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Complete resolution of advanced Mycoplasma pneumoniae encephalitis mimicking brain mass lesions: Report of two pediatric cases and review of literature

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Abstract

Mycoplasma pneumoniae is a well-known cause of atypical pneumonia. CNS involvement is a relatively frequent extrapulmonary manifestation, most commonly manifesting as encephalitis in the pediatric population. We present two unusual cases of M. pneumoniae encephalitis that presented with symptoms and imaging findings suggesting mass occupying lesions, and worsening altered mental status. Biopsy of the lesions was necessary in both cases to aid with diagnosis. Histopathologic features excluded neoplasm, and established the diagnosis of encephalitis, but did not point toward its etiology. The only finding that indicated M. pneumoniae as the most likely pathogen was serum IgM positivity in the absence of any other identifiable infectious source, and complete neurologic recovery following specific anti-mycoplasmal treatment. The patients were successfully treated with antibiotics and steroids, with the second case also requiring intravenous immunoglobulin and anti-epileptics. The clinical presentation and histopathologic findings suggested an immune-mediated pathogenesis, but acute disseminated encephalomyelitis was excluded due to extensive gray matter involvement. Disease resolution despite status epilepticus and herniation in case 2 is a novel finding of the study. Current principles of diagnosis and management of encephalitis as the presenting manifestation of mycoplasmal infection are discussed.

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... Cerebellitis has been constantly reported as part of a disease involving multiple parts of the brain (Christo et al., 2010;Bae et al., 2011;Meyer Sauteur et al., 2014a) or as an isolated disease (Shkalim et al., 2009;Simpkins et al., 2012;Schmucker et al., 2014). Immune-mediated pathogenesis has been advocated for cerebellitis and is most likely an indirect type manifestation. ...
... Immune-mediated pathogenesis has been advocated for cerebellitis and is most likely an indirect type manifestation. The fact that lymphocytic infiltration was found in the cerebellar tissue in the late onset case (Simpkins et al., 2012) is of some interest because the neutrophilic infiltration has typically been found in the cerebral tissues of early onset cases (Bruch et al., 2001;Stamm et al., 2008). Implication of these observations on pathogenesis remains unclear, but accumulation of histological investigations should provide us with clues for further understanding of the pathogenesis of neurological manifestations. ...
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... Based on multiple case reports immune-modulating therapy, with intravenous methylprednisolone (20-30 mg/ kg/day, maximum 1gm/day) for 3-5 days, followed by tapered oral corticosteroids over 4-6 weeks; has a beneficial effect. 23,24 The role of antimicrobials treatment remains controversial as it depends on associated mechanism. It is indicted in direct invasion, while if immune -mediated mechanism is suspected, it is not quite understood if antimicrobial therapy is appropriate, particularly after the acute illness has been resolved. ...
... 1,13 Practically, it is administered in association with steroid when other causative agents have been excluded and should be continued irrespective of prodromal or neurological manifestations until more evidence becomes available. 24 The use of others; IVIG at 2 g/kg divided over 2-5 days or plasmapheresis depends on complexity of the case and the rate of responses to steroid therapy. 7 Our patient responded dramatically to intravenous steroid therapy and IVIG, and the vision improves over 3 weeks. ...
Article
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A case of a 4-year-old boy who developed acute disseminated encephalomyelitis (ADEM) and optic neuritis (ON) following Mycoplasma pneumoniae infection is reported. His symptoms, including excessive sleepiness, frontal headache, bilateral vision impairment, retro-auricular pain and unbalanced gait, were resolved after methylprednisolone pulse therapy, intravenous immunoglobulin (IVIG) and ciprofloxacin. Cerebrospinal fluid myelin basic protein (MBP) and Mycoplasma serology IgM were detected in our patient. This is the first report of a child with ADEM and ON associated with mastoditis caused by M. pneumoniae infection. Combined immunomodulatory therapy (pulse steroids and immunoglobulin) with anti- mycoplasma microbial therapy resulted in favorable visual recovery. Bilateral isolated optic neuritis as the first presenting feature in childhood ADEM is rare and requires proper evaluation and early therapeutic management. This case highlights the need for physician awareness of the association of mycoplasma infection with optic neuritis and ADEM.
