577961
research-article2015
CPJXXX10.1177/0009922815577961Clinical PediatricsDawson et al
Brief Report
Asymptomatic Mycoplasma Infection Causing Acute Demyelinating Encephalomyelitis: Case Report and Review of Literature
Clinical Pediatrics 1–4 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815577961 cpj.sagepub.com
Erin Dawson, BS1, Dinesh Singh, MBBS, MD, DCH1, Carissa Armstrong, MD1, Omar Maatouk, MD1, Olugbenga Akingbola, MD1, and Stephen Nelson, MD, PhD1 Introduction Acute demyelinating encephalomyelitis (ADEM) is a rare autoimmune acute demyelinating disease with an incidence of 0.64 per 100 000 persons per year with a slight male predominance. It is characterized by an intense inflammatory reaction that leads to demyelination in the brain and spinal cord. The pathological changes are localized to perivenous regions; hence, it is also known as perivenous encephalomyelitis. It has been reported to occur following various bacterial and viral infections (postinfectious encephalomyelitis) and after vaccinations (postvaccination encephalomyelitis).1 Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). Central nervous system (CNS) complications occur in up to 0.1% of patients with M pneumoniae infection. These complications include encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. Rarely, ADEM has been seen following infection with M pneumoniae.2 We report and discuss a case of severe ADEM following asymptomatic mycoplasma infection.
Case Presentation A previously healthy 4-year-old boy of Chinese origin presented to the referring hospital emergency department (ED) with low-grade fever for 2 days associated with new-onset mild dysphagia, ataxia, and drooling. All family members had upper respiratory illness few weeks prior to the onset of his illness. On admission to the ED, he was found to have altered mental status and urinary incontinence with worsening ataxia. Emergent computed tomography (CT) scan was normal. Urine analysis, urine toxicology, complete blood count, and complete metabolic panel were within normal limits. Rapid influenza screen was negative. Lumbar puncture was performed and clear cerebrospinal fluid (CSF) was obtained, which showed 26 white blood cells units/µL
(82% lymphocytes), 0 red blood cells units/µL, glucose 71 mg/dL, protein 39.6 µL. Gram stain showed no organisms. Empiric antibiotic therapy with intravenous ceftriaxone was initiated and he was transferred to a regional pediatric intensive care unit (PICU). On arrival to the regional PICU, he was found to be tachypneic with shallow breathing with a Glasgow Coma Score of 9. He was noticed to have nuchal rigidity, severe hypotonia, and decreased power in all 4 extremities. He was electively intubated to protect his airway and transferred to our facility. On admission to our PICU, repeat lumbar puncture was performed and CSF was obtained for viral studies. Electroencephalogram showed changes consistent with encephalopathy with no epileptiform discharges. Seizure prophylaxis with intravenous levetiracetam (Keppra) was initiated. Blood cultures, viral polymerase chain reaction, and mycoplasma serology studies were obtained. CSF cultures showed no growth for 3 days. CSF myelin basic protein was increased to more than 200 (reference range = 0-1.2 ng/mL), consistent with an acute demyelinating process. The CSF oligoclonal bands were normal. Serum ammonia and thyroid function tests were within normal limits. Results of all other studies are summarized in Table 1. Broad-spectrum antibiotic therapy with ceftriaxone, vancomycin, and azithromycin and empiric acyclovir therapy was initiated. Magnetic resonance imaging (MRI) of the brain showed innumerable scattered hyperintense lesions involving deep white matter, basal ganglia, thalamus, brainstem, and cervical/thoracic spinal cord (Figures 1 and 2) consistent with 1
Tulane University School of Medicine, New Orleans, LA, USA
Corresponding Author: Dinesh Singh, Division of Pediatric Critical Care, Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, SL-37, New Orleans, LA 70448, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
2
Clinical Pediatrics
Table 1. Viral and Mycoplasma Studies. Serum and CSF St. Louis encephalitis virus East equine encephalitis virus West equine encephalitis virus West Nile virus California encephalitis virus Mycoplasma pneumoniae (serum only)
Results IgM and IgG negative IgM and IgG negative IgM and IgG Negative IgM negative and IgG positive IgM and IgG negative IgM positive (992 U/mL; normal = 0-99); IgG positive (876 U/mL; normal = 0-769)
Polymerase Chain Reaction Serum Adenovirus Cytomegalovirus Enterovirus Epstein–Barr virus Herpes virus
Results Negative Negative Negative Negative Negative
Abbreviation: CSF, cerebrospinal fluid.
