He Almost Couldn’t Walk His Daughter Down the Aisle. What Is Causing His Leaden Feet?

The 60-year-old man held tight to his daughter’s arm as they waited for their cue to walk down the gravel path of the garden to the altar where the bridegroom waited. As the first notes played, Joe’s daughter gave him a smile and a nod, and they started down the aisle. Joe could hear the crunch of the gravel beneath his feet, but he couldn’t feel it. For the past several months, his feet had felt like numb lumps of clay. In his other hand, he gripped the cane that provided his much-needed stability. He had to concentrate with every step, but he was determined not to embarrass his daughter, or himself, by falling. He’d already fallen once that morning, but luckily only his wife and in-laws had been there.

Walking with his daughter on her wedding day had been Joe’s goal for the past few months, and it wasn’t at all clear that he would get here. Certainly, when Joe, a dentist in Fairfield, Conn., first noticed the feeling of pins and needles in his feet, he had no idea that he would be struggling to walk just a year and a half later.

A Life-Saving Therapy

Joe already knew he was a very lucky man. Nearly 15 years earlier, he was found to have Waldenstrom macroglobulinemia (W.M.), a type of slowly progressive lymphoma that can’t be cured. And based on what he was told, and what he read, he had already outlived most patients with this disease by a good three to four years. When the disease was diagnosed, he had no symptoms. His doctor noticed that his lifelong anemia had worsened and that his red-blood-cell count had dropped even lower than normal. Concerned, the doctor sent off some tests, including a bone-marrow biopsy.

The biopsy provided the answer. Most of the room in Joe’s bone marrow — the place where blood is made — had been given over to one type of white blood cell, leaving very little room for the cells that made the other blood products, like red cells and platelets. The type of white blood cell filling up the space was what is known as a B lymphocyte, and its job is to produce antibodies. In Joe’s case, a single white blood cell had gone wild, reproducing vigorously, loading his bone marrow with clones, all of them making antibodies, which now crowded into his circulation.

Joe went to the Dana Farber Cancer Institute in Boston, where one of the world’s experts on W.M. practices, and was treated with the best therapies available at the time. They didn’t work. When his oncologists looked at his bone marrow after treatment, it was worse than when they started. Despite their best efforts, the disease had progressed. Now they turned to an experimental drug called Ibrutinib. The drug was being tested on patients with W.M. as well as several other types of cancers. His response to this new medication was immediate and remarkable — the kind of response that every patient enrolled in a study of an experimental drug prays for. Within months, his disease was in what’s called V.G.P.R., or very good partial response. Although the disease remained in his bone marrow, the number of antibodies in his circulation dropped, and his red blood cells rose; each is nearly normal in number. The only side effect he has had from the medication was a rash on his upper chest, and so for Joe, the decision to continue to take it was an easy one.

A Good Walk Ruined

Because of the effectiveness of the medication, Joe never had to leave his dental practice. For years, only his assistant even knew he had an illness at all. He had been on Ibrutinib for more than four years when he first noticed the funny pins-and-needles feeling in his left foot and ankle. It started around Christmas. It was no big thing. He only mentioned it in passing when he travelled to the Dana Farber Clinical Institute where he was being treated for his W.M. By summer, that had changed.

In June, Joe traveled to Ireland with his wife and in-laws. After they settled into their hotel in Dublin, Joe and his wife, Linda, headed out to see the city, but Joe didn’t get far. For the past few months, he had been feeling that uncomfortable sensation of pins and needles in both feet and ankles, as if they had gone to sleep. He also began to notice a subtle loss of sensation in his feet, and that made walking difficult. He had to watch every step he took; he walked more slowly and tired more quickly. Even his octogenarian in-laws walked faster than he did.

Losing His Nerve

At his next appointment, Joe explained how bad his feet and lower legs felt. His hematologist sent him to see a neurologist to get some testing to help identify the cause of the odd sensation. He also sent off blood samples to look for some of the most common causes of what is called a peripheral neuropathy. When the results of those studies were normal, he ordered an M.R.I. of Joe’s brain and spine.

