The spectrum of MRI findings of progres­sive multifocal leukoencephalopathy in patients with multiple sclerosis in the Czech Republic


Authors: M. Vaněčková 1;  A. Martinková 2;  R. Tupý 3;  J. Fiedler 4;  I. Štětkářová 5;  E. Medová 5;  M. Vachová 6;  J. Marková 7;  M. Grunermelová 7;  E. Meluzínová 8;  J. Adámková 9;  J. Kubále 10;  M. Talábová 11;  D. Horáková 12;  E. Kubala Havrdová 12
Authors‘ workplace: Oddělení MR, Radiodiagnostická klinika 1. LF UK a VFN v Praze 1;  Radiologické oddělení, Nemocnice České Budějovice, a. s. 10;  MS centrum, Neurologická klinika FN Hradec Králové 11;  RS centrum, Neurologická klinika a Centrum klinických neurověd, 1. LF UK a VFN v Praze 12;  MS centrum, Neurologická klinika Pardubická krajská nemocnice 2;  Klinika zobrazovacích metod LF v Plzni UK a FN Plzeň 3;  Neurologická klinika LF v Plzni UK a FN Plzeň 4;  Neurologická klinika 3. LF UK a FN Královské Vinohrady, Praha 5;  Neurologické oddělení, Krajská zdravotní, a. s. – Nemocnice Teplice, o. z. 6;  Neurologická klinika 3. LF UK a Thomayerova nemocnice 7;  Neurologická klinika 2. LF UK a FN Motol 8;  Neurologické oddělení, Nemocnice České Budějovice, a. s. 9
Published in: Cesk Slov Neurol N 2019; 82(4): 381-390
Category: Original Paper
doi: 10.14735/amcsnn2019381

Overview

Aim: To show the full spectrum of MRI findings in all patients ever dia­gnosed with progres­sive multifocal leukoencephalopathy (PML), which is as­sociated with natalizumab ther­apy in patients with MS in the Czech Republic.

Patients and methods: The first case was described in 2009, the last case in December 2018, with a total of 14 dia­gnosed cases of PML in MS patients. This paper evaluates the MRI findings that showed the presence of PML; the dia­gnosis was subsequently confirmed by detection of the John Cun­ningham virus (JCV) DNA from cerebrospinal fluid using polymerase chain reaction. All patients met the American Academy of Neurology criteria from 2013 for dia­gnosis of this dis­ease. The MRI protocol used was variable, both because patients were examined at dif­ferent MRI sites across the Czech Republic, and because of evolution of protocols over time. In all patients, the protocol contained fluid attenuated inversion recovery (FLAIR), which is the most sensitive sequence for early PML detection.

Results: 13 patients (92.9%) had a positive MRI find­­ing. The most frequent find­­ing was typical white matter involvement in the subcortical area of the frontal lobe (42.9%), fol­lowed by the parietal (28.6%) and temporal lobes (28.6%). The extent of the pathology was also very variable, from very small discrete lesions to extensive dif­fuse lesions af­fect­­ing multiple lobes. Two patients were found to have cerebel­lar and pons foci (14.3%), one patient in the mesencephalon and another in the medula oblongata. There were thalamic lesions in two cases, and one case of putamen lesions. In some cases, MRI presentation of PML was very similar to the MRI presentation of MS and suspicion of PML was considered because there was new progression of MRI. One patient was completely atypical compared to the rest of the group. PML was dia­gnosed from a routine lumbar puncture done when ther­apy was changed, and the MRI find­­ing at that time was negative. Positive findings appeared only 6 months after the PML dia­gnosis. This case involved the JCV-granulocytic neuronopathy with cerebel­lum af­fection subtype.

Conclusion: The Czech cohort of PML patients confirms the great variability in MRI findings and points out the importance of careful MRI monitor­­ing to detect the dis­ease in the subclinical phase.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Keywords:

multiple sclerosis – progressive multifocal leukoencephalopathy – MRI – asymptomatic imaging


Sources

1. Keen DL, Legare C, Taylor E et al. Monoclonal antibodies and progres­sive multifocal leukoencephalopathy. Can J Neurol Sci 2011; 38: 565– 571.

2. Sahraian MA, Radue EW, Eshaghi A et al. Progres­sive multifocal leukoencephalopathy: a review of the neuroimag­­ing features and dif­ferential dia­gnosis. Eur J Neurol 2012; 19(8): 1060– 1069. doi: 10.1111/ j.1468-1331.2011.03597.x.

