“OK, I give up,” said the 74-year-old man. “I’ll go to the hospital.” His wife of 46 years gave an inner sigh of relief. Her husband was stubborn, a seventh-generation Mainer, not given to complaining. But a few weeks earlier, she noticed that he was parking his tractor next to the back porch so he could get on it without pulling himself up. Then he needed help getting out of his big chair. Now he could barely walk. It happened so suddenly it scared her.
She eased the car right next to the porch. He needed both hands on the railing to get down, grunting with each step. His legs moved awkwardly, as if they had somehow forgotten what to do.
At the LincolnHealth-Miles Campus Hospital in nearby Damariscotta, it was clear to the E.R. doctors that the patient wasn’t weak but ataxic, lacking not strength but coordination. Virtually every movement the body makes requires several muscles working together — a collaboration that occurs in the cerebellum. The uncertain and awkward way the patient moved made doctors at LincolnHealth worry that something — maybe a stroke, maybe a tumor — had injured that part of the brain. But two CT scans and an M.R.I. were unrevealing.
When his doctors weren’t sure what to do next, the patient decided it was time to go home. His wife was supportive but worried. How could she help him get around? He was a big guy and outweighed her by 50 pounds. And they still needed to figure out what was wrong with him. Couldn’t they try another hospital? Maybe, he said, but first he wanted to go home. So that’s where she took him. Once there, it took only a day for the man to recognize, again, that he couldn’t just tough it out at home. There was another hospital, a larger one a couple of towns over in Brunswick: Mid Coast Hospital. His wife was happy to take him there. Those few steps he took from porch to car, supported by his wife, were the last he would take for weeks.
Down the Wrong Tube
He couldn’t walk, the older man told Dr. Roople Unia, the neurologist on call that day. He could barely stand up, he continued. And that wasn’t the only thing: He was seeing double. And he had a terrible cough. Of course, at 74, he had a bunch of medical problems — diabetes, high blood pressure, some heart disease, even gout. But nothing had laid him this low before. His tanned round face reddened as he surrendered to a violent cough.
Unia suspected that his swallow was as uncoordinated as his walk. The esophagus (the swallowing tube) is right next to the trachea (the breathing tube). Normally the epiglottis, a leaf-shaped flap located at the base of the throat, folds over the trachea as we swallow to prevent the food meant for the esophagus from going down the wrong tube. The cough, she suspected, was his body’s last-ditch effort to keep food, liquids and his own saliva out of his lungs.
Unia knew from the records from the first hospital visit that this wasn’t a brain tumor or stroke. Could it be a vitamin B12 deficiency? Loss of this key nutrient can cause a wide variety of neurological symptoms — usually difficulty walking and a loss of feeling in the hands and feet, sometimes double vision and trouble swallowing as well. And it’s common — seen in up to 15 percent of those over 60. Vitamin B1 and E deficiencies, while less common, can also cause these kinds of neurological symptoms.
Something else that can affect the brain and nerves are autoimmune diseases. These disorders occur when the immune system gears up to take on some kind of invader, and the antibodies generated to protect the body attack it instead. Some of these autoimmune diseases are associated with cancers. These paraneoplastic syndromes, as they are called, are a rare consequence of the immune system’s attacking cancer but can cause devastating injuries to the nervous system as well as other parts of the body.
An Unusual Variant
But highest on Unia’s list of suspects was an unusual version of Guillain-Barré syndrome (G.B.S.) known as the Miller Fisher variant. G.B.S. is also an autoimmune disorder, usually triggered by an infection. Antibodies created to fight the infection mistakenly attack the nerves that control movement, usually starting with the legs and ascending up the body. In the Miller Fisher variant of G.B.S., the disease attacks the nerves controlling the muscles of the head and neck as well as those of the feet and legs, causing double vision and difficulty swallowing.