... Cerebellar syndrome, polyradiculitis, cranial nerve palsies, aseptic meningitis, meningoencephalitis, acute disseminated encephalomyelitis, coma, optic neuritis, diplopia, mental confusion and, acute psychosis secondary to encephalitis, cranial nerve palsy, brachial plexus neuropathy, ataxia, choreoathetosis, and ascending paralysis (Guillain-Barre syndrome) are neurologic complications seen with M. pneumoniae infection [1] . Encephalitis is most frequent extrapulmonary complication of M. pneumoniae manifested with fever, seizures, meningeal signs, ataxia, focal neurologic deficits, and altered behavior, ranging from minor changes to lethargy in pediatric population [2][3][4][6][7][8] . Twenty percent of patients or more with CNS findings have no preceding or concomitant diagnosis of respiratory infection [2][3][4][6][7][8] . ...
... Encephalitis is most frequent extrapulmonary complication of M. pneumoniae manifested with fever, seizures, meningeal signs, ataxia, focal neurologic deficits, and altered behavior, ranging from minor changes to lethargy in pediatric population [2][3][4][6][7][8] . Twenty percent of patients or more with CNS findings have no preceding or concomitant diagnosis of respiratory infection [2][3][4][6][7][8] . Among our five cases, two had respiratory symptoms at the beginning of M. pneumoniae infection. ...
Article
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Extrapulmonary complications of Mycoplasma pneumoniae (M. pneumoniae) infection include encephalitis, optic neuritis, acute psychosis, stroke, cranial nerve palsies, aseptic meningitis and also it may be implicated in immune mediated neurological diseases such as acute demyelinating encephalomyelitis, Guillain-Barre syndrome and transverse myelitis. We present five cases with acute neurological diseases after M. pneumoniae infection. The clinical presentations were characterized by encephalitis in 2 patients, Gullain-Barre syndrome in 2 patients, transverse myelitis in 1 patient. M. pneumoniae infection was detected in serum by serological method. Only two patients had respiratory symptoms preceding M. pneumoniae infection. Brain MRI revealed hyperintensities on corpus striatum and mesencephalon in one patient with encephalitis, the other had front parietal coalescent periventricular white matter lesions on T2 images. The patient with transverse myelitis had cervical, dorsal and lumbar scattered hyperintense lesions on T2 images. Two patients were treated with high dose steroid, the other two patients received treatment with intravenous immune globuline. M. pneumoniae may reveal different neurologic complications with different radiologic findings.
... 12 Mycoplasma has been associated with CNS disease including vasculitis, ADEM, Guillain-Barr e syndrome, and encephalitis mimicking brain mass. 13,14 A mechanism of vasculitic necrosis associated with Mycoplasma has been proposed; however, this has only been reported in the thalamus, basal ganglia, pons, and splenium of the corpus callosum, which is not consistent with our patient's presentation, nor is the enlargement of our patient's lesion after treatment with azithromycin. 14 Although multisystem inflammatory syndrome in children (MIS-C) has arisen during the SARS-CoV-2 pandemic, our patient never met diagnostic criteria due to lack of daily fevers, other additional clinical features consistent with MIS-C, or significant inflammatory response at time of presentation. ...
Article
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... An indirect pathogenesis was mainly suggested by the long latency between respiratory and neurological symptoms (Schmucker et al., 2014). However, in a case, nervous tissue infiltration with macrophages and lymphocytes, typical of directly determined cases, seemed to indicate a possible pathogenetic alternative (Simpkins et al., 2012). ADEM is known as an immune complex-mediated vasculopathy in which circulating immune complexes are deposited in small venules in the CNS, leading to activation of the serum complement system. ...
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Chapter
Dieses Kapitel behandelt die Infektionen durch Erreger, deren Vermehrung gänzlich oder teilweise auf Leistungen der Wirtszelle angewiesen ist. Diese enge Verknüpfung macht die spezifische Bekämpfung schwierig. Ansatzpunkte bieten nur die wenigen erregereigenen Vermehrungsmechanismen. Daher galten Virusinfektionen lange als untherapierbar. Im Vordergrund medizinischen Interesses stand die Prophylaxe. Ihre wesentlichen Instrumente sind die (möglichst aktive) Immunisierung und Hygienemaßnahmen. Impfungen sind im ▸ Kap. 28 beschrieben. Meldepflicht und Regeln zur Wiederzulassung zu Gemeinschaftseinrichtungen nach dem Infektionsschutzgesetz finden sich jeweils bei den einzelnen Erregern.
