OBJECTIVETo study the clinicopathologic features of fatal enterovirus 71 (EV71) infection.

METHODSAutopsy was performed in 5 neonates died of EV71 infection. Tissue samples from major organs were collected, formalin-fixed and examined under light microscopy. Immunohistochemical study was carried out in selected examples.

RESULTSFour of the 5 cases showed predominant changes in central nervous system, with encephalitis and encephalomyelitis identified mainly in brainstem and upper cervical spinal cord. Histologic findings included neuronal degeneration and necrosis, neuronophagia, perivascular cuffing and diffuse or nodular hyperplasia of macrophages/microglia. Cerebral edema, brain herniation and aseptic meningitis were also noted. The lungs showed mainly pulmonary congestion, neurogenic pulmonary edema and focal hemorrhage. There were minimal changes in the intestinal epithelium. The intestinal lymphoid tissue however was hyperplastic and associated with apoptosis of follicular center cells. The remaining case had cerebral edema and mild meningitis. The lung alveolar septa were thickened with lymphocytic infiltrates. Some alveolar cells were hyperplastic and associated with diffuse hyaline membrane formation. No specific abnormalities were identified in gastrointestinal tract. In all the 5 cases studied, there was enlargement of lung hilar and mesenteric lymph nodes, coupled with apoptosis of follicular center cells. In general, no significant pathologic changes were demonstrated in heart, liver and kidneys.

CONCLUSIONSIn fatal EV71 infection, the major pathologic changes lie in the central nervous system. The pulmonary lesions are mainly secondary in nature. The usual cause of death is cerebral edema complicated by brain herniation and pulmonary edema. It is also noteworthy that some cases show only lung damages, without classic neurologic changes.

Autopsy ; Brain Edema ; etiology ; pathology ; Brain Stem ; pathology ; Child, Preschool ; Encephalitis, Viral ; etiology ; pathology ; Encephalomyelitis ; etiology ; pathology ; Enterovirus A, Human ; isolation & purification ; Enterovirus Infections ; complications ; pathology ; virology ; Female ; Humans ; Infant ; Male ; Pulmonary Edema ; etiology ; pathology ; Spinal Cord ; pathology

Acyclovir ; therapeutic use ; Anti-Inflammatory Agents ; therapeutic use ; Antiviral Agents ; therapeutic use ; Brain Stem ; pathology ; virology ; Encephalitis ; complications ; diagnosis ; drug therapy ; virology ; Herpes Zoster ; complications ; diagnosis ; drug therapy ; virology ; Herpes Zoster Oticus ; diagnosis ; drug therapy ; etiology ; virology ; Humans ; Male ; Methylprednisolone ; therapeutic use ; Middle Aged

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.
Acute Disease ; Brain/diagnostic imaging ; Central Nervous System Diseases/etiology/*pathology ; Child ; Child, Preschool ; Encephalitis/pathology ; Enterovirus A, Human/genetics/*isolation & purification ; Enterovirus Infections/drug therapy/*pathology/virology ; Feces/virology ; Female ; Humans ; Immunoglobulins/administration & dosage ; Infant ; Injections, Intravenous ; Leukocytes/cytology ; Leukocytosis/cerebrospinal fluid/pathology ; Magnetic Resonance Imaging ; Male ; RNA, Viral/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Seasons

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.
Antibodies, Monoclonal/pharmacology/*therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm/pharmacology/*therapeutic use ; Antineoplastic Agents/pharmacology/*therapeutic use ; Cord Blood Stem Cell Transplantation/*adverse effects ; Cytomegalovirus/drug effects ; Cytomegalovirus Infections/*drug therapy/*etiology/physiopathology ; *Encephalitis/etiology/pathology/virology ; Fatal Outcome ; Humans ; Male ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications/drug therapy/virology ; Transplantation Conditioning/methods