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      COVID-19

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Cape Verde)

      March 3, 2021

      General interest

      Fellow of EAN awarded 2021 Brain Prize

      March 3, 2021

      General interest

      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Cape Verde)

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      COVID-19

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

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      Severe COVID-19-related encephalitis can respond to immunotherapy

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      Country of the Month: Lithuania

      March 1, 2021

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      March 1, 2021

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      Research Paper of the month: Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)

      March 1, 2021

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      COVID-19 Paper of the month: Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

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      Research Paper of the month: Trial of dexamethasone for chronic subdural hematoma

      February 1, 2021

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      First Virtual EAN Regional Teaching Course in Moscow, Russia

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      March 1, 2021

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      COVID-19 around the World: Clinician interviews on experience and impact of the virus (South Africa)

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      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      COVID-19

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

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      Scientific Committee Snapshot: Didier Leys

      April 1, 2020

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      August 11, 2020

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      June 3, 2020

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      Rare Neurological Diseases in the COVID-19 era: Suggestions for information to patients and caregivers

      May 13, 2020

      Scientific panels reports

      Scentific Panel of the Month: Higher Cortical Functions

      March 2, 2020

      Breaking news

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      Breaking news

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      Breaking news

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

      Breaking news

      Inflammatory cytokine patterns associated with neurological diseases in COVID-19

      March 3, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and cognitive disorders

      February 18, 2021

      Eur J Neurol

      EAN is proud to announce the 2020 Virtual Master Classes Christmas Special

      November 13, 2020

      Eur J Neurol

      EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic

      October 22, 2020

      Eur J Neurol

      BREAKING NEWS: A systematic review of neurological manifestations of SARS‐CoV‐2 infection: the devil is hidden in the details

      June 30, 2020

      Eur J Neurol

      EUROPEAN JOURNAL OF NEUROLOGY: CONTRIBUTIONS FROM SPANISH AUTHORS

      November 4, 2019

      Top 10 Articles

      EAN is proud to announce the 2020 Virtual Master Classes Christmas Special

      November 13, 2020

      Top 10 Articles

      EUROPEAN JOURNAL OF NEUROLOGY – TOP 15 ARTICLES 2018

      February 1, 2019

      Top 10 Articles

      Interview with Prof. Patrick Cras – UEMS Section of Neurology (SN)

      February 3, 2018

      Top 10 Articles

      Interview with Mr. Bertrand Daval and Mrs. Nathalie Paulus

      February 3, 2018

      Scientific Corner

      The Future of Brain Research: EU-Initiatives and Experts Together for a Shared European Brain Research Agenda

      March 1, 2021

      Scientific Corner

      New Scales & Scores on Sleep-wake disorders

      January 21, 2021

      Scientific Corner

      Registrar’s Reading List: Epilepsy Panel

      November 2, 2020

      Scientific Corner

      Registrar’s Reading List: Dementia

      September 22, 2020

  • Educational
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      March 1, 2021

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      Academic/Scientific

      New Scales & Scores on Dementia

      February 11, 2021

      E-Brain

      EBRA launches 3rd call for clusters

      May 1, 2020

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      February 28, 2020

      E-Brain

      ebrain to host the 2019 Neurology Formative Test Questions, from 15 April to 26 May

      April 1, 2019

      E-Brain

      ebrain update: Changes in the ebrain team

      November 1, 2018

      Grand Rounds

      eBrain: virtual case report from Belgium

      October 2, 2017

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      July 1, 2016

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      Ebrain granted Royal College of Physicians (UK) CPD/CME accreditation

      July 1, 2016

      Grand Rounds

      ebrain session of the month: neuromuscular junction

      February 1, 2016

      Continuing medical education

      CME online – June 2019 

      June 3, 2019

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      February 21, 2019

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      Continuing medical education

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      July 24, 2018

      Resident and Research Fellows

      EAN Spring School 2020 – Virtual – Webcasts

      November 20, 2020

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      November 13, 2020

      Resident and Research Fellows

      EAN VIRTUAL CONGRESS -Resident and Research Fellow Section General Assembly

      May 26, 2020

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      May 24, 2020

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      March 1, 2021

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      March 1, 2021

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      February 1, 2021

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      February 1, 2021

      Education corner

      First Virtual EAN Regional Teaching Course in Moscow, Russia

      March 1, 2021

      Education corner

      New Scales & Scores on Dementia

      February 11, 2021

      Education corner

      The First EAN Virtual Master Classes 2020 – Report

      January 1, 2021

      Education corner

      EAN Spring School – Application Deadline is 5 February 2021

      December 21, 2020

  • Miscellanea
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      March 3, 2021

