A 68-year-old male presents to the Physical Medicine and Rehabilitation (PM&R) clinic with a complaint of “pins and needles” in both feet. The sensation has gradually been getting worse over the past 2 years. He has no complaints of weakness. The patient describes the sensation as mildly painful (3/10) but it impedes his ability to walk comfortably.
Past medical history: History of diabetes for 20 years. He also has a history of obesity (BMI 31 kg/m 2 ), hypertension, and increased cholesterol. His medications include metformin, hydrochlorothiazide, and Lipitor.
Social history: He is currently retired. He used to work as a janitor for 41 years. He has smoked approximately one pack per day since the age of 16 years. He drinks about four to eight beers a day. He is independent in activities of daily living and ambulation. The patient lives with his wife in a ranch home with no steps. No other family members have had this type of problem.
Past surgical history: None.
Allergies: No known drug allergy.
Medications: Metformin 500 mg, two tablets twice a day, hydrochlorothiazide 25 mg twice a day, and Lipitor 20 mg once a day.
BP: 140/90 mmHg; RR: 15/min, PR: 72 per min, Temp: 98° F, Height: 5’8”, Weight: 204 lbs, BMI: 31 kg/m 2 .
Well-developed male in no acute distress
Head, ear, eyes, nose, and throat (HEENT): Extraocular movements full, no ptosis.
General: He is alert and oriented. He is in no severe pain.
Extremities: No edema, no surgical scars.
Range of motion (ROM) of neck and back: Full range of motion in all directions.
Bilateral upper and lower extremity strength 5/5.
There is no muscle wasting.
Deep tendon reflexes: 2+ in biceps, triceps and patella, 1+ in the ankle. Plantar response down going bilaterally. Negative Hoffmann.
Decreased to light touch and pinprick in both legs distal to the ankle. Mild decrease to light touch and pinprick in the fingers distally and bilaterally. Proprioception impaired bilateral lower extremities. Decreased vibration sensation bilateral lower extremities.
Skin: No rashes or skin breakdown.
Gait: Within normal limits without any deviations. Tandem walks with mild difficulty.
Cerebellar: Normal finger to nose.
Labs: Complete blood count (CBC) within normal limits, coagulation panel within normal limits, hemoglobin A1c (HbA1c) elevated at 8.9, complete metabolic panel elevated glucose 220, normal kidney parameters.
B12 and folate: Normal.
Serum protein electrophoresis (SPEP): Normal.
Heavy metal testing: Negative.
Chest x-ray: Negative for infiltrates or other lesions.
Electromyography (EMG): Distal sensory motor, axonal and demyelinating peripheral polyneuropathy, affecting the lower extremities more than the upper extremities. Distal lower extremity muscle abnormal spontaneous potentials (denervation) is noted. These findings are not in a myotomal or peripheral nerve distribution.
Patients with tingling and numbness in distal extremities bilaterally should prompt the clinician to consider peripheral polyneuropathy. Peripheral polyneuropathy can be either acquired or congenital. A pertinent family history asking about other family members must be included as part of the history. An assessment should be performed for peripheral polyneuropathy, as well as other causes for distal numbness. Note that peripheral polyneuropathy and other disorders can coexist. For example, patients with peripheral polyneuropathy are more prone to entrapment neuropathy, and peripheral polyneuropathy may exist in the setting of other disorders. In addition, it is important to assess the reason that patients has peripheral neuropathy, as that will affect the treatment plan.
When taking a history, ask patients about recent viral illnesses, any new medication they are taking, or if they have had any exposure to solvents or heavy metals.
Common Differential Diagnoses
Diabetic peripheral neuropathy —possible given the previous diagnosis diabetes, as well as poorly controlled blood sugars (as evidenced by elevated HbA1c levels).
Alcoholic peripheral neuropathy —patient has a long history of drinking alcohol. Alcoholic neuropathy can present after prolonged drinking.
