Wednesday, March 28, 2018

An Interview with Body Builder David Lyons

Competitive bodybuilding is one way that David Lyons conquers multiple sclerosis (MS). Diagnosed with MS in 2006, David is motivated to educate and inspire people living with the disease to focus on fitness and nutrition and to develop a mindset that anything is possible.

In 2012, with his wife Kendra Lyons, R.N., David founded the MS Fitness Challenge (MSFC) charity to help bring his message worldwide. David has received the Milestone Award from the National MS Society, and in 2015, he was presented the Health Advocate Lifetime Achievement Award by Arnold Schwarzenegger.

He’s also the author of “David’s Goliath: Winning the Battle Against All Odds” (2013) and “Everyday Health and Fitness with Multiple Sclerosis: Achieve Your Physical Wellness While Working with Limited Mobility” (2017). He’s working on a new show called “Pumped: The Muscle Hustle” with Lou Ferrigno.

He spoke with HealthCentral about his experience.

HealthCentral (HC): What were the initial symptoms that led to your diagnosis?

David Lyons: MS caught me off guard in the gym. Initially I experienced severe pain, numbness, tingling, and lack of coordination in my left arm while working out. Within a few weeks, the symptoms radiated throughout my body and moved into my legs. I became bedridden for months during the pre-diagnosis and diagnosis stage. When I was finally hospitalized, I was almost paralyzed from the chest down.

HC: What did you most fear when you learned of your diagnosis?

David: After a five-day stay in the hospital, the symptoms were still so severe that I felt I could not continue as a bodybuilder, or might not step foot in a gym again. The neurologists said that MS would quickly make me wheelchair bound due to the tremendous nerve damage I experienced during that initial attack. I began to fear that would become my reality. Twelve years later and almost 60 years old, I’m still not using a wheelchair.

Read this post in its entirety:

Building Your Fitness Future With MS: An Interview with David Lyons

Wednesday, March 21, 2018

How to Reduce the Pain of Injections

Self-injectable medications

Several of the medications used to treat multiple sclerosis are injectable drugs. The requirements for storage and administration differ for each drug, but here are some universal tips that will help reduce the pain of the injections. Please note that if you have questions or difficulties with a specific drug, call the drug company’s helpline or ask your own MS nurse for help.

Room temperature medication

Medications which must be kept in the refrigerator for storage are often much less painful upon injection when at room temperature. Before injecting, remove one pre-filled syringe from the refrigerator and leave the syringe out for at least 30 minutes before using. Or alternatively, while still in the wrapper, hold it in your armpit to bring it to body temperature.

Read this post in its entirety:

7 Tips To Reduce the Pain of Injections

Wednesday, March 14, 2018

What is Spinal MS?

Maybe you have heard the term “Spinal MS.” What is that? I thought MS could be relapsing, primary progressive, secondary progressive, or “benign.”

The lesions caused by multiple sclerosis can occur anywhere within the central nervous system, which includes the brain, the spinal cord, and the optic nerves. Approximately 55-75 percent of patients with MS will have spinal cord lesions at some time during the course of their disease. If a patient does have lesions in the spinal cord, he/she may be said to have Spinal MS.

A smaller number of MS patients, approximately 20 percent, may have only spinal lesions and not brain lesions. I am an example of one of those 20 percent of MS patients who only have spinal lesions.

Symptoms of Spinal MS

Spinal MS occurs more commonly with lesions in the cervical spine (the neck area) in approximately 67 percent of cases. Lesions in this area often affect the corticospinal tract. Neurological signs which indicate lesions in the corticospinal tract include the Babinski Sign and the Hoffmann Sign. Additional indicators of lesions in the upper spine include the l’Hermittes phenomenon and the Romberg Sign. At one time or another, I have shown each of these signs of neurological involvement/interference due to MS lesions.

Although the location of lesions do not always closely correlate to areas of clinical disability, there are cause/effect patterns which do emerge. Patients with spinal cord lesions are more likely to develop bladder dysfunction (e.g., urinary urgency or hesitancy, partial retention of urine, mild urinary incontinence), bowel dysfunction (e.g., constipation or urgency), and sexual dysfunction (e.g., erectile dysfunction or impotence in men, genital anesthesia or numbness in women, pain with intercourse for either sex). Complete loss of bladder and bowel control may be lost in more advanced cases of MS.

