The Lupus Group of WA

Systemic Lupus And The Nervous System

Daniel J. Wallace, MD FACP FACR, Clinical Professor of Medicine, Cedars Sinai Medical Center/ UCLA School of Medicine, Los Angeles, CA
A reprint from Lupus Foundation of America Article Library 2001

Introduction
Although nervous system involvement in systemic lupus erythematosus ( SLE ) is unclear and controversial, people with lupus do often experience signs associated with the body's nervous system, such as :

headaches
confusion
difficulty with concentration
fatigue
occasional seizures or strokes.

Therefore, this brochure will :

briefly discuss the nervous system and how it may be affected by lupus
categorize the many signs and symptoms associated with nervous system involvement
review the diagnostic work-up
discuss disease management.

The body's nervous system
The nervous system is divided into three parts :

The central nervous system (CNS) consists of the brain and spinal cord.
The peripheral nervous system is comprised of nerve fibers that supply the skin and muscles with the power needed for sensation and movement.
The autonomic nervous system helps to regulate spinal nerves and peripheral nerves, and innervates, or supplies nerves to, the internal organs. Its role in SLE is poorly defined.

How does lupus affect the nervous system ?
The nervous system requires an uninterrupted flow of blood to supply its tissues with oxygen and nutrients necessary for normal functioning. A number of possibilities have been suggested to explain how lupus may cause the many symptoms of nervous system involvement :

Nerve tissue may be damaged when antibodies attack nerve cells or blood vessels.
Nutrients and oxygen are delivered through blood vessels that feed the brain, spinal cord and nerves. If blood flow is slowed or interrupted, the cells of the nervous system are injured, unable to function normally, and symptoms develop.
The symptoms that occur vary depending on the location and extent of the tissue injury.

Signs and symptoms of central nervous system lupus
Central nervous system ( CNS ) vasculitis
CNS vasculitis is inflammation of the blood vessels of the brain. It is the most serious form of systemic lupus. CNS vasculitis is characterized by :

high fevers
seizures
psychosis
meningitis-like stiffness of the neck.

It can rapidly progress to stupor and coma if not aggressively managed. Seizures occur when injured or scarred brain tissue becomes the focus of abnormal electrical discharges.

These seizures may be a one-time occurrence or a persistent problem.
Anti-convulsant medications are used to prevent seizures by controlling the brain's abnormal electrical discharges.

CNS vasculitis usually requires hospitalization and high doses of corticosteroids.

Infection should be ruled out before treatment is initiated.
CNS vasculitis occurs in up to 10 percent of all lupus patients
It is the only form of central nervous system disease that is included in the American College of Rheumatology ( ACR ) criteria for defining SLE.

Cognitive dysfunction
At some point during the course of their lupus, up to 50 percent of lupus patients describe feelings of

confusion,
fatigue,
memory impairment, and
difficulty expressing their thoughts.

This collection of symptoms is called cognitive dysfunction and is found in people with mild to moderately active SLE. These symptoms may be clearly documented by neuropsychological testing, and a newer neurodiagnostic test called the single positron emission computed tomography ( SPECT ) scan shows reproducible blood flow abnormalities.
The reasons for these symptoms are not known. It may have something to do with changes in how a group of chemicals known as cytokines are handled or may be related to certain parts of the brain not getting enough oxygen.
Other tests including :

Spinal taps,
brain wave tests ( EEG ),
magnetic resonance imaging ( MRI ) or
computerized tomography ( CT ) scans of the brain may all be normal.

Cognitive dysfunction may come and go on its own, so the management of cognitive dysfunction is often frustrating and currently no optimal therapy is available.

Antimalarials and/or steroids may be useful.
Counseling, cognitive behavioral therapy and other interventions that assist a person in developing coping skills may be helpful.

Lupus headache
People with lupus experience headaches which are unrelated to their lupus, ie. sinus headache, tension headache and bone spurs from osteoarthritis. Approximately 20 percent of patients with SLE experience severe headaches which are related to the disease and known as lupus headache.

The lupus headache phenomenon is similar to migraine and may be seen more often in people who also have Raynaud's phenomenon.
SPECT scans indicate abnormalities in blood vessel tone or the ability of a vessel to dilate or constrict.
Lupus headache is treated like tension headaches or migraine, although corticosteroids are occasionally useful.

The antiphospholipid syndrome ( APS )
One-third of all people with lupus have a false positive syphilis test, a positive anticardiolipin antibody or a prolonged clotting time test ( PTT ). Collectively these are known as the lupus anticoagulant or the antiphospholipid antibody.
One-third of these patients ( one-ninth of all people with lupus ) will develop blood clots in various parts of the body. These patients have the antiphospholipid syndrome. When a blood clot occurs in the nervous system, it can cause a stroke.

Symptoms of stroke usually include the painless onset of neurologic deficits ( e.g., paralysis on one side of the body, inability to speak ) without any signs of active lupus.
A stroke is managed with blood-thinning medications such as low dose aspirin, coumadin or heparin.

The type of blood vessel involved and the patient's symptoms are considered when determining which medical therapy should be used.

