OBJECTIVE: To explore the distribution of inflammatory cells and positive expression of P-se- lectin glycoprotein ligand-1 (PSGL-1) in infant brainstem tissue from hand-foot-mouth disease related fatal brainstem encephalitis. METHODS: Twenty brainstem samples from infants suffered from brainstem en- cephalitis were collected as the experimental group. Ten brainstem samples from infants died of non- brain diseases and injuries were collected as the control group. The distribution of inflammatory cells and the expression of PSGL-1 in the two groups were examined by immunohistochemical method. The characteristics of the positive cells were observed. RESULTS: In brainstem tissue of the experimental group, there were sleeve infiltrations of inflammatory cells around the vessels and in the glial nodule. Microglia was the most and following was neutrophils around the vessels and in the glial nodule. There was a significant statistical difference among microglias, neutrophils and lymphocytes (P < 0.05). There was no sleeve infiltration in the control group. PSGL-1 protein was expressed widely in inflammatory cells in the experimental group, especially in the inflammatory cells around the vessels and in the glial nodule. But PSGL-1 positive staining could be observed significantly less in the control group comparing with the experimental group (P < 0.05). CONCLUSION Microglia is the main type of inflammatory cells involved in the progress of the fatal disease. Moreover, PSGL-1 could participate in the pathogenesis of hand-foot-mouth disease related fatal brainstem encephalitis.
Brain Stem/pathology* ; Encephalitis/pathology* ; Hand, Foot and Mouth Disease/pathology* ; Humans ; Infant ; Membrane Glycoproteins/metabolism* ; Microglia/pathology* ; Neutrophils/pathology*

OBJECTIVETo investigate the pathogenic and clinical presentation and laboratory tests of bullous rash in hand, foot and mouth disease (HFMD) in Xi'an from January 2013 to December 2014 by retrospective analysis.

METHODA total of 224 specimens were collected from clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions in Xi'an Children's Hospital from January 2013 to December 2014, the identification and subtyping of the isolates were conducted with real-time fluorescent quantitative RT-PCR. A retrospective analysis was performed to analyze the clinical presentation, laboratory tests and late follow-up problems of the HFMD.

RESULTIn the clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions, 207 were caused by coxsackievirus A6 (CA6), accounting for 92. 4% of all cases with bullous, 4 were caused by enterovirus 71 (EV71), accounting for 1.8%, 10 were caused by coxsackievirus A16 (CA16), accounting for 4. 5%; 4 cases were negative for these viruses. In the cases positive for intestinal virus-nucleic acid, 130 were male, 90 were female; male to female ratio was 1. 44: 1, 203 were <5 years old, accounting for 92. 3%. Leukocytosis was found in 75 cases (34. 1%); high-sensitivity C-reactive protein (hsCRP) increased in 200 cases (90. 9%); elevated myocardial enzyme CK-MB was found in 35 cases (15. 9%), alanine aminotransferase increased in 15 cases (6. 8%); 187 cases had fever (85. 0%). None of the cases had serious complications such as encephalitis or myocarditis. In the course of the critical phase bullous rash or large vesicle-like changes, obvious itching, and facial rash appeared. After the fluid in the bullae was absorbed or the bullae ruptured or became ulcerated, scar formation and large areas of exfoliation occurred, with no effusion on the newly formed epithelium in the base, without significant pigmentation on later follow-up. In the late follow up process, 52 cases in CA6-positive patients (25. 1%) developed onychomadesis within 2-4 weeks after onset, 1 to 8 nails, an average of 4. 3 fell off, new nails grew, the nail bed showed no structural abnormalities and hyperplasia after falling off, the surface was smooth, had no hypertrophy, left no sequelae.

CONCLUSIONThe pathogen in HFMD characterized by widespread bullous reactions was mainly the CA6, this kind of HFMD was mainly mild type, with significant itching, later the bullae may have scar formation and skin exfoliation, in some cases onychomadesis may occur.

Child ; Enterovirus A, Human ; Enterovirus Infections ; pathology ; Exanthema ; pathology ; Female ; Fever ; Hand, Foot and Mouth Disease ; pathology ; Humans ; Male ; Pruritus ; Retrospective Studies

Brain Edema ; etiology ; Brain Stem ; pathology ; Encephalitis ; etiology ; Female ; Hand, Foot and Mouth Disease ; complications ; therapy ; Humans ; Infant, Newborn

Brain Stem ; pathology ; Child ; Encephalitis, Viral ; etiology ; Enterovirus A, Human ; Female ; Hand, Foot and Mouth Disease ; complications ; Humans ; Infant

OBJECTIVETo understand the features of magnetic resonance imaging (MRI) findings and the results of clinical follow-up study in 8 infants and children with hand-foot-and-mouth disease (HFMD) complicated with acute flaccid paralysis (AFP) who were admitted to Beijing Ditan Hospital during the outbreak of HFMD in 2008.

