The incidence of multiple sclerosis is about 60 to 100 out of 100,000. The prevalence seems to rise as one moves farther away from the equator. Multiple sclerosis is most commonly seen in northern latitudes of North America and Europe and remains rare in more tropical environments. Canada is considered high risk area for multiple sclerosis and more than 50,000 Canadians are believed to be afflicted.

Multiple sclerosis is characterized by a multiplicity of presentations and course. At onset, 65 per cent of patients develop a relapsing-remitting form of multiple sclerosis. These patients experience exacerbations which usually develop subacutely and eventually resolve over weeks to months. In 20 per cent of patients, a chronic progressive form starts with the initial symptoms. More often, this form develops over time out of the relapsing-remitting disorder. Multiple sclerosis can be further classified as benign or malignant. About 20 to 35 per cent of patients have a very benign disease with minimal or no disability. At the other extreme, from 3 to 12 per cent have a very malignant condition with severe disability within months to a few years. Most patients have a course somewhere in between, usually with the initial symptoms totally resolving only to relapse with progressive residual disability after each flare and significant neurologic dysfunction developing over a period of several years.

The age of onset for multiple sclerosis can range from 10 to 59 years, with average being 29 to 33 years. Women are stricken more than men by a factor approaching 2:1. Men have a mean age of onset about a year or two later than women and also have a greater tendency to develop the chronic-progressive form of multiple sclerosis. Multiple sclerosis does not directly diminish the life expectancy; however, the development of complications may lead to a shorter than expected life span, with average multiple sclerosis patient living 30 years or more after diagnosis.

Factors associated with poor outcome are:

- late onset of disease (>40 years)

- short interval between the first two relapses

- chronic-progressive form onset

- many different symptoms

- cerebellar or pyramidal signs.

Factors associate with good outcome are:

- younger than 40 years onset

- long interval between first two relapses

- ability to walk

- only one symptom

- onset with optic neuritis

- absence of cerebellar signs

- no residual deficit

There are no definitive diagnostic tests for multiple sclerosis. Especially in the early stages of the disease, the diagnosis can be difficult to verify because of the unpredictable nature of the disease and the lack of more specific lab tests and imaging techniques. Diagnosis is made clinically, based on the occurrence of at least two episodes of neurologic disturbances reflecting distinct sites of damage in the central nervous system that can not be explained by another mechanism. The term "lesions separated in space and time" refers to these neurologic signs. Tests such as cerebral spinal fluid (CSF) evaluations, magnetic resonance imaging (MRI), computerized tomography (CT) scan and evoked potentials may be used in conjunction with the clinical history to help in making the diagnosis.

The Symptomatic Treatment of Multiple Sclerosis.

When treating any disease there are 4 goals in treatment

1) Prevent the disease

2) Cure the patient

3) Restore back to health (no residual effect)

4) Manage the symptoms

With MS we do not know what the cause is, so we are unable to prevent it at this time.

We do not have a cure and we are unable to reverse the damage done. MS remains a chronic progressive disorder.

We do have some medications to manage the symptoms of the disease, and we have been able to reduce the severity of the exacerbations.

More recently there have been some new drugs released which offer hope in reducing the frequency and severity of exacerbations and I will talk about those later.

Acute exacerbations, also called relapses or attacks are thought to be related to inflammatory processes. Severity of each relapse and symptoms vary depending on the area of the central nervous system which is affected.

Adrenocorticotropic hormone (ACTH) or methylprednisolone are the most commonly used drugs in treating acute attacks.

The mechanism of action of these drugs in MS is not known but is thought to be related to reducing the edema in the area of loss of myelin.

Both these drugs have been shown to shorten the duration of an acute attack but do not affect the progression of the disease.

Methylprednisolone is the one I see used almost exclusively. The advantages of using it over ACTH are:

i) shorter infusion time

ii) can be given in pulse therapy (a few days in a row followed by oral prednisone) whereas ACTH is given daily and the dose tapered off over a 4 week period.

iii) ACTH is associated with greater changes to the sodium and potassium balance of the body

Milder attacks can be managed with oral prednisone alone.

