#Fulminant #Hepatitis Associated With #Echovirus 25 During #Treatment With #Ocrelizumab for #MS (JAMA Neurol., abstract)

[Source: JAMA Neurology, full page: (LINK). Abstract, edited.]

Research Letter / April 8, 2019

Fulminant Hepatitis Associated With Echovirus 25 During Treatment With Ocrelizumab for Multiple Sclerosis

Laura Ambra Nicolini, PhD1,2; Paola Canepa, BI1; Patrizia Caligiuri, BI1; et al Malgorzata Mikulska, PhD1,2; Giovanni Novi, MD3; Claudio Viscoli, MD1,2; Antonio Uccelli, MD3,4

Author Affiliations: 1 Department of Health Sciences, University of Genoa, Genoa, Italy; 2 Infectious Diseases Unit, Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico, Genoa, Italy; 3 Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; 4 Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico, Genoa, Italy

JAMA Neurol. 2019;76(7):866-867. doi:10.1001/jamaneurol.2019.0522

 

Abstract

Ocrelizumab (Ocrevus [Roche-Genentech]), a second-generation humanized anti-CD20 antibody, has been recently approved for multiple sclerosis (MS). Echoviruses and other enteroviruses have been associated with life-threatening infections in patients receiving anti-CD20 antibodies other than ocrelizumab.1-4 In this case study, we report a case of fulminant echovirus 25–associated hepatitis in a patient with relapsing-remitting MS who received ocrelizumab monotherapy.

(…)

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Article Information

Corresponding Author: Laura Ambra Nicolini, MD, PhD, Department of Health Science, University of Genoa, Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico, Largo Rosanna Benzi, 10, 16132 Genoa, Italy (nicolini.la@gmail.com; lauraambra.nicolini@hsanmartino.it) and Antonio Uccelli, MD, Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research, University of Genoa, Via Balbi, 5, 16126 Genoa, Italy (auccelli@neurologia.unige.it).

Published Online: April 8, 2019. doi:10.1001/jamaneurol.2019.0522

Author Contributions: Drs Nicolini and Uccelli had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Viscoli and Uccelli are co–first authors.

Concept and design: Nicolini, Mikulska, Viscoli, Uccelli.

Acquisition, analysis, or interpretation of data: Nicolini, Canepa, Caligiuri, Novi, Uccelli.

Drafting of the manuscript: Nicolini, Canepa, Caligiuri, Mikulska, Uccelli.

Critical revision of the manuscript for important intellectual content: Novi, Viscoli, Uccelli.

Administrative, technical, or material support: Nicolini, Canepa, Caligiuri.

Supervision: Mikulska, Viscoli, Uccelli.

Conflict of Interest Disclosures: Dr Uccelli reports receiving honoraria for speaking and consulting for Biogen, Genzyme, Merck, Novartis, Roche, and Teva and research grants from Biogen, Merck, and Novartis. Dr Novi received honoraria from Biogen and Novartis and received travel grants from Merck. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information. In addition, Enzo Andorno, MD, Hepato-biliary-pancreatic Surgical Unit, Department of Surgery, and Simona Marenco, PhD, Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico, and Antonino Picciotto, MD, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico, contributed to the manuscript as members of the Liver Transplant Study Group. Bianca Bruzzone, MD, Hygiene Unit, Ospedale Policlinico San Martino–Istituto Di Ricovero e Cura a Carattere Scientifico contributed interpretation of data, and Domenico Pinelli, MD, Department of Surgery and Transplantation, ASST-Papa Giovanni XXIII, contributed technical support. These individuals were not compensated for their contributions.

Keywords: Multiple Sclerosis; Echovirus 25; Oreclizumab; Viral hepatitis.

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#Clinical #analysis of seven cases of #H1N1 #influenza-associated #encephalopathy in #children (Zhonghua Er Ke Za Zhi, abstract)

[Source: US Naitonal Library of Medicine, full page: (LINK). Abstract, edited.]

Zhonghua Er Ke Za Zhi. 2019 Jul 2;57(7):538-542. doi: 10.3760/cma.j.issn.0578-1310.2019.07.009.

[Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children].

[Article in Chinese; Abstract available in Chinese from the publisher]

Li XF1, Ai B2, Ye JW1, He DM1, Tan LM1, Chen MX1, Yang HM1, Zeng FS1, Yang FX1, Liu HS2, Xu Y1.

Author information: 1 Department of Infectious Diseases, Guangzhou Women and Children’s Medical Center, Guangzhou 540120, China. 2 Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou 540120, China.

Abstract in English, Chinese

Objective:

To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children.

Methods:

The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children’s Medical Center from December 2018 to January 2019 were retrospectively analyzed.

Results:

Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge.

