How is polyneuropathy diagnosed? Tests and what they can show

I have neuropathy myself, and when I started reading about diagnosis I wanted a plain map: what happens, in what order, and what each test can and can’t show. Here’s the short version. Polyneuropathy is usually diagnosed in steps: your story and a neurological examination first, then a few targeted tests, usually blood tests and often nerve conduction studies with EMG, to confirm the pattern and look for a treatable cause. More specialised tests come in only when there’s a specific question to answer. This is about adults with the most common pattern, the one that starts in both feet.

Where does a polyneuropathy diagnosis start?

For most people it starts with a family doctor or GP, where much of the first round can happen. If more is needed, you’re referred to a neurologist, a neurophysiology lab for nerve tests, or both. How this works varies between countries and health systems, and your own doctor will follow local guidance.

The conversation and the examination are the real foundation. A 2023 review in the Canadian Medical Association Journal (CMAJ) describes tests as a way to sort between the possibilities they raise.^{1, 3}

The most common form is distal symmetric polyneuropathy (DSP). “Distal” means furthest from the body’s centre and “symmetric” means both sides are affected in a similar way. It typically begins in the feet and mainly affects feeling.¹ Most research on diagnostic testing is about this pattern.

What your doctor will probably ask about

These are the topics the US National Institute of Neurological Disorders and Stroke (NINDS) lists, and it helps to think them through beforehand:⁴

• When and how it started, and how quickly it has changed.
• Other health conditions, such as diabetes, kidney or liver disease, or hormone problems.
• Alcohol and other everyday habits.
• Your diet, since low vitamin B12 is one of the best-known vitamin-related causes.
• Medicines, since some drugs, including some cancer and infection treatments, can occasionally affect nerves.
• Your work and any exposure to toxins.
• Nerve disease in the family.

What happens in the examination

Your doctor tests feeling, such as vibration and pain, plus reflexes and strength. In DSP, typical findings are reduced feeling in the feet and weak or missing ankle reflexes, sometimes with some weakness far down in the legs. Signs that a neuropathy has been there a long time, such as high-arched feet (pes cavus), hammer toes or thin calves, can point towards an inherited form.¹

This step matters a lot. The CMAJ review estimates that for DSP, the history and examination point to a likely cause in nearly 60% of people, and screening blood tests find one in roughly another 10%. These are approximate figures from a narrative review.¹

Which blood tests are used for polyneuropathy, and why?

Blood tests can show diabetes, vitamin deficiencies, liver or kidney problems, other metabolic disorders, infections and signs of abnormal immune activity. Each answers its own question: glucose and HbA1c look for diabetes, vitamin B12 for a deficiency, and serum protein electrophoresis for an abnormal antibody protein (a paraprotein) that can be linked to some neuropathies.^{4, 5, 6}

A US guideline on DSP from the American Academy of Neurology (AAN), AANEM and AAPM&R found that glucose, B12 with its metabolites, and serum protein immunofixation electrophoresis turned up abnormal results most often. It says these screening tests “may be considered” and rates the evidence as weak (Level C). It dates from 2009 and was reaffirmed in 2025. If routine tests don’t clearly show diabetes, a glucose tolerance test may also be considered.^{5, 7}

Lists differ. The CMAJ review adds a blood count, salts (electrolytes), kidney and liver tests and HbA1c.¹ Recommendations also differ between countries, so there’s no single panel everyone should have.

Even with diabetes, other treatable causes should still be considered. Many causes that blood tests find can be treated, which gives a real possibility of improvement, though not a guarantee.^{1, 3}

What do nerve conduction studies and EMG actually measure?

• Nerve conduction studies measure how fast, and how well, your nerves carry electrical signals, using electrodes on the skin and brief, weak electrical pulses.
• Electromyography (EMG) uses a hair-thin needle in a few selected muscles to record their electrical activity at rest and when you tense them.

Both can be somewhat uncomfortable, but no local or general anaesthesia is needed. You do need to be able to cooperate, especially during EMG.⁸

The results help confirm and describe a polyneuropathy: whether the damage mainly affects the nerve fibre itself (axonal) or its insulating layer, the myelin (demyelinating); whether it involves the nerves for movement, for feeling, or both; and whether it looks acquired or inherited. That narrows down the likely causes. Some conditions, such as demyelinating neuropathies, can only be diagnosed this way.^{1, 4, 8}

Does everyone have them?

The CMAJ review suggests them for most people with polyneuropathy, especially when the cause is unclear, but says it’s uncertain whether everyone with suspected DSP needs them. It cites four observational studies where testing was linked to a change in diagnosis or treatment for more than 40% of patients, though only one focused on people referred for DSP. A reference from the American Academy of Physical Medicine and Rehabilitation (AAPM&R) calls them essential when the neuropathy is atypical, uneven, mainly affects strength, progresses quickly or may be immune-related.^{1, 6}

What they can’t show

Standard nerve conduction studies only test the larger fibres, the large and medium-sized ones that conduct fastest, so in a neuropathy affecting only the small fibres the results are normal.^{1, 8} So a normal result doesn’t rule out every neuropathy, but on its own it doesn’t mean you have small-fibre neuropathy either.