Figure 1. T2/Flair MRI (spine) sagittal view showing patchy hyperintense lesions involving mainly the cervical and thoracic spine cord.
Figure 2. T2/Flair MRI (brain) axial view showing innumerable scattered hyperintense lesions, predominately in the deep white matter of the brain.
ADEM. Pediatric neurology consultation was obtained. A high-dose methylprednisolone therapy at 30 mg/kg/ day was initiated and continued for a total duration of 7 days. He was also given one dose of 2 g/kg of intravenous immunoglobulin (IVIG) therapy over 24 hours. On day 8, a repeat MRI showed interval decrease in the number of lesions within deep white matter. Improvement was also observed in basal ganglia, thalami, brain stem, and spinal cord lesions. However, clinical improvement was less apparent despite the improvement in the imaging studies. Hence, a decision was made to initiate plasmapheresis for a total of 6 days. On day 2 of plasmapheresis, the patient showed improved tone with good cough and gag reflex and was successfully extubated. However, after completion of plasmapheresis, poor head control, dysphagia, and communication deficits persisted. Due to continued deficits, repeat IVIG at
400 mg/kg/day was given for 5 days after which he showed a gradual but consistent neurological improvement with minimal communicative and cognitive deficits and was transferred to an inpatient rehabilitation facility.
Discussion Mycoplasma pneumoniae (Eaton’s Agent) is a smallest self-replicating organism. It primarily causes mild and self-limiting upper and lower respiratory tract infection. However, it can occasionally cause severe and fulminant disease. It is the second most common cause of CAP and accounts for up to 40% of CAP in children over 5 years of age. Nearly 20% of the M pneumoniae infections are asymptomatic, and asymptomatic carriage of the organism in the upper respiratory tract is not uncommon. It is
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
3
Dawson et al transmitted by respiratory droplets and has a mean incubation period of 2 to 3 weeks.3 Extrapulmonary manifestations of M pneumoniae are common and involve various organ systems. The most common extrapulmonary manifestation includes CNS involvement, which account for about 0.1% of all mycoplasma infections. Encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, myelitis, optic neuritis, and ADEM are some of the reported CNS manifestations.2 The exact pathogenesis of these CNS manifestations is multifactorial and not clearly understood. The important theories that have been proposed include a direct injury secondary to locally released cytokines; indirect injury secondary to immune modulation and autoimmunity; both the cell membrane and the cytoplasm of the M pneumoniae contain substances like lipoproteins, glycolipids, and glycoproteins, which due to their resemblance to the human cellular components and molecular mimicry result in intense autoimmune response resulting in indirect injury. In addition, vasculitis and a vascular thrombosis induced by hypercoagulable state secondary to release of cytokines are also known to induce injury.4 All the 3 proposed pathogenic mechanisms might be involved in the widespread injuries or lesions that are noted in mycoplasma-induced ADEM. ADEM is classically a monophasic acute or subacute immune-mediated demyelinating disease primarily involving the white matter resulting in multifocal neurological disturbances. The most common precipitants of ADEM are exanthematous illnesses like measles, rubella, chickenpox, and so on. It has also been reported to occur after a variety of other illnesses like hepatitis, HIV, group A streptococcus, influenza, and mycoplasma. Vaccines, particularly those that contain the neural extracts like rabies and Japanese encephalitis vaccines, are known to cause ADEM. The incidence of postvaccination ADEM is declining due to newer recombinant methods of production of vaccines.5 The International Pediatric Multiple Sclerosis Study Group has recently revised the criteria for the diagnosis of ADEM6 (Table 2). The most common clinical characteristics of ADEM include encephalopathy or altered sensorium, meningeal signs, pyramidal long tract signs, cerebellar signs (ataxia, aphasia, hypotonia), cranial nerve involvement (bilateral optic neuritis presenting with blindness), and transverse myelitis (presenting with paraplegia and urinary retention). Seizures and extrapyramidal signs (chorea and dystonia) are also not uncommon in ADEM. Blood or CSF findings in ADEM are nonspecific but they are helpful in identification of specific infective etiologies and differentiating them from conditions that have similar clinical presentation. In addition, they also help in tailoring the management toward the treatment
Table 2. International Pediatric Multiple Sclerosis Study Group Criteria for Pediatric Acute Disseminated Encephalomyelitis of the Central Nervous System. Disorder Monophasic acute disseminated encephalomyelitis
Multiphasic acute disseminated encephalomyelitis
Definition •• A first polyfocal clinical central nervous system even with presumed inflammatory cause •• Encephalopathy that cannot be explained by fever is present •• Brain MRI is abnormal during the acute (3 month) phase •• MRI typically shows ° Diffuse, poorly demarcated, large (greater than 1-2 cm) lesions involving predominantly the cerebral white matter ° T1 hypointense white matter lesions are rare ° Deep grey matter lesions (eg, thalamus or basal ganglia) can be present •• No new symptoms, signs, or MRI findings after 3 months of the incident acute disseminated encephalomyelitis •• New event of acute disseminated encephalomyelitis 3 months or more after the initial event that can be associated with new or reemergence of prior clinical and MRI findings
Abbreviation: MRI, magnetic resonance imaging.
