Natalizumab-associated progressive multifocal leukoencephalopathy in Germany

Area of Science:

• Neurology
• Virology
• Immunology

Background:

• Natalizumab therapy for multiple sclerosis is associated with a risk of progressive multifocal leukoencephalopathy (PML).
• Accurate diagnosis and risk stratification of PML are crucial for patient management.

Purpose of the Study:

• To evaluate diagnostic characteristics for JC polyomavirus-associated PML.
• To assess PML risk stratification in multiple sclerosis patients on natalizumab therapy.

Main Methods:

• Analysis of 292 adverse drug reaction reports of suspected PML cases in Germany until July 2017.
• Exclusion of patients not meeting PML criteria or with insufficient data.

Main Results:

• 142 confirmed PML cases: 72.3% female, median age 43. 7.7% asymptomatic at diagnosis.
• PML was fatal in 9.1% of cases. Infratentorial lesions seen in 40%.
• JC polyomavirus DNA in CSF was undetectable in 23.8%. Three patients with negative antibodies pre-diagnosis seroconverted.

Conclusions:

• JC polyomavirus DNA detection in CSF has limited sensitivity in early PML.
• Clinical and imaging presentations can be atypical, necessitating revised diagnostic criteria.
• Negative anti-JC polyomavirus antibodies do not preclude PML; close monitoring is essential.