ReviewCentral nervous system manifestations of Mycoplasma pneumoniae infections
Introduction
Mycoplasma pneumoniae is a frequent cause for human infection. The association between Mycoplasma spp. infection and CNS involvement is known for a long time.1 However, the pathogenesis of CNS disease seen in association with M. pneumoniae infection is still a matter of intensive research with several potential mechanisms explaining the neurological disease after such infections. The evolution of diagnostic testing with newer molecular techniques including PCR and Western blot helped to better define this association.2, 3, 4, 5 The purpose of this review is to clarify clinical-epidemiological data, diagnostic pitfalls and treatment approaches on M. pneumoniae associated CNS manifestations. All published literature (Entrez-Pubmed database years: 1966–2004) on CNS involvement seen in association with. M. pneumoniae infection was reviewed.
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Epidemiology
Approximately 1–10% of serologically confirmed M. pneumoniae infections deemed severe enough to require hospitalization are associated with neurological manifestations.6, 7, 8 However, the overall incidence of CNS complications for all M. pneumoniae infections may be much lower, less than 0.1%.1, 9 M. pneumoniae is considered as one of the major causes of encephalitis in children3, 10, 11 and in most prospective studies 5–10% of these cases is attributed to M. pneumoniae.3, 8, 12 For other CNS
Pathogenesis of M. pneumoniae related CNS disease
Several mechanisms could theoretically explain the CNS manifestations seen in association with M. pneumoniae infections. These include direct invasion of the CNS, immune phenomena, vascular injury and hypercoagulable state and toxic effects (Fig. 1). Encephalitis provides the best example to describe the obscure pathogenesis of these manifestations as it was the most frequent CNS manifestation observed in the reviewed series.
Early and late onset encephalitis represent two distinct encephalitic
Clinical findings of CNS manifestations associated with M. pneumoniae infection
M. pneumoniae infections can be completely asymptomatic.63 In most of the cases reviewed, respiratory illness, usually mild, has preceded or coincided with the CNS findings.2, 3, 10, 16 The interval between the onset of respiratory symptoms and neurologic manifestations had a range of 2–14 days.13, 26
M. pneumoniae infection has been associated with the development of several neurological findings indicative of focal or diffuse injury and there may be cerebellar involvement3, 6, 8, 9, 22, 26, 40
Diagnosis
Routine laboratory tests such as the peripheral leucocyte count, erythrocyte sedimentation rate, and chest radiograph are not helpful in establishing a definitive diagnosis of M. pneumoniae infection.
M. pneumoniae related CNS disease and co-infections
Frequently there is evidence of co-infection with another pathogen such as a member of the herpes viruses group especially in encephalitis cases.3, 11, 12 Isolation of a coinfecting organism was evident by use of culture, PCR, or antigen detection in 5 of the 11 (45%) patients who were classified as having probable M. pneumoniae encephalitis by Bitnun et al.3 The co-identification of more than one pathogen especially if made on the basis of serology testing only must in many circumstances draw
Treatment of M pneumoniae related CNS disease
Several therapeutics measures have been used for the treatment of M. pneumoniae related CNS disease such as antibiotics, corticosteroids, intravenous immunoglobulin and plasmapheresis with various success.
Antibiotic therapy has been associated with clinical improvement in several encephalitis cases14, 16, 20, 21, 22, 27, 39, 43, 48, 143 but not in others.2, 6, 8, 16, 28, 30 Most authors use the intravenous route of administration. On the other hand complete neurologic recoveries without
Prognosis
M. pneumoniae associated encephalitis can be a severe disease.8 High CSF pleocytosis and protein levels likely do not carry any significance8 in contrast to previous reports.109 Intensive care unit treatment was necessary in 30% of the patients of a large Finnish study10 and in the same study the mean duration of hospital stay was 2–3 weeks.10 In another report13 5 out of 17 (29%) patients required intensive care because of intractable seizure or respiratory failure. Cases following a more
Conclusion
In conclusion, the recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between infection with M. pneumoniae and CNS disease. Clinicians should be aware of this potential association between M. pneumoniae infection and several CNS manifestations, when confronted with neurologic symptoms of unknown cause especially if the patient's history includes prior symptoms from the respiratory tract. They should attempt to
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