Mycoplasma pneumoniae infection: neurologic complications …

John E Greenlee MD

Infectious Disorders

Updated 06.20.2024
Released 08.20.2007
Expires For CME 06.20.2027

Mycoplasma pneumoniae infection: neurologic complications

Author: John E Greenlee MD

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Mycoplasma pneumoniae infection: neurologic complications

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Introduction

Overview

Mycoplasma pneumoniae has been associated with a wide variety of infectious and postinfectious neurologic illnesses. The agent almost certainly causes neurologic disease; however, many aspects of its association with central and peripheral nervous system injury remain controversial. Possible mechanisms of injury include direct infection, postinfectious (ie, autoimmune) events, and vascular compromise. In this article, the author reviews the pathogenesis, clinical features, diagnosis, and treatment of this disorder.

Key points

	• The role of Mycoplasma pneumoniae as an agent causing neurologic disease has been controversial, both because the organism is difficult to isolate and because elevated titers of antibody against M pneumoniae may be detected in patients with neurologic conditions due to other infectious agents.
	• Two major groups of neurologic conditions have been associated with the agent: cases of meningoencephalitis, in which Mycoplasma organisms or DNA can be detected in CSF, and conditions that appear to be postinfectious and caused by host immune response. Less frequently, a syndrome of cerebrovascular thrombosis involving large or small vessels has been associated with M pneumoniae infection.
	• A second Mycoplasma organism, M hominis, may occasionally cause meningitis or brain abscess in infants and rarely in adults following neurosurgical procedures or head trauma.
	• Because Mycoplasma species lack a cell wall, penicillins, cephalosporins, and vancomycin are ineffective. Erythromycin and tetracyclines have traditionally been used to treat cases of acute M pneumoniae meningitis or encephalitis, although a variety of other antibiotics have been used in individual patients. Tetracyclines are avoided in children because of their effects on developing teeth and bones.
	• There are no controlled studies of immunosuppressive or immunomodulatory treatment for postinfectious neurologic complications of Mycoplasma infection. In individual cases, improvement of symptoms has followed treatment with methylprednisolone, plasma exchange, and intravenous immunoglobulin G.

Historical note and terminology

Following the introduction of sulfonamides and antibiotics, clinicians identified cases of pneumonia in which organisms could not be identified and that did not respond to usual antibiotic therapy. These cases came to be termed “primary atypical pneumonia.” In 1944, Eaton discovered that sputum and lung tissue from such cases contained an agent that could pass through 45 µm filters, which were permeable to viruses but not bacteria, and he demonstrated that this filtered agent could cause focal pulmonary infiltrates in rodents (50). Eaton, along with others, subsequently demonstrated that convalescent sera from patients with primary atypical pneumonia could neutralize this agent. Soon thereafter, Finland and colleagues demonstrated that sera from approximately 70% of such patients could agglutinate red blood cells at cold temperatures (56). Transmission of the agent to human volunteers was accomplished in 1946, followed by growth of the agent in tissue culture and then in cell-free media. Confirmation that the “Eaton agent” was in fact the cause of primary atypical pneumonia came only later, in the 1960s, with transmission of pneumonia to human volunteers using organisms isolated in cell-free culture (75; 13).

Early descriptions of primary atypical pneumonia noted accompanying headaches and myalgias, and the first association of primary atypical pneumonia infection with neurologic symptoms was observed in 1943 (34). Over the years, individual case reports have described a wide variety of complications associated with Mycoplasma pneumoniae infection, including cases with neurologic complications in the absence of systemic symptoms and cases that appear to be postinfectious rather than being caused directly by the organism (85; 84; 09). Despite many case reports over many years, however, the extent to which M pneumoniae is involved in the causation of human neurologic disease remains uncertain (43). Three reasons have existed for this uncertainty. First, mycoplasma are frequent laboratory contaminants, with an accompanying risk of falsely positive studies: this was of particular concern in some early case reports. Second, actual isolation of M pneumoniae is technically demanding, with handling and culture requirements that are more exacting than those in routine use; this can now be circumvented through the use of polymerase chain methods (09; 110). Third, serological testing for mycoplasma is imprecise in its diagnostic utility because of false negatives and, of significant importance for neurologists, because patients with neurologic involvement due to other agents may sometimes develop elevated antibody titers to M pneumoniae (24; 65).

