The Neuroscientist Who Lost Her Mind

by Barbara K. Lipska

  In late March, about two months after neurosurgery and after several sessions of radiotherapy, I finally leave Boston and return home to Virginia. The incision on the back of my head has turned into a long scar, which is clearly visible, since my hair, shaved for surgery, hasn’t grown back yet.

  My new white bike is waiting. Orphaned in a dark corner of the garage, it looks at me reproachfully, as if asking, Why did you bring me here if you’re going to die? I pat its soft, white handlebar, and, for the first time since this ordeal began, I cry. “I promise I will ride you,” I whisper.

  A day later, I keep my word. I climb on the bike and start riding slowly through the quiet streets of my neighborhood, steering cautiously so I don’t fall and hurt my recently stitched and radiated head.

  Roughly two months after brain surgery, I tentatively train in the streets of suburban Annandale, Virginia.

  My doctors have told me I have to wait a few weeks after radiation before I can start another treatment. And so, at the end of March, Mirek and I—along with Kasia, my sister Maria, and her husband, Ryszard—escape to the Big Island of Hawaii to forget our dark thoughts of death and to gather strength from one another. Mirek, Kasia, and I bicycle more than two hundred miles through the lava mountains. My vision is perfect, my brain working as it always has, and the fact that I’m not experiencing any symptoms gives me some hope that I’m getting better. I’m filled with optimism. I begin running a few miles every day and working out nearly as vigorously as ever. Out in the open ocean, I swim part of the course of the famous Lavaman Waikoloa Triathlon that is soon to take place. On a whim, I even enter a 5K race through lava fields, and I place fourth in my age group.

  Hawaii affords us a blissful respite from the chaos of the past two months. But in the back of my mind I am endlessly turning over Dr. Flaherty’s advice. I’m imagining what the immunotherapy trial at Georgetown might be like and whether it could actually work if I’m able to enroll in it upon our return home. If not, what then? Will I be able to run, bike, and swim for much longer? Will I ever see this beautiful place again? And what of my family? Will this be the last happy time they remember spending with me?

  Every night in Hawaii, all five of us stretch out on the tropical lawn in front of our bungalow, hold hands, and stare for hours into the enormous, glittering sky. I don’t want to die. I lift my foot to touch a star with my big toe, and then another star, and another, and make wish after wish. Soon, five pairs of feet are dancing across the stars, skipping over the vastness from which we came and to which we’ll return. We are together now, tight as can be.

  When we come back from Hawaii at the beginning of April, I call Dr. Atkins at Georgetown Medical School, which is about twenty miles from where we live. Two days later, Mirek and I meet with him.

  Dr. Atkins describes the protocol of the upcoming clinical trial, known as CA209-218, which is taking place in sixty-six locations and will include several hundred people in the United States and Canada. Every three weeks, he explains, a combination of two monoclonal antibody drugs, called checkpoint inhibitors, will be simultaneously infused into my veins to boost my immune system. These drugs are supposed to teach dysfunctional T cells, which are fooled by cancer into ignoring the disease, how to recognize, attack, and (we hope) kill off the melanoma cells invading the body. The drugs, ipilimumab and nivolumab, are used for the treatment of advanced melanoma. They were separately approved by the FDA, in 2011 and 2014, and in a very short time, they’ve revolutionized treatment of what was considered to be a terminal illness. Combining the two drugs is more effective than using them individually but carries a larger risk of serious adverse effects, including severe rashes, thyroid problems, and other autoimmune reactions, he says. This combination has been tried on melanoma that has metastasized to the brain, but only in a few cases and with mixed results.

  Some of what Dr. Atkins shares with us is familiar by now, but much of it is not. Chemotherapy, which for many years has been the gold standard for cancer treatment, isn’t effective against melanoma, one of the most aggressive cancers, he says. What’s more, chemotherapy indiscriminately attacks all fast-growing cells, including healthy ones—and it causes many side effects, from hair loss to infections, neuropathies, nausea, vomiting, and fatigue. By contrast, immunotherapy drugs don’t directly target cells but instead treat the patient’s immune system so that it can seek out and attack the tumor cells. While there can be serious side effects with immunotherapy too, it holds great promise for treating melanoma.

  Then, the magic words: Dr. Atkins invites me to join the clinical trial. It’s tremendous news. Clinical trials have a limited number of patients. I’m going to be a guinea pig or, better yet, an experimental rat, I think to myself with a smile.

  Just hours earlier, Mirek and I realized that we’d reached a wall with this whole nightmare, that there was nothing more to do but wait. Now, all of a sudden, a gate in the wall has opened and we are ready to run through it without knowing what’s awaiting us on the other side. We thank Dr. Atkins and brace ourselves for the unknown.

  “It can work,” Dr. Atkins promises. “Absolutely, I have seen it work.”

  We cling to his confidence. He seems so certain.

  I will have four treatments, one every three weeks, starting on April 16—just two weeks away. But first, I need to jump through a few more hoops, including a dentist’s appointment, to make sure I don’t have any pressing dental problems, and a series of blood tests. Most important, I need another brain MRI, to make sure I have no brain tumors besides the ones that have already been radiated. If there are any new brain tumors, I can’t join the clinical trial, at least not right away.