Symptoms that MS patients most often complain to me about are:

Pain

Weakness

Spasticity

Fatigue

Bowel symptoms

Bladder symptoms

These symptoms are due to frank loss of myelin in the central nervous system

Pain Management:

The kind of pain usually experienced by MS patients is what we call neuropathic pain. It is caused by neurons misfiring, transmitting extra impulses.

This type of pain will often respond to the same drugs used to control epilepsy.

Epilepsy is similar to MS in that it also involves abnormal nerve discharges.

These anticonvulsant drugs calm down the nerve discharges. They are not sedatives.

The two main drugs are

Phenytoin (Dilantin) and Carbamazepine (Tegretol)

When taken for epilepsy blood tests are required to ensure blood levels are appropriate.

When given for neuropathic pain blood tests are less critical but are done to ensure that blood levels are not toxic.

Phenytoin

HOW TO TAKE THIS MEDICATION:

Take with food or milk if stomach upset occurs.

Capsules should be swallowed whole unless otherwise directed.

The tablets must be chewed thoroughly before swallowing.

The suspension must be shaken well before measuring each dose.

SIDE EFFECTS:

Constipation, dizziness and drowsiness may occur. If these effects continue or worsen, inform your doctor. Unlikely but report blurred vision, unsteadiness, nausea, mood changes or confusion, slurred speech, rash, insomnia or headache. Very unlikely but report vomiting, stomach pain, uncoordinated movements, tingling in hands or feet, fever, yellowing of the eyes or skin, trouble breathing, swollen glands, sore throat or unusual bleeding or bruising. May cause enlargement of the gums. This can be minimized by maintaining good oral hygiene with regular brushing, flossing and massaging of the gums.

PRECAUTIONS:

Tell your doctor if you have any blood disorders (e.g., porphyria), allergies (especially drug allergies) or liver disease. Use caution operating machinery or performing tasks requiring alertness. Limit alcohol use as it may increase the drowsiness effect of this medication. Limit your caffeine usage. Phenytoin is not recommended for use during pregnancy. Consult your doctor before taking this drug. This drug is excreted into human breast milk.Consult your doctor before breast-feeding.

DRUG INTERACTIONS:

Inform your doctor about all the medicine you use (both prescription and nonprescription) especially if you take "blood thinners" (warfarin), cimetidine, omeprazole, sucralfate, disulfiram, oral antifungal medication (azoles), xanthine drugs to treat asthma (theophylline), isoniazid, folic acid, pyrimethamine, sulfa antibiotics, birth control pills, rifampin, trimethoprim, amiodarone, fluoxetine, anticancer drugs, valproic acid or divalproex, estrogens, disopyramide, levodopa (e.g., Sinemet), felodipine, primidone, felbamate, digoxin, metyrapone, dopamine, chloramphenicol, phenylbutazone, quinidine, doxycycline, diazoxide, cyclosporine or corticosteroids (e.g., prednisone, hydrocortisone) as your dose may need to be adjusted.

STORAGE:

Store at room temperature away from moisture and sunlight. Do not store in the bathroom.

Carbamazepine(Tegretol)

HOW TO TAKE THIS MEDICATION:

Take with food to prevent stomach upset.

The CR tablets should be swallowed whole- not crushed or chewed.

SIDE EFFECTS:

May cause drowsiness, dizziness, or blurred vision. Other side effects include stomach upset, loss of appetite, dry mouth, mood changes, changes in vision, muscle aches, and restlessness. These should subside as your body adjusts to the medication. To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use saliva substitute. Notify your doctor if you develop a sore throat, fever, chills, stomach pain, unusual bleeding or bruising, yellowing of the skin or eyes, dark urine, decreased sexual ability, nightmares, hair loss, mouth sores, ringing in the ears. This drug can increase sensitivity to sunlight. Avoid prolonged exposure to the sun. Wear a sunscreen and protective clothing. In the unlikely event you have an allergic reaction to this drug, seek immediate medical attention. Symptoms of an allergic reaction include rash, itching, swelling, dizziness or trouble breathing.

