Sequential #Neuroimaging of the #Fetus and #Newborn With In Utero #Zika Virus Exposure (JAMA Pediatr., abstract)

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

JAMA Pediatr. 2018 Nov 26. doi: 10.1001/jamapediatrics.2018.4138. [Epub ahead of print]

Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure.

Mulkey SB1,2,3, Bulas DI4, Vezina G4, Fourzali Y5, Morales A5, Arroyave-Wessel M1, Swisher CB1, Cristante C1, Russo SM1, Encinales L6, Pacheco N7, Kousa YA8, Lanciotti RS9, Cure C10, DeBiasi RL2,11,12, du Plessis AJ1,2,3.

Author information: 1 Division of Fetal and Transitional Medicine, Children’s National Health System, Washington, DC. 2 Department of Pediatrics, School of Medicine and Health Sciences, The George Washington University, Washington, DC. 3 Department of Neurology, School of Medicine and Health Sciences, The George Washington University, Washington, DC. 4 Division of Radiology, Children’s National Health System, Washington, DC. 5 Sabbag Radiologos, Barranquilla, Colombia. 6 Allied Research Society, Miami, Florida. 7 Bacteriologa, Bio-Nep, Barranquilla, Colombia. 8 Division of Neurology, Children’s National Health System, Washington, DC. 9 Arbovirus Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, Colorado. 10 BIOMELAB, Barranquilla, Colombia. 11 Division of Infectious Diseases, Children’s National Health System, Washington, DC. 12 Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC.




The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described.


To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities.


A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program.


Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV.


The neuroimaging studies were evaluated for brain injury and cerebral biometry.


Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%).


In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.

PMID: 30476967 DOI: 10.1001/jamapediatrics.2018.4138

Keywords: Zika Virus; Zika Congenital Infection; Neurology.



#Risk of #neuropsychiatric adverse events associated with the use of #oseltamivir: a nationwide population-based case-crossover study (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Risk of neuropsychiatric adverse events associated with the use of oseltamivir: a nationwide population-based case-crossover study

Hye-Rim Kang, Eui-Kyung Lee, Woo Jung Kim, Ju-Young Shin

Journal of Antimicrobial Chemotherapy, dky445,

Published: 12 November 2018




Although the potential risk of neuropsychiatric adverse events (NPAEs) upon administration of oseltamivir has been raised in case reports, the association between the use of oseltamivir and the risk of NPAEs is unclear.


We aimed to evaluate whether the use of oseltamivir triggers NPAEs.

Patients and methods

We conducted a population-based case-crossover study using the National Sample Cohort data from the National Health Insurance Service in South Korea. From a total of 236 348 incident patients with NPAEs as either a primary or secondary diagnosis, our final case series included 5322 patients with a prior prescription for oseltamivir between 2009 and 2013. Exposure to oseltamivir was assessed during 2, 7, 14, 28 and 56 day hazard periods prior to each patient’s NPAE. Three pre-consecutive control periods were matched using the same time windows. Conditional logistic regression analysis was used to estimate adjusted ORs (aORs), adjusting for time-variant diagnosis of influenza and concomitant medications.


Matched analyses found a consistently increased risk of NPAEs associated with the use of oseltamivir in the 2 day (aOR 1.90, 95% CI 1.29–2.81), 7 day (aOR 1.32, 95% CI 1.00–1.74), 14 day (aOR 1.28, 95% CI 1.03–1.60), 28 day (aOR 1.25, 95% CI 1.06–1.47) and 56 day (aOR 1.13, 95% CI 0.99–1.29) hazard periods compared with use in the three control periods.


This study found that the short-term use of oseltamivir triggers the incidence of NPAEs. Early monitoring of NPAEs may be required when prescribing oseltamivir with careful consideration of the risk–benefit balance of oseltamivir.


© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email:

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Antivirals; Drugs Safety; Oseltamivir; Neurology; Psychiatry.


Potential role of #dengue virus, #chikungunya virus and #Zika virus in #neurological diseases (Mem Inst Oswaldo Cruz, abstract)

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

Mem Inst Oswaldo Cruz. 2018 Oct 29;113(11):e170538. doi: 10.1590/0074-02760170538.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases.

