MR Imaging Trailing Clinical Expression of Natalizumab-Associated PML in Multiple Sclerosis: A Rare But Serious Diagnostic and Management Problem (P5.196)

OBJECTIVE: To describe a multiple sclerosis (MS) patient with natalizumab-associated progressive multifocal leukoencephalopathy (PML) in whom clinical expression preceded MRI findings by several months. BACKGROUND: PML is readily diagnosed using a combination of clinical features, characteristic imaging findings, and supportive laboratory tests. Clinically evident PML rarely lacks supportive imaging findings at initial presentation. DESIGN/METHODS: Case report. RESULTS: A 37-year-old JC virus antibody positive woman with previously well-controlled MS treated with natalizumab since March 2007 developed episodes of transient whole body stiffness and involuntary movements of her left arm in March 2013, six months after the frequency of natalizumab infusions had been decreased. Brain MRI revealed two new small subcortical lesions, indicative of MS. As a precaution, natalizumab was discontinued in April 2013. In May 2013, she developed dysarthria and difficulty walking, prompting treatment with a 3-day course of intravenous corticosteroids without improvement. Repeat brain MRI on June 12, 2013 showed several new lesions in the subcortical white matter and brainstem, interpreted as worsening MS. Mistrusting MRI, cerebrospinal fluid (CSF) was obtained on June 13, 2013, showing >180,000 copies/mL of JC virus by PCR and thus establishing a diagnosis of PML. The patient began empirical treatments for PML, while subsequent MRIs showed no evidence of PML until July 9, 2013 when a typical confluent fluffy T2/FLAIR hyperintensity appeared in the right posterior frontal subcortical white matter. Serial clinical and imaging data will be presented. CONCLUSION: Clinical symptoms of PML may precede its appearance on MR imaging. In suspected similar situations, a high index of suspicion for PML should be maintained - even in the absence of supportive imaging findings - prompting definitive investigations (e.g., CSF JC virus PCR testing, or biopsy). Delay in diagnosing PML portends worse prognosis by delaying appropriate management. Disclosure: Dr. Muth has nothing to disclose. Dr. Hernandez has nothing to disclose. Dr. Stefoski has received personal compensation for activities with Biogen Idec, Acorda Therapeutics, Serono Inc., and Teva Neuroscience as a consultant, and Biogen Idec, Teva Neuroscience, EMD Serono, Elan Corp., and Acorda Therapeutics as a speaker bureau member. Dr. Stefoski has received royalty payments from Acorda Therapeutics. Dr. Stefoski has received research support from Biogen Idec, Novartis, Serono Inc., and Pfizer Inc. Dr. Balabanov has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Questor, and Acorda Therapeutics. Dr. Balabanov has received research support from Biogen Iden and Teva Neuroscience. Dr. Kohas received personal compensation for activities with Biogen Idec, EMD Serono, and Acorda Therapeutics as a consultant and speaker.