Multiple Sclerosis

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[edit] Multiple Sclerosis

T. Jock Murray

William Pryse-Phillips

Multiple sclerosis (MS) is a recurrent and progressive neurologic disorder characterized by signs and symptoms due to plaques of demyelination in the white matter of the brain, brainstem, and spinal cord of the central nervous system (CNS). Magnetic resonance imaging (MRI) scans demonstrated that there is continuing activity even though the patient is unaware of new symptoms. Although MS is defined as a demyelinating disease, it is the changes in the blood-brain barrier that initiate new lesions, and axonal damage is likely responsible for progression.

[edit] PATHOLOGY

The plaques of demyelination within the CNS are characterized by breakdown of myelin, perivascular edema and inflammation, and later gliosis (scarring). The axons are preserved initially but may be damaged eventually. Although the multifocal involvement suggests a random process, lesions tend to occur in the brainstem and periventricular regions and within the thickly myelinated areas of the brainstem (e.g., medial longitudinal fasciculi). Such lesions may occur suddenly and then apparently heal, perhaps because of remyelination (thin layers of new myelin being formed by oligodendrocytes) and compensation. The remyelinated nerves conduct more slowly, as shown in evoked-potential studies, and are likely to show conduction block with heat. Thus symptoms that have disappeared can reappear with a hot bath or exercise or on a hot, humid day.

[edit] EPIDEMIOLOGY

One case of MS per 500 population probably occurs in temperate climates, where the disease has an incidence rate of about 5 per 100,000, but due to its chronicity, prevalence is high, about 200 per 100,000. MS occurs rarely in children or the elderly; most patients develop their first symptoms between ages 20 and 40, with 30 the average age of onset. The disease is two to three times more common in women.

[edit] Latitudes

The most intriguing finding in the epidemiology of MS is the increasing prevalence at latitudes farthest from the equator, both north and south. Thus it is a rare disease in tropical countries but is a common serious neurologic disorder in the northern United States, Canada, Great Britain, and central Europe. Isolated areas of increased prevalence have been found in New England, the Orkney Islands, Washington State, Nova Scotia, and Alaska.

[edit] Migration Studies

Migration studies have demonstrated that the risk factor in MS is carried along if a person moves from an area of high incidence to one of low incidence. Conversely, if one moves from an area of low incidence to an area of high incidence, one takes on the greater risk of the new country, but this is age related; a critical age of 15 years has been calculated, suggesting that some environmental risk factor for developing MS may be acquired at about the time of puberty. Studies of migration to Israel suggested that the disease has an incubation period of 3 to 23 years.

Many factors have been considered to explain the world distribution of MS, including temperature, solar radiation, local infections, diet, and other environmental factors, but none is convincing. Under consideration is the role of genetic factors, because the concordance rate in identical twins is about 40% but is about 5% for fraternal twins and nontwin siblings. Some suggest that the disease originated in central Europe and that the world distribution corresponds to the areas to which these peoples migrated. Degenerative, vascular, biochemical, infectious, and allergic theories explain MS. Although a viral infection might explain the disease trigger and continuation in a susceptible person, no virus has been isolated consistently, and only weak evidence suggests Epstein-Barr virus (EBV), canine distemper viruses, measles, and herpesvirus type 6. A slow virus with a long incubation period, causing progressive neurologic deficits many years later, would be a plausible explanation, but all transmission experiments have been negative. Different viruses may initiate demyelination in predisposed patients, because it was noted that MS populations have slightly elevated levels of antibody to various viruses compared with control groups. However, this may merely reflect abnormalities in the immune system.

An immunologic reaction in the CNS mediates the neurologic events, as shown by assessment of the cerebrospinal fluid (CSF) and by examination of the plaques. In the CSF the gamma globulin fraction is increased; this appears to be active antibody produced within the CNS, appearing as oligoclonal IgG bands on CSF immunoelectrophoresis.