Over time, two major overlapping patterns of neurologic involvement have been associated with M pneumoniae infection: cases which appear to represent direct CNS invasion by the agent, and cases in which neurologic injury is thought to occur through autoimmune, “postinfectious” mechanisms (118; 109; 107; 70; 09; 76; 105; 113; 168; 169). In the former group, organisms may be detected in CSF by culture or polymerase chain reaction methods. The latter, apparently postinfectious group is comprised in large part of cases in which diagnosis was made by serological methods or PCR detection of the organism in oropharyngeal samples, without detection of the organism in CSF (54; 55; 47; 109; 107; 70; 09; 76; 105; 113; 168; 169; 26). In a minority of these cases, however, M pneumoniae has been identified in CSF by culture or polymerase chain reaction methods (114; 115; 118; 107; 09; 76; 105; 113).

Less frequently, other species of Mycoplasma may cause neurologic disease; these will be discussed separately, below.

Clinical manifestations

Presentation and course

	• The majority of cases of Mycoplasma pneumoniae infection present with respiratory symptoms, with a paucity of findings on chest auscultation despite unequivocal abnormalities on chest radiographs. However, a variety of systemic presumably postinfectious complications may also occur.
	• The great majority of cases of Mycoplasma pneumoniae infection are not accompanied by neurologic illness. However, up to 20% of cases presenting with neurologic symptoms will have no history of respiratory symptoms.
	• Neurologic complications of Mycoplasma pneumoniae infection include meningitis or encephalitis, a variety of postinfectious complications, and, less frequently, CNS vasculitis or hemorrhage.
	• A second Mycoplasma species, Mycoplasma hominis, may cause meningoencephalitis or brain abscess in neonates and, rarely, CNS infections in adults, usually following neurosurgical procedures or head trauma.

Systemic infection by Mycoplasma pneumoniae. The onset of typical Mycoplasma pneumonia is usually gradual but may be acute, with throat irritation and dry cough. Symptoms of systemic illness are common and include fever, headache, which may at times be severe, and chest pain. Physical examination is usually benign, and initial chest findings often minimal or absent on auscultation, with râles appearing only later in the course of infection. In contrast, chest radiographs at presentation frequently show pulmonary infiltrates that are out of keeping with findings on physical examination. The classical presentation of M pneumoniae infection, then, is of a systemically ill patient with a cough, with little in the way of findings on chest auscultation, and yet with unequivocal pulmonary infiltrates on x-ray. Clinical recovery and resolution of chest infiltrates in untreated cases may be extremely prolonged and, even in treated cases, resolution of symptoms may take up to several weeks.

Although symptomatic infection is usually confined to the pulmonary system, a wide variety of extrapulmonary complications have been reported. These include autoimmune renal syndromes; hemolytic anemia; thrombocytopenic purpura; disseminated intravascular coagulation; severe rhabdomyolysis; dermatological conditions, including Stevens-Johnson syndrome; Raynaud phenomenon, cardiac involvement with chest pain, arrhythmias, and EKG changes; polyarthralgias; arthritis; and uveitis with retinal vasculitis (77; 13; 15; 156; 102; 113; 33; 63; 27).

The majority of cases of Mycoplasma pneumoniae infection are not accompanied by neurologic illness. Conversely, as many as 20% of cases presenting with neurologic symptoms will have no history of respiratory symptoms (147; 114; 109).

Neurologic conditions directly associated with Mycoplasma pneumoniae infection. These may occur with or without accompanying respiratory symptoms or findings (84; 147; 114; 76; 106; 113). Neurologic syndromes associated with M pneumoniae infection include aseptic meningitis, encephalitis, and, less frequently, a syndrome of CNS vasculitis (77; 02; 84; 148; 73; 35; 46; 24; 172; 129; 09; 76; 106). The clinical picture of meningitis in these patients typically resembles that seen in viral meningitis, with nuchal rigidity and photophobia (84; 35; 138; 107; 09); and many cases of M pneumoniae encephalitis have a presentation and course similar to that seen in enteroviral encephalitis (46). Although most cases run a benign course, fatalities have occurred (161; 95; 84; 99; 148; 73; 126), as have cases with severe permanent disability (53; 07; 46; 97; 11; 76).

