Journal of the Neurological Sciences 340 (2014) 213–214
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Short communication
Atypical MRI features at early onset natalizumab-associated progressive multifocal leukoencephalopathy: A case report Mirko Piola a,⁎, Franco Di Palma a, Nerina Mascoli a, Sandro Binda b, Marco Arnaboldi a, Monica Rezzonico a a b
Neurology Unit, Department of Medicine, S. Anna Hospital, Como, Italy Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
a r t i c l e
i n f o
Article history: Received 23 October 2013 Received in revised form 17 February 2014 Accepted 27 February 2014 Available online 5 March 2014
a b s t r a c t We report the case of a woman with natalizumab-treated Multiple Sclerosis (MS) that developed progressive multifocal leukoencephalopathy (PML) with atypical MRI features at early onset. This case shows that PML can have variable radiological patterns in natalizumab-treated MS patients thus expanding the possible MRI patterns at onset in these patients. © 2014 Elsevier B.V. All rights reserved.
Keywords: Progressive multifocal leukoencephalopathy Natalizumab MRI
1. Case report A 55-year-old woman with relapsing–remitting Multiple Sclerosis (MS) and no other relevant illnesses was admitted to the emergency department in May 2013 for vertigo, nausea and mood depression. Our patient was diagnosed with MS in April 2000 following second clinical relapse, MRI lesion dissemination and detection of CSF oligoclonal bands at lumbar puncture. From May 2000 to January 2009 she was treated with sub-cutaneous high dose interferon beta1a three times weekly. Because of increasing relapse rate and disability the patient was switched to natalizumab in March 2009. Noteworthy, she was never treated with immune suppressor. In March 2013, patient was on treatment with natalizumab without relapses for 4 years since she started and she had a positive status for anti-JCV antibodies for 2 years. Brain MRI showed no additional lesions since natalizumab was started (Fig. 1A–B–C–D). In April 2013, the neurological examination was stable, showing mild gait ataxia and sporadic urge incontinence, thus the patient had the last natalizumab infusion. Disability was scored 2.5 points at the expanded disability status scale (EDSS). On admission, the neurological examination revealed self-limiting nystagmus without cerebellar involvement while neuropsychological tests showed memory impairment and depression. Disability was scored 3.0 points at EDSS. Brain MRI scans showed T2W hyperintensity
⁎ Corresponding author at: Department of Neurosciences, S. Anna Hospital, Como, Via Ravona, San Fermo della Battaglia 22020, Italy. Tel.: +39 0315859986. E-mail address:
[email protected] (M. Piola).
http://dx.doi.org/10.1016/j.jns.2014.02.037 0022-510X/© 2014 Elsevier B.V. All rights reserved.
in the left insular and parahippocampal cortical gyri (Fig. 1E) with normal diffusion-weighted (DWI) and apparent diffusion coefficient (ADC) imaging sequences (Fig. 1F–H), without contrast enhancement (Fig. 1G). In the suspicion of progressive multifocal leukoencephalopathy (PML), natalizumab infusion was thus discontinued. CSF evaluation revealed normal protein and cell count, as well as normal viral PCR for HSV1, HSV2, VZV, CMV and HIV, while JCV resulted strongly positive (26,633 copies/mL). Since the last natalizumab infusion was 1 month ago and the clinical, neuropsychological and brain MRI pictures were stable, we decided not to treat the patient with plasma exchange (PLEX) in order to avoid the risk of a possible immune reconstitution inflammatory syndrome (IRIS). However, in July 2013, after three months of natalizumab washout, the patient developed severe gait ataxia, disorientation and aphasia and brain MRI showed extensive white matter involvement without contrast enhancement (Fig. 1I–L–M–N). The rapid neurological deterioration after immune reconstitution could suggest an IRIS, however an additional trial with IV corticosteroids was performed without clinical improvement. On this basis, the clinical and MRI pictures supported the diagnosis of PML. The patient finally died in October 2013. 2. Discussion PML is a rare opportunistic viral brain disease occurring in patients treated with natalizumab because of the reactivation of latent JCV infection favoured by immunodepression [1,2]. Our patient presented a high risk to develop PML because she was treated more than 4 years with natalizumab and she had a positive anti-JCV antibodies status [2]. The
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Fig. 1. Magnetic resonance imaging carried out on 1.5 T system using a standard head coil (TR/TE/excitations 540/18 ms/2). Upper panel shows normal axial Fluid-Attenuated Inversion Recovery (FLAIR) (A), diffusion-weighted imaging (DWI) (B), T1 weighted image sequence (C) and apparent diffusion coefficient (ADC) map (D). Middle panel shows: axial FLAIR MRI image with large lesion of left insular and parahippocampal cortical gyrus (E), normal axial DWI (F) and ADC map (H) sequences; axial T1 weighted image showing no contrast enhancement (G). Lower panel shows: extensive white matter involvement of the left temporal lobe in axial FLAIR sequence (I), white matter loss and occipital restriction in axial DWI sequence (L) and ADC map (N); axial T1 weighted image showing no contrast enhancement (M).
typical radiological pattern in early PML is that of large, confluent and subcortical lesions, with low signal on T1W images and a high signal on T2W and DWI images [3]. Noteworthy, DWI has been reported to be always abnormal in natalizumab-associated PML, whereas contrast enhancement was observed from 59 to 76% [3,4]. Our patient showed atypical MRI features at early onset PML: 1) selective involvement of insular lobe and mesio-temporal structures; 2) normal DWI, ADC and T1W images; and 3) no contrast enhancement. The extensive involvement of the mesio-temporal structures supported the initial clinical picture of mood disorder and memory impairment. The stability of EDSS score, neuropsychological tests and MRI picture performed monthly during the first three months suggested an “indolent” course of PML [5], thus we decided not to treat the patient with PLEX judging IRIS as more dangerous than PML progression. Noteworthy, the rapid clinical and radiological worsening occurring after three months of natalizumab last infusion, during immune reconstitution, could suggest an IRIS. However, the poor clinical improvement after corticosteroid treatment and the lack of contrast enhancement supported the diagnosis of PML instead of an IRIS [6,7]. Our case suggests that atypical MRI features, with normality of the DWI and T1 images, could be found at the onset in natalizumabassociated PML, thus expanding the possible MRI patterns at onset in these patients. Prompt recognition of natalizumab-associated PML is advisable in order to reduce high mortality and severe neurologic disability through immediate suspension of natalizumab [8].
Disclosure The authors report no conflict of interest.
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