of those specific etiologies. Electroencephalogram usually reveals diffuse slowing consistent with encephalopathy as was seen in our patient. CT scan may be normal (like in our case) in a large proportion of cases; hence, magnetic resonance imaging (MRI) is the imaging modality of choice. MRI reveals multifocal, diffuse, asymmetrical lesions particularly involving the white matter, which are best seen on FLAIR and T2-weighted sequences. Bilateral involvement of the deep gray matter structures like basal ganglia and thalamus and extensive spinal cord lesions are also frequently reported.7 Magnetic resonance spectroscopy (MRS) during the acute phase of ADEM reveals increase of lipids and a decrease of the myoinositol–creatinine ratio and vice versa during the chronic phase. In addition, MRS reveals elevated acetyl-aspartate, choline and lactate peaks, and low N-acetyl aspartate peaks during the acute phase of ADEM.1 Admission to PICU, intubation, and mechanical ventilation may be needed during the acute phase of illness.
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
4
Clinical Pediatrics
Supportive therapies for seizure control and management of cerebral edema may be required. Early treatment with high-dose steroids, IVIG, and plasmapheresis has been recommended and has resulted in favorable outcomes including complete recovery in a few cases.5,8 Our patient required all the aforementioned treatment modalities and treatment with azithromycin for mycoplasma. He showed considerable improvement after the second dose of IVIG. Patients with significant neurological deficits will need inpatient rehabilitation. It is unclear which one of the aforementioned treatment modalities resulted in improvement in the clinical status in our patient. Multicenter prospective studies in future will be needed to compare the benefits of different treatment modalities. Author Contribution DS, CA, OM, and ED conceptualized and designed the study, drafted the initial manuscript, reviewed and revised the manuscript, and approved the final manuscript as submitted. OA and SN, carried out the initial analyses and approved the final manuscript as submitted.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Wender M. Acute disseminated encephalomyelitis (ADEM). J Neuroimmunol. 2011;231:92-99. 2. Tsiodras S, Kelesidis I, Kelesidis T, Stamboulis E, Giamarellou H. Central nervous system manifestations of Mycoplasma pneumoniae infections. J Infect. 2005;51:343-354. 3. Atkinson TP, Waites KB. Mycoplasma pneumoniae infections in childhood. Pediatr Infect Dis J. 2014;33:92-94. 4. Narita M. Pathogenesis of neurologic manifestations of Mycoplasma pneumoniae infection. Pediatr Neurol. 2009;41:159-166. 5. Tenembaum SN. Disseminated encephalomyelitis in children. Clin Neurol Neurosurg. 2008;110:928-938. 6. Krupp LB, Tardieu M, Amato MP, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19:1261-1267. 7. Dale RC. Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 2003;14:90-95. 8. Khurana DS, Melvin JJ, Kothare SV, et al. Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis. Pediatrics. 2005;116:431-436.
