Chronic #Traumatic #Encephalopathy (Continuum, abstract)

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

Chronic Traumatic Encephalopathy

Katherine W. Turk, MD; Andrew E. Budson, MD

p. 187-207 / February 2019, Vol.25, No.1 / doi: 10.1212/CON.0000000000000686 / REVIEW ARTICLES

 

ABSTRACT

PURPOSE OF REVIEW:

This article provides a discussion on the current state of knowledge of chronic traumatic encephalopathy (CTE), with an emphasis on clinical features and emerging biomarkers of the condition.

RECENT FINDINGS:

The results of several large brain bank case series among subjects with a history of contact sports or repetitive head trauma have indicated that a high frequency of CTE may exist in this population. However, the true prevalence of CTE among individuals with a history of head trauma remains unknown, given that individuals who experienced cognitive, behavioral, and mood symptoms during life are more likely to have their brains donated for autopsy at death and epidemiologic studies of the condition are lacking. Neuropathologic consensus criteria have been published. Research-based clinical criteria have been proposed and are beginning to be applied, but the definitive diagnosis of CTE in a living patient remains impossible without effective biomarkers for the condition, which is an active area of study.

SUMMARY:

The field of CTE research is rapidly growing and parallels many of the advances seen for other neurodegenerative conditions, such as Alzheimer disease decades ago.

 

AUTHOR INFORMATION

Address correspondence to Dr Katherine W. Turk, VA Boston Healthcare System, 150 S Huntington Ave, 151-C, Jamaica Plain, MA 02130, kturk@bu.edu.

RELATIONSHIP DISCLOSURE: Dr Turk receives research/grant support from the Alzheimer’s Association. Dr Budson has served as a consultant for Axovant Sciences, Inc, and Eli Lilly and Company and has received personal compensation for speaking engagements from Eli Lilly and Company. Dr Budson receives research/grant support from the US Department of Veterans Affairs (I01CX000736) and publishing royalties from Elsevier and Oxford University Press.

UNLABELED USE OF PRODUCTS/INVESTIGATIONAL USE DISCLOSURE: Drs Turk and Budson discuss the unlabeled/investigational use of several classes of medications for chronic traumatic encephalopathy, including cholinesterase inhibitors for memory-related issues, selective serotonin reuptake inhibitors for mood and behavioral issues, memantine for attentional issues in those with advanced dementia, and atypical antipsychotics for those who are disinhibited and violent.

Keywords: Neurology; Psychiatry.

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#Incidence study of #GBS in the province of #Ferrara, Northern #Italy, between 2003 and 2017. A 40-year follow-up (Neurol Sci., abstract)

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

Neurol Sci. 2019 Jan 7. doi: 10.1007/s10072-018-3688-4. [Epub ahead of print]

Incidence study of Guillain-Barré syndrome in the province of Ferrara, Northern Italy, between 2003 and 2017. A 40-year follow-up.

Granieri E1, Andreasi NG2, De Martin P2, Govoni V2, Castellazzi M2, Cesnik E2, Pugliatti M2, Casetta I2.

Author information: 1 Department of Biomedical and Specialty-Surgical Sciences, Section of Neurology, Psychology and Psychiatry, University of Ferrara, Via Aldo Moro 8, 44124, Cona, Ferrara, Italy. enrico.granieri@unife.it. 2 Department of Biomedical and Specialty-Surgical Sciences, Section of Neurology, Psychology and Psychiatry, University of Ferrara, Via Aldo Moro 8, 44124, Cona, Ferrara, Italy.

 

Abstract

BACKGROUND:

Guillain-Barré syndrome (GBS) is an acute/subacute autoimmune inflammatory polyradiculoneuropathy. Previous epidemiological studies carried out in the province of Ferrara, Italy, from 1981 to 2002 indicated that GBS incidence had tendency of increase in the period considered.

OBJECTIVES:

We aimed at updating the epidemiology of GBS in the years 2003-2017 and carrying on the work started in the 1980s.

METHODS:

We conducted an incidence study, by adopting a complete enumeration approach. Cases were identified from administrative, medical records, and database of the Ferrara Hospital and other provincial structures of the study area. Case ascertainment and definition are analogous to those adopted in previous surveys.

RESULTS:

In the period 1 January 2003 to 31 December 2017, 73 patients living in the province of Ferrara (mean population 353,142) were found to be new cases of GBS fulfilling the NINCDS criteria. Male/female ratio 1.15. The mean incidence rate was 1.38 per 100,000 (95% CI 1.08-1.74), 1.54 per 100,000 for men and 1.23 per 100,000 for women, a nonsignificant difference. During the period considered, the rates had slow increase or mild decrease, without nonsignificant difference. The highest rates were observed for the age groups 70-79 years for both sexes. A half of patients reported infectious events in the weeks before the onset of symptoms.

