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Title: Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children.
Author: Teoh HL, Mohammad SS, Britton PN, Kandula T, Lorentzos MS, Booy R, Jones CA, Rawlinson W, Ramachandran V, Rodriguez ML, Andrews PI, Dale RC, Farrar MA, Sampaio H.
Journal: JAMA Neurol; 2016 Mar; 73(3):300-7. PubMed ID: 26785318.
Abstract:
IMPORTANCE: Enterovirus 71 (EV71) causes a spectrum of neurological complications with significant morbidity and mortality. Further understanding of the characteristics of EV71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines. OBJECTIVE: To further characterize EV71-related neurological disease and neurological outcome in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective 2-hospital (The Sydney Children's Hospitals Network) inpatient study of 61 children with enterovirus-related neurological disease during a 2013 outbreak of EV71 in Sydney, Australia. The dates of our analysis were January 1, to June 30, 2013. MAIN OUTCOMES AND MEASURES: Clinical, neuroimaging, laboratory, and pathological characteristics, together with treatment administered and functional motor outcomes, were assessed. RESULTS: Among 61 patients, there were 4 precipitous deaths (7%), despite resuscitation at presentation. Among 57 surviving patients, the age range was 0.3 to 5.2 years (median age, 1.5 years), and 36 (63%) were male. Fever (100% [57 of 57]), myoclonic jerks (86% [49 of 57]), ataxia (54% [29 of 54]), and vomiting (54% [29 of 54]) were common initial clinical manifestations. In 57 surviving patients, EV71 neurological disease included encephalomyelitis in 23 (40%), brainstem encephalitis in 20 (35%), encephalitis in 6 (11%), acute flaccid paralysis in 4 (7%), and autonomic dysregulation with pulmonary edema in 4 (7%). Enterovirus RNA was more commonly identified in feces (42 of 44 [95%]), rectal swabs (35 of 37 [95%]), and throat swabs (33 of 39 [85%]) rather than in cerebrospinal fluid (10 of 41 [24%]). Magnetic resonance imaging revealed characteristic increased T2-weighted signal in the dorsal pons and spinal cord. All 4 patients with pulmonary edema (severe disease) demonstrated dorsal brainstem restricted diffusion (odds ratio, 2; 95% CI, 1-4; P = .001). Brainstem or motor dysfunction had resolved in 44 of 57 (77%) at 2 months and in 51 of 57 (90%) at 12 months. Focal paresis was evident in 23 of 57 (40%) at presentation and was the most common persisting clinical and functional problem at 12 months (observed in 5 of 6 patients), with 1 patient also requiring invasive ventilation. Patients initially seen with acute flaccid paralysis or pulmonary edema had significantly greater frequencies of motor dysfunction at follow-up compared with patients initially seen with other syndromes (odds ratio, 15; 95% CI, 3-79; P < .001). CONCLUSIONS AND RELEVANCE: Enterovirus 71 may cause serious neurological disease in young patients. The distinct clinicoradiological syndromes, predominantly within the spinal cord and brainstem, enable rapid recognition within evolving outbreaks. Long-term functional neurological morbidity is associated with paresis linked to involvement of gray matter in the brainstem or spinal cord.

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