Postinfectious complications of Mycoplasma pneumoniae infection. In addition to presentation with meningitis or encephalitis, a large number of patients have been reported with other neurologic events occurring in association with M pneumoniae infection. These include psychosis, acute disseminated encephalomyelitis, brainstem encephalitis, cerebellar ataxia, diffuse or transverse myelitis, a poliomyelitis-like syndrome, optic neuritis, radiculopathies, brachial plexopathies, demyelination with anti-MOG antibodies, and Guillain-Barré syndrome (139; 158; 83; 112; 133; 114; 28; 123; 165; 01; 69; 74; 80; 46; 14; 24; 23; 130; 138; 124; 11; 61; 150; 151; 141; 12; 107; 09; 108; 106; 27; 122). Several cases of opsoclonus-myoclonus associated with serologically diagnosed M pneumoniae have been described in adolescents and adults (71; 104; 120). Several cases have been reported in which serological, culture, or DNA evidence of mycoplasma infection has accompanied a syndrome of bilateral thalamic or striatal involvement (07; 133; 28; 93; 165; 10; 134; 11; 92; 51; 168). Reversible splenial lesions detectable on MRI have also been described (39; 152; 48), as has posterior reversible encephalopathy syndrome (127). The relationship between many of these illnesses and M pneumoniae infection has been uncertain: in the majority of these cases, attempts to detect M pneumoniae or its DNA in CSF have either not been attempted or have been unsuccessful, and diagnosis has been based on serology or isolation of the organism from other sites. In a few cases, however, CSF has been positive for organisms (133; 01; 130; 42; 09; 152). Stamm and colleagues have reported detection of Mycoplasma antigens postmortem in the brain of a patient who died of disseminated encephalomyelitis and polyradiculitis in the setting of Mycoplasma-associated pneumonia (140). In studies employing immunofluorescence methods, Powers and Johnson detected Mycoplasma antigen in macrophages/microglia, oligodendrocytes, and occasional neurons in the brain of a child dying of acute encephalitis (126). Electron microscopy in this case revealed organisms lacking a cell wall, consistent with Mycoplasma, in perivascular cells and neurons.

Mycoplasma-associated CNS vasculitis. In a few patients, M pneumoniae infection has been associated with a syndrome of cerebrovascular thrombosis involving large or small vessels, as well as capillary injury without evidence of demyelination (49; 155; 58; 121; 143; 113; 60; 103; 04). Symptoms and findings are referable to the central nervous system alone but cortical blindness, related to posterior cerebral artery occlusion has also been reported (60). Sarathchandran and colleagues have reported an unusual case of meningoencephalitis accompanied by aortic and subclavian aneurysms in a patient developing positive serology for M pneumonia (135). The pathogenesis of neurologic injury in these cases and their relationship to M pneumoniae infection is not known. Although it has been suggested that vasculitis in these patients is immune-mediated, in one of these cases M pneumoniae DNA was recovered from CSF (121), and in one other case, Mycoplasma-like organisms were detected within capillary endothelial cells (129).

Infection by Mycoplasma hominis and other mycoplasma species. M hominis is an organism most usually associated with vaginal infection and is a cause of meningoencephalitis or brain abscess in newborns (25; 101; 08; 145; 81; 88; 89; 164). The agent may occasionally cause meningitis in infants (142). A single report in the Japanese literature describes detection of Mycoplasma genitalium DNA in the CSF of a 5-year-old girl with brainstem encephalitis, and a case of meningitis due to Mycoplasma maculosum, acquired from a family pet, has been described in an adolescent with common variable immune deficiency (145).

Central nervous system infection by M hominis is rare: a 2012 review of the literature revealed that 11 cases of M hominis brain abscess (nine cases) or meningitis (two cases) have been reported in adults (94; 16). Of these, eight cases occurred following either cranial trauma or neurosurgical intervention; one case occurred in the setting of an infected cavernous hemangioma; one case occurred following abortion; and one in the postpartum period. Whitson and colleagues have reported a case of cervical intramedullary abscess due to M. hominis in a patient following C6 corpectomy and C7-7 fusion after severe trauma (162). These authors identified 10 additional cases from the literature in which M. Hominis brain or spine infection followed neurosurgical procedures (162). In both series, microbiological diagnosis was frequently difficult and required prolonged incubation in culture. Zhou and colleagues reported meningitis developing in an adult after surgery for intracranial hemorrhage, with M hominis being identified by CSF culture and 16S rDNA sequencing (171). In one other report M hominis was identified by 16S rDNA sequencing alone (94).