[edit] Genetics

About 20% of patients with MS have a family history of this disorder, which is strong evidence for genetic influences in MS. A first-degree relative of an MS patient has about a 2% risk of also developing the disease, about 10 times the risk in the normal population. In identical twins the risk is one in three, but still not 100%, so some environmental factor must also be involved. HLA typing in MS patients has shown an overrepresentation of the A3, B7, Dw2, and DR2 haplotypes. A person seems genetically predisposed to the disease; then another factor determines whether they develop the clinical picture of MS.

[edit] Clinical Course

The following categories are usually defined in the course of MS.

[edit] Relapsing-remitting MS.

Patients with relapsing-remitting MS have discrete motor, sensory, cerebellar, or visual attacks that come on over 1 to 2 weeks, resolving in 4 to 8 weeks.

[edit] Relapsing-progressive MS.

Patients with relapsing-progressive MS have attacks but eventually have progression of disability, with or without continuing attacks.

[edit] Progressive-relapsing MS.

Patients with progressive-relapsing MS begin with a slowly progressive course, then have attacks occasionally during their course. Ninety percent of patients with these latter two forms eventually go on to primary progressive MS.

[edit] Primary Progressive MS.

Primary progressive MS is characterized by progressive worsening without periods of stability. The primary form has no initial relapsing-remitting course, as does the secondary form. The primary form has less female preponderance, affects mainly middle-aged males, and involves especially the cervical or thoracic cord. Visual and sensory symptoms are less common. MRI studies show less “activity” and “disease burden,” and more axonal loss. The prognosis is worse. The disorder may differ fundamentally from the usual forms of MS.

[edit] Stable MS.

In stable MS there is no clinical disease activity nor worsening of state in the previous 12 months. When this is obtained for over 10 to 15 years, the term benign MS is sometimes used, even though these patients usually show some progression late in the course of the disease.

[edit] Attacks and Remissions.

By the end of the first 5 years it is usually clear which pattern the patient's disease is following, although it may take much longer to know whether the course will continue to be benign. About 80% of patients begin as relapsing-remitting, but by 5 years, half have become relapsing-progressive. Most frequently an attack occurs without any obvious precipitant, but two factors have been shown to be related to attacks: acute infections and the 6-month postpartum period. Patients often relate an exacerbation of the disease to physical or emotional stress, but little evidence indicates that these are related; this may reflect only the attempt of patients to find some reason for an attack. Although there is a 70% increase in attacks in the 6-months postpartum over a 9-month period without pregnancy, a similar 70% decrease in attacks occurs during the pregnancy itself. Again, most attacks occur without any evident cause, and the mechanism is undoubtedly internal.

The course varies in individual patients. An occasional patient has an acute onset with a rapidly progressive course to disability within a few months (Marburg disease) or years. Most patients have a much more benign course, however, and may remain functioning normally 30 years later. The most common pattern, particularly among those with onset in early adulthood, is acute attacks and remissions that slowly change to a more progressive course. When the onset is in the 40s and 50s or later, a gradual onset with a slow but relentless course, particularly of progressive paraplegia, is characteristic.

It is common for the first attack to be followed by complete remission. As attacks recur, however, more and more deficit is left. Despite this, about 10% of the patients with MS have a benign course. The prognosis is much better than previously thought, and most patients have a normal life span, although usually with disability. About 32% are functioning well at work 10 years after the onset of the disease. At 25 years, 75% of patients were alive in one study, and two thirds of the original group were still able to walk.

[edit] Clinical Features

MS is a condition with a multiplicity of lesions and a variable course, but it is progressive over the long term. A monosymptomatic onset occurs in about 40% of cases, although other sites are affected within the nervous system as time progresses. Initial events that cause difficulty in diagnosis when they occur alone include the appearance of eye pain and visual impairment due to retrobulbar neuritis, vertigo, facial myokymia, facial numbness, extraocular palsy, or facial weakness, resembling Bell's palsy. Internuclear ophthalmoplegia, long tract motor or sensory signs, and Lhermitte's sign are other presentations that may occur entirely alone and recover spontaneously. Later, they are replaced by combinations of symptoms that suggest the diagnosis of MS (Box 171-1).