Spinal cord lesions can also lead to sensory and motor deficits, including dysesthesias, spasticity, limb weakness, ataxia or other gait disturbances.

Read this post in its entirety:

What is Spinal MS?

Wednesday, March 7, 2018

Common Multiple Sclerosis Symptoms

Multiple sclerosis is a disease of the central nervous system (CNS) with symptoms that can affect almost anything from head to toes. The disease is so variable that no two people with MS are likely to have exactly the same combination of symptoms. As MS symptoms mimic dozens of other conditions, it is also important to consider that this list is not exclusive to MS.

Here are 50 of the most common MS symptoms:

Sensory problems

  • Abnormal sensations (dysesthesias)
  • Numbness, tingling, burning, or tightness
  • Pins and needles
  • Severe itchiness (pruritus)
  • Hypersensitivity to touch
  • Pain - acute or chronic, mild to severe
  • Loss of proprioception (sense of body position in space)
  • Inability to detect vibrations
  • Impaired sense of taste or smell
  • Trigeminal neuralgia - stabbing pain in the face
  • L’Hermitte’s sign - electrical shock-like sensation running down the spine and into the limbs when you bend your neck forward or backward
  • The MS hug

Motor problems

  • Loss of strength or muscle weakness
  • Loss of muscle tone (hypotonicity) or increased muscle tone (hypertonicity)
  • Spasticity - continuously contracted muscles and/or muscle spasms
  • Myoclonus - sudden involuntary muscle contractions
  • Tremor
  • Foot drop
  • Problems walking, impaired gait, or mobility problems
  • Paralysis
  • Loss of balance
  • Loss of coordination (ataxia)
For more MS symptoms, read this post in its entirety:

Top 50 MS Symptoms

Wednesday, February 28, 2018

Marcus Gunn Syndrome and Multiple Sclerosis

One test which my neurologist, ophthalmologist, and primary care doctor each conduct during every office visit is the “swinging flashlight test.” You know the one. The doctor asks you to look ahead then shines a penlight first toward one eye, then the other, alternating quickly to observe your pupils’ response to light.

I strangely enjoy this test because I know that my pupils will show something unique. Something which proves that I have damage to my optic nerve. My pupils show a Relative Afferent Pupillary Defect (RAPD) or Marcus Gunn Sign.

What does the doctor look for during the “swinging light test”?

The pupils (the black centers of the eyes which dilate or constrict in response to light) are inspected for size, equality, and regularity. Did you know that the pupils will constrict or dilate when you look at objects far or near? They do, which is kinda cool.

More importantly, each pupil should constrict quickly and equally during exposure to direct light and to light directed at the other pupil (the consensual light reflex). Using the swinging light test, the doctor can test and observe the pupillary response to consensual light in order to determine if there is a defect present.

Normally, the pupil constriction does not change as the light is swung from eye to eye. When the light is moved quickly from eye to eye, both pupils should hold their degree of constriction.

What is a Relative Afferent Pupillary Defect?

The Afferent Pupillary Defect (APD) or Relative Afferent Pupillary Defect (RAPD) is an abnormal and unequal response in the pupils of the eyes when exposed to light. It basically demonstrates that one optic nerve transmits a different message to the brain than the other one. Testing for RAPD is a good way to implicate or rule out optic nerve damage such as is caused by optic neuritis.

My temporarily blinding case of optic neuritis in 2000 left my right eye impaired. It doesn’t register light in the same way as my left eye as the optic nerve has permanent damage. When the doctor shines the light in my left eye (the “good” eye), both pupils will constrict. This is normal. When the doctor quickly moves the light to my right eye (the “bad” eye), my pupils begin to dilate since the brain thinks that less light is coming in. This shows that there is damage to the corresponding optic nerve.

Read this post in its entirety:

MS Signs and Symptoms: What is Marcus Gunn Syndrome?

Wednesday, February 21, 2018

Nystagmus and Multiple Sclerosis

Nystagmus is a condition that causes the eyes to make quick, repetitive, uncontrolled movements — from side to side, up and down, or in a circular pattern — making the eyes appear to bounce around. The jerky motion may be triggered by optical stimuli or physical motion, or may occur at rest.

