The Neuroradiology Journal 27: 322-326, 2014 - doi: 10.15274/NRJ-2014-10040

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Progressive Multifocal Leukoencephalopathy: a Rare Cause of Cerebellar Edema and Atypical Mass Effect A Case Report CHRIS OJEDA1, RACHID ASSINA2, MAUREEN BARRY3, ADA BAISRE4, CHIRAG GANDHI2 Biomedical Engineering, 2 Neurosurgery Department, 3 Radiology Department, 4 Pathology Department, Rutgers New Jersey Medical School; Newark, NJ, USA

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Key words: leukoencephalopathy, progressive multifocal, MRI, mass effect

SUMMARY – Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating disease of the CNS caused by the JC papovavirus (JCV). Demyelination due to oligodendrocyte death leads to multifocal, asymmetric lesions. MRI is a valuable tool for detecting and differentiating PML from other neuropathies. Radiographically, PML classically presents as bilateral, subcortical white matter lesions with a lack of brain atrophy. As the disease progresses, lesions become larger and coalesce to become confluent. Minor edema and mass effect are infrequently described and the presence of significant mass effect suggests an alternative diagnosis. In our case, a patient demonstrated atypical marked infratentorial mass effect. Bilaterally, cerebellar lesions with associated mass effect were observed, as well as effacement of cerebellar folia and partial effacement of the fourth ventricle. The diagnosis of PML was confirmed with a biopsy of the right cerebellar lesion showing classic PML histology, with JCV DNA detection by polymerase chain reaction in the biopsy material.

Introduction Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by infection by the JC papovavirus (JCV). Although more than 70% of the adult population in the United States carries the virus, JCV is an opportunistic infection that primarily affects those with acquired immunodeficiency syndrome (AIDS) undergoing immunosuppressive therapy. PML is characterized by the destruction of infected oligodendrocytes resulting in myelin breakdown and the destruction of white matter 1. PML has a variable clinical presentation depending on the location of the lesion, but most commonly presents with neurological symptoms including cognitive deterioration, apraxia, visual deficits and motor problems that develop over weeks. Pathological findings include focal demyelination with macrophage infiltrates and viral particles in the nuclei of oligodendrocytes 322

with a ground-glass appearance. MRI reveals widespread asymmetric, multifocal areas of hypointensity on T1 and hyperintensity on T2. Mass effect and enhancement are typically absent or mild, whereas marked mass effect suggests an alternative diagnosis 2. In this case, the radiological presentation of PML with atypical infratentorial marked mass effect is described. Case Report A 45-year-old woman with a medical history significant for poorly managed HIV, anemia, and malnutrition presented to the emergency department with a seven-day history of weakness, fatigue and decreased appetite. Physical examination revealed altered mental status, visual deficits, limited range of motion and difficulty with sitting and standing balance. She was alert, oriented only to self, her motor strength was 5/5 throughout her right upper

Chris Ojeda

Progressive Multifocal Leukoencephalopathy: a Rare Cause of Cerebellar Edema and Atypical Mass Effect

and lower extremities, 3/5 and 2/5 on her left upper and lower extremities respectively. Sensation was decreased on her left side. Reflexes were +2 throughout with negative Hoffman and clonus. Hematology workup showed a CD4 count of 14 cells/—l (normal = 300-1400 cells/—l), and lymphocyte count of 95 cells/—l (normal = 1000-3500 cells/—l). A contrast-enhanced MRI revealed an ill-defined T2 hyperintense confluent lesion in the right cerebellar hemisphere with extension to the brainstem (Figure 1). The T2 hyperintense signal extended superiorly to the midbrain and internal capsule and inferiorly throughout the pons (Figures 2). There was associated mass effect with effacement of cerebellar folia and partial effacement of the fourth ventricle. There was also an ill-defined T2 signal in the left cerebellar hemisphere. There was no abnormal enhancement of the lesion. A few millimeters, non-enhancing T2 hyperintense lesions were also noted in the cerebral hemispheres, subcortical and periventricular white matter. Stereotactic needle biopsy of the right cerebellar lesion revealed a well circumscribed area of demyelination containing several foamy macrophages, perivascular lymphocytes, oligodendrocytes with ground-glass enlarged nuclei, large reactive astrocytes some with bizarre appearance in a background with relative preservation of axons (Figure 3). JCV DNA was detected by PCR in formalin-fixed paraffin-embedded tissue from the brain biopsy. Once the diagnosis of PML was established the patient began highly active antiretroviral therapy (HAART) and was given prophylactic antibiotics.

Figure 1 Axial T2 MRI showing large confluent regions in the right cerebellum causing 4th ventricle effacement. Smaller focal lesions are seen in the left cerebellum and pons. Mass effect is seen bilaterally.