When might a skin biopsy or other specialist test come in?

These aren’t part of a standard work-up. They answer particular questions.

Skin biopsy for small-fibre neuropathy

Small-fibre damage mainly causes pain and changed sensation, such as burning or unusual sensitivity to touch.¹ In a skin biopsy, a 3 mm piece of skin is taken from the lower leg under local anaesthetic. The nerve fibres in the outer skin layer are stained, counted and compared with normal values for your age.

A European guideline from the EFNS and the Peripheral Nerve Society (PNS) treats it as validated, and it’s regarded as the reference test for small-fibre neuropathy. Ten laboratories reported no serious side effects in about 35,000 biopsies and minor ones in 0.19%, their own reported experience rather than trial data.^{3, 9}

It shows that small fibres are reduced, not why. The count doesn’t reflect how bad the pain is, results depend on careful lab quality control, and availability varies.^{1, 9}

Other specialist tests

Autonomic function tests check the nerves that control sweating, heart rate and blood pressure, with sweat recordings and heart rate and blood pressure measurements during deep breathing, blowing into a tube and standing up. They may be considered when an autonomic neuropathy is suspected.^{1, 3}

A lumbar puncture (spinal fluid sample) is done less often. It looks for abnormal proteins or immune cells, so it’s mostly relevant when an inflammatory neuropathy is suspected. For CIDP (chronic inflammatory demyelinating polyradiculoneuropathy), an immune-related neuropathy, the European EAN/PNS guideline advises considering it only in defined situations, such as an uncertain diagnosis, not routinely.^{4, 10}

A nerve biopsy removes a small piece of a sensory nerve, usually at the lower leg (the sural nerve). It’s an older, more invasive specialist-centre test, useful when causes such as vasculitis (inflamed blood vessels), sarcoidosis or infiltrative disorders are suspected. It can leave lasting nerve pain and loss of feeling, and for many, but not all, people a skin biopsy can replace it.^{1, 3, 4}

Genetic testing is used when an inherited neuropathy is suspected, with the test chosen from the clinical picture, the inheritance pattern and the nerve conduction findings. For an unexplained neuropathy with no signs of an inherited form, the AAN guideline found not enough evidence to support routine genetic testing.⁵

Imaging: MRI of the brain or spine isn’t indicated for peripheral neuropathy unless something points to the brain or spine. Spinal MRI can show pinched nerves, and nerve ultrasound can find trapped nerves and is proving useful in inflammatory neuropathies.^{3, 4, 6}

Polyneuropathy tests at a glance

This is the overview I wanted when I started reading. It’s not a checklist: most people only have a few of these, chosen for the questions their own symptoms raise.

Test	What it helps answer	What happens	Its limits
Your history and a neurological examination	What pattern is this, how fast is it changing, is there an obvious cause?	Talking, then checks of feeling, reflexes and strength.	Can’t show on its own whether the damage is axonal or demyelinating.
Glucose and HbA1c, sometimes a glucose tolerance test	Could diabetes or raised blood sugar be the cause?	Blood tests; a tolerance test adds a sugary drink.	Finding diabetes doesn’t rule out other treatable causes.
Vitamin B12, sometimes with methylmalonic acid	Am I low in B12?	A blood test.	Support for routine screening rests on weak evidence.
Serum protein electrophoresis with immunofixation	Is there a paraprotein that can be linked to some neuropathies?	A blood test.	Support for routine screening rests on weak evidence.
Other blood tests (blood count, salts, kidney and liver tests)	Is another condition affecting the nerves?	Blood tests.	No single agreed panel; sources list different tests.
Nerve conduction study	Are the larger nerves affected? Axonal or demyelinating? Movement, feeling or both?	Skin electrodes and brief, weak electrical pulses.	Normal in pure small-fibre neuropathy.
EMG	Are the muscles affected by nerve damage?	A thin needle in a few muscles, at rest and when you tense them.	Can be uncomfortable; doesn’t assess small fibres.
Skin biopsy	Are there fewer small nerve fibres in the skin than there should be?	A 3 mm skin sample from the lower leg, under local anaesthetic.	Shows that, not why; doesn’t measure pain; needs a specialised lab.
Autonomic function tests	Are the nerves for sweating, heart rate or blood pressure affected?	Sweat, heart rate and blood pressure recordings.	Specialised; mainly when autonomic neuropathy is suspected.
Lumbar puncture	Are there signs of an inflammatory neuropathy such as CIDP?	A small spinal fluid sample via a needle in the lower back.	Used less often, only in selected situations.
Nerve biopsy	Is there vasculitis, sarcoidosis or infiltration of the nerve?	A small piece of sensory nerve is removed.	Invasive; can cause lasting pain or numbness.
Genetic testing	Is this an inherited neuropathy?	A sample for genetic analysis.	Not enough evidence for routine use without hereditary features.
Imaging (MRI, nerve ultrasound)	Is there a spine or brain problem, or a trapped nerve?	Scans.	MRI doesn’t help typical polyneuropathy unless something points to the brain or spine.

