CASE REPORT Open Access

Central retinal artery occlusion and cerebralinfarction associated with Mycoplasmapneumonia infection in childrenYunguang Bao1, Xiaobing Li1, Kaixuan Wang1, Chan Zhao1, Xiumei Ji1 and Mizu Jiang2*

Abstract

Background: Central retinal artery occlusion (CRAO) is an arterial ischemic stroke, rarely occurred in childrenaccompanied with asymptomatic cerebral infarction and almost never involved in severe pneumonia related toMycoplasma pneumonia infection.

Case presentation: An 8-year-old boy with severe pneumonia related to Mycoplasma pneumonia infection thatdeveloped loss of vision in the left eye on the 14th day. No light perception and no pupillary reaction to light werefound in the left eye. The fundus examination revealed a cherry red spot with severe retinal edema at the macularand peripapillary area, and the optic disc was pale in the left eye but normal in the right eye, suggesting CRAO inthe left eye. No obvious neurological symptoms and signs were observed on presentation. Magnetic resonanceimaging of the brain showed an abnormal signal of the left lentiform nucleus, caudate nucleus and within thetemporal lobe, suggesting an acute cerebral infarction. The analysis of cerebrospinal fluid showed an increasingleukocyte count, but no any pathogenic microorganisms were found. His respiratory symptoms disappearedpromptly after therapy, and the patient was discharged after 11 days later, but there was no light in the left eye 2months after discharge.

Conclusion: M. pneumoniae infection could be developed the risk for cerebral ischemic stroke, including CRAO inchildren with severe pneumonia. CRAO is a devastating ophthalmologic event leading to a severe impairment ofvision. Patients treated within about 6 h of vision loss had a better visual outcome after the onset of vision loss.

Keywords: Mycopasma pneumonia, Central retinal artery occlusion, Brain infarction, Pneumonia, Children

BackgroundChildhood stroke is a cerebrovascular event that occursbetween 30 days and 18 years of age. The annual inci-dence of stroke in children is estimated to be 2–4/100,000 in the United States. Ischemic stroke is morecommon than hemorrhagic stroke [1]. Furthermore, in-fectious diseases typically precede a significant propor-tion of acute ischemic strokes (AIS) in children [2]. Themost common infectious agent is Varicella zoster virus,followed by Mycoplasma pneumoniae (M. pneumoniae),Chlamydia pneumonia, Parvovirus B19, influenza Avirus, and mumps virus infection. These microorganismshave been identified as potential risk factors for arterial

ischemic stroke during childhood [1–3]. M. pneumoniaemay cause a vascular occlusion type with an extrapulmon-ary manifestation through local vascular injury in theabsence of a systemic hypercoagulable state [4]. In thepresent case, the patient presented with central retinalartery occlusion (CRAO) in the left eye and cerebral in-farction in the left lentiform nucleus and caudate nucleuson the 14th day after onset of the M. pneumoniae respira-tory infection. This study was approved by the ethicalcommittee at Jinhua Municipal Central Hospital and Chil-dren’s Hospital, Zhejiang University School of Medicine,China. Consent was obtained from their parents.

Case presentationA previously healthy 8-year-old boy with a fever andcough lasting for 1 week was admitted to the Departmentof Pediatrics in Jinhua Hospital of Zhejiang University.

* Correspondence: mizu@zju.edu.cn2Children’s Hospital, Zhejiang University School of Medicine, Hangzhou310003, Zhejiang Province, ChinaFull list of author information is available at the end of the article

© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Bao et al. BMC Pediatrics (2016) 16:210 DOI 10.1186/s12887-016-0750-3

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Four days prior to admission, the symptoms did not im-prove after intravenous antibiotic treatment at a localclinic, but more detailed medical history was unavailable.The patient reported no history of cardiovascular disease,coagulation disorders or any other systemic immunedisorder, nor was there any recent history of trauma. Thepatient’s family history was unremarkable. He was alert onadmission. His weight was 24 kg, his body temperaturewas 37.8° Celsius, his pulse rate was 112/min, his respira-tory rate was 24/min and his blood pressure was 108/65 mmHg. A physical examination revealed mild conges-tion of his throat and moderate enlargement of his tonsils.A chest examination revealed coarse breathing soundsand decreased sounds on the right side without anyrespiratory distress. No crackles were heard in the lung.The neurological examination and the rest of the systemicphysical examination were normal.A laboratory investigation revealed a white blood cell