The scattered plaques of demyelination may affect most nerve fiber pathways in the spinal cord, brainstem, or hemispheres, but the common patterns of deficit result from lesions in the motor and sensory systems, the brainstem nuclei, and the optic nerves. Involvement of the pyramidal tract anywhere along its course results in spasticity with the characteristic findings of hyperreflexia, clonus, loss of abdominal reflexes, and Babinski's signs, eventually developing into progressive limb weakness. Cerebellar involvement typically produces nystagmus, incoordination, dysarthria, and ataxia. Numbness, tight feeling in the limbs, paresthesias, and impaired sensation are common symptoms and at the onset of MS often have a distribution similar to that of peripheral neuropathy, but the reflexes are usually increased. Involvement of the posterior columns is often associated with a Lhermitte's sign, as well as the usual diminution in vibration and joint position sense.

Any of the brainstem nuclei may be involved by the plaques of MS. Thus ocular muscle weakness is common, causing diplopia and mild facial numbness; weakness or fine rippling of the facial muscles (myokymia) may occur. Involvement of the vestibular system results in vertigo, nausea, and unsteadiness. Nystagmus is common, but an ataxic nystagmus is particularly important, greater in the abducting eye and associated with poor adduction of the other eye. This internuclear ophthalmoplegia results from a lesion in the medial longitudinal fasciculus, which coordinates movements of all the oculomotor muscles. This common finding in MS is almost diagnostic in young people, particularly when bilateral. In patients less than 50 years old who complain of pain in the face resembling that of trigeminal neuralgia, MS should always be suspected.

The optic nerves are often involved, resulting in blurring, dimming or loss of vision, and alteration of visual fields. A common problem is acute optic neuritis (retrobulbar neuritis), presenting with pain on eye movement, blurring or loss of vision, altered visual fields, or scotomas. About 4% of patients with MS develop optic neuritis at some time, and 75% of those presenting with optic neuritis develop signs of MS. After one attack of optic neuritis, the patient is examined for evidence of any other neurologic signs and kept under watchful review.

Mental changes may occur but usually only late in the disease. Patients may note subtle problems in learning new information, identifying this as a memory problem, although memory may be normal on testing. Euphoria was once said to be the most common emotional abnormality, but depression is more common. The development of marked emotional changes in a patient with MS should always suggest demyelination involving the periventricular areas and the frontal lobes. After years, neuropsychologic testing may show intellectual changes, but these may be missed on standard tests and only recognized by tests specially designed for MS.

The quality of patients' coping skills and their attitude are very important in determining how well they manage their MS. In all patients, personal characteristics, experiences, and personality strongly affect their response. Not surprisingly, anxiety and depression may occur in these patients. Even numbness of a hand has ominous meaning for the patient. Conversion symptoms may occur and may be difficult to differentiate from another attack of demyelination. A mistaken diagnosis of “hysteria” is often made in these patients because the fleeting signs of MS are not recognized.

Grand mal seizures occur in about 6% of MS patients during the course of the disease. They respond well to the usual anticonvulsants. Patients with bilateral corticospinal lesions may have a spastic bladder, with complaints of urgency, frequency, and incontinence. Such symptoms may be caused by detrusor muscle or sphincter spasticity, dyssynergia of these, or some other change; a full urologic assessment is required to choose appropriate therapy. Impotence occurs in about half the men with MS, usually in association with progressing spasticity. When this first occurs, a strong psychogenic reaction is common.

[edit] LABORATORY TESTS AND DIAGNOSTIC PROCEDURES

MS is a diagnosis made clinically or by autopsy, but some tests support the presence of plaques of demyelination throughout the CNS with accompanying immunologic changes. MRI scans may show scattered lesions in the white matter as a result of inflammation with swelling and subsequent demyelination. The CSF may contain increased gamma globulins, often in an oligoclonal band pattern, indicating immunologic activity. Evoked-potential tests may show slowing of conduction in the optic nerves, the auditory system, or the posterior columns, but these are all nonspecific in that such impaired conduction may also be caused by other conditions. The most definitive diagnostic method is still the clinical assessment, and tests merely support or confirm the diagnosis.

