Multiple Sclerosis (MS)

Benign Multiple Sclerosis (MS)

- Benign MS is a mild course where an individual will have mild disease after having MS for about 15 years. - This occurs in about 5-10% of patients. - There is no good way of predicting which patients will follow this course. - The only way to identify benign MS is AFTER someone has had the diagnosis of MS for at least 15 years and has had no evidence of worsening (both in functional ability and as evidenced on the MRI). - Benign MS cannot be predicted at the time of diagnosis or even after a few years with MS.

Multiple Sclerosis (MS) Symptoms

- Bladder problems (frequent urination, urgency) - Depression - Dizziness or vertigo - Fatigue - Impaired coordination (ataxia) - Sensory symptoms (numbness, pain) - Spasticity (muscle stiffness or spasms) - Temperature sensitivity - worsening of MS symptoms by heat - Tremors - Trouble with short-term memory and concentration - Visual symptoms (optic neuritis, association with pain and eye movement, double vision) - Weakness

Secondary Progressive Multiple Sclerosis (MS)

- If the relapsing-remitting condition changes to a point where there are no discernable relapses and remissions; the course of the disease has transitioned to secondary progressive MS. - All those with secondary progressive MS began the disease with a relapsing-remitting disease course. - In secondary progressive MS, symptoms accumulate and worsen without any remission. - There may be periods where symptoms are stable, but the overall course is one of worsening over time. - Often an individual will describe a change in their abilities when comparing current function to past function but without identifying an episode that led to the worsening. - Sometimes, after the onset of secondary progressive MS an individual may experience a relapse. - The course would then be considered secondary progressive MS with relapses.

Physical therapy for multiple sclerosis

(Physical therapy can build muscle strength and ease some of the symptoms of MS) - physical therapy - muscle relaxants - medications to reduce fatigue - medications to increase walking speed - medications for depression, pain, sexual dysfunction, insomnia, bladder/bowel control

Treatment options for relapsing-remitting MS include:

(injectable and oral medications) Injectable treatments include: - interferon beta medications - glatiramer acetate (Copaxone, Glatopa) Oral treatments include: - Fingolimod (Gilenya) ** - Dimethyl fumarate (Tecfidera)** - Diroximel fumarate (Vumerity) - Teriflunomide (Aubagio) - Siponimod (Mayzent) - Cladribine (Mavenclad)

Interferon beta medications

- These injectable drugs are among the most commonly prescribed medications to treat MS. They are injected under the skin or into muscle and can reduce the frequency and severity of relapses. - Side effects of interferons may include flu-like symptoms and injection-site reactions. - You'll need blood tests to monitor your liver enzymes because liver damage is a possible side effect of interferon use. People taking interferons may develop neutralizing antibodies that can reduce drug effectiveness.

Dimethyl fumarate (Tecfidera)

- This twice-daily oral medication can reduce relapses. Side effects may include flushing, diarrhea, nausea and lowered white blood cell count. - This drug requires blood test monitoring on a regular basis.

Mitoxantrone

- a chemotherapy drug indicated for worsening forms of relapsing MS and secondary progressive MS. It is given by intravenous infusion every 3 months. - Because this drug can be very toxic, it can only be given in a limited number of doses over the course of someone's life. - Mitoxantrone works by suppressing the immune system and reducing the overall numbers of immune cells that could be causing inflammation in MS - Mitoxantrone is associated with many side effects including cardiotoxicity

disease-modifying therapy (DMT)

- treatments that can reduce the activity and progression of multiple sclerosis (MS). - They can be useful for both people with relapsing-remitting MS (RMS) and relapses of progressive forms of MS.

common courses of MS

1. relapsing-remitting multiple sclerosis (MS) 2. Secondary progressive multiple sclerosis (MS) 3. Primary progressive multiple sclerosis (MS) 4. Benign multiple sclerosis (MS)

what percent of patients will have gradual worsening from the start of their MS disease.