count of 9900/cubic mm3, with 79.3% neutrophils and10.2% lymphocytes as well as hemoglobin concentrationof 11.3 g/dl and a platelet count of 476,000/cubic mm3.The serum biochemistry and lipid profiles were allwithin normal ranges. The erythrocyte sedimentationrate (ESR) was 22 mm/hr, and C-reactive protein (CRP)was 44.2 mg/dl (normal

right eye. The fundus examination revealed a cherryred spot with severe retinal edema at the macular andperipapillary area, and the optic disc was pale in the lefteye, but the examination was normal in the right eye,suggesting central retinal artery occlusion in the lefteye. The detailed neurological examination was perfor-emed as follows: the nasolabial fold was symmetric, andthe tongue was midline protrusion; There was no devi-ation of the mandible, no involuntary movement; Limbmuscle strength was grade IV, and muscular tensionwas normal; Knee reflex and abdominal reflex wasnormal, and pathological reflex were negative. Initially,he was given oxygen and a low molecular dextran treat-ment and carteolol hydrochloride to lower the intraoc-ular pressure 29 h after the onset of vision complaint.Electrocardiogram, echocardiography, and Dopplerultrasound of the bilateral carotid artery and vertebralartery were all normal. Magnetic resonance imaging(MRI) of the brain showed an abnormal signal of theleft lentiform nucleus, caudate nucleus and within thetemporal lobe, suggesting an acute infarction of thebrain including the above regions (Fig. 3a–b). He wasprescribed tienam to escalate the anti-infection treat-ment, and early rehabilitation therapy with neurosup-plement treatment was initiated, and prepared totransfer the patient to higher level hospital.One day after the brain infarction, the patient was

transferred to Children’s Hospital of Zhejiang UniversitySchool of Medicine. Laboratory investigations revealed anormal serum coagulation test. The ESR was 105 mm/hr, and CRP was 106.0 mg/dl. The serum titer of the M.

pneumoniae particle agglutination test (IgG and IgM)was more than 1:320 (normal

fast bacilli of the CSF and Cryptococcus neoformanswere negative. Polymerase chain reaction (PCR) for M.pneumoniae of the CSF was negative. The pathogenDNA detection of M. pneumoniae from respiratory se-cretion was positive (4.2 × 105 copies). The bacterio-logical cultures of blood, CSF and pleural effusion weresterile. The PPD test on skin was negative. The levels ofserologic cytokines, such as interleukin-6 (IL-6) 159.7(normal 1.7–16.6) and IL-10 7.6 (normal 2.0–4.0), wereobviously increased, whereas the levels of IL-2, IL-4,TNF-ɑ, IFN- were all normal. The ophthalmologicexamination showed no light perception, no pupillary re-action to light and a cherry red spot with severe retinaledema in the macular and peripapillary area in the lefteye, but no issues in the right eye. A chest X-ray showeda high patchy density over his right lower lung lobe anda large right-sided pleural effusion. The right rib dia-phragm angle was lost. The heart shadow had no obvi-ous increase, and the left diaphragm was normal on thesecond day after transfer (Fig. 1b). On the basis of hisrecent medical history and diagnostic workups, we con-cluded that the diagnosis was acute severe pneumoniawith pleural effusion, cerebral infarction and CRAO inthe left eye associated with M. pneumoniae infection.Therapy with oxygen inhalation, Tazocin (PiperacillinSodium and Tazobactam Sodium) antibiotics, low mo-lecular dextran treatment, methylprednisone, gammaglobulin, mannitol and nicotinic acid was given, and at-ropine was injected in the left retrobulbar. The bodytemperature was normal, CSF was also returned to nor-mal on the 6th day and the cough had disappeared onthe 11th day after transfer. MRI of the brain indicated anabnormal signal in the left lentiform nucleus and caud-ate nucleus (patchy long T1 and long T2 signal), sug-gesting infarction on the 10th day (not shown), andrevealed a softening tendency of the lesions on the leftbasal ganglia on the 16th day after transfer. Ophthalmo-logic examination showed no light perception and nopupillary reaction to light, but the retinal edema sub-sided, the retinal artery was sclerosed, the optic disc waspale and the disc margin was slightly fuzzy at that time.During the 18 days of hospitalization in the children’shospital, his respiratory symptoms totally subsided andhe was discharged.At the 2 week follow-up, his vision had deteriorated to

no light perception OD in the left eye. The retinal cherryred spot had resolved, the disc boundary was clear andpale and the retinal edema had resolved remarkably, butthe macular pigment was mildly disordered (not shown).At the 2-month follow-up, there was no light in the lefteye, the fundus examination in the left eye revealed theoptic disc was clear and pale and the retina was normal,but the macular pigment was severely disordered (Fig. 4).The fundus examination was normal in the right eye.