PRECAUTIONS:

Before using this drug tell your doctor your medical history especially of glaucoma, high blood pressure, a history of blood clots, blood disorders; of heart, blood vessel, liver or mental conditions and of any drug allergies. Use caution performing tasks that require alertness and limit alcohol consumption.

Carbamazepine is not recommended for use during pregnancy. Consult your doctor before taking this drug. This drug is excreted into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

DRUG INTERACTIONS:

Tell your doctor of all over-the-counter and prescription medication you may use including other seizure medication, birth control pills, doxycycline, warfarin, danazol, erythromycin-like antibiotics, calcium channel blockers, lithium, haloperidol, certain SSRI antidepressants, nefazodone, cimetidine, propoxyphene and isoniazid. Tell your doctor if you have taken MAO inhibitors (e.g., furazolidone, phenelzine, selegiline, tranylcypromine) within the last two weeks. Be very careful to read all labels on any over-the-counter preparations used to treat cough and colds, allergies or sleeplessness. Carbamazepine may decrease the effectiveness of birth-control pills; use another method of birth control.

NOTES:

It is recommended that you wear or carry identification indicating you are using this drug. Do not share this medication with others.This drug may interfere with certain pregnancy tests.

MISSED DOSE:

If you miss a dose, take as soon as remembered; do not take if it is almost time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up"the dose to catch up. Call your doctor if you miss more than one dose daily.

STORAGE:

Store at room temperature between 59 and 86 degrees F (between 15 and 30 degrees C) away from moisture and sunlight. Do not store in the bathroom. Do not freeze liquid forms of this medication.

If Phenytoin and Carbamazepine are ineffective we now have newer anticonvulsants that may be tried.

Gabapentin (Neurontin)

Sometimes the antidepressant Amitriptyline (Elavil) may be effective. It modulates pain response. But it can be quite sedating or make you drowsy. Therefore it is used mainly at night. The dose used is much lower than when it is used as an antidepressant.

Weakness and Fatigue

These are probably the most common and most disabling symptoms of MS, at least early in the course of the disease.

These symptoms are probably best managed with energy conservation.

It is important to schedule rest periods throughout the day.

Getting a restful sleep at night will help.

Good physical fitness improves fatigue. Keeping close to your ideal weight will help.

Also being well hydrated is important. Water and salt depletion increase fatigue.

Keep cool. We know that being over-heated aggravates these symptoms.

Eating large meals can make you fatigued.

Eating a lot of carbohydrates can make you fatigued.

Stress level plays a roll as well. Try to reduce the stress level.

Some drugs have been tried to reduce fatigue.

Amantadine, an antiviral drug , has been the most successful but the reduction in fatigue has only been modest.

Amantadaine

HOW TO TAKE THIS MEDICATION:

This medication is best taken on an empty stomach, but may be taken with food or milk if stomach upset occurs. This medication works best when the amount of medicine in your body is kept at a constant level. Do this by taking the medication at evenly spaced intervals throughout the day and night. Tolerance may develop following long term use.

SIDE EFFECTS:

This medication may cause stomach upset, nausea, loss of appetite, constipation, headache, dizziness, anxiety, confusion or purplish-red blotchy spots on the skin during the first few days as your body adjusts to the medication. If these symptoms persist of become severe, inform your doctor. Because this medication may cause blurred vision or dizziness, use caution when driving or operating machinery while taking this medication. Notify your doctor if you develop slurred speech, shortness of breath, swelling of the arms or legs, vision disturbances, difficulty urinating, skin rash, or mood changes while taking this medication.

PRECAUTIONS:

Amantadine should be used during pregnancy only if clearly needed. Since small amounts of the drug do appear in breast milk, consult with your doctor before breast-feeding. Alcohol should be avoided since it can increase unwanted side effects of drowsiness and lightheadedness.

DRUG INTERACTIONS:

Before taking amantadine, tell your doctor what medicines you are taking, especially if you are taking other drugs to treat Parkinson's disease or other stimulants (like decongestants which are commonly found in cough and cold products) as your dose may need to be altered.

