Community-Acquired Neonatal SARS-CoV-2 Infection Associated with Neurological Symptoms in Colombia.

INTRODUCTION: The SARS-CoV-2/COVID-19 may produce neurological manifestations, including its occurrence in children, and newborns, which has been little reported so far in newborns with COVID-19. CASE: We present a case in Colombia, of community-acquired neonatal infection of SARS-CoV-2, with suggestive symptoms, such as fever, and showing neurological findings, such as drowsiness, poor suction and mild hypotonia for a short time. DISCUSSION: The clinical manifestations of SARS-COV-2 in neonates are beginning to be described in detail. We report a case of SARS-COV-2-associated neurological compromise in a newborn, with features of drowsiness, poor suction and hypotonia.

Acute Flaccid Myelitis: A Clinical Overview for 2019.

Acute flaccid myelitis (AFM) is characterized by flaccid paralysis of one or more limbs, often following a viral illness, with magnetic resonance imaging findings consistent with inflammation of the spinal cord gray matter. It is unclear whether all patients with AFM will have full recovery of neurologic function. Since 2014, there have been several clusters of AFM in the United States, with a 3-fold increase in reported AFM cases recorded in 2018 compared with the previous year. Epidemiological evidence supports a temporal association between respiratory enteroviral illness, particularly with enteroviruses D68 and A71, and clustering of AFM cases. However, causality has yet to be established. Treatment of AFM is primarily supportive. Adjunctive therapies such as intravenous immunoglobulin, corticosteroids, plasmapheresis, and fluoxetine have not been found to improve long-term outcomes. Further research is urgently needed to characterize and optimize management of this emerging, yet poorly understood, condition.

An increase in reports of acute flaccid paralysis (AFP) in the United Kingdom, 1 January 2018-21 January 2019: early findings.

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.

Hepatitis E virus is not detected in association with neurological disorders among Brazilian children.

Hepatitis E virus is increasingly being associated with idiopathic neurological disease. We tested 325 stool samples from Brazilian children presenting acute flaccid paralysis or Guillain-Barré syndrome using a broadly reactive and sensitive Reverse-transcription Polymerase chain reaction. Hepatitis E genome was not detected in any of the samples tested. Our results suggest that hepatitis E virus does not seem to be associated as the etiologic agent of acute flaccid paralysis and Guillain-Barré syndrome cases occurred in Brazilian children during the period of investigation (2010-2012).

Twenty-nine Cases of Enterovirus-D68-associated Acute Flaccid Myelitis in Europe 2016: A Case Series and Epidemiologic Overview.

BACKGROUND: Enterovirus-D68 (EV-D68) is a respiratory virus within the genus Enterovirus and the family of Picornaviridae. Genetically, it is closely related to rhinovirus that replicates in the respiratory tract and causes respiratory disease. Since 2014, EV-D68 has been associated with the neurologic syndrome of acute flaccid myelitis (AFM). METHODS: In October 2016, questionnaires were sent out to a European network including 66 virologists and clinicians, to develop an inventory of EV-D68-associated AFM cases in Europe. Clinical and virologic information of case patients was requested. In addition, epidemiologic information on EV testing was collected for the period between March and October 2016. RESULTS: Twenty-nine cases of EV-D68-associated AFM were identified, from 12 different European countries. Five originated from France, 5 from Scotland and 3 each from Sweden, Norway and Spain. Twenty-six were children (median age 3.8 years), 3 were adults. EV-D68 was detected in respiratory materials (n = 27), feces (n = 8) and/or cerebrospinal fluid (n = 2). Common clinical features were asymmetric flaccid limb weakness, cranial nerve deficits and bulbar symptoms. On magnetic resonance imaging, typical findings were hyperintensity of the central cord and/or brainstem; low motor amplitudes with normal conduction velocities were seen on electromyography. Full clinical recovery was rare (n = 3), and 2 patients died. The epidemiologic data from 16 European laboratories showed that of all EV-D68-positive samples, 99% was detected in a respiratory specimen. CONCLUSIONS: For 2016, 29 EV-D68-related AFM cases were identified in mostly Western Europe. This is likely an underestimation, because case identification is dependent on awareness among clinicians, adequate viral diagnostics on respiratory samples and the capability of laboratories to type EVs.

Clinical Features of Acute Flaccid Myelitis Temporally Associated With an Enterovirus D68 Outbreak: Results of a Nationwide Survey of Acute Flaccid Paralysis in Japan, August-December 2015.

Background: Acute flaccid myelitis (AFM) is an acute flaccid paralysis syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. Methods: An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens. Results: Fifty-nine AFM cases (58 definite, 1 probable) were identified, including 55 children and 4 adults (median age, 4.4 years). The AFM epidemic curve showed strong temporal correlation with EV-D68 detection from pathogen surveillance, but not with other pathogens. EV-D68 was detected in 9 patients: 5 in nasopharyngeal, 2 in stool, 1 in cerebrospinal fluid (adult case), and 1 in tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from 1- to 4-limb involvement, but all definite cases had longitudinal spinal gray matter lesions on magnetic resonance imaging (median, 20 spinal segments). Cerebrospinal fluid pleocytosis was observed in 50 of 59 cases (85%), and 8 of 29 (28%) were positive for antiganglioside antibodies, as frequently observed in Guillain-Barré syndrome. Fifty-two patients showed variable residual weakness at follow-up. Good prognostic factors included a pretreatment manual muscle strength test unit score >3, normal F-wave persistence, and EV-D68-negative status. Conclusions: EV-D68 may be one of the causative agents for AFM, while host susceptibility factors such as immune response could contribute to AFM development.