Vieira MADCES1,2,3, Costa CHN4, Linhares ADC5, Borba AS2, Henriques DF6, Silva EVPD6, Tavares FN5, Batista FMA7, Guimarães HCL7, Martins LC6, Monteiro TAF3,5, Cruz ACR6, Azevedo RDSDS6, Vasconcelos PFDC6.

Author information: 1 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Neurologia, Teresina, PI, Brasil. 2 Fundação Municipal de Saúde de Teresina, Diretoria de Vigilância em Saúde, Teresina, PI, Brasil. 3 Instituto Evandro Chagas, Programa de Pós-Graduação em Virologia, Ananindeua, PA, Brasil. 4 Secretaria de Estado da Saúde do Piauí, Instituto de Doenças Tropicais Natan Portella, Departamento de Infectologia, Teresina, PI, Brasil. 5 Instituto Evandro Chagas, Seção de Virologia Geral, Ananindeua, PA, Brasil. 6 Instituto Evandro Chagas, Seção de Arbovirologia e Febres Hemorrágicas, Ananindeua, PA, Brasil. 7 Secretaria de Estado da Saúde do Piauí, Diretoria da Unidade de Vigilância e Assistência à Saúde, Teresina, PI, Brasil.



This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

PMID: 30379197 DOI: 10.1590/0074-02760170538

Keywords: Arbovirus; Chikungunya Fever; Dengue Fever; Zika Virus; Encephalitis; GBS; Encephalomyelitis.


#Safety, Tolerability, and Feasibility of Young #Plasma #Infusion in the Plasma for #Alzheimer #Symptom Amelioration Study – A #RCT (JAMA Neurol., abstract)

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

Original Investigation / October 29, 2018

Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration StudyA Randomized Clinical Trial

Sharon J. Sha, MD, MS1; Gayle K. Deutsch, PhD1; Lu Tian, ScD, MS2; et al Kara Richardson3; Maria Coburn4; Jennifer L. Gaudioso1; Tatiana Marcal5; Ethan Solomon, MS6; Athanasia Boumis1; Anthony Bet4; Maarten Mennes, PhD7; Erik van Oort, MSc7; Christian F. Beckmann, PhD7; Steven P. Braithwaite, PhD8; Sam Jackson, MD, MBA8; Karoly Nikolich, PhD8; Darby Stephens8; Geoffrey A. Kerchner, MD, PhD1; Tony Wyss-Coray, PhD1

JAMA Neurol. Published online October 29, 2018. doi: 10.1001/jamaneurol.2018.3288


Key Points

  • Question  – Is young plasma safe, feasible, and tolerable in patients with mild to moderate Alzheimer disease dementia?
  • Findings  – This randomized clinical trial consisted of a double-blind crossover group of 9 patients and an open-label group of 9 patients. Patients with mild to moderate Alzheimer disease dementia were able to tolerate 4 weekly infusions of young plasma.
  • Meaning  – Safe and well tolerated in a small sample of patients with mild to moderate Alzheimer disease dementia, young plasma infusions warrant further analysis in a larger study using a double-blinded design with a placebo control.




Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD).


To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD.

Design, Setting, and Participants 

The Plasma for Alzheimer Symptom Amelioration (PLASMA) study randomized 9 patients under a double-blind crossover protocol to receive 4 once-weekly infusions of either 1 unit (approximately 250 mL) of yFFP from male donors or 250 mL of saline, followed by a 6-week washout and crossover to 4 once-weekly infusions of an alternate treatment. Patients and informants were masked to treatment and subjective measurements. After an open-label amendment, 9 patients received 4 weekly yFFP infusions only and their subjective measurements were unmasked. Patients were enrolled solely at Stanford University, a tertiary academic medical center, from September 2014 to December 2016, when enrollment reached its target. Eighteen consecutive patients with probable mild to moderate AD1 dementia, a Mini-Mental State Examination (score of 12 to 24 inclusive), and an age of 50 to 90 years were enrolled. Thirty-one patients were screened and 13 were excluded: 11 failed the inclusion criteria and 2 declined to participate.


One unit of yFFP from male donors/placebo infused once weekly for 4 weeks.

Main Outcome and Measures 

The primary outcomes were the safety, tolerability, and feasibility of 4 weekly yFFP infusions. Safety end point analyses included all patients who received the study drug/placebo.


