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Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide
Tobias Moser1, Georg Zimmermann1,2,3, Anna Baumgartner4
1Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria.
Background/Objective:
The use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria.
Methods:
Retrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome.
Results:
As of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11.
Conclusions:
The number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.
Insights
Progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab (NAT) can lead to severe disability. However, inflammatory MS activity post-PML recovery is infrequent, and NAT-PML cases are declining.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious opportunistic brain infection complicating natalizumab (NAT) treatment for multiple sclerosis (MS).
- Understanding the long-term outcomes of NAT-associated PML (NAT-PML) and the subsequent course of MS is crucial for patient management.
Purpose of the Study:
- To analyze the clinical course of MS following PML recovery in patients treated with NAT.
- To evaluate the long-term outcomes of NAT-PML cases in Austria.
Main Methods:
- A retrospective study was conducted using data from the Austrian MS treatment registry (AMSTR) and MS centers.
- Patient records were reviewed, and neurological disability was assessed using the Expanded Disability Status Scale (EDSS).
Main Results:
- Fifteen NAT-PML cases were identified in Austria by December 2022, with a 20% mortality rate.
- Median EDSS significantly increased from 3.5 pre-PML to 6.5 post-PML, indicating persistent neurological deficits.
- Despite severe deficits, inflammatory MS activity post-PML recovery was rare, with only a few cases of relapses or new MRI lesions.
Conclusions:
- The incidence of NAT-PML cases in Austria is decreasing, possibly due to increased vigilance.
- While many patients experience severe long-term neurological deficits after NAT-PML, the risk of inflammatory MS activity appears low.
