Multiple Sclerosis: Understanding Neurological Deterioration and How Disease-Modifying Therapies Work

What Happens Inside the Nervous System in Multiple Sclerosis?

Multiple Sclerosis isn’t just about flare-ups and fatigue. At its core, it’s a slow, silent breakdown of your nervous system. The immune system, which normally protects you from viruses and bacteria, starts attacking the myelin sheath-the fatty coating that wraps around nerve fibers in your brain and spinal cord. Think of myelin like the insulation on an electrical wire. When it’s damaged, signals from your brain struggle to reach your muscles, eyes, or bladder. That’s when symptoms like numbness, blurred vision, or trouble walking show up.

What makes MS different from other neurological diseases is that early damage isn’t always permanent. If the inflammation stops and myelin gets repaired, function can come back. But over time, something deeper goes wrong. The nerve fibers themselves-the axons-start breaking down. And once an axon dies, it doesn’t grow back. That’s why many people with MS eventually face lasting disability, even when flare-ups stop.

Why Do Some People Get Worse Over Time?

Most people are first diagnosed with relapsing-remitting MS (RRMS). This means they have clear flare-ups followed by periods of recovery. About 85% of MS cases start this way. But here’s the hard truth: 40% of those people will transition to secondary progressive MS (SPMS) within 10 to 15 years. In SPMS, the disease stops being about sudden attacks. Instead, the damage creeps forward, like rust spreading through metal.

Doctors used to think this progression was just more inflammation. But scans and tissue studies show something else: inflammation fades. The immune cells that once flooded the brain become quieter. Yet, disability keeps getting worse. The real culprit? Axonal degeneration. Nerve fibers that lost their myelin insulation start starving. They lose mitochondria-their power source-and their internal structure breaks down. Sodium channels, which help send signals, disappear. Without myelin and without energy, the axons die.

Even areas of the brain that look normal on MRI show hidden damage. This is called normal-appearing white matter. Studies using advanced imaging show these regions have microglial activation-brain immune cells stuck in overdrive-and early signs of axon loss. That’s why someone can have no new lesions on an MRI but still be losing strength, balance, or memory.

What Do Disease-Modifying Therapies Actually Do?

There are 21 FDA-approved disease-modifying therapies (DMTs) for MS today. All of them target inflammation. They work by calming the immune system-blocking immune cells from crossing into the brain, reducing their activity, or wiping out certain types of immune cells entirely. For people with RRMS, these drugs can cut relapse rates by 30% to 50%. Some reduce new MRI lesions by 70% or more.

But here’s the gap: DMTs don’t stop the slow burn of axon loss. They’re great at preventing new attacks, but they can’t repair dead nerves or restore lost function. That’s why someone on a powerful DMT might still need a cane five years later. The inflammation is under control, but the damage beneath it keeps growing.

Current DMTs include injectables like interferon beta, oral pills like fingolimod and dimethyl fumarate, and infusions like ocrelizumab and natalizumab. Each has different risks and benefits. Ocrelizumab, for example, targets B cells-a type of immune cell now known to play a big role in progressive MS. It’s one of the few DMTs approved for primary progressive MS, but even then, it only slows decline modestly.

Why Progressive MS Doesn’t Respond Like RRMS

Progressive MS-whether it starts as primary progressive (PPMS) or evolves from RRMS-is a different beast. In RRMS, the problem is mostly outside the brain: immune cells from the blood cross the blood-brain barrier and attack. In progressive MS, the fight moves inside. B cells gather in the meninges-the membranes around the brain-and form structures that look like lymph nodes. These act like local factories, producing inflammatory chemicals that slowly poison the tissue underneath.

That’s why anti-inflammatory drugs that work wonders for RRMS often fail in SPMS or PPMS. The immune cells causing damage aren’t coming from the blood anymore. They’re already inside, entrenched, and not easily reached by current drugs. Studies show that people with these lymphoid-like structures in their meninges tend to have earlier onset, faster decline, and higher death rates.

Also, the brain’s own repair system gets worn out. Oligodendrocytes-the cells that make myelin-can’t keep up. The environment becomes toxic: low oxygen, high free radicals, and failing mitochondria. Even if you could stop inflammation tomorrow, the neurons would still be dying from the inside out.

What’s on the Horizon: New Treatments Beyond Inflammation

Scientists aren’t giving up. There are 17 active clinical trials targeting the neurodegenerative side of MS-not just the inflammation. One promising area is protecting axons. Researchers are testing drugs that block sodium channels, which become overactive in demyelinated nerves and cause energy overload. Another targets mitochondria, trying to boost their function so axons don’t starve.

Then there’s remyelination. Drugs like opicinumab and clemastine are being studied to wake up the brain’s own repair cells and get them to rebuild myelin. Early results are mixed, but the idea is simple: if you can restore insulation, you might restore function-even in damaged nerves.

Another frontier is the brain’s immune cells, microglia. In progressive MS, they turn from protectors into attackers. New therapies aim to reset them. And then there’s the role of astrocytes-star-shaped brain cells that support neurons. Loss of their β2-adrenergic receptors seems to worsen both inflammation and neurodegeneration. Drugs that reactivate these receptors could be a double win.

None of these are approved yet. But they represent a shift: from treating attacks to saving nerves.

What You Can Do Now

While we wait for better drugs, there are things that matter. Exercise isn’t just good for your mood-it helps preserve brain volume and keeps nerves functioning longer. Studies show people with MS who do regular aerobic activity have less brain atrophy over time.

Vitamin D isn’t a cure, but low levels are strongly linked to higher MS risk and faster progression. If your levels are low, supplementing may help slow things down.

Smoking is a major red flag. People with MS who smoke decline twice as fast as non-smokers. Quitting is one of the most powerful things you can do.

And don’t ignore mental health. Depression and stress raise inflammation. Cognitive rehab, therapy, and mindfulness practices can help your brain adapt and compensate for damage.

Measuring Progress-Beyond the EDSS

Doctors still rely heavily on the Expanded Disability Status Scale (EDSS) to track MS. But it’s flawed. It measures walking ability more than anything else. Someone could lose memory, coordination, or bladder control and still score the same on EDSS.

More accurate tools are emerging. The Multiple Sclerosis Functional Composite (MSFC) looks at walking speed, arm function, and thinking tests. Brain scans that measure gray matter atrophy are even better. Studies show gray matter shrinkage predicts disability better than EDSS over the long term.

If you’re on a DMT, ask your neurologist about tracking these measures-not just relapses and MRI lesions. You need to know if your treatment is protecting your brain, not just stopping flare-ups.

Final Thoughts: The Real Battle

Multiple Sclerosis isn’t a single disease. It’s two diseases in one: an inflammatory one, and a degenerative one. The first can be tamed. The second is still fighting back.

Today’s treatments give you time. But the goal now isn’t just to reduce relapses-it’s to keep your nerves alive. The next generation of drugs won’t just quiet the immune system. They’ll feed the axons, rebuild the insulation, and protect the brain from its own slow collapse.

For now, the best strategy is simple: treat inflammation aggressively, protect your nerves with lifestyle, and stay informed about new trials. You’re not just managing symptoms. You’re buying time-for yourself, and for the science that’s coming.