Elsevier

Journal of Infection

Volume 51, Issue 5, December 2005, Pages 343-354
Journal of Infection

Review
Central nervous system manifestations of Mycoplasma pneumoniae infections

https://doi.org/10.1016/j.jinf.2005.07.005Get rights and content

Abstract

Mycoplasma pneumoniae infection is associated with several manifestations from the central nervous system (CNS) such as encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy. In the current paper epidemiologic, clinical, laboratory and treatment data on these manifestations are reviewed. The M. pneumoniae induced immune dysregulation and its contributing role in the pathogenesis of neurological insult is discussed. The recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between M. pneumoniae infection and CNS disease especially encephalitis. Clinicians should be aware of the potential association between M. pneumoniae infection and several CNS manifestations. The role of various anti-microbial or immunomodulating therapies in treating such manifestations should be further explored.

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.

Section snippets

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

References (163)

  • H. Merkx et al.

    Miller Fisher syndrome associated with Mycoplasma pneumoniae infection: Report of a case

    Clin Neurol Neurosurg

    (1994)
  • D. Kountouras et al.

    Fulminant Mycoplasma pneumoniae infection with multi-organ involvement: A case report

    Eur J Intern Med

    (2003)
  • M.C. Delmas et al.

    Neurologic manifestations of Mycoplasma pneumoniae infections

    Arch Pediatr

    (1996)
  • C.C. Tijssen et al.

    Transverse myelitis associated with Mycoplasma pneumoniae infection

    Clin Neurol Neurosurg

    (1982)
  • L. Yesnick

    Central nervous system complications of primary atypical pneumonia

    AMA Arch Intern Med

    (1956)
  • M. Narita et al.

    Survey of mycoplasmal bacteremia detected in children by polymerase chain reaction

    Clin Infect Dis

    (1996)
  • A. Bitnun et al.

    Acute childhood encephalitis and Mycoplasma pneumoniae

    Clin Infect Dis

    (2001)
  • M.F. Duffy et al.

    Indirect enzyme-linked immunosorbent assay for detection of immunoglobulin G reactive with a recombinant protein expressed from the gene encoding the 116-kilodalton protein of Mycoplasma pneumoniae

    J Clin Microbiol

    (1999)
  • M.F. Duffy et al.

    The immunoreactive 116 kDa surface protein of Mycoplasma pneumoniae is encoded in an operon

    Microbiology

    (1997)
  • K. Lind et al.

    Mycoplasma pneumoniae infection associated with affection of the central nervous system

    Acta Med Scand

    (1979)
  • G. Sterner et al.

    Central nervous system complications of Mycoplasma pneumoniae infection

    Scand J Infect Dis

    (1969)
  • A. Ponka

    Central nervous system manifestations associated with serologically verified Mycoplasma pneumoniae infection

    Scand J Infect Dis

    (1980)
  • B. Pfausler et al.

    Post-infectious central and peripheral nervous system diseases complicating Mycoplasma pneumoniae infection. Report of three cases and review of the literature

    Eur J Neurol

    (2002)
  • M. Koskiniemi

    CNS manifestations associated with Mycoplasma pneumoniae infections: Summary of cases at the University of Helsinki and review

    Clin Infect Dis

    (1993)
  • H. Kolski et al.

    Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994–1995

    Clin Infect Dis

    (1998)
  • E. Lehtokoski-Lehtiniemi et al.

    Mycoplasma pneumoniae encephalitis: A severe entity in children

    Pediatr Infect Dis J

    (1989)
  • W.C. Lin et al.

    Mycoplasma pneumoniae encephalitis in childhood

    J Microbiol Immunol Infect

    (2002)
  • M. Narita et al.

    Analysis of mycoplasmal central nervous system involvement by polymerase chain reaction

    Pediatr Infect Dis J

    (1995)
  • G. Lum et al.

    Severe encephalitis in a three-year-old girl

    Pediatr Infect Dis J

    (1996)
  • N.H. Thomas et al.

    Mycoplasma pneumoniae infection and neurological disease

    Arch Dis Child

    (1993)
  • M. Abele-Horn et al.

