Enterovirus D68 (EV-D68) is a non-polio enterovirus that occasionally causes respiratory illnesses. EV-D68 infections have occurred over the last couple of years and have a high prevalence worldwide. This virus has recently been linked to acute flaccid paralysis and particularly affects children. We report the case of a young adult who presented with acute neurological manifestations along with respiratory involvement. EV-D68 was detected in the patient\'s broncho-alveolar lavage and was followed by a prolonged recovery period. Clinicians should consider EV-D68 infection in the differential diagnosis of acute flaccid paralysis (AFP) and respiratory failure.

BACKGROUND: Acute flaccid myelitis (AFM) are reported to be associated with enterovirus D68 infection. Though an increasing number of AFM cases were reported with EV-D68 infection in the US, few such cases have been found in China.
METHODS: A 6-year-old boy presented with acute flaccid myelitis (AFM) involving left arm after fever and respiratory symptoms for 6 days. Computed Tomography (CT) revealed inflammation in both lungs and magnetic resonance imaging (MRI) of the brain and spine showed swelling in the left frontal lobe and brain stem. The patient was diagnosed with meningomyelitis. EV-D68 was detected from pharyngeal samples 36 days after the onset of the disease.
CONCLUSIONS: We report the first EV-D68 infection in case of AFM in mainland China. AFM surveillance systems is recommended to be established in China to guide diagnosis, case reporting, and specimen collection and testing for better understanding its etiologies.

Many cases of acute flaccid paralysis occurred during an enterovirus D68 (EV-D68) outbreak in North America in the fall of 2014, and this epidemic has been newly defined as a distinct disease entity named acute flaccid myelitis (AFM). This disease entity is relatively popular among pediatricians, whereas it remains little-known among neurologists in Japan. We reported a 7-year-old girl with AFM, in whom severe limb weakness and respiratory failure developed five days after appearance of respiratory symptoms. Clinical features of our case were mimicked by those of acute axonal motor neuropathy at early stage of the disease, and this resulted in delayed diagnosis of AFM. DNA of EV-D68 was not detected. There are few reported cases of severe AFM, in which artificial ventilation is needed for a long time including both acute and recovery phases of the illness, and functional prognosis of AFM is discussed by literature.

Since, early 2000s, there have been several clusters of enterovirus-D68 (EV D68) associated respiratory illness reported from various countries. Recent largest and most wide-spread outbreak of EV-D68 associated severe acute respiratory illness (SARI) occurred in North America. Present report describes a case of EV-D68 associated severe acute respiratory illness from India with a whole genome sequence. The case was identified through retrospective analysis of Influenza SARI surveillance sample collected during September 2017 using Next Generation sequencing. EV D68 positive child aged two years and presented with asthma like symptoms for which he was admitted to ICU. The child tested negative for Influenza, RSV, Rhinovirus, PIV, hMPV and adenovirus, on real time RT-PCR. And on NGS full EV D68 genome was retrieved belonging to sub-clade B3. In ICU, child received anti-bacterial and anti-viral therapy. The child recovered with-out any sequelae and was discharged one week later. Present report highlights the importance of studying this emergent virus EV-D68 through prospective studies to understand the burden and epidemiological pattern in the country and its implications.

During 2018, the United Kingdom experienced an increase in reports of cases of acute flaccid paralysis (AFP). As at 21 January 2019, 40 cases had been identified with a peak in October 2018. The increase was temporally associated with an upsurge in enterovirus (EV) D68 activity. Enterovirus was detected in 15 cases, mainly from respiratory tract samples; nine were typed as EV-D68. A national task force has been established and investigations are ongoing.

