The Lupus Book: A Guide for Patients and Their Families, Third Edition (22 page)

result of steroid therapy, water intoxication with low blood levels of sodium,

seizures, inadequate antidiuretic hormone secretion, central hyperventilation, or antimalarial therapy. Psychosis may, however, be evident without CNS vasculitis.

Psychosis is managed with corticosteroids when active lupus is evident.

I attempt to take a careful history to ascertain the exact use of prescription

drugs, over-the-counter medications, street drugs, and herbal or vitamin remedies in order to assess any possible interactions. Antipsychotic preparations (such

as Thorazine, Haldol, Zyprexa, and Risperdal) are usually used to treat this

syndrome. (The management of steroid-related behavior problems is discussed

in Chapter 27.)

Functional Behavioral Syndromes

Depression and anxiety are present in at least half of all lupus patients as a

consequence of stress, inflammation (which induces a rapid pulse), cytokines

(which may alter mood and behavior), generalized pain (which may result from

fibromyalgia), other sources of nonrestorative sleep because of medication or

steroids, or inadequate coping mechanisms. These behavioral features of lupus

as well as their management are discussed fully in Chapter 25.

OTHER CENTRAL NERVOUS SYSTEM ABNORMALITIES

THAT MAY ACCOMPANY LUPUS

Complications of Medications Used to Treat Lupus

Agents used to treat lupus can cause CNS symptoms that must be distinguished

from what I have described as CNS lupus. The
nonsteroidal anti-inflammatory
drugs
are infrequently the cause of headaches and may induce dizziness. Headache and confusion have been reported by 5 to 15 percent of patients taking

indomethacin, tolmetin, and sulindac; ibuprofen has, on rare occasions, been

associated with aseptic meningitis.

Very high doses of the
antimalarials
(chloroquine, hydroxychloroquine, and quinacrine) have been associated with manic behavior, seizures, and psychosis,

Heady Connections: The Nervous System and Behavioral Changes

[117]

while
corticosteroids
can produce agitation, confusion, mood swings, depression, and psychosis. Certain drugs that treat
hypertension
may cause a loss of sexual desire as well as depression. Nearly every prescription medication can

affect the CNS.

Abnormalities Not Related to Lupus Activity

Michelle had severe active multisystem lupus. Maintained on high doses

of prednisone and monthly intravenous Cytoxan, she still had rashes, fevers,

swelling, pleurisy, and advanced kidney disease. One day, her fevers rose

higher than usual and she began experiencing seizures as well as headaches

and a stiff neck. Her doctors hospitalized Michelle for presumptive CNS

lupus. An MRI of her brain, however, suggested an abscess. Her spinal tap

showed evidence of
Cryptococcus
, which is a fungus not usually seen in

healthy people. She was started on antifungal medication, and Cytoxan was

discontinued to facilitate the medication’s ability to kill the microbes. How-

ever, Michelle still required high doses of steroids.

Infections
of the CNS mimic CNS lupus; they must be carefully considered and ruled out, since lupus patients are especially susceptible to infection. The most common infectious agents include
Mycobacterium tuberculosis, Menin-gococcus, Salmonella, Shigella, Staphylococcus
, and
Streptococcus
. Opportunistic organisms are microbes that cause infection only in immunologically com-

promised individuals, such as those with cancer, patients taking chemotherapy

and high doses of steroids, or those who have AIDS. In these people, unusual

forms of bacteria, viruses, and fungi can be present. Brain imaging and spinal

taps can usually allow doctors to make a definitive diagnosis.

Lupus patients develop
strokes, hypertension, psychiatric disorders, malig-

nancies, aneurysms
, and
Parkinson’s disease
at the same or greater frequency as healthy people. However, an established diagnosis of lupus clues the physician into considering other possibilities in evaluating the CNS.