There was no difference in the age (mean [SD], 74.17 [7.96] years), sex (12 women [67%]), or baseline Mini-Mental State Examination score (mean [SD], 19.39 [3.24]) between the crossover (n = 9) and open-label groups (n = 9). There were no related serious adverse events. One patient discontinued participation because of urticaria and another because of an unrelated stroke. There was no statistically significant difference between the plasma (17 [94.4%]) and placebo (9 [100.0%]) cohorts for other adverse events, which were mild to moderate in severity. The most common adverse events in the plasma group included hypertension (3 [16.7%]), dizziness (2 [11.1%]), sinus bradycardia (3 [16.7%]), headache (3 [16.7%]), and sinus tachycardia (3 [16.7%]). The mean visit adherence (n = 18) was 86% (interquartile range, 87%-100%) and adherence, accounting for a reduction in the total visit requirement due to early patient discontinuation, was 96% (interquartile range, 89%-100%).

Conclusions and Relevance 

The yFFP treatment was safe, well tolerated, and feasible. The study’s limitations were the small sample size, short duration, and change in study design. The results warrant further exploration in larger, double-blinded placebo-controlled clinical trials.

Trial Registration Identifier: NCT02256306

Keywords: Alzheimer’s Disease; Serotherapy; Neurology.


Review: #Evidence of #Neurological #Sequelae in #Children With Acquired #Zika Virus #Infection (Pediatr Neurol., abstract)

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

Pediatr Neurol. 2018 Aug;85:16-20. doi: 10.1016/j.pediatrneurol.2018.03.001. Epub 2018 Apr 3.

Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection.

Lebov JF1, Brown LM2, MacDonald PDM3, Robertson K4, Bowman NM5, Hooper SR6, Becker-Dreps S7.

Author information: 1 RTI International, Center for Applied Public Health Research, Durham, North Carolina. Electronic address: 2 RTI International, Center for Applied Public Health Research, Rockville, Maryland. 3 RTI International, Center for Applied Public Health Research, Berkeley, California. 4 Department of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 5 Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 6 Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina. 7 Department of Family Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.



Limited information is available on health outcomes related to Zika virus infection acquired during childhood. Zika virus can cause severe central nervous system malformations in congenitally exposed fetuses and neonates. In vitro studies show the capacity of Zika virus to infect neural progenitor cells, induce central and peripheral neuronal cell deaths, and target different brain cells over the course of brain development. Studies of postnatally infected mice and nonhuman primates have detected degradation of neural cells and morphologic brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and in adolescents secondary to Zika virus infection suggest that Zika virus may have a broader impact on neurological health beyond that observed in congenitally exposed newborns. Long-term neurological complications have been observed with other acquired flaviviral infections, with clinical symptoms manifesting for years after primary infection. The extent to which postnatal Zika virus infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage or cognitive effects is currently unknown. To better understand the potential for neurological sequelae associated with acquired Zika virus infection in children, we reviewed the biological, clinical, and epidemiologic literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of Zika virus infection in experimental studies. Second, we review observational studies of congenital Zika virus infection and case studies and surveillance reports of neurological sequelae of Zika virus infection in adults and in children. Lastly, we discuss the challenges of conducting Zika virus-neurological sequela studies and future directions for pediatric Zika virus research.

KEYWORDS: Child development; Flavivirus infections; Malformations of cortical development; Neurological sequelae; Zika virus infection

PMID: 30343688 DOI: 10.1016/j.pediatrneurol.2018.03.001

Keywords: Zika Virus; Zika Congenital Syndrome; Neurology.


Mega-Analysis of #GrayMatter #Volume in #Substance #Dependence: General and Substance-Specific Regional Effects (Am J Psychiatry, abstract)

[Source: American Journal of Psychiatry, full page: (LINK). Abstract, edited.]