Organic brain syndrome
Patients with a history of stroke or vasculitis experience damage to the brain that is repaired by scar tissue. This results in seizures as well as varying degrees of difficulty with muscular movement, memory, concentration and orientation.

These patients have organic brain syndrome and usually show no evidence of lupus activity in the blood or spinal fluid.
Steroids make the symptoms worse.
Organic brain syndrome is treated with emotional support.

Fibromyalgia ( fibrositis syndrome )
Up to 20 percent of people with SLE have a simultaneous fibromyalgia ( fibrositis ) syndrome manifested by tender points and increased pain in the soft tissues. In addition, patients may experience :

cognitive dysfunction
decreased ability to concentrate
difficulty sleeping
lack of stamina.

This syndrome is treated with

anti-depressants,
counseling and
physical therapy if needed.

People with symptoms of fibrositis who have no physical or laboratory evidence of increased lupus activity should not be given corticosteroids, since this treatment may make them worse.

Central nervous system symptoms due to medication
Medications used to treat SLE can cause side effects that are similar to the symptoms of central nervous system lupus :

Non-steroidal anti-inflammatory drugs ( NSAIDs ) occasionally cause headache, dizziness, and, although rarely, meningitis-like symptoms.
Anti-malarials in very high doses may cause psychosis.
Anti-hypertensive medications may be associated with loss of libido or depression.
Corticosteroids are associated with agitation, confusion, mood swings, psychosis, depression, and in high doses, seizures.
Withdrawal from steroids can lead to : fatigue, aching, weakness, seizures.

The physician must determine what is a side-effect of medication and what is a symptom of CNS lupus.

Uncommon causes of CNS symptoms in SLE

A research study of people with both lupus and Sjogren's syndrome showed these individuals may be inclined to develop vasculitis or cognitive dysfunction.
Certain circulating proteins in the blood can occasionally lead to cryoglobulinemia or hyperviscosity syndrome, where the blood is too thick and slows blood flow to nervous system tissues. These complications are alleviated with plasmapheresis, or filtering of the blood.
Sometimes, marked decreases in platelet counts ( blood components important in blood clotting ) may be associated with bleeding. People with lupus, idiopathic thrombocytopenic purpura ( ITP ) and kidney failure may bleed.
Those with thrombotic thrombocytopenic purpura or who lack Protein S or Protein C may clot.
Occasionally, infections of the central nervous system can be present and mimic lupus.

Signs and symptoms of peripheral nervous system lupus
In peripheral nervous system lupus, a variety of symptoms may occur depending on which nerves are involved.

Involvement of the cranial nerves can cause :
- visual disturbances
- facial pain
- drooping of the eyelid( s )
- ringing in the ear( s )
- dizziness.
Inflammation of the blood vessels supplying the peripheral nerves can lead to symptoms of
- numbness or
- tingling in the arms or legs.
Occasionally, loss of sensation or muscular weakness in the extremities ( e.g., carpal tunnel syndrome in the hands ) can occur.

These symptoms may be due to conditions other than lupus. Electrical studies, such as electromyogram ( EMG ) and nerve conduction tests are usually helpful in determining if symptoms are due to some other cause. For example, a herniated disc or a metabolic abnormality as in diabetes can cause similar nervous system symptoms, but show different electrical study results. Inflammation of the peripheral nerves ( called mononeuritis multiplex ) is treated with corticosteroids.

How your doctor evaluates nervous system symptoms
If you have any nervous system symptoms, it is important for your doctor to know. The cause of your symptoms may be due to a condition other than lupus, or a medication, or a particular aspect of your lifestyle. The proper clinical evaluation will consist of :

an interview with your doctor,
a physical examination, and
a laboratory evaluation, including :
- a blood chemistry panel
- complete blood count ( CBC )
- urinalysis.

Diagnosis is difficult, as there is not one specific diagnostic test to detect nervous system involvement in lupus. However, certain diagnostic tests may be useful in determining nervous system involvement :

Diagnostic blood tests such as :
- sedimentation rate
- ANA
- anti-DNA
- anti-ribosomal P antibodies
- complement.
Neurodiagnostic tests currently available include :
- CT, SPECT and MRI brain scans
- brain waves or electroencephalogram ( EEG )
- spinal taps
- PET scans are only available in a few hospitals.
The spinal fluid may be examined for cells, protein components and antineuronal antibodies.
Neuropsychologic tests may be helpful in patients with cognitive dysfunction.

How your doctor treats nervous system symptoms
As noted above, the treatment of nervous system lupus depends upon its source. If any diagnostic difficulties are evident, a rheumatologist and/or neurologist should be involved in your care.

Treatment may included :
- steroids
- immunosuppressants
- blood thinners
- antibiotics
- anti-convulsants
- anti-depressants
- counseling
- surgery.
Response to treatment may be dramatic, or gradual improvement may occur over several months.
For many people with lupus, nervous system involvement is completely reversible.

Disclaimer :
The Lupus Group of WA ( Inc ) does not recommend or endorse any products, drugs, treatments, procedures, medical or health professional in this article. We suggest you discuss this information with your doctor or specialist.