Mr. D, a semiretired businessman in his 70s, had been feeling quite well until midwinter, when he suddenly developed painful blisters along the back of his left leg. He went to see his primary doctor.
Mr. D had been diagnosed 30 years earlier with chronic lymphocytic leukemia (CLL), a disease that sounds awful, but that usually allows those afflicted to go about their lives for decades with no need for treatment and no significant symptoms.
His doctor made a straightforward diagnosis of dermatomal herpes zoster, or shingles. Mr. D was placed on valacyclovir, an excellent oral antiviral agent that is active against shingles.
Ten days later, the blisters had disappeared and the pain had subsided, although not completely. He felt well enough, nevertheless, to resume his daily activities of visiting family, traveling, and working part time.
Several weeks passed. His wife began to notice that Mr. D was not himself. He had become forgetful and would do silly things.
The changes accelerated quickly. When he no longer recognized her and became confused about where he was, she took him to the emergency department at their local hospital.
A variety of laboratory studies were performed, including a complete blood count, liver-function tests, and electrolyte studies.
Later, CT scans and a spinal tap were performed. Nearly all the test results were fairly normal. He did have a very high white blood count, but most of the white blood cells were the kind you would expect to see in a patient with chronic lymphocytic leukemia. The CT scan of his head showed nothing out of the ordinary.
The spinal tap, however, revealed a problem. The spinal fluid sample contained several hundred white blood cells - all lymphocytes - and his protein was four times the normal level.
What was going on? His doctors were stumped.
Mr. D. was transferred to another hospital.
By the time he arrived, he was so groggy that it was hard to wake him up.
The doctors began to explore additional rare diseases. Perhaps leukemic meningitis. Mr. D's leukemia might have entered his meninges, the membranes surrounding his brain. This is a very unusual complication of chronic lymphocytic leukemia.
A new round of tests was ordered: more blood work and another spinal tap. Some results would take several days, but the laboratory was able to immediately look for leukemia cells in the spinal fluid.
There were none.
His doctors then wondered whether he might be suffering from a viral infection. But it was winter, the only virus making its way through the community was influenza, and he had not complained of any flulike symptoms over the previous few months.
What about a drug reaction? Could the valacyclovir have done this? Unlikely. His symptoms are not normally associated with the drug.
Perhaps he self-medicated with a drug that his physicians didn't know about? His wife dismissed the idea, and a drug screen taken from Mr. D's urine sample confirmed that he had not taken anything other than what the doctors had given him.
They turned their attention to shingles. Usually, this illness resolves over several weeks, and even faster with the help of valacyclovir. Perhaps something had gone awry in an elderly man with CLL, which can affect the immune system.
Rarely, the shingles virus (varicella zoster) can invade the brain parenchyma, or nervous tissue, a condition known as zoster encephalitis. The parenchyma, akin to the white part of an apple, is the substantive part of the brain. It is the part responsible for thinking, breathing, and motor function.
Mr. D's CT scan, however, showed that his brain parenchyma was normal. That made this diagnosis very unlikely.
The doctors thought of one more possibility. They would have liked to have him undergo an MRA, a magnetic resonance angiogram, but he had a pacemaker, and the powerful magnets would have damaged it.
So they ordered an alternative test, a CT angiogram. During this procedure, dye is injected into the patient's arm. Then a rapid series of images are taken of the brain as the dye flows through the arteries. The images showed that the large arteries of Mr. D's brain were inflamed.
Varicella zoster vasculitis is an extremely rare condition in which the virus provokes an inflammation of the arteries feeding the brain parenchyma. The CT scan showed that this was what had hit Mr. D like a Taser. Several days later, the final results of the spinal tap showed DNA evidence for shingles and antibodies to the virus, confirming the diagnosis.
By then, the high doses of steroids and acyclovir that he would take for several weeks had already started to work. He woke up, thanked his doctors, and gave his wife a kiss.
Not necessarily in that order.