METHODSThe clinical characteristics of the 8 HFMD cases were investigated, and MRI findings were analyzed. The recovery of their impairment in limbs was followed up for three months.

RESULTSAll the 8 cases showed poliomyelitis-like syndrome. MRI of spinal cord showed unilateral or bilateral hyperintense lesions which chiefly occurred in the anterior horn regions of the spinal cord (C(2)-C(7) or T(12)-L(1)) on T(1)/T(2)-weighted images. Lesions of spinal cord chiefly occurred in T(12)-L(1). Most of the cases showed mild paralysis, which occurred in more than half of cases in single lower extremity. The patients who had acute paralysis of single lower extremity recovered faster than those with paralysis of four limbs.

CONCLUSIONSIn HFMD with AFP cases, MRI of spinal cord showed unilateral or bilateral lesions in the anterior horn regions of the spinal cord (C(2)-C(7) or T(12)-L(1)) on T(1)/T(2)-weighted images. AFP may be to some degree reversible in HFMD cases. MRI can directly and completely show the range and degree of changes associated with AFP in HFMD cases, thus provide instructive suggestions to its treatment. The acute paralysis of HFMD cases may be benefited from earlier treatment for AFP.

Female ; Follow-Up Studies ; Hand, Foot and Mouth Disease ; complications ; pathology ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Paralysis ; etiology ; pathology ; Spinal Cord ; pathology

OBJECTIVETo explore the development and prognosis of the acute flaccid paralysis (AFP) associated with enterovirus 71 (EV71) infection through clinical follow-up study for clinical and magnetic resonance imaging (MRI) features based on the research progress of virology and pathology.

METHODSixteen children with HFMD associated with AFP in hospital from May 1, 2011 to August 31, 2011 were investigated and the patients received intensive rehabilitation training. The 16 cases were divided into two groups (the recovery or the sequela) by if the muscle strength recovered to level 4 after intensive rehabilitation. The MRI findings of 15 children were analyzed and among them, 6 patients were reexamined after one month. The clinical markers were compared between groups including course of disease, WBC, WBC in cerebrospinal fluid (CSF), ventilator support, therapy, the worst muscle strength, the initial tendon reflex, the muscle atrophy, and multi-limb paralysis. The data were analyzed by t test and χ2 test with SPSS10.0.

RESULTAll the 16 children were infected with enterovirus 71 (EV71). The myodynamia of 7 children were level 0, 4 children had serious upper limbs paralysis. The neck muscle in 3 cases and the brain stem motor ruckus in 4 cases were involved. The ankle clonus of non-completely paralyzed limbs in 14 cases occurred during rehabilitation. Eight children had the better prognosis, the other 8 children had sequela. 0 level muscle strength (0 case vs. 7 cases, χ2=12.4), the initial tendon reflex (2 cases vs. 8 cases, χ2=9.6), obvious muscle atrophy (0 case vs. 8 cases, χ2=16), were significantly different in the children with the recovery when compared to the sequela (P<0.01). The severe upper limbs paralysis had the worse prognosis than the severe lower limbs paralysis. MR imaging showed signs of spinal nerve root inflammation and the bilateral hyperintense lesions, symmetrical in the posterior portions of the medulla, pons, and asymmetrical in the ventral horns of cervical spinal cord. Signal enhancement occurred only in the early MRI examination.

CONCLUSIONIn the evolution of AFP due to EV71 infection, the upper motor neuron damage is common, the prognosis is related with the severity of early paralysis and neuron damage. MR imaging is helpful to understand the pathological mechanism of AFP.

Child, Preschool ; Enterovirus A, Human ; pathogenicity ; Female ; Follow-Up Studies ; Hand, Foot and Mouth Disease ; diagnosis ; pathology ; virology ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Paralysis ; diagnosis ; pathology ; virology ; Prognosis

Autopsy ; Coxsackievirus Infections ; Enterovirus ; isolation & purification ; Enterovirus B, Human ; isolation & purification ; Enterovirus Infections ; Hand, Foot and Mouth Disease ; pathology ; virology ; Humans ; Infant ; Male

OBJECTIVETo understand clinicopathologic characteristics of hand-foot-and-mouth disease.

METHODSThe data of two autopsy cases with brainstem encephalitis caused by enterovirus type 71 infection were analyzed.

RESULTSThe age of the two patients was younger ( < or = 3 age). The clinical course was rapidly progressive, vesicular rashes were found in one case and the other case had no rashes. Both patients had clinical manifestations of central nervous system. Rapid progression to death were preceded by the development of pulmonary edema and hemorrhage. The results of the autopsy showed that the brain and brain stem were most severely involved and there were inflammation and necrosis. There were lung edema and hemorrhage. The myocardium and other organs were not infiltrated by inflammatory cells.

