Idiopathic neuropathy: what it means when no cause is found

What “idiopathic” means

Idiopathic simply means “of unknown cause.” Doctors use it when the history, the examination, blood tests and usually a nerve conduction study have not shown why the nerves are failing. It is a diagnosis of exclusion, and family doctors’ guidance calls it a presumptive one, which means it can be revisited if something new turns up. You may also see it called cryptogenic neuropathy.

When a nerve conduction study shows that the nerve fibers themselves are damaged, rather than their insulating coating, the full name is chronic idiopathic axonal polyneuropathy, or CIAP: a slowly creeping sensory, or sensory and motor, neuropathy of older adults. What “axonal” means on a nerve test report.

How common it is

Very. Peripheral neuropathy affects roughly 1 to 7 percent of the general population, more after 50, and in a large share of people no cause is ever found. Estimates of that share range from about a tenth to nearly half, depending on who is studied and how thoroughly. Family-medicine guidance puts it at 25 to 46 percent, rising with age; specialist clinics report lower figures; and in one Dutch population study, almost half of the middle-aged and older people found to have polyneuropathy had no cause.

It usually begins in a person’s 50s or later, and it is more common in men: in one large Dutch study, about two in three people with CIAP were men.

What it usually feels like

• Numbness, tingling or burning that starts in the toes and feet on both sides and creeps slowly upward. Once it reaches about the knees, the hands may begin to be affected.
• Pain in some people but not all: in a UK study of 50 people with CIAP, 22 had painful neuropathy. Burning pain is typical when mainly the small fibers are affected.
• Balance trouble, usually later in the course, such as unsteadiness in the dark or walking “more carefully.” Polyneuropathy is linked with walking problems and a higher risk of falls.
• Little or no weakness. Most people have full strength or only slight weakness of the ankles and toes. Marked weakness is a reason to look harder for another cause.

Numb feet, by pattern and cause.

Has everything been checked?

A neurology-led practice guideline from 2009, since reaffirmed, names the three blood tests most likely to turn up a problem in this kind of neuropathy. Family-medicine guidance adds a few routine ones. A complete work-up usually includes:

Two of these are easy to miss. A 2012 University of Michigan study of US patients found that almost a quarter of people diagnosed with neuropathy had an expensive, low-yield MRI, while very few had the inexpensive glucose tolerance test. And methylmalonic acid is easy to skip when the B12 level is in the low-normal range. If your B12 was low-normal, or you take metformin, which can lower B12, ask whether methylmalonic acid was checked. How B12 deficiency neuropathy is tested and treated.

The history matters as much as the blood tests. Bring a list of every medicine and supplement, including doses. Too much vitamin B6, usually from supplements, can cause neuropathy; the US upper limit for adults is 100 mg a day, and Europe’s food safety agency has set a much lower limit of 12 mg a day. Some medicines can too, such as certain chemotherapy drugs and some antibiotics taken for months. Fluoroquinolone antibiotics, such as ciprofloxacin or levofloxacin, can cause nerve damage even after a short course. Ask your prescriber before stopping anything. Long-term heavy drinking is a known cause worth discussing openly. How much vitamin B6 is too much.

Causes that sometimes turn up later

• Prediabetes. Impaired glucose tolerance was found in 25 to 36 percent of people with idiopathic neuropathy, compared with 15 percent of people in comparison groups, and more often when the neuropathy was painful. Experts still debate how much it causes the nerve damage: in one UK controlled study, the difference could have been due to chance once age and sex were taken into account.
• Metabolic and heart-health risk factors. In a Dutch study, 55 percent of people with CIAP met the criteria for metabolic syndrome, compared with 34 percent of a comparison group from the general population. Waist size, blood pressure, blood fats and blood sugar have all been linked with neuropathy, even in people without diabetes.
• Sjögren’s disease, an autoimmune condition that often causes dry eyes and a dry mouth. When Sjögren’s affects the nerves, nerve symptoms can come before the Sjögren’s diagnosis in up to 90 percent of cases, and the dryness may be mild or go unnoticed, so it is worth asking about, especially for women.
• Celiac disease, which is sometimes checked, especially when the pattern is unusual. In one UK clinic series, biopsy-proven celiac disease was found in at least 9 percent of people with idiopathic neuropathy, compared with 1 percent of healthy controls.
• Inherited neuropathy, such as Charcot-Marie-Tooth disease, which can be mild enough to go unnoticed until later life. How Charcot-Marie-Tooth disease affects the feet.

How often does a second look find something? It depends on the kind of look. In a Dutch study that followed 75 people with CIAP for about five years, a definite cause turned up in only four, and simply repeating the same blood tests was not useful. Specialist neuromuscular centers sometimes find more. When a cause does turn up, it is often an inherited or inflammatory neuropathy, as in three of the four people in that Dutch study. So a targeted re-look is worthwhile, by a neuromuscular specialist, prompted by new or unusual symptoms or by a test that was never done. Re-running the same panel without a new reason is not.

