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Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS
1Division of NeuroVirology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Objective:
Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab therapy in patients with multiple sclerosis (MS), which is often accompanied by an immune reconstitution inflammatory syndrome (IRIS) after removal of the drug. We describe a patient with MS who presented with simultaneous PML-IRIS 2 months after stopping natalizumab for other reasons.
Case Report And Results:
The patient had widespread PML and severe IRIS. He received corticosteroids and displayed a vigorous JC virus-specific cellular immune response. Elevated myoinositol and lipid/creatine peaks measured in PML lesions by proton magnetic resonance spectroscopy ((1)H-MRS) corresponded to episodes of contrast enhancement on MRI scans and persisted after the enhancement subsided. He demonstrated steady clinical improvement, but developed marked residual atrophy in areas affected by PML and inflammation, as well as seizures.
Conclusions:
New enhancing white matter lesions, occurring after discontinuation of natalizumab, can be the manifestation of PML-IRIS rather than an MS exacerbation. Elevated myoinositol and lipid/creatine peaks appear to be more sensitive markers of inflammation in PML lesions than contrast enhancement. (1)H-MRS may become useful as a biomarker for PML-IRIS by helping clinicians determine the need for corticosteroid administration and anticipate continuing clinical recovery.
Insights
Progressive multifocal leukoencephalopathy (PML) with immune reconstitution inflammatory syndrome (IRIS) can occur simultaneously after natalizumab discontinuation in multiple sclerosis (MS) patients. Proton magnetic resonance spectroscopy ((1)H-MRS) may aid in diagnosing PML-IRIS and guiding treatment.
Area of Science:
- Neuroimmunology
- Neurology
- Radiology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab therapy for multiple sclerosis (MS).
- Immune reconstitution inflammatory syndrome (IRIS) often accompanies PML after natalizumab withdrawal.
- This case highlights simultaneous PML and IRIS presentation post-natalizumab therapy.
Observation:
- A multiple sclerosis patient developed widespread PML and severe IRIS two months after stopping natalizumab.
- The patient exhibited a strong JC virus-specific cellular immune response and received corticosteroids.
- Proton magnetic resonance spectroscopy ((1)H-MRS) revealed elevated myoinositol and lipid/creatine peaks in PML lesions.
Findings:
- Elevated myoinositol and lipid/creatine peaks on (1)H-MRS correlated with contrast enhancement on MRI scans.
- These spectroscopic changes persisted even after contrast enhancement subsided.
- The patient showed clinical improvement but developed residual atrophy and seizures.
Implications:
- Enhancing white matter lesions post-natalizumab may indicate PML-IRIS, not MS relapse.
- (1)H-MRS shows promise as a sensitive biomarker for PML-IRIS inflammation.
- Biomarkers like (1)H-MRS could guide corticosteroid use and predict recovery in PML-IRIS.