CONCLUSIONHand-foot- and-mouth disease with enterovirus type 71 infection often affected central nervous system, rapid progression to death was preceded by the development of brain stem encephalitis and pulmonary edema.

Brain Stem ; Cause of Death ; Child, Preschool ; Encephalitis, Viral ; pathology ; Enterovirus A, Human ; Female ; Hand, Foot and Mouth Disease ; virology ; Humans ; Infant ; Male ; Myocarditis ; virology

OBJECTIVETo investigate the epidemiological and clinical features of hand, foot and mouth disease (HFMD) since several outbreaks of HFMD caused by enteroviruses were documented in China between 2007 and 2008.

METHODSHFMD cases reported to the National Infectious Disease Information Management System database between May 2008 and April 2009 were assessed. Clinical features in some of the severe and fatal cases were analyzed the etiology of the outbreaks was investigated.

RESULTS89.1% of reported HFMD cases were found in children<5 year-old with an age-specific incidence rate of 834.1/100 000 in the first year as the notifiable disease in China from May 2008 to April 2009. The incidence, mortality and percentage of severe cases were studied for three regions of China and found to be highest in the central region. The incidence of severe cases and mortality in rural population were significantly higher than those in urban population. Among the laboratory confirmed EV17 positive cases there were 52.6% mild, 83.5% severe, and 96.1% fatal cases. More myoclonic jerks were found in the severe case group than in group that died. Tachypnea, lip purpling, pink foaming and low limb temperature occurred more frequently in the fatal cases than in the severe cases.

CONCLUSIONThe epidemic of HFMD in China was characterized predominantly by EV71 infections, had relatively high mortality rates especially in the central region, and was most prevalent in young, rural populations.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Hand, Foot and Mouth Disease ; epidemiology ; pathology ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Young Adult

OBJECTIVETo understand the clinical and epidemiological characteristics of hand-foot-and-mouth disease (HFMD) deceased cases.

METHODInformation of demographics, diagnosis and treatment, clinical symptoms and signs, laboratory test results, and epidemiological contact history of 72 HFMD cases who died between May 2008 and September 2011, in Zhejiang Province, were collected and analyzed.

RESULTThe average age of the 72 cases was 1.8 years, 45 were males, accounting for 62.5%, 63 (87.5%) of the cases were scattered children. Eighteen counties reported 2 or more deaths, accounting for 46.1% (18/39) among the counties where the deaths were reported. The deaths occurred mainly in April to August, the peak occurred in May and June. Fever (98.4%, 63/64) and rash (95.1%, 58/61) were the most common symptoms, but the rash was not obvious at the first diagnosis. Fever occurred before the rash (79.0%, 49/62), persisted for 4 days in average. Vomiting (71.9%, 46/64), dyspnea (65.6%, 42/64), cyanosis (53.1%, 34/64) and impaired consciousness (51.6%, 33/64) were often seen among the cases; 53.1% (34/64) cases went to see the doctor on the first day, but 82.5%(52/63)cases were misdiagnosed. Time to diagnosis of HFMD was in average 3 days. About 3 to 4 days after the onset, the disease deteriorated sharply, deaths occurred within 1 day after admission in 78.9%(45/57)of the deceased cases; 85.0% (34/40) cases had high white blood cells level, mainly neutrophils increased, the ratio of neutrophil was more than 70% in 55.6% (15/27) of cases. Enterovirus 71 (EV71) infection was found in 93.3% (56/60) cases, the deceased cases often died of pulmonary hemorrhage (42.9%, 21/49) and encephalitis (34.7%, 17/49). The sanitary conditions of the cases' family were poor (65.5%, 36/55), but 73.3% (33/45) cases had no exposure history.

CONCLUSIONThe HFMD deceased cases were mostly younger aged boys, scattered children, nonlocal-residents, and had poor sanitation. They were often infected with EV71, had high fever but had no typical rash, no clear exposure history, they had increased leukocyte, and were often misdiagnosed. Three or 4 days after onset, the disease deteriorated abruptly, most cases died within 1 week after onset. To decrease the HFMD mortality, early detection of severe cases should be stressed, and relative measures should be taken. The guardian should be aware of having good sanitary situation and healthy habits.

Animals ; Child, Preschool ; China ; epidemiology ; Disease Outbreaks ; Enterovirus A, Human ; isolation & purification ; Feces ; virology ; Female ; Fever ; etiology ; pathology ; Hand, Foot and Mouth Disease ; epidemiology ; mortality ; pathology ; Humans ; Infant ; Male ; Retrospective Studies ; Sex Distribution