CONCLUSION:

In line with many epidemiological data, in the whole period 2003-2017, we observed a trend towards increase or decrease in incidence and periods of relative stability. Similar temporal heterogeneity with the comparison to our previous works was found.

KEYWORDS: Epidemiology; Ferrara; Guillain-Barré syndrome; Incidence; Italy

PMID: 30617450 DOI: 10.1007/s10072-018-3688-4

Keywords: GBS; Neurology; Italy.

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Association of #Infants Exposed to Prenatal #Zika Virus #Infection With Their Clinical, #Neurologic, and Developmental Status Evaluated via the #GMA #Tool (JAMA Netw Open., abstract)

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

JAMA Netw Open. 2019 Jan 4;2(1):e187235. doi: 10.1001/jamanetworkopen.2018.7235.

Association of Infants Exposed to Prenatal Zika Virus Infection With Their Clinical, Neurologic, and Developmental Status Evaluated via the General Movement Assessment Tool.

Einspieler C1, Utsch F2, Brasil P3, Panvequio Aizawa CY4, Peyton C5,6, Hydee Hasue R4, Françoso Genovesi F4, Damasceno L3, Moreira ME7, Adachi K8, Marschik PB1,9,10, Nielsen-Saines K8; GM Zika Working Group.

Author information: 1 Interdisciplinary Developmental Neuroscience-iDN, Medical University of Graz, Graz, Austria. 2 Rede SARAH de Hospitais de Reabilitação, Reabilitação Infantil, Belo Horizonte, Brazil. 3 Laboratorio de Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil. 4 Department of Physical Therapy, Communication Sciences & Disorders, and Occupational Therapy, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. 5 Department of Physical Therapy and Human Movement Science, Northwestern University, Chicago, Illinois. 6 Department of Pediatrics, University of Chicago, Chicago, Illinois. 7 Department of Pediatrics, Instituto Fernandes Figueira, Fiocruz, Rio de Janeiro, Brazil. 8 Division of Pediatric Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles. 9 Interdisciplinary Developmental Neuroscience-iDN, Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. 10 Center of Neurodevelopmental Disorders (KIND), Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.

 

Abstract

IMPORTANCE:

There is an urgent need to assess neurodevelopment in Zika virus (ZIKV)-exposed infants.

OBJECTIVES:

To perform general movement assessment (GMA) at 9 to 20 weeks’ postterm age and to evaluate whether the findings are associated with neurodevelopmental outcomes at age 12 months in infants prenatally exposed to acute maternal illness with rash in Brazil during the ZIKV outbreak and in age-matched controls.

DESIGN, SETTING, AND PARTICIPANTS:

In this cohort study, infants prenatally exposed to acute maternal illness with rash were recruited at medical institutions in Rio de Janeiro and Belo Horizonte, Brazil, from February 1, 2016, to April 30, 2017, while infants without any exposure to maternal illness originated from the Graz University Audiovisual Research Database for the Interdisciplinary Analysis of Neurodevelopment. Participants were 444 infants, including 76 infants without congenital microcephaly, 35 infants with microcephaly, and 333 neurotypical children matched for sex, gestational age at birth, and age at GMA.

MAIN OUTCOMES AND MEASURES:

General movement assessment performed at 9 to 20 weeks’ postterm age, with negative predictive value, positive predictive value, sensitivity, and specificity generated, as well as clinical, neurologic, and developmental status (Bayley Scales of Infant and Toddler Development, Third Edition [Bayley-III] scores) at age 12 months. Motor Optimality Scores were generated based on the overall quality of the motor repertoire. Adverse outcomes were defined as a Bayley-III score less than 2 SD in at least 1 domain, a score less than 1 SD in at least 2 domains, and/or atypical neurologic findings.

RESULTS:

A total of 444 infants were enrolled, including 111 children prenatally exposed to a maternal illness with rash and 333 children without any prenatal exposure to maternal illness (57.7% male and mean [SD] age, 14 [2] weeks for both groups); 82.1% (46 of 56) of ZIKV-exposed infants without congenital microcephaly were healthy at age 12 months. Forty-four of 46 infants were correctly identified by GMA at 3 months, with a negative predictive value of 94% (95% CI, 85%-97%). Seven of 10 ZIKV-exposed children without microcephaly with adverse neurodevelopmental outcomes were identified by GMA. The GMA positive predictive value was 78% (95% CI, 46%-94%), sensitivity was 70% (95% CI, 35%-93%), specificity was 96% (95% CI, 85%-99%), and accuracy was 91% (95% CI, 80%-97%). Children with microcephaly had bilateral spastic cerebral palsy; none had normal movements. The Motor Optimality Score differentiated outcomes: the median Motor Optimality Score was 23 (interquartile range [IQR], 21-26) in children with normal development, 12 (IQR, 8-19) in children with adverse outcomes, and 5 (IQR, 5-6) in children with microcephaly, a significant difference (P = .001).