Discussion PML is a progressive, opportunistic demyelinating disease of the CNS caused by the JC virus whose prevalence has increased in tandem with the rise in AIDS. Demyelination due to oligodendrocyte death leads to multifocal, asymmetric lesions. PML classically presents as bilateral, subcortical white matter lesions with a lack of brain atrophy. As the disease progresses, lesions become larger, coalesce and become confluent along with the appearance of some brain atrophy 3. Lesions are most commonly observed supratentorially in the parietooccipital and frontal lobes, and involve the periventricular region and centrum semiovale. Most cases demonstrate no or mild ventricular

Figure 2 Axial T2 MRI showing the upper boundary of lesions at the level of the thalamus and posterior internal capsule.

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Progressive Multifocal Leukoencephalopathy: a Rare Cause of Cerebellar Edema and Atypical Mass Effect

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Chris Ojeda

Figure 3 A) Abundant foamy macrophages mixed with enlarged oligodendrocyte nuclei showing a ground-glass appearance. A small vessel is also shown in the center with perivascular mononuclear cell infiltrate. H&E 400×. B) Foamy macrophages, enlarged oligodendrocytes and reactive, bizarre astrocytes. H&E 400×. C) Normal myelinated white matter to the left, contrasts with the pale area showing loss of myelin to the right. LFB-PAS, 100×. D) Several macrophages are highlighted with a CD68 immunohistochemical stain, 200×. E) Relative preservation of axons is noted with a neurofilament immunohistochemical stain, 200×. F) SV40 immunostain showing nuclear reactivity in the infected cells. H&E 400×.

dilation. Infratentorial lesions of the pons, midbrain and middle cerebellar peduncle are seen in addition to supratentorial lesions in many cases 4. On MRI, lesions have a scalloped shape and appear hypointense on T1 and hyperintense on T2 relative to normal white matter. 324

Mass effect and enhancement are uncommon in untreated PML, but temporary enhancement of PML lesions has been reported as a response to HAART. Diffusion-weighted MRI demonstrates a high signal in newer lesions and at the advancing edge of large lesions 5.

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The Neuroradiology Journal 27: 322-326, 2014 - doi: 10.15274/NRJ-2014-10040

Restricted diffusion in older lesions and at the core of large lesions has been observed 3. Atypical presentations of PML have been reported in the literature focusing on lesion distribution, imaging manifestation and as the result of therapy. In a study of 48 HIVpositive patients pretreatment by Post et al., supratentorial and infratentorial lesions were reported in 58.3% of patients, while Berger et al. reported that solely infratentorial lesions are only observed in 20% of cases. Post et al. also reported unilateral white matter lesions in 8.3% of pretreatment patients. Gray matter involvement can be seen in up to 50% of patients but rarely occurs in regions other than the thalamus, basal ganglia, or cortical gray matter 3. Typically, PML lesions do not enhance, but faint peripheral enhancement has been reported 6. While minor edema and mild mass effect are infrequently observed, a marked mass effect has been noted as a differentiating feature suggesting an alternative diagnosis to PML 4,7-9. Focal hemorrhage in PML lesions is rare 3,10. Certain monoclonal antibodies, such as Natalizumab, Efalizumab, and Rituximab, used to treat autoimmune diseases such as multiple sclerosis, have been associated with cases of PML. MRI findings in monoclonal antibody-associated PML are similar to those of classic PML. The two major differences include the presence of destructive cavitary lesions and a significantly higher rate of gadolinium enhancement at diagnosis 11. In our patient, the largest T2 hyperintense lesion burden was atypically located primarily infratentorially with a large associated mass effect. The largest confluent lesion extended from the right cerebellar hemisphere involving the right aspect of the pons extending to the midbrain and internal capsule. A smaller left cerebellar lesion with mass effect was also noted. Both white and gray matter were af-

fected and no abnormal enhancement was observed with gadolinium contrast. Nonspecific areas of T2 hyperintensity in supratentorial white matter were also seen. This abnormal signal, along with mild cerebral volume loss was assumed to represent changes due to HIV encephalopathy. Based on the initial MRI appearance, notably the mass effect and posterior fossa infiltrating lesion, a neoplasm such as primary lymphoma or an infectious process such as toxoplasmosis were suggested. Slight edema and contrast enhancement have occasionally been reported in the initial period after starting HAART as a result of improved immune response. Our patient was not on antiretroviral therapy at or prior to presentation making this post-treatment scenario an unlikely cause of edema and mass effect. Additionally, our patient presented in an immunocompromised state with a CD4 count of 14 cells/—l (normal = 300-1400 cells/—l), and lymphocyte count of 95 cells/—l (normal = 10003500 cells/—l). Diagnosis was confirmed by the morphological findings, including the characteristic triad of: well demarcated foci of demyelination, oligodendrocytes with large, bizarre, hyperchromatic nuclei with a ground-glass appearance. Additionally there was positive SV40 immunostain and JCV DNA was detected on the brain biopsy specimen. Conclusion We present a unique case of an atypical radiographic presentation of PML in an immunocompromised patient showing a cerebellar lesion with a widespread mass effect. The PML diagnosis should be included in the differential workup of posterior fossa infiltrating lesions with mass effect.

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Progressive multifocal leukoencephalopathy: a rare cause of cerebellar edema and atypical mass effect. A case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating disease of the CNS caused by the JC papovavirus (JCV). Demyelinatio...
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