MRI preclinical detection and asymptomatic course of a progressive multifocal leucoencephalopathy (PML) under natalizumab therapy: Figure 1

Abstract

Early detection of progressive multifocal leucoencephalopathy (PML) in the setting of natalizumab therapy currently is performed by rapid evaluation of new symptoms occurring in treated patients. The role of MR scanning has not been investigated but holds promise since MR detection is highly sensitive for PML lesions. The authors report a case of presymptomatic PML of the posterior fossa detected by MR scans. Immediate suspension of natalizumab and plasma exchanges resulted in a rapid decline of natalizumab serum concentration. Intravenous steroids started together with plasma exchanges followed by an oral tapering course were used to minimise the immune reconstitution inflammatory syndrome. No symptoms (beyond mild headache) developed, and the repeat PCR for JC Virus (JCV) DNA detection performed 10 weeks later was negative. This case suggests that: (1) periodic brain MR scans may detect signs of presymptomatic PML in MS patients treated with natalizumab, (2) corticosteroid management of inflammatory reaction may contribute to optimal control of the immune reconstitution inflammatory syndrome routinely seen with natalizumab-associated PML and (3) early radiological detection of PML can have an excellent outcome even in a clinically critical region and despite prior immunosuppressant exposure. The potential benefit of regular MR scanning just using the T2/FLAIR modalities could be further investigated in order to detect early natalizumab-associated PML, leading to benign outcomes.

The earlier, the smaller, the better for natalizumab-associated PML: In MRI vigilance veritas?

“…We are not aware of the specific context and outcome of the 4 other N-PML cases, which were diagnosed and treated in other centers. The reported cases emphasize that 1) N-PML can have a long presymptomatic course while still being clearly detectable with MRI, 2) N-PML can have a benign outcome provided it is diagnosed and treated early, 3) a clinically symptomatic N-PML may be a further advanced infection with a poorer prognosis, and 4) periodic brain MRI scans, particularly in high-risk situations, are likely to provide earlier detection of N-PML 4 and better outcomes. Written informed consent was obtained from all 4 patients.…”

“…2 In patients with prior JCV infection detected by serum anti-JCV antibodies, 3 duration of therapy and prior use of immunosuppressants (IS) increase the risk of N-PML. The clinical outcome of patients with MS who developed N-PML was highly variable, ranging from asymptomatic case 4 to varying degrees of neurologic disability or even death. 5 It was also observed in real-life setting that the earlier N-PML was diagnosed and treated, the better was the clinical outcome.…”

“…Consistent with previous data, the Expanded Disability Status Scale status, the size of the MRI lesion, and the age of the patient at the time of diagnosis may correlate with the clinical outcome. 4 In cases 2, 3, and 4, the emergence of N-PML symptoms was concurrent with the development of T1 hypointensity (dark) within the lesion due to immune reconstitution inflammatory syndrome (IRIS) occurrence in cases 2 and 3 (not shown) and at the time of a late-stage clinical diagnosis in case 4 ( figure).The 4 N-PML cases were confirmed by PCR detection of JCV DNA in the CSF (all performed at Focus Diagnostics, Cypress, CA). Natalizumab infusions were interrupted and plasma exchanges (PLEX) were immediately performed in all cases at the time of diagnosis.…”

Treatment options for patients with multiple sclerosis who have a suboptimal response to interferon‐β therapy

“…Natalizumab treatment requires a 1-h infusion plus a 1-h observation period every month [18,19,70], giving a total burden of at least 48 h over 2 years. For early detection of PML, it has been suggested that MRI analysis may be needed as often as every 6 months in patients who are positive for anti-JCV antibodies, in addition to regular assessment by medical and nursing staff and cerebrospinal fluid analysis [68,76].…”

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2—Surveillance for Treatment Complications and Disease Progression

“…19,20 Most interesting, compared with other PML cohorts, contrast enhancement can be observed quite frequently in natalizumab-associated PML (NTZ PML), occurring in approximately 30% of all patients at diagnosis, and can be the leading radiologic sign in asymptomatic patients. [22][23][24] Substantial evidence indicates that FLAIR is the most sensitive sequence for detecting PML. 22 DWI is known to be highly sensitive for depicting acute demyelination but can also aid in the differentiation of acute PML lesions from chronic and subacute demyelinating MS lesions.…”