Simultaneous PML-IRIS after discontinuation of natalizumab in a patient with MS

• Published in: Neurology Vol. 78; no. 18; pp. 1390 - 1393
• Main Authors: GHEUENS, S, SMITH, D. R, WANG, X, ALSOP, D. C, LENKINSKI, R. E, KORALNIK, I. J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-05-2012
• Subjects: Alcoholic Intoxication - complications; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Atrophy; Biological and medical sciences; biomarkers; Biomarkers - analysis; Brain - drug effects; Brain - pathology; Case reports; Corticoids; Creatine; Follow-Up Studies; Humans; Immune reconstitution; Immune Reconstitution Inflammatory Syndrome - chemically induced; Immune Reconstitution Inflammatory Syndrome - diagnosis; Immune response; Immunosuppressive agents; Inflammation; Leukoencephalopathy, Progressive Multifocal - chemically induced; Leukoencephalopathy, Progressive Multifocal - diagnosis; Lipids; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Medical sciences; Multiple sclerosis; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Natalizumab; Neurologic Examination; Neurology; Progressive multifocal leukoencephalopathy; Seizures; Spinal Cord - drug effects; Spinal Cord - pathology; Substance Withdrawal Syndrome - diagnosis; Substantia alba; Young Adult; Human; Natalizumab; Nervous system diseases
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.0b013e318253d61e

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.
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.
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.