Not Just the Flu

Common symptoms actually point to a deadly virus

By John R. Pettinato|Tuesday, January 01, 2002
RELATED TAGS: INFECTIOUS DISEASES
Melissa's first brush with death, an automobile accident that put her in a coma, came when she was 15. After extensive rehabilitation, her youthful vitality returned. Her next bout with death came 10 years later, and this time I was afraid her luck had run out.

It was April, and the freshness of spring had just begun to wash away the gloom of winter. But this spring brought Melissa shaking chills, night sweats, and vomiting—the flu. Her prescription was simple: plenty of rest, plenty of fluids.

The plan worked until she became angry and mean-spirited, and lost interest in her personal appearance. "Just the flu," her doctor said to her anxious husband. Then she stopped eating, and the seizures she'd had since her car accident began to last longer. Her husband took her to the emergency room. He later told me that he was so sure that she would be admitted that he brought an overnight bag with toiletries and extra clothes. Again they were told it was just the flu, and Melissa was sent home.

Within days, she was almost catatonic, unable to do little more than drool. This time her husband, in an act of devotion that saved Melissa's life, refused to leave the emergency room until the attending physician agreed to admit her.

I was on call. I started by reviewing the lab data. The only hint of infection was her elevated white-blood-cell count. Where was the infection? Blood and urine cultures were negative, and her chest X ray didn't show any pneumonia. The clinical presentation, fever and mental-status changes, suggested a central nervous system disease. A lumbar puncture showed spinal fluid consistent with a viral infection. But another detail about the spinal-fluid analysis caught my eye—red blood cells, a sign of bleeding in the brain. Perhaps she had encephalitis. Many viruses can infect the brain, but I knew of only one with that signature: herpes simplex.

Herpes simplex viruses type 1 and type 2 tend to infect mucous membranes and the central nervous system. HSV-1 causes cold sores and 95 percent of all central nervous system infections.

HSV-2 is associated with genital disease.

HSV-1 spreads through contact with virus-laden saliva or sores. People usually get infected in childhood or adolescence. Sometimes there are no symptoms, but more often people have cold sores, or "fever blisters," in or around the mouth. After the first infection the virus lies latent in the trigeminal ganglia, a structure in the base of the brain that gives rise to the trigeminal nerve, which predominantly provides sensation to the face. For reasons that are not clear, the virus can reactivate years later and travel along the trigeminal nerve to the meninges, the coverings of the brain and spinal cord, at the base of the brain. From there it can launch an attack on its preferred target: the temporal lobes, brain regions just above each ear that help carry out the complex functions of hearing, learning, memory, and emotion.

Untreated herpes-based encephalitis can be fatal in up to 70 percent of cases. Malaise, fever, and headache herald its onset, often quickly followed by behavioral abnormalities, seizures, olfactory hallucinations, and bizarre or psychotic behavior—all symptoms of disease in the temporal lobes.

Fortunately, effective antiviral therapy is available, and early treatment reduces mortality to 30 percent. But making the diagnosis promptly is vital. And even with treatment, survivors of herpes encephalitis are almost never neurologically normal and will often experience amnesia, seizures, and anosmia, the loss of smell.

When I first examined Melissa, she was comatose. An electroencephalogram showed slowing of the normally brisk electrical activity of the brain. That finding fit with her comatose condition, but it is not typical of the waveforms often seen in herpes encephalitis. The only good news I had to share with her family was a normal CAT scan. I could test the cerebrospinal fluid for viral DNA using the polymerase chain reaction (PCR) technique to pin down the diagnosis of herpes simplex, but the results wouldn't be available for days.

Melissa was dying and something had to be done now. I followed my instinct and treated her for herpes encephalitis with acyclovir, an antiviral drug.

Two days later, the PCR results came back positive for HSV.

Melissa recovered, but her return home was like stepping onto the set of a movie she'd never seen. She couldn't find the guest bedroom, and she would often joke that her husband had moved it when she wasn't looking. She didn't remember that she had been taking tennis lessons. She didn't even recognize her tennis racket. She also had a bigger problem: She couldn't recognize faces. Pictures of high school friends were the faces of strangers. Patients with this condition, called prosopagnosia, can identify a face as a face, its parts, and even certain emotions, but they are unable to identify a particular face as belonging to a specific person. Prosopagnosics often do not recognize their own faces in the mirror, although they will recognize that they are looking at a face.

Still, Melissa didn't lose her knowledge of people's identities. She just couldn't count on using facial recognition to make identifications. Because humans are remarkably adaptive, patients like Melissa can often be taught how to compensate. Over time, Melissa learned to recognize people by context, such as where she last saw a person and what he or she was wearing. I saw this firsthand when I met her for a follow-up visit. Only when we were seated in the customary positions in my office did I see a glimmer of recognition flash across her face.

After several months of rehabilitation, Melissa was able to return to teaching. She leads a near-normal life. During my last visit with her, I said I was pleased at her recovery. With a twinkle in her eye, and as if to make light of it, she smiled slyly and said, "Dr. Pettinato, it's just a matter of recognition."
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