On Thursday, we challenged Well readers to solve the mystery of a 68-year-old woman who lost her vision over the course of a few months. More than 250 readers wrote in with their take on this terrifying case. A couple of you nailed it, but frankly this case was a super-zebra – at least to me.
The correct diagnosis is …
Paraneoplastic optic neuropathy
While several readers correctly suggested that this was a paraneoplastic syndrome, Dr. Eileen Broomall, a neurologist in Covington, Ky., was the first to properly identify this rare disorder by name. Dr. Broomall said she thought of these diseases because the progression of the blindness was so rapid and the eye and brain looked normal on M.R.I. Thank you, Dr. Broomall!
The Diagnosis
The term paraneoplastic refers to complications of a cancer that are not caused directly by the cancer itself. Usually these are injuries caused by an immune response to the tumor. Normally when a cancer develops in the body, the patient’s immune system will attack it with antibodies, dronelike proteins that seek and destroy anything they perceive to be alien. That’s the normal response.
In a paraneoplastic syndrome, the anti-tumor antibodies start to attack healthy cells that in some way look like the cancer cells they are supposed to destroy. In this patient’s case, the anti-tumor antibodies attacked the cells in the optic nerve, cells that were not cancerous but that the antibodies destroyed as if they were.
This type of disorder was first identified by Dr. Charles Thirkill, a researcher at the University of California at Davis. A paper published in 1987 described four patients who lost their vision over the course of weeks or months and were subsequently diagnosed with cancer. Each of these patients was found to have an antibody in their bloodstream that attacked cells in the eye as well as cancerous cells.
Dr. Thirkill’s initial paper was about antibodies that attacked the retina. In more recent research he has shown that there are also antibodies that attack the optic nerve, as was the case with this patient.
How the Diagnosis Was Made
Once Dr. Thomas Slamovits examined the patient and saw that despite her very significant visual losses, her eyes appeared completely normal, he realized that there had to be some injury to the nerves that carry information from the eye to the visual center of the brain. Initially he repeated the M.R.I., asking for detailed images of the visual tracks; again, it was normal. So what could cause this dramatic loss of vision without showing up in the eye or on the M.R.I.?
There was a very short list of possibilities. Two autoimmune disorders — multiple sclerosis and neuromyelitis optica — could do this. In these diseases, the immune system attacks both the optic nerve and the spinal cord. In addition to the loss of vision, patients with either of these diseases usually have tingling or numbness or transient weakness in other parts of the body. There is also an inherited disease called Leber’s hereditary optic atrophy that can cause this kind of blindness in middle age, although it usually affects men. And certain vitamin deficiencies, especially of the B vitamins, can cause vision problems as well.
When the tests for all those possibilities came back negative, Dr. Slamovits was momentarily at a loss. It wasn’t a disease of the eye. There was no evidence it was a disease of the brain. What was left?
That’s when he began to consider this very rare syndrome of cancer-related ophthalmopathy. He sent samples of his patient’s blood to Dr. Thirkill’s lab in Sacramento. It took a couple of weeks, but Dr. Slamovits finally got the results. The patient didn’t have the somewhat more common paraneoplastic syndrome that attacks the retina. Instead she had antibodies directed against her optic nerve. These cancer-fighting proteins were eating away her sight.
Dr. Slamovits was relieved to get this first positive result. But he was worried, too. There was a very good chance that his patient had some kind of cancer, although he had no idea where in her body it was or how to treat it if he found it.
He referred her to Dr. Jerome Posner, a neuro-oncologist at Memorial Sloan Kettering Cancer Center who had identified many other paraneoplastic syndromes. Dr. Posner ordered a series of blood tests, a spinal tap, yet another M.R.I. of the brain and a PET scan — a type of scan that looks for cancer by measuring the uptake of specially-labeled glucose. Cancer cells are more active than normal cells and so will gobble up more glucose. The PET scan lit up in two spots: the pancreas and the liver. A biopsy showed that the patient had a slow-growing tumor in the insulin-producing cells in her pancreas that had spread to her liver.
Good News, Bad News
When the patient heard her diagnosis, her first question was not about the cancer but about her vision. Now that they found the cause, could they get her vision back? Would she ever be able to see again?
None of the doctors could answer that question. Sometimes vision returned after treatment; other times, it did not.
So first her doctors went after the tumors in her liver. They cut off the blood supply to the tumor without injuring the rest of the liver. Only then could they try to restore her sight.
Paraneoplastic syndromes are treated with intravenous immunoglobulin, or IVIG, which is a serum made up of millions of antibodies taken from thousands of donors. For reasons that are not well understood, flooding the body with this tidal wave of new disease-fighting proteins helps stop the person’s own antibodies from attacking the wrong cells.
She received four doses of IVIG and waited. Days turned into weeks. Nothing happened. In the meantime, she started chemotherapy to treat her cancer. She went into remission. But she still couldn’t see.
A Son’s Face
Then one day several weeks after being given IVIG, her adult son arrived for a visit. Though he lived nearly 300 miles away, he came frequently. Especially now.
As they sat over the breakfast dishes, the woman took off her glasses and rubbed her eyes. She looked up at her 36-year-old son as he spoke. All of a sudden she realized that for the first time in over a year, she could see a face. It was far from clear, but she could just barely make out his familiar features. She couldn’t speak. Tears streamed down her cheeks. She could see again.
Her vision returned the way it had disappeared — a little at a time. First faces, then text, then finally, six months later, she felt as if she could see well enough to drive.
As for the tumor, it is probably with her for life. But she has had five good years, and so far, she is still going strong.