DiscussionM. pneumoniae is one of the most common pathogensof respiratory tract infections in children. M. pneumo-niae infection has been recognized to be associated withmany extra-pulmonary manifestations. including neuro-logic, cardiac, dermatologic, hematologic, immunologicaland gastrointestinal complications, among others [5, 6].The central nervous system is one of the most commonsites of infection of M. pneumoniae. They occur in noless than 3 days after onset of M. pneumonia respiratorydisease (para-infectious type) and up to 2–3 weeks afterrespiratory disease subsides (post-infectious type) with aheterogeneous spectrum of clinical manifestations, suchas menigoencephalitis, polyradiculitis, acute dissemi-nated encephalomyelopathy, transverse myelitis, asepticmeningitis, seizures, and stroke [3, 6, 7]. The incidenceof neurological complications was estimated to rangefrom 1 to 10%, and the mean interval between the onsetof respiratory symptoms and neurological manifestationswas 9.6 days (range: 2–14 days) [2]. Stroke in children israre, but it is one of the most severe neurologic compli-cations associated with M. pneumoniae infection, whichinvolves direct central nervous system invasion, immunemechanisms, vascular occlusion, and a hypercoagulablestate [4, 6]. CRAO is a devastating ophthalmologic eventleading to a severe impairment of vision that presentswith acute, painless loss of monocular vision [8]. Fre-quent etiologies include hypercoagulable states, embolifrom cardiac valvular disease, vasculitis, and other riskfactors, such as smoking, oral contraception use andvasospasm in migraine histories [9]. To the best of ourknowledge, there was no report on the concomitantinvolvement of both CRAO and cerebral infarction inchildren associated with M. pneumoniae infection.

Fig. 4 Fundus examination showed that the optic disc on the left eyewas clear and pale, C/D = 0.3. The central retinal artery was sclerosed,the retina was normal, but the macular pigment was severelydisordered at the 2-month follow-up after CRAO

Bao et al. BMC Pediatrics (2016) 16:210 Page 4 of 6

To date, 12 children with M. pneumoniae-associatedstroke have been reported in the literature [1]. Most pa-tients presented with weakness of one side of the bodyor face with dysarthria or aphasia. Two cases were foundto have arterial occlusion at the level of anterior circula-tion in the brain and concomitant occlusion of theanterior and posterior cerebral circulation [10]. TheCRAO in the left eye that resulted in severe and per-manent visual loss, as in this case, has not been reportedbefore. The mechanism of M. pneumoniae infection-associated stroke is still unclear. Thrombosis and hyper-coagulable states have been noted in those cases with M.pneumoniae infection. However, the thrombophilia pro-files among all 11 patients were normal except for onewith a positive anti-cardiolipin IgM antibody [2]. Theserum coagulation test in this case was also normal. Animmune mechanism had been proposed because of a 2–3 week delay between the occurrence of stroke and therespiratory disease. The immune-mediated response in-cludes autoimmunity, organism-induced immune sup-pression, immune complex vasculopathy and thrombosisof vessels. In this case, the interval between the onset ofrespiratory symptoms and the visual loss in the left eyewas 14 days. Leonardi et al. proposed that M. pneumoniaeinfection-related ischemic stroke can be divided into earlyand late types [3]. Proposed hypotheses include direct in-vasion of M. pneumoniae occurring in the early type andimmune-mediated damage contributing to a 2–3 weeksdelay type. Vascular occlusion extrapulmonary manifesta-tions comprise disorders of vascular origin involving bothdirect and indirect mechanisms. Narita et al. reported ele-vated levels of IL-6, IL-8, and IL-18 mostly in patientswith mycoplasma encephalitis classified as the late-onsettype [4]. M. pneumoniae has been isolated from the cere-brovascular fluid of stroke patients [11], and it may inducechemokines, such as TNF-ɑ and IL-8, in the vasculature,resulting in local vasculitic or thrombotic vascular occlu-sion without a systemic hypercoagulable state (directmechanism) [4]. We found elevated serologic levels of IL-6 and IL-10 in this case, suggesting that the CRAO couldbe associated with an immune response induced by M.pneumonia infection.The management of mycoplasma-associated stroke re-

