Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab.

We present the case of a young woman being treated with rituximab for rheumatoid arthritis who developed a severe enteroviral meningoencephalitis and acute flaccid myelitis (AFM). Cerebrospinal fluid (CSF) and stool reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis and additional sequencing studies performed at the CDC further characterized the enterovirus as enterovirus A71 (EV-A71). After treatment with intravenous immunoglobulin (IVIg) and fluoxetine (based on previous reports of possible efficacy) the patient experienced a remarkable improvement over time. This case highlights the importance of considering enteroviral infection in patients treated with rituximab, depicts a possible clinical course of enteroviral meningoencephalitis and AFM, and illustrates the importance of testing multiple sites for enterovirus infection (CSF, stool, nasopharyngeal swab, blood). Here we present the case with a brief review of the literature pertaining to EV-A71.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Pontine Tegmentum Lesions Accompanying Myelitis During an Enterovirus Outbreak: Differential Diagnosis and Outcome.

AIM: To investigate etiology and prognostic significance of pontine tegmentum lesions accompanying a cluster of acute flaccid myelitis. METHOD: We retrospectively examined patients from 6 centers in Turkey who manifested encephalitis or myelitis associated with dorsal pontine lesions on magnetic resonance imaging (MRI) between July 2018 and February 2019. RESULTS: Twenty-two patients were evaluated. Ten of 22 (45%) presented with acute paralysis and 12 of 22 (55%) with brainstem symptoms only. Reverse transcription polymerase chain reaction for enterovirus was positive in 2 patients' respiratory tract. Other etiologic factors were detected in 10 cases. On follow-up, patients presenting with symptoms of myelitis developed motor sequalae although spinal cord lesions on MRI resolved in 5 of 9 (55%). Encephalitic symptoms, present in 17 cases, recovered in 13 (76%), and brain MRI showed complete or near-complete resolution in 11 of 14 (78%). CONCLUSION: Various etiologic agents can be detected in patients with pontine involvement, even in a series collected during an outbreak of EV-D68. Encephalitis has a fair outcome but clinical recovery is slow and motor sequalae are frequent in spinal involvement, irrespective of follow-up spinal MRI findings.

Acute Flaccid Myelitis With Neuroradiological Finding of Brachial Plexus Swelling.

BACKGROUND: Acute flaccid myelitis is a recently defined clinically distinct syndrome of polio-like acute flaccid paralysis. Acute flaccid myelitis cases show characteristic neuroradiological features of longitudinal spinal cord lesions with predominant gray matter involvement. Current evidence suggests injury to the anterior horn neurons as the underlying mechanism. METHODS: We describe three patients with acute flaccid myelitis who developed flaccid upper limb weakness with diminished deep tendon reflexes after prodromal fever. Spinal magnetic resonance imaging (MRI) (axial and sagittal T1- and T2-weighted sequences) and brachial plexus MRI (coronal short tau inversion recovery sequence) at the acute stage were performed. RESULTS: Spinal MRI showed extensive longitudinal lesion in the spinal cord with predominant gray matter involvement. We were able to demonstrate concurrent swelling and hyperintensity in the brachial plexus in all the three patients at the acute stage. CONCLUSION: The coexisting signal intensities suggest an extension of acute flaccid myelitis pathology to the brachial plexus, highlighting the possible peripheral nerve involvement in acute flaccid myelitis.

COVID-19: A primer for Neuroradiologists.

The potential for central nervous system (CNS) involvement in coronavirus disease 2019 (COVID-19) is a matter of grave concern and there is a relevant body of evidence in the basic sciences to support this possibility. A neuroradiologist should be aware of the potential mechanisms involved in the neuropathogenesis of this virus, as we begin to see cases with abnormal brain scans emerging from all parts of the world.

Enterovirus D68 in a 6-year-old acute flaccid myelitis case in China, 2018: a case report.

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. CASE PRESENTATION: 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. CONCLUSION: 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.

Neuroimaging of Emergent and Reemergent Infections.

