Treatment of multiple sclerosis

There is as yet no cure for multiple sclerosis (MS). Many individuals living with MS do well with no therapy at all, especially since many medications have serious side effects and some carry significant risks.

Medications:

Corticosteroids: The mainstay of treatment for MS is the use of corticosteroids. Corticosteroids, such as prednisone (Deltasone©) and intravenous (IV) methylprednisolone (SoluMedrol©), are frequently used for visual symptoms of MS and have been shown to prolong the onset of MS if used early in its course. Corticosteroids are also used for acute worsening in those people already diagnosed with MS. Corticosteroids are used in high doses and slowly tapered off over several weeks. Side effects may include: heart failure, high blood pressure (hypertension), high blood sugar levels (hyperglycemia), high or low levels of sodium in the blood (hyper- or hyponatremia), increased risk for infection, low level of potassium in the blood (hypokalemia), personality changes (such as mood swings), stomach ulcer, and swelling (edema) caused by fluid retention.

Immune system modulators: Substances called interferons have also been approved to treat MS. Interferons are normally made by the body, mainly to combat viral infections. Interferons have been shown to decrease the worsening or relapse of MS. Unfortunately, the overall disease progression is not changed, and the side effects of interferons are poorly tolerated. Three forms of beta interferon (Avonex©, Betaseron©, and Rebif©) have now been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing-remitting MS. Beta interferon has been shown to reduce the number of exacerbations and may slow the progression of physical disability. When attacks do occur, they tend to be shorter and less severe. Immune system modulators have been reported to reduce exacerbations and physical disability. Side effects include flu-like symptoms (such as malaise, muscle aches, and fever) and inflammation (including pain, redness, and infection) at the injection site.

Glatiramer acetate (Copaxone©) is a drug that modifies actions of the immune system that may affect the progression of MS. Glatiramer acetate has been shown to decrease the relapse rates of MS by 30% and appears to also have an effect on the overall disabling effects of MS. It is given by subcutaneous injection every day and usually is well tolerated. Glatiramer acetate is better tolerated than the interferons and has fewer side effects. Side effects include chest tightness and palpitations (irregular heart beat).

Natalizumab (Tysabri©) is a monoclonal antibody for the treatment of patients with relapsing forms of MS. Natalizumab was withdrawn from the U.S. market in 2004, but in 2006, the FDA re-approved the limited use of natalizumab in the treatment of MS. The safety and efficacy of natalizumab beyond two years are unknown. Natalizumab has caused a confirmed case and one suspected case of progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal demyelinating disease of the central nervous system.

Other medications:

An immunosuppressant treatment normally used in cancer, mitoxantrone (Novantrone©), is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced or chronic MS. Side effects of this medication include extreme fatigue, nausea, and vomiting. During clinical trials, this drug was shown to significantly reduce the frequency of attacks in people with relapsing MS. After receiving FDA approval, however, the drug was withdrawn from the market because of reports from three people who developed a rare, often fatal, brain disorder called progressive multifocal leukoencephalopathy. In 2006, after reconsideration of the drug's benefits for people with multiple sclerosis, the FDA agreed to allow the drug to be marketed again under specific conditions. Mitoxantrone is only used for short term (less than three years). Other medications used for MS that suppress immunity include the chemotherapy drugs methorexate (Rheumatrex©), azathioprine (Imuran©), and cyclophosphamide (Cytoxan©).

Muscle weakness, numbness, and stiffness (spasticity) may be treated using medication taken regularly or as needed. These drugs include muscle relaxants, such as tizanidine (Zanaflex©) and baclofen (LIoresal©), benzodiazepines, such as diazepam (Valium©), and anticonvulsants, such as carbamazepine (Tegretol©). Side effects of baclofen and tizanidine include drowsiness, dizziness, and fatigue. Side effects of benzodiazepines include downiness, fatigue, and a potential for addiction. Anticonvulsants may cause drowsiness, fatigue, and headache.

