Neurology Patient C


History

The following patient was described in the New England Journal of Medicine, 2013, 368:23.

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Patient's Comments

A 65 year old man reported fevers and progressive weakness. He had been well until 4 months previously, when daily fevers, sweats, fatigue, impaired concentration, and weakness developed. His strength had gradually diminished over a period of several weeks, preventing him from hiking, which he otherwise did regularly. He had fatigue on chewing and difficulty buttoning his shirt, and he began wearing a rigid foot brace to stabilize his right ankle. He also reported that pain in his feet and calves was sufficiently distracting that he could no longer enjoy reading. He reported no jaw pain, headaches, joint swelling, rash, or weight loss.

Doctors's Comments

On physical examination, the patient appeared comfortable, with no fever. His pulse was 76 beats per minute, the blood pressure was 140/88 mm Hg and the body mass index 27.1. The lungs were clear and there was no lymphadenopathy. The liver of normal size.

Strength was normal in proximal arms, but decreased in both wrists and the fingers,right hip, and dorsiflexion of the right foot.

The deep tendon reflexes were symmetric in the arms, but could not be elicited in the knees and ankles.

The circumference of the left calf was less than the right calf, and there was some muscle wasting in the left hand.

Sensation was diminished in the hands, and there was diminished vibration sense and nocioception.

The right foot had a marked foot drop.

Watch the video (URL = http://www.nejm.org/doi/full/10.1056/NEJMcps1210603) to see the foot drop.

The patient's medical history included hepatitis B virus, gout, hyperlipidemia, hypertension, gastroesophageal reflex and hypothyroidism. He also had had a coronary artery bypass operation 15 months earlier.

Medications included aspirin, a HMG-CoA reductase inhibitor (statin), a beta-blocker (adrenergic blocker), an ACE inhibitor, ibuprofen, levothyroxine, and a proton pump inhibitor.

The patient was a retired engineer living in the Southwest. His last travel outside the U.S. ws 10 years ago. He had worked in Vietnam 30 years ago and been sexually active at that time. At one time he had had genital herpes. Presently, he was married and monogamous.

Secondary tuberculosis would be a possibility due to his time in Vietnam. Tuberculosis, as well as tertiary syphylis and HIV, can cause peripheral neuropathy.



QUESTION: What is suspicious here and quite different from the preceding two patients?

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QUESTION: What further information is needed?

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Tests and Diagnosis

Laboratory testing revealed a normal basic metabolic panel.

The blood level of alanine aminotransferase was 44 U per liter (normal range, 3 to 78), aspartate aminotransferase 44 U per liter (normal range, 3 to 70), alkaline phosphatase 110 U (normal range, 20 to 145)


QUESTION: Why are enzymes in the blood being tested?

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The creatine kinase level was normal.

QUESTION: What is the significance of this enzyme in the blood?

Answer

The thyrotropin (TSH) level was normal.

QUESTION: What would elevated thyrotropin (TSH) indicate?

Answer

C-reactive protein was normal.

QUESTION: Do you recall what this is about?

Answer

QUESTION: Are you surprised that it is normal?

Answer

..and the erythrocyte sedimentation rate was 18 mm per hour (normal range, 0 to 20)...

This is another marker of inflammation that occurs if fibrinogen levels in the blood are elevated.

..testing for HIV, HCV, and treponemal antibodies was negative...

The hepatitis B viral load was 2.5 billion copies per milliliter...

HCV means hepatitis C. Treponemes are bacteria of the type that cause syphylis.

Nerve conduction studies revealed features of an asymmetric, axonal sensory and motor ..neuropathy, primarily affecting the legs, but also involving the left arm.

The nerve conduction studies indicate overlapping, multiple mononeuropathies. The use of "multiple mononeuropathies" implies that, while many nerves are affected, they are affected on a nerve by nerve basis; that is, a widespread effect, but not generalized.

..right superficial peroneal-nerve biopsy showed active vasculitis with ischemic damage to the nerve and acute axonal degeneration.

Go to figure 1 (URL = http://www.nejm.org/doi/full/10.1056/NEJMcps1210603) in the article to see the biopsy. This shows the vasculitis, which matches up with the hepatitis B viremia (viruses in blood). (The CD3 protein is used as a histological marker for lymphocytes.)

..A specimen from a concurrent peroneus brevis muscle biopsy also showed an acute inflammatory myopathy with ongoing muscle-fiber destruction and regeneration, as well as a vasculitis and early changes of secondary neurogenic atrophy.

"neurogenic atrophy" here means that the muscle fibers degenerate because they lack innervation.

Thus, the overall diagnosis is multiple mononeuropathy due to vasculitis. The hepatitis B infection is causing inflammation of many small blood vessels. As a result, blood flow is cut off to populations of axons in nerves, causing the peripheral neuropathy. The vasculitis gives a specific appearance to the blood arteries, so an even more specific diagnosis is polyarteritis nodosa.

Treatment

Prompt treatment for the hepatitis B and the polyarteritis nodosa was clearly important.

The patient was treated with antiviral medications and plasma exchange. The latter refers to a procedure that replaces the blood proteins and notably the specific antibodies of the patients blood.

After several weeks glucocorticoids were added to the treatment. This was continued until the dose was tapered after a year. The glucocorticoid treatment, of course, was used to suppress inflammation occuring in the small and medium sized arteries.

The leg pain and weakness gradually improved over a period of months, but the patient did not have full recovery of function. After 2 years of antiviral therapy, testing showed he had antibodies against hepatitis B antigens and the hepatitis B viral concentration was below the assay's limit of detection.