Figure 1
Teaching Case
SectionNeuroradiology
Case TypeClinical Cases
AuthorsWeerakkody Y, Kin Kok M (FRACP), Clark P(FRANZCR)
Connected authors
84 years, female
Gradual left sided limb weakness and decline in cognitive status over two weeks. Background chronic lymphocytic leukaemia (CLL) diagnosed four years before. Recent disease progression but with subsequent complete remission following chemotherapy (Fludarabine / Cyclophosphamide). Not leukopenic or on any immunosuppressants on admission.
Progressive multifocal leukoencephalopathy
Atherosclerotic leukoaraiosis (white matter low attenuation)
Infective encephalopathy affecting white matter
Multifocal glial tumour with minimal mass effect
Two intracranial metastases with minimal mass effect
An initial non contrast CT examination (Figure 1) demonstrates two focal areas of sub cortical low attenuation with no mass effect. Despite active multidisciplinary rehabilitation, she continued to decline and became bedridden, dyspraxic and displayed echolalia. A repeat CT examination (Figures 2 and 3) performed approximately three weeks later shows the extent of sub-cortical low attenuation for both regions increasing over the 3 week interval. There was no enhancement or mass effect. A surveillance CT for the chest, abdomen was performed (not shown) to look for any complication of CLL was negative.
Cerebrospinal fluid (CSF) analysis showed lymphocytosis and yielded a positive result for JC virus on PCR, supporting a diagnosis of progressive multifocal leukoencephalopathy.
The patient unfortunately passed away less than 2 months after the onset of symptoms
Background
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the human neurotropic polymyxovirus (JC virus). The term “PML” was coined in 1958 to describe extensive demyelination associated with CLL and Hodgkin’s lymphoma.
It usually results from reactivation of the JC virus during immunosuppression. The JC virus is distributed worldwide and seroconversion occurs in approximately 85% by young adulthood [1-2]. It remains latent and could reactivate in susceptible cases with neuroinvasion targeting oligodendrocytes. Prior to the 1980’s, PML was a rare complication of haematological malignancies or systemic inflammation (e.g. sarcoidosis). Due to the increased prevalence of AIDS, the incidence of PML has increased over the past few decades [3-5]. HIV affected cases currently account for approximately 80% of those with PML. In the recent years, PML has also been associated with increased usage of immunosuppressive drugs and the advent of immunomodulatory therapies (e.g. Natalizumab, Rituximab, Efalizumab) [4].
Imaging perspective
Imaging features are usually best assessed with MRI with many recent imaging publications focusing on this modality [6-9]. However, in the appropriate clinical setting, CT features such as described in this case, could point towards the diagnosis. Asymmetric focal zones of low attenuation that involve the periventricular and sub-cortical white matter have been described as typical findings on CT [10]. Lesions usually do not demonstrate mass effect or contrast enhancement (except with rare cases of immune reconstitution inflammatory syndrome – IRIS) [10-12]. Lesions classically affect the sub-cortical white matter and the parietal lobes are thought to be the most commonly involved [2]. Involvement can occur anywhere where there are oligodendrocytes and due to the greater number of oligodendrocytes supratentorially, involvement here is commoner.
The diagnosis is usually confirmed by the detection of JC virus DNA in CSF [13-14].
Outcome
The usual course of progressive multifocal leukoencephalopathy (PML) is an inexorable deterioration in clinical status and an increase in both the number and size of lesions. A reduction in size of lesions is extremely uncommon and is usually confined to
occasional patients who are on highly active anti retroviral therapy (HAART) for AIDS associated PML [15]. In general, PML is almost always a fatal disease and carries a 3 month mortality in approximately half of affected cases.
The patient unfortunately passed away less than 2 months after the onset of symptoms
Background
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the human neurotropic polymyxovirus (JC virus). The term “PML” was coined in 1958 to describe extensive demyelination associated with CLL and Hodgkin’s lymphoma.
It usually results from reactivation of the JC virus during immunosuppression. The JC virus is distributed worldwide and seroconversion occurs in approximately 85% by young adulthood [1-2]. It remains latent and could reactivate in susceptible cases with neuroinvasion targeting oligodendrocytes. Prior to the 1980’s, PML was a rare complication of haematological malignancies or systemic inflammation (e.g. sarcoidosis). Due to the increased prevalence of AIDS, the incidence of PML has increased over the past few decades [3-5]. HIV affected cases currently account for approximately 80% of those with PML. In the recent years, PML has also been associated with increased usage of immunosuppressive drugs and the advent of immunomodulatory therapies (e.g. Natalizumab, Rituximab, Efalizumab) [4].
Imaging perspective
Imaging features are usually best assessed with MRI with many recent imaging publications focusing on this modality [6-9]. However, in the appropriate clinical setting, CT features such as described in this case, could point towards the diagnosis. Asymmetric focal zones of low attenuation that involve the periventricular and sub-cortical white matter have been described as typical findings on CT [10]. Lesions usually do not demonstrate mass effect or contrast enhancement (except with rare cases of immune reconstitution inflammatory syndrome – IRIS) [10-12]. Lesions classically affect the sub-cortical white matter and the parietal lobes are thought to be the most commonly involved [2]. Involvement can occur anywhere where there are oligodendrocytes and due to the greater number of oligodendrocytes supratentorially, involvement here is commoner.