Fatigue may be treated using amantadine hydrochloride (Symmetrel©), pemoline (Cylert©), or modafinil (Provigil©) when frequent napping, adequate sleep at night, and daily exercise do not help. Side effects include nausea, dizziness, and headache. Immune system improvement and alterations in brain chemistry are the likely mechanism of amantadine's action in MS.

Balance and equilibrium abnormalities (such as difficulty walking, uncoordinated movements, tremor) may be treated using medications such as diazepam (Valium©), clonazepam (Klonopin©), propranolol (Inderal©), and mysoline (Primidone©).

Bladder dysfunction, including incontinence (inability to control bladder emptying) and nocturia (frequent urination at night), may be treated using medications such as oxybutynin (Ditropan©), tolterodine (Detrol©), and hyoscyamine (Levsin©). Bladder-emptying regimens, intermittent catheterization, and surgery may also be used. Side effects of medication include headache, dry mouth, constipation, blurred vision, and dizziness.

Constipation may be worsened by inactivity. Treatment includes eating a high-fiber diet, increasing fluid intake, daily exercise, and stool softeners, such as docusate sodium (Colace©). Rectal suppositories or enemas occasionally may be required.

Sexual dysfunction may occur in men and women with MS. Treatments are available for erectile dysfunction and female sexual dysfunction. Vaginal dryness can be improved by using over-the-counter (OTC) lubricants such as KY Jelly©. Male impotence is treated with drugs for erectile dysfunction, including sildenafil (Viagra©) and tadalafil (Cialis©).

Other treatments:

• Psychotherapy: Central nervous system abnormalities associated with MS and the psychological and social impact of the disorder often results in mood swings and depression. MS support groups, counseling, and/or antidepressants may be helpful. Tricyclic antidepressants, particularly amitriptyline (Elavil©), are effective for the treatment of nerve pain. Side effects of these antidepressants include dry mouth, constipation, blurred vision, and sedation.
• Rehabilitation: Treatment for MS may also include physical therapy, occupational therapy, and speech therapy. Physical therapy uses exercises to help strengthen muscles, reduce pain and spasticity, and improve balance and walking. Assistive devices (such as canes, braces, or walkers) may be used to help individuals remain as independent as possible.
• Occupational therapy: Occupational therapy increases independent function in activities of daily living that focus on grooming, dressing, eating, driving, and handwriting. Adaptations in the work and home environment (such as shower chairs, hand rails, or ramps) are based on individual needs.
• Speech therapy: Speech therapy may be helpful if slurred speech (dysarthria) or difficulty swallowing (dysphagia) develops.
• Caregiver support: Movement disorders confront individuals and their caregivers with many complex problems that must be dealt with for the life of the patient. While it may be emotionally difficult, it is important for patients and caregivers to make informed, carefully considered decisions regarding the future while the patient is capable of making his or her contribution to a planned course of action. Many support groups exist for caregivers of individuals with MS. A doctor or other healthcare professional can help with caregiver support choices.
• Plasma exchange (plasmapheresis): Plasma exchange may help restore neurological function in individuals with sudden severe attacks of MS-related disability who do not respond to high doses of steroid treatment. This procedure involves removing some of the blood and mechanically separating the blood cells from the fluid (plasma). The blood cells then are mixed with a replacement solution, typically albumin, or a synthetic fluid with properties like plasma. The solution with the individual's blood is then returned to their body. Replacing plasma may dilute the activity of the destructive factors in the immune system, including antibodies that attack myelin, and help the individual to recover. Plasma exchange has no proven benefit beyond three months from the onset of the neurological symptoms.

Prognosis:

Most individuals with MS have a relatively normal life span and life expectancy is about 35 years after onset. After 25 years, approximately two-thirds of patients remain mobile. The disorder eventually results in physical limitations in about 70% of patients.

Integrative therapies

Unclear or conflicting scientific evidence:

Bovine colostrum: Colostrum, or bovine (cow) colostrum, is the pre-milk fluid produced by cow mammary glands during the first two to four days after giving birth. Bovine colostrum delivers growth, nutrient, and immune factors to the offspring. Bovine colostrum has been used for multiple sclerosis, although early results do not indicate any benefit. Additional study is needed in this area.

