Enterovirus 71 Meningoencephalitis With Extensive White Matter Damage

To the Editor: Enterovirus (EV) infections are common in infants, mostly during summer and fall. Central nervous system involvement is frequent. Clinical manifestations vary from nonspecific febrile symptoms to a potentially life-threatening illness.1 A 31-day-old girl was admitted for poor feeding and insufficient weight gain. She was born uneventfully at term. Her birth weight was on the third percentile and she was being closely followed since birth, with good weight recovery until the previous week. Her physical examination was unremarkable except for mild hypotonia and poor suck reflex. She had no rash, petechiae or vesicular lesions. Laboratory results revealed normal hemoglobin (14.3 g/dL), white blood cell count of 6230/μL, with 58% neutrophils, platelet count of 254,000/μL, C-reactive protein of 0.49 mg/L and elevated liver enzymes (AST-80 U/L, ALT-243 U/L). On the day after admission, she had an episode of hyporeactivity, severe hypotonia, cyanosis and fixed gaze that lasted few minutes, after which she maintained global hypotonia, weak reaction to stimuli and fixed bilateral miosis. The cerebrospinal fluid had normal white blood cell and glucose and slightly increased protein (0.97 g/dL). Intravenous fluids, phenobarbital, cefotaxime, ampicillin and acyclovir were administered. She was transferred to intensive care unit, where she was ventilated for apnea. She also presented a seizure episode, with hyperextension movements of the upper limbs, mouth myoclonus and gaze deviation, with diffuse paroxysmal activity on electroencephalogram. Seizures were controlled after phenytoin administration. Brain magnetic resonance imaging revealed multiple supra and infratentorial lesions, mostly in the subcortical white matter. The lesions were predominantly T2 hyperintense and T1 hypointense and showed reduced diffusion; there were also focal T1 hyperintense areas, suggesting a hemorrhagic component (Fig. 1).FIGURE 1: Coronal T2-weighted (A) and axial T1-weighted (B) images show multiple bilateral parenchymal lesions, mainly in the subcortical white matter (arrows in A). The largest lesion on the left has a T1 hyperintense component, likely from hemorrhage (arrowhead in B). Axial and coronal diffusion-weighted images (C, D) reveal extensive areas of restricted diffusion in both cerebral hemispheres and also in the corpus callosum.Clinical improvement was apparent within 72 hours, with a steady recovery. Her neurologic examination at discharge (day 19) was normal, and at 3 months old her development was appropriate. Blood and cerebrospinal fluid bacterial cultures were negative. Cerebrospinal fluid polymerase chain reaction for EV was positive and negative for herpes simplex virus 1 and 2 and herpesvirus 6. EV71 was identified by viral culture in feces, followed by PCR amplification and nucleotide sequencing. Although rare, neurologic complications of EV71 infection are well known, including meningitis, brainstem encephalitis and acute flaccid paralysis.2,3 Involvement of the posterior portions of the medulla oblongata and pons are characteristic findings,3 not present in our patient. In the literature, there are scarce descriptions of severe white matter damage associated with neonatal EV meningoencephalitis. These infections occurred mostly during the first week of life and in 2 cases a few weeks after preterm birth (28–33 weeks), none related to EV71.4,5 Fever, poor suckling, lethargy, irritability, diarrhea and rash were common symptoms.5 The pathogenesis of white matter damage is unclear and may be attributable to inflammatory cytokines generated during the infectious process or to direct viral invasion.5 Correlation between severity of imaging abnormalities and neurodevelopmental outcome is not well established.5 We report the first case of EV71 meningoencephalitis in a 1-month-old girl, characterized by extensive white matter damage, a finding previously described in association with other EV serotypes during neonatal period. Joana Correia, MD Department of Pediatrics Centro Hospitalar do Porto Porto, Portugal José Eduardo Alves, MD Department of Neuroradiology Centro Hospitalar do Porto Porto, Portugal Paula Ferreira, MD Pediatric Intensive Care Unit Centro Hospitalar do Porto Porto, Portugal Manuela Ferreira, MD Department of Pediatrics Unidade Local de Saúde do Nordeste – Unidade Hospitalar de Bragança Bragança, Portugal Paula Pires, MD Cristina Garrido, MD Department of Neuropediatrics Centro Hospitalar do Porto Porto, Portugal