A Window into the Neuropsychiatry of MS

Patient Expert

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 and16% 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 relationshipswith MRI were between euphoria and hallucinations and moderatelysevere MRI abnormalities. The authors concluded that diversetypes of Neuropsychiatric symptoms are common in MS; symptomsare present between exacerbations; and there are variable correlationswith 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.

Contrast that with apathy or irritability in MS. These problems are often   strong disease related issues but have no definitive explanation. It is true that anyone with a disease can be anxious or depressed because of their illness. It just so happens that MS is a disease where Neuropsychiatric problems are more common than expected. In other words, Neuropsychiatric aspects of MS often occur as some kind of consequence of the disease rather than a simple reaction to it.

In the last column I discussed some Movement Disorders in MS. They can be Neuropsychiatric because such abnormal movements are often noted in patients who have Psychiatric problems. However, unusual movements can exist without any mental instability.   McFarling and Susac way back in 1979 described constant hiccups as a manifestation of MS. Hiccups can reflect a primitive gastrointestinal reflex that is brought on by some kind white matter injury seen in the disease, but there is no "hiccups center" in the brain.   Yawning is also seen in MS. Again, this may be some kind of primordial reflex (it's seen in the 12 week old fetus and persists throughout life, decreasing in the elderly). It's linked with stretching so appears to have something to do with arousal. When excessive yawning is seen in MS or other neurological conditions, it may again be some kind of unmasking of some evolutionary tendency due to poorly understood "disease activity".

Earlier this year, Dr. Maria Aguirregomozcorta et al. from   Hospital Dr Josep Trueta, Girona, Spain described paroxysmal dystonia and pathological laughter as a first manifestation of MS. I mentioned dystonia in the last column as a disturbance in muscle posturing or tone.   Paroxysmal means "a brief attack", so characteristic of symptoms in relapsing and remitting MS. And in this case, the dystonia, occurred with an attack of pathological laughter, i.e. laughter for no reason. In MS the white matter damage can in a general sense explain these problems. One can also see crying for no reason. There are new treatments for the involuntary laughing and crying (part of what are called pseudobulbar problems and IED- Involuntary Emotional Disorder).

Returning to the original Diaz-Olaverrieta article I cited, it would be naïve to believe that this study with its limited patient number (less than 100) and finite number of Neuropsychiatric conditions reviewed is all-inclusive in delving into the world of Neuropsychiatry, movements and stereotyped behaviors in MS.

For example, to give you a broader feel, there is the complicated personality issue of alexithymia seen in MS patients. It is associated with no consistently noted MRI result. Alexithymia is a multidimensional condition linked with difficulty describing feelings and a non-introspective way of thinking. The Sapienza University of Rome team of Bodini et al. in 2007 found the frequent coexistence of alexythymia and fatigue/depression in patients with MS.