Prognosis and complications

The prognosis of Mycoplasma pneumoniae meningitis is benign, with most patients making an uneventful recovery (125). In contrast, encephalitis due to M pneumoniae can be extremely severe (161; 53; 07; 95; 84; 99; 148; 73; 46; 97; 11). Bitnun and colleagues have estimated that 20% to 60% of patients with encephalitis associated with M pneumoniae infection will have neurologic sequelae (23). In Daxboeck’s series of 58 children with M pneumoniae encephalitis, 20 patients (34%) had major or minor neurologic sequelae, and five patients (9%) died. In this series, high CSF cell count and older age were associated with unfavorable outcome (44). Lin and colleagues reported that 47% of patients surviving acute encephalitis with positive Mycoplasma serology went on to develop postencephalitic epilepsy (96). Termine and colleagues reported 4-year follow-up on a patient with M pneumoniae-associated striatal necrosis, who was left with neuropsychiatric sequelae suggestive of a subcortical dementia, with severe obsessive-compulsive disorder, cognitive decline, and deficient executive functioning (146).

Biological basis

Etiology and pathogenesis

Mycoplasma are prokaryocytes lacking a cell wall and represent the smallest known free-living organisms. Because early studies demonstrated that these were “filterable” agents, (ie able to pass through filters that were impermeable to conventional bacteria), Mycoplasma were initially thought to be viruses. Unlike viruses, however, Mycoplasma contain both DNA and RNA and are able to grow in cell-free media. Thirteen strains of Mycoplasma infect humans. Of these, three subgroups of organisms are of particular importance. Mycoplasma pneumoniae produces both upper respiratory infections and pneumonia and is the agent that has most frequently been associated with neurologic infections. Mycoplasma hominis typically causes a variety of non-neurologic conditions including cervicitis, vaginitis, conjunctivitis, peripartum sepsis, and, in particular in immunocompromised patients, sternotomy infections and arthritis, but, as discussed above, can also cause neurologic disease in both children and adults. Mycoplasma fermentans (incognitus strain) has also been associated with severe systemic infection in immunologically normal individuals, as well as in patients with AIDS (05). Rarely, nonhuman Mycoplasma species such as Mycoplasma arginini have been associated with severe human infection (159).

Mycoplasma pneumoniae infection is acquired by the respiratory route, with an incubation period of between 1 and 3 weeks. In most patients, symptomatic infection is confined to the lungs. As mentioned above, however, blood-borne invasion of other organs can occur. CNS invasion by M pneumoniae has been repeatedly demonstrated by culture, amplification of Mycoplasma DNA from CSF, or production of specific antibodies within the CNS. M hominis may be acquired transplacentally or during delivery.

The immune response to M pneumoniae infection involves both B and T cells. Of these, B cell response has received far more attention. Antibody response to M pneumoniae infection involves neutralizing and other antibodies directed specifically against the organism. In addition, infection with M pneumoniae may also result in production of autoantibodies to lung, brain, cardiolipins (in two cases in association with splenic infarcts), and smooth muscle (18; 19; 22; 163; 31). Cold agglutinins, traditionally associated with M pneumoniae infection, are oligoclonal IgM antibodies produced against an altered antigen (the “I” antigen) found on the surface of erythrocytes (13). A number of case reports have identified autoantibodies in cases of neurologic disease associated with the agent. These have included antibodies to GQ1b in patients with brainstem encephalitis or cranial nerve palsies (79; 45), antibodies to anti-GM1b in a patient with M pneumoniae-associated Guillain-Barré syndrome (80), and antibodies to gangliosides (GM1, GM2, and GT1b) in a patient with M pneumoniae-associated encephalitis and cerebellitis (82). Axonal neuropathy has been reported following M pneumoniae infection and has been associated with circulating IgM anti-GM1 antibodies (68; 170). M pneumoniae-associated acute demyelinating peripheral neuropathy has been associated with antibodies to Gal-C (90). A review of patients studied in the California encephalitis project identified a subset of 10 younger patients (aged 11 to 31 years old) who had circulating levels of antibodies to N-methyl-D-aspartate receptors (NMDAR) and who presented with a progressive illness characterized by prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures (59). Two of these patients were found to have ovarian teratomas, as has been reported by other investigators. Of note, however, four of the remaining eight patients had serologic evidence of acute M pneumoniae infection, and the presence of M pneumoniae has subsequently been reported in a patient with NMDAR encephalitis (59; 154). The role of Mycoplasma infection in precipitating NMDAR encephalitis is as yet undetermined.

