The Disease That Looks Different Every Time

A deep dive into multiple sclerosis — what causes it, how it’s diagnosed, and where treatment is headed

I have heard MS described in many ways — as “the snowflake disease” (no two cases look alike), as invisible, as something that “steals things slowly.” All of those things are true, and none of them fully capture what it actually feels like to live with it. March is MS Awareness Month, so it felt like the right time to add to our ongoing autoimmune disease series (we've previously tackled rheumatoid arthritis and lupus) a disease that affects nearly 3 million people worldwide and remains one of the most misunderstood conditions in public health. That’s why we asked our colleague Selena Buongiorno to help us tell this story. She’s a physician assistant, an MS researcher, and a person living with the diagnosis — and that combination is rare. We’re honored to share her perspective alongside the science. Let’s discuss…

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When I (Selena) first heard the words multiple sclerosis (MS), I thought my life was over. My mind jumped to worst-case scenarios and all of the unknowns ahead. As a physician assistant, I understood MS from a medical standpoint, but nothing prepares you for hearing it attached to your own name. Understanding a disease and living with it are two very different things.

At first, I believed strength meant pushing through and refusing to let anything change. Over time, I realized that true strength looked different. It meant listening to my body, redefining success, and giving myself grace on the hard days.

My diagnosis didn’t just change my personal life; it reshaped my professional path. I felt called to go deeper, to learn more, and to be part of the solution. I became involved in neuroscience and MS research and pursued board certification in lifestyle medicine, focusing on how nutrition, movement, stress management, and community can support brain and immune health. These are not cures, but they are powerful tools that help people live well.

What is Multiple Sclerosis?

Multiple sclerosis is a chronic and predominantly immune-mediated disease of the central nervous system (CNS), affecting the brain, spinal cord, and optic nerves. It affects nearly 2.9 million people worldwide, including around 1 million people in the United States.

In MS, there is damage to myelin, the protective coating that surrounds nerve fibers and helps electrical signals travel quickly and efficiently through the nervous system. Think of myelin as insulation around electrical wiring. When that insulation is damaged, communication between different parts of the brain and body slows down or gets disrupted. This is why MS can present with such a wide range of neurological symptoms, including fatigue, vision changes, numbness, tingling, movement difficulties, and cognitive changes.

One of the main features of MS is that it looks different for everyone. Some people experience periods of symptom flare-ups followed by recovery, while others may notice gradual changes over time. Clinically, MS is categorized into three main patterns based on how symptoms evolve:

1. Relapsing remitting MS (RRMS): The most common type. Well-defined relapses with full or partial recovery.

2. Primary progressive MS (PPMS): Gradual and steady increase in disability from onset, without distinct relapses.

3. Secondary progressive MS (SPMS): A transition from RRMS, with initial relapses shifting into a phase of gradual neurological decline.

Knowing these patterns helps physicians and other clinicians tailor monitoring and treatment plans. But it’s important to remember that each person’s experience with MS is unique.

TL;DR from Jess: MS is a disease where the immune system mistakenly attacks the nervous system’s own protective wiring, disrupting signals between the brain and body. There are different types, wildly different symptom profiles, and no two people’s experiences look the same.

When the Immune System Mistakes Myelin For a Threat

The immune system is a highly trained surveillance system, constantly scanning for threats. In MS, this system misidentifies myelin as harmful. Instead of protecting the nervous system, immune cells launch an inflammatory response against it, leading to demyelination and disrupted nerve signaling.

What causes this misfiring? Like many immune-mediated diseases, MS does not have a single cause. It develops through a combination of genetic vulnerability, environmental exposures, and immune system changes:

Genetics: A family history of MS increases risk, but genetics alone does not determine whether someone will develop the disease. Variants in genes involved in immune regulation (particularly the human leukocyte antigen (HLA) system) are associated with susceptibility to MS. These variants may increase the likelihood that the immune response will misfire. Genetics creates susceptibility, but additional factors are needed to trigger the disease.

Environmental Factors: Several environmental exposures have been linked to MS risk, especially in genetically susceptible people: low sunlight exposure and vitamin D insufficiency, cigarette smoking, and Epstein-Barr virus (EBV) infection. In fact, EBV is one of the strongest known risk factors for MS. Research has found that almost all MS cases occur in people who have previously been infected with it, suggesting that EBV may trigger the kind of immune changes that lead to attacks on myelin. Broader changes in the microbiome may also shape immune responses linked to MS. (A note of caution: some wellness companies sell microbiome tests that falsely claim to diagnose autoimmune conditions like MS. They cannot.)

Hormonal and Health Factors: MS is more common in women than men, suggesting hormonal influences on immune function. Factors such as obesity and metabolic health may also affect inflammation and immune regulation, shaping both disease risk and progression.

TL;DR from Jess: No single switch gets flipped. It's genetics plus environment plus immune misfiring, and we still don't fully understand why it hits women so much harder than men.