CONCLUSIONS AND RELEVANCE:

This study suggests that although a large proportion of ZIKV-exposed infants without microcephaly develop normally, many do not. The GMA should be incorporated into routine infant assessments to enable early entry into targeted treatment programs.

PMID: 30657537 DOI: 10.1001/jamanetworkopen.2018.7235

Keywords: Zika Virus; Zika Congenital Infection; Zika Congenital Syndrome; Neurology.

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#Viral #Infections of the #CNS in #Africa (Brain Res Bull., abstract)

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

Brain Res Bull. 2019 Jan 15. pii: S0361-9230(18)30341-1. doi: 10.1016/j.brainresbull.2018.12.019. [Epub ahead of print]

Viral Infections of the Central Nervous System in Africa.

Kakooza-Mwesige A1, Tshala-Katumbay D2, Juliano SL3.

Author information: 1 Department of Paediatrics & Child Health, Makerere University College of Health Sciences and Mulago Hospital, Kampala, Uganda; Astrid Lindgren Children’s Hospital, Neuropediatric Research Unit, Karolinska Institutet, Sweden. Electronic address: akakooza246@gmail.com. 2 Department of Neurology and School of Public Health, Oregon Health & Science University, Portland, OR, USA; Department of Neurology, University of Kinshasa, Democratic Republic of the Congo; Institut National de Recherches Biomedicales, University of Kinshasa, Democratic Republic of the Congo. Electronic address: tshalad@ohsu.edu. 3 Neuroscience, USUHS, Bethesda, MD, 20814, USA. Electronic address: sharon.juliano@usuhs.edu.

 

Abstract

Viral infections are a major cause of human central nervous system infection, and may be associated with significant mortality, and long-term sequelae. In Africa, the lack of effective therapies, limited diagnostic and human resource facilities are especially in dire need. Most viruses that affect the central nervous system are opportunistic or accidental pathogens. Some of these viruses were initially considered harmless, however they have now evolved to penetrate the nervous system efficiently and exploit neuronal cell biology thus resulting in severe illness. A number of potentially lethal neurotropic viruses have been discovered in Africa and over the course of time shown their ability to spread wider afield involving other continents leaving a devastating impact in their trail. In this review we discuss key viruses involved in central nervous system disease and of major public health concern with respect to Africa. These arise from the families of Flaviviridae, Filoviridae, Retroviridae, Bunyaviridae, Rhabdoviridae and Herpesviridae. In terms of the number of cases affected by these viruses, HIV (Retroviridae) tops the list for morbidity, mortality and long term disability, while the Rift Valley Fever virus (Bunyaviridae) is at the bottom of the list. The most deadly are the Ebola and Marburg viruses (Filoviridae). This review describes their epidemiology and key neurological manifestations as regards the central nervous system such as meningoencephalitis and Guillain-Barré syndrome. The potential pathogenic mechanisms adopted by these viruses are debated and research perspectives suggested.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS: CNS viral infections; Ebola; HIV; Herpes; Rabies; Zika

PMID: 30658129 DOI: 10.1016/j.brainresbull.2018.12.019

Keywords: Emerging Diseases; Neurology; Flavivirus; Filovirus; Rhabdovirus; Herpesvirus; HIV/AIDS; Bunyavirus; Retrovirus.

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Age-Associated #Deviations of #Amygdala Functional #Connectivity in #Youths With #Psychosis Spectrum Disorders: Relevance to Psychotic Symptoms (Am J Psychiatry, abstract)

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

Age-Associated Deviations of Amygdala Functional Connectivity in Youths With Psychosis Spectrum Disorders: Relevance to Psychotic Symptoms

Maria Jalbrzikowski, Ph.D., Vishnu P. Murty, Ph.D., Brenden Tervo-Clemmens, M.S., William Foran, M.S., Beatriz Luna, Ph.D.

Published Online: 18 Jan 2019 / DOI: https://doi.org/10.1176/appi.ajp.2018.18040443

 

Abstract

Objective:

The authors created normative growth charts of amygdala functional connectivity in typically developing youths, assessed age-associated deviations of these trajectories in youths with psychosis spectrum disorders, and explored how these disruptions are related to clinical symptomatology.

