Eur Radiol (2008) 18: 1526–1528 DOI 10.1007/s00330-007-0788-6
INTERPRETATION CO RNER
Per-Åke Svensson Elna-Marie Larsson
Infratentorial progressive multifocal leucoencephalopathy (PML) in a patient with SLE (2008: 4b)
Received: 7 November 2006 Revised: 4 August 2007 Accepted: 7 September 2007 # European Society of Radiology 2007
E.-M. Larsson (*) Department of Radiology, Aarhus University Hospital/Aalborg Hospital, 9000 Aalborg, Denmark e-mail:
[email protected] Tel.: +45-99-323218 Fax: +45-99-323264
P.-Å. Svensson Department of Diagnostic Radiology, University Hospital, SE-221 85 Lund, Sweden
Abstract Progressive multifocal leucoencephalopathy (PML) is a viral infection occurring in immunocompromised patients. The typical magnetic resonance imaging (MRI) findings include supratentorial asymmetric nonenhancing white matter lesions without mass effect. We present a patient with progressive
Introduction Progressive multifocal leucoencephalopathy (PML) is an opportunistic viral infection affecting patients with impaired cellular immunity [1]. The ultimate diagnosis is based on cerebrospinal fluid (CSF) examination and biopsy, but usually magnetic resonance imaging (MRI) is performed first. The diagnosis may be difficult when the imaging findings are atypical.
Case report A 51-year-old man suffered from systemic lupus erythematosus (SLE) for more than ten years. Over a period of 3 months he developed progressive neurological symptoms, including right-sided hemiparesis, dysarthria, diplopia and tremor of the head. Computed tomography (CT) performed 2 weeks after symptom onset was normal. MRI on the following day showed subtle white matter signal changes without mass effect of nonspecific appearance in the right cerebellar hemisphere on T2-weighted turbo spin echo and FLAIR images with minimal contrast enhancement on T1-
cerebellar and brain stem lesions, emphasizing the fact that the diagnosis of PML should be considered also in cases with selective infratentorial involvement. Keywords Progressive multifocal leucoencephalopathy . Magnetic resonance imaging . Posterior fossa . Immunodeficiency . Diffusionweighted imaging
weighted images (Fig. 1). Diffusion-weighted images (DWI) showed some signal increase without detectable ADC changes. No other intracranial abnormalities were seen. The diagnosis was unclear. Repeat MRI examinations during clinical deterioration showed progression of the cerebellar lesion and additional lesions emerging in the left cerebellar hemisphere and in the brainstem (Figs. 2, 3). DWI showed increased diffusion on the fourth MRI performed 9 weeks after symptom onset (DWI was not included in the other follow-up examinations). The contrast enhancement regressed completely and the signal intensity of the lesion decreased on T1-weighted images (Figs. 2, 3). A surgical biopsy from the cerebellum obtained 14 weeks after symptom onset established the diagnosis of PML. The patient has improved clinically but has residual ataxia and dysarhtria three years after the disease period described above.
