In 1999, Diaz-Olaverrieta et al. out of Mexico City published a study on Neuropsychiatric Manifestations of Multiple Sclerosis (MS). This research was highly instructive because it was one of the first to catalogue the range of Neuropsychiatric problems in MS patients including those with only mild complaints or difficulties. It also showed that most of these features did not have an MRI explanation- that is, there was no obvious reason for the Neuropsychiatric conditions based upon where MS lesions were found on MRI.

The authors noted that Neuropsychiatric symptoms were present in 95% of MS patients and 16% of control subjects (those without MS who were evaluated). Changes present were depression symptoms (79%), agitation (40%), anxiety (37%), irritability (35%), apathy (20%), euphoria (13%), disinhibition (inappropriate or outlandish "acting out")  (13%), hallucinations (10%), aberrant motor behavior (abnormal movements) (9%), and delusions (7%). The only relationships with MRI were between euphoria and hallucinations and moderately severe MRI abnormalities. The authors concluded that diverse types of Neuropsychiatric symptoms are common in MS; symptoms are present between exacerbations; and there are variable correlations with MRI abnormalities.

Translation? When a patient with MS has a problem in their mood or behavior, it is not often understandable the way a right-sided weakness or a balance problem is.

This speaks to the complexity of the human brain, not to mention the confounding nature of the human mind. If the brain doesn't show "damage" on MRI, it of course may still have disease. However, spinal cord issues aside, it would be rare to see an MS patient with a paralyzed left arm and left leg who did not have a plaque in the brain to explain it. Obviously, when a patient with MS has no MRI explanation for a mood or behavior problem, there may indeed be no "disease activity" in the region that would reasonably explain said problem. It could be "chemical" without showing up on a scan. It could be "physiological" and not visible on a scan, having to do with transmission of impulses or electrical changes to membranes. It could be "immunological", hovering below the MRI radar screen, having to do with lymphocyte or antibody changes in MS patients' brains. But it also may have something to do with aspects of MS we just don't understand or some kind of "totality of disease" phenomenon that leads to Neuropsychiatric problems.

Why am I telling you all of this you may ask? Oh, just trying to tell you that neuroscience doesn't have all the explanations about MS.

Let's return to the one-sided paralysis analogy. X lesion of the brain causes Y problem to the patient. If you have low insulin, you get Diabetes. If you have the TB bacteria eating your lung, you get a lung cavity due to Tuberculosis. If you have an MS plaque in a left motor region of your brain white matter, you can't move your right side.