Methods:

Resting-state functional neuroimaging data from four samples (three cross-sectional, one longitudinal) were collected for 1,062 participants 10–25 years of age (622 typically developing control youths, 194 youths with psychosis spectrum disorders, and 246 youths with other psychopathology). The authors assessed deviations in the psychosis spectrum and other psychopathology groups in age-related changes in resting-state functional MRI amygdala-to-whole brain connectivity from a normative range derived from the control youths. The authors explored relationships between age-associated deviations in amygdala connectivity and positive symptoms in the psychosis spectrum group.

Results:

Normative trajectories demonstrated significant age-related decreases in centromedial amygdala connectivity with distinct regions of the brain. In contrast, the psychosis spectrum group failed to exhibit any significant age-associated changes between the centromedial amygdala and the prefrontal cortices, striatum, occipital cortex, and thalamus (all q values <0.1). Age-associated deviations in centromedial amygdala–striatum and centromedial amygdala–occipital connectivity were unique to the psychosis spectrum group and were not observed in the other psychopathology group. Exploratory analyses revealed that greater age-related deviation in centromedial amygdala–thalamus connectivity was significantly associated with increased severity of positive symptoms (r=0.19; q=0.05) in the psychosis spectrum group.

Conclusions:

Using neurodevelopmental growth charts to identify a lack of normative development of amygdala connectivity in youths with psychosis spectrum disorders may help us better understand the neural basis of affective impairments in psychosis, informing prediction models and interventions.

Keywords: Psychosis; Psychiatry; Neurology.

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#Amyloid‐β #Immunotherapy for #Alzheimer’s Disease – Is It Now A Long Shot…? (Ann Neurol., abstract)

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

Amyloid‐β Immunotherapy for Alzheimer’s Disease – Is It Now A Long Shot…?

Francesco Panza MD, PhD ,  Madia Lozupone MD, PhD,  Davide Seripa PhD, Bruno P. Imbimbo PhD

First published: 11 January 2019 / DOI: https://doi.org/10.1002/ana.25410

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.25410.

 

Abstract

The amyloid‐β (Aβ) cascade hypothesis of Alzheimer’s disease (AD) holds that brain accumulation of Aβ initiates the disease process. Accordingly, drug research has targeted Aβ production, clearance or deposition as therapeutic strategies. Unfortunately, candidate drugs have failed to show clinical benefit in established, early or prodromal disease, or those with high AD risk. Currently, monoclonal antibodies specifically directed against the most neurotoxic Aβ forms are undergoing large scale trials to confirm initially encouraging results. However, recent findings on the normal physiology of Aβ suggest that accumulation may be compensatory rather than the pathological initiator. If this is true, alternative strategies will be needed to defeat this devastating disease.

This article is protected by copyright. All rights reserved.

Keywords: Alzherimer’s Disease; Neurology.

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EARLY‐ONSET #CEREBRAL #AMYLOID #ANGIOPATHY FOLLOWING #CHILDHOOD EXPOSURE TO CADAVERIC #DURA (Ann Neurol., abstract)

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

EARLY‐ONSET CEREBRAL AMYLOID ANGIOPATHY FOLLOWING CHILDHOOD EXPOSURE TO CADAVERIC DURA

Gargi Banerjee MRCP,  Matthew E Adams FRCR,  Zane Jaunmuktane FRCPath, G. Alistair Lammie FRCPath,  Ben Turner MD, Mushtaq Wani FRCP,  Inder M S Sawhney DM, Henry Houlden MD,  Simon Mead PhD,  Sebastian Brandner MD FRCPath,  David J Werring FRCP

First published: 31 December 2018 / DOI:  https://doi.org/10.1002/ana.25407

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.25407.

 

Abstract

Amyloid‐β transmission has been described in patients both with and without iatrogenic Creutzfeldt‐Jakob disease; however, there is little information regarding the impact of this acquired amyloid‐β pathology during life. Here, for the first time, we describe in detail the clinical and neuroimaging findings in three patients with early‐onset symptomatic amyloid‐β cerebral amyloid angiopathy following childhood exposure to cadaveric dura (by neurosurgical grafting in two patients, and tumour embolization in a third). Our observations provide further in vivo evidence that cerebral amyloid angiopathy might be caused by transmission of amyloid‐β seeds (prions) present in cadaveric dura, and has diagnostic relevance for younger patients presenting with suspected cerebral amyloid angiopathy.

This article is protected by copyright. All rights reserved.

Keywords: Prions; Amyloid angipopathy.

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