Toxic peripheral neuropathy because of chemicals —patient worked as a janitor, and therefore might have been exposed to chemicals that are toxic to the peripheral nervous system (heavy metals, lead, mercury, arsenic, etc.).
Peripheral neuropathy because of other causes —could include undiagnosed thyroid disorder, human immunodeficiency virus (HIV), or other diseases.
Malignancy —Paraneoplastic syndrome can cause neuropathy. This is usually because of small cell carcinoma of the lung. This patient has a history of smoking, so is at increased risk for this type of neuropathy.
Nerve entrapment proximally in the legs —less likely given the symmetry of the symptoms, and the mild findings in the hands. Nerves can be entrapped anywhere in the legs. Common areas include:
Tarsal tunnel— commonly cause numbness in the plantar surface of the feet and spare the dorsum of the feet.
Peroneal neuropathy at the fibular head —commonly cause numbness on the top of the feet and spare the plantar surface of the feet.
Lumbosacral plexopathies— less likely because these lesions are rarely bilateral and patients usually present with numbness in a peripheral nerve distribution (as opposed to a stocking/glove distribution). Motor function is also likely to be affected.
Radiculopathy —less likely because the symptoms are bilateral and do not go above the ankles. Symptoms of radiculopathy would usually include back pain, motor weakness, and numbness in a nerve root distribution.
Spinal stenosis —less likely because spinal stenosis usually presents with back pain (improved with flexion), as well as pain and numbness that does not go distal to the knees. Symptoms can be bilateral.
Upper motor neuron lesion —a central nervous system lesion is less likely given the distribution of the sensory impairment (distal and bilateral, affecting upper, as well as lower extremities), as well as normal tone, negative Hoffmann, and down-going plantar reflexes.
Hereditary peripheral neuropathy— less likely given the lack of family history but should not be excluded.
Peripheral vascular disease— is usually distal and may mimic the symptoms of peripheral polyneuropathy. However, pulses on this patient were normal.
Diabetic amyotrophy —can occur in diabetic patients. It frequently presents with the acute onset of unilateral pain and weakness (however, it may be bilateral). This is followed by severe atrophy. Affected nerves are usually more proximal than in a distal peripheral polyneuropathy. This patient did not have proximal pain, the onset was chronic, and there was no muscle wasting.
Neuropathy as a side effect of medication— numerous medications can cause peripheral polyneuropathy as a side effect, including some cancer medications, antialcohol drugs, anticonvulsants, immune suppression medications, antibiotics, and heart or blood pressure medications.
Autoimmune inflammatory neuropathy— includes Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy [AIDP], as well as chronic inflammatory demyelinating polyneuropathy [CIDP]). Patients may report an antecedent viral infection. Usually, in Guillain-Barré, the symptoms are acute and ascending. Here, the symptoms were more chronic and limited to a distal distribution.
Neuropathy caused by vitamin deficiency— can be secondary to vitamin deficiency, especially vitamin B12 and folate. This may be seen in patients with alcoholism.
Idiopathic neuropathy —up to 46% of patients develop peripheral polyneuropathy for which the reason is not clear.
Small fiber neuropathy —this type of neuropathy affects the small c fibers. Because nerve conduction testing only assesses for larger nerve fiber types, this type of neuropathy will yield a negative nerve conduction study (NCS)/electromyography (EMG).
Our patient has several reasons to have a peripheral polyneuropathy, including diabetes, alcohol use, possible toxic chemical exposure, and smoking. He complains of numbness and tingling in the feet, but on physical examination, the hands are mildly affected as well. This is common in peripheral polyneuropathy because the nerves in the legs are longer and cooler than those in the arms. However, other diseases that can mimic peripheral neuropathy or coexist with peripheral neuropathy must be excluded.
