritis. A large North American follow-
up study of childhood optic neuritis reported a development
of MS in only 26% of paediatric patients, as opposed to more
than 50% in adults (Lucchinetti et al. 1997). However, there
might be regional differences: in Finland, a country with a high
prevalence of MS, Riikonen et al. (1988) observed that 56% of
children with optic neuritis later developed MS. The pathogen-
esis of optic neuritis is not yet understood, but similar to the
aetiology of MS, an autoimmune response to myelin antigens,
possibly triggered by infectious agents, is suggested.
Chlamydiae are obligate intracellular pathogens able to
cause chronic persistent infection and immune mediated tis-
sue injury. C. pneumoniae was reported to be possibly invol-
ved in the pathogenesis of inflammatory CNS diseases, includ-
ing MS, by some research groups (Sriram et al. 1999, Buljevac
et al. 2003, Munger et al. 2003, Stratton and Sriram 2003,
Contini et al. 2004, Dong-Si et al. 2004), while others did not
support any association between C. pneumoniae and MS
(Chatzipanagiotou et al. 2003, Furrows et al. 2004, Munger et
al. 2004). However, two recent reports suggest a role for C.
pneumoniae,especially in relapsing remitting MS, as opposed
to primary or secondary chronic progressive MS (Contini et al.
2004, Dong-Si et al. 2004). The pathogen was significantly
more frequent in active than in stable MS (Contini et al. 2004),
and an increased risk of MS attacks during episodes of C. pneu-
moniae infections was reported (Buljevac et al. 2003). Altho-
ugh it cannot be excluded that C. pneumoniae is only an
opportunistic pathogen that takes advantage of a disease
process initiated by other means, it has been shown to induce
and worsen experimental autoimmune encephalomyelitis, a
rodent model for human MS (Lenz et al. 2001, Du et al. 2002).
Remarkably, the detection of C. pneumoniaeDNA in CSF is not
specific for MS, the pathogen was also found in other inflam-
matory neurological diseases (Gieffers et al. 2001, Contini et al.
2004, Dong-Si et al. 2004).
The mechanisms by which C. pneumoniaecould contribute
to CNS inflammation are still elusive, but myelin-reactive T-cells
might be cross-reactive with a peptide motif present within
the C. pneumoniae antigen (Lenz et al. 2001). Alternatively,
autoreactive lymphocytes could be stimulated via nonanti-
In rodents infected with C. pneumoniae, inflammatory
CNS disease was attenuated with anti-infective therapy (Du et
al. 2002). In humans, successful treatment of bacterial CNS
Table I: Clinical history and evidence for C. pneumoniae in
cerebral spinal fluid (CSF)
Clinical Nested PCR
PCR, polymerase chain reaction; PMBC, peripheral blood
mononuclear cells; MIF, microimmunofluorescence test; IgM,
immunoglobulin M; IgG, immunoglobulin G; ND, not determined.
Developmental Medicine & Child Neurology 2006, 48: 770–772
infections with antibiotics can be difficult in the presence of an
intact blood–CSF barrier due to difficulties in attaining bacteri-
cidalCSF concentrations. This might explain the failure of the
initial antibiotic therapy with erythromycin and co-trimoxa-
zole in our patient. Only after therapy with rifampicin, an
antichlamydial agent with good CSF penetration, a lasting
remission of the recurrent optic neuritis was achieved.
However, since the natural course of relapsing optic neuritis is
variable, the contribution of the rifampicin treatment to the
clinical remission of the patient is difficult to assess.
While there is still little known about the frequency and
clinical spectrum of CNS infections with C. pneumoniae, the
possible benefit of antibiotic treatment should lead to its con-
sideration as a contributing factor in optic neuritis and other
inflammatory CNS diseases. We would, therefore, recommend
including C. pneumoniaein the diagnostic work-up for patients
with optic neuritis or other inflammatory CNS diseases of
Accepted for publication 12th December 2005.
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List of abbreviations
Acute disseminated encephalomyelitis
Polymerase chain reaction