10-15%

What is multiple sclerosis?

A chronic disease affecting the central nervous system (brain and spinal cord) where the immune system attacks the protective sheath (myelin) that covers the nerve fibers and causes communication problems between the brain and the rest of the body. Eventually the disease can cause permanent damage or deterioration of the nerves.

Monofocal episode

experiencing a single neurologic sign or symptom — for example, an attack of optic neuritis — that is caused by a single lesion.

Multifocal episode

experiencing more than one sign or symptom — for example, an attack of optic neuritis accompanied by numbness or tingling in the legs — caused by lesions in more than one place.

Without treatment, most people with MS will develop disease symptoms that will:

gradually worsen over time (known as relapsing).

unsteady gait

instability while walking

myelin sheath

layer of fatty tissue that surrounds/insulates healthy nerve fibers

the only FDA-approved disease-modifying therapy (DMT) for primary-progressive MS

ocrelizumab (Ocrevus) - Those who receive this treatment are slightly less likely to progress than those who are untreated.

Clinically isolated syndrome (CIS)

one of the MS disease courses. CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS). CIS can be either monofocal or multifocal:

evoked potential studies

record the electrical signals produced by your nervous system in response to stimuli. An evoked potential test may use visual stimuli or electrical stimuli. In these tests, you watch a moving visual pattern, or short electrical impulses are applied to nerves in your legs or arms. Electrodes measure how quickly the information travels down your nerve pathways.

at the time of diagnosis, 90% of patients will have what course of MS?

relapsing-remitting course of disease

Sometimes, after the onset of secondary progressive MS an individual may experience a relapse. The course would then be considered:

secondary progressive MS with relapses.

Much of the immune response associated with MS occurs in the early stages of the disease. Aggressive treatment with these medications as early as possible can lower:

the relapse rate, slow the formation of new lesions, and potentially reduce risk of brain atrophy and disability accumulation.

Is there a cure for multiple sclerosis?

there is no cure, however treatments can help speed recovery from attacks, modify the course of the disease and manage symptoms

intravenous means

through a vein

cardiotoxicity

toxicity to the heart

In relapsing-remitting multiple sclerosis, MS symptoms tend to persist for days or weeks, and then disappear partially or completely on their own or with treatment. Patients may then remain symptom-free for

weeks, months or even years (known as remission)

plasmapheresis for the treatment of MS attacks involves:

(plasma exchange) - The liquid portion of part of your blood (plasma) is removed and separated from your blood cells. The blood cells are then mixed with a protein solution (albumin) and put back into your body. Plasma exchange may be used if your symptoms are new, severe and haven't responded to steroids.

Primary Progressive Multiple Sclerosis (MS)

- About 10-15% of patients will have gradual worsening from the start of their MS disease. This is referred to as primary progressive MS. - People with primary-progressive MS describe a gradual change in mobility; often walking, over time. They often describe heaviness and stiffness in the lower limbs. - People with primary-progressive MS almost never have an exacerbation (relapse). *** - If a relapse occurs after a primary progressive course is well established, the pattern is known as Progressive-Relapsing MS.

Lhermitte sign

- Lhermitte's sign (pronounced Ler-meets) is a sudden sensation resembling an electric shock that passes down the back of your neck and into your spine and may then radiate out into your arms and legs. - It is usually triggered by bending your head forward towards your chest. - It is also known as Lhermitte's syndrome or barber's chair syndrome.

relapsing-remitting multiple sclerosis (MS)

- at the time of diagnosis, 90% of patients will have relapsing-remitting course of disease - this form of MS is characterized by the onset of the neurological symptoms over a period of hours to days common symptoms of a relapse may include: - fatigue - numbness - tingling - blurred vision, double vision or loss of vision - unsteady gait - weakness - these symptoms tend to persist for days or weeks, and then disappear partially or completely on their own or with treatment - patients may then remain symptom-free for weeks, months, or even years - without treatment, most people with MS will develop disease symptom that will gradually worsen over time

Vision symptoms of MS

- partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement - prolonged double vision - blurry vision - optic neuritis

what is a relapse in MS?

