Controversies in Neurological Infectious Diseases

John E. Greenlee, MD and John W. Rose, MD, Neurology Service, Veterans Affairs Medical Center and Department of Neurology, University of Utah Health Science Center, Salt Lake City, Utah.

Semin Neurol. 2000;20(3) 

In This Article

What is the Role of Mycoplasma Pneumoniae in Central Nervous System Disease?

Myalgias and headaches are common complications of infection with Mycoplasma pneumoniae. Neurological illness was first associated with M. pneumoniae in 1943.[102] Over the years, both peripheral and central nervous system complications of M. pneumoniae infection have been reported with and without antecedent systemic symptoms.[103,104,105,106] Nonetheless, however, the actual ability of M. pneumoniae to cause neurological disease has remained a matter of debate.

Peripheral complications of M. pneumoniae infection have included both demyelinating and axonal neuropathies, plexopathies, radiculopathies, and Guillain-Barré syndrome. These are, in comparison with CNS complications, better understood and more clearly the result of host immune response. Axonal neuropathy has been reported following M. pneumoniae infection and has been associated with circulating IgM anti-GM1 anti-bodies.[107]M. pneumoniae-associated acute demyelinating peripheral neuropathy has been associated with anti-bodies to Gal-C.[108]

The respective roles of acute infection per se and the host immune response in the CNS complications of M. pneumoniae infection are less well understood. That M. pneumoniae may invade the CNS is unquestioned.[109,110] Furthermore, although very few workers have studied persistence of mycoplasma in CSF over time, Abramovitz et al, in studies of two patients, were able to demonstrate the organism in CSF up to 8 weeks following the onset of neurological symptoms.[110] Our current knowledge suggests three groups of syndromes that may complicate M. pneumoniae infection: acute meningoencephalitis, which appears to be associated with direct CNS invasion; delayed neurological complications, which may or may not be solely autoimmune; and, least commonly, a CNS vasculitis.

Neurological Complications Directly Associated With M. Pneumoniae Infection

These include aseptic meningitis and encephalitis. [104,111,112,113] In a number of cases in the literature, however, the duration of apparent M. pneumoniae infection prior to the onset of neurological symptoms is not known.[109]

"Postinfectious" Complications of M. Pneumoniae Infection

The majority of neurological illnesses associated with M. pneumoniae infection have occurred at some interval of time following infection and, in cases with a fatal outcome, have involved neuropathological findings of perivascular infiltrates or demyelination, ball hemorrhages, or edema consistent with postinfectious leukoencephalitis.[114,115,116,117] Transverse myelitis has also been described, as has an encephalitis lethargica-like illness with magnetic resonance imaging (MRI) changes in the basal ganglia.[118,119,120] In these cases, organisms have not been detectable in brain or spinal fluid by electron microscopy, culture, or PCR.[121,122] Fernandez et al studied two patients with encephalomyelitis whose onset followed systemic M. pneumoniae infection. Organisms could not be cultured from CSF or detected in CSF using a genomic probe. Specific antibody could not be detected in CSF from one of the patients, and low titers found in the second patient were thought secondary to contamination of CSF with blood.[122] In contrast to these findings, a few reports have described detection of organisms in patients with postinfectious encephalomyelitis. Both patients reported by Abramovitz et al developed neurological symptoms over 2 weeks after the onset of respiratory symptoms. Narita et al,[122a] in 1992, detected M. pneumoniae DNA sequences in four of six patients with neurological complications of M. pneumoniae infection. In three patients, the onset of neurological symptoms followed respiratory symptoms by 8 to 14 days; the fourth patient did not have respiratory symptoms. The continued presence of organisms in patients with otherwise typical postinfectious encephalomyelitis does not, of course, exclude an immune causation of the neurological illness.

In a few patients, M. pneumoniae infection has been associated with a syndrome of cerebrovascular thrombosis or of capillary injury without evidence of demyelination.[104,123] The pathogenesis of neurological injury in these cases and their relationship to M. pneumoniae infection are not known.


That M. pneumoniae can invade the nervous system is certain, and a growing body of evidence supports the ability of this agent to cause neurological disease directly. Similarly, a number of individual case reports demonstrate that the organism is associated with postinfectious central and peripheral nervous system injury. In some of these cases, the mechanism of autoimmune injury has been defined.[107,108,117] In many cases, however, the respective pathogenic roles of the organism it-self and of host immune response remain undefined and await further studies employing careful imaging as well as modern serological and molecular diagnostic methods.


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