[edit] Cerebrospinal Fluid Findings

Until MRI provided better and noninvasive test results in confirming MS, tests of CSF were sometimes helpful. Cell counts are usually in the normal range, although up to 30% of samples may contain increased lymphocytes. About half the patients show slight elevation of total CSF protein, usually 0.45 to 0.70 gm/L, and again about half have an increase in the CSF IgG; a greater than 13% increase in total CSF protein supports a diagnosis of MS. The test's accuracy is compromised by the need to concentrate the CSF. An improvement in gamma globulin assessment is the technique of oligoclonal banding of the CSF protein, which may be positive in up to 90% of “definite” cases in a laboratory with experience. Unfortunately the “possible MS” cases most require an accurate test, and patients with “possible MS” often have a negative test. The level of myelin basic protein may measure the degree of demyelination activity, but this test is nonspecific and not routinely done.

[edit] Scanning Techniques

MRI is a powerful noninvasive tool assisting in the diagnosis of MS, showing scattered white matter lesions in about 90% of cases of confirmed MS. Few of these lesions are visible even on an enhanced computed tomography (CT) scan. MRI is the best test to confirm a clinical suspicion and is now done routinely (Box 171-2). If the patient is known to have MS, however, MRI is of little value because treatment approaches should not be altered based on whether the scan shows few or many lesions. In clinical trials of the interferons and glatiramer (Copaxone) the MRI has shown that the number of new lesions can be dramatically reduced, but these findings do not correlate well with the patient's clinical condition. Care must be taken in the interpretation of lesions seen in the white matter, since they are not pathognomonic of MS and can be seen in ischemia and other conditions (Box 171-3).

[edit] Evoked-potential Tests

When demyelination lesions remyelinate, with variable gliosis, the new myelin is thinner and conducts impulses more slowly than normal. This slowing can be detected by measuring the time for a stimulus (to the eye, ear, or peripheral nerve) to reach the cerebral cortex. Visual, auditory or brainstem, and somatosensory evoked potentials can indicate the presence of lesions scattered within the CNS in the absence of symptoms, helping clinical diagnosis.

[edit] MANAGEMENT

At present, no specific cure exists for MS. Therapy is directed at the acute attacks, at the underlying disease mechanisms, and at the symptoms of the disease and its complications.

[edit] Acute Attacks

Steroids marginally improve the symptoms and signs of acute attack, as long as the disease is active. No evidence indicates that increased benefits result from continuous therapy, and patients usually develop complications from the steroids if they are used long term, but the steroid-induced sensation of well-being may convince them they are benefiting from the therapy. Such treatment is difficult to stop in these patients, since they feel worse from withdrawal and are then convinced the drug helps. Intrathecal steroids were used in the past, but the effects were transient, and the complication of arachnoiditis led to abandonment of this therapy.

High-dose intravenous methylprednisolone is often used to treat acute attacks of MS. Doses of 500 to 1000 mg intravenously are well tolerated when given over an hour each day for 3 to 5 days (pulsed therapy). Such treatment can be given in an outpatient setting. Cimetidine or ranitidine is also prescribed for a total of 10 days.

[edit] Underlying Disease

Various immunosuppressants have been tried in MS but none has proved to produce appreciable benefit to the patient, and the potential side effects and complications of these drugs are a concern.

Azathioprine suppresses cell-mediated hypersensitivity reactions. A meta-analysis of 22 trials concluded that although it was effective in reducing disease progression, the effect was not statistically significant, although its ability to reduce the relapse rate was significant. The drug has the convenience of easy oral use. Long-term trials have shown no substantial risk of malignancy; this is the concern preventing its wide use in North America, although it is a common drug in Europe. Azathioprine may be used in relapsing-remitting MS if the interferons or Copaxone cannot be given.

Cyclophosphamide is an alkylating agent with cytotoxic and immunosuppressant functions. Its short-term effect is marginal, its side effects are potentially life-threatening, and it may be indicated only in patients with rapidly progressive MS.