The role of Mycoplasma-associated autoantibodies in production of neurologic disease has not been delineated (86). Many of these antibodies can also be identified in patients with M pneumoniae infection but without neurologic illness. Nishimura and colleagues have reported high titers of antibodies to Gal-C in all three patient studies with CNS involvement but only in 8 of 32 patients with M pneumoniae infection without CNS involvement and in 2 of 52 uninfected controls (119), and Kuwahara and colleagues have reported detection of both anti-Gal-C IgG and IgM in a series of patients presenting with Guillain-Barre syndrome or Miller Fisher syndrome (91). Smolders and colleagues reported a 9-year-old boy with presumed M pneumoniae infection diagnosed by serum serology who presented high IgM and IgG levels of antibody to galactocerebroside in serum (but not CSF), with encephalopathy characterized by MRI intensities in cortex and basal ganglia (137). Bencina and colleagues have described intrathecal immunoglobulin synthesis of both IgG and IgM to Mycoplasma antigens in patients with neurologic disease in whom M pneumoniae has been detected in CSF by culture, antigen detection, or PCR (14). Elevation of interleukin-18 has been associated with pulmonary manifestations of M pneumoniae infection (116). In one report, elevated levels of interleukin 6, interleukin 8, and interleukin 18 were detected in CSF of patients with M pneumoniae-associated encephalitis, whereas interferon gamma, tumor necrosis factor, and transforming growth factor beta1 were not (117). The actual role of these cytokines in the pathogenesis of neurologic disease has not been delineated. Several earlier workers found that M pneumoniae infection could be associated with depression of T lymphocyte function (20; 21; 132; 111); but the role of this phenomenon in the pathogenesis of mycoplasma-associated neurologic disease has not been investigated.

Epidemiology

Mycoplasma are ubiquitous human agents worldwide. It is estimated that the incidence of diagnosed Mycoplasma pneumonia is approximately one case per 1000 individuals per year, with an even larger number of unreported cases, both with and without actual pneumonia (13). The organism is spread by the respiratory route; children under three years of age tend to develop upper respiratory infections, individuals from 5 to 20 years of age develop bronchitis and pneumonia, and older adults more usually develop pneumonia. Typically, M pneumoniae is introduced into the family by a young child, with subsequent infection of older family members. In populations such as colleges, boarding schools, or military bases, the agent may cause contained epidemics. Although a few studies have suggested that Mycoplasma pneumonia infection is more common in autumn, associated with return of children to school, most studies have shown no seasonal prevalence. Guliera and colleagues have suggested that up to 7% of children hospitalized with M pneumoniae may have neurologic illnesses (65). Although M pneumoniae is not usually considered in the differential diagnosis of meningitis or encephalitis, data suggest that the organism may cause 5% to 10% of cases of childhood encephalitis and may be more common in girls than boys (85). Urquhart, in 1979, reported neurologic complications in 6.7% of patients hospitalized with M pneumoniae infection (153). Bitnum and colleagues, in a prospective study of children with acute encephalitis, detected serological evidence of M pneumoniae infection in 50 of 159 children (31%); in 6.9% of these cases, M pneumoniae was felt to be causative, based on its detection in CSF by polymerase chain reaction methods or by positive serology coupled with culture or PCR detection of the organism in throat samples (24). In a multi-institutional study involving 278 children hospitalized with confirmed encephalitis, Britton and colleagues diagnosed M pneumoniae in 16 (6%) (30). Additional support for CNS invasion by M pneumoniae comes from work by Bencina and colleagues who detected synthesis of anti-Mycoplasma antibodies in the cerebrospinal fluid of 14 of 19 patients in whom M pneumoniae organisms, DNA, or antigen had been detected in CSF (14). In Bitnun’s study, 18.9% of patients with acute encephalitis who were seropositive for M pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis. This observation is important in that it indicates that reliance on serology alone in patients with acute encephalitis is not sufficient to prove that M pneumoniae is the cause of the illness, and it may lead to a misdiagnosis of the actual agent (24).