An exacerbation (known as relapse, flare-up, or episode) is defined as new or returning neurological symptoms that have evolved over at least 24-48 hours and have not been provoked by a metabolic cause - such as a fever. Exacerbations can interrupt the ability to function, thus the goal of treatment is to accelerate recovery.

The use of steroids for the treatment of MS attacks involves:

Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve inflammation. Side effects may include insomnia, increased blood pressure, increased blood glucose levels, mood swings and fluid retention.

Natalizumab has been associated with a rare, serious and potentially fatal infection of the brain known as:

PML (progressive multifocal leukoencephalopathy)

If a relapse occurs after a primary progressive course is well established, the pattern is known as:

Progressive-Relapsing MS.

Siponimod (Mayzent)

Research shows that this once-daily oral medication can reduce relapse rate and help slow progression of MS. It's also approved for secondary-progressive MS. Possible side effects include viral infections, liver problems and low white blood cell count. Other possible side effects include changes in heart rate, headaches and vision problems. Siponimod is harmful to a developing fetus, so women who may become pregnant should use contraception when taking this medication and for 10 days after stopping the medication. Some might need to have the heart rate and blood pressure monitored for six hours after the first dose. This drug requires blood test monitoring on a regular basis

Natalizumab (Tysabri)

This medication is designed to block the movement of potentially damaging immune cells from your bloodstream to your brain and spinal cord. It may be considered a first line treatment for some people with severe MS or as a second line treatment in others. This medication increases the risk of a potentially serious viral infection of the brain called progressive multifocal leukoencephalopathy (PML) in people who are positive for antibodies to the causative agent of PML JC virus. People who don't have the antibodies have extremely low risk of PML.

Teriflunomide (Aubagio)

This once-daily oral medication can reduce relapse rate. Teriflunomide can cause liver damage, hair loss and other side effects. This drug is associated with birth defects when taken by both men and women. Therefore, use contraception when taking this medication and for up to two years afterward. Couples who wish to become pregnant should talk to their doctor about ways to speed elimination of the drug from the body. This drug requires blood test monitoring in a regular basis.

Fingolimod (Gilenya)

This once-daily oral medication reduces relapse rate. - You'll need to have your heart rate and blood pressure monitored for six hours after the first dose because your heartbeat may be slowed. Other side effects include rare serious infections, headaches, high blood pressure and blurred vision.

Diroximel fumarate (Vumerity)

This twice-daily capsule is similar to dimethyl fumarate but typically causes fewer side effects. It's approved for the treatment of relapsing forms of MS.

Diagnosing Multiple Sclerosis (MS)

- It is not always easy to make a confirmed diagnosis of multiple sclerosis because early symptoms may be minor and sporadic. - It can also be difficult because other diseases can have similar warning signs, and there is no definitive single laboratory test to confirm MS. - The diagnosis is made based on a neurological examination and a history of neurological symptoms. Some of the tests typically used for this evaluation include: - MRI of the brain and/or spinal cord: (The MRI often shows plaques or scars typical of MS.) - Cerebrospinal fluid (CSF) evaluation: (Using a lumbar puncture or spinal tap, the CSF evaluation may show immunological abnormalities that help in the diagnosis.) - Evoked potential studies: (Measuring conduction of electrical impulses along the optic nerve (in patients suspected of having optic neuritis) and along nerve pathways in the brain and spinal cord.)

Causes of Multiple Sclerosis (MS)

- The exact cause of MS is unknown. It appears to be an autoimmune disease in which the immune system is stimulated to attack myelin in the central nervous system. The source of the initial stimulus has not been clearly identified. - In certain people who inherit a predisposition to MS, the trigger may be infections (such as viruses) or other factors in the environment. Individuals may also have a genetic predisposition for developing the disease as people with family members diagnosed with MS are at a slightly higher risk.

how to identify if a patient has/will have benign multiple sclerosis (MS)?