Outlook

The outlook is usually reassuring. In the Dutch five-year study, the neuropathy progressed slowly and any handicap was not severe. In a later Dutch study, people with CIAP were still walking more than 10 years after it began, without severe disability. It is not harmless, though: it reduces quality of life. In the five-year study, nearly half of the people with the sensory and motor type needed a walking cane, and many also wore ankle braces, while only 1 of 21 people with the purely sensory type needed a cane.

Is it fatal? Idiopathic neuropathy is not described as a fatal condition. Large population studies have linked neuropathy, including in people without diabetes, with a higher risk of death, but that is an association, and one of them, in UK adults, suggested that part of it runs through metabolic factors such as blood sugar and waist size. That is one more reason to have blood pressure, blood fats, blood sugar and weight looked after. The real risks of neuropathy, explained.

Treatment

No drug has been proven to slow or reverse CIAP itself; a Cochrane review found no adequate trials. Treatment therefore targets what can be changed:

• Nerve pain. The UK’s NICE recommends starting with one of amitriptyline, duloxetine, gabapentin or pregabalin, and trying another if the first doesn’t help or isn’t tolerated. That advice covers nerve pain generally; the American Academy of Neurology’s guidance for diabetic nerve pain, the best-studied kind, lists the same families of medicines plus sodium-channel blockers and advises against opioids. The aim is to reduce pain, not necessarily to stop it: in trials, a reduction of about 30 percent counts as success. Several of these medicines can cause dizziness and sleepiness, which matters for balance. Neuropathy medicines compared.
• Balance and strength. Physical therapy with balance training is a core part of care, sometimes with a cane or brace. Strengthening exercise can build strength in weak muscles, and recent reviews in diabetic neuropathy found modest gains in balance, walking speed and leg strength, though they have not shown fewer falls, and trials specifically in idiopathic neuropathy are lacking. Exercises for neuropathy.
• Metabolic health. In a small 2006 study of 32 people with prediabetes-related neuropathy, with no comparison group, a year of diet and exercise counseling increased the number of small nerve fibers in skin biopsies by about a third, and pain improved, though people with the most nerve loss did not improve. In a University of Michigan study of people who had weight-loss surgery for obesity, nerve fiber density two years later had improved in the thigh and held steady in the lower leg. Stopping smoking also protects the feet.
• Foot protection. Check numb feet every day for blisters, cuts and calluses, wear well-fitting padded shoes and socks, and see a podiatrist regularly if your feet are at high risk. How to do a daily foot check.

Idiopathic small fiber neuropathy

When the damage is mainly in the small fibers that carry pain and temperature, burning feet can come with a normal nerve conduction study. A skin biopsy that counts nerve fibers is the test most often used to confirm it. About half or more of small fiber neuropathy stays idiopathic. Prediabetes has been found in up to half of the idiopathic cases, Sjögren’s disease accounts for nearly 10 percent of small fiber neuropathy, and B12 deficiency may be underdiagnosed, so those are worth checking.

It usually progresses slowly and then levels off, and a minority, up to about a third, later spread to the large fibers. In a Mayo Clinic study, most people with idiopathic small fiber neuropathy did not develop major disability, but they had more heart attacks than people without it, another reason to look after heart health. More on small fiber neuropathy.

When to ask for a neurologist or a second look

Family-medicine guidance suggests seeing a neurologist when the history, examination and first tests haven’t explained the neuropathy, and more urgently when symptoms came on quickly or are severe or getting worse. Ask for a fresh look if you notice any of these, because they don’t fit typical idiopathic neuropathy:

• one side much worse than the other, or patches rather than both feet evenly
• symptoms that came on over days or weeks, or are getting worse quickly
• weakness out of proportion to the numbness, or marked loss of balance and position sense
• symptoms that started in the hands, or a pattern that doesn’t begin at the toes
• weight loss, fever, joint inflammation, skin changes, or autonomic symptoms such as dizziness on standing, bowel or bladder changes, or changes in sweating

Which kind of doctor treats neuropathy.

When to get help urgently

• Go to an emergency department for weakness or tingling that is spreading over hours or days, and call 911 if you also have trouble breathing or swallowing. These can be signs of Guillain-Barré syndrome.
• Call 911 for sudden numbness or weakness of the face, arm or leg, especially on one side, or sudden trouble speaking, seeing or walking. These can be signs of a stroke.
• See a clinician the same day for a wound on a numb foot, or for redness, swelling or warmth in one. If the redness is spreading or you feel feverish, go to urgent care or an emergency department.

Common questions

Related reading

Axonal neuropathy · Small fiber neuropathy · Vitamin B12 neuropathy · Nerve conduction study and EMG · Types of neuropathy · Can neuropathy be reversed? · Neuropathic pain