Conclusions:

The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

KEYWORDS: Child; Encephalopathy, influenza; Influenza A virus, H1N1 subtype

PMID: 31269554 DOI: 10.3760/cma.j.issn.0578-1310.2019.07.009

Keywords: Seasonal Influenza; H1N1pdm09; Encephalopathy; Pediatrics; Neurology; Guangdong; China.

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Expanding traditional tendon-based techniques with #nerve #transfers for the #restoration of upper #limb #function in #tetraplegia: a prospective case series (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Expanding traditional tendon-based techniques with nerve transfers for the restoration of upper limb function in tetraplegia: a prospective case series

Natasha van Zyl, MBBS, Bridget Hill, PhD, Catherine Cooper, BAppSc, Jodie Hahn, BAppSc, Prof Mary P Galea, PhD

Published: July 04, 2019 / DOI: https://doi.org/10.1016/S0140-6736(19)31143-2

 

Summary

Background

Loss of upper extremity function after cervical spinal cord injury greatly affects independence, including social, vocational, and community engagement. Nerve transfer surgery offers an exciting new option for the reanimation of upper limb function in tetraplegia. The aim of this study was to evaluate the outcomes of nerve transfer surgery used for the reanimation of upper limb function in tetraplegia.

Methods

In this prospective case series, we consecutively recruited people of any age with early (<18 months post-injury) cervical spinal cord injury of motor level C5 and below, who had been referred to a single centre for upper extremity reanimation and were deemed suitable for nerve transfer. All participants underwent single or multiple nerve transfers in one or both upper limbs, sometimes combined with tendon transfers, for restoration of elbow extension, grasp, pinch, and hand opening. Participants were assessed at 12 months and 24 months post-surgery. Primary outcome measures were the action research arm test (ARAT), grasp release test (GRT), and spinal cord independence measure (SCIM).

Findings

Between April 14, 2014, and Nov 22, 2018, we recruited 16 participants (27 limbs) with traumatic spinal cord injury, among whom 59 nerve transfers were done. In ten participants (12 limbs), nerve transfers were combined with tendon transfers. 24-month follow-up data were unavailable for three patients (five limbs). At 24 months, significant improvements from baseline in median ARAT total score (34·0 [IQR 24·0–38·3] at 24 months vs 16·5 [12·0–22·0] at baseline, p<0·0001) and GRT total score (125·2 [65·1–154·4] vs 35·0 [21·0–52·3], p<0·0001) were observed. Mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference, and the mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months. Median Medical Research Council strength grades were 3 (IQR 2–3) for triceps and 4 (IQR 4–4) for digital extensor muscles after 24 months. Mean grasp strength at 24 months was 3·2 kg (SD 1·5) in participants who underwent distal nerve transfers (n=5), 2·8 kg (3·2) in those who had proximal nerve transfers (n=9), and 3·9 kg (2·4) in those who had tendon transfers (n=8). There were six adverse events related to the surgery, none of which had any ongoing functional consequences.

Interpretation

Early nerve transfer surgery is a safe and effective addition to surgical techniques for upper limb reanimation in tetraplegia. Nerve transfers can lead to significant functional improvement and can be successfully combined with tendon transfers to maximise functional benefits.

Funding

Institute for Safety, Compensation, and Recovery Research (Australia).

Keywords: Neurology; Surgery; Tetraplegia.

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#Zika virus #infection and #risk of #GBS: A meta-analysis (J Neurol Sci., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Neurol Sci. 2019 Jun 21;403:99-105. doi: 10.1016/j.jns.2019.06.019. [Epub ahead of print]

Zika virus infection and risk of Guillain-Barré syndrome: A meta-analysis.

Bautista LE1.

Author information: 1 Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, 610 Walnut Street, WARF 703, Madison, WI 53726-2397, United States. Electronic address: lebautista@wisc.edu.

 

Abstract

OBJECTIVE:

Findings from studies of the association between Zika virus (ZIKV) infection and Guillain-Barré syndrome (GBS) are inconsistent. I conducted a systematic review and meta-analysis to clarify the nature of this association.

METHODS:

I searched PubMed, Scopus, Cochrane, CINAHL, Web of Science, Scielo, and DOAJ for case report, ecological, and analytic studies with “Zika” and “Guillain-Barré syndrome” as keywords, published up to July 1stth 2018. I evaluated if ZIKV infection status influenced the diagnosis of GBS (detection bias) in case-report and analytic studies; assessed if changes in weekly number of cases of ZIKV infection during outbreaks were followed by changes in number of GBS cases 1-8 weeks later; gauged the likelihood of selection, confounding, information, sparse data, and time-dependent bias (i.e. when ZIKV infection was ascertained after GBS onset) in analytic studies; and calculated the average ZIKV-GBS odds ratio (OR) in studies without time-dependent bias.