One of the first tests done to understand a peripheral neuropathy is a nerve-conduction study, which measures how well nerve fibers are working. The test can determine if it is the nerve fibers themselves that are damaged or if the injury is focused on the fatty sheath surrounding the nerve, known as myelin. Based on the results of the nerve-conduction study and his own exam, the neurologist focused on what he considered the two most likely causes of the man’s neuropathy: the kind of neuropathy sometimes seen with W.M. or a side effect of Ibrutinib, the medication Joe was taking to treat his W.M.

The M.R.I. showed bright spots in two places in the spine: one in the neck and a second in the upper chest. These abnormalities raised a third possibility: that Joe’s cancer, while appearing well controlled, had secretly invaded the central nervous system in a rare complication known as Bing-Neel syndrome — named for the two doctors who first described the devastating, often deadly complication of W.M. nearly 100 years ago. If that’s what Joe had, the cerebrospinal fluid, which surrounds his spine and brain, would be dotted with the same lymphocytes that took over his bone marrow.

Joe had to stop taking Ibrutinib a few days before he had a lumbar puncture to get the cerebrospinal fluid to look for Bing-Neel. However, before he could restart the medication, Joe suddenly became confused. He developed a fever. He became incontinent. Linda called the doctors in Boston from their home in southern Connecticut. He needed to go to the hospital, they told her.

Linda rushed him to Yale New Haven Hospital. He had a thorough evaluation, looking for an infectious cause of his symptoms. When none was found, he was restarted on his chemotherapy and Ibrutinib, and almost immediately he got better. Joe and Linda recalled that something similar happened the last time he stopped the medicine — that time for a colonoscopy — but they hadn’t made the connection between the stopped medicine and the strange symptoms, until it happened this second time.

While at Yale New Haven Hospital, Joe was seen by a hematologist and a specialist in the neurological effects of cancer known as a neuro-oncologist. After his hospitalization, he continued to see these two doctors to learn if they had any answers to why his feet and legs were now numb and his hands and fingers had that same prickly sensation, as if they’d gone to sleep and never woken up.

Something Old? Or Something New?

The good news was that there was no evidence that Joe’s cancer had infiltrated his spine or brain. There was no sign that he had Bing-Neel. Some of his spinal fluid was sent to Washington University in St. Louis, and there they found evidence that the advancing neuropathy could be from an autoimmune process in which his immune system was mistakenly attacking his own body. These revved-up, misdirected antibodies could be connected to his cancer, or they could be independent of his cancer. Joe’s brother had an autoimmune disorder, rheumatoid arthritis, and the tendency to develop autoimmune diseases can run in families. No matter where the neuropathy was from, the treatment was the same — suppression of the rogue immune system. He was started on a six-month course of intermittent high-dose steroids and intravenous immunoglobulins, or IVIG.

At the end of the six months, Joe’s neuropathy was no better. But it wasn’t any worse either. Joe was grateful for that, because it allowed him to continue to work. And best of all, he was able to walk his daughter down the aisle with the help of his cane. But two months later, after the immune suppression was stopped, the cane wasn’t enough. He needed a walker. When he went back to Dana Farber, his oncologist was worried by the rapid progression of his symptoms. Indeed, he was so worried that he wanted Joe admitted to the hospital to give them a chance to figure out why he was losing his sensation in his legs and now his strength as well.

During this hospitalization, the focus shifted from his peripheral nerves — which send information and instructions to and from the spine and brain — to the central nervous system. In addition to the areas that lit up in his earlier scan, an M.R.I. done at Brigham and Women’s Hospital during this admission showed some possible inflammation of the bottom of the spinal cord. The concern was that this was evidence that his W.M. had invaded his central nervous system, even though they had not found evidence of this in the spinal fluid. But his symptoms seemed to be progressing in front of their eyes; by the time he left the hospital, he was using a wheelchair. And so, when he came back to Dana Farber for a follow-up, his doctors recommended that Joe get radiation directed at the bottom of his spine. He had the radiation therapy. It didn’t help. Although it saddened him, Joe let his office know that he would not be returning until he got better.

