[Source: The Journal of the American Medical Association (JAMA) Neurology, full page: (LINK). Abstract, edited.]
Original Investigation | March 2016
Clinical Characteristics and Functional Motor Outcomes of Enterovirus 71 Neurological Disease in Children [ ]
Hooi-Ling Teoh, MBBS1,2; Shekeeb S. Mohammad, FRACP3,4; Philip N. Britton, FRACP4,5,6; Tejaswi Kandula, FRACP1; Michelle S. Lorentzos, MBBS3; Robert Booy, PhD4,5,7; Cheryl A. Jones, PhD4,5,6; William Rawlinson, PhD8; Vidiya Ramachandran, MBBS8; Michael L. Rodriguez, FRCPA9; P. Ian Andrews, FRACP1; Russell C. Dale, PhD3,4; Michelle A. Farrar, PhD1,2; Hugo Sampaio, FRACP1,2
Author Affiliations: 1Department of Neurology, Sydney Children’s Hospital, Sydney, Australia 2Discipline of Pediatrics, School of Women’s and Children’s Health, UNSW Medicine, The University of New South Wales, Sydney, Australia 3T. Y. Nelson Department of Neurology and Neurosurgery, The Children’s Hospital at Westmead, Sydney, Australia 4Discipline of Pediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia 5Marie Bashir Institute, Sydney Medical School, University of Sydney, Sydney, Australia 6Department of Infectious Diseases and Microbiology, The Children’s Hospital at Westmead, Sydney, Australia
7National Centre for Immunization Research and Surveillance, Kid’s Research Institute, Sydney, Australia 8Serology and Virology Division, Prince of Wales Hospital, Sydney, Australia 9Department of Forensic Medicine, NSW Health Pathology, Sydney, Australia
JAMA Neurol. 2016;73(3):300-307. doi:10.1001/jamaneurol.2015.4388.
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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Keywords: Research; Abstracts; Enterovirus 71; Encephalitis.
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