MKSAP: Neuropathy

The following cases and commentary, which address neuropathy, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP14).

Case 1: Sensory symptoms

A 32-year-old woman is hospitalized for an episode of sensory symptoms that began as numbness and tingling in both feet and progressed over several days to include gait instability, hand weakness, diplopia, and dyspnea. The symptoms began 11 days after a viral illness. On admission, she has sinus tachycardia, proximal and distal weakness in her upper and lower extremities bilaterally, areflexia, and marked vibratory and position sense loss in the toes and fingers. She cannot walk.

Which of the following is the most appropriate treatment?

A. Prednisone
B. Pyridostigmine
C. Plasma exchange
D. Intravenous methylprednisolone

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Case 2: Diabetic foot ulcer

A 62-year-old man who has had diabetes for 10 years reports a six-week-old right foot ulcer that has not completely healed despite local dressing and oral antibiotics. He is obese and also has mild osteoarthritis, hypertension, and hypercholesterolemia. He has a 60-pack-year history of cigarette smoking but was able to quit five years ago after a transient ischemic attack. He reports no symptoms of leg claudication. His current medications include glipizide, lisinopril, hydrochlorothiazide, atenolol, simvastatin, and aspirin.

His body mass index is 32.5 kg/m2 and blood pressure is 140/80 mm Hg. He is afebrile. A three-cm plantar ulcer surrounded by a callus at the base of the second metatarsal head is noted on the right foot; the ulcer edges are necrotic. Dorsalis pedis and posterior tibialis pulses are weakly palpable. The ankle reflexes and microfilament sensation for all toes are absent bilaterally.

Which of the following should be the next step in the treatment of this patient?

A. Change the antihypertensive regimen
B. Debride the callus and provide wet and dry dressings
C. Perform nerve conduction studies
D. Refer to a vascular surgeon

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Case 3: Severe, worsening foot pain

A 56-year-old man who has had type 2 diabetes for 12 years is evaluated. He has hypertension, hyperlipidemia, and coronary artery disease. He underwent coronary artery bypass graft surgery two years ago. His medications include atorvastatin 80 mg/day, lisinopril 40 mg/day, hydrochlorothiazide 12.5 mg/day, amlodipine 5 mg/day, aspirin 81 mg/day, metformin 1,000 mg twice daily, and a 75/25 insulin lispro mix—35 U in the morning and 15 U before dinner.

He reports pain in his feet for the past three months that is severe and worsening. The pain is described as lancinating and worse at night, especially in bed. The pain has disturbed his sleep, which he believes is affecting his glucose control. His most recent hemoglobin A1c value was 8.5%, with fasting glucose concentrations ranging from 155 to 188 mg/dL (8.6 to 10.43 mmol/L).

On physical examination, the patient is somewhat uncomfortable. His body mass index is 24 kg/m2. Blood pressure is 130/70 mm Hg, and pulse is 72 beats/min. Background retinopathy is evident. Neurologic examination reveals some reduction in vibration perception in both feet up to the ankles and a loss of Achilles reflexes bilaterally. The urine albumin-creatinine ratio is 65 mg/g.

In addition to intensified insulin treatment, a regimen of which of the following drugs is most appropriate?

A. Duloxetine
B. Oxycodone
C. Topical capsaicin
D. Tramadol

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Answers and commentary

Case 1

Correct answer: C. Plasma exchange.

Guillain-Barré syndrome is an immune-mediated demyelinating polyneuropathy characterized by proximal and distal weakness, distal sensory loss, autonomic symptoms, cranial nerve involvement, and respiratory failure in 25% of patients. Treatment consists of either intravenous immunoglobulin therapy or plasmapheresis, both of which have been shown in clinical studies to be equally effective. Plasmapheresis should be avoided in patients who have labile blood pressures or infection. Intravenous immunoglobulin is contraindicated in patients with renal insufficiency, congestive heart failure, or IgA deficiency. Both of these treatments are expensive and have potential morbidity and should therefore be reserved for patients who are unable to walk independently, have impaired respiratory function, or have rapidly progressive weakness.

Studies of oral corticosteroid therapy and intravenous methylprednisolone have shown no significant clinical improvement in patients with Guillain-Barré syndrome.

Key points

  • Guillain–Barré syndrome is characterized by proximal and distal weakness, autonomic symptoms, cranial nerve involvement, and respiratory failure.
  • Treatment of Guillain–Barré syndrome with either intravenous immunoglobulin or plasmapheresis is indicated in patients who cannot walk independently or who have impaired respiratory function or rapidly progressive weakness.

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Case 2

Correct answer: D. Refer to a vascular surgeon.

This patient has clear evidence of peripheral neuropathy, given his history and physical examination. Absence of claudication does not rule out distal vessel disease, which is more common in patients who have diabetes. This patient has several risk factors for peripheral arterial disease, including type 2 diabetes, cigarette smoking, hypertension, hyperlipidemia, and prior history of a vascular episode. Chronic neuropathic ulcers are often complicated by peripheral arterial disease and will not heal if the peripheral circulation remains compromised. Further work-up should therefore include an estimation of the ankle-brachial index and a referral to a vascular surgeon for consideration of an angiogram to define the vascular anatomy and determine the possible need for surgical intervention. No medical treatments (for example, changing his antihypertensive regimen) other than prophylactic measures such as risk factor management that includes smoking cessation are very effective in the treatment of advanced peripheral arterial disease. Debridement and local dressings only delay the healing process in the absence of further assessment. A nerve conduction study is not likely to further contribute to an already established diagnosis.

Key point

  • Screen for peripheral arterial disease and refer for vascular studies in patients with neuropathic foot ulcers.

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Case 3

Correct answer: A. Duloxetine.

This patient has painful peripheral neuropathy that is affecting his quality of life. Two drugs have recently been approved for diabetic neuropathic pain—duloxetine (a selective norepinephrine reuptake inhibitor) and pregabalin (an antiepileptic agent). In a recent statement on diabetic neuropathy, the American Diabetes Association has recommended a stepwise approach to management that includes the stabilization of glucose control (because hyperglycemia reduces pain thresholds) followed by the addition of antidepressants and then antiepileptic agents; if these treatments fail to control the pain, the use of opioid drugs and a referral to a pain clinic are recommended. This patient has suboptimal glycemic control; hence, the most appropriate treatment would be to stabilize or improve glucose control and attempt to control the pain with a selective norepinephrine reuptake inhibitor, such as duloxetine, or an anti-epileptic drug. Using an opioid or opioid-like drug, such as oxycodone or tramadol, as the initial treatment for the pain is not appropriate. There is no evidence that topical capsaicin treatment is effective for the management of severe painful neuropathy.

Key point

  • Painful neuropathy in patients with diabetes is treated with a stepwise approach that includes use of antidepressants and anticonvulsants.