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
research-article2015
CPJXXX10.1177/0009922815577961Clinical PediatricsDawson et al
Brief Report
Asymptomatic Mycoplasma Infection Causing Acute Demyelinating Encephalomyelitis: Case Report and Review of Literature
Clinical Pediatrics 1–4 © The Author(s) 2015 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0009922815577961 cpj.sagepub.com
Erin Dawson, BS1, Dinesh Singh, MBBS, MD, DCH1, Carissa Armstrong, MD1, Omar Maatouk, MD1, Olugbenga Akingbola, MD1, and Stephen Nelson, MD, PhD1 Introduction Acute demyelinating encephalomyelitis (ADEM) is a rare autoimmune acute demyelinating disease with an incidence of 0.64 per 100 000 persons per year with a slight male predominance. It is characterized by an intense inflammatory reaction that leads to demyelination in the brain and spinal cord. The pathological changes are localized to perivenous regions; hence, it is also known as perivenous encephalomyelitis. It has been reported to occur following various bacterial and viral infections (postinfectious encephalomyelitis) and after vaccinations (postvaccination encephalomyelitis).1 Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP). Central nervous system (CNS) complications occur in up to 0.1% of patients with M pneumoniae infection. These complications include encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. Rarely, ADEM has been seen following infection with M pneumoniae.2 We report and discuss a case of severe ADEM following asymptomatic mycoplasma infection.
Case Presentation A previously healthy 4-year-old boy of Chinese origin presented to the referring hospital emergency department (ED) with low-grade fever for 2 days associated with new-onset mild dysphagia, ataxia, and drooling. All family members had upper respiratory illness few weeks prior to the onset of his illness. On admission to the ED, he was found to have altered mental status and urinary incontinence with worsening ataxia. Emergent computed tomography (CT) scan was normal. Urine analysis, urine toxicology, complete blood count, and complete metabolic panel were within normal limits. Rapid influenza screen was negative. Lumbar puncture was performed and clear cerebrospinal fluid (CSF) was obtained, which showed 26 white blood cells units/µL
(82% lymphocytes), 0 red blood cells units/µL, glucose 71 mg/dL, protein 39.6 µL. Gram stain showed no organisms. Empiric antibiotic therapy with intravenous ceftriaxone was initiated and he was transferred to a regional pediatric intensive care unit (PICU). On arrival to the regional PICU, he was found to be tachypneic with shallow breathing with a Glasgow Coma Score of 9. He was noticed to have nuchal rigidity, severe hypotonia, and decreased power in all 4 extremities. He was electively intubated to protect his airway and transferred to our facility. On admission to our PICU, repeat lumbar puncture was performed and CSF was obtained for viral studies. Electroencephalogram showed changes consistent with encephalopathy with no epileptiform discharges. Seizure prophylaxis with intravenous levetiracetam (Keppra) was initiated. Blood cultures, viral polymerase chain reaction, and mycoplasma serology studies were obtained. CSF cultures showed no growth for 3 days. CSF myelin basic protein was increased to more than 200 (reference range = 0-1.2 ng/mL), consistent with an acute demyelinating process. The CSF oligoclonal bands were normal. Serum ammonia and thyroid function tests were within normal limits. Results of all other studies are summarized in Table 1. Broad-spectrum antibiotic therapy with ceftriaxone, vancomycin, and azithromycin and empiric acyclovir therapy was initiated. Magnetic resonance imaging (MRI) of the brain showed innumerable scattered hyperintense lesions involving deep white matter, basal ganglia, thalamus, brainstem, and cervical/thoracic spinal cord (Figures 1 and 2) consistent with 1
Tulane University School of Medicine, New Orleans, LA, USA
Corresponding Author: Dinesh Singh, Division of Pediatric Critical Care, Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, SL-37, New Orleans, LA 70448, USA. Email: [email protected]
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
2
Clinical Pediatrics
Table 1. Viral and Mycoplasma Studies. Serum and CSF St. Louis encephalitis virus East equine encephalitis virus West equine encephalitis virus West Nile virus California encephalitis virus Mycoplasma pneumoniae (serum only)
Results IgM and IgG negative IgM and IgG negative IgM and IgG Negative IgM negative and IgG positive IgM and IgG negative IgM positive (992 U/mL; normal = 0-99); IgG positive (876 U/mL; normal = 0-769)
Polymerase Chain Reaction Serum Adenovirus Cytomegalovirus Enterovirus Epstein–Barr virus Herpes virus
Results Negative Negative Negative Negative Negative
Abbreviation: CSF, cerebrospinal fluid.