3. Paz SP, Branco L, Pereira MA et al. Systematic review of the published data on the worldwide prevalence of John Cun­ningham virus in patients with multiple sclerosis and neuromyelitis optica. Epidemiol Health 2018; 40: e2018001. doi: 10.4178/ epih.e2018001.

4. Fragoso YD, Brooks JB, Eboni AC et al. Seroconversion of JCV antibodies is strongly as­sociated to natalizumab ther­apy. J Clin Neurosci 2019; 61: 112– 113. doi: 10.1016/ j.jocn.2018.10.128.

5. Vaněčková M, Seidl Z. Roztroušená skleróza a onemocnění bílé hmoty v MR zobrazení. Praha: Mladá fronta 2018: 286.

6. Yousry TA, Pel­letier D, Cadavid D et al. Magnetic resonance imag­­ing pattern in natalizumab-as­sociated progres­sive multifocal leukoencephalopathy. Ann Neurol 2012; 72(5): 779– 787. doi: 10.1002/ ana.23
676.

7. Tan CS, Koralnik IJ. Progres­sive multifocal leukoencephalopathy and other disorders by JC virus: clinical features and pathogenesis. Lancet Neurol 2010; 9(4): 425– 437. doi: 10.1016/ S1474-4422(10)70040-5.

8. Honce JM, Nagae L, Nyberg E. Neuroimag­­ing of natalizumab complications in multiple sclerosis: PML and other as­sociated entities. Mult Scler Int 2015; 2015: 809252. doi: 10.1155/ 2015/ 809252.

9. Rosenkrantz T, Novas M, Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N Engl J Med 2015; 372(15): 1476– 1478. doi: 10.1056/ NEJMc1415408.

10. Berger JR, Aksamit AJ, Clif­ford DB et al. PML dia­g­nostic criteria: consensus statement from the AAN Neuroinfectious Dis­ease Section. Neurology 2013; 80(15): 1430– 1438. doi: 10.1212/ WNL.0b013e31828c2fa1.

11. Dong-Si T, Richman S, Wattjes MP et al. Outcome and survival of asymp­tomatic PML in natalizumab--treated MS patients. Ann Clin Transl Neurol 2014; 1(10): 755– 764. doi: 10.1002/ acn3.114.

12. Dong-Si T, Gheuens S, Gangadharan A et al. Predictors of survival and functional outcomes in natalizumab-
-as­sociated progres­sive multifocal leukoencephalopathy. J Neurovirol 2015; 21(6): 637– 644. doi: 10.1007/ s13365-015-0316-4.

13. Zhang Y, Wright C, Flores A. Asymp­tomatic progres­sive multifocal leukoencephalopathy: a case report and review of the literature. J Med Case Rep 2018; 12(1): 187. doi: 10.1186/ s13256-018-1727-7.

14. Vaněčková M, Seidl Z, Čáp F et al. Návrh bezpečnostní MR monitorace pa­cientů s roztroušenou sklerózou léčených natalizumabem. Cesk Slov Neurol N 2016; 79/ 112(6): 663– 669.

15. Wattjes MP, Steenwijk MD, Stangel M. MRI in the dia­gnosis and monitor­­ing of multiple sclerosis: an update. Clin Neuroradiol 2015; 25 (Suppl 2): 157– 165. doi: 10.1007/ s00062-015-0430-y.

16. Ho PR, Koendgen H, Campbell N et al. Risk of natalizumab-as­sociated progres­sive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol 2017; 16(11): 925– 933. doi: 10.1016/ S1474-4422(17)30282-X.

17. Wattjes MP, Richert ND, Kil­lestein J et al. The chameleon of neuroinflam­mation magnetic resonance pag­­ing characteristics of natalizumab –  as­sociated progres­sive multifocal leukoencephalopathy. Mult Scler 2013; 19(4): 1826– 1840. doi: 10.1177/ 1352458513510224.

18. Tan IL, McArthur JC, Clif­ford DB et al. Im­mune reconstitution inflam­matory syndrome in natalizumab-
-as­sociated PML. Neurology 2011; 77(11): 1061– 1067. doi: 10.1212/ WNL.0b013e31822e55e7.