    Molecular approaches to diagnosis of pulmonary diseases due to Mycoplasma pneumoniae

    J Clin Microbiol

    (1998)
  • A.R. Tunkel et al.

    Pathogenesis and pathophysiology of bacterial meningitis

    Clin Microbiol Rev

    (1993)
  • R.J. Koletsky et al.

    Fulminant Mycoplasma pneumoniae infection. Report of a fatal case, and a review of the literature

    Am Rev Respir Dis

    (1980)
  • I. Kasahara et al.

    Isolation and characterization of Mycoplasma pneumoniae from cerebrospinal fluid of a patient with pneumonia and meningoencephalitis

    J Infect Dis

    (1985)
  • K. Suzuki et al.

    A case of Mycoplasma pneumoniae pneumonia associated with meningoencephalitis

    Nihon Kyobu Shikkan Gakkai Zasshi

    (1982)
  • P. Abramovitz et al.

    Direct invasion of the central nervous system by Mycoplasma pneumoniae: A report of two cases

    J Infect Dis

    (1987)
  • Y. Nagayama et al.

    Isolation of Mycoplasma pneumoniae from pleural fluid and/or cerebrospinal fluid: Report of four cases

    Scand J Infect Dis

    (1987)
  • M. Narita et al.

    DNA diagnosis of central nervous system infection by Mycoplasma pneumoniae

    Pediatrics

    (1992)
  • C.S. Padovan et al.

    Detection of Mycoplasma pneumoniae DNA in cerebrospinal fluid of a patient with M. pneumoniae infection-‘associated’ stroke

    Clin Infect Dis

    (2001)
  • M. Socan et al.

    Neurological symptoms in patients whose cerebrospinal fluid is culture—and/or polymerase chain reaction—positive for Mycoplasma pneumoniae

    Clin Infect Dis

    (2001)
  • D. Dionisio et al.

    Encephalitis caused directly by Mycoplasma pneumoniae

    Scand J Infect Dis

    (1999)
  • J.H. Tjhie et al.

    Fatal encephalitis caused by Mycoplasma pneumoniae in a 9-year-old girl

    Scand J Infect Dis

    (1997)
  • J. Launes et al.

    Direct invasion of the brain parenchyma by Mycoplasma pneumoniae

    Acta Neurol Scand

    (1997)
  • M. Ieven et al.

    Fatal encephalitis caused by Mycoplasma pneumoniae diagnosed by the polymerase chain reaction

    Clin Infect Dis

    (1998)
  • P. Fleischauer et al.

    Demonstration of Mycoplasma pneumoniae in cerebrospinal fluid in acute polyneuritis

    Dtsch Med Wochenschr

    (1972)
  • S. Rottem et al.

    Mycoplasma interaction with host eukaryotic cells

  • D.F. Talkington et al.

    Emerging from obscurity: Understanding pulmonary and extrapulmonary syndromes, pathogenesis, and epidemiology of human Mycoplasma pneumoniae infections

  • D.F. Talkington

    Mycoplasmal and ureaplasmal infections of the central nervous system

  • M.F. Balish et al.

    Cytadherence and the cytoskeleton

  • K.B. Waites et al.

    Mycoplasma pneumoniae and its role as a human pathogen

    Clin Microbiol Rev

    (2004)
  • Cited by (161)

    • Anisocoria and optic neuritis associated with Mycoplasma pneumoniae infection

      2023, Enfermedades Infecciosas y Microbiologia Clinica
    • Who gets a laboratory positive diagnosis of Mycoplasma pneumoniae: A 10-year retrospective analysis

      2021, Clinical Infection in Practice
      Citation Excerpt :

      Despite the potential long-term impact of neurological disease, the pathophysiology is poorly understood (D'Alonzo et al., 2018). Three main mechanisms of damage to the nervous system have been proposed: direct structural and functional damage; immune-modulated changes; and vascular microthrombotic disease (Tsiodras et al., 2005; D'Alonzo et al. 2018). Treatment options are limited and include immunoglobins and antimicrobials.

    • A Case of Mycoplasma Pneumoniae Encephalopathy Presenting as Mania

      2021, Journal of the Academy of Consultation-Liaison Psychiatry
    View all citing articles on Scopus
    View full text