Diagnosis of Peripheral Neuropathy

Diagnostic Evaluation of Peripheral Neuropathy

The diagnosis of peripheral neuropathy is often difficult to establish. One of the major reasons that the diagnosis may go unrecognized is that peripheral neuropathy is multidimensional and, in many instances, an underlying cause cannot be found. In the course of diagnosing peripheral neuropathy, it is important to establish certain parameters which help determine treatment, progression, and prognosis:

• Distribution pathway of the neuropathy
• Type of neuropathy (axonal or demyelinating)
• Duration of neuropathy
• How neuropathy has progressed over time

A complete diagnostic evaluation usually includes:

• Patient history
• Physical and neurological examination
• Laboratory evaluation
• Electrodiagnostic studies
• Other diagnostic studies as needed

Patient History

Patient history regarding symptoms (e.g., acute or gradual onset, parts of the body involved, medications used, and other medical conditions) provides very important information that is helpful in determining the type of neuropathy and, possibly, its underlying cause. Since many of the symptoms are highly variable, may fluctuate in intensity and may be intermittent or relapsing, some patients do not report all symptoms for fear of not being believed. The physician needs to encourage patients to discuss:

• All symptoms, even if they don't think of them as significant, (e.g., if symptoms seems to be worse at various times of the day/night, if symptoms are associated with weight bearing activities)
• Any other family members who suffer from neuropathy as this may indicate an inherited peripheral neuropathy
• Any other coexisting medical conditions
• Recent infections or viral diseases
• New medications the patient may be taking

Physical Examination

A thorough physical examination should be performed that usually includes:

• Palpation of major organs
• Palpation of pulses in legs and other parts of the body
• Examination of skin for rashes
• Auscultation for bruits (listening for sounds in the blood vessels)

• Neurological examination:

  • evaluation of cranial nerve function
  • assessment of sensory responses to various types of stimulation, (e.g., vibration, light touch, cold temperature, pinpricks)
  • assessment of proprioception - balance and sensation in maintaining an erect stance with eyes open and closed
  • inspection for signs of muscle wasting
  • muscle and movement coordination
  • examination of deep tendon reflexes and pathologic reflexes

• Evaluation of muscle strength

• Observation of walking on toes, heels, tandem walking, hopping on either foot, or getting up from a chair or squatting position.
• Posture

Some patients may have paradoxical reactions such as limited sensitivity to pinprick but abnormally increased pain sensation to light touch.

Laboratory Evaluation

Blood tests may be helpful in determining or ruling out various potential causes of peripheral neuropathy. Some blood tests that may be performed include:

• Complete blood count (CBC)
• Erythrocyte sedimentation rate
• Thyroid function tests
• Levels of vitamin B12 and folate in the serum
• Metabolic panel - fasting blood glucose level, glycosylated hemoglobin levels (highly accurate measure of blood glucose), and renal/liver function
• HIV testing (if suspected)
• Lyme disease test (if the patient is aware of a recent tick bite or was at high risk of tick bite)
• Blood chemistry panel to evaluate various enzymes, electrolytes, and chemicals
• Urine screening - if there is reason to believe that the neuropathy may be due to patient exposure to toxic substances (e.g., arsenic)
• Immunological markers

Electrodiagnostic Studies

Electrodiagnostic studies assess peripheral nerve function and are considered by many clinicians to be an essential part of the initial evaluation. As a general rule, large fiber neuropathy is associated with abnormal electrodiagnostic scores while scores for small fiber neuropathy are normal. Electrodiagnostic studies include nerve conduction study and electromyography. They help determine important issues such as:

• Axonal or demyelinating neuropathy- this is an important distinction since the cause, treatment and prognosis for each is different
• Type of neuropathy (i.e. mononeuropathy, polyneuropathy, mononeuropathy multiplex). For example, with mononeuropathy, electrodiagnostic studies can provide an accurate diagnosis as well as information about the site and severity of neural injury
• Muscle disorder or nerve disorder The nerve conduction study is typically performed first since it is less invasive and less uncomfortable for the patient and may yield enough information to help with a diagnosis.

Nerve Conduction Study

A nerve conduction study measures the speed of signals transmitted through a nerve. Flat disc-like electrodes are placed in several locations on the skin over the nerve(s) being tested. They adhere to the skin either with tape or with a special cream or paste. An electrical impulse is introduced at one point and the nerve's electrical activity is recorded by the electrodes. The distance between electrodes and the time it takes for electrical impulses to travel between electrodes are used to determine the speed of the nerve signals.

Nerve conduction study (NCS), also known as nerve conduction velocity (NCV) provides information such as:

• How fast a motor nerve conducts impulses
• Precise degree of damage in large nerve fibers
• If nerve damage is related to the deterioration of the myelin sheath or the axon

Electromyography

An electromyogram measures electrical activity of the muscles. A needle is inserted through the skin into the muscle. The electrical activity is detected by this needle and is displayed either on an oscilloscope or is recorded through a microphone. After placement of the electrode(s), the patient may be asked to contract the muscle (for example, to bend the leg). Since skeletal muscles are often large, several needle electrodes may need to be placed at various locations to obtain accurate information.

Electromyography (EMG) is useful for differentiating between muscle and nerve disorders as well as measuring:

• How a muscle responds to the signals from the nerves responsible for muscle movement (motor nerves)
• Comparison of electrical activity of the muscle at rest and when contracted

Other Diagnostic Studies

• Quantitative Sudomotor Axon Reflex Test - this test assesses small nerve fibers linked to the sweat glands. It has a sensitivity of approximately 80% for the identification of small fiber neuropathy and is one of the best diagnostic tools for small fiber neuropathy when nerve conduction studies are normal. The test is usually performed on the arms and/or legs and measures:

  • resting skin temperature
  • resting sweat output
  • stimulated sweat output

• Skin biopsy - a sample of skin tissue is removed and evaluated for loss of small nerve fibers since there is a correlation between the degeneration of small nerve fibers in the skin and neuropathic pain. The number and shape of nerve endings is examined under a microscope. This test is nonspecific for the cause or type of small fiber neuropathy but usually can establish its presence and/or severity. It may be slightly more sensitive than the Sudomotor Axon Reflex Test.

• Nerve biopsy - nerve tissue, typically a segment of the sural nerve (found below the knee and which runs through the calf and into the foot) is removed from the lower leg and upon examination, yields information regarding the degree of nerve damage. This procedure is not frequently performed since it is an invasive procedure and can have neuropathic side effects. However, if this procedure is necessary, it is recommended that it be performed by a physician with extensive experience performing this test and that the laboratory processing the biopsy should be one with experience in analyzing this type of tissue. Skin biopsy is preferred over nerve biopsy since it can visualize small fiber involvement, is less invasive, and is not associated with side effects. Under certain circumstances, nerve biopsy is helpful for documenting inflammatory disorders that may be the cause of neuropathy including:

  • Vasculitis
  • Sarcoidosis
  • CIDP
  • Infectious diseases
  • Cancer

• Computerized Axial Tomography (CAT scan) - to evaluate the presence of any vascular abnormalities, spinal stenosis (narrowing), or tumors

• Magnetic Resonance Imaging (MRI) - to evaluate muscle quality and size as well as compression of any nerves