Desperate, Joe and his wife reached out to the Mayo Clinic in Rochester, Minn. He spent several days there and had dozens and dozens of tests performed. They were unrevealing.

A Fight From the Brink

Back in Connecticut, the neurology team at Yale was also concerned by Joe’s continued progression. He was unable to walk at all. He was incontinent of urine and stool. He had almost no sensation below his waist. Earlier studies suggested the presence of antibodies that were attacking the nerves in his legs and lower body. Perhaps if they could take out the fluid containing these antibodies — the plasma that carries the red blood cells through the body — and filter out the antibodies, they could stop the destruction. There was no evidence that such an approach, a technique called plasmapheresis, would work in this disease. It hadn’t been studied. But it seemed reasonable that it could work.

The neurologists reviewed the very real risks and unclear benefits with Joe and Linda. Given how much Joe had lost, he was ready to try anything. A thick catheter was placed under his skin and into the large vessels that carried blood to the heart. That allowed the circulating plasma in his body to be diverted into a machine that eliminated the antibodies, and then the fluid was reintroduced to his circulation. He had plasmapheresis performed five times.

He was to be sent to Gaylord Rehabilitation Center in Wallingford, Conn., to help get him stronger and see if removing these antibodies had any effect. But before he was even able to leave the hospital, a huge blood clot slammed into Joe’s lungs. His ability to circulate oxygen collapsed. So did his blood pressure. And Joe spent the next two months — 72 days — in the hospital. He hovered near death for weeks. The only medications he received were those directed at keeping him alive. Even the Ibrutinib, which had kept his W.M. at bay for the past several years, was stopped.

Joe fought his way back from the pulmonary embolus and all the subsequent complications. His family had been called in to say their goodbyes twice, but Joe always, somehow, made it through each of these life-threatening complications. He was tough. And lucky. And he survived, despite his doctor’s fears.

Finally, early this fall, he recovered enough to travel back to Gaylord and begin his recovery. And slowly, with incredibly hard work and toughness of spirit, Joe has gotten stronger. After his long hospital stay, he was too weak to even sit up. He described himself as a salamander — able only to lie on his back. Even talking was exhausting, at first. Now he can sit up. He can feed himself. He can transfer himself in and out of his chair. He felt lucky to be able to get back to nearly the same level of (dis)ability he had before he got so very sick. But he is still incontinent. He still can’t walk. He is still mostly numb and mostly paralyzed below his waist.

But mostly — that’s new. He had been completely numb and paralyzed. One morning, not too long ago, Joe noticed, almost accidentally, that he could move the toes on one foot. He couldn’t wait to show this to anyone who walked into his room. His wife, his two daughters and everyone who has come to know Joe at Gaylord were excited to see even this tiny bit of progress. Now he can move the toes on both feet.

Since leaving the hospital, Joe has also started to feel a burning sensation in his legs and feet. Though not really painful, it’s not a particularly pleasant sensation — unless you haven’t felt anything at all for nearly a year. To Joe, feeling anything feels like progress. He’s still far, far from being able to even stand. But having any sensation, any ability to move, is new.

Why is he getting better? And how much better will he get? None of that is clear. Not to Joe. Not to his doctors. Is it because his W.M. is better? The disease is still there but has progressed very slowly, even though his Ibrutinib was stopped. Or was the neuropathy caused by the Ibrutinib itself? And now that the medication has been stopped, can his body can recover? That kind of side effect has not been reported with this medication. Or was it from the plasmapheresis performed months earlier?

What do you think is going on here? Is this something you recognize? Do you know these medications, these diseases? Can you help Joe get back on his feet? Enter your comments below, and I’ll let you know what happens in the case as it develops. Please briefly describe your thinking. How a diagnosis is made is often as revealing as the diagnosis itself. Let’s see if we can figure this one out.

All answers will be reviewed, and the most promising will be shared with the patient, who will be able to discuss them with his physicians.