RESULTS:

In case reports, ZIKV infection prevalence in GBS cases was 2.4 to 25 times higher than expected. Changes in the number of ZIKV-infection cases during outbreaks were not consequentially followed by changes in the number of GBS cases (OR: 1.01; 95% CI: 0.99-1.03). Major biases were likely in all but one analytic study, which showed a non-significant ZIKV-GBS association. The average ZIKV-GBS OR in studies without time-dependent bias was 1.57 (95% CI: 0.86-2.86).

INTERPRETATION:

These findings indicate the available evidence is insufficient to claim ZIKV infection causes GBS. Therefore, stakeholders may want to reconsider current ZIKV-GBS public health and patient care recommendations.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Disease outbreaks; Guillain-Barre syndrome; Systematic review; Zika virus

PMID: 31255970 DOI: 10.1016/j.jns.2019.06.019

Keywords: Zika Virus; GBS.

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Alterations in #visual acuity and visual #development in #infants 1-24 months old either exposed to or infected by #Zika virus during #gestation, with and without #microcephaly (J AAPOS., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J AAPOS. 2019 Jun 20. pii: S1091-8531(19)30137-5. doi: 10.1016/j.jaapos.2019.03.005. [Epub ahead of print]

Alterations in visual acuity and visual development in infants 1-24 months old either exposed to or infected by Zika virus during gestation, with and without microcephaly.

Baran LCP1, da Costa MF2, Vidal KS2, Damico FM3, Barboni MTS4, da S Lima D2, de C R de M França V5, Martins CMG2, Tabares HS2, Dias SL5, Silva LA2, Decleva D2, Hamer RD6, Zatz M7, Bertozzi APAP8, Gazeta RE8, Passos SD8, Ventura DF2.

Author information: 1 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. Electronic address: baranejbio@gmail.com. 2 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil. 3 Department of Ophthalmology, University of São Paulo College of Medicine, São Paulo, SP, Brazil. 4 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Ophthalmology, Semmelweis University, Budapest, Hungary. 5 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil. 6 Department of Experimental Psychology, University of São Paulo Institute of Psychology, São Paulo, SP, Brazil; Nucleus of Neurosciences and Behavior, University of São Paulo, São Paulo, SP, Brazil; Department of Psychology, Florida Atlantic University, Boca Raton, Florida. 7 Human Genome and Stem Cells Center, Bioscience Institute, University of São Paulo. 8 University of Jundiai Medical School, Jundiai, São Paulo, SP, Brazil.

 

Abstract

PURPOSE:

To evaluate visual acuity and visual acuity development in children from the state of São Paulo, Brazil, who were exposed to the Zika virus (ZIKV) gestationally.

METHODS:

Children who had been exposed to ZIKV during gestation and age-matched control subjects received visual acuity and funduscopic examination. ZIKV exposure was confirmed by maternal quantitative polymerase chain reaction testing or serology assay. The ZIKV group was divided into two subgroups: Zika-exposed (ZE), with only the mother having confirmed ZIKV-infection, and Zika-infected (ZI), with confirmed infection. Visual acuity development was compared with prior norms and quantified by measuring visual acuity correlation with age.

RESULTS:

A total of 110 children were included: 47 who had been exposed to ZIKV (ZE, 23; ZI, 24) and 63 controls. Abnormal visual acuity was found in 5 of 24 ZI children. Of the 4 children with microcephaly, only 2 had visual acuity loss (only 1 also had abnormal funduscopic findings). There was significant correlation between age and visual acuity in both the control group (R2 = 0.8; P < 0.0000) and the ZE subgroup (R2 = 0.6; P < 0.0000). However, visual acuity did not correlate with age in the ZI subgroup (R2 = 0.04; P = 0.38). Furthermore, the increment in octaves/month was much lower in the ZI subgroup.

CONCLUSIONS:

Our data indicates that visual acuity losses only occur in infants who suffered gestational-infection, not simply exposure. Lack of correlation between age and visual acuity in the ZI subgroup suggests a slowing of visual development even in the absence of microcephaly. This result may have broad implications for the deleterious effects of ZIKV on the central nervous system.

Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

PMID: 31229606 DOI: 10.1016/j.jaapos.2019.03.005

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Microcephaly; Pediatrics; Ophthalmology; Neurology.

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#EBV and #MS #risk in the #Finnish #Maternity #Cohort (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Epstein‐Barr virus and multiple sclerosis risk in the Finnish Maternity Cohort

Kassandra L. Munger ScD,  Kira Hongell MD,  Marianna Cortese MD, PhD,  Julia Åivo MD, Merja Soilu‐Hänninen MD, PhD,  Heljä‐Marja Surcel PhD,  Alberto Ascherio MD, DrPH

First published: 21 June 2019 / DOI:  https://doi.org/10.1002/ana.25532

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.25532.