Mycoplasma hominis, in contrast to M pneumoniae, is primarily a reproductive tract organism. Infants may be colonized during passage through the birth canal, and M hominis may be isolated from the nose, throat, or both, of up to 15% of neonates. Colonization does not usually persist beyond two years of age, although the organism may persist in a minority of girls. In adult life, transmission of M hominis is predominantly through sexual contact. The agent is most frequently associated with genitourinary infections but may cause sepsis in women following abortion. Occasionally, in infants, M hominis may cause meningitis or brain abscess (25; 101; 08; 145; 81; 88; 89; 164; 66). A review by Lee and colleagues identified reported cases of central nervous system invasion by M hominis in only 11 adults (94). Of these, the organism was associated with brain abscess in nine patients and with meningitis in two patients. Ten of the cases occurred in patients with neurosurgical intervention (six patients), cranial trauma (four patients), vaginal delivery, or abortion with uterine curettage (two patients); one brain abscess was reported in the setting of an infected cavernous angioma (94). Whitson and colleagues have reported a patient developing a M hominis intramedullary abscess following cervical trauma and surgery (162). In one other adult, M hominis was associated with iliopsoas abscess in the setting of total discectomy (57). M hominis has been associated with meningitis in adults and should be kept in mind as a possible agent in patients with “culture-negative meningitis” (128; 171).

Diagnostic workup

Mycoplasma pneumoniae infection is primarily a pulmonary agent, and clinical or radiographic lung abnormalities may provide a clue to the presence of M pneumoniae in patients with neurologic illness. It is important to remember, however, that patients may also present with neurologic involvement without pulmonary manifestations. Hematological studies in affected patients may demonstrate a moderate leukocytosis. CSF in M pneumoniae meningitis or encephalitis usually contains a lymphocytic pleocytosis, normal or minimally depressed glucose, and elevated protein (100). Rarely, a polymorphonuclear response may also be seen (03). CSF may be normal in cases of apparently postinfectious illness (78). Electroencephalography may show slowing, seizure activity, transient extreme spindles, or periodic lateralized discharges (72; 17; 06; 32; 167; 67). MRI may be normal but may also show evidence of white matter disease in brain, including unilateral or bilateral injury to thalami or basal ganglia, lesions in the splenium of the corpus callosum, or transverse or diffuse myelitis. In rare cases of vascular occlusion associated with M pneumoniae infection, MRI may show findings consistent with cerebral ischemia (07; 123; 165; 82; 62; 11; 44).

As noted above, elevated titers of antibody to M pneumoniae may be seen in patients with conditions caused by other agents (24). For this reason, diagnosis of M pneumoniae encephalitis should ideally be based on strong evidence of M pneumoniae infection including not only serology but also isolation of the organism in culture or molecular detection techniques, along with exclusion of other potential etiologies (23; 113). Isolation of M pneumoniae in culture is both difficult and time consuming, and for this reason diagnosis of M pneumoniae infection has traditionally relied on detection of serum cold agglutinins or complement-fixing antibodies, as well as tests developed to identify mycoplasma-specific IgM or IgG antibodies. Cold agglutinins usually appear early in the illness and are useful in diagnosis. Cold agglutinins are not specific for M pneumoniae, however, and may be seen in infection with other agents such cytomegalovirus or Epstein-Barr virus (13). Complement-fixing and other anti-Mycoplasma antibodies, although specific, may not appear during the first 7 to 10 days of illness and, hence, may not be detectable at the time of presentation. Increasingly, antigen-capture or polymerase chain reaction methods have been applied to detection of the organism in sputum or nasopharynx, in cases of systemic M pneumoniae infection (13; 98; 113; 87; 110).

Specific identification of M pneumoniae as the causative agent in cases of neurologic illness is complicated by several factors. First, because the organism is extremely fastidious, efforts to culture the organism may fail where polymerase chain reaction identifies Mycoplasma DNA (144; 98). In addition, as mentioned above, serological diagnosis may be delayed or may at times be positive when the condition is caused by some other agent (24; 65). Diagnosis of M hominis CNS infection may also require prolonged incubation of CSF or other cultured material. In one case, diagnosis of M hominis infection was confirmed by 16S rDNA gene sequencing (94). Because of these difficulties, attempts to detect M pneumoniae in CSF has increasingly relied on polymerase chain reaction (110). Next generation metagenomic sequencing (mNGS) has been used to detect M pneumoniae nucleic acids in bronchial secretions and has been used to detect M hominis in cases of neonatal meningitis (157; 166; 38).