MISSED DOSE:

If you miss a dose, take as soon as remembered; do not take if it is almost time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up.

Pemoline (Cylert) is another drug that has been tried. It is a stimulant drug.

The advantages over Ritalin and Dexedrine is that it is not a narcotic and does not require the

triplicate prescription form.

HOW TO TAKE THIS MEDICATION:

Take this medication in the morning as directed. This may be taken with food if stomach upset occurs. Do not increase the dose or takethis more often than directed without first consulting your doctor.

SIDE EFFECTS:

Stomach upset, loss of appetite, weight loss, sleeplessness, headache, dizziness or irritability may occur the first few days as your body adjusts to the medication. Inform your doctor if any of these effects persist or worsen. Promptly notify your doctor if you experience uncontrollable movements of the face, tongue, lips or eyes; seizures, hallucinations, skin rash, yellowing of the eyes or skin, fever, stomach/abdominal pain or unusual fatigue. Long-term use of this medication may hinder growth. Discuss this with your doctor.

PRECAUTIONS:

Tell your doctor if you have any liver disease, kidney disease or if you have any allergies. Use caution performing tasks requiring alertness. This medication should be used only if clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known if this medication is found in breast milk.Consult your doctor before breast-feeding.

DRUG INTERACTIONS:

Tell your doctor of any over-the-counter or prescription medication you may take.

NOTES:

It may take 3 to 4 weeks of therapy before improvements are noticed. Your doctor may want to stop this medication occasionally to determine if it is still necessary.

MISSED DOSE:

If you miss a dose, take it as soon as remembered; do not take it if it is near the time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up.

Spasticity

Spasticity is another common complaint. It is basically an increase in muscle tone and exaggerated tendon reflexes. This results in decreased dexterity and inability to produce intended movement. Spasticity contributes to pain, energy expenditure, and interferes with limb functions.

Ironically in some cases spasticity can be beneficial in some cases in supporting a person's weight during walking or during transfer from chair etc.

The drugs which have been the most beneficial in treating this symptom are:

Baclofen (Lioresal) , Diazepam (Valium) and Dantrolene.

Baclofen is the preferred drug. It is usually started at low doses and is gradually titrated up to achieve maximum response.

Most patients can be maintained at 40-80 Mg daily dose. Some may require higher doses.

Important thing to note is that when the dose is too high there is a decline in strength. At that point the dose is reduced gradually until optimum level of functioning is achieved.

Diazepam (Valium) is used in patients who do not tolerate Baclofen.

Dantrolene is reserved for after Baclofen and diazepam have been tried.

In general the most troublesome adverse effects of the anti-spasticity drugs are drowsiness, dizziness, weakness.

Bowel Symptoms

Difficulties in bowel emptying and severe constipation are common in people who have had MS for a long time. There could be several causes to constipation.

Incoordination of bowel muscles, limited activity, and diet.

Treating constipation should begin by looking at the diet and activity level.

Increasing fiber and fluid in the diet will help move things along. Gravity helps, which means try to increase the level of activity by walking more.

Metamucil, a bulk forming laxative can help. It is usually taken with a full cup of water. If the stool is too loose reduce the amount of fluid you take it with.

Stimulant laxatives can help. Examples are Senokot, Dulcolax. Adding a stool softener such as docusate sodium or docuate calcium may help.

Managing bowel function is sometimes more of an art than science.

Cisapride (Prepulsid) or some other drugs that stimulate peristalsis may be helpful as well.

If you are taking Cisapride you need to be aware of the drugs which you should not be taking with it.

Revised labeling for Prepulsid emphasize that the drug should not be used in patients taking certain antibiotics, antidepressants, antifungals, protease inhibitors, or various other drugs. The strengthened warnings also contraindicate the drug's use in patients with certain disorders--such as congestive heart failure, multiple organ failure, chronic obstructive pulmonary disease which causes serious respiratory problems, and advanced cancer.