Discussion PML is a subacute viral demyelinating disease of the central nervous system caused by a neurotropic papovavirus named JC virus. The infection is probably acquired
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Fig. 1a, b MRI at 1.5 T performed 2 weeks after symptom onset. a T2-weighted image (TR/TE: 4,000 ms/96 ms) shows a subtle lesion with increased signal intensity in the right cerebellar hemisphere. b T1weighted image (TR/TE: 630 ms/17 ms) after intravenous gadolinium-based contrast agent injection shows minimal enhancement
early in life, but remains latent. Interference with the immune system, such as human immunodeficiency virus infection, malignancy or immunosuppressive drugs, may reactivate the virus and lead to the disease [2, 3]. The disease affects predominantly patients who are immunocompromised due to, e.g., AIDS or lymphoid malignancies and patients who have undergone immunosuppressive therapy. The course of the disease is most often rapidly progressive and fatal, but several cases with prolonged survival and even remission have been reported [4]. The most frequently affected regions are the cerebral hemispheres, followed by the cerebellum and brain stem [3]. Selective infratentorial involvement, as in our patient, has only been reported in a small number of cases [5, 6]. MRI is much more sensitive than CT with respect both to early lesion detection and determination of the extent and character of the abnormalities. The typical PML lesions are diffuse and asymmetric, located in the supratentorial white matter and have no contrast enhancement or mass effect. Fig. 2 a Follow-up MRI examination four weeks after symptom onset shows increasing size of the lesion in the right cerebellar hemisphere on T2weighted images. b On post gadolinium T1-weighted images, the contrast enhancement has regressed completely and the signal intensity of the lesion has decreased slightly
Rarely, faint contrast-enhancement can be seen at the periphery of the lesions. T2-weighted MRI demonstrates high signal intensity areas and T1-weighted sequences show low signal intensity areas in the white matter [3, 7]. Involvement of arcuate fibers, i.e., the subcortical U-fibres, is common and creates a sharp border towards the cortex. DWI has been reported to show restricted diffusion especially in the periphery of progressive lesions [7, 8, 9]. High signal on DWI and low ADC probably represents active infection with cell swelling in new lesions and in the advancing edge of large lesions, whereas old lesions and the center of large lesions show reparative gliosis with increased ADC [2]. The latter diffusion pattern was seen at 9 weeks in our case. Diffusion tensor imaging may identify additional areas of demyelination in the normal appearing white matter outside the focal lesions seen on conventional MRI and DWI [10]. Brain biopsy is the only specific test. Our patient had a history of immunosuppressive therapy of his SLE during the last 7 years, which was most likely
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Fig. 3 a Follow-up MRI examination 14 weeks after symptom onset shows further progression of the lesion and a new left-sided lesion on T2weighted images. b On post gadolinium T1-weighted images, the signal intensity of the lesion has decreased further
the predisposing factor. PML in SLE patients treated with immunosuppression is uncommon but has been described previously [9]. Because of the growing population of immunocompromised patients due to, e.g., HIV infection and immuno-
suppressive therapy, the diagnosis of PML should be considered when white matter lesions of unclear aetiology are detected on MRI. It should be emphasized that selective involvement of the cerebellum and the brain stem may occur in PML.
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5. Parr J, Dikran S, Horoupian DS, Winkelman AC (1979) Cerebellar form of progressive multifocal leukoencephalpathy (PML). Can J Neurol Sci 6:123–128 6. Lipton RB, Krupp L, Horoupian D, Hershkovitz S, Arezzo JC, Kurtzberg D (1988) Progressive multifocal leukoencephalopathy of the posterior fossa in an AIDS patient: clinical, radiographic and evoked potential findings. Eur Neurol 28:258–261 7. Mader I, Herrlinger U, Klose U, Schmidt F, Küker W (2003) Progressive multifocal leukoencephalopathy: analysis of lesion development with diffusion-weighted MRI. Neuroradiology 45:717–721
8. Ohta K, Obara K, Sakauchi M, Obara K, Takane H, Yogo Y (2001) Lesion extension detected by diffusionweighted magnetic resonance imaging in progressive multifocal leukoencephalopathy. J Neurol 248:809–811 9. Henderson RD, Smith MG, Mowat P, Read SJ (2002) Progressive multifocal leukoencephalopathy. Neurology 58:1825 10. Huisman TAGM, Boltshauser E, Martin E, Nadal D (2005) Diffusion tensor imaging in progressive multifocal leukoencephalopathy:early predictor for demyelination? AJNR Am J Neuroradiol 26:2153–2156
Precisely correct answer was received by closing date from: Mustafa Kemal Demir, Istanbul, Turkey Annemie Snoeckx, Zandhoven, Belgium Jorge Argimiro López García, Santa Cruz de Tenerife, Spain K. Gopinathan, Chennai, India Shinichi Kan, Kitasato, Japan
Marc Engelhardt, Rotenburg/Wümme, Germany N.B.S. Mani, Miami, USA Tatsuya Yamamoto, Eiheiji-cho, Yoshida-gun, Fukui, Japan Vincenzo Genchi, Bari, Italy