Nystagmus can be mild, occurring only when a person looks to the side, or it may be severe enough to impair vision. Nystagmus often makes it difficult to focus steadily on a fixed object.

What causes nystagmus?

Nystagmus can be an inherited condition, showing up in early childhood, or it can develop later in life due to an accident or illness. Nystagmus is often a symptom of an underlying medical problem, such as stroke, multiple sclerosis, or head trauma. Other causes of nystagmus include severe nearsightedness, albinism, inflammation of the inner ear, central nervous system diseases, and medication side-effects. Sometimes the cause may be unknown.

In persons with multiple sclerosis, lesions in the brainstem and cerebellum may interfere with the nerve signals that affect motion of the eyes causing nystagmus. According to the MS Foundation, approximately 35 percent of individuals with multiple sclerosis may develop nystagmus. Abnormal gaze-holding mechanisms, vestibular imbalance, and impaired fixation are the most common causes of nystagmus in multiple sclerosis.

Read this post in its entirety:

MS Signs and Symptoms: What is Nystagmus?

Wednesday, February 14, 2018

MS Pain: What is the MS Hug?

Pain is not a symptom of multiple sclerosis, right? Wrong. That has got to be one of the more frustrating myths for those of us living with MS. Pain in MS can show up as neuropathic pain or musculoskeletal pain. A particularly disturbing type of pain in MS that can sometimes feel like a boa constrictor is squeezing the breath out of you has commonly been called the MS hug.

Neuropathic pain

Symptoms of MS stem from damaged myelin (the coating that protects nerves) that impacts proper nerve function and health. Neuropathic pain can be caused by disrupted nerve signals. Symptoms of neuropathic pain may include abnormal sensations — tingling, numbness, skin crawling, itching, burning, or prickly sensations — which are called paresthesias. These can be acute or chronic, severe or mild, painful or just plain weird.

Musculoskeletal pain

In MS, disrupted nerve signals and overly sensitive motor neurons can lead to spasticity and/or painful muscle spams. Musculoskeletal pain caused by muscle spams, muscle weakness, physical stress on joints, or poor coordination are commonly associated with MS. These pains may be acute or chronic. When they show up suddenly, last only a brief period of time, and disappear rapidly, they are called paroxysmal symptoms. Paroxysmal symptoms may occur once or repeat over a longer period of time. If they show up repeatedly, that might be a sign of an MS relapse.

Treatment for MS pain

Common pharmacological management of neuropathic pain in MS includes anti-seizure drugs, corticosteroids, anti-spasticity drugs, or benzodiazepines. Antidepressant agents and opioids may help to modulate the experience of pain. Musculoskeletal pain may respond to physical therapy, stretching, spasticity medications, and conventional painkillers such as ibuprofen.

The MS hug: Definition and causes

The MS hug is a highly unpleasant, painful banding sensation that occurs anywhere around the torso. Some people in the online community have referred to the MS hug as the “Squeeze o’ Death.” Symptoms of the MS hug can show up anywhere on the torso, on one side or the other, or circling all the way around the body. The pain can range from mild numbness or tingling to excruciatingly sharp pain or pressure. Each person’s experience is unique and may even differ from one episode to the next.

Explanations of the cause of the MS hug vary. The pain may be neuropathic in origin such as dysesthesia (which is basically a really bad paresthesia). The pain might stem from extreme spasticity in the intercostal muscles of the rib cage. There are three layers of muscle fibers in the intercostal muscles that connect the ribs and assist with breathing. If these muscles are involved, symptoms may include chest tightening, difficulty breathing, and limited mobility.

What to do if you have the MS hug

If you suddenly experience chest pain or asthma-like symptoms, or you feel like a big snake is trying to squeeze the life out of you, don’t assume that it is your MS. Seek medical attention immediately. There may be another cause of your symptoms or pain. It’s better to err on the side of caution when your health is concerned......

Read this post in its entirety:

What is the MS Hug?

Wednesday, February 7, 2018

Why Does the Neurologist Tap My Finger?

The neurologist is looking to see if there is a finger flexor response.  The finger flexor response is demonstrated by a sudden flexing of the thumb and/or index finger.  There are two ways to cause this response:
  • The doctor snaps or flicks the nail of the middle or 4th finger.  A positive finger flexor response elicited in this manner is known as the Hoffmann reflex or sign.
  • The doctor holds the middle finger while partially flexing it between his/her finger and thumb, then taps or flicks the underside of that finger.  A positive finger flexor response elicited in this manner is known as the Trömner sign.