Avoid if allergic to dairy products. Use bovine colostrum cautiously because toxic compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlordiphenyldichloroethylene (DDE), have been found in human colostrum and breast milk. Thus, it is possible that these agents may be found in bovine colostrum. Avoid with, or if at risk of, cancer. Use cautiously with immune system disorders or atherosclerosis (hardening of the arteries). Use cautiously if taking medications, such as anti-diarrheal agents (e.g. Imodium©), insulin, or CNS agents (such as amphetamines, caffeine). Avoid if pregnant or breastfeeding.

Creatine: Creatine is naturally synthesized in the human body from amino acids primarily in the kidney and liver, and transported in the blood for use by muscles. Approximately 95% of the body's total creatine content is located in skeletal muscle. Results from clinical study suggest that creatine supplementation does not improve work production in individuals with multiple sclerosis. Large, well designed studies are needed.

Creatine may increase the risk of adverse effects, including stroke, when used with caffeine and ephedra. In addition, caffeine may reduce the beneficial effects of creatine during intense intermittent exercise. Avoid if allergic to creatine or with diuretics (like hydrochlorothiazide, furosemide (Lasix©)). Use caution in asthma, diabetes, gout, kidney, liver or muscle problems, stroke, or a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding.

Evening primrose oil: Evening primrose (Oenothera biennis) oil (EPO) contains an omega-6 essential fatty acid, gamma-linolenic acid (GLA), which is believed to be the active ingredient. It is theorized that primrose oil may be helpful in patients with multiple sclerosis (MS) based on laboratory studies. Limited evidence is available in humans, and a firm conclusion is not possible at this time.

Avoid with seizure disorders. Use cautiously if taking drugs prescribed for mental illness. Stop use two weeks before surgery with anesthesia. Avoid if pregnant or breastfeeding.

Feldenkrais Method©: Early evidence suggests that steadiness and comfort with daily movements, depression, anxiety, self-esteem, and overall quality of life may improve in patients with multiple sclerosis who use Feldenkrais bodywork or participate in Awareness Through Movement© sessions. More research is necessary. There is currently a lack of available scientific studies or reports of safety of the Feldenkrais Method©.

Ginkgo: Ginkgo (Ginkgo biloba) has been used medicinally for thousands of years. Today, it is one of the top selling herbs in the United States. Based on laboratory study, it has been suggested that ginkgo may provide benefit in multiple sclerosis (MS). Human research is limited to several small studies that have not found consistent benefit. Additional research is needed.

Avoid if allergic or hypersensitive to members of the Ginkgoaceae family. If allergic to mango rind, sumac, poison ivy or oak or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (like aspirin or warfarin (Coumadin©)) due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Do not use ginkgo in supplemental doses if pregnant or breastfeeding.

Magnet therapy: The use of magnets to treat illness has been described historically in many civilizations, and was suggested by ancient Egyptian priests and in the 4th century BC by Hippocrates. The 15th Century Swiss physician and alchemist Paracelsus theorized that magnet fields play an important role in Western medicine, including use for magnetic resonance imaging (MRI), pulsed electromagnetic fields, and experimental magnetic stimulatory techniques. Initial studies of electromagnetic field therapy for multiple sclerosis report varied results, with one trial suggesting improvement in spasticity but not other symptoms, and a different study finding improvement in a combined rating for bladder control, cognitive function, fatigue level, mobility, spasticity, and vision (but no change in overall symptom score). Due to methodological weaknesses of these studies, it remains unclear if electromagnetic field therapy is beneficial in patients with multiple sclerosis.