      General interest

      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      Miscellanea

      Alzheimer Europe adds two new trials to its Clinical Trials Watch

      March 1, 2021

      Miscellanea

      EMA public stakeholders meeting on the approval, safety monitoring and impact of COVID-19 vaccines in the EU

      March 1, 2021

      Holiday Calendar

      EAN Calendar 2020 – Template For Printing

      December 12, 2019

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      24.12. The last day

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      Grant opportunities

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      November 1, 2019

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      October 29, 2019

      Grant opportunities

      The Clinical Fellowship application deadline is approaching

      October 1, 2019

      News from EAN member societies

      News from EMA: First oral treatment for spinal muscular atrophy (SMA) recommended for approval

      March 3, 2021

      News from EAN member societies

      EMA’s Webinar on ”COVID-19 vaccination – what you need to know as a health professional”

      February 5, 2021

      News from EAN member societies

      Personalized plans, blood biomarkers and early interventions: Think Brain Health conference highlights

      February 1, 2021

      News from EAN member societies

      New gene therapy to treat rare genetic disorder metachromatic leukodystrophy

      January 18, 2021

      EBC

      EBC launches statement on the impact of COVID-19 on brain health

      February 1, 2021

      EBC

      EBC launches new series of disease fact sheets!

      December 1, 2020

      EBC

      Present Your Business or Idea at the Brain Innovation Days Pitch Competition

      October 27, 2020

      EBC

      Save the date for the Brain Innovation Days launch!

      October 1, 2020

      EFNA

      EFNA launch eLearning Platform for neurology advocates

      February 1, 2021

      EFNA

      ‘Me and My Brain’ – Art Competition winners announced!

      February 1, 2021

      EFNA

      Survey on the impact of COVID-19 on neurology service delivery

      November 1, 2020

      EFNA

      EFNA Advocacy Awards 2021 – ‘Action Against Stigma’

      October 1, 2020

      News in general

      WFN Brain Health Awareness Public Webinar

      February 16, 2021

      News in general

      EBC launches statement on the impact of COVID-19 on brain health

      February 1, 2021

      News in general

      European Neuromuscular Centre (ENMC) – Mid-Career Mentoring Programme

      February 1, 2021

      News in general

      Alzheimer Europe launches new guide targeted at health and social care workers and a policy briefing on intercultural care and support

      January 1, 2021

      Topic of the Month/Week

      Brain Awareness Week (BAW) is the global campaign to increase public awareness of the progress and benefits of brain research

      March 13, 2018

      Topic of the Month/Week

      Dystonia Europe celebrates 25 years

      March 13, 2018

      Patients societies reports

      News from Alzheimer Europe

      March 2, 2020

      Patients societies reports

      News from the WHO

      January 9, 2020

      Patients societies reports

      News from EFIC and the European Pain Forum

      January 3, 2020

      Patients societies reports

      News from EFIC and the European Pain Forum

      January 2, 2020

      Surveys

      Driving with an intracranial tumor

      July 13, 2020

      Surveys

      SURVEY: Driving with an intracranial tumor

      June 25, 2020

      Surveys

      EAN SURVEY: Neurological Symptoms in COVID-19 Patients

      April 10, 2020

      Surveys

      EMA communication: ICH Good Clinical Practice Guidelines (ICH E6) – Open Comment Opportunity – Deadline: 1 November 2019

      October 7, 2019

      Forum

      Call for Applications: e-Learning Platform Editor-in-Chief

      August 4, 2020

      Forum

      Neurological News from Denmark VI – the land of the 2nd EAN congress 2016: Pain Research in Denmark from a neurological perspective

      April 1, 2016

      Forum

      Neurological News from Denmark V – the land of the 2nd EAN congress 2016: Clinical Dementia Research in Denmark

      March 1, 2016

      Forum

      Updated recommendations to minimise the risk of the rare brain infection PML with Tysabri – Comment to EMA recommendation

      March 1, 2016

      Uncategorized

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Saudi Arabia)

      January 12, 2021

      Uncategorized

      Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform

      December 2, 2020

      Uncategorized

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (New Zealand)

      November 24, 2020

      Uncategorized

      Report from the annual Pain Forum meeting

      November 2, 2020

  • EAN
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eanpages

  • General interest
    • All COVID-19 Executive Page Country of the Month Paper of the Month EAN News EAN Congress news Interviews
      COVID-19