- The only way to identify benign MS is AFTER someone has had the diagnosis of MS for at least 15 years and has had no evidence of worsening (both in functional ability and as evidenced on the MRI). - Benign MS cannot be predicted at the time of diagnosis or even after a few years with MS.

treatment for acute MS attacks

- corticosteroids - plasma exchange (plasmapheresis)

Many of the disease-modifying therapies used to treat MS carry significant health risks. Selecting the right therapy will depend on careful consideration of many factors, including:

- duration and severity of disease - effectiveness of previous MS treatments - other health issues - cost - child-bearing status.

common symptoms of a MS relapse include

- fatigue - numbness - tingling - blurred vision, double vision or loss of vision - unsteady gait - weakness

movement symptoms of MS

- numbness or weakness in one or more limbs that typically occurs on one side of your body at a time, or your legs and trunk - electric-shock sensations that occur with certain neck movements, especially bending the neck forward (Lhermitte sign) - tremor, lack of coordination or unsteady gait (ataxia)

Variability of signs and symptoms of MS

- signs and symptoms of MS can vary widely and depend on the amount of nerve damage and which nerves are affected. - some people with severe MS may lose the ability to write, speak, or walk independently or at all, while others may experience long periods of remission without any new symptoms.

percentage of patients with benign multiple sclerosis?

5-10%

Over the past 17 years, how many preventive treatments have been FDA approved to reduce the frequency and severity of multiple sclerosis exacerbations or to treat worsening MS?

7

best approach for the long-term management of multiple sclerosis:

A coordinated, comprehensive, interdisciplinary approach

If the relapsing-remitting condition changes to a point where there are no discernable relapses and remissions; the course of the disease has transitioned to:

Secondary Progressive Multiple Sclerosis (MS)

Alemtuzumab (Campath, Lemtrada)

This drug helps reduce relapses of MS by targeting a protein on the surface of immune cells and depleting white blood cells. This effect can limit potential nerve damage caused by the white blood cells. But it also increases the risk of infections and autoimmune disorders, including a high risk of thyroid autoimmune diseases and rare immune mediated kidney disease. Treatment with alemtuzumab involves five consecutive days of drug infusions followed by another three days of infusions a year later. Infusion reactions are common with alemtuzumab. The drug is only available from registered providers, and people treated with the drug must be registered in a special drug safety monitoring program. Alemtuzumab is usually recommended for those with aggressive MS or as second line treatment for patients who failed another MS medication.

Ocrelizumab (Ocrevus)

This humanized monoclonal antibody, infusion medication is the only DMT approved by the FDA to treat both the relapse-remitting and primary-progressive forms of MS. Clinical trials showed that it reduced relapse rate in relapsing disease and slowed worsening of disability in both forms of the disease. Ocrelizumab is given via an intravenous infusion by a medical professional. Infusion-related side effects may include irritation at the injection site, low blood pressure, a fever and nausea, among others. Some people may not be able to take ocrelizumab, including those with a hepatitis B infection. Ocrelizumab may also increase the risk of infections and some types of cancer, particularly breast cancer.

Glatiramer acetate (Copaxone, Glatopa)

This injectable medication may help block your immune system's attack on myelin and must be injected beneath the skin. Side effects may include skin irritation at the injection site.

Cladribine (Mavenclad)

This oral medication is generally prescribed as second line treatment for those with relapsing-remitting MS. It was also approved for secondary-progressive MS. It is given in two treatment courses, spread over a two-week period, over the course of two years. Side effects include upper respiratory infections, headaches, tumors, serious infections and reduced levels of white blood cells. People who have active chronic infections or cancer should not take this drug, nor should women who are pregnant or breast-feeding. Men and women should use contraception when taking this medication and for the following six months. You may need monitoring with blood tests while taking cladribine.