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects

Scott Mackey, Ph.D., Nicholas Allgaier, Ph.D., Bader Chaarani, Ph.D., Philip Spechler, B.A., Catherine Orr, Ph.D., Janice Bunn, Ph.D., Nicholas B. Allen, Ph.D., Nelly Alia-Klein, Ph.D., Albert Batalla, M.D., Ph.D., Sara Blaine, Ph.D., Samantha Brooks, Ph.D., Elisabeth Caparelli, Ph.D., Yann Ying Chye, Ph.D., Janna Cousijn, Ph.D., Alain Dagher, M.D., Sylvane Desrivieres, Ph.D., Sarah Feldstein-Ewing, Ph.D., John J. Foxe, Ph.D., Rita Z. Goldstein, Ph.D., Anna E. Goudriaan, Ph.D., Mary M. Heitzeg, Ph.D., Robert Hester, Ph.D., Kent Hutchison, Ph.D., Ozlem Korucuoglu, Ph.D., Chiang-Shan R. Li, M.D., Ph.D., Edythe London, Ph.D., Valentina Lorenzetti, Ph.D., Maartje Luijten, Ph.D., Rocio Martin-Santos, M.D., April May, M.A., Reza Momenan, M.D., Angelica Morales, Ph.D., Martin P. Paulus, M.D., Godfrey Pearlson, M.A., M.B.B.S., Marc-Etienne Rousseau, M.Sc., Betty Jo Salmeron, M.D., Renée Schluter, Ph.D., Lianne Schmaal, Ph.D., Gunter Schumann, M.D., Ph.D., Zsuzsika Sjoerds, Ph.D., Dan J. Stein, Ph.D., Elliot A. Stein, Ph.D., Rajita Sinha, Ph.D., Nadia Solowij, Ph.D., Susan Tapert, Ph.D., Anne Uhlmann, Ph.D., Dick Veltman, M.D., Ph.D., Ruth van Holst, Ph.D., Sarah Whittle, Ph.D., Margaret J. Wright, Ph.D., Murat Yücel, Ph.D., Sheng Zhang, Ph.D., Deborah Yurgelun-Todd, Ph.D., Derrek P. Hibar, Ph.D., Neda Jahanshad, Ph.D., Alan Evans, Ph.D., Paul M. Thompson, Ph.D., David C. Glahn, Ph.D., Patricia Conrod, Ph.D., Hugh Garavan, Ph.D., the ENIGMA Addiction Working Group

Published Online: 19 Oct 2018 / DOI:




Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes.


Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings.


Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects.


The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Keywords: Psychiatry; Neurology.


#CJD with unusual presentation of peripheral #neuropathy and #ophthalmoplegia (Avicenna J Med., abstract)

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

Avicenna J Med. 2018 Oct-Dec;8(4):153-156. doi: 10.4103/ajm.AJM_77_18.

Creutzfeldt-Jakob disease with unusual presentation of peripheral neuropathy and ophthalmoplegia.

Arwani M1, Purohit A2, Haddad A1, Rana S2,3.

Author information: 1 Department of Internal Medicine, Allegheny General Hospital, Western Pennsylvania Hospital Medical Education Consortium, Pittsburgh, PA, USA. 2 Department of Neurology, Allegheny General Hospital, Western Pennsylvania Hospital Medical Education Consortium, Pittsburgh, PA, USA. 3 Department of Neurology, Temple University School of Medicine, Pittsburgh, PA, USA.



Creutzfeldt-Jakob disease (CJD) is a well-described disease. It is characterized by rapidly progressive dementia, myoclonus, ataxia, pyramidal, and extrapyramidal signs. There are well-defined electroencephalogram and magnetic resonance imaging (MRI) findings, and markers found in the cerebrospinal fluid (CSF). The gold standard for diagnosing CJD remains brain biopsy. We present a case of a patient with a family history of biopsy-proven CJD who initially presented with symptoms of peripheral neuropathy. A month later, he developed ataxia, ophthalmoparesis, and then dysarthria. His initial workup was relatively unrevealing, showing an elevated protein in his CSF. He was thought to have Miller Fisher syndrome variant of Guillain-Barré syndrome. He neither, however, responded to plasmapheresis nor IVIG. He later started to develop progressive dementia. Repeated MRI showed restricted diffusion in the caudate and putamen, as well as in the cortex (cortical ribboning). Lumbar puncture was then found to be positive for 14-3-3 protein, total-tau protein, and real-time quaking-induced conversion assay, which are highly suggestive of CJD. We present a case of CJD with an unusual presentation resulting in misdiagnosis, prolonged workup, and potentially harmful treatment modalities. This case highlights the importance of broadening our definition of CJD to encompass more cases with unusual presentations.

KEYWORDS: Ataxia; Creutzfeldt–Jakob disease; dementia; neuropathy; ophthalmoplegia

PMID: 30319957 PMCID: PMC6178565 DOI: 10.4103/ajm.AJM_77_18

Keywords: Prions; CJD; Neurology; Neuropathy; Ophthalmoplegy.