 Lupus Ontario Working together to conquer lupus |
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Central Nervous System
Lupus Among the many manifestations of lupus, one that has most confounded our attempts at understanding is the involvement of the nervous system. Approximately one half of all patients at some point or other during the course of their illness will develop an overt neurological or psychiatric problem for which no other cause apart from the lupus itself can be found. Problems include seizures (fits), strokes, numbness in one are of the body or another, hallucinations or other bizarre thinking, and movement disturbances (for example, Parkinson-like features). Studies have shown that involvement of the nervous system is closely related to the severity of the lupus and in some studies is connected with a higher mortality rate overall in lupus patients. The problem is deciding when any of these events is due to a cause apart from lupus and when it is the lupus itself which is the cause.. A second problem is distinguishing, among the many manifestations the nervous system can offer, including bizarre behaviour and other non-specific signs such as headaches, mood swings, irritability and difficulty in getting along with one’s spouse, how much the lupus has actually initiated and how much the person is reacting to having a chronic disease such as lupus. For a long time doctors have noted, along with their lupus patients, that there were many things in day-to-day life that led to patients having difficulty coping, which were difficult to explain and were passed off as lupus patients just not handling their disease properly. We now know that it is no as simple as that. The problem is difficult to resolve, since we don’t have one specific diagnostic test (so-called gold standard) for nervous system involvement in lupus. There are many different proposed diagnostic tests and many different classification schemes for the various manifestations in the nervous system and there is no concesnsus, at least until now, on this issue. The main way of diagnosing nervous system involvement is by a clinical description problem such as a seizure in a lupus patient for which there is no other obvious cause; this is taken to mean that the lupus itself is the cause. Difficulties further arise when the patient is on corticosteroids, which itself can cause manifestations such as bizarre behaviour and thus the doctor is left with the dilemma of deciding whether to increase or decrease the steroids to see what will happen. Usually the steroids are not the culprit and it seems as though the lupus itself is somehow responsible for the nervous system manifestation. Various types of X-rays, electrical tests of the brain (EEG) or tests of the blood for autoantibodies until recently have not been able to diagnose this problem with any accuracy. We therefore have begun to systematically study the function of the nervous system in lupus patients, whether or not they have had clinical problems that lupus patients encounter, noting every major or minor problem and deciding arbitrarily whether these will or will not be given the weight of a full-blown flareup in the nervous system. The results of this clinical approach have then been related to results of painstaking, piece by piece investigation of the thinking and other intellectual functions of the brain as measured through psychological tests administered over two to three hours to every patient we have seen. After having studied approximately 150 lupus patients with only one exclusion over a seven year period, we found that many lupus patients have had bona fide problems in their thinking skills and sometimes in their attention, concentration, ability to do designs or recall words or remember sequences or in the emotional spheres, and that these problems cannot be accounted for by just being ill, since other ill patients with other diseases do not appear to have these problems. Many patients whom a clinician would not cite as having a neurological or psychiatric problem nonetheless have deficits on our psychological tests, and this is whether or not we have classified them clinically as having nervous system lupus. We thus have measures of brain function that have not until now been available and mark either unnoticed (subclinical) or early involvement of the nervous system. It is not the distress that lupus patients have over their disease that causes most of these problems. Moreover, benefit could arise to lupus patients if we diagnose their problems early and plan coping or other remedial strategies to deal with their problem whether along or together with their spouse. Assurances can be given as to the gravity of the problem or not, and the problems can be more accurately monitored in response to therapy. We have discussed the psychological approaches we have taken with a number of colleagues and quite a few are intending in one way or another to look at the issue more carefully in their lupus patients. Others have used these types of approaches in patients with a related condition (Sjogren’s syndrome) and have also uncovered a number of problems which up to now have not been discovered clearly. Since we don’t know how the lupus may cause nervous system involvement, another approach by many investigators and ourselves has been to look for a diagnostic test based on what we think lupus does to involved the nervous system. Again here there is no gold standard but a number of possibilities have been proposed: vasculitis or inflammation of the blood vessels of the brain which leads to some of the manifestations, or antibodies to the nerve cells themselves which causes them not to function properly, at least in some patients. Two types of antibodies at least have been proposed, some of which are directed against the nerve cells and some of which may be directed against blood vessels or blood components to cause clotting. It is not clear even to the present time which of these mechanisms ins the correct one. Chances are that different lupus patients have different problems but all could lead to the same manifestations. We have been
investigating antibodies against nerve cells based on observations
many yeas ago now by Bluestein and his colleagues that antibodies
to white blood cells (Lymphocytes) in lupus patients actually
can also attack the brain. It was found by these and other investigators
that these white cell/brain antibodies may be found in the blood
or in the cerebrospinal fluid (i.e. the fluid that bathes the
brain) more often I patients who develop nervous system problems
than in those who do not. However, since everybody was using
a different definition of nervous system lupus, some studies
showed clearcut relationships while others did not and confusion
arose. We therefore began to measure these while blood cell/brain
antibodies in our lupus patients who had been well characterized
with regard to their psychological and thinking functions. We
have found, quite amazingly, that the antibodies to white blood
cells or to brain tissue are found in about one quarter of all
lupus patients with problems in their nervous system as defined
by our psychological tests ("cognitively impaired"
patients). These means that at least in some patients the cognitive
(thinking) problems and other nervous system difficulties, including
"soft" neurological or psychiatric signs such as headaches
and mood swings, may be due to the action of lupus. Thus, the
future holds great promise in the understanding and therefore
the treatment of the so prevalent nervous system manifestations
in lupus. |
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