A conduction problem arising in peripheral nerves is called peripheral neuropathy. Depending on the cause, the damage may be to the axons or the myelin sheaths. The neurons involved may be afferent (sensory), efferent (motor), or both.
The size of axons affected is an important first issue. Some cases of sensory neuropathy involve only the small axons, which are the C unmyelinated fibers and the A-delta fibers. If these are damaged, symptoms are linked to pain sensors in the skin and to autonomic neurons. On the other hand, damage to large sensory fibers, which are the A-alpha and A-beta fibers, cause deficits in proprioception, vibration sensation, and reduced muscle-stretch reflexes.
Consider, for example, a patient with painful sensory neuropathy due to diabetes mellitus, which is a leading cause of peripheral neuropathy. Initially, the patient might complain of burning or tingling sensations in her feet. Abnormal sensations of this type are called paresthesias. There may be hyperalgesia, in which mild stimuli cause pain, and allodynia, in which ordinarily nonpainful stimuli, such as touch, cause pain. The symptoms tend to have a "glove and stocking" distribution, because the longest axons tend to be affected first. The damage in diabetes mellitus is to axons rather than myelin. The fine, unmyelinated nerve endings in the epidermis seem to degenerate first.
Sometimes a skin biopsy is performed to establish a diagnosis of neuropathy of the small, pain nerve endings. To visualize the fine nerve endings, a special immunohistochemical technique is used based on a protein found in these nerve endings. To compare such a skin biopsy from a normal person with a patient with early, diabetic sensory neuropathy, CLICK HERE (Incidentally, a skin biopsy from a patient who has been rubbing capsiacin cream on the skin would show similar degeneration of fine, unmyelinated nerve endings.)
Indeed, the symptoms described above may be an early initial indication of diabetes. The degeneration appears to be linked to impaired glucose tolerance, which seems to impede regeneration of the fine nerve endings. Later, however, larger axons may be involved as well. With sufficient loss of pain sensation, it can be easy for a patient to seriously damage the hands or feet.
If you like, look to the very end of this page, where there is a description of a specific patient with diabetic peripheral neuropathy
Alcoholism is another leading cause of neuropathy linked to axonal damage. Various pathogens, such as the leprosy bacillus, also can interfer with axonal conduction. Vitamin B12 deficiency is another possibility. But often no cause is established for sensory neuropathy, especially with the small axon type.
The Guillain-Barre Syndrome is another example of peripheral neuropathy and is one of the leading causes of severe neuromuscular paralysis. Its pathogenesis is unknown, but the symptoms typically began to develop a few days to a few weeks after an otherwise ordinary infection. Both motor and sensory deficits are found and result from inflammation and subsequent demyelination of peripheral nerves. Accumulations of lymphocytes and monocytes are found around the nerves. Weakness and paresthesias often begin in the legs and progress to the arms. The disorder can be life-threatening due to respiratory failure or autonomic problems. But most patients begin to recover in a few weeks and can return to work in a few months. The incidence increases with age.
Charcot-Marie-Tooth disease is a set of genetic disorders of nerve conduction. Most of the types are demyelinating. Both motor and sensory deficits occur, most commonly showing up during adolescence. This disorder is diagnosed with nerve conduction studies and a nerve biopsy, in which the myelin is observed much like you did last quarter in lab. There are also specific genetic tests. Patients tend to have a very high arch in the foot.
Carpal tunnel syndrome arises when over-use causes inflammation of the region where the median nerve and tendons pass through the carpal bones. At first, damage to the median nerve is primarily demyelinating, but eventually can become axonal.
Bell's palsy is usually due to inflammmation and swelling of the facial nerve at the point where it passes through a narrow foramen in the temporal bone. Facial muscles on the affected side are paralyzed, while those on the opposite side are normal. The eyelid typically droops, although the eye cannot be closed. The onset is typical fairly sudden and then usually clears up after a month or so.
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QUESTION: Why would the symptoms in diabetes mellitus tend to have a "glove and stocking" distribution?
QUESTION: Define "paresthesia". QUESTION: Define "allodynia". |
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The following is a description of a patient with diabetic peripheral neuropathy that was presented in the Journal of the American Medical Association, volume 302, number 1.
I noticed pain in my left foot—it was always the left foot first—and that's when I had just started nursing, back in ’88. I spoke to a friend who was a podiatrist and he started wrapping it and giving me cortisone shots. As time went by, it started developing in my right foot as well. Years later, he sent me for an EMG, and they came back with the finding that I had diabetic neuropathy.
Initially I was put on small dose of amitriptyline at bed time and that caused terrible dryness of my mouth. I would wake up and not even be able to open my mouth. So that stopped. Then I started on Neurontin [gabapentin], and I think dry mouth was still a problem.
My diabetic doctor started me on [lidocaine] patches, and prior to that, he started me on [duloxetine], 60 mg at bedtime. The [duloxetine] really helped initially, a whole lot. It was like a wonder drug for me.