Prepulsid should also not be administered to patients with electrolyte disorders (hypokalemia or hypomagnesemia). These include patients with severe dehydration, vomiting, diarrhea, or malnutrition, or those taking potassium-wasting diuretics and/or insulin in acute settings, or who might experience rapid reduction of plasma potassium.

Furthermore, because of the risks associated with the drug and the many factors that need to be considered when properly administering it, doctors are being advised that Prepulsid should usually be used in patients who have not responded adequately to lifestyle modifications or other drugs."

Bladder Symptoms

Bladder symptoms include: frequent urination, urge incontinence, incomplete emptying , and bladder infections.

Frequent urination and urge incontinence are caused by spastic bladder muscles.

These symptoms can sometimes be controlled by limiting fluid intake before and during activities when frequent urination is not feasible. (Long car rides, social events)

If this is ineffective medications can be tried.

The two most common ones are Oxybutynin (Ditropan) and Flavoxate (Urispas)

Oxybutynin

SIDE EFFECTS:

Stomach pain, gas, cramping or constipation may occur as your body adjusts to the medication. Inform your doctor if these effects continue or become bothersome. This medication may cause drowsiness or blurred vision. Use caution when driving or performing tasks requiring alertness. Dry mouth, nose or throat are common while taking this medication. To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use saliva substitute. Notify your doctor if you develop a rapid heart rate, fast pulse, pounding heartbeat, difficult or painful urination, diarrhea, fever or shortness of breath while taking this medication. This medication can reduce sweating. To prevent heatstroke or overheating, avoid exercise in hot weather or saunas.

Avoid consumption of alcohol while taking this medication since it can cause excessive drowsiness. This medication may cause restlessness, vivid dreams or hallucinations especially in children.

PRECAUTIONS:

Alcoholic beverages may increase the drowsiness caused by oxybutynin. Before taking oxybutynin, tell your doctor what prescription and nonprescription drugs you are taking. Oxybutynin can affect certain medical conditions. Tell your doctor if you have heart, liver, kidney, stomach, or intestinal disease; glaucoma; colitis; intestinal obstruction; an overactive thyroid or prostate gland; or myasthenia gravis. Women who are pregnant or breast-feeding should inform their doctors before taking oxybutynin. Before surgery, including dental surgery, tell the doctor or dentist in charge that you are taking oxybutynin.

DRUG INTERACTIONS:

Tell your doctor if you are taking digoxin, haloperidol or any phenothiazine-type drug.

NOTES:

Do not allow anyone else to take this medication.

MISSED DOSE:

Take the missed dose as soon as possible but not if it is almost time for the next dose. If it is time for the next dose, skip the missed dose and resume your regular schedule. Do not "double up" the dose.

Flavoxate

USES:

This medication relaxes the muscles of the urinary tract. It is used to relieve pain, burning, urinary urgency and frequency and other symptoms associated with urinary tract infections, bladder infections and prostate infections.

HOW TO TAKE THIS MEDICATION:

This medication is taken by mouth 3 or 4 times a day as directed.

Take this with food if stomach upset occurs.

SIDE EFFECTS:

Nausea, vomiting, dry mouth, headache, drowsiness, dizziness, blurred vision, and nervousness may occur the first several days as your body adjusts to the medication. If any of these effects continue or become bothersome, inform your doctor. To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use saliva substitute. Notify your doctor if you develop chest pain, a rapid pulse, fever, eye pain, mental confusion or skin rash while taking this medication. Because this medication may cause drowsiness or blurred vision, use caution driving or performing tasks requiring alertness.

PRECAUTIONS:

This medication should be used only if clearly needed during pregnancy. Discuss the risks and benefits with your doctor. It is not known if this medication appears in breast milk. Consult your doctor before breast-feeding. Tell your doctor if you have any pre-existing kidney disease, stomach or intestinal disorders or glaucoma, or if you have any allergies.

DRUG INTERACTIONS:

Tell your doctor of any over-the-counter or prescription medication you may take especially any medication for blood pressure or depression.