Figure 1. T2/Flair MRI (spine) sagittal view showing patchy hyperintense lesions involving mainly the cervical and thoracic spine cord.
Figure 2. T2/Flair MRI (brain) axial view showing innumerable scattered hyperintense lesions, predominately in the deep white matter of the brain.
ADEM. Pediatric neurology consultation was obtained. A high-dose methylprednisolone therapy at 30 mg/kg/ day was initiated and continued for a total duration of 7 days. He was also given one dose of 2 g/kg of intravenous immunoglobulin (IVIG) therapy over 24 hours. On day 8, a repeat MRI showed interval decrease in the number of lesions within deep white matter. Improvement was also observed in basal ganglia, thalami, brain stem, and spinal cord lesions. However, clinical improvement was less apparent despite the improvement in the imaging studies. Hence, a decision was made to initiate plasmapheresis for a total of 6 days. On day 2 of plasmapheresis, the patient showed improved tone with good cough and gag reflex and was successfully extubated. However, after completion of plasmapheresis, poor head control, dysphagia, and communication deficits persisted. Due to continued deficits, repeat IVIG at
400 mg/kg/day was given for 5 days after which he showed a gradual but consistent neurological improvement with minimal communicative and cognitive deficits and was transferred to an inpatient rehabilitation facility.
Discussion Mycoplasma pneumoniae (Eaton’s Agent) is a smallest self-replicating organism. It primarily causes mild and self-limiting upper and lower respiratory tract infection. However, it can occasionally cause severe and fulminant disease. It is the second most common cause of CAP and accounts for up to 40% of CAP in children over 5 years of age. Nearly 20% of the M pneumoniae infections are asymptomatic, and asymptomatic carriage of the organism in the upper respiratory tract is not uncommon. It is
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
3
Dawson et al transmitted by respiratory droplets and has a mean incubation period of 2 to 3 weeks.3 Extrapulmonary manifestations of M pneumoniae are common and involve various organ systems. The most common extrapulmonary manifestation includes CNS involvement, which account for about 0.1% of all mycoplasma infections. Encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, myelitis, optic neuritis, and ADEM are some of the reported CNS manifestations.2 The exact pathogenesis of these CNS manifestations is multifactorial and not clearly understood. The important theories that have been proposed include a direct injury secondary to locally released cytokines; indirect injury secondary to immune modulation and autoimmunity; both the cell membrane and the cytoplasm of the M pneumoniae contain substances like lipoproteins, glycolipids, and glycoproteins, which due to their resemblance to the human cellular components and molecular mimicry result in intense autoimmune response resulting in indirect injury. In addition, vasculitis and a vascular thrombosis induced by hypercoagulable state secondary to release of cytokines are also known to induce injury.4 All the 3 proposed pathogenic mechanisms might be involved in the widespread injuries or lesions that are noted in mycoplasma-induced ADEM. ADEM is classically a monophasic acute or subacute immune-mediated demyelinating disease primarily involving the white matter resulting in multifocal neurological disturbances. The most common precipitants of ADEM are exanthematous illnesses like measles, rubella, chickenpox, and so on. It has also been reported to occur after a variety of other illnesses like hepatitis, HIV, group A streptococcus, influenza, and mycoplasma. Vaccines, particularly those that contain the neural extracts like rabies and Japanese encephalitis vaccines, are known to cause ADEM. The incidence of postvaccination ADEM is declining due to newer recombinant methods of production of vaccines.5 The International Pediatric Multiple Sclerosis Study Group has recently revised the criteria for the diagnosis of ADEM6 (Table 2). The most common clinical characteristics of ADEM include encephalopathy or altered sensorium, meningeal signs, pyramidal long tract signs, cerebellar signs (ataxia, aphasia, hypotonia), cranial nerve involvement (bilateral optic neuritis presenting with blindness), and transverse myelitis (presenting with paraplegia and urinary retention). Seizures and extrapyramidal signs (chorea and dystonia) are also not uncommon in ADEM. Blood or CSF findings in ADEM are nonspecific but they are helpful in identification of specific infective etiologies and differentiating them from conditions that have similar clinical presentation. In addition, they also help in tailoring the management toward the treatment
Table 2. International Pediatric Multiple Sclerosis Study Group Criteria for Pediatric Acute Disseminated Encephalomyelitis of the Central Nervous System. Disorder Monophasic acute disseminated encephalomyelitis
Multiphasic acute disseminated encephalomyelitis
Definition •• A first polyfocal clinical central nervous system even with presumed inflammatory cause •• Encephalopathy that cannot be explained by fever is present •• Brain MRI is abnormal during the acute (3 month) phase •• MRI typically shows ° Diffuse, poorly demarcated, large (greater than 1-2 cm) lesions involving predominantly the cerebral white matter ° T1 hypointense white matter lesions are rare ° Deep grey matter lesions (eg, thalamus or basal ganglia) can be present •• No new symptoms, signs, or MRI findings after 3 months of the incident acute disseminated encephalomyelitis •• New event of acute disseminated encephalomyelitis 3 months or more after the initial event that can be associated with new or reemergence of prior clinical and MRI findings
Abbreviation: MRI, magnetic resonance imaging.