Cyclosporine inhibits helper T cells. In one trial there was a statistically significant reduction in disease progression, but the clinical effects were slight. Methotrexate inhibits cell-mediated and humoral immunity. A dose of 7.5 mg weekly by mouth significantly slowed disease progression over 2 years in a small trial of subjects with secondary progressive MS, with minimal adverse effects; another study found it to be ineffective. When effective, cyclosporine helps mainly arm function. Mitoxantrone and cladribine reduce the MRI “lesion burden” but have not been shown to affect disability.

A trial producing almost total immunosuppression with antilymphocytic serum, cyclophosphamide, steroids, and thoracic duct drainage showed that acute attacks may be reduced. The frequency of relapse was reduced in the short term, but efficacy was minimal and side effects serious, so the regimen is not used. Total lymphoid irradiation produces some immediate benefit in rapidly progressing patients, but further studies need to be evaluated before this approach can be recommended. Studies on bone marrow replacement are in progress. Hyperbaric oxygen treatment (widely promoted but very expensive) and plasmapheresis are not helpful.

Interferons have been shown to be beneficial in MS and were the first agents shown to alter the course of the disease. Interferon beta-1a (Avonex, Rebif) reduces the number and severity of attacks and also may modestly alter the progression of the disease. Avonex is given by weekly intramuscular injection and Rebif by subcutaneous injection three times a week. Interferon beta-1b (Betaseron) reduces the number and severity of attacks by 30% and may reduce progression; it is administered by a subcutaneous injection every second day. The reduction of attacks is only by about one third; their severity is reduced by about half, but attacks still occur in many patients. Betaseron should not be expected to improve current problems or stop the disease. Patients should be aware of the reasonable expectations for the treatment, or they will discontinue therapy.

The most troublesome side effects from the interferons are a flu-like reaction soon after the injection and local injection site reactions. The flu-like symptoms can be managed by ibuprofen or acetaminophen, and in most they decrease and disappear within 2 months. Glatiramer (Copaxone) is a designer drug, synthesized to mimic myelin basic protein, which also reduces the number and severity of acute attacks, as well as the progression to some extent. It is injected subcutaneously daily. Glatiramer has fewer side effects than the interferons, although rashes, allergic reactions, and injection site reactions occur. An acute sensation of chest tightness can occur, although this is infrequent, benign, and may not recur if the drug is continued.

Numerous other agents are currently under study, and the future of therapy is promising but a slow process.

[edit] Treatment of Symptoms

[edit] Spasticity.

Spasticity is overall the most disabling problem in MS and is particularly difficult to manage. Many simple muscle relaxants have been used with poor results. Diazepam can reduce spasticity, but the doses required for good effect are so high that drowsiness is a major problem, which makes it impractical. Baclofen is the most effective drug, but it is more useful for treating spasms and pain than for the underlying disability and the functional change induced by spasticity. Thus patients may have relief from spasms, but they do not walk any better. It is best to start with a low dose of baclofen, 5 to 10 mg per day, increasing to a maintenance of 10 mg four times a day. Patients should be warned that they may experience weakness and a “washed- out” feeling at higher doses; they can skip one day and go back to the previous dose if this occurs. Baclofen pumps inserted under the skin allow higher doses to be given directly into the intrathecal space. This is helpful in severe spasticity when the patient is having difficulty staying mobile, but the procedure is complicated and expensive and takes a dedicated staff to monitor the patient, refill the pump, and manage the complications.

Tizanidine (Zanaflex) is a new antispasticity agent that can be used alone (4 mg one to four times daily) or with baclofen. Dantrolene (25 mg daily, slowly increasing to 100 mg four times daily) is sometimes used but has limited utility. The use of cannabis for the treatment of spasticity is controversial; studies have shown that the patients felt better but all measures of their performance, such as balance, mobility, alertness, and concentration, were worse.

[edit] Ataxia.