What causes the thumb to flex?

The finger flexor response (Hoffmann relex or Trömner sign) is somewhat similar to the Babinski sign in that it is suggestive of a lesion or impingement along the corticospinal tract.

What is the corticospinal tract?

Very long nerve axons which originate in the part of the brain called the cerebral cortex travel through the brainstem, cross over at the top of the cervical spine and travel down each side of the spinal cord. This path is the corticospinal tract which is sometimes called the pyramidal tract since the area where the crossover of nerves occurs has a pyramid-like shape.

Corticospinal tract neurons are referred to as “upper motor neurons” but they do not control muscles directly. Neurons in the ventral horn that directly innervate (or stimulate) muscle are called lower motor neurons.  It is damage in lower motor neurons which causes atrophy of muscle, while damage in upper motor neurons does not.

How do the Hoffmann or Trömner signs differ from the Babinski sign?

Each of these signs indicate damage in the corticospinal tract. The Babinski sign indicates damage anywhere along the corticospinal tract. However, the Hoffman and Trömner signs are a bit more specific in that they indicate a lesion or damage above the C5 or C6 level of the cervical spine.

Read this post in its entirety:

MS Signs and Symptoms: What is the Hoffmann Reflex?

Wednesday, January 31, 2018

Staying With Rituxan Rather Than Switching to Ocrevus

The latest disease-modifying therapy, called Ocrevus (ocrelizumab), was approved in March 2017 for relapsing and primary progressive forms of MS. Ocrelizumab works differently than other DMTs for MS in that it selectively depletes B-cells. B-cells are a type of white blood cell that develops antibodies in response to specific antigens, a process which helps the immune system to fight invaders. However, abnormal B-cells may mistakenly produce autoantibodies that contribute to autoimmune diseases such as multiple sclerosis, rheumatoid arthritis (RA), lupus, or scleroderma.

Ocrevus is very closely related to the drug Rituxan (rituximab) which is used to treat certain autoimmune diseases, such as rheumatoid arthritis and myasthenia gravis, as well as cancers like non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Both therapies work in the same way to alter the immune system. Rituxan is also commonly used off-label to treat MS, and I have personally used it since 2009.

Ocrelizumab specifically targets and destroys CD20+ B-cells in a way that serves to lower the immune system. Studies of ocrelizumab demonstrated that it could reduce relapses by 46 to 47 percent in people with relapsing MS compared to treatment with subcutaneous interferon beta-1a. People with primary progressive MS (PPMS) who received ocrelizumab were 24 percent less likely to experience disability progression than those who received placebo in a clinical study.

Ocrelizumab is an intravenous infusion therapy which is delivered twice a year in an infusion center or doctor’s office. The first dose is divided in half and given as two separate infusions, two weeks apart. Pre-medications, such as corticosteroids and an antihistamine, are given in advance to reduce the risk of infusion-related reactions that may include itchy skin, hives, coughing or wheezing, throat irritation, flushing, shortness of breath, dizziness, or fatigue. Since ocrelizumab weakens the immune system, patients are at greater risk of developing infections. Additional risks include reactivation of the hepatitis B virus and progressive multifocal leukoencephalopathy.

The decision to switch treatment or not

The MS community has received ocrelizumab with excitement and open arms. I personally know several people who have either switched to Ocrevus already or are considering it. Several factors come into play when making treatment decisions, including comparing efficacy, side effects, impact on lifestyle, and insurance coverage. Twelve years ago, MS patients would choose a treatment and stick with it, even if their disease remained active. Now, patients have options and may switch DMTs when their disease fails to reach NEDA (no evidence of disease activity).

Like many people living with multiple sclerosis, I am determined to do all I can to slow down the disease. Although I might not always exercise as much as I should or I might indulge in rich food on occasion, I still try to focus on healthy lifestyle habits and reduce stress. An important part of fighting this disease for me is to consistently use a disease-modifying therapy.

Read this post in its entirety:

Why I Am Not Considering Ocrevus?

Wednesday, January 24, 2018

Is CIS the same as MS?