of those specific etiologies. Electroencephalogram usually reveals diffuse slowing consistent with encephalopathy as was seen in our patient. CT scan may be normal (like in our case) in a large proportion of cases; hence, magnetic resonance imaging (MRI) is the imaging modality of choice. MRI reveals multifocal, diffuse, asymmetrical lesions particularly involving the white matter, which are best seen on FLAIR and T2-weighted sequences. Bilateral involvement of the deep gray matter structures like basal ganglia and thalamus and extensive spinal cord lesions are also frequently reported.7 Magnetic resonance spectroscopy (MRS) during the acute phase of ADEM reveals increase of lipids and a decrease of the myoinositol–creatinine ratio and vice versa during the chronic phase. In addition, MRS reveals elevated acetyl-aspartate, choline and lactate peaks, and low N-acetyl aspartate peaks during the acute phase of ADEM.1 Admission to PICU, intubation, and mechanical ventilation may be needed during the acute phase of illness.
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
4
Clinical Pediatrics
Supportive therapies for seizure control and management of cerebral edema may be required. Early treatment with high-dose steroids, IVIG, and plasmapheresis has been recommended and has resulted in favorable outcomes including complete recovery in a few cases.5,8 Our patient required all the aforementioned treatment modalities and treatment with azithromycin for mycoplasma. He showed considerable improvement after the second dose of IVIG. Patients with significant neurological deficits will need inpatient rehabilitation. It is unclear which one of the aforementioned treatment modalities resulted in improvement in the clinical status in our patient. Multicenter prospective studies in future will be needed to compare the benefits of different treatment modalities. Author Contribution DS, CA, OM, and ED conceptualized and designed the study, drafted the initial manuscript, reviewed and revised the manuscript, and approved the final manuscript as submitted. OA and SN, carried out the initial analyses and approved the final manuscript as submitted.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Wender M. Acute disseminated encephalomyelitis (ADEM). J Neuroimmunol. 2011;231:92-99. 2. Tsiodras S, Kelesidis I, Kelesidis T, Stamboulis E, Giamarellou H. Central nervous system manifestations of Mycoplasma pneumoniae infections. J Infect. 2005;51:343-354. 3. Atkinson TP, Waites KB. Mycoplasma pneumoniae infections in childhood. Pediatr Infect Dis J. 2014;33:92-94. 4. Narita M. Pathogenesis of neurologic manifestations of Mycoplasma pneumoniae infection. Pediatr Neurol. 2009;41:159-166. 5. Tenembaum SN. Disseminated encephalomyelitis in children. Clin Neurol Neurosurg. 2008;110:928-938. 6. Krupp LB, Tardieu M, Amato MP, et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler. 2013;19:1261-1267. 7. Dale RC. Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 2003;14:90-95. 8. Khurana DS, Melvin JJ, Kothare SV, et al. Acute disseminated encephalomyelitis in children: discordant neurologic and neuroimaging abnormalities and response to plasmapheresis. Pediatrics. 2005;116:431-436.
Downloaded from cpj.sagepub.com at University of Birmingham on November 14, 2015