Management

	• Mycoplasma pneumoniae infection may result in direct CNS invasion, postinfectious complications, or both conditions simultaneously or sequentially.
	• Antibiotic treatment of Mycoplasma pneumoniae infection most commonly employs a tetracycline or erythromycin. However, erythromycin may not achieve adequate CNS levels, and use of tetracyclines in children may affect developing bone or teeth.
	• Alternative agents for treatment of Mycoplasma pneumoniae CNS infection include azithromycin or clarithromycin as well as newer quinolone antibiotics, such as ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and trovafloxacin. Controlled trials of these agents in Mycoplasma pneumoniae CNS infection have not been reported.
	• Corticosteroids, plasma exchange, and immunoglobulin G have been used as therapeutic modalities in individual patients with postinfectious complications of Mycoplasma pneumoniae infection. However, extensive case series and controlled trials employing these agents have not been reported.

Mycoplasma pneumoniae infection may result in direct CNS invasion, postinfectious complications, or both; and for this reason, decisions as to therapy involve consideration of both antibiotics and also treatments directed at host immune response. Controlled studies, however, do not exist for either of these therapeutic approaches. Because Mycoplasma species lack a cell wall, penicillins, cephalosporins, and vancomycin are ineffective. The drugs of most use for systemic M pneumoniae infection have been erythromycin and tetracyclines, including doxycycline (156). Resistance to erythromycin may occur, however, and erythromycin may not achieve adequate CSF concentrations (149). Tetracycline has been avoided in children because of its effects on developing teeth and bone. Chloramphenicol, which has excellent penetration into CSF and brain, was used in the past as an alternate choice but is no longer available in the United States. Azithromycin and clarithromycin also penetrate the CNS and have been used successfully in cases in which there has been CNS involvement (156). The newer quinolone antibiotics, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and trovafloxacin have been used to treat systemic M pneumoniae infection and warrant consideration in cases with CNS involvement (156; 52; 160). Neurologic complications of infection by M hominis are almost always the result of direct CNS invasion, and considerations of antibiotic therapy are similar to those for M pneumoniae. In one case of neonatal infection with M hominis, recovery followed treatment with ciprofloxacin (164), and in a case by Bergin and colleagues, a patient with M hominis brain abscess responded to surgical drainage and doxycycline (16).

Because many cases of neurologic involvement associated with M pneumoniae appear to have an autoimmune basis, steroids or other measures should be considered, in addition to antibiotic therapy. Here again, no controlled data are available. Carpenter, in a review of 14 cases of M pneumoniae infection with neurologic complications, found significant or complete recovery in 11 of 14 patients (36). Gucuyener and colleagues have reported similar improvement in patients treated with methylprednisolone (64; 71). Relapse in symptoms has been reported following tapering of steroids, with improvement after reinstitution at higher doses (64; 136; 36). Plasma exchange, intravenous immunoglobulin G, and immunoabsorption therapy have all been used in individual cases and could be considered where response to steroids is inadequate (40; 141; 131; 37; 104; 41).

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Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: None
Population groups selectively affected: None selectively affected
Occupation groups selectively affected: None selectively affected

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Mycoplasma pneumoniae infection: neurologic complications

Associated Disorders

Acute demyelinating polyneuropathy
Acute disseminated encephalomyelitis
Acute inflammatory axonal polyneuropathy
Acute inflammatory demyelinating polyneuropathy
Aseptic meningitis
- Brachial plexopathies
- Brainstem encephalitis
- Cerebellar ataxia
- CNS vasculitis
- Encephalitis
- Guillain-Barre syndrome
- Meningitis
- Miller-Fisher syndrome
- Myelitis
- Optic neuritis
- Transverse myelitis

Differential Diagnosis

viral meningitis
viral encephalitis
postinfectious syndromes
CNS large vessel vasculitis
CNS small vessel vasculitis

Mycoplasma pneumoniae infection: neurologic complications …

Mycoplasma pneumoniae infection: neurologic complications

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

Patient Profile

ICD & OMIM codes

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Questions or Comment?

Also in This Category

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Mycoplasma pneumoniae infection: neurologic complications

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Prion diseases

Rabies

Malaria

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Neurocysticercosis

Trichinosis

Zika virus: neurologic complications

This is an article preview.
Start a Free Account
to access the full version.