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Related Concept Videos

Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

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Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
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Encephalitis l: Introduction01:19

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Encephalitis is inflammation of the brain parenchyma, most often due to infections or autoimmune processes. It presents with neuropsychiatric features such as fever, altered mental status, behavioral changes, cognitive dysfunction, seizures, focal deficits, and sometimes autonomic instability. In some cases, the meninges are also involved, resulting in meningoencephalitis.Infectious CausesInfectious encephalitis is most commonly viral but can also result from bacterial, fungal, or parasitic...
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Related Experiment Video

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Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
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Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence?

Gary R Cutter1, Olaf Stüve2

  • 1Section on Research Methods and Clinical Trials, University of Alabama at Birmingham, Birmingham, USA.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|May 10, 2014
PubMed
Summary
This summary is machine-generated.

Natalizumab use for multiple sclerosis is limited by progressive multifocal leukoencephalopathy (PML). A risk algorithm using JCV antibodies, prior immunosuppressants, and therapy duration did not reduce PML incidence, despite modifiable factors.

Keywords:
Disease-modifying therapiesmultiple sclerosisoutcome measurement

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Area of Science:

  • Neurology
  • Immunology
  • Infectious Diseases

Background:

  • Natalizumab is an effective multiple sclerosis (MS) treatment but carries a risk of progressive multifocal leukoencephalopathy (PML).
  • PML is a rare but serious opportunistic infection caused by the John Cunningham virus (JCV).
  • Risk factors for natalizumab-associated PML include JCV antibody status, prior immunosuppressant use, and treatment duration.

Purpose of the Study:

  • To evaluate the effectiveness of a risk stratification algorithm for natalizumab-associated PML.
  • To analyze the incidence of PML in natalizumab-treated MS patients between April 2010 and February 2014.
  • To discuss reasons for the lack of success in reducing PML incidence despite identified risk factors.

Main Methods:

  • Analysis of PML incidence in a cohort of natalizumab-treated multiple sclerosis patients.
  • Assessment of a risk stratification algorithm incorporating JCV serostatus, immunosuppressant history, and treatment duration.
  • Review of potential factors limiting the efficacy of risk stratification strategies.

Main Results:

  • The identified risk stratification algorithm did not lead to a reduction in PML incidence.
  • PML incidence remained a concern in natalizumab-treated patients during the study period.
  • Despite modifiable risk factors like treatment duration and JCV serostatus, PML rates were not decreased.

Conclusions:

  • Current risk stratification strategies for natalizumab-associated PML have not effectively reduced its incidence.
  • Further investigation is needed to understand why modifiable risk factors have not translated into reduced PML rates.
  • The limitations of companion diagnostics in managing natalizumab-associated PML require further discussion and potential re-evaluation.