mains controversial [6, 12]. The therapeutic window forrescuing ischemic but still viable tissue is very short [13].Neuronal death and retinal infarction evolve progres-sively in a time-dependent fashion that is determined byboth the duration and severity of the ischemic insult.Early reperfusion of ischemic tissue has the potential tolimit the cellular, biochemical and metabolic consequencesof retinal ischemia that ultimately lead to irreversible vi-sion loss. Retinal artery occlusion is associated with a poorvisual prognosis, and aggressive management with ocularmassage, anterior chamber paracentesis, and carbogen

therapy does not appear to improve the outcome [13, 14].Animal model studies have suggested that the ideal thera-peutic window for CRAO is less than 4 h [15]. However, itis likely that 6 h is acceptable for many patients with in-complete CRAO. Hattenbach et al. showed that patientstreated within 6.5 h of vision loss had a better visual out-come than those treated between 6.5 and 12 h after theonset of vision loss [16]. Our patient was diagnosed withCRAO approximately 29 h after the onset of CRAO. Thepatient was suddenly crying in the infusion process, to-gether with a transient shaking of right upper limb, anda complaint of blurred vision, which should be consid-ered to be cerebral embolism and retinal arterialembolization because of inflammatory embolus. As thechild was not clearly described his complaint, and thedoctor was short of experience, also the physical exam-ination was not careful especially in the occurrence ofvision complaint. Therefore, the diagnosis of this casewas initially delayed when the onset of CRAO. In spiteof the immunosuppressive therapy, including steroidsand intravenous immunoglobulin, as well as other con-servative treatments, such as reducing intra-ocularpressure, ocular massage, and vasodilators, the visualprognosis in the left eye is very poor.

ConclusionsWe should be aware of the risk for cerebral ischemicstroke, including CRAO, as a complication during theclinical course of M. pneumoniae respiratory disease inchildren. CRAO is a devastating ophthalmologic eventleading to a severe impairment of vision and should betreated within about 6 h after the onset of vision loss.

AbbreviationsAIS: Acute ischemic strokes; CRAO: Central retinal artery occlusion;CRP: C-reactive protein; CSF: Cerebrospinal fluid; CT: Computed tomography;ELISA: Enzyme-linked immunosorbent assay; ESR: Erythrocyte sedimentationrate; M. pneumonia: Mycoplasma pneumonia; MRI: Magnetic resonanceimaging; PCR: Polymerase chain reaction

AcknowledgementWe thank Elsevier Language Editing Services for reviewing the manuscriptand for editorial assistance.

FundingNot applicable.

Availability of data and materialNot applicable.

Authors’ contributionsYB reviewed the literature and prepared the manuscript, XL and KW helpedto draft the manuscript and made a critical reading, CZ and XJ participatedto revisions and helped to draft the manuscript, MJ reviewed the literature,prepared the manuscript and is the corresponding author. All authors readand approved the final version of the manuscript.

Competing interestsThe authors declare that they have no competing interests.

Bao et al. BMC Pediatrics (2016) 16:210 Page 5 of 6

Consent for publicationWritten informed consent was obtained from the parents of the patient forpublication of this case report and the accompanying images. A copy of thewritten consent is available for review by the Editor of this journal.

Ethics approval and consent to participateAll the experiments complied with the requirement of “The Ethics of ClinicalResearch” issued by Ministry of Healthy, China. The research was approvedby Jinhua Municipal Central Hospital and Children’s Hospital, Zhejiang UniversitySchool of Medicine, China.

Author details1Department of Pediatrics, Jinhua Hospital of Zhejiang University, JinhuaMunicipal Central Hospital, Jinhua 321000, Zhejiang Province, China.2Children’s Hospital, Zhejiang University School of Medicine, Hangzhou310003, Zhejiang Province, China.

Received: 19 August 2015 Accepted: 2 December 2016

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Bao et al. BMC Pediatrics (2016) 16:210 Page 6 of 6

AbstractBackgroundCase presentationConclusion

BackgroundCase presentationDiscussionConclusionsAbbreviationsAcknowledgementFundingAvailability of data and materialAuthors’ contributionsCompeting interestsConsent for publicationEthics approval and consent to participateAuthor detailsReferences