Non-polio enteroviruses in faeces of children diagnosed with acute flaccid paralysis in Nigeria.

BACKGROUND: The need to investigate the contribution of non-polio enteroviruses to acute flaccid paralysis (AFP) cannot be over emphasized as we move towards a poliovirus free world. Hence, we aim to identify non-polio enteroviruses recovered from the faeces of children diagnosed with AFP in Nigeria. METHODS: Ninety-six isolates, (95 unidentified and one previously confirmed Sabin poliovirus 3) recovered on RD cell culture from the stool of children <15 years old diagnosed with AFP in 2014 were analyzed. All isolates were subjected to RNA extraction, cDNA synthesis and three different PCR reactions (one panenterovirus 5'-UTR and two different VP1 amplification assays). VP1 amplicons were then sequenced and isolates identified. RESULTS: 92.71% (89/96) of the isolates were detected by at least one of the three assays as an enterovirus. Precisely, 79.17% (76/96), 6.25% (6/96), 7.30% (7/96) and 7.30% (7/96) of the isolates were positive for both, positive and negative, negative and positive, as well as negative for both the 5'-UTR and VP1 assays, respectively. In this study, sixty-nine (69) of the 83 VP1 amplicons sequenced were identified as 27 different enterovirus types. The most commonly detected were CV-B3 (10 isolates) and EV-B75 (5 isolates). Specifically, one, twenty-four and two of the enterovirus types identified in this study belong to EV-A, EV-B and EV-C respectively. CONCLUSIONS: This study reports the circulating strains of 27 non-polio enterovirus types in Nigerian children with AFP in 2014 and Nigerian strains of CV-B2, CV-B4, E17, EV-B80, EV-B73, EV-B97, EV-B93, EV-C99 and EV-A120 were reported for the first time. Furthermore, it shows that being positive for the 5'-UTR assay should not be the basis for subjecting isolates to the VP1 assays.

Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016.

OBJECTIVE: To report a outbreak of 11 cases of acute asymmetric flaccid myelopathy due to spinal motor neuron injury. MATERIAL AND METHODS: Eleven children, six male, with a mean age of 3 years presented with acute flaccid myelitis. We analyzed clinical features, etiology, neuroradiological images, treatment, and outcome. RESULTS: Nine children had bilateral and asymmetric flaccid myelitis of the upper limbs, 1 had upper limb monoplegia, and 1 presented with hemiparesis. The cranial nerves were involved in 6 patients and 4 required mechanical ventilation. In all cases acute flaccid myelitis co-occurred with upper airway infection and/or fever. Spinal cord magnetic resonance imaging was abnormal in all, showing 2 different patterns: A linear pattern involving the anterior horns and another that was more heterogeneous showing spinal cord expansion. The lesions were non-enhancing in all. In 5/11 patients involvement of the medulla oblongata and pons was also observed. None of the patients presented with supratentorial lesions. In 4/11 children, the human enterovirus subtype D68 (HEV-D68) was identified in the airway and in 1/11 in the cerebrospinal fluid as well. In the remaining patients different enterovirus species A, B, and C variants were detected, as well as rhinovirus in 1 and influenza in another. Ten children received treatment with intravenous immunoglobulin and steroids and 4 of these children also underwent plasma exchange. Treatment did not lead to clinical improvement. CONCLUSIONS: In a patient with acute flaccid myelitis, HEV-D68 infection should be ruled out. Cases in which the virus was not detected were considered as "false negatives" as samples were collected late in course of the disease. The lack of response to anti-inflammatory and immunomodulatory treatment suggests a direct viral mechanism. This study is to our knowledge the first on an HEV-D68-infection-related cluster in Latin America.

Acute segmental poliomyelitis-like flaccid paralysis in an adult in the UK, associated with enterovirus D68.

Enterovirus D68 has been associated with a poliomyelitis-like illness, notably during an outbreak in 2014, and particularly affecting children in the USA. We report a case of acute segmental flaccid paralysis with respiratory involvement in an adult in the UK, with enterovirus D68 detected in a sputum sample. MR imaging of cervical spinal cord showed a longitudinally extensive T2 hyperintensity in the anterior cord. Cerebrospinal fluid showed an elevated white cell count, predominantly lymphocytic, with otherwise normal constituents and negative viral PCRs. His respiratory function improved after intravenous immunoglobulin, suggesting that this may be useful in such cases. Clinicians should consider enterovirus D68 infection in the differential diagnosis of Guillain-Barré syndrome, particularly the pharyngeal-cervical-brachial variant.

Pediatric Acute Flaccid Paralysis: Enterovirus D68-Associated Anterior Myelitis.