Unia ordered the blood test that looks for this version of G.B.S. But the results could take weeks. In the meantime, the neurologist decided to treat him even without this proof. Treatment involves suppressing the wayward immune system — first with steroids and then, if needed, with intravenous immunoglobulin (IVIg), an infusion of antibodies that block the destructive ones of G.B.S.
New Developments in Cancer Research
Progress in the field. In recent years, advancements in research have changed the way cancer is treated. Here are some recent updates:
Pancreatic cancer. Scientists are exploring whether the onset of diabetes may be an early warning sign of pancreatic cancer, which is on track to become the second leading cause of cancer-related deaths in the U.S. by 2040.
Chemotherapy. A quiet revolution is underway in the field of cancer treatment: A growing number of patients, especially those with breast and lung cancers, are being spared the dreaded treatment in favor of other options.
Prostate cancer. An experimental treatment that relies on radioactive molecules to seek out tumor cells prolonged life in men with aggressive forms of the disease — the second-leading cause of cancer death among American men.
Leukemia. After receiving a new treatment, called CAR T cell therapy, more than a decade ago, two patients with chronic lymphocytic leukemia saw the blood cancer vanish. Their cases offer hope for those with the disease, and create some new mysteries.
Esophageal cancer. Nivolumab, a drug that unleashes the immune system, was found to extend survival times in patients with the disease who took part in a large clinical trial. Esophageal cancer is the seventh most common cancer in the world.
The patient had just finished his last day of treatment when the hospitalist Dmitry Opolinsky took over his care. Opolinsky asked him how he was feeling. Much better, the patient exclaimed, but then exploded into a paroxysm of coughing. Unia had warned Opolinsky that the patient was eager to feel better but that his exam had not really changed since his arrival. Still, it often takes a week or two for any improvement following the IVIg. They needed to give him time.
As he waited for his patient to start to get better, Opolinsky kept his eye on the results that were still trickling in. His vitamin B12 was normal. So were the other vitamin deficiencies he was tested for. The biggest disappointment came from the Mayo Clinic, where the neuroimmunology lab looks for evidence of any of a dozen paraneoplastic syndromes. They were all negative. This probably was G.B.S., though nearly a week after treatment, the patient was no better.
The next day Opolinsky got a text to call a number he didn’t recognize. The voice, deep with a hint of an Irish accent, identified himself as Dr. Andrew McKeon, co-director of the Mayo Clinic lab. “Oh, yes, we got those results yesterday,” Opolinsky told him. “All negative.” Actually, McKeon interjected, that result was wrong — or rather, incomplete. There was a newly discovered antibody identified a couple of years earlier by McKeon’s lab, still so new that it had not yet made it onto the automated result form used in testing. This patient had a very strong positive result for this antibody, which attacks something known as neuronal intermediate filaments in the brain. “If he’s a smoker,” McKeon predicted, “then he has small-cell lung cancer. If he’s not, he probably has Merkel cell skin cancer.”
The patient had never smoked, so Opolinsky focused on the possibility that he had this rare type of skin cancer. What Opolinsky remembered from his training was that Merkel cell carcinoma was an aggressive form of skin cancer caused by sun damage and had a much higher rate of spreading than most other forms of skin cancer. He looked at the images on the internet, which showed a bluish red nodule, usually found on the head or face. He didn’t find any of these odd growths, but he ordered a CT scan to look for metastases. There, deep in the patient’s left underarm, was an enlarged lymph node — about the size of a lime. Opolinsky hurried to the patient to feel for the mass, yet even knowing it was there, he couldn’t locate it. But the surgeons could, and removed a mass that tested positive for Merkel cell carcinoma. After his surgery, a PET scan showed that he was free of cancer.
It took some time, and an immune-suppressing medication, but slowly the patient began to recover. That was this past summer. These days he can walk, but only with a walker. And he still coughs a lot. But he’s hopeful that, come spring, he’ll be back on his tractor, even if he has to get onto it from the porch.
Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at [email protected].