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Cape Verde)

      March 3, 2021

      General interest

      Fellow of EAN awarded 2021 Brain Prize

      March 3, 2021

      General interest

      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Cape Verde)

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      COVID-19

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

      Executive Page

      Executive page: From Website editor to Co-Chair Communication Committee

      February 1, 2021

      Executive Page

      Severe COVID-19-related encephalitis can respond to immunotherapy

      January 5, 2021

      Executive Page

      Executive Page: Happy New Year 2021 from the EAN, the Home of Neurology

      January 4, 2021

      Executive Page

      Executive Page: Recap of 2020 from Secretary-General

      December 1, 2020

      Country of the Month

      Country of the Month: Lithuania

      March 1, 2021

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      Country of the Month: Albania

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      Country of the Month

      Country of the Month: The Netherlands

      November 1, 2020

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      Country of the Month: Serbia

      October 1, 2020

      Paper of the Month

      COVID-19 Paper of the month: A non-inflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis

      March 1, 2021

      Paper of the Month

      Research Paper of the month: Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study)

      March 1, 2021

      Paper of the Month

      COVID-19 Paper of the month: Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

      February 1, 2021

      Paper of the Month

      Research Paper of the month: Trial of dexamethasone for chronic subdural hematoma

      February 1, 2021

      EAN News

      First Virtual EAN Regional Teaching Course in Moscow, Russia

      March 1, 2021

      EAN News

      European Academy of Neurology endorses the ALBA declaration on Equity and Inclusion

      January 25, 2021

      EAN News

      The First EAN Virtual Master Classes 2020 – Report

      January 1, 2021

      EAN News

      Welcome to new year by Editor-in-Chief

      January 1, 2021

      EAN Congress news

      Congress Registration is open

      December 15, 2020

      EAN Congress news

      Abstract Submission is open

      December 15, 2020

      EAN Congress news

      EAN announces Virtual Congress in 2021

      December 1, 2020

      EAN Congress news

      Investigator Award Winners 2020

      September 14, 2020

      Interviews

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Cape Verde)

      March 3, 2021

      Interviews

      Prof. Dafin Muresanu, Chair of the EAN Communication Committee interviews Prof. Raad Shakir, CBE

      March 1, 2021

      Interviews

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (South Africa)

      February 5, 2021

      Interviews

      COVID-19 around the World: Clinician interviews on experience and impact of the virus (Japan)

      February 1, 2021

  • Academic/Scientific
    • All Scientific committee reports Scientific panels reports Breaking news Neurology updates Eur J Neurol Top 10 Articles Scientific Corner
      General interest

      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      COVID-19

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      COVID-19

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      COVID-19

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

      Scientific committee reports

      Scientific Committee Snapshot: Didier Leys

      April 1, 2020

      Scientific committee reports

      Scientific Committee Snapshot: Rigmor Hojland

      February 26, 2020

      Scientific committee reports

      Scientific Committee Snapshot: Christian Enzinger

      December 1, 2019

      Scientific committee reports

      Scientific Committee Snapshot: Maurizio Leone

      November 1, 2019

      Scientific panels reports

      Coma and DOC Panel Update (May-June): news from the EAN Virtual Congress, personalized pain assessment, NIRS-EEG and machine learning to predict outcomes, prevalence of swallowing disorders and new multimodal predictive algorithms.

      August 11, 2020

      Scientific panels reports

      Statement of the EAN Sleep-Wake-Panel

      June 3, 2020

      Scientific panels reports

      Rare Neurological Diseases in the COVID-19 era: Suggestions for information to patients and caregivers

      May 13, 2020

      Scientific panels reports

      Scentific Panel of the Month: Higher Cortical Functions

      March 2, 2020

      Breaking news

      Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms

      March 3, 2021

      Breaking news

      COVID-19 continuous-EEG case series: A Descriptive Study

      March 3, 2021

      Breaking news

      Acute ischemic stroke and COVID-19: An analysis of 27 676 Patients

      March 3, 2021

      Breaking news

      Inflammatory cytokine patterns associated with neurological diseases in COVID-19

      March 3, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and Cognitive Disorders

      February 18, 2021

      Neurology updates

      Neurology Update: Dementia and cognitive disorders

      February 18, 2021

      Eur J Neurol

      EAN is proud to announce the 2020 Virtual Master Classes Christmas Special

      November 13, 2020

      Eur J Neurol

      EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic

      October 22, 2020

      Eur J Neurol

      BREAKING NEWS: A systematic review of neurological manifestations of SARS‐CoV‐2 infection: the devil is hidden in the details