Another disabling feature of some MS cases is cerebellar ataxia. Ataxia is probably the most disabling feature of MS, since training and effort do not improve the incoordination, imbalance, and gait disturbance. Weighting of the wrists with 250-to 350-mg increases inertia and reduces tremor slightly. A number of agents have been tried, including high doses of INH, β-blockers, glutethimide, neurontin, and primidone, but the results are disappointing and the side effects disturbing.

[edit] Temperature Sensitivity.

Many patients notice that a warm room, a muggy day, sitting in front of a hot fire, or taking a hot bath causes an increase in symptoms. Conversely, treatment with ice packs or submerging in a cool swimming pool sometimes improves symptoms and allows the patient 2 or 3 hours of painless increased mobility and strength, far outlasting the cooling effect of the ice or cold water. The cooling suits available give some relief for the 60% to 80% of MS patients who find this a troublesome symptom. The use of 4-aminopyridine and 3,4-aminopyridine in heat-sensitive patients is growing, although their place in therapy is uncertain; side effects include dizziness and seizures.

[edit] Contractures.

Surgical procedures are done for contractures, spasticity, and deformities. The major thrust has been in reducing spasticity and muscle spasms by various destructive procedures on nerves, roots, and spinal cord or by phenol or alcohol injections into the intrathecal space.

[edit] Incontinence.

Urologic assessment is needed to clarify what type of bladder dysfunction is present when the MS patient begins to complain of frequency, urgency, or incontinence. Mild degrees of upper motor neuron bladder dysfunction may respond to anticholinergic drugs such as oxybutynin (Ditropan) or propantheline (Pro-Banthine). Patients should schedule their fluid intake and activities in relation to bladder function. If necessary with a more significantly spastic bladder with incontinence, a condom drainage system can be used. A catheter should be avoided if possible because of the great dangers of infection, but if a catheter must be used, intermittent catheterization should be tried. The patient should have a high intake of fluid, urine cultures must be performed regularly, and appropriate antibiotics must be used if significant infection develops. In a few cases an indwelling catheter is needed. In the male the penis should be taped to the abdominal wall to avoid a penile-scrotal junction fistula.

[edit] Constipation.

Inactivity predisposes to constipation, and MS patients should be on a high-fiber diet, with regular bran and adequate fluids. When constipation is a problem, other agents may be needed, such as psyllium hydrophilic colloid (Metamucil).

[edit] Sexual Dysfunction.

Impotence is common in males after years with pyramidal involvement from MS. Understanding and support are important. Sensation changes may also alter sexual responses and prevent orgasms in women. Oral sildenafil (Viagra) is likely to become the treatment of choice for impotence. Formerly, injection of papaverine into the penis with a fine needle was useful to produce satisfactory erections and was reasonably well tolerated. Penile implants may produce satisfactory results but are less often needed with the advent of Viagra.

[edit] Pain.

Pain is much more common in MS than thought; symptomatic trigeminal neuralgia, muscle spasms, and dermal hyperesthesias or dysesthesias are examples. Carbamazepine (Tegretol) is effective for trigeminal neuralgia and other lancinating pains in MS, whereas spasms in the back and limbs are often relieved by local cooling, massage, hydrotherapy, and exercise. Limb spasms, trigeminal neuralgia, and other pains also respond to baclofen (Lioresal), clonazepam (Klonopin), and gabapentin (Neurontin), which are useful in patients who cannot tolerate carbamazepine. Tricyclic drugs are also useful in chronic diffuse pain, but transcutaneous electrical stimulation (TENS) was found to be helpful only in those with muscular pains.

[edit] Fatigue.

Fatigue is the most common complaint of MS patients, occurring in 80%, and is their major complaint in 40% of cases. It is an unusual fatigue, consisting of a feeling of inertia as if the subject's mainspring had broken rather than increasing weakness with persisting muscular activity; it can be very severe and disabling. Rest periods and naps may help, but the fatigue often continues despite adequate rest and good sleep. Amantadine (Symmetrel), 100 mg twice a day, helps about half of the patients, dramatically in some. In the long term, many patients develop livedo reticularis, although this is not a serious side effect and clears when the drug is stopped. Pemoline (Cylert), methylphenidate (Ritalin), and fluoxetine (Prozac) have less effect but may be useful.

