Table 1 Differential diagnoses of tumefactive demyelinated lesions, malignant glial tumours, progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathy associated with immune reconstitution syndrome

Clinical sy

motor, cognitive (aphasia, apraxia, agnosia, Gerstman, coma) sensitive, cerebellar, brain stem. Visual field defects, Epileptic seizures

epileptic seizures, cognitive and memory deficit, motor, sensitive.

altered mental status (aphasia), motor, limb and gait ataxia, visual symptoms: homonymous hemianopia, cortical blindness, diplopia. Epileptic seizures. No optic nerve and spinal cord involvement.

altered mental status (aphasia), motor, limb and gait ataxia, visual symptoms: hemianopia, cortical blindness, diplopia. Epileptic seizures. No optic nerve and spinal cord involvement

[8–14], [52]

MRI T2w/

FLAIR

Unilateral or bilateral. Frontal, parietal. Periventricular, juxta cortical. 2 cm, large lesion with little mass effect and edema Variable rate of hyper-intensity. Central dilated vessel.

Irregular border. Supra-tentorial WM, partially GM involvement.

Unilateral. Supra-tentorial.

Hyper or hypo intense.

Irregular border. Central necrosis.

Intensive vascular edema and mass effect

Bilateral. Supra-Intra-tentorial. Cortex, deep gray matter. (Frontal, parietal, occipital. Subcortical location, U-fibers, cortex, basal ganglia). 3 cm.

Early new lesions. Hyper-intense. Ill-defined to WM, sharp to GM.

No mass effect. Punctuate perilesional lesions.

Bilateral, spreading. Cortex and subcortical WM. Edema

[11–18], [16, 26, 54]

MRI T1w

Hypo-intense.

CT- hypo-intensity

Hypo-intense. CT-hypo-intensity

Hypo-intense.

CT-hypo intensity

Hypo-intense with hyper- intense rim

[11–18], [26, 54]

MRI Gd +

incomplete rim enhancement

complete rim enhancement

negative or variable, punctuate and rim like

positive or variable, punctate and rim like

[11–18], [26, 54]

MRI - PWI, DWI

decreased PWI in lesions, increased DWI in active demyelination

increased PWI, increased DWI in central necrosis

DWI always hyper-intense, with peripheral rim.

+/− restricted DWI

[9–18, 26]

1H- MRS

increased Cho, lipids, lactate, mildly decreased NAA and NAA/Cr (differ from malignant GT)

elevation of the β,γ-Glx peaks

increased Cho and Cho/Cr, lipids, lactate, decreased NAA, lack of β,γ-Glx elevation

A decrease of NAA/Cr ratio, NAA and Cr. An increase of Lac/Cr, Cho/Cr, Cho, lipids/Cr, mIns, Lac, Lip.

increased Cho, decreased NAA, the presence of Lac/lipids at 1.3 ppm, and the presence of mIns, Higher Cho/Cr, mIns/Cr, Lip1/Cr, and Lip2/Cr in PML-IRIS than PML .

Lower NAA/Cr than PML.

[11], [13, 14], [28,29,30,31]

CSF native

normal or mild increased proteinorhachia and white blood count.

Positive oligoclonal bands, elevated IgG index

GFAP+ cells

mildly increased cellularity, normal proteinorhachia

mild to moderate increase of lymphocytes and protein levels

[10, 11], [14, 15]

CSF JCV DNA

negative, infrequently low positivity (less than 25)

negative? unknown

JCV-specific IgG, DNA copies, infrequently negative

JCV-specific IgG, DNA copies. Sometimes negative

[12–18, 31]

Response to corticoids

very good

only partial

none

good

[2, 9,10,11], [15, 27]

Histology

Hyper-cellularity, myelin protein-laden macrophages, variable lymphocytic inflammation, reactive gliosis and relative axonal preservation.

moderate cellularity, bizarre cells with hyperchromatic nuclei, moderate pleomorphic, gemistocytes, perivascular lymphocytes, rare areas of necrosis, neo-vascularization

GFAP + cells: immature,

reactive, and neoplastic astrocytes and ependymal cells

swelling of oligodendrocyte and multi-lobular astrocytes, basophilic nuclei, eosinophilic inclusion bodies,

2/3 of number of T cells in PML-IRIS.

Positive DNA JCV staining in all types of cells. Active gene copies in high numbers of virally infected cells, as well as a low inflam- matory infiltrate.

Hyper-cellularity, CD8+ positive T cells dominate - their number the same as in active MS lesions, fewer CD4+ and CD20+ T cells in perivascular cuffs.

High plasma and B cells in PML-IRIS-lesions.

No or low number JCV-infected cells.

[2, 10], [15, 17,18,19,20, 49], [41,42,43, 46,47,48],

[54, 55]

Outcome

as typical MS

progressive worsening

progressive worsening

worsening, regression possible

[6, 10–20, 49], [24, 25], [47, 48], [51]

Immunological markers in peripheral blood

upregulation of transcription factors of Th1 (pSTAT1 and T-bet) and Th17 (pSTAT3) in circulating CD4+, CD8 + T-cells and monocytes. CD4+ T-cells with a proinflammatory Th1 and Th17 phenotype,

lower T-bet, pSTAT1, and pSTAT3 in CD4+, CD8 + T-cells, and monocytes. Lower CD4 Th1 and Th17. Increased IL-10, TGF-β, PGE2, down modulation of co-stimulation molecules by APCs. Tumor angiogenesis, expression of CD34+ progenitor cells.

Deficit of NK cells

variable data: stable CD4+ and CD8+, non-significant decrease or increased T cells but unchanged CD4/CD8 ratio. Decrease expression of CD49d, CD29 (VLA-4), CD11a, CD62L, CXCR3 on T cells. Decreased expression of VLA4 on myeloid dendritic cells, decreased count of dendritic cells. Production of CD34+ cells, increase of memory B cells. Increased IL-10.

Increased IFN-γ, IL-12p70, IL-4, IL-10, IL-5, IL-13.

CD4+,T1 + PSTAT3+, CD8+, PSTAT1+,T-bet + .

Decreased CD4+, CD25+ FoxP3+

[36,37,38,39,40,41,42,43,44,45,46,47,48, 56] [54]