When someone experiences a single demyelinating or inflammatory attack of the central nervous system that causes neurological symptoms resembling MS, it is called clinically isolated syndrome, or CIS. Here are some common questions about CIS and how it is distinguished from other forms of MS.

Is CIS the same as MS?

According to updated recommendations redefining the phenotypes of MS made in 2014, CIS is considered an official form of MS. However, not everybody who experiences an episode of CIS will go on to develop full-blown multiple sclerosis.

How does CIS resemble other forms of MS?

An episode of CIS includes neurological symptoms that last for 24 hours or longer and are caused by inflammation or demyelination within the central nervous system (CNS). Myelin is the fatty substance that surrounds and protects nerves. Myelin helps to speed messages along nerves, and a loss of myelin serves to slow down the messages or keep them from getting through in the first place. A place where inflammation has attacked the myelin is called a lesion. The effects of demyelination are the same for each form of MS.
An attack of CIS can be monofocal — involving a single symptom related to a single lesion — or multifocal — involving more than one symptom caused by lesions in different locations in the CNS. The CNS includes the brain, spinal cord, and optic nerves. An episode of CIS is often followed by complete or partial recovery.

How is CIS diagnosed?

Similar to other diseases of the central nervous system, diagnosis of CIS may include laboratory tests to eliminate other potential causes of symptoms, a complete neurological exam to access function of the nerves, a thorough medical history, and magnetic resonance imaging (MRI) to look for evidence of inflammation or demyelination within the CNS. Depending upon symptoms, the recommended MRI given at this stage of diagnosis may only include the brain and not the spinal cord.

Read this post in its entirety:

What Is Clinically Isolated Syndrome?

Wednesday, January 17, 2018

Focus On Yourself At Least Once Every Day

Each New Year brings hope and a sense of optimism amidst a potentially gloomy season with brittle cold weather and often gray skies. It is a time to begin with a proverbial clean slate. A time to start fresh and improve something about your life — eat better, exercise more, spend less money, read more books, learn a new skill — practically any goal can become a New Year’s resolution.

But there’s something about resolutions — they’re hard to keep. Each January, many people make an effort to do something different and end up disappointing themselves when a month later their resolve has fizzled into the gray sky. It can be total resolution evaporation.

My suggestion to prevent the evaporation? Make only one resolution: Focus on yourself once every day.

Life presented many challenges to me in the past 9 months. It was a really tough year. As a result, I did not take care of myself as I should. I stopped exercising. I stopped going out and having a blast on my bike. I stopped caring what I ate. I focused simply on surviving and taking care of others.

Maybe you can relate. At some time in your life, perhaps you have fallen victim to ignoring your own needs too. It’s an all too common situation, no matter what the details of the circumstances are. What you and I need to do now is to find a way to begin to take care of ourselves without a total resolution meltdown.

Once I realize what I really need — to show myself kindness and love — I can find ways to do just that. It’s not an easy task, honestly, because I’m so programmed to take care of everybody and everything else first. But there’s always going to be something else to do.
Since my neglected needs are primarily physical, I have chosen a physical solution. Your needs may be emotional, social, recreational, or financial, thus your solution should match the corresponding need.

Here are the questions I asked myself in order to identify what I need to do to show myself kindness and love within my current circumstances.

Read this post in its entirety:

The Only Resolution You Need to Make

Wednesday, January 10, 2018

Shingrix versus Zostavax for People with MS

People with MS may be at higher risk of getting shingles because of reduced immune system function due to disease-modifying treatments. High-dose steroids, often used during relapses, may also increase the risk of a shingles outbreak.

One of the biggest differences between these two shingles vaccines is the fact that Zostavax contains a live-attenuated (weakened) virus to stimulate the immune system, while Shingrix is a non-live, subunit vaccine that works by introducing only a small part of the actual microbe. Those of us living with multiple sclerosis or many other chronic diseases take medications that reduce the effectiveness of our immune systems. Because of this we can’t receive vaccines that contain live virus, which would put us as even greater risk of developing the very disease we’re trying to protect ourselves from.

Since Shingrix does not contain live virus, it should be much safer for people with lowered immune systems. My doctor was very happy to inform me of this during our routine medical visit. I was thrilled to learn the news. ACIP should issue recommendations on the use of Shingrix in people with compromised immunity in February 2018.