NOTES:

This medication relieves the symptoms of the infection and must be taken along with an antibiotic which will treat the infection itself.

MISSED DOSE:

If you miss a dose, take it as soon as remembered; do not take it if it is near the time for the next dose, instead, skip the missed dose and resume your usual dosing schedule. Do not "double-up" the dose to catch up.

Incomplete emptying is managed with self catheterization.

Incomplete emptying can lead to increased bladder infection. These can be managed with suppressing antibiotic therapy, and/or acidifying the urine with Vitamin C.

Up until now I have discussed symptomatic treatments that do not change the course of the disease but improve the quality of life MS.

The first breakthrough in treatment that offered hope in changing the course of the disease was in 1995 when Betaseron was released to the Canadian market. Since then there have been 4 new approved treatments that may change the course of MS.

These are:

Betaseron (Interferon beta 1b)

Rebif (Interferon beta 1a)

Copaxone ( also called Co-polymer-1, Copaxone)

Avonex ( Interferon beta-1a)

The following table compares these new agents as therapeutic options for relapsing remitting multiple sclerosis

             Interferon         Interferon beta-1b  Glatiramer acetate  Interferon beta-1a  
             beta-1a            Betaseron           (Copaxone)                              
             Avonex                                                     Rebif               

Description  - A form of        - A form of         - A synthetic       - A form of         
             interferon beta    interferon beta     mixture of 4 amino  interferon beta     
             produced in        produced by         acids               produced in         
             mammalian cells    Escherichia coli                        mammalian cells     
             - Amino acid       bacteria                                - Amino acid        
             sequence           -Amino acid                             sequence identical  
             identical to       sequence                                to natural human    
             natural human      substituted at                          interferon beta     
             interferon beta    position 17                                                 

Indication   Patients with      - Ambulatory        - Patients with     - Patients with     
             relapsing forms    patients with       relapsing-remitting relapsing-remitting 
             of MS              relapsing-remitting  MS                  MS                 
             - Slows the         MS                 - Reduces the       - Reduces the       
             accumulation of    - Reduces the       frequency of        frequency of        
             physical           frequency of        relapses            relapses            
             disability         clinical                                - Slows the         
             - Decreases the    exacerbations                           progression of      
             frequency of                                               physical            
             clinical                                                   disability          
             exacerbations                                                                  

MRI          effect             Effect              Data unavailable    Effect              
             demonstrated       demonstrated                            demonstrated        

Dosing       One intramuscular  One subcutaneous    one subcutaneous    One subcutaneous    
frequency    injection per      injection every     injection daily (7  injection every     
             week               other day (3-4 per  per week)           other day (3 per    
                                week)                                   week)               

Storage      Refrigerated,      Refrigerated        Refrigerated        Refrigerated        
             stable @ room                                                                  
             temp x 30 days                                                                 

Packaging    All components     Needles, syringes,  All components      Prefilled syringes  
             required supplied  and other supplies  required supplied                       
             with prescription  purchased           with prescription                       
                                separately                                                  

Adverse      - Unspecified      - Injection site    -Immediate          - Injection site    
events       flu-like symptoms  reaction            post-injection      reaction            
             - Muscle ache      - Flu-like          reaction            - Flu-like          
             - Fever, chills    symptoms            - Chest pain        symptoms            
             - Weakness         -Laboratory         - Injection site    - Fever             
                                abnormalities       reaction                                
                                - Menstrual         - Vasodilatation                        
                                symptoms                                                    

New Research.

"Herpes virus linked to multiple sclerosis

Deborah Josefson, San Francisco

Researchers at the National Institute of Neurologic Disorders and Stroke in the United States

have uncovered more evidence linking the herpes virus to multiple sclerosis (Nature Medicine

1997;3:1394-7).

Epidemiological studies have pointed to a link between multiple sclerosis and early childhood exposure to an infectious or environmental agent. Herpes viruses are good candidates because they stay in the body for a long time and affect the neurological system. Typically, they cause an initial infection in infancy or childhood followed by a reactivated syndrome later in life. For instance, varicella zoster causes chicken pox in childhood and shingles in the immunocompromised adult. Recently discovered herpes viruses have been implicated in Kaposi's sarcoma (HHV-8) and in roseola or exanthem subitum (HHV-6)-a reticular rash with fever occurring in infancy.