19. Wattjes MP, Wijburg MT, Ven­negoor A et al. MRI characteristics of early PML-IRIS after natalizumab treatment in patients with MS. J Neurol Neurosurg Psychiatry 2016; 87(8): 879– 884. doi: 10.1136/ jn­np-2015-311411.

20. Štětkářová I, Medová E, Bučilová V et al. Progresivní multifokální leukoencefalopatie u nemocné s roztroušenou sklerózou léčenou natalizumabem. Ces Radiol 2013; 67(1): 577– 583.

21. Vaněčková M, Seidl Z, Krásenský J et al. Naše zkušenosti s MR monitorací pa­cientů s roztroušenou sklerózou v klinické praxi. Cesk Slov Neurol N 2010; 73/ 106(6): 716– 720.

22. Wattjes MP, Ven­negoor A, Steenwijk MD et al. MRI pattern in asymp­tomatic natalizumab-as­sociated PML. J Neurol Neurosurg Psychiatry 2015; 86(7): 793– 798. doi: 10.1136/ jn­np-2014-308630.

23. Clif­ford DB, De Lucca A, Simpson DM et al. Natalizumab-as­sociated progresive multifocal leukoencefalopathy in patiens with multiple sclerosis: les­sons from 28 cases. Lancet Neurol 2010; 9(4): 438– 446. doi: 10.1016/ S1474-4422(10)70028-4.

24. Sahraian MA, Radue EW, Eshaghi A et al. Progres­sive multifocal leukoencephalopathy: a review of the neuroimag­­ing features and dif­ferential dia­gnosis. Eur J Neurol 2012; 19(8): 1060– 1069. doi: 10.1111/ j.1468-1331.2011.03597.x.

25. Blair NF, Brew BJ, Halpern JP. Natalizumab-as­sociated PML identified in the presymp­tomatic phase us­­ing MRI surveil­lance. Neurology 2012; 78(7): 507– 508. doi: 10.1212/ WNL.0b013e318246d6d8.

26. Hodel J, Outteryck O, Dubron C et al. Asymp­tomatic progres­sive multifocal leukoencephalopathy as­sociated with natalizumab: dia­gnostic precision with MR imaging. Radiology 2016; 278(3): 863– 872. doi: 10.1148/ radiol.2015150673.

27. Wijburg MT, Witte BI, Ven­negoor A et al. MRI criteria dif­fetentiat­­ing asymp­tomatic PML from new MS lesions dur­­ing natalizumab pharmacovigilance. J Neurol Neurosurg Psychiatry 2016; 87(10): 1138– 1145. doi: 10.1136/ jn­np-2016-313772.

28. Phan-Ba R, Lom­mers E, Tshibanda L et al. MRI preclinical detection and asymp­tomatic course of a progres­sive multifocal leucoencephalopathy (PML) under natalizumab ther­apy. J Neurol Neurosurg Psychiatry 2012; 83(2): 224– 226. doi: 10.1136/ jn­np-2011-300511.

29. Hodel J, Bapst B, Outteryck O et al. Magnetic resonance imag­­ing changes fol­low­­ing natalizumab discontinuation in multiple sclerosis patients with progres­sive multifocal leukoencephalopathy. Mult Scler 2018: 1352458517750765. doi: 10.1177/ 1352458517750
765.

30. Taieb G, Renard D, Thouvenont E et al. Transient punctate enhanc­­ing lesions precid­­ing natalizumab-
-as­sociated progres­sive multifocal leukoencephalopathy. J Neurol Sci 2014; 346(1– 2): 364– 365. doi: 10.1016/ j.jns.2014.09.007.

31. Mathew RM, Murname M. MRI in PML: bilateral medul­lary lesions. Neurology 2004; 63(12): 2380. doi: 10.1212/ 01.wnl.0000141860.97900.8a.

32. Wijburg MT, van Oosten BW, Murk JL et al. Heterogeneous imag­­ing characteristics of JC virus granule cell neuronopathy (GCN): a case series and review on the literature. J Neurol 2015; 262(1): 65– 73. doi: 10.1007/ s00415-014-7530-5.

33. Eichinger P, Schon S, Pongratz V et al. Accuracy of unenhanced MRI in the detection of new brain lesions in multiple sclerosis. Radiology 2019; 291(2): 429– 435. doi: 10.1148/ radiol.2019181568.

Labels
Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 4

2019 Issue 4

Most read in this issue

This topic is also in:


Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account