Neurologic Aspects of Sjögren's Syndrome An Update
Stewart J. Tepper, MD
Clinical Assistant Professor of Medicine, University of Washington, Department of Medicine, Division of Neurology
Note: The following article is based on Dr. Tepper's presentation at the August SSF Conference in Seattle. Although the frequency of nervous system involvement in SS patients is small, those who have it need good information in order to help, them understand their problems and find good medical care. Hence, this important article.
* Reprinted with
permission of the Sjögren
Syndrome Foundation, Inc.
"The Moisture Seekers" Newsletter. Vol.11 No.11, November 1993 pages 1-6
The information that we have about Sjögren's syndrome involvement of the nervous system is relatively new. It is incomplete, in terms of statistics as to how many people develop neurologic manifestations, how they develop them and what causes each aspect of nervous system involvement. Information is also incomplete in terms of treatment.
The first question that we all want answered is, "how often can nervous system involvement occur in Sjögren's? "We don't really have good studies to tell us. The nervous system may be involved in as many as 20-30% of patients with primary Sjögren's, and involvement can occur in brain, spinal cord and nerves. There may be a slightly higher rate of development of nervous system involvement in patients who have the SS-A antibody (anti-Ro). Having an SS-A antibody present can increase the frequency of involvement of a variety of target organs in Sjögren's.
It appears that neurologic involvement can occur at almost any place in the nervous system. The central nervous system is defined as the brain and spinal cord, and Sjögren's can involve the brain and spinal cord. It can also involve the spinal fluid around the brain and spinal cord, and it can involve the nerves which leave the brain or which leave the spinal cord and go out into the rest of the body.
The cranial nerves are those which leave the brain to go out and serve functions in the skull, and the peripheral nerves go out into the arms and legs and internal organs. Both types of nerves have been described as involved in Sjögren's. We will start at the top and work our way down.
Neurologists always think about anatomy first, when the brain is involved. The top of the brain is where thinking occurs. The lower brain is the automatic portion of the brain or the brain stem, which involves regulating all the autonomic (automatic) functions of the body-breathing and pulse and other automatic functions. Both areas can be involved in Sjögren's.
Within the thinking portion of the brain, both gray and white matter can be involved. The gray matter is the portion of the brain which generates signals, sort of the equivalent of the generating areas in the telephone relay station. The gray matter is where the neuron cell bodies are located. The white matter is the telephone wire, the cables that connect from one area of generating telephone signals to another area of generating signals. So both the wires and the major sections of the brain where thinking is initiated can be affected in Sjögren's.
Now, if thinking can be affected, then behavior can be affected. Psychiatric manifestations can occur in Sjögren's and can be overlooked. A doctor who is not thinking about autoimmune disease might miss behavioral alterations, and even with a known diagnosis of Sjögren's, the doctor might dismiss these as being unrelated to the Sjögren's when, in fact, they may be a manifestation of structural disease. Thus, the psychiatric symptoms may be the effect of the Sjögren's on the brain. Sjögren's patients can have depression, and they can have the opposite of depression and feel a little hyper. They can have anxiety, and they can experience panic attacks. It is interesting to note what has not been described psychiatrically in Sjögren's - the very profound psychiatric disturbances in which patients really can't think properly at all- psychosis, schizophrenia and true manic depressive disorders. These psychotic disorders can occur in lupus but have not been described in Sjögren's. People can get depressed because they have autoimmune disease, and they can get anxious because they have autoimmune disease, so separating out whether something is going on neurologically that can trigger the psychiatric manifestations or whether these are manifestations of the disease itself can be tricky, and testing is necessary to do that.
Patients can also have trouble with cognitive thinking function. This is separated out from behavior, but once again, the gray matter is involved here, as the brain thinking aspects are involved here. When the patient begins to lose, thinking ability, this is referred to as dementia - the neurologic term. A significant cognitive loss can occur, and this can become a very, very serious problem.'
The kinds of cognitive loss which have been described in Sjögren's include diminished attention and concentration; changes in language which neurologists can aphasia; difficulty with 'processing information; disorientation; and trouble with learning and recall.
