Table 3:

comparisons of clinical and biological differences between acute and chronic progressive NBD

Category		Acute NBD	Chronic progressive NBD	Reference
Common clinical features		Headache and fever Relapsing and remitting disease attacks Residual permanent damage or disability without disease progression.	Slowly progressive neurological symptoms including dementia, ataxia, confusion, and dysarthria Severe disability and a poor prognosis	[47, 48]
MRI features		Hypointense lesions on T2, FLAIR, and proton density Mesodiencephalic lesions as typical pathologic sign, along with cascade signs extending from the thalamus to the midbrain Other major sites of involvement: pons, medulla, basal ganglia, and internal capsule	Slightly hypertense in proton density and T2 Brain atrophy especially asymmetrical pattern is a typical feature High frequency of abnormality in cerebellum Larger monthly rate of enlargement of the width of the third ventricle (ΔWTVm) and relative value of ΔWTVm to the transverse cerebral diameter (ΔWTVIm)	[1, 47, 49–52]
Therapy		Self-limiting and responding to corticosteroid therapy Mycophenolate mofetil and azathioprine are more valuable	Intractable to empirical immunotherapy (corticosteroid, cyclophosphamide, or azathioprine) Low weekly dose of methotrexate is suggested	[53, 54]
Biomarkers	CSF cell counts	Higher in acute NBD than chronic progressive ones (including PMN cells) Differential diagnosis: Sensitivity: 97.4% Specificity: 97.0%, (cutoff 6.2/mm3) for the diagnosis of acute NBD and non-NBD		[4, 48, 49, 55]
	CSF IL-6	Increased CSF IL-6 was found in both two groups but no difference existed Differential diagnosis: Sensitivity: 86.7 % Specificity: 94.7%, in distinguishing CP NBD and acute NBD at the recovery phase (cutoff 16.55 pg/ml). CSF IL-6 and IL-6 index were dramatically decreased in chronic progressive NBD after infliximab treatment Higher CSF IL-6 related to long-term disease (≥3 years) outcome		[4, 47, 56]
	CSF BAFF	Higher in chronic progressive NBD than acute ones Significantly downregulated after receiving immunosuppressive therapies Correlated with progressive dementia and psychosis		[57]
	Infiltration pattern in brain tissue from NBD	Distinct histopathological feature of chronic progressive NBD: perivascular infiltration of CD68 + monocytes/macrophages throughout the brain		[58]