      June 30, 2020

      Eur J Neurol

      EUROPEAN JOURNAL OF NEUROLOGY: CONTRIBUTIONS FROM SPANISH AUTHORS

      November 4, 2019

      Top 10 Articles

      EAN is proud to announce the 2020 Virtual Master Classes Christmas Special

      November 13, 2020

      Top 10 Articles

      EUROPEAN JOURNAL OF NEUROLOGY – TOP 15 ARTICLES 2018

      February 1, 2019

      Top 10 Articles

      Interview with Prof. Patrick Cras – UEMS Section of Neurology (SN)

      February 3, 2018

      Top 10 Articles

      Interview with Mr. Bertrand Daval and Mrs. Nathalie Paulus

      February 3, 2018

      Scientific Corner

      The Future of Brain Research: EU-Initiatives and Experts Together for a Shared European Brain Research Agenda

      March 1, 2021

      Scientific Corner

      New Scales & Scores on Sleep-wake disorders

      January 21, 2021

      Scientific Corner

      Registrar’s Reading List: Epilepsy Panel

      November 2, 2020

      Scientific Corner

      Registrar’s Reading List: Dementia

      September 22, 2020

  • Educational
    • All E-Brain Grand Rounds Continuing medical education Resident and Research Fellows Fellowship reports Education corner
      Educational

      Clinical Fellowship Reports 2020

      March 1, 2021

      Educational

      First Virtual EAN Regional Teaching Course in Moscow, Russia

      March 1, 2021

      Educational

      Clinical Fellowship Reports 2019

      March 1, 2021

      Academic/Scientific

      New Scales & Scores on Dementia

      February 11, 2021

      E-Brain

      EBRA launches 3rd call for clusters

      May 1, 2020

      E-Brain

      News from ebrain

      February 28, 2020

      E-Brain

      ebrain to host the 2019 Neurology Formative Test Questions, from 15 April to 26 May

      April 1, 2019

      E-Brain

      ebrain update: Changes in the ebrain team

      November 1, 2018

      Grand Rounds

      eBrain: virtual case report from Belgium

      October 2, 2017

      Grand Rounds

      Free access to Ebrain for EAN members

      July 1, 2016

      Grand Rounds

      Ebrain granted Royal College of Physicians (UK) CPD/CME accreditation

      July 1, 2016

      Grand Rounds

      ebrain session of the month: neuromuscular junction

      February 1, 2016

      Continuing medical education

      CME online – June 2019 

      June 3, 2019

      Continuing medical education

      Continuing Medical Education

      February 21, 2019

      Continuing medical education

      CME online – October 2018

      October 1, 2018

      Continuing medical education

      CME online – July 2018

      July 24, 2018

      Resident and Research Fellows

      EAN Spring School 2020 – Virtual – Webcasts

      November 20, 2020

      Resident and Research Fellows

      EAN is proud to announce the 2020 Virtual Master Classes Christmas Special

      November 13, 2020

      Resident and Research Fellows

      EAN VIRTUAL CONGRESS -Resident and Research Fellow Section General Assembly

      May 26, 2020

      Resident and Research Fellows

      EAN Virtual Congress: Round table Special Session: Unleash your potential with EAN!

      May 24, 2020

      Fellowship reports

      Clinical Fellowship Reports 2020

      March 1, 2021

      Fellowship reports

      Clinical Fellowship Reports 2019

      March 1, 2021

      Fellowship reports

      Clinical Fellowship Reports III 2019

      February 1, 2021

      Fellowship reports

      Clinical Fellowship Reports II 2019

      February 1, 2021

      Education corner

      First Virtual EAN Regional Teaching Course in Moscow, Russia

      March 1, 2021

      Education corner

      New Scales & Scores on Dementia

      February 11, 2021

      Education corner

      The First EAN Virtual Master Classes 2020 – Report

      January 1, 2021

      Education corner

      EAN Spring School – Application Deadline is 5 February 2021

      December 21, 2020

  • Miscellanea
    • All Holiday Calendar Grant opportunities News from EAN member societies EBC EFNA News in general Topic of the Month/Week Patients societies reports Surveys Forum Uncategorized
      News from EAN member societies

      News from EMA: First oral treatment for spinal muscular atrophy (SMA) recommended for approval

      March 3, 2021

      General interest

      Brain Talks: Professor Günther Deuschl addresses burden of neurological diseases in Europe