Even if you've already had shingles, it is still a good idea to be vaccinated. An episode of shingles might provide a few years of protection from recurrence, but that protection fades away. People who have already had the Zostavax vaccine can also receive the Shingrix vaccine. In fact, the ACIP recommends it.

My experience with shingles

In August 2005, I was still in the process of being diagnosed with multiple sclerosis and was prescribed a five-day course of intravenous solumedrol (IVSM), followed by an oral steroid taper, to reduce inflammation. It was an extraordinarily stressful time because the steroids temporarily reduced my immune system. By the time September rolled around, I began to develop small, itchy blisters on one side of my face and neck. I recognized the outbreak as shingles because a family member had recently contracted the virus.

Several antiviral medications — acyclovir, valacyclovir, and famciclovir — may be used to reduce the severity of shingles and shorten its duration. But these medications need to be taken as soon as possible after the shingles rash appears in order to be effective. Since I recognized my own case of shingles, I went to the ER for assessment and treatment. It’s a good thing I did because my rash was very close to my eye. The ER doctor had an ophthalmologist examine my eye carefully to make sure that the virus had not entered it. Thankfully, it was fine.

Read this post in its entirety:

The New Shingles Vaccine is Good News for People with MS

Wednesday, January 3, 2018

Using Disease-Modifying Therapies to Slow Down Multiple Sclerosis

Currently available disease-modifying therapies (DMTs) are primarily used in relapsing forms of the disease, including relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS) in patients still having relapses, and progressive-relapsing MS (PRMS). Some DMTs are also approved for delaying a second exacerbation in people who have been diagnosed with clinically isolated syndrome (CIS). One DMT has been approved for primary progressive MS (PPMS).

Disease-modifying therapies (DMTs) can be grouped together in a variety of ways. They can be categorized as oral drugs, self-injectables, or infusible medications; or they may be identified by their mechanism of action (MOA, or how they work). DMTs can also be divided into so-called first-line agents, which are common initial treatment choices for people diagnosed with MS, or second-line agents, which are typically reserved for patients who have not responded adequately or are unable to tolerate first-line drugs.

Self-injectable DMTs

Self-injectable disease-modifying therapies considered to be first-line options include Avonex (interferon beta-1a), Rebif (interferon beta-1a), Betaseron (interferon beta-1b), Extavia (interferon beta-1b), Copaxone (glatiramer acetate), and Glatopa (glatiramer acetate). Interferon beta drugs are FDA- approved to treat all relapsing forms of MS. With the exception of Rebif, interferon beta drugs are also approved for use in CIS. Copaxone is a synthetic polypeptide agent which is approved for RRMS and CIS. An additional injectable medication includes Plegridy (pegylated interferon beta-1a).

Oral DMTs

Since 2010, three oral therapies, each with different mechanisms of action, have been approved by the FDA for treatment of relapsing forms of MS. Gilenya (fingolimod) is the first in a new class of oral MS medications, called sphingosine 1-phosphate receptor modulators, which suppress lymphocyte circulation in the immune system. Two other agents in this class are currently in clinical trials. Aubagio (teriflunomide) is also the first in a new class of oral MS medications called pyrimidine synthesis inhibitors which have anti-inflammatory and immunoregulatory properties that have been used to treat rheumatoid arthritis and psoriatic arthritis. Tecfidera (dimethyl fumarate) is in a class of drugs called Nrf2 activators believed to have anti-inflammatory and cytoprotective properties.

Intravenous DMTs

Intravenous therapies include Tysabri (natalizumab), Ocrevus (ocrelizumab), Lemtrada (alemtuzumab), and Novatrone (mitoxantrone) which are typically reserved as second-line treatment choices. Tysabri, a humanized monoclonal antibody that binds to alpha-4 integrin and inhibits T-cells from crossing the blood-brain-barrier, is administered every 4 weeks by specially trained healthcare providers. Tysabri is approved for relapsing forms of MS and is highly effective, but carries the risk of a serious brain infection called progressive multifocal leukoencephalopathy (PML). Ocrevus, a humanized monoclonal antibody that binds to and depletes CD20+ B-cells, is administered twice a year with the first dose split into two infusions. Ocrevus is associated with infusion-related reactions and increased risk of breast cancer.

Read this post in its entirety:

Slowing Down Long-Term Progression of Multiple Sclerosis With Disease-Modifying Therapies