Other things that help are sometimes a massage or arnica rubbed into it to create a little bit of heat. Also ice massages help quite a bit, but I’m hesitant to use that because of vascular complications from the diabetes. Acupuncture helped, but the price of the acupuncture is a deterrent.
I notice a correlation between the control of the diabetes and the pain, the neuropathy symptoms. If I lapse into a sugar binge, I will feel heat and pain in my feet.
My symptoms have gotten much worse since it was first diagnosed. There are cramps that have recently kicked in. My pain has become bilateral, and the numbness seems to be crawling up my legs as well as the swelling in my ankles and my legs.
My understanding of the treatment of neuropathy is that ultimately, there is very little to do for it. Treat the symptoms is what I’ve been doing. It is not something that is going to go away. It may, with better control of the diabetes, become less uncomfortable. I was planning to have a gastric bypass to help reduce my intake, but that's a little too scary for me. So now I’m reconsidering having a band done.
I’d like to know if it ever gets better, instead of progressively worse. There are new medications on the market that are supposed to help it—I don't know why I’m not on them, or if those medications could be helpful for me, or if there is anything else that I could do.
Ms Q is a 52-year-old registered nurse with lower extremity neuropathy diagnosed 6 years ago. She lives in the greater Boston area and has managed care health insurance.
Ms Q's symptoms began about 8 years ago with pain at the base of her left foot. She was seen by a podiatrist, initially diagnosed with plantar fasciitis, and underwent serial cortisone injections. The injections minimized symptoms initially, but her pain persisted. Her pain spread to her right foot, and, given the lack of improvement, she was referred for nerve conduction studies and electromyography (EMG). The studies showed mild reduction in the sural sensory response amplitudes bilaterally with normal conduction velocities; these findings were consistent with a mild distal axonal sensorimotor polyneuropathy.
Ms Q was diagnosed with diabetes about a year before her EMG findings. Her hemoglobin A1C was 7.6% at the time of diagnosis.
Ms Q says that her neuropathic symptoms, which include numbness, tingling, pain, and burning bilaterally, have worsened over the years. Her symptoms seem to worsen when her diabetes is less well controlled. She has had difficulty keeping her diabetes under tight control, however, and her hemoglobin A1C is currently 8.8%.
She has tried a range of medications with only moderate relief. Amitriptyline caused intolerable mouth dryness. Topiramate and gabapentin were ineffective. To treat her pain, she currently uses lidocaine patches, takes 60 mg of duloxetine daily, and uses alternative treatments including arnica cream. Her other medications include atenolol, 100 mg once a day; atorvastatin, 80 mg once a day; fluticasone, 50 µg spray, 1 to 2 sprays daily; glyburide, 10 mg twice daily; hydrochlorothiazide, 25 mg once a day; lisinopril, 40 mg 4 times a day; metformin, 1000 mg twice daily; oxycodone/acetaminophen (5 mg/325 mg), 1 to 2 tablets every 4 hours as needed for pain; trazodone, 100 mg before bed; and ranitidine, 150 mg twice daily.
Ms Q's other medical problems include obesity, hypercholesterolemia, depression, hypertension, and back pain which persists after a left L5 to S1 hemilaminectomy, medial facetectomy, and microdiskectomy for disk disease in 2000.
Her vitamin B12 and thyrotropin levels were normal. On examination, her blood pressure was 146/74 mm Hg; pulse, 68/min; weight, 237 lb (106.6 kg); and height, 5 ft, 4 in (162.5 cm). Distal strength in the legs and feet was normal. Reflexes were 2+ at the knees and trace at both ankles; no Babinski signs were present. There was a graded reduction in sensation to pinprick and cold in both feet, normalizing at the midshins bilaterally. Vibration was reduced to 2 to 3 seconds in the great toes but was normal proximally. Joint position sense was intact in both feet. Gait was narrow-based, and a Romberg sign was absent.
Amitriptyline is a tricyclic antidepressant, which has various cellular actions, including inhibition of serotonin-norepinephrine re-uptake. While tricyclic antidepressants are, of course, used for depression, certain drugs in this class are also used for pain.
Gabapentin is a drug originally used to control seizures, but is also used for a variety of purposes, as illustrated here. It's exact mechanism of action is unknown. Its structure is similar to GABA, although it is more likely to act by binding to voltage gated Ca++ channels.
Duloxetine is a serotonin-norepinephrine re-uptake inhibitor used for both depresssion and painful peripheral neuropathy. It is substantially more expensive than the above two drugs.
The EMG here refers to a nerve condition study. The nerve is shocked at one place and the summed effect of all the action potentials is recorded at a specific distance. With diabetic neuropathy, you would expect the calculated conduction velocity to be normal, since the problem is axonal rather than the myelin. Degeneration of axons, by contrast, should make the amplitude of the summed response smaller, which was observed. The sural nerve is a cutaneous nerve in the lower leg and foot.
The substantial fascia covering the bottom of the foot is called the plantar fascia. Plantar fasciitis is inflammation of this fascia at the point where it attaches to the calcaneus. It is a common problem in athletes, the obese, and others who put extra stress on their plantar fascia during walking and running.