[edit] Psychologic Problems.

MS patients must be educated about their disease to gain any confidence about their future. Most have many conflicts and problems related to their families, income, and future, many of which can be resolved by a caring physician. Tranquilizers and antidepressants are effective when used in appropriate situations, but they should not be used to replace the personal impact of the physician. Patients often relate acute exacerbations to periods of physical or emotional strain. They cannot avoid all these situations but should recognize the importance of avoiding such stresses when possible; the family should understand this as well. The physician should not overemphasize the need to reduce stress, since the relationship between stress and exacerbation is not that clear. When an attack occurs, it tends to evoke guilt in the patient and family. MS societies are active in North America and in Europe. Community chapters are able to provide information, expertise, companionship, reassurance, social benefits, and health care aids (Box 171-4).

[edit] Diet.

Many diets have been used in MS with various rationales, but none has yet proved to benefit patients permanently. The diet undergoing most careful evaluation at present is low in cholesterol and supplemented by linoleic acid (sunflower seed, evening primrose oil, or corn oil). Linoleate may be an immunosuppressant or may be necessary to maintain the integrity of myelin against immunologic challenge.

[edit] Aids to Improve Function.

The many aids to assist the MS patient overcome problems include prisms for double vision; adapted cutlery; canes and walkers for gait difficulty; braces for foot drops; wheelchairs and electric scooters for mobility in the community; lifts and special beds for bedridden patients; and house, kitchen, and bath adaptions. Occupational therapists are important advisors on how to adapt the environment to cope with handicaps.

[edit] Primary Care Needs

With a chronic illness, the patient, family, and physician tend to focus on the problems of MS as the patient's only health needs. This leads to neglect of the health and wellness needs. Although MS is usually diagnosed and managed by neurologists, the general needs of an MS patient are best managed by a primary care physician. MS patients do not experience more diseases but do experience the same diseases as other people. Patients with chronic disease may receive inadequate management of other conditions. Symptoms possibly caused by other disorders may be dismissed as diverse manifestations of MS.

Self-assessment of health status is encouraged. Women should examine their breasts monthly; if hand dexterity or sensation is a problem, a partner assists. Men also need to perform self-examination of the testicles for any changes or lumps. General health care should include regular general checkups by the physician. Assessment of symptoms and problems, blood pressure assessment, Pap smears, prostate examination, and tests and examinations appropriate for age are indicated. Vision should be checked regularly, and visual effects that can be corrected with lenses should be managed normally. MS visual problems are not corrected by lenses, but the incidence of glaucoma, uveitis, cataract, and other disorders is the same as for other people.

Although most women with MS do not notice a change in their symptoms with their periods, some may notice increased fatigue or numbness or other symptoms just before menses, improving as the period begins. If this is a significant problem, oral contraceptives may alleviate these symptoms. Pregnancy does not aggravate MS. Slight amelioration of symptoms may even occur but the number of attacks increases 6 to 9 months postpartum. An attack is managed as is any attack. Even if no additional problems occur during pregnancy or postpartum, the MS patient experiences all the symptoms of pregnancy with the additional stress of increased fatigue and other MS symptoms. Prenatal and postnatal counseling and support are important to guarantee adequate rest, avoidance of infection, and management of stress. First-time parents need education and advice, and the experienced mother needs additional support. Since MS patients are prone to osteoporosis because of inactivity, hormone replacement therapy (HRT) may be important to reduce symptoms and possible fractures in addition to menopausal symptoms.

MS symptoms can be aggravated by heat in about 80% of patients; this can mistakenly be identified as an attack, even though the symptoms may disappear as soon as the person moves to a cool place. Patients may become so weak after a hot bath that they must lie down to rest; they may even have difficulty climbing from the bath. On a hot, muggy day, MS patients may feel dizzy, weak, and ill. These are not attacks, and patients must be advised about avoiding heat, drinking cold liquids, taking cool showers, and using air conditioning.

