Peripheral Neuropathy vs MS: Key Differences Explained by an Expert Neurologist

Numbness. Tingling. Weakness. These symptoms can be frightening, especially when you don't know what's causing them. Two conditions that commonly cause these symptoms are peripheral neuropathy and multiple sclerosis (MS)—and telling them apart isn't always straightforward.

If you're experiencing neurological symptoms and wondering whether you might have peripheral neuropathy, MS, or something else entirely, this guide will help you understand the key differences between these conditions, how doctors distinguish between them, and when to seek specialist evaluation.

Understanding the Nervous System

To understand the difference between peripheral neuropathy and MS, it helps to know how the nervous system is organized:

Central Nervous System (CNS):

• Brain and spinal cord
• Processes information, controls thinking, and initiates movement
• Affected in MS

Peripheral Nervous System (PNS):

• All nerves outside the brain and spinal cord
• Carries signals between the CNS and the rest of your body
• Affected in peripheral neuropathy

Both systems work together, but they respond to disease differently and require different diagnostic approaches.

Key Differences at a Glance

How Symptoms Compare

Numbness and Tingling

Peripheral Neuropathy:

• Typically begins in the toes and gradually spreads upward
• Often described as "stocking-glove" distribution (affecting areas covered by socks and gloves)
• Usually symmetric (both sides affected equally)
• Tends to progress slowly over months to years
• May include burning, "pins and needles," or electric sensations

Multiple Sclerosis:

• Can occur anywhere in the body
• Often affects one side more than the other (asymmetric)
• May involve the trunk, face, or other areas unusual for neuropathy
• Often comes on over days to weeks, then may improve (relapsing pattern)
• May be associated with a tight "band-like" sensation around the trunk (MS hug)

Weakness

Peripheral Neuropathy:

• Usually affects the feet first, then hands
• Difficulty lifting the front of the foot (foot drop) is common
• Weakness tends to be distal (further from the body core)
• Generally symmetric

Multiple Sclerosis:

• Can affect any muscle group
• May involve one limb while sparing others
• Can cause spasticity (stiffness and muscle tightness)
• Often associated with increased reflexes

Vision Problems

Peripheral Neuropathy:

• Vision is typically not affected (peripheral nerves don't control vision)

Multiple Sclerosis:

• Vision problems are common and often an early symptom
• Optic neuritis: Pain with eye movement and blurred vision in one eye
• Double vision (diplopia)
• Involuntary eye movements (nystagmus)

Balance and Coordination

Peripheral Neuropathy:

• Balance problems from sensory loss (can't feel the floor properly)
• Typically worse in the dark or with eyes closed
• Coordination usually preserved unless motor nerves are affected

Multiple Sclerosis:

• Balance and coordination problems from cerebellar or brainstem involvement
• May include tremor, difficulty with fine movements
• Ataxia (uncoordinated movement)

Bladder and Bowel Function

Peripheral Neuropathy:

• Usually only affected in autonomic neuropathy
• Not typical in common sensory neuropathies

Multiple Sclerosis:

• Bladder urgency, frequency, or retention is common
• Often develops as the disease progresses
• Results from spinal cord involvement

Fatigue

Peripheral Neuropathy:

• Fatigue is not a primary symptom
• Sleep may be disrupted by pain

Multiple Sclerosis:

• Profound, debilitating fatigue is one of the most common symptoms
• Often described as different from normal tiredness
• Can occur even with minimal physical activity

Cognitive Changes

Peripheral Neuropathy:

• Does not affect thinking or memory

Multiple Sclerosis:

• Cognitive symptoms occur in 40-65% of patients
• May include memory problems, slowed thinking, difficulty concentrating
• Often subtle but can impact daily function

Diagnostic Approaches

Testing for Peripheral Neuropathy

The workup for suspected peripheral neuropathy typically includes:

Nerve Conduction Studies and EMG:

• Measures how well nerves conduct electrical signals
• Can identify large fiber damage
• Helps determine the type and location of nerve injury

Small Fiber Skin Biopsy:

• Gold standard for diagnosing small fiber neuropathy
• Important when EMG is normal but symptoms persist
• Measures nerve fiber density in the skin

Blood Tests:

• Checks for diabetes, vitamin deficiencies, thyroid dysfunction
• Screens for autoimmune conditions and infections
• Identifies treatable causes

Nerve Ultrasound:

• Visualizes nerve structure
• Can identify compression or inflammation

Testing for Multiple Sclerosis

The workup for suspected MS includes:

MRI of Brain and Spinal Cord:

• Shows characteristic white matter lesions
• Can identify lesions "disseminated in space and time"
• Most important test for MS diagnosis

Lumbar Puncture:

• Analyzes cerebrospinal fluid
• Looks for oligoclonal bands (immune markers)
• Helps support diagnosis when MRI is uncertain

Evoked Potentials:

• Measures electrical activity in response to stimulation
• Can detect slowed conduction in the optic nerve or spinal cord
• Useful when symptoms suggest MS but MRI is inconclusive

Optical Coherence Tomography (OCT)

• Uses light waves to create detailed images of the optic nerve
• Can help track disease progression over time

Blood Tests:

• Rules out other conditions that can mimic MS
• Checks for related autoimmune conditions

When Symptoms Overlap

Some situations make distinguishing between these conditions challenging:

MS with Peripheral Involvement

While rare, some MS patients also develop peripheral neuropathy. Additionally, certain MS symptoms can mimic peripheral involvement:

• Lhermitte's sign (electric sensation down the spine with neck flexion)
• Sensory symptoms from spinal cord lesions

Autoimmune Conditions Affecting Both Systems

Some autoimmune diseases can affect both the central and peripheral nervous systems:

• Sarcoidosis
• Sjögren's syndrome
• Lupus

Central Nervous System Causes of "Neuropathy-Like" Symptoms

Spinal cord problems can sometimes mimic peripheral neuropathy:

• Cervical myelopathy (spinal cord compression in the neck)
• B12 deficiency (can affect both CNS and PNS)
• Vitamin E deficiency

Red Flags That Suggest MS Rather Than Neuropathy

Certain features should raise concern for MS rather than peripheral neuropathy:

• Vision problems: Pain with eye movement, sudden vision loss in one eye
• Symptoms affecting the face or trunk: Numbness in patches on the body or face
• Increased reflexes: Brisk, exaggerated reflex responses
• Lhermitte's sign: Electric sensation down the spine when bending the neck
• Episodes that come and go: Symptoms lasting days to weeks, then improving
• Cognitive changes: New problems with memory or thinking
• Young age at onset: Symptoms beginning between ages 20-40
• Bladder/bowel symptoms: New urgency or difficulty with urination

When Both Need to Be Considered

In some cases, a thorough evaluation for both conditions may be appropriate:

• Symptoms don't fit a typical pattern for either condition
• Initial testing is inconclusive
• Symptoms involve both central and peripheral nervous system features
• Underlying autoimmune condition may affect multiple systems

A comprehensive neurological evaluation can help sort through these complexities.

The Importance of Accurate Diagnosis

Getting the right diagnosis matters for several reasons:

Treatment differs significantly:

• MS: Disease-modifying therapies to prevent relapses and progression
• Neuropathy: Treating the underlying cause, symptom management

Prognosis varies:

• Both conditions have variable outcomes depending on type and cause
• Early, accurate diagnosis leads to better outcomes

Monitoring requirements differ:

• MS: Regular MRI surveillance, monitoring for disease activity
• Neuropathy: May include repeat nerve testing, addressing underlying causes

Life planning:

• Understanding your diagnosis helps with lifestyle modifications and planning

Getting the Right Specialist Evaluation

If you're experiencing neurological symptoms that could represent either peripheral neuropathy or MS (or something else entirely), seek evaluation from a neurologist who can:

• Perform a thorough neurological examination
• Order and interpret appropriate testing
• Consider the full range of diagnostic possibilities
• Develop a tailored treatment plan

At Achilles Neurology Clinic, we specialize in both multiple sclerosis evaluation and peripheral neuropathy diagnosis. Our comprehensive approach ensures that nothing is overlooked in determining the cause of your symptoms.

Frequently Asked Questions

Can you have both peripheral neuropathy and MS?

Yes, though it's uncommon. Some patients with MS develop peripheral neuropathy from other causes (diabetes, medication effects), and certain autoimmune conditions can affect both systems. If you have both central and peripheral symptoms, comprehensive evaluation is important.

What's the main difference between MS and neuropathy symptoms?

The main difference is location and pattern. Peripheral neuropathy typically causes symptoms in a "stocking-glove" pattern starting in the feet and hands. MS can cause symptoms anywhere, often affects one side more than the other, and commonly involves vision, balance, or cognition—features not seen in typical neuropathy.

Can neuropathy turn into MS?

No. Peripheral neuropathy does not progress to or cause MS. They are separate conditions affecting different parts of the nervous system. However, some symptoms may initially be attributed to one condition before the correct diagnosis is made.

How do doctors tell the difference between MS and neuropathy?

Doctors use a combination of clinical examination, history, and testing. Key tests include MRI (for MS) and nerve conduction studies/EMG (for neuropathy). The pattern of symptoms, examination findings (like reflexes), and response to treatment also help distinguish between them.

Is numbness and tingling more likely to be MS or neuropathy?

It depends on the pattern. Numbness starting in the feet and spreading symmetrically upward is more typical of peripheral neuropathy. Numbness affecting one side, the trunk, face, or coming and going in episodes is more suggestive of MS or other central causes. A neurological evaluation is needed to be sure.

Should I see a neurologist for numbness in my feet?

Yes. Persistent numbness in the feet warrants evaluation by a neurologist who can determine whether you have peripheral neuropathy, a central nervous system condition, or another cause—and recommend appropriate treatment.

Take the Next Step

If you're experiencing numbness, tingling, weakness, or other neurological symptoms and aren't sure what's causing them, getting an accurate diagnosis is essential. Whether your symptoms point toward peripheral neuropathy, MS, or another condition, the right diagnosis leads to the right treatment.

About the Author

Dr. Achillefs Ntranos MD

Board-Certified Neurologist
Achilles Neurology Clinic

Dr. Achillefs Ntranos MD is a board-certified neurologist and MS specialist known for his thorough evaluations and compassionate approach. Originally from Greece, he trained at Johns Hopkins University and Mount Sinai Hospital before founding Achilles Neurology Clinic in Beverly Hills to deliver comprehensive, patient-centered neurological care. He specializes in MS, autoimmune neurology, neuropathy, headaches, and other neurological disorders, blending research-driven insights with personalized treatment plans.

Learn More About Dr. Ntranos(310) 774-7025