Is the disruption of the blood-brain barrier a prerequisite for cellular infiltration in autoimmune encephalitis?

Sir, We read with great interest the recent article by Floris et al. (2004) on the application of iron oxide particles as MR contrast medium in experimental autoimmune encephalitis (EAE). Infiltration of iron-labelled inflammatory cells was visualized in vivo by MRI. Most notably, local iron accumulation was present at an early clinical stage of disease, i.e. day 11. For assessment of the integrity of the blood–brain barrier (BBB), the authors applied gadoliniumDTPA (Gd-DTPA). Significant enhancement was also present beginning at day 11 after immunization. The authors estimated the area of signal loss on T2-weighted images as an indicator of local iron accumulation. Moreover, maps of Gd-DTPA enhancement were calculated in predefined regions of interest based on non-enhanced and contrast-enhanced T1weighted images. The mean percentage signal increase after application of Gd-DTPA was more extensive in certain brain regions (i.e. spinal cord and brainstem) than the percentage of pixels exhibiting a signal loss above 2 SDs of the mean T2 value indicating iron deposition in the area of interest. Therefore, the authors conclude that ‘Gd-DTPA leakage clearly preceded monocyte infiltration as imaged by the contrast agent based on ultra small particles of iron oxide’. It is an important question whether disturbance of the BBB is a prerequisite for subsequent invasion of inflammatory cells, or whether macrophages independently can gain access to the brain parenchyma in autoimmunity of the nervous system. In our view, the data presented by Floris et al. do not sufficiently substantiate the assumption that alterations of the BBB precede cellular infiltration in EAE due to the following reasons.