Exercise is important for MS patients, but some note increasing symptoms and weakness when their body heat increases. An unusual symptom is increased blurring of vision during exercise, with improvement as the person cools off (Uhthoff's sign). MS patients do well with exercises in a swimming pool because water cools the body during exercise, increasing their exercise tolerance. Patients should learn to cope with the heat problem and exercise as much as possible, with a reasonable balance between the benefits of exercise and the resulting fatigue.

Infections can increase symptoms by increasing body temperature. Patients must be assessed carefully to see if this is a transient episode related to the temperature and symptoms of the infection or a longer-lasting attack that needs treatment with steroids. MS patients are not more prone to infection, except when they develop bladder involvement or when inactivity or being bedridden makes them less resistant to respiratory infections. Viral infections not only make the patient weaker but also may precipitate an attack of MS. Because viral infections do not respond to antibiotics, prevention is the best plan. Vaccinations to prevent influenza are helpful for MS patients and do not pose a significant risk for acute attacks from the injection. Amantadine, an antiviral agent that can prevent influenza, also can help treat the fatigue so common in MS patients. General management of infections includes fluids, acetaminophen, nonsteroidal antiinflammatory drugs (NSAID), and rest until the infection has passed.

Pseudorelapses may occur when the MS patient first begins interferon therapy, when the side effects and aggravation of spasticity may resemble an acute attack. A reduction in dosage, with a gradual increase as the patient adjusts to the drug, usually manages this situation. Some patients may switch to glatiramer if the side effects continue to be intolerable.

[edit] Other Diseases

Other illnesses in MS patients can be divided into three categories: (1) unrelated to MS, (2) complications of MS, and (3) complications of MS treatments. Illnesses can be difficult to identify, especially if the symptoms are similar to MS. Hypothyroidism can cause slowing down, fatigue, weight gain, slowing of thinking, and even neurologic symptoms. Hypertension must be assessed in MS patients as in any patient and treated if blood pressure remains high. The aches and pains of arthritis and fibromyalgia are often attributed only to MS; nonspecific pain occurs in about half of MS patients and requires careful assessment to determine the best treatment. Insomnia is another common problem that can make dealing with other symptoms of MS difficult, especially fatigue.

Bladder infection is a common complication of the neurologic involvement of the bladder. Adequate fluids, cranberry juice, and local hygiene are important in preventing infections, and prophylactic antibiotics may be necessary. Decubiti (pressure sores) can be prevented by good skin care and turning of the patient, with attention to the mattresses, pillows, and chair seats. Pressure palsies develop with pressure on a peripheral nerve, and the sensory loss or weakness can be mistakenly attributed to the MS. Trigeminal neuralgia occurs in a few patients with MS and responds to carbamazepine, baclofen, or local neurosurgical procedures on cranial nerve V. Epilepsy occurs in 5% of MS patients and responds to the usual treatments for seizures.

Many of the treatments for MS also cause drug side effects and complications. Physicians should outline common side effects and complications for patients. Interferons can aggravate symptoms when initiated and can cause allergic responses, as can glatiramer. Steroids can cause cushingoid features if used for weeks or more, which is not recommended. Repeated steroid administration may result in aseptic necrosis of the hip.

Few diseases are associated with MS. Although MS has an immunologic aspect, little evidence indicates an association with other immunologic diseases. With 50,000 MS patients in the United States, many diseases occur due to the natural incidence of these conditions.

Principles of and resources for end of life care are described and extensively referenced in Chapter 164 .

[edit] ADDITIONAL READINGS

• A Compston,et al.: McAlpine's multiple sclerosis ed 3. Edinburgh: Churchill Livingstone; 1998:
• Cook SD Handbook of multiple sclerosis. New York: Marcel Dekker; 1991:
• J Halper, TJ Murray: Primary care needs of multiple sclerosis patients. van den Noort S Holland N Multiple sclerosis in clinical practice. New York: Demos; 1999:
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• DA Redelmeier, SH Tan, GL Booth: The treatment of unrelated disorders in patients with chronic medical disease. N Engl J Med 1998; 338:1516 - 1520.
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