Headache can occur in Sjögren's, and in a study by Dr. Gibson in London, who looked at thirty-five patients with primary Sjögren's in his Sjögren's clinic, about forty-six percent (46%) met the International Headache Society classification criteria for migraine. It may be that the headaches are a manifestation of the Sjogren's
Visual change can be quite profound in Sjögren's. The most worrisome visual change that occurs is an inflammation around the eye or behind the eye, called optic neuritis or retrobulbar neuritis. This is treatable, but involves the potential for loss of vision and can be seen in a variety of other neurologic conditions. There is a similarity that sometimes bedevils us between multiple sclerosis and Sjögren's involvement in the nervous system, and one aspect that makes that differentiation most difficult is involvement of the eye in optic neuritis.
Patients with Sjögren's can also have muscle weakness, paralysis, or complete loss of motor function, and they can have numbness on one side of the body (which is a hemisensory dysfunction) or numbness all over. These symptoms can be from involvement of sensation areas of the brain.
When the gray matter is irritated enough, patients can develop epilepsy and frank seizures Once again, one can see how development of these neurologic problems might not immediately make Sjögren's leap to mind.
Should neurologic symptoms develop in a patient who has Sjögren's, the doctor obviously should consider an involvement of the disease in the nervous system. Occasionally Sjögren's will be diagnosed because a patient presents with an optic neuritis or a seizure or a cognitive problem or a behavioral problem. A good neurologist thinks about autoimmune disease when these kinds of problems present in anybody.
Next, we'll review the automatic sections of the brain and the lower portion of the, brain (the brain stem and cerebellum), involving a variety of functions. The symptoms that have been, described in Sjögren's include various forms of uncoordination and trouble with walking, various problems with coordinating eye movements, and other kinds of abnormal movements that occur in the, lower portion of the brain. Any automatic function can be affected if the brain stem is involved.
Surrounding the brain and spinal cord is spinal fluid. It turns out that the same kind of outpouring of inflammation cells, white cells like lymphocytes, that can occur in the tissue of people with Sjögren's in the mucous membranes in the mouth, skin, lungs, and kidneys, can also occur in the spinal fluid. This outpouring of lymphocytes and other white cells into the spinal fluid, results in a meningitis A meningitis means that the coverings of the brain and spinal cord are inflamed, generally due to an abnormality within the spinal fluid.
Below the level of the brain, there can be spinal cord involvement. Patients can develop abnormalities in arms and legs, and difficulty with walking, called spasticity. Spasticity means involvement of spinal cord or levels above, affecting motor function of arms or legs. Both the motor and sensory aspects of the patient can be involved, either alone or together, so a patient can simply be numb on one side or just have weakness on one side.
If the spinal cord is involved, there is often bladder involvement and there can also be bowel involvement and other changes of automatic function. Bladder involvement in Sjögren's is often missed. There are a variety of neurologic manifestations of bladder involvement. Sometimes bladder involvement will tip off a doctor that the spinal cord is involved which will then tip off the doctor that there is something else going on. Neurologic bladder involvement can be treated.
Moving out from the brain and spinal cord to the peripheral nerves, remember that peripheral nerves can come out in the skull, called cranial nerves, or they can come out from the spinal cord into the arms or legs. When a nerve is involved, then that particular function may be altered or lost.
Cranial nerves involve eye movements and they can involve muscle function of the face. 'If one half of the face loses its muscle function, this is referred to as Bell's palsy.
Cranial nerve involvement can result in numbness or pain in the face The trigeminal nerve is responsible for facial sensation. A patient can develop "trigeminal neuralgia" which is an inflammation of the Trigeminal nerve.
I have seen a patient who had gradual increasing deafness over a year and a half as the nerves which served her hearing on both sides, were involved by the immune process. Any of the cranial nerves of the head can be involved in Sjögren's.
Peripheral nerves going into arms or legs can also be involved in Sjögren's. This occurred in ten percent (10%) of patients in one large study. Once again, the peripheral nerves are divided into sensation and motor function, and both can be involved, or one or the other.
Muscles can be affected by Sjögren's. Remember, a neurologist is always thinking anatomically, so we think brain, spinal cord, nerves going out to the body, and muscles at the end. And every single area, as one goes out from the brain to the periphery can be involved in Sjögren's, together or singly. The muscles themselves, isolated from the nerves that serve them, can be involved. The nerves can be healthy, but the muscles can be directly inflamed by the process of Sjögren's, causing a myopathy. Symptoms of "myopathy" can include muscle aching and weakness.
1) Vascular Involvement
The causes of the nervous system abnormalities in Sjögren's syndrome can be very serious. Hemorrhages can occur. Blood vessels themselves can become inflamed, called vasculitis. When blood vessels are involved, they can close off, and when they close off, the tissue that they serve dies, which is a stroke. So in Sjögren's syndrome, small strokes can occur, small hemorrhages can occur, blood vessels can become inflamed or abnormal, and can be infiltrated by white cells and lymphocytes. The more severe Sjögren's nervous system involvement is associated with these kinds of changes.
