the following is a blog posting from Medscape which I thought might be of interest.... http://boards.medscape.com/forums/?128@@.2a7aa2c4!comment=1 Samuel Pleasure, MD, Neurology, 03:48PM Jan 26, 2015 Relapsing remitting multiple sclerosis is associated with episodic attacks on the CNS by the immune system where myelin-directed immune injury leads to demyelination, local inflammation and neurologic dysfunction. Patients usually present with a discrete neurologic deficit that persists for weeks to months. The hallmark of the existing treatment approaches is to modulate immune system function so that attacks don't occur as frequently. One of the interesting featurs of the disease that is largely not understood is why attacks occur when and where they do in patients. Why the optic nerve this time and the spinal cord next time? A recent study in the Annals of Neurology (Maggi et al, October 2014) sheds some interesting light on an initial step needed to perhaps someday understand this type of disease tropism. In this study the authors used a primate EAE model, which is highly similar to MS in many ways, and performed repeated imaging with 7T MRI to examine the appearance of lesions over time. Since this model has regular and predictable appearance of lesions that closely resemble MS lesions pathologically, it allows imaging of lesions at the very onset of their appearance before clinical symptoms. Using this approach the authors found that there is major increase in blood brain barrier permeability for about 4 weeks prior to the appearance of a demyelinating lesion. At this same time pathology showed the appearance of perivascular infiltrates and innate immune system (microglial) activation. The take home for this is that for several weeks prior to the appearance of an overt demyelinating lesion that areas that will have an attack are identifiable by transient major increases of vascular permeability. Perhaps therapies directed at this type of increased permeability may yield novel approaches to block acute attacks?