BACKGROUND: Enteroviral infections can cause acute flaccid paralysis secondary to anterior myelitis. Magnetic resonance imaging (MRI) is important in the diagnosis of this potentially devastating pediatric disease. Before the 2014 outbreak of Enterovirus D68 (EV-D68), the virus was considered a relatively benign disease. CASE REPORT: A fully immunized 8-year-old boy was brought to the emergency department complaining of a cough, headache, neck pain, and right arm pain and weakness. Deep tendon reflexes in the weak arm could not be elicited. MRI of the brain and cervical spine revealed anterior myelitis of the cervical spine. The patient was given intravenous antibiotics, acyclovir, and methylprednisolone with no initial improvement. He was then given intravenous immunoglobulin over 3 days with improvement in symptoms. Nasal swab polymerase chain reaction revealed EV-D68. Despite medical management, the child was left with long-term motor disability in the effected extremity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acute flaccid paralysis is a potential devastating complication of enteroviral infections. Extremity complaints in the clinical setting of central nervous system infection should raise concern for encephalomyelitis. MRI is extremely helpful in establishing this diagnosis. Prevalence of non-polio enteroviral paralytic events is increasing in the United States. Potential EV-D68 cases should be reported to local health departments. Emergency medicine providers should consider this complication in the child with acute, unexplained significant respiratory illness with new neurologic complaints.

Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child.

BACKGROUND: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. CASE PRESENTATION: A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 °C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm3, 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient's four limbs. MRI acquired after 3 weeks showed that the previously reported alterations were no longer present. CONCLUSION: This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM.

[Investigation of adenovirus isolation frequency from the stool samples of patients suspected with acute flaccid paralysis]. / Akut flask paralizi süpheli olgularin diski örneklerinden adenovirus izolasyon sikliginin arastirilmasi.

Although adenoviruses (AdVs) generally cause upper respiratory tract infections, conjunctivitis/epidemic keratoconjunctivitis, gastroenteritis and pneumonia, they can lead to the involvement of central nervous system. Acute flaccid paralysis (AFP) is a type of seizure, characterized by rapid and sudden onset of extreme weakness in hands and feet, including (less frequently) weakness of respiratory and swallowing, representing with decreased muscle tone, especially in children below 15-year-old. The major viral cause of AFP is polioviruses, however non-polio enteroviruses, mumps virus, rabies virus and flaviviruses can also be responsible for AFP. The data of some recent studies have pointed out the probable aetiological role of AdVs in AFP. The aim of this study was to investigate the frequency of AdVs from stool samples of AFP-suspected patients and their contacts. A total of 6130 stool samples from patients (age range: 0-15 years) prediagnosed as AFP (n= 3185) and their contacts (n= 2945), which were sent to our laboratory from the health care centers located at different regions of Turkey for the monitorization of poliomyelitis as part of national AFP surveillance programme, between 2000-2014, have been retrospectively evaluated in terms of adenovirus isolation frequency. Samples were analyzed according to the algorithm recommended by World Health Organization and inoculated in Hep-2, RD, and L20B cell lines for cultivation. Apart from enteroviruses, in case of the presence of characteristic cytopathic effects for AdVs observed in L20B cells were confirmed by a commercial Adeno agglutination kit (Diarlex Adeno; Orion Diagnostica, Finland). It was noted that AdVs have been isolated from 1.6% (97/6130) of the samples, and out of positive samples 76.3% (74/97) were from AFP-suspected cases, while 23.7% (23/97) were from their contacts. Accordingly the frequencies of AdVs from AFP-suspected cases and their contacts were found as 2.3% (74/3185) and 0.8% (23/2945), respectively. The frequencies of Adenovirus positivity between the patients and their contacts were statistically significant (Z-Score 4.8347; p< 0.05). It was determined that 52.6% of the detected AdVs among AFP-suspected cases were between 1-4 age group and the positivity was 1.6 times more among males than the females. Although the data of this study are in agreement with the studies that support the relationship of AdVs with AFP, it is obvious that further molecular and clinical studies are needed.

Acute Flaccid Paralysis Associated with Novel Enterovirus C105.

An outbreak of acute flaccid paralysis among children in the United States during summer 2014 was tentatively associated with enterovirus D68 infection. This syndrome in a child in fall 2014 was associated with enterovirus C105 infection. The presence of this virus strain in North America may pose a diagnostic challenge.

West Nile virus-associated acute flaccid paralysis.

A 43-year-old woman presented to George Washington emergency department with 48 h of new-onset inguinal pain. Physical examination revealed a diffuse maculopapular rash involving the palms and soles, as well as inguinal lymphadenopathy. The patient denied recent travel outside of Washington, DC, and had no known sick contacts. She was admitted to the hospital for observation. Within 24 h of admission she developed left lower extremity flaccid paralysis, with loss of left patellar and Achilles reflexes. cerebrospinal fluid was positive for West Nile virus IgG and IgM antibodies, so methylprednisone 125 mg intravenously two times per day was started. On day 7, the patient recovered reflexes and continued to regain strength in the left lower extremity. She was discharged on day 9 on prednisone taper, with outpatient follow-up.