  This trial is not for patients with active, untreated brain tumors, Dr. Atkins tells me. He doesn’t explain further, but later, in reading the scientific literature, I learn that it’s essential that there are no active tumors, meaning ones that haven’t yet been radiated. Active brain tumors subjected to immunotherapy can become inflamed, and the patient may suffer serious brain swelling, which can be deadly. At this early phase in the clinical trial, when not much is known about the response of active brain tumors to immunotherapy, it’s just too dangerous to try this treatment on anyone with tumors that are still growing.

  We drive home, elated and hopeful. As we pass the supermarket construction site, I realize I am desperate to see it completed. I cut a silent deal with my brain, begging it to keep any new tumors at bay so I can get the immunotherapy infusions—my best shot at survival, and perhaps my only one.

  Stay clean, stay clean, I tell it. It’s our only hope.

  A week later, a few days before the trial is to begin, I lie as still as a corpse for the most important MRI ever. I’m deeply anxious about what it might show, terrified that my last chance for life will be snatched away.

  The next day, I get a phone call at work. It’s the nurse from Dr. Atkins’s office.

  “What did the MRI show? Any new tumors? Is everything okay?”

  “Yeah, it’s okay,” she says, her tone less excited than I think it should be. “We’ll see you on April sixteenth.”

  I am ecstatic.

  I undergo a full-body CT scan, a requirement before starting the trial, and it shows three small tumors in my lung. But we aren’t alarmed. Tumors in the rest of the body are to be expected with metastatic melanoma, since melanoma cells traveling in the bloodstream often invade other organs. These lung tumors are less dangerous and easier to treat than brain tumors, and the immunotherapy will likely kill them. Even if they initially swell due to the treatment, they won’t cause the same devastation as inflamed tumors in the brain, so their presence does not disqualify me from the clinical trial. Mirek and I are thrilled to get that news.

  But Lance Armstrong’s advice rings loudly. I decide to get a second opinion on the new MRI of my brain. I really like and feel a connection with Dr. Aizer, the radiation oncologist in Boston. So I e-mail him, tell him about our recent trip to Hawaii, mention that I’
m about to enter the clinical immunotherapy trial, and ask if he’ll review the MRI.

  He writes back to say that he’s glad I’m so physically active. “I wish more of my patients could do even a tenth of what you routinely do from an activity perspective,” he says. He adds that he thinks the combination-drug immunotherapy “sounds like a great initial plan.” He says he is happy to review my MRI and future scans. I FedEx him a CD of the MRI.

  A couple of days later, on Wednesday, April 15, I’m at the hospital very early in the morning for a blood test, my last remaining pretrial exam. If everything is in order, as I’m sure it will be, I’ll be cleared for the first immunotherapy infusion, which is scheduled for tomorrow.

  At 6:22 a.m., I get an e-mail from Dr. Aizer.

  Hi, Dr. Lipska, Do you have a moment to touch base over the phone today by chance? I want to check in with you. Best, Ayal

  This kind of e-mail can’t be good. I step outside to call him. The cherry trees are in full blossom, white clouds are rolling by in the blue sky, and it’s so early that the sun is throwing long shadows across the lawn. I shiver from the cold and worry.

  “Dr. Lipska, I am so sorry,” he tells me. “I see new tumors in your brain. They are very small but you should get them radiated before immunotherapy.”

  I can’t believe what he’s saying.

  “No, I can’t, I can’t wait!” I insist. “I’m going in for my first infusion tomorrow! There’s no time for radiation—they’ll kick me out of the trial! Dr. Atkins says I’m fine. He doesn’t see anything on the scan. Are you sure?”

  “The tumors are very small. They could easily be missed, but they’re definitely there,” he says. “One is in the frontal cortex, where it could be dangerous for your intellect and cognition, as you know so well, Dr. Lipska. You really should get them treated before you start immunotherapy.”

  “I can’t!” I repeat. “They will kick me out of the protocol!”

  For half an hour, he tries to convince me to get radiation. He repeats that the tumor in the frontal cortex could be especially problematic. Without radiation, it will almost certainly grow, and, if subjected to immunotherapy, it could also become inflamed, causing my brain to swell uncontrollably. It could quickly begin to seriously damage all the highest functions of my mind: my ability to think and remember, to express emotion, to understand language. In short, it could cut off all the things that make me human. If it causes too much swelling, it could even kill me.

  “But of course, another possibility is that all the tumors will be destroyed by immunotherapy drugs, yes? Don’t you think so, Dr. Aizer?” I ask.

  “Perhaps,” he responds, and he says again how sorry he is. I thank him and we hang up.

  I stare at the darkened cell phone.

  Shit. I’m dead.

  I’m dead either way. If I tell anyone at Georgetown what Dr. Aizer found on the scans, they’ll refuse to give me the infusion, which is my only chance at salvation. But I’m dead if I don’t tell them because subjecting these new tumors to immunotherapy could kill me.

  What do I do?

  Dr. Atkins’s report states I have no new tumors. And his nurse told me the scan was clean. They cleared me for treatment! Did he misread the MRI? Radiology is more an art than a precise science, and it’s possible he didn’t see them. Dr. Aizer did say they are very small.

  Or maybe Dr. Aizer is wrong. Maybe what he saw aren’t tumors but something else, a scar from my radiation, perhaps, or an artifact?

  I don’t know.

  I can postpone the treatment. I can get the new tumors radiated, as Dr. Aizer insists, and then wait two weeks after radiation—as the protocol requires—before getting another scan. If that one comes out clean