What MS Looks and Feels Like

MS is often an invisible illness. From the outside, I (Selena) may look the same, but internally, my perspective has shifted. What once felt like an ending became a turning point that clarified what matters most.

I am still a clinician, a wife, a mother, a friend, and a person with big goals. MS is part of my story, but it’s not the whole story. In many ways, it pushed me to turn pain into purpose. I stepped into advocacy and started the MSwired Podcast to support people who are newly diagnosed, helping them navigate MS from the dual perspective of a clinician and a patient.

Resilience isn’t pretending things are easy. It’s meeting reality with courage, adapting when needed, and continuing forward with hope. This diagnosis didn’t take my life away. It gave me a new way to live it, with more intention, courage, and purpose than I ever had before.

Part of what makes MS so disorienting is that the immune system may have been quietly attacking myelin for years before anything surfaces. In some people, distinctive autoantibodies or molecular signs of myelin injury can be detected several years before symptom onset. When symptoms do surface, they often emerge gradually and can follow unpredictable patterns — periods of flare-ups, when neurologic symptoms intensify, followed by remissions, when symptoms stabilize or partially improve. Where symptoms show up depends entirely on where demyelination occurs, which is why no two MS journeys look the same. The disease can develop at any age, but is most commonly diagnosed between ages 20 and 40.

The Most Common Symptoms

Symptoms of MS depend on where demyelination occurs, but frequently include:

• Vision problems, such as blurry vision or optic neuritis (inflammation of the optic nerve, which can cause pain and vision loss)

• Numbness or tingling in limbs or face

• Weakness in arms or legs

• Difficulty with balance or coordination

• Fatigue, often profound and unrelated to exertion

• Muscle spasms or stiffness

• Cognitive changes, such as trouble with memory or processing speed

Beyond the Most Common Symptoms

Since MS disrupts nerve signaling broadly, it can cause other symptoms:

• Mood changes, such as depression or anxiety, which can arise from both brain inflammation and the chronic burden of disease

• Bladder or bowel dysfunction, due to disrupted nerve signaling

• Heat sensitivity (Uhthoff’s phenomenon), where symptoms temporarily worsen with increased body temperature

• Mobility impairment over time if progressive nerve damage occurs

• Persistent neurologic deficits following relapses, especially if nerve fibers themselves are damaged, a process that can begin years before symptoms appear

Because MS involves complex immune mechanisms and affects different regions of the CNS in each person, the pattern and severity of symptoms vary widely. Some people experience infrequent relapses and long periods of stability, while others may develop progressive symptoms despite treatment.

Piecing Together a Diagnosis

Diagnosing MS requires assembling multiple pieces of clinical, radiologic, and laboratory evidence. Historically, diagnosis relied on symptoms and physical examination alone, but advances in imaging and biomarkers have made it possible to identify MS with greater accuracy and at earlier stages.

MRI plays a central role in detecting CNS lesions. Cerebrospinal fluid (CSF) analysis, particularly the identification of CSF‑restricted oligoclonal bands, provides evidence of inflammation within the space between the brain and spinal cord and helps distinguish MS from conditions that can mimic it. The recently updated 2024 McDonald Criteria have expanded the diagnostic toolkit, allowing clinicians to confirm MS earlier and start disease‑modifying therapies sooner.

Because MS affects multiple systems and presents differently across individuals, diagnosis and ongoing care typically require a multidisciplinary healthcare team:

• Neurologists coordinate evaluation and treatment, ordering diagnostic tests and interpreting imaging findings.

• Primary care physicians manage general health concerns and identify other health conditions that may influence symptoms.

• Nurses and nurse practitioners often act as care navigators, guiding patients through testing, coordinating referrals, and providing education about symptoms and treatments.

• Additional specialists may include neuro‑ophthalmologists (for visual disturbances), urologists (for bladder dysfunction), and rehabilitation therapists (for mobility changes).

Diagnostic tests

MS diagnosis relies on several key tests used in combination. No single test confirms it on its own.

MRI imaging identifies demyelinating lesions in characteristic CNS regions, including the periventricular, cortical, infratentorial, and spinal cord areas. The optic nerve can now also serve as an additional diagnostic site. Newer MRI techniques can help distinguish MS lesions from those caused by other conditions, reducing the chance of misdiagnosis.

CSF analysis evaluates for CSF‑restricted oligoclonal bands, which serve as strong evidence of immune activity. Most people with MS show these bands. CSF analysis can significantly reduce the time to diagnosis for some patients.

Additional biomarkers (biological signals that can be measured in blood or spinal fluid). Kappa free light chains (fragments of antibodies) may offer an alternative pathway to diagnosis when other criteria are harder to satisfy.

The 2024 McDonald Criteria

To diagnose MS, clinicians historically needed to show two things: that lesions or symptoms had occurred in more than one location in the CNS (dissemination in space), and that they had occurred at more than one point in time (dissemination in time). The 2024 McDonald Criteria updates revised how both can be established. Key changes include:

• Removal of the mandatory waiting time before confirming dissemination in time, allowing many patients to receive a diagnosis without prolonged delays.

• Addition of the optic nerve as a fifth anatomical region that can support a diagnosis.

• Recognition of radiologically isolated syndrome (RIS), where MS-like lesions are found on MRI but the person has no symptoms, as sufficient for diagnosis under certain conditions. This means that people with typical MRI findings may receive a diagnosis and start treatment before symptoms appear.

These revisions reflect an international effort to diagnose MS earlier, more accurately, and with fewer misdiagnoses.

How is MS Treated?

There is no cure for MS. Most treatments focus on controlling inflammation, reducing relapses, and slowing disease progression. With more than 20 FDA-approved therapies now available, treatment is very individualized.

Disease-modifying therapies (DMTS) aim to reduce relapses, slow the progression of disabilities, and prevent the formation of new lesions. They are generally more effective for relapsing-remitting MS (RRMS) than for later-stage progressive disease.

• B-cell targeting therapies: Antibodies to CD20, a marker on B cells, deplete B cells, which are key drivers of disease. Examples include ocrelizumab (Ocrevus), ofatumumab (Kesimpta), and ublituximab (Briumvi).

• Sphingosine-1-phosphate (S1P) receptor modulators: Siponimod (Mayzent) is an oral medication that works by trapping immune cells in lymph nodes and preventing them from entering the CNS and causing damage.

• Selective immune cell reducers: Cladribine (Mavenclad) is given intermittently as a tablet and is used for relapsing and some progressive forms of MS to reduce the proliferation of B and T cells.

Symptom Management

These treatments improve quality of life by managing specific symptoms but do not target the underlying disease:

• Muscle relaxants such as baclofen and tizanidine

• Dalfampridine which improves nerve signals in demyelinated neurons to support walking

• Additional therapies for fatigue, pain, bladder or bowel issues, and depression

TL;DR from Jess: There’s no single test for MS. Diagnosis means assembling MRI findings, spinal fluid analysis, and clinical history over time. The good news: updated 2024 criteria now allow for earlier diagnosis, and earlier treatment genuinely changes long-term outcomes.

What’s on the Horizon

Companies are developing new ways to deliver medicines so patients don’t need to visit infusion centers (e.g., subcutaneous delivery). Many new therapies are currently in clinical trials or have recently received approval, including:

• BTK inhibitors (Bruton’s tyrosine kinase inhibitors) work by blocking a protein that B cells and microglia need to drive inflammation. Unlike some older therapies, they can cross the blood-brain barrier, meaning they may be able to address inflammation within the brain itself, not just in the rest of the immune system. Some BTK inhibitors are currently under FDA review, with approvals expected soon.

• Foralumab (intranasal anti-CD3) is a therapeutic antibody given as a nasal spray that activates a type of immune cell (regulatory T cell), which can calm inflammation in the brain. It is still in clinical trials.

• Neuroprotective & remyelinating agents work to protect nerve cells from further damage by reducing inflammation and promoting repair pathways. Remyelinating agents go a step further by working to repair the myelin sheath that has already been damaged. These medications represent an important shift in focus. They don’t just slow the disease; they potentially reverse some of its effects. No therapies in either category have been approved yet, but several are currently in clinical trials.

• Stem cell therapies take several forms, and a number of approaches are in development. The most established involve resetting the faulty immune system (similar to rebooting a computer). This is already available at specialized centers in some countries, though it is not broadly FDA-approved for MS. Other approaches aim to reduce inflammation and repair damage to myelin, and are still in clinical trials.

• CAR-T cell therapy is an emerging approach that engineers a patient’s own immune system to target the specific immune cells that drive the attack on myelin. It’s still in early clinical trials.

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Final Thoughts

MS is one of those conditions where the science and the lived experience are both essential to actually understanding it. No clinical explainer captures what Selena describes, and no personal story alone conveys why the 2024 diagnostic criteria update matters. We need both. If you or someone you love is navigating a new diagnosis or chasing answers, the resources below are a good place to start. And if this piece made something click that didn’t before, share it — that’s exactly what we’re here for. If you’re living with MS, you’re not alone. Knowledge is power. Early detection matters. So does having a team you trust.

Stay curious,

Unbiased Science

Resources for MS support

Support resources:

https://www.nationalmssociety.org/resources/get-support/find-support-groups-and-programs

https://multiplesclerosisnewstoday.com/support-groups-and-resources/

https://msfocus.org/Get-Help/Support-Groups.aspx

General MS resources:

https://msfocus.org/Get-Educated/Educational-materials.aspx?lang=en-us

https://www.nationalmssociety.org/

https://mymsaa.org/