      March 3, 2021

      Miscellanea

      Alzheimer Europe adds two new trials to its Clinical Trials Watch

      March 1, 2021

      Miscellanea

      EMA public stakeholders meeting on the approval, safety monitoring and impact of COVID-19 vaccines in the EU

      March 1, 2021

      Holiday Calendar

      EAN Calendar 2020 – Template For Printing

      December 12, 2019

      Holiday Calendar

      24.12. The last day

      December 24, 2018

      Holiday Calendar

      23.12. Last-minute gift idea

      December 23, 2018

      Holiday Calendar

      22.12. A chance to win…

      December 22, 2018

      Grant opportunities

      European Commission: Innovation and novelty in medical devices and in vitro diagnostic devices; towards common concepts of innovation-related risk assessments

      November 1, 2019

      Grant opportunities

      GBS|CIDP Foundation International 2020 Research Grant Opportunity

      October 29, 2019

      Grant opportunities

      The Clinical Fellowship application deadline is approaching

      October 1, 2019

      News from EAN member societies

      News from EMA: First oral treatment for spinal muscular atrophy (SMA) recommended for approval

      March 3, 2021

      News from EAN member societies

      EMA’s Webinar on ”COVID-19 vaccination – what you need to know as a health professional”

      February 5, 2021

      News from EAN member societies

      Personalized plans, blood biomarkers and early interventions: Think Brain Health conference highlights

      February 1, 2021

      News from EAN member societies

      New gene therapy to treat rare genetic disorder metachromatic leukodystrophy

      January 18, 2021

      EBC

      EBC launches statement on the impact of COVID-19 on brain health

      February 1, 2021

      EBC

      EBC launches new series of disease fact sheets!

      December 1, 2020

      EBC

      Present Your Business or Idea at the Brain Innovation Days Pitch Competition

      October 27, 2020

      EBC

      Save the date for the Brain Innovation Days launch!

      October 1, 2020

      EFNA

      EFNA launch eLearning Platform for neurology advocates

      February 1, 2021

      EFNA

      ‘Me and My Brain’ – Art Competition winners announced!

      February 1, 2021

      EFNA

      Survey on the impact of COVID-19 on neurology service delivery

      November 1, 2020

      EFNA

      EFNA Advocacy Awards 2021 – ‘Action Against Stigma’

      October 1, 2020

      News in general

      WFN Brain Health Awareness Public Webinar

      February 16, 2021

      News in general

      EBC launches statement on the impact of COVID-19 on brain health

      February 1, 2021

      News in general

      European Neuromuscular Centre (ENMC) – Mid-Career Mentoring Programme

      February 1, 2021

      News in general

      Alzheimer Europe launches new guide targeted at health and social care workers and a policy briefing on intercultural care and support

      January 1, 2021

      Topic of the Month/Week

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Paper of the Month

Paper of the month: Efficacy and safety of andexanet to reverse factor Xa inhibitors activity.

February 1, 2016

Elena Moro by Elena Moro

For February 2016 we have selected: Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015;33:2413-2424.

There is an increased use of direct factor Xa inhibitors (like apixaban, rivaroxaban, and edoxaban) to prevent stroke in patients with nonvalvular atrial fibrillation since these medications have several advantages compared to vitamin K antagonists. However, there has been no specific antidote able to reverse their anticoagulant effects, for example in case of major bleeding or emergency surgery. Recently, andexanet alfa has shown the ability to bind and sequestrate factor Xa inhibitors in the vascular space, thus reestablishing the activity of endogenous factor Xa and decreasing the levels of anticoagulant activity. This anticoagulant reversal capability can be assessed by measuring thrombin generation and anti-factor Xa activity.

A randomized, dual-center, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of andexanet to reverse the anticoagulant effects of apixaban (ANNEXA-A trial) and rivaroxaban (ANNEXA-R trial) in healthy subjects (50-75 years old). Subjects were randomized to receive intravenously andexanet as a bolus, or the bolus followed by a 2-hour intravenous andexanet infusion. Subjects were housed at the study site for 8 days, with safety outcomes assessed 15, 36 and 43 days after drug administration. In the ANNEXA-A group, 5 mg of apixaban were given twice a day for 4 days before being randomized to 400-mg intravenous bolus of andexanet (or placebo), or to the same bolus followed by a continuous infusion of 4-mg andexanet (or placebo) per minute for 120 minutes (480 mg in total). In the ANNEXA-R group, subjects received 20 mg of rivaroxaban once a day for 4 days, and then randomized to an 800-mg intravenous bolus of andexanet (or placebo), or to the same bolus followed by a continuous infusion of 8-mg andexanet (or placebo) per minute for 120 minutes (960 mg in total). Main outcome was the percent change in anti-factor Xa activity, measured with validated chromogenic assay of factor Xa enzymatic activity before and after andexanet or placebo (2-5 minutes after the bolus, and 5 minutes after the continuous infusion). As secondary outcomes, the proportion of participants with 80% reduction in anti-factor Xa activity, the changes in unbound (active) inhibitor plasma concentration and in thrombin generation, and the occurrence of an endogenous thrombin potential above the lower limits were also assessed.