The earlier EMG is helpful to further narrow down the differential diagnosis. Diabetic peripheral polyneuropathy typically presents as a distal sensory motor, axonal, and demyelinating peripheral polyneuropathy. The other main cause of this type of neuropathy is uremic peripheral polyneuropathy. Because kidney functions were normal, this is less likely. Distal denervation can be explained by the motor axonal component of the neuropathy. The patient’s laboratory results further indicate that the most likely reason for the peripheral polyneuropathy is diabetes.
Review of Proposed Pathology
The exact mechanism of injury to the nerves in diabetic peripheral polyneuropathy is not clear. The toxic effects of hyperglycemia probably play a role. Other factors include inflammatory, metabolic, and ischemic damage to the nerve.
Clinical Signs and Symptoms of Neuropathy
Symptoms of peripheral polyneuropathy usually present in a “stocking and glove” distribution because of its distal prevalence. The feet are usually affected before the hands. Symptoms are rarely prominent proximal to the knees and elbows. Symptoms depend on the types of nerve fibers involved. Sensory symptoms may include numbness, tingling, pain, burning, and/or hyperesthesia or dysesthesia. If motor fibers are affected, distal weakness may be noted. The autonomic nervous system may also be affected, involving the cardiovascular system, gastrointestinal system, and sweat glands. Complaints might include abdominal pain, diarrhea, constipation, orthostatic hypotension, arrhythmias, syncope, voiding disorders, sweating disorders, and heat intolerance. Symptoms are usually gradual in onset. Patients may notice progressive difficulty walking or performing fine motor activities.
Physical examination findings will reflect the type and severity of nerve damage. Light touch and pinprick may be affected, as well as vibratory sensation. Balance may be decreased because of decreased proprioception. Deep tendon reflexes may be diminished, especially distally. If motor fibers are affected, strength may be decreased and muscle atrophy may be present (again, distal more than proximal). Autonomic dysfunction may be present as well. As patients may not be able to feel pain distally, it is important to look for skin breakdown, especially under the feet.
EMG testing (especially the nerve conduction component of the test) can be used to differentiate peripheral polyneuropathy from other nerve involvement, including focal nerve entrapment syndromes (i.e., tarsal tunnel syndromes) and radiculopathy. It is also helpful in diagnosing nerve and muscle pathology that may coexist with the neuropathy. EMG can assess the type of neuropathy (axonal, demyelinating, or both; sensory, motor, or both; distal or proximal; uniform or segmental).
EMG testing can further help to prognosticate. The amount of conduction velocity slowing and increased distal latency indicates the severity of the demyelinating component. Dispersion of the compound motor action potential (CMAP) and sensory nerve action potential (SNAP) may also be noted, especially in acquired peripheral polyneuropathies. The reduction in amplitude indicates the severity of the axonal component. If distal denervation is severe, the motor units in that muscle are severely compromised. This indicates severe axonal damage and a poorer prognosis. Chronicity can be assessed by changes in the motor unit.
Other causes of peripheral neuropathy noted in the differential diagnosis can be excluded based on the findings of the EMG study ( Table 11.1 ). Alcoholic peripheral neuropathy usually presents as an axonal sensory motor neuropathy. Toxic neuropathies also usually present as axonal sensory motor neuropathies. Paraneoplastic syndrome peripheral neuropathy typically presents on EMG as a sensory axonal neuropathy. Entrapment neuropathies will typically demonstrate conduction velocity slowing across the area of entrapment or conduction block (neurapraxia). Radiculopathy will typically demonstrate normal nerve conduction studies, but may demonstrate denervation in a nerve root distribution. Spinal stenosis will typically show bilateral multilevel paraspinal denervation with few findings in the limb (but usually proximal findings more than distal findings). Upper motor neuron lesions will have normal nerve conduction studies and no denervation. There may be decreased recruitment in muscles affected by the central lesion. Hereditary neuropathies usually present with uniform demyelination as opposed to acquired neuropathies, where some segments have faster conduction velocities and some have slower conduction velocities.