Neurological complications and risk factors of cardiopulmonary failure of EV-A71-related hand, foot and mouth disease

Abstract

From 2010 to 2012, large outbreaks of EV-A71-related- hand foot and mouth disease (HFMD) occurred annually in China. Some cases had neurological complications and were closely associated with fatal cardiopulmonary collapse, but not all children with central nervous system (CNS) involvement demonstrated a poor prognosis. To identify which patients and which neurological complications are more likely to progress to cardiopulmonary failure, we retrospectively studied 1,125 paediatric inpatients diagnosed with EV-A71-related HFMD in Hunan province, including 1,017 cases with CNS involvement. These patients were divided into cardiopulmonary failure (976 people) group and group without cardiopulmonary failure (149 people). A logistic regression analysis was used to compare the clinical symptoms, laboratory test results, and neurological complications between these two groups. The most significant risk factors included young age, fever duration ≥3 days, coma, limb weakness, drowsiness and ANS involvement. Patients with brainstem encephalitis and more CNS-involved regions were more likely to progress to cardiopulmonary failure. These findings can help front-line clinicians rapidly and accurately determine patient prognosis, thus rationally distributing the limited medical resources and implementing interventions as early as possible.

Figure 1. Number of Cases of EV-A71-related HFMD hospitalizations in the Children’s Hospital of Hunan province from January 1, 2010 to December 31, 2012.

Figure 2. Spin-Echo T2-weighted MRI scan of a 28-month-old boy with encephalitis, brainstem encephalitis and myelitis from EV-A71 infection.

The child had fever; rashes on the mouth, palms, and soles of the feet; vomiting; myoclonus; tachypnea; and drowsiness, followed by coma. Physical examination revealed skin rashes, weakness in four limbs, hypermyotonia, and positive reflex of Babinski’s sign. At the basal ganglia level (Panel A), there was an increased signal intensity of the bilateral globus pallidus (arrows). At the midbrain level (Panel B), there was an increased signal intensity of the bilateral cerebral peduncle (arrows). At the pons and medulla oblongata level (Panel C,D), lesions of high signal intensity were observed in the bilateral tegmentum (arrows). In the sagittal view (Panel E), there was a high signal intensity from the brain-stem to the anterior horn of the cervical spinal cord (arrows).

Figure 3. ROC curve of the final model.

Panel (A) is the ROC of the first model, AUC = 0.916; 95% CI, 0.890–0.941, p = 0.000, Panel (B) is the ROC of the second model, AUC = 0.927; 95% CI, 0.903–0.952, p = 0.000, both panels indicate good internal validity.