A total of 101 subjects received andexanet, whereas 44 subjects had placebo. After the bolus, andexanet was able to quickly (within 2 to 5 minutes) reduce anti-factor Xa activity by 94% (vs. 21% placebo, 9 subjects; P<0.001) and by 92% (vs. 18% placebo, 14 subjects; P<0.001) in the 24 ANNEXA-A subjects and in the 27 ANNEXA-R subjects, respectively. Similar results were found within subjects who received andexanet bolus followed by continuous infusion. The reversal effects lasted for about 2 hours after both the bolus and the bolus followed by infusion. Andexanet induced at least 80% reversal of anti-factor Xa activity in the participants and normalized thrombin generation within 10 minutes after the bolus. The mean concentrations of unbound apixaban and rivaroxaban were significantly reduced within 2 to 5 minutes after andexanet administration vs. placebo (by 9.3 ng/ml vs. 1.9 ng/ml, P<0.001, and by 23.4 ng/ml vs. 4.2 ng/ml, P<0.001, respectively). Transient elevation of D-Dimer and prothrombin fragments 1 and 2 were observed.

“This study shows that andexanet is effective in reversing the apixaban and rivaroxaban anticoagulant action,” says Prof L. Jaap Kappelle, Division of Neurology, University Medical Centre Utrecht, The Netherlands. “The andexanet reversal ability reached its maximal effect within few minutes after the bolus and remained constant during the continuous infusion. Any biomarker of anticoagulation resumed placebo levels between 1 and 3 hours after andexanet administration. These results are very important due to the real need of a specific antidote for factor Xa inhibitors. Moreover, no major adverse events due to andexanet (in particular, thrombotic events) were reported.”
“Although these results come only from healthy subjects, andexanet seems to be a flexible, potent and rapid drug to quickly restore hemostasis in patients taking factor Xa inhibitors”, says Prof. Thierry Moulin, Department of Neurology, CHU of Besancon, France. “We are impatiently waiting for further clinical trials results, such as the ongoing ANNEXA-4 phase 3b-4 trial (ClinicalTrials.gov identifier: NCT02329327) which is evaluating the efficacy and safety of andexanet in patients with factor Xa inhibitor–associated acute major bleedings, and from those which will evaluate its use in the real stroke world.”

The other nominees for the FEBRUARY paper of the month are:

Strupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 2015;314:2535-2543. In this multicenter, open-label trial, the interim analysis showed that combined treatment with tumor-treating fields (locoregionally delivered continuously) combined with temozolomide (150-200 mg/m2/d) was significantly superior to temozolomide alone in improving survival in 325 patients with glioblastoma.

Arya R, Kothari H, Zhang Z, Han B, Horn PS, Glauser TA. Efficacy of nonvenous medications for acute convulsive seizures: a network meta-analysis. Neurology 2015; 85:1859-1868. Results coming from this network meta-analysis about non venous drugs used to treat convulsive seizures and convulsive status epilepticus show that intramuscular midazolam was superior to other drugs concerning time to seizure termination. Intranasal midazolam was the most effective to terminate seizure with 10 minutes of administration.

Franz DN, Agricola K, Mays M, et al. Everolimus for subependymal giant cell astrocytoma: 5-year final analysis. Ann Neurol 2015; 78:929-938. 2015. This paper presents data coming from an open-label phase II study in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex treated with everolimus for 5 years. Most patients had both tumor volume and daily seizures reduction. No safety concerns were reported.

Fitzgerald KC, Munger AL, Kochert K, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol 2015;72:1458-1465. Results from 1482 patients with multiple sclerosis undertaking interferon beta-1b (BEYOND study) and prospectively followed for 2 years showed that low serum 25-hydroxyvitamin D levels were associated with higher rates of disease activity observed on brain MRI.

Paper of the month: Efficacy and safety of andexanet to reverse factor Xa inhibitors activity. was last modified: November 13th, 2018 by Editor
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