The diagnosis is usually confirmed by the detection of JC virus DNA in CSF [13-14].
Outcome
The usual course of progressive multifocal leukoencephalopathy (PML) is an inexorable deterioration in clinical status and an increase in both the number and size of lesions. A reduction in size of lesions is extremely uncommon and is usually confined to
occasional patients who are on highly active anti retroviral therapy (HAART) for AIDS associated PML [15]. In general, PML is almost always a fatal disease and carries a 3 month mortality in approximately half of affected cases.
References
[1] Hou J, Major EO. (2000) Progressive multifocal leukoencephalopathy: JC virus induced demyelination in the immune compromised host. J Neurovirol May; 6 Suppl 2:S98-S100 (PMID: 10871795)
[2] Bag AK, Curé JK, Chapman PR, Roberson GH, Shah R. (2010) JC virus infection of the brain. AJNR (American Journal of Neuroradiology) Oct; 31(9):1564-76 (PMID: 20299430)
[3] Berger JR, Major EO (1999) Progressive multifocal leukoencephalopathy. Semin Neurology 19(2): 193- 200 (PMID: 10718540)
[4] Lima MA, Koralnik IJ (2005) New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumab. J Neurovirol 11 Suppl 3:52-7. (PMID: 16540456)
[5] Whiteman ML, Post MJ, Berger JR, Tate LG, Bell MD, Limonte LP (1993) Progressive multifocal leukoencephalopathy in 47 HIV-seropositive patients: neuroimaging with clinical and pathologic correlation. Radiology Apr; 187(1):233-40 (PMID: 8451420)
[6] Buckle C, Castillo M (2010) Use of diffusion-weighted imaging to evaluate the initial response of progressive multifocal leukoencephalopathy to highly active antiretroviral therapy: early experience. AJNR (American Journal of Neuroradiology) 31:1031-5 (PMID: 20360338)
[7] Thurnher MM, Post MJ, Rieger A, Kleibl-Popov C, Loewe C, Schindler E (2001) Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy. AJNR (American Journal of Neuroradiology) 22:977-84 (PMID: 11337345)
[8] Garrels K, Kucharczyk W, Wortzman G, Shandling M. (1996) Progressive multifocal leukoencephalopathy: Clinical and MR response to treatment. AJNR (American Journal of Neuroloradiology) 17:597-600 (PMID: 8881262)
[9] Post MJ, Yiannoutsos C, Simpson D, Booss J, Clifford DB, Cohen B, McArthur JC, Hall CD (1999) Progressive multifocal leukoencephalopathy in AIDS: are there any MR findings useful to patient management and predictive of patient survival? AIDS Clinical Trials Group, 243 Team. AJNR (American Journal of Neuroradiology) Nov-Dec; 20(10):1896-906 (PMID: 10588116)
[10] Smith AB, Smirniotopoulos JG, Rushing EJ (2008) From the archives of the AFIP: central nervous system infections associated with human immunodeficiency virus infection: radiologic-pathologic correlation. Radiographics Nov-Dec; 28(7):2033-58 (PMID: 19001657)
[11] Lima MA, Hanto DW, Curry MP, Wong MT, Dang X, Koralnik IJ (2005) Atypical radiological presentation of progressive multifocal leukoencephalopathy following liver transplantation. J Neurovirol Feb;11(1): 46-50 (PMID: 15804958)
[12] Martinez JV, Mazziotti JV, Efron ED, Bonardo P, Jordan R, Sevlever G, Martinez M, Verbanaz SC, Salazar ZS, Pardal MF, Reisin R (2006) Immune reconstitution inflammatory syndrome associated with PML in AIDS: a treatable disorder. Neurology Nov 14; 67(9):1692-4 (PMID: 17101910)
[13] Küker W, Mader I, Nägele T, Uhl M, Adolph C, Klose U, Herrlinger U (2006) Progressive multifocal leukoencephalopathy: value of diffusion-weighted and contrast-enhanced magnetic resonance imaging for diagnosis and treatment control. Eur J Neurol Aug; 13(8):819-26 (PMID: 16879291)
[14] Shah R, Bag AK, Chapman PR, Curé JK (2010) Imaging manifestations of progressive multifocal leukoencephalopathy. Clinical Radiology Jun; 65(6):431-9 (PMID: 20451009)
[15] Thurnher MM, Thurnher SA, Mühlbauer B (1997) Progressive multifocal leukoencephalopathy in AIDS: initial and follow-up CT and MRI. Neuroradiology 39:611-618 (PMID: 9335057)
Case information
| URL: | https://www.eurorad.org/case/10056 |
| DOI: | 10.1594/EURORAD/CASE.10056 |
| ISSN: | 1563-4086 |