Acute flaccid myelitis (AFM) was increasingly detected in recent years, coinciding with upsurges of enterovirus D68 (EV-D68) infections. We reviewed the evidence for a causal relationship between both. Based on reported cases, we provide case definitions for AFM caused by EV-D68 infections to enable a standard procedure for affected patients. Current case definitions are focussing on epidemiological aspects but clinical case definitions are still missing. We propose the following case definitions to be used in clinical practice in order to mirror clinical realities and facilitate a common systematic approach in case management: A possible case is defined as a person presenting with either acute myelitis/paralysis or Guillain-Barré Syndrome (GBS), particularly during periods of EV-D68 circulation. A probable case is defined as a person presenting with symptoms of either acute myelitis/paralysis or GBS and at least one of the following criteria: i) MRI abnormality representing with T2 hyperintensity in spinal cord grey matter with or without hyperintensity at dorsal brain stem, ii) investigations showing an axonal neuropathy including reduced compound motor action potentials with normal conduction velocities and absence of conduction blocks compatible with anterior horn cell disease or iii) detection of enteroviruses in a respiratory specimen obtained from the lower respiratory tract during periods of EV-D68 circulation. A confirmed case is defined as a person presenting with acute flaccid myelitis/paralysis, MRI abnormality and detection of enterovirus-D68-specific nucleic acids in a respiratory specimen using a validated PCR assay targeting the VP1 gene with subsequent sequencing and typing.

BACKGROUND: Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection.
METHODS: A 5-year-old girl developed acute respiratory distress. On the fourth hospital day, both her legs became paralyzed except for slight muscle contraction in the right lower limb. Tendon reflexes in the lower limbs were diminished and there was a positive Babinski sign on the right. Sensation was normal in all modalities, and there was no uro-rectal disturbance. Spinal magnetic resonance imaging identified T2-hyperintense lesions with spinal cord edema, mainly involving the bilateral T11 to L1 anterior horns, with left side dominance extending to the left posterior horn. The neurological and neuro-radiological findings of our case were suggestive of HS; however, she had no history of bronchial asthma. An acetylcholine inhalation challenge eventually proved the presence of reversible airway hyper-responsiveness, allowing us to diagnose HS. We identified enterovirus D68 in the patient\'s intratracheal aspirates using a sensitive polymerase chain reaction assay. Intravenous immunoglobulin administrations at 2 g/kg2 for 5 consecutive days were repeated every month up to four times. After these treatments, the muscle strength of her right lower limb slightly improved while her left lower leg remained completely paralyzed.
CONCLUSIONS: This case emphasizes the importance of provocation tests to reveal the presence of airway hyper-responsiveness when a child shows neurological signs mimicking HS following acute respiratory distress. Furthermore, the present case suggests a possible link between HS and acute flaccid paralysis following lower respiratory tract infection by enterovirus D68.

A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10-year-old boy was reported in Hong Kong in 2014. To examine if a new strain has emerged in Hong Kong, we sequenced the partial genome of the EV-D68 strain identified from the fatal case and the complete VP1, and partial 5\'UTR and 2C sequences of nine additional EV-D68 strains isolated from patients in Hong Kong. Sequence analysis indicated that a cluster of strains including the previously recognized A2 strains should belong to a separate clade, clade D, which is further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7 (including the fatal case) belonged to the previously described, newly emerged subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV-D68 strains, each from subclades B1, B3, and D1, were selected for complete genome sequencing and recombination analysis. While no evidence of recombination was noted among local strains, interclade recombination was identified in subclade D2 strains detected in mainland China in 2008 with VP2 acquired from clade A. This study supports the reclassification of subclade A2 into clade D1, and demonstrates interclade recombination between clades A and D2 in EV-D68 strains from China.

Cystic fibrosis (CF) causes airways obstruction and a decline in percent predicted forced expiratory volume in 1 s (FEV1%). FEV1% is an objective measure of a pulmonary exacerbation of CF; improvement in FEV1% is the endpoint used often to determine success of treatment of these acute declines in pulmonary health. Lung Clearance Index (LCI), derived from multiple breath inert gas washout (MBW) test, measures ventilation inhomogeneity and small airways dysfunction. In the United States in 2014-2015, enterovirus D68 (EV-D68), a novel virus, led to hospitalizations in children because of respiratory distress. This report describes 2 patients with CF admitted for pulmonary exacerbations who were enrolled in an inpatient study to assess patient satisfaction and utility of MBW to measure LCI. Diagnostic testing indicated that these patients were infected with EV-D68. Although their FEV1% improved to their previous baseline following treatment for pulmonary exacerbation, it was discordant with LCI. We discuss LCI as a novel measure of pulmonary function and hypothesize that, based on these cases, it may be a more sensitive indicator of ongoing post-viral airways dysfunction as compared to FEV1%.