Avoid with implantable medical devices, such as heart pacemakers, defibrillators, insulin pumps, or hepatic artery infusion pumps. Avoid with myasthenia gravis or bleeding disorders. Avoid if pregnant or breastfeeding. Magnet therapy is not advised as the sole treatment for potentially serious medical conditions, and should not delay the time to diagnose a condition. It should not replace treatment with more proven methods. Patients are advised to discuss magnet therapy with their qualified healthcare providers before starting treatment.

Massage: Initial research reports that massage may improve anxiety, depression, self-esteem, body image, and social functioning in patients with multiple sclerosis. Benefits on the disease process itself have not been well evaluated. Additional research is necessary before a firm conclusion can be drawn.

Avoid with bleeding disorders, low platelet counts, or if on blood-thinning medications (such as heparin or warfarin/Coumadin©). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

Physical therapy: There is currently insufficient evidence for the treatment of multiple sclerosis with physical therapy (PT). Additional research is needed in this area.

Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Both morning stiffness and bone erosion in patients have been reported, although the cause is unclear. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health professional (psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). Its purpose is the exploration of thoughts, feelings and behavior for the purpose of problem solving or achieving higher levels of functioning. Psychotherapy, including group therapy and individual cognitive-behavioral therapy, may reduce major depression in multiple sclerosis patients and improve quality of life. More research is needed to verify these preliminary results.

Psychotherapy is not always sufficient to resolve mental or emotional conditions. Psychiatric medication is sometimes needed. The reluctance to seek and use appropriate medication may contribute to worsening of symptoms or increased risk for poor outcomes. In order to be successful, psychotherapy requires considerable personal motivation and investment in the process. This includes consistent attendance and attention to treatment recommendations provided by the practitioner. Not all therapists are sufficiently qualified to work with all problems. The client or patient should seek referrals from trusted sources and should also inquire of the practitioner's training and background before committing to work with a particular therapist. Some forms of psychotherapy evoke strong emotional feelings and expression. This can be disturbing for people with serious mental illness or some medical conditions.

Reflexology: Reflexology involves the application of manual pressure to specific points or areas of the feet that are believed to correspond to other parts of the body. Reflexology treatment may be beneficial in the management of some motor or sensory symptoms of multiple sclerosis.

Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle, or severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease or the presence of a pacemaker, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, or kidney stones. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.

Vitamin D: Vitamin D is found in numerous dietary sources such as fish, eggs, fortified milk, and cod liver oil. The sun is also a significant contributor to our daily production of vitamin D. Scientists have detected multiple sclerosis rates to be lower in areas with greater sunlight and higher consumption of vitamin D rich fish. Preliminary research suggests that long-term vitamin D supplementation decreases the risk of multiple sclerosis. However, additional research is necessary before a firm conclusion can be reached.

Avoid if allergic or hypersensitive to vitamin D or any of its components. Vitamin D is generally well-tolerated in recommended doses; doses higher than recommended may cause toxic effects. Use cautiously with hyperparathyroidism (overactive thyroid), kidney disease, sarcoidosis, tuberculosis, and histoplasmosis. Vitamin D is safe in pregnant and breastfeeding women when taken in recommended doses.

Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Yoga has been described as "the union of mind, body, and spirit," which addresses physical, mental, intellectual, emotional, and spiritual dimensions towards an overall harmonious state of being. There is limited study of yoga therapy in patients with multiple sclerosis. Further research is needed.

Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, cervical spondylitis, or if at risk for blood clots. Certain yoga breathing techniques should be avoided with heart or lung disease. Use cautiously with a history of psychotic disorders. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction. However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

Strong negative scientific evidence:

Phenylalanine: In clinical study, treatment with Cari Loder's regimen (L-phenylalanine, lofepramine, and intramuscular vitamin B12) did not show benefit for patients with multiple sclerosis. Additional research is needed to confirm these preliminary results.

Use cautiously in patients on a monoamine oxidase inhibitor (MAOI), or with hypertension, anxiety disorders, psychiatric disorders, or sleep disorders. Avoid in patients with Parkinson's disease or tardive dyskinesia. Avoid in patients with hypersensitivity to phenylalanine or with phenylketonuria (PKU).