Autoimmune disorders that affect the CNS include
myasthenia gravis
and
multiple sclerosis
; they have an increased incidence among lupus patients. Myasthenia gravis is characterized by rapid muscle fatigue with repetitive tasks, while multiple sclerosis causes blurred vision, loss of bladder and bowel control, as well as difficulty walking. What may add to the confusion is that one-third

of multiple sclerosis patients have a positive ANA test. Brain imaging and spinal fluid evaluations usually help differentiate multiple sclerosis from systemic lupus.

Table 15.3 summarizes the clinical, laboratory, and therapeutic features of

some of the important CNS syndromes.

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Where and How Can the Body Be Affected by Lupus?

Table 15.3.
Major CNS Syndromes and Their Management

Syndrome

Incidence in Lupus (%)

Treatment

Cerebral vasculitis

10

High-dose intravenous steroids,

immunosuppressives may be

used

Antiphospholipid syndrome

5–10

Platelet inhibitors, anticoagulants

with brain clots

Lupus headache

15

Migraine therapy, steroids

Cognitive dysfunction

50

Antimalarials, psychotropics,

sometimes steroids, emotional

support

Chronic organic brain syndrome

5

Emotional support, seizure pre-

vention if needed

Fibromyalgia

10–20

Nonsteroidals, counseling, anti-

depressants, physical therapy

CNS infection

1

Antibiotics

Cryoglobulinemia or hypervis-

1

Steroids, apheresis, chemother-

cosity

apy, interferon

Bleed due to low platelet

2

Steroids, apheresis, chemother-

counts

apy, factor replacement, trans-

fusion

NEURODIAGNOSTIC TESTING

A neurologic workup includes a lot more than blood tests and x-rays. Many of

the diagnostic techniques used are unique to the CNS. Neurologic testing in

lupus patients is divided into several categories, including blood tests, spinal fluid evaluations, brain imaging, electrical studies, and neuropsychological tests.

Blood Testing

Blood testing is often helpful yet frequently unsatisfactory. It enables physicians to confirm whether lupus is present or active outside the CNS. Inflammation of

the brain’s blood vessels (called cerebral vasculitis) is usually associated with elevated sedimentation rates, low blood complement levels, and high values for

anti-DNA. The presence of antiphospholipid antibodies along with a focal neu-

rologic deficit suggests the antiphospholipid syndrome. Platelet counts should

be checked to rule out sources of bleeding. Blood cultures should be obtained

if fevers are present. On occasion, it may be important to obtain a serum vis-

cosity or cryoglobulin level. Ribosomal P antibody has a weak association with

psychotic behavior and is found mostly in lupus patients. The finding of anti-

bodies to nerve cells in the blood is also weakly linked with active CNS vas-

culitis. (These antibodies are discussed in Chapter 11.)

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[119]

Spinal Fluid Analysis

A spinal tap or lumbar puncture yields cerebrospinal fluid (CSF). If blood testing does not help make the diagnosis, analysis of spinal fluid becomes important.

In CNS vasculitis, spinal fluid often shows a high white cell count, elevated

protein levels, LE (lupus) cells, and low sugar values. If available, high levels of antineuronal antibodies may also be found. An immunologic reaction (but

not necessarily acute CNS vasculitis) is suggested if oligoclonal bands or in-

creased IgG synthesis rates are found. Patients with the antiphospholipid syn-

drome usually have normal spinal fluid. If large numbers of red blood cells are present in all the tubes of spinal fluid obtained, bleeding from the brain’s blood vessels is suggested. Infections yield positive spinal fluid cultures for bacteria or fungi. Viruses are detected by measuring levels of viral antibodies.

Brain Imaging

X-rays of the skull are rarely helpful. Isotopic brain scans were used from 1970-1985. Now
computed tomography (CT) scans
and
magnetic resonance imaging
(MRI)
are used to reveal strokes, tumors, bleeding, and abscesses. The MRI scans are particularly sensitive and reliable in detecting these conditions. Unfortunately, there has been a tendency to misread any scan abnormality in a

patient with known lupus and call it ‘‘vasculitis.’’ Focal lesions, or lesions

limited to a specific area, suggest the antiphospholipid syndrome, whereas gen-

eralized changes are consistent with CNS vasculitis. However, many normal

patients and some individuals with inactive disease have minor MRI abnormal-

ities that are difficult to interpret and mean little.