Do you really need every test?

Almost certainly not, and that isn’t anyone cutting corners. No test is perfectly accurate. In DSP, the history reveals most of the causes that can be identified, and screening blood tests add a smaller share. The advanced tests mainly help when the pattern is atypical or a specific cause is suspected.^{1, 3, 6}

A test that isn’t aimed at a real question adds burden without adding information. Brain or spine MRI in typical polyneuropathy is one example, and routine genetic testing without hereditary features is another.^{5, 6} Nerve biopsy and lumbar puncture are also invasive. A short, focused work-up can be exactly right.

If you’re offered a test and want to understand it, these are the three questions I’d want answered:

• What question is this test meant to answer?
• How could the result change what we do next?
• If the result is normal, what would that tell us, and what wouldn’t it?

What if no cause is found?

Then you’re far from alone. In many people no cause is found, and it’s called idiopathic or cryptogenic polyneuropathy. Chronic idiopathic axonal polyneuropathy (CIAP) is the term for a slowly progressing polyneuropathy in people who can walk independently, typically starting after 60.^{1, 11}

Estimates vary: the CMAJ review gives around 30% of people with DSP, the AAPM&R reference about 25% of people with peripheral neuropathy in a referral population, and a Cochrane review 10–25% of people referred with polyneuropathy.^{1, 6, 11} These figures describe groups, not what will happen to you.

The Cochrane review describes CIAP as slowly progressive, affecting feeling, or feeling and strength. Severe disability is uncommon, but it does reduce quality of life. Based on evidence up to 2016, there’s no proven drug treatment aimed at CIAP itself, so care focuses on symptoms and everyday function.¹¹

How often you’re seen again is for you and your doctor to agree. What matters most is a change: faster worsening, new weakness, symptoms on one side, or spread beyond the usual pattern. Those call for a prompt specialist assessment, and they’re good reasons to get back in touch if they turn up later.¹

I’m not a doctor. I’ve written this from published research and guidance, and to help you prepare questions for your own care. I hope it makes the process feel a little less like a black box.

Sources

1. Mirian A, Aljohani Z, Grushka D, Florendo-Cumbermack A. Diagnosis and management of patients with polyneuropathy. CMAJ 2023;195(6):E227–E233 (correction: CMAJ 2023;195(11):E415). https://www.cmaj.ca/content/195/6/E227
2. National Institute of Neurological Disorders and Stroke. Guillain-Barré Syndrome. Last reviewed 13 March 2026. https://www.ninds.nih.gov/health-information/disorders/guillain-barre-syndrome
3. NeuropathyCommons (Mass General Brigham). Diagnosing Peripheral Neuropathy. Undated. https://neuropathycommons.org/neuropathy/tests-diagnosing-small-fiber-polyneuropathy
4. National Institute of Neurological Disorders and Stroke. Peripheral Neuropathy. Last reviewed 13 March 2026. https://www.ninds.nih.gov/health-information/disorders/peripheral-neuropathy
5. England JD, Gronseth GS, Franklin G, et al. Practice Parameter: Evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Neurology 2009;72:185–192. https://www.neurology.org/doi/10.1212/01.wnl.0000336370.51010.a1
6. Smith M, Nwankwo J. Peripheral Polyneuropathy Part 1: Evaluation and Differential Diagnosis. PM&R KnowledgeNow, American Academy of Physical Medicine and Rehabilitation. Last updated 14 May 2026. https://now.aapmr.org/approach-to-peripheral-polyneuropathy-evaluation-and-differential-diagnosis/
7. American Academy of Neurology. Evaluation of Distal Symmetric Polyneuropathy: Role of Laboratory and Genetic Testing (guideline status: reaffirmed 8 February 2025). https://www.aan.com/Guidelines/home/GuidelineDetail/315
8. Horowitz SH; NeuropathyCommons. Electromyography (EMG) and Nerve Conduction Studies. Undated. https://neuropathycommons.org/diagnosis/electromyography-nerve-conduction
9. Lauria G, Hsieh ST, Johansson O, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2010;17(7):903–e49. https://onlinelibrary.wiley.com/doi/10.1111/j.1468-1331.2010.03023.x
10. Van den Bergh PYK, van Doorn PA, Hadden RDM, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force – Second revision. Eur J Neurol 2021. https://onlinelibrary.wiley.com/doi/10.1111/ene.14959
11. Warendorf J, Vrancken AFJE, van Schaik IN, Hughes RAC, Notermans NC. Drug therapy for chronic idiopathic axonal polyneuropathy. Cochrane Database of Systematic Reviews, 20 June 2017. https://www.cochrane.org/evidence/CD003456_drug-therapy-chronic-idiopathic-axonal-polyneuropathy

Sources checked on 24 September 2026.