 

Abstract

Objective

To determine whether maternal Epstein‐Barr virus (EBV) IgG antibody levels are associated with risk of multiple sclerosis (MS) in the offspring.

Methods

We conducted a prospective nested case‐control study in the Finnish Maternity Cohort (FMC) with serum samples from over 800,000 women collected during pregnancy since 1983. Cases of MS among offspring born between 1983 and 1991 were identified via hospital and prescription registries; 176 cases were matched to up to 3 controls (n=326) on region and dates of birth, sample collection, and mother’s birth. We used conditional logistic regression to estimate relative risks (RR) and adjusted models for sex of the child, gestational age at sample collection, and maternal serum 25‐hydroxyvitamin D and cotinine levels. Similar analyses were conducted among 1,049 women with MS and 1,867 matched controls in the FMC.

Results

Maternal viral capsid antigen IgG levels during pregnancy were associated with an increased MS risk among offspring (RRtop vs. bottom quintile=2.44, 95%CI: 1.20‐5.00, p trend=0.004); no associations were found between maternal EBNA‐1, EA‐D, or cytomegalovirus IgG levels and offspring MS risk. Among women in the FMC, those in the highest versus lowest quintile of EBNA‐1 IgG levels had a 3‐fold higher risk of MS (RR=3.21, 95%CI: 2.37‐4.35, p trend <1.11e‐16). These associations were not confounded or modified by 25‐hydroxyvitamin D.

Interpretation

Offspring of mothers with high VCA IgG during pregnancy appear to have an increased risk of MS. The increase in MS risk among women with elevated pre‐diagnostic EBNA‐1 IgG levels is consistent with previous results.

This article is protected by copyright. All rights reserved.

Keywords: EBV; Multiple Sclerosis; Pregnancy; Finland; Neurology.

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#Neurogenic #bladder in the settings of #congenital #Zika #syndrome: a confirmed and unknown condition for #urologists (J Pediatr Urol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Pediatr Urol. 2019 Apr 30. pii: S1477-5131(19)30090-7. doi: 10.1016/j.jpurol.2019.04.018. [Epub ahead of print]

Neurogenic bladder in the settings of congenital Zika syndrome: a confirmed and unknown condition for urologists.

Costa Monteiro LM1, Cruz GNO2, Fontes JM2, de Araujo GF2, Ventura T3, Monteiro AC4, Moreira MEL2.

Author information: 1 Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), RJ, Brazil. Electronic address: luciacostamonteiro@gmail.com. 2 Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/FIOCRUZ), RJ, Brazil. 3 CAPES Research Student at Instituto Nacional de Saúde da Mulher, da Criança e Do Adolescente Fernandes Figueira (IFF/FIOCRUZ), RJ, Brazil. 4 UCLA. Division of Pulmonary and Critical Care Medicine, CA, USA.

 

Abstract

INTRODUCTION:

Congenital Zika syndrome (CZS) is a recently discovered condition that affects central nervous system structures that control the lower urinary tract. The first cases of neurogenic bladder (NB) were recently reported as a sequalae of CZS in neurologically impaired children.

OBJECTIVE:

Our goal is to further evaluate NB in the setting of CZS, identifying urological risk indicators in hopes that early diagnosis will mitigate the impact of the disease.

STUDY DESIGN:

Urological assessment was performed in all patients with CZS and neurological impairment who were referred to our urodynamic clinic between June 2016 and May 2018. Neurogenic bladder was confirmed by urodynamic evaluation, and urological risk was based on urodynamic results.

RESULTS:

Sixty-nine patients with CZS were tested. The majority (63 patients, 91.3%) presented with overactive bladder with increased pressures and reduced capacity for age (table 1). Different urodynamic patterns were observed, and the association of reduced bladder capacity for age, high bladder-filling pressure, and increased postvoid residual were frequently observed.

DISCUSSION:

NB continues to be consistently diagnosed in our cohort of CZS, mostly with high-risk indicators for renal impairment. When not intervened upon in a timely manner, NB can cause progressive damage to the urinary tract, but the lack of knowledge that CZS causes NB delays investigation and treatment. Parents and health professionals will need to be sensitized to the risks that ZIKV can pose to the urinary tract so that appropriate therapies are initiated to prevent irreversible renal damage.

CONCLUSION:

NB is a common condition among our patients with CZS and microcephaly. This is a new cause of NB, unknown to urologists. While further investigation is necessary to understand long-term disease behavior and therapeutic response, increased knowledge among urologists may help to reduce morbidity related to untreated NB and to mitigate the disease burden for patients and families.

Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: Congenital Zika syndrome; Microcephaly; Neurogenic bladder; Urinary tract infection; Zika virus

PMID: 31142443 DOI: 10.1016/j.jpurol.2019.04.018

Keywords: Zika Virus; Zika Congenital Syndrome; Neurogenic bladder; Neurology; Pediatrics.

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