Efforts to study cerebral dynamics, or how the brain works as opposed to the

strictly anatomic information derived from CT or MRI, have led to the devel-

opment of
PET (positron emission tomography)
and
SPECT (single-positron-emission computed tomography
). PET scanners require a cyclotron and are thus restricted to university medical centers. The major use of such scans (including functional MRI) is to locate the part of the brain that a seizure is coming from and to show areas of decreased blood flow (hypoperfusion), which suggest cognitive dysfunction.

A
cerebral angiogram
, where dye is injected into the blood vessels of the brain, is a risky procedure that is not always positive even in the presence of vasculitis. Noninvasive MR angiography can provide nearly as much information, but is abnormal in only 10 to 20 percent of patients with CNS vasculitis.

Electrical Studies

Electroencephalograms (EEGs)
have been available for decades but are of little help except to identify seizure disorders. Quantitative EEGs and brain mapping

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Where and How Can the Body Be Affected by Lupus?

studies are more precise for localizing the part of the brain that the seizures are coming from. Multiple sclerosis and lupus symptoms can be localized by using

electrical studies with fancy names like
brainstem evoked potentials, visual
evoked responses
, and
auditory evoked response measurements
.

Electromyograms (EMGs)
with nerve conduction velocity testing evaluate peripheral nerve problems. They can differentiate a herniated disc from inflam-

matory nerve or muscle lesions, diabetic numbness, and nerve compressions

such as the carpal tunnel syndrome.

Behavioral Surveys

Several psychological tests have been employed to detect cognitive dysfunction, ranging from the
MMPI (Minnesota Multiphasic Personality Inventory)
to the
Luria-Nebraska test
, the
Halsted-Reitan test
, and the
Wechsler Adult Intelligence
Scale
. Most neuropsychologists have their own battery of tests customized to the nature of their practice. Although no combination of testing has been validated as being more reliable than any other, these evaluations can help physi-

cians identify depression, psychosis, cognitive dysfunction, and neuroses, among other behavioral disorders.

Summing Up

The majority of patients with systemic lupus have neurocognitive problems or

active inflammation that leads to CNS problems. A wide array of possibilities

may account for any given symptom, and a careful workup is necessary in order

to avoid inappropriate therapy. The most common complaints include cognitive

dysfunction, headache, and fatigue. Manifestations of vasculitis, the antiphos-

pholipid syndrome, and altered behavior are not infrequent. Drugs, infections,

and non-lupus-related disorders first have to be ruled out as a cause of the

complaint or manifestation. Blood and spinal fluid testing, brain imaging, electrical studies, and neurocognitive evaluations help the physician arrive at a diagnosis. The treatment of CNS lupus can include a combination of anti-

inflammatory medications, blood thinners, and emotional support.

16

The Head, Neck, and Sjo¨gren’s

Syndrome

If you are a lupus patient, do you find it hard to see clearly? Do your ears ring?

Do you get crops of mouth sores? Do you suck on Lifesavers constantly to

make your mouth less dry? Have you ever lost your voice? The eyes, ears, nose,

mouth, salivary glands, and larynx are occasionally affected by lupus either as a manifestation of active disease, the antiphospholipid antibody syndrome, or

an adverse reaction to lupus medication. Even though they are present in only

a minority of cases, pertinent head and neck symptoms and signs are too im-

portant to be overlooked. This section reviews the head and neck areas and how

problems in these areas are related to lupus.

HOW DOES LUPUS AFFECT THE OUTER EYES?

There’s more to the eye than what we see. Our body’s sight organ is divided

into several layers, all of which can be inflamed with active SLE.
Discoid lesions
resembling the skin condition called eczema are occasionally observed around