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.

Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection.

West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue.IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available. Antiviral inflammatory responses are a crucial component of WNV pathology, and understanding how they are regulated is important for tailoring effective treatments. Proinflammatory responses during WNV infection have been extensively studied, but anti-inflammatory responses (and their potential protective and reparative capabilities) following WNV infection have not been investigated. Minocycline induced the expression of genes associated with the anti-inflammatory (M2) activation of CNS macrophages (microglia) in WNV-infected SCSC while inhibiting the expression of genes associated with proinflammatory (M1) macrophage activation and was protective for multiple CNS cell types, indicating its potential use as a therapeutic reagent. This ex vivo culture system can uniquely address the ability of CNS parenchymal cells (neurons, astrocytes, and microglia) to respond to minocycline and to modulate the inflammatory environment and cytotoxicity in response to WNV infection without peripheral immune cell involvement.

Case Report: Spinal Subarachnoid Hemorrhage: A Rare Complication of Hemorrhagic Fever with Renal Syndrome.

Hemorrhagic fever with renal syndrome (HFRS), caused by hantavirus, is occasionally seen in tropical areas. The virus is carried by specific rodent host species. Hemorrhagic fever with renal syndrome is characterized by renal failure and hemorrhagic manifestations, and its complications may be severe, including massive bleeding, multi-organ dysfunction, and possibly death. In this patient case, a 46-year-old woman diagnosed with HFRS initially presented with fever, impaired renal function, and thrombocytopenia. Four days after symptom onset, the patient complained of abrupt right lower abdominal pain and numbness. Magnetic resonance imaging revealed a spinal subarachnoid hemorrhage (SAH) beyond the T7 to S2 vertebrae. No cases of spinal SAH in HFRS have been reported until now. This case demonstrates that when a patient's symptoms are atypical, bleeding-related complications must be considered.

Intrathecal humoral responses are inversely associated with the frequency of simian immunodeficiency virus macrophage-tropic variants in the central nervous system.

Sustained simian immunodeficiency virus (SIV) infection of the central nervous system (CNS) depends on macrophage-tropic (M-tropic) strains that are often easily neutralizable. The CNS is often thought of as an immunologically privileged site that fosters replication of M-tropic quasispecies. Yet, there are limited data addressing the intrathecal antibody response or the role of the humoral response, in general, to control M-tropic strains. We investigated the temporal course of the intrathecal fusion inhibitory activity against an M-tropic viral variant and found an inverse relationship between the magnitude of this neutralization and the prevalence of M-tropic populations. These studies suggest a role for the humoral response in the suppression of M-tropic viral species in the CNS in experimental SIV infection.

Virtual Spine: A Novel, International Teleconferencing Program Developed to Increase the Accessibility of Spine Education During the COVID-19 Pandemic.

BACKGROUND: The coronavirus identified in 2019 (COVID-19) pandemic effectively ended all major spine educational conferences in the first half of 2020. In response, the authors formed a "virtual" case-based conference series directed at delivering spine education to health care providers around the world. We herein share the technical logistics, early participant feedback, and future direction of this initiative. METHODS: The Virtual Global Spine Conference (VGSC) was created in April 2020 by a multiinstitutional team of spinal neurosurgeons and a neuroradiologist. Biweekly virtual meetings were established wherein invited national and international spine care providers would deliver case-based presentations on spine and spine surgery-related conditions via teleconferencing. Promotion was coordinated through social media platforms such as Twitter. RESULTS: VGSC recruited more than 1000 surgeons, trainees, and other specialists, with 50-100 new registrants per week thereafter. An early survey to the participants, with 168 responders, indicated that 92% viewed the content as highly valuable to their practice and 94% would continue participating post COVID-19. Participants from the United States (29%), Middle East (16%), and Europe (12%) comprised the majority of the audience. Approximately 52% were neurosurgeons, 18% orthopedic surgeons, and 6% neuroradiologists. A majority of participants were physicians (55%) and residents/fellows (21%). CONCLUSIONS: The early success of the VGSC reflects a strong interest in spine education despite the COVID-19 pandemic and social distancing guidelines. There is widespread opinion, backed by our own survey results, that many clinicians and trainees want to see "virtual" education continue post COVID-19.

The impact of SARS-CoV-2 pandemic on Oncologic and Degenerative Spine Surgery Department activity: the experience of Rizzoli Orthopaedic Institute under COVID-19 lockdown.

OBJECTIVE: Experience of Department of Oncologic and Degenerative Spine Surgery of Rizzoli Orthopaedic Institute during SARS-CoV-2 pandemic lockdown. PATIENTS AND METHODS: Retrospective observational study of surgically treated patients from 09th March 2020 to 04th May 2020. DATA COLLECTED: age, sex, type of disease, neurological status, days of hospitalization, complications and type of discharge. A comparison analysis with same period of the last year was performed in order to evaluate the impact of COVID-19 spreading on daily surgical activity. RESULTS: A total of 107 surgical procedures in 102 patients were performed from 09th March 2020 to 04th May 2020. Analysis showed a statistically significant difference in age, sex, ASIA class and type of treated disease compared to the same period of the last year (p=0.042, 0.006, 0.022 and 0.007, respectively). No statistically significant differences were observed in type of discharge, length of hospitalization and complications (p= 0.447, 0.261 and 0.127, respectively). 3 COVID-19 infections have been identified in hospitalized patients. 1 COVID-19 patient wad admitted from Emergency Department and was managed according to a dedicated path. CONCLUSIONS: Surgical activity was paradoxically increased during SARS-CoV-2 pandemic lockdown through the management of urgent and non-deferrable spinal disease with a low rate (3,9%) of COVID-19 infections.

ApoE4 is more efficient than E3 in brain access by herpes simplex virus type 1.

Apolipoprotein E (ApoE) plays a relevant role in herpes simplex type 1 (HSV-1) infection of the CNS; after infection by the hematogenous route, the viral neuroinvasiveness directly depends on the APOE gene dose. To analyze the effect of ApoE isoforms on the HSV-1 infectivity to the brain, we have used a model of hematogenous infection of mice humanized for the ApoE3 or the ApoE4 alleles, and we have analyzed the presence of viral DNA in several organs by real time quantitative PCR. We have found that animals expressing human ApoE4 present very high levels of virus in the brain when compared to those expressing the ApoE3 allele; in contrast, there were no significant differences in the viral levels found in peripheral organs. Apolipoprotein E4 seems to facilitate the entry and/or spread of HSV-1 in the brain much more efficiently than E3, pointing to a novel potential mechanism underlying the susceptibility to neurodegenerative processes associated with the ApoE4 allele.

Zoster-associated segmental paresis in a patient with cervical spinal stenosis.

Segmental zoster paresis is a rare complication of herpes zoster, characterized by focal motor weakness that does not always present simultaneously with skin lesions. Zoster paresis can be easily confused with other neuromuscular or spinal diseases. This case report describes the case of a 72-year-old woman with herpes zoster and cervical spinal stenosis at the same spinal level, where it was difficult to distinguish segmental zoster paresis from cervical radiculopathy combined with motor neuropathy. Although segmental zoster paresis in the upper extremity is rare, it should be included in the differential diagnosis of segmental pain and weakness in the extremities, especially in older or immunocompromised patients. Correct diagnosis is required, to avoid unnecessary surgery and allow timely antiviral treatment.