2) Chemical Changes
There is also the possibility that some of the Sjögren's involvement of the nervous system is not due to stroke or vasculitis, but rather related to waxing and waning chemical changes that can occur. There are clinical reasons for thinking that not all Sjögren's involvement in the nervous system involves strokes, hemorrhage, vasculitis, and inflammatory changes in white cells, and I will discuss this below.
Obviously when we see all this long litany of potentially disastrous neurologic problems, we all wish to know the outcome for the patient. Unfortunately, we do not have good data as to what happens with most patients who have neurologic involvement. We do know that although some patients have very serious outcomes in terms of the nervous system involvement, one characteristic of Sjögren's neurologic symptoms is that they are evanescent. This means that the symptoms can be quite fleeting, quite short, even when they are severe. A symptom can be quite prominent and then gone in a day. A symptom can be present on a weekend and gone on the following Monday, and those of us who take care of Sjögren's patients have seen this over and over again.
That represents both good news and bad news. It's good news because a lot of these symptoms just simply go away. It's bad news because it's very difficult to evaluate treatment for the symptoms because they can disappear whether or not the treatment is given, making it tough to tell whether or not the treatment was responsible for the improvement.
Two patients who have weakness or numbness in a limb on a Friday might give two different responses. In one response, the patient sees her doctor, and the rheumatologist or neurologist gives that patient thousands of milligrams of steroids over the weekend, and by Monday the patient looks well.
The other patient does not call the doctor, and by Monday, that patient, too, is fine. Then, at the doctor's visit the next month, the second patient says, "By the way, you know, I had an episode where my right arm went numb and kind of weak and uncoordinated over the weekend a month ago."
Therefore, it becomes difficult to set up studies to determine how to treat patients with evanescent neurologic symptoms. If the symptoms are fleeting, it is also clear we don't understand why they occur. If a symptom is present on Friday and gone on Monday, it can't be a stroke, it can't be a hemorrhage, and it can't be a blood vessel problem or a vasculitis because the symptoms disappeared in a matter of a day or two.
These fleeting symptoms may represent the abnormal functioning of immune chemicals that alter nerve function, and there are a variety of chemicals in the immune system cascade that can interfere with the nerve's ability to fire or function properly. If those chemicals are slightly kicked up over a weekend, the nerves may not function properly, and by Monday, after the inflammatory process has died down a little bit, the nerve functions perfectly well. It's like the nerve was drunk for the weekend.
If these immune chemicals are a cause for some of the evanescent neurologic problems, then it might be possible to target these chemicals and save patients a lot of worry and grief and more toxic treatment. This gives us the hope, then, that the manipulation of these chemicals could reduce the neurologic symptoms and perhaps prevent their becoming permanent.
It is increasingly clear, though, that patients who have vasculitis, stroke, hemorrhage, and anticardiolipin antibody require more significant treatment. We tend to unleash our arsenal to treat very serious, progressive neurologic symptoms to see if we can reverse them and change the course of the disease. We do that with mixed success, so it is important to emphasize the spectrum of neurologic disease.
To summarize, at least seventy-five percent (75%) of patients with primary Sjögren's do not have neurologic symptoms, as best as we can tell. The amount' of patients with primary Sjögren's neurologic involvement is somewhere between twenty and thirty percent (20% and 30%). Ten percent (10%) of the patients with primary Sjögren's have peripheral neuropathy. We don't know how many have central nervous system involvement versus peripheral nervous system involvement. Symptoms can involve an aspect of neurologic function - brain, spinal fluid, spinal cord, peripheral nerves, cranial nerves and muscle. Remember that symptoms can affect behavior and psychiatric function because they are included as brain and neurologic function. Neurologic symptoms can be permanent and can be very incapacitating and require very aggressive treatment or they can be evanescent. Treatments have been therefore, difficult to evaluate, and good studies for the treatment of neurologic Sjögren's have not yet been done.
* The articles identified as originally published in The Moisture Seekers Newsletter, are the only materials contained in this website that have been reviewed by the Sjogren's Syndrome Foundation. The SSF in no way endorses any of the medications or treatments mentioned in these articles. We strongly advise that you check any drugs, treatments or products mentioned with your own healthcare provider.