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To report an unusual case of mycoplasma-associated encephalitis that responded to corticosteroid therapy and relapsed after cessation. Clinical case report. Tertiary care pediatric intensive care unit. A single patient admitted to the pediatric intensive care unit. Intravenous corticosteroids and antibiotics. Resolution of neurologic symptoms with initial steroid therapy, relapse after withdrawal of steroids, and resolution again with re-institution of steroid therapy. Encephalitis is a well-recognized and potentially severe complication of mycoplasma infections. Treatment with corticosteroids has been proposed for this illness, but experience with this therapy is limited to case reports and small series; neither efficacy nor appropriate courses of treatment are well established. The relapsing course of this patient, along with a review of prior reported cases, suggests that corticosteroids may be beneficial for mycoplasma encephalitis, that moderate doses may be sufficient, and that consideration should be given to a prolonged tapering course when these medications are used for this illness.
Article
Anti-galactocerebroside (GalC) antibodies are reported to be present in GBS patients with preceding Mycoplasma pneumoniae (MP) infection. We investigated the presence of anti-GalC reactivity in serum of a large group of GBS patients using ELISA and compared this with healthy controls and individuals with an uncomplicated MP infection. Anti-GalC antibody reactivity was present in 12% of the GBS patients. Furthermore, anti-GalC antibodies were associated with MP infections, a relatively mild form of the disease and demyelinating features. Anti-GalC antibodies cross-reacted with MP antigen. In conclusion, anti-GalC antibodies in GBS patients may be induced by molecular mimicry with MP.
Mycoplasma pneumoniae causes between 5 and 10 percent of acute childhood encephalitis in Europe and North America. Encephalitis due to this organism may be caused by direct infection of the brain, immune-mediated brain injury or thromboembolic phenomenon. The prognosis is guarded with 20 to 60 percent suffering neurologic sequelae. The diagnosis of M. pneumoniae encephalitis should be based on strong evidence of M. pneumoniae infection that includes detection of the organism in culture or using molecular detection techniques in addition to serology and exclusion of other potential etiologies. Antibiotic therapy should be considered for all children with suspected M. pneumoniae encephalitis; antibiotics with good central nervous system (CNS) penetration such as ciprofloxacin, doxycycline, chloramphenicol or azithromycin are appropriate under most circumstances. Immune modulating therapies, such as corticosteroids, intravenous immune globulin or plasmapharesis, should be considered in those with immune-mediated syndromes such as acute disseminated encephalomyelitis.
Article
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. Little is known about the extrapulmonary manifestations of this organism. Numerous central nervous system (CNS) manifestations have been described with M. pneumoniae. CNS involvement is probably the most common site of involvement in addition to the respiratory system. Up to 7% of patients hospitalized with M. pneumoniae may have CNS symptoms. Common CNS presentations include encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. The mechanism behind these CNS manifestations remains unclear. Direct invasion, neurotoxin production, or an immune-mediated mechanism has been proposed. Newer diagnostic techniques for the direct detection of the antigen and the microorganism are proving useful for the detection of extrapulmonary disease. This review comprehensively reviews the CNS complications that have been reported with M. pneumoniae.
Article
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.
Article
Mycoplasma pneumoniae is associated with a wide range of central nervous system diseases, most importantly with childhood encephalitis. This review summarizes and discusses recent findings in the field of M. pneumoniae central nervous system infections in context with previously published findings, with reference to clinical spectrum, pathogenesis, diagnosis, and treatment. Further insight into the pathogenesis has been provided by studies on cytokine production and autoantibody formation. Some new manifestations have been described (e.g. Kluver-Bucy syndrome, intracranial hypertension). Anecdotal descriptions on the association of M. pneumoniae with uncommon neurologic diseases remain to be confirmed by additional reports, however, especially when aetiologic diagnosis relied exclusively on serology. New knowledge on treatment options targeting the immune system has been provided by isolated reports. Recent diagnostic advances refer to general methods (polymerase chain reaction, serology), without specific reference to neurologic disease. M. pneumoniae must be considered as causative agent of various neurologic diseases. The recent literature shows, however, that the clinical spectrum of M. pneumoniae central nervous system disease is still not well defined. In addition, the main future challenges are the investigation of the pathogenesis of M. pneumoniae central nervous system disease and the establishment of therapeutic approaches.
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Acute transverse myelitis associated with Mycoplasma pneumoniae infection: a case report and review of the literature
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