Acting on the recent demonstration that copies of HHV-6 are present in plaques in multiple sclerosis, the investigators screened serum samples of 102 people, 36 of whom had multiple sclerosis (of whom 22 had the relapsing-remitting type and 14 the chronic progressive form).

Of the patients with relapsing-remitting multiple sclerosis, 73% carried antibodies to an early antigen of HHV-6, compared with 18% of normal controls. Overall, 35% of patients with multiple sclerosis had antibodies to the HHV-6 early antigen; moreover, the serum of 30% of patients with the disease carried the DNA of HHV-6, a marker for active HHV-6 infection. In contrast, none of the normal controls tested positive for HHV-6 DNA.

Although these findings may be merely circumstantial, they do show the strongest association between a specific virus and multiple sclerosis seen so far. Dr. Steven Jacobson, principal investigator of the study, said: "We've suspected a possible role for a virus in multiple sclerosis for quite some time, and these results certainly point to this particular virus. But we need to know more before we move to the clinical stage. We've thought for a long time that genetics, an autoimmune factor, or something in the environment-like a virus-might cause multiple sclerosis. One can certainly make a case for a combination of these factors-namely, that a small group of individuals may be genetically susceptible to a virus. If HHV-6 is really behind multiple sclerosis then we also need to know why infection with such a common virus causes disease in so few people." Additional testing for the presence of HHV-6 in patients with multiple sclerosis is under way to strengthen the link."

Strategies for Myelin Repair and Regeneration

Growth factor and Myelin Regeneration

Title

Growth factors and myelin regeneration in multiple sclerosis.

Author

Webster HD

Address

Laboratory of Experimental Neuropathology, NINDS, National Institutes of Health,

Bethesda, Maryland 20892, USA.

Source

Mult Scler, 3(2):113-20 1997 Apr

Abstract

Insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and ciliary neurotrophic factor (CNTF) are multifunctional growth factors which are found in the CNS. Oligodendroglia are the cells that form and maintain myelin sheaths and many in vitro experiments have shown that these growth factors promote the proliferation, differentiation and survival of cells in the oligodendroglial lineage. Since myelin breakdown is often severe in multiple sclerosis (MS), the possibility of growth factor use in the treatment of MS has been considered and recently,

IGF-I treatment has been shown to reduce lesion severity and promote myelin regeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This review briefly summarizes the structural characteristics of these growth factors and the actions which might help reduce oligodendrocyte-myelin sheath injury in MS and promote myelin regeneration.

Myelin Transplantation

Title

Schwann cell transplantation and myelin repair of the CNS.

Author

Baron-Van Evercooren A; Avellana-Adalid V; Lachapelle F; Liblau R

Address

INSERM CJF9608, H^opital de la Salp^etri`ere, Paris, France.

Source

Mult Scler, 3(2):157-61 1997 Apr

Abstract

Studies with experimental models of dysmyelination and demyelination have shown that rodent Schwann cells including a Schwann cell line, transplanted in the central nervous system compete with host oligodendrocytes to remyelinate denuded central axons of the spinal cord. The myelin produced by transplanted SC around these central nervous system axons is structurally normal and restores, secure nerve conduction. In the presence of a favorable substrate, transplanted Schwann cells migrate over considerable distances (several mm) and are recruited by a demyelinated lesion which they will partially repair Thus Schwann cells, which can also support axonal growth, may be instrumental in central nervous system repair. In addition, the possibility of obtaining large quantities of human and non-human primate Schwann cells, makes it possible to consider autologous Schwann cell transplantation as a potential therapy for demyelinating or traumatic diseases. The various differences which may exist between rodents and humans, however, require further investigation of this possibility in a non-human primate model of demyelination.

These experiments should provide not only insights on the potential of autologous transplantation in primates but also a better understanding of the process of central remyelination.