Infectious diseases emerge and reemerge over the years, and many of them can cause neurologic disease. Several factors contribute to the emergence and reemergence of these conditions, including human population growth, an increase in international travel, the geographic expansion of recognized pathogens to areas where they were previously nonendemic, and greater contact with wild animal reservoirs. The antivaccination social movement has played an important role in the reemergence of infectious diseases, especially some viral conditions. The authors review different viral (arboviruses such as dengue, chikungunya, and Zika virus; enterovirus 71; measles; and influenza), bacterial (syphilis, Lyme disease, and listeriosis), and parasitic (Chagas disease) diseases, focusing primarily on their neurologic complications. Although there are several additional infectious diseases with central nervous system manifestations that could be classified as emergent or reemergent, those listed here are the most relevant from an epidemiologic standpoint and are representative of important public health issues on all continents. The infections caused by these pathogens often show a variety of neuroimaging patterns that can be identified at CT and MRI, and radiology is central to the diagnosis and follow-up of such conditions. Given the increasing relevance of emerging and reemerging infections in clinical practice and public health scenarios, radiologists should be familiar with these infections. Online supplemental material is available for this article. ©RSNA, 2019.

Head ultrasound, CT or MRI? The choice of neuroimaging in the assessment of infants with congenital cytomegalovirus infection.

BACKGROUND: Despite growing interest in universal screening for congenital CMV infection (cCMV), and data to support treatment for cases with central nervous system (CNS) involvement, there is limited regarding the optimal imaging modalities to identify CNS involvement. The objective of this study was to assess the concordance between head ultrasound (US) and magnetic resonance imaging (MRI) or computed tomography (CT), in identifying neurological abnormalities in infants with cCMV infection, and to determine whether the addition of advanced neuroimaging after US had an impact on clinical management. METHODS: Retrospective review of infants with cCMV infection, referred to the Centre d'Infectiologie Mère-Enfant (CIME) at Sainte-Justine Hospital Center in Montreal, between 2008 and 2016. Only patients who underwent head US followed by and brain MRI or CT scan were included in this analysis. RESULTS: Of 46 cases of cCMV identified during the study period, 34 (74%) had a head US followed by MRI (n = 28, 61%), or CT scan (n = 6, 13%). In the majority of cases (n = 24, 71%), both images were concordant (11 both reported abnormal, 13 both reported normal). In 5 cases, US was reported normal and subsequent imaging (MRI = 4, CT = 1); reported abnormal. In all 5 cases patients were clinically symptomatic and met treatment criteria even in the absence of neuroimaging findings. In 5 cases, US was reported abnormal with a subsequent normal MRI (4) or CT (1); in 2 of these cases, patients were clinically symptomatic and met treatment criteria regardless of neuroimaging findings. However, in 3 cases, the patients were clinically asymptomatic, and in 2 of these cases, treated based only on the abnormal US findings. CONCLUSIONS: In this study, we found that that sequential US and MRI were concordant in the majority (71%) of cases in detecting abnormalities potentially associated with cCMV infection. While the addition of MRI to baseline head ultrasound did not influence the decision to treat in clinically symptomatic infants, the addition of MRI to infants with abnormal HUS imaging who are clinically asymptomatic could help refine treatment decisions in these cases.

Zika Virus: Obstetric and Pediatric Anesthesia Considerations.

As of November 2016, the Florida Department of Health (FDH) and the Centers for Disease Control and Prevention have confirmed more than 4000 travel-related Zika virus (ZIKV) infections in the United States with >700 of those in Florida. There have been 139 cases of locally acquired infection, all occurring in Miami, Florida. Within the US territories (eg, Puerto Rico, US Virgin Islands), >30,000 cases of ZIKV infection have been reported. The projected number of individuals at risk for ZIKV infection in the Caribbean and Latin America approximates 5 million. Similar to Dengue and Chikungunya viruses, ZIKV is spread to humans by infected Aedes aegypti mosquitoes, through travel-associated local transmission, via sexual contact, and through blood transfusions. South Florida is an epicenter for ZIKV infection in the United States and the year-round warm climate along with an abundance of mosquito vectors that can harbor the flavivirus raise health care concerns. ZIKV infection is generally mild with clinical manifestations of fever, rash, conjunctivitis, and arthralgia. Of greatest concern, however, is growing evidence for the relationship between ZIKV infection of pregnant women and increased incidence of abnormal pregnancies and congenital abnormalities in the newborn, now medically termed ZIKA Congenital Syndrome. Federal health officials are observing 899 confirmed Zika-positive pregnancies and the FDH is currently monitoring 110 pregnant women with evidence of Zika infection. The University of Miami/Jackson Memorial Hospital is uniquely positioned just north of downtown Miami and within the vicinity of Liberty City, Little Haiti, and Miami Beach, which are currently "hot spots" for Zika virus exposure and transmissions. As the FDH works fervently to prevent a Zika epidemic in the region, health care providers at the University of Miami and Jackson Memorial Hospital prepare for the clinical spectrum of ZIKV effects as well as the safe perioperative care of the parturients and their affected newborns. In an effort to meet anesthetic preparedness for the care of potential Zika-positive patients and perinatal management of babies born with ZIKA Congenital Syndrome, this review highlights the interim guidelines from the Centers for Disease Control and Prevention and also suggest anesthetic implications and recommendations. In addition, this article reviews guidance for the evaluation and anesthetic management of infants with congenital ZIKV infection. To better manage the perioperative care of affected newborns, this article also reviews the comparative anesthetic implications of babies born with related congenital malformations.

Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

PURPOSE: The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. MATERIAL AND METHODS: Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. RESULTS: The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). CONCLUSIONS: We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

Imaging of topographic viral CNS infections.

Infections caused by enteroviruses, rabies, adenoviruses, and Nipah and Hanta viruses are discussed. Several studies defined the pattern of MR imaging findings in these disease processes that reflect parenchymal infiltration with inflammatory cells, typically visualized as areas of low attenuation on CT, as well as of low T1 and high T2 signal intensity on MR imaging. Diffusion-weighted MR imaging has been shown to be superior to conventional magnetic resonance imaging for the detection of early signal abnormalities in encephalitis. Focal unilateral hyperperfusion as visualized by SPECT appears to be an indicator of severe inflammation of the brain tissue and was found to be an independent predictor of poor prognosis, whereas clinical outcome variables, CSF, or EEG findings are not.

Expression of neurotrophic factors in cerebrospinal fluid and plasma of children with viral and bacterial meningoencephalitis.

AIM: To evaluate the expression of neurotrophic factors (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) and their association with the clinical-radiological characteristics and outcome of children with viral and bacterial meningoencephalitis (ME). METHODS: Prospective observational clinical study performed on 13 children with ME and 12 controls with non-inflammatory obstructive hydrocephalus. Neurotrophic factor levels in the cerebro-spinal fluid (CSF) and plasma were measured using an immunoenzymatic assay. RESULTS: High levels of NGF and BDNF were demonstrated in all patients, while GDNF levels did not undergo significant variations. NGF expression in the CSF was higher in viral ME than in bacterial ME and was correlated with CSF cellularity (particularly mononuclear cells). BDNF expression in the CSF was higher in bacterial ME than in viral ME and was correlated with CSF cellularity and blood platelet count. No relationships were noted between CSF protein or serum C-reactive protein levels and the expression of neurotrophic factors. Regarding clinical and radiological features, elevated NGF/BDNF levels in the CSF correlated with higher incidence of seizures and prolonged comatose state and with specific radiological lesions. No correlation was found between NGF/BDNF levels and final outcome. CONCLUSIONS: The variations in neurotrophic factor levels may reflect an endogenous attempt at neuroprotection against biochemical and molecular changes during both viral and bacterial ME. The expression of these factors is likely to play a neuro-immunomodulatory or neurosurvival role in ME infections.

Cranial viral infections in the adult.

Viral infections of the adult are fortunately rare conditions but may carry serious clinical sequelae. Infection is usually acquired by haematogenous spread during a systemic viral illness and may be acute, subacute or chronic. The pathological basis of neuronal degeneration and attempt to repair is common to all illnesses and diagnosis is generally made by analysis of the pattern of disease. Magnetic resonance imaging is now the mainstay of imaging diagnosis. Acute infections include encephalitis due to a wide range of infecting agents and outcome depends on the severity of the acute episode. Subacute and chronic infections, including HIV encephalopathy, most often produce a progressive leucoencephalopathy and ultimately cerebral atrophy. Additionally, disease may also be immune mediated, that most closely associated with viral infection being acute disseminated encephalomyelitis, which is usually a monophasic illness. Finally, prion diseases are characterised by long incubation period and progressive course, leading to death.