This Podcast Will Kill You

Episode 92: Multiple Sclerosis - Scarred Nerves & Skating Saints (March 8, 2022)

Hosts: Erin Welsh, Ph.D. & Erin Allmann Updyke, MD, Ph.D.
Theme: An in-depth exploration of Multiple Sclerosis (MS)—its biology, history, patient experience, and how our understanding (and treatment) have evolved.

Overview

In this episode, Erin Welsh and Erin Allmann Updyke unravel the complex world of multiple sclerosis, a chronic autoimmune disease affecting the nervous system. Grounding the episode in the real-life experience of Nikki, who lives with MS, the Erins explore the science behind the disease, its history, epidemiology, challenges in diagnosis and treatment, its mysterious origins, and the extraordinary impact of advocacy.

Patient Story: Nikki’s MS Journey

[Starts: 01:39]

• Diagnosis & Emotional Impact

  • Nikki was diagnosed with MS at age 27 after an incidental finding from an MRI intended for severe headaches.
  • Faced with her own mortality, she describes overwhelming fear and anxiety over her future and being able to “live the life that everybody gets to live.”

    “Now I'm thinking, I’m going to die, and I’m 27. I haven’t lived the life that everybody gets to live. ... What’s going to happen?” — Nikki [03:05]

  • The diagnosis process was long and grueling—four to five months, including a painful spinal tap.

• Years of Difficult Treatment

  • It took nine years to find an effective medication. Oral medications caused allergic reactions, and self-injections led to painful scarring and failed to halt her disease.
  • Eventually, Nikki started an infusion treatment which helped slow her progression, though the cost ($7,000/month) and side effects were daunting.
  • Infusions increased her risk for a potentially deadly brain infection (PML) due to JC virus reactivation.

• Symptoms and Daily Struggles

  • Nikki details constant symptoms: poor coordination, frequent falls, numbness, “band-like” tightness around her torso, fatigue, slurred speech, bladder issues, and worsening short-term memory.
  • She describes the social and mental challenges—misconceptions about her symptoms, embarrassment, fear of being a burden, and confronting the reality that MS isn’t fatal, but immune suppression could leave her vulnerable to fatal infections.

    "I'm scared as to how my final days will play out, because multiple sclerosis won't kill me, but the fact that I don't have an immune system will kill me." — Nikki [11:18]

  • Despite hardships, Nikki emphasizes gratitude for retained mobility and the importance of focusing on the present.

    "You can't focus on what could be coming. You have to just take every day as it is and be thankful that that's where you are at that moment." — Nikki [12:23]

Hosts React:

"As much as you can learn about the specific biology. ... it just doesn't fully encompass the experience of someone who is living with this." — Erin Allmann Updyke [14:18]
"MS, like many other diseases, are described by a series of signs and symptoms, but those signs and symptoms vary from person to person, and they don't capture the feeling..." — Erin Welsh [14:53]

Key Concepts & Biology of MS

[Begins: 21:21]

What is Multiple Sclerosis?

• Definition: Chronic, autoimmune, inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS).
• Main Pathologies:
  • Demyelination: The immune system attacks myelin (the insulation for nerve fibers), impairing nervous system signaling.
  • Gliosis (Scarring): Scar tissue forms where myelin is lost, disrupting nerve function.

    "You can think of [myelin] as like the insulation around an electrical wire." — Erin Allmann Updyke [23:21]

Disease Course & Symptoms

• Clinical Forms:
  • Relapsing-Remitting (RRMS): Most common (~90%). Flare-ups followed by periods of remission.
  • Primary Progressive (PPMS): Steady worsening from onset (~10%).
  • Secondary Progressive: Can follow RRMS, marked by continuous progression without clear flares.
• Symptom Diversity:
  • First signs can include optic neuritis (blurred vision, pain), limb weakness/numbness, muscle stiffness, bladder/bowel dysfunction, ataxia (coordination problems). Varies greatly because any CNS region can be affected.

    “Anything and everything is the real answer.” — Erin Allmann Updyke [24:22]

Progression and Pathophysiology

• Clinically Isolated Syndrome (CIS): First neurological episode, often resolves 80–100% with potential remyelination.
• Relapses: Over time, more relapses, more scarring, and accumulated disability.

  "Every attack results in like, 80 to 100% recovery... but as these relapses accumulate, the recovery is further and further from the initial baseline." — Erin Allmann Updyke [36:00]

• Fatigue: Extremely common and poorly understood; not just a single nerve malfunction but possibly generalized disrupted signaling.

Diagnosis

• MRI: Detects characteristic lesions/scars in the CNS—key for diagnosis.
• Other Tests: Lumbar puncture (to detect immune changes in CSF), bloodwork, testing for other causes.

  “...For a really long time, it was the case that you could really only make the diagnosis of MS if somebody had a recurrent CIS, and that would then lead you to the diagnosis…” — Erin Allmann Updyke [32:47]

Treatment Advances

• Early and aggressive use of disease-modifying therapies (DMTs), especially B cell–targeting drugs, can reduce relapses and slow progression.
• Symptom management requires multidisciplinary care.
• Primary progressive MS has fewer treatment options.

The Mystery of Causes: Why and How Does MS Develop?

[41:20]

Genetics & Environmental Factors

• Genetics: Multiple gene variants associated with immune function contribute risk, sometimes overlapping with other autoimmune diseases like lupus or type 1 diabetes.
• Environment:
  • Low Vitamin D/sunlight—suggested increased risk, but evidence is “mediocre.”
  • Smoking—associated with higher risk.

Epidemiology

• 3x more common in those assigned female at birth (not always the case historically).
• Striking variation globally: high rates in North America and Western Europe, lower in sub-Saharan Africa and Asia.

Epstein-Barr Virus (EBV) Link

[43:41]

• Major Discovery Highlighted:
  • Groundbreaking 2022 studies suggest EBV infection is a necessary precursor to MS—raising the risk 32-fold.

    "This paper... showed that infection with EBV increases your risk of MS by 32 times." — Erin Allmann Updyke [47:21]

• How? EBV infects B-cells, and in susceptible people, triggers autoimmunity against myelin. A second paper found cross-reactive antibodies between EBV and proteins on human nerve cells.

  "...They found antibodies that were produced in people with MS that bind to a specific EBV viral antigen and cross react on a specific human cell surface protein that is associated with autoimmune demyelination." — Erin Allmann Updyke [49:25]

• Not everyone with EBV gets MS: Requires other risk factors (genetic, immune).
• Potential for prevention: development of EBV vaccines, using mRNA technology from COVID-19 research.

The Elusive Origins and History of MS

[56:13]

Searching for Origins—Why Only Humans? Why Now?

• No definitive answer. Humans may be predisposed due to heavily myelinated brains.
• Onset often coincides with the period when myelination ends (~20s), fitting the typical age of MS onset.

Noteworthy Historical Cases and First Medical Descriptions

• Saint Ludwina of Schiedam (1380): Chronic disabling illness after a fall, considered by some as a possible early MS case.
• Augustus d’Este (1822): Kept detailed diaries describing recurrent neurological symptoms now recognized as classic MS.

  “Sitting produces a numbness all down the back part of my thighs and legs… When standing or walking, I cannot keep my balance without a stick…” — Augustus d’Este (via Erin Welsh) [63:15]

• Jean-Martin Charcot (1868): French neurologist who defined MS as a distinct disease by identifying characteristic plaques during post-mortem studies.
  • Early theories linked MS to stress, “illegitimate pregnancy,” and other social factors—a legacy of bias and misunderstanding that contributed to misdiagnosis as “hysteria,” especially in women.

Evolution of Diagnosis and Perception

• Over time, MS shifted from being classified as paraplegia, neurosyphilis, or “hysteria” (wastebasket diagnoses) to a defined neurodegenerative disease as clinical neurology advanced.
• The advent of MRI in the late 1970s revolutionized early diagnosis and validated patient experiences.

Patient Advocacy and the National MS Society

• Sylvia Lawry (1945): Frustrated by her brother’s illness, she posted a New York Times ad, which sparked the formation of the National MS Society and later the International Federation. Her advocacy fostered collaboration, research funding, and celebrity-driven awareness.

  "She brought over 20 leaders in the field of neurology together to try to set objectives for an organization that was dedicated to understanding the disease and finding a cure." — Erin Welsh [82:15]

MS Epidemiology and Today’s Landscape

[88:47]

• Global Prevalence (2016): 2.2 million+ cases, with highest rates in North America (164/100,000) and Western Europe (127/100,000).

  "It is the most common non-traumatic cause of neurologic disability in young adults." — Erin Allmann Updyke [88:55]

• Latitude Effect: Higher rates further from the equator, supporting (but not proving) environmental factors like sunlight/vitamin D deficiency.

  • But, variations within groups (e.g. low rates among some northern indigenous populations) suggest a multifactorial cause.

• Immigration Patterns: First-generation migrants retain MS risk of country of origin; their children’s risk matches their new home.

• Increasing Prevalence: Diagnosed earlier, treated better, people live longer with MS.

Memorable Quotes & Insights

• On the complexity of MS:

  "As much as you can learn about the specific biology... it just doesn't fully encompass the experience of someone who is living with this." — Erin Allmann Updyke [14:18]

• On historic misdiagnosis and stigma:

  "MS is not that difficult to diagnose. But there are a lot of misdiagnoses, with doctors most commonly confusing it with hysteria." — Maya Dusenberry, quoted by Erin Welsh [78:36]

• On the future and hope for prevention/treatment:

  "These new studies really showing that EBV is likely... a necessary precursor to the development of MS, meaning that MS is like viral sequelae of infection with this virus. That means that we could prevent MS... if we could prevent infection with EBV." — Erin Allmann Updyke [95:53]

Notable Timestamps

• 01:39 – Nikki’s MS journey and firsthand symptoms
• 14:53 – Discussion on how standard descriptions fail to capture lived experience
• 21:21 – Biological breakdown: definition, forms, symptoms
• 36:00 – Explanation of how relapses and scarring lead to permanent disability
• 43:41 – EBV breakthrough: recent science summary
• 56:13 – Historical mysteries: why MS? why humans?
• 61:33 – Historical case of Augustus d’Este and earliest clinical accounts
• 73:25 – Changing theories: bacteria, viruses, the “hysteria” era
• 82:15 – Sylvia Lawry: patient advocacy and the National MS Society
• 88:47 – Modern prevalence, latitude patterns, and the current state of MS

Final Thoughts

The Erins emphasize hope: major progress in the science of MS, the massive new focus on EBV as a key trigger, promising vaccine trials, and a robust culture of patient advocacy. But there is a clear acknowledgment of the ongoing challenges—both scientific uncertainty and the crucial need for compassionate, patient-centered care.

“We are now so much better than we used to be in our knowledge about multiple sclerosis. But at the same time, there are still so many unanswered questions. Why? First and foremost, because without a why, it’s going to be nearly impossible to find a cure.” — Erin Welsh [88:08]

Resources Mentioned

• National MS Society: Comprehensive resource for symptoms, support, research (https://www.nationalmssociety.org)
• Book: Multiple: The History of a Disease by Jock Murray

For more about EBV and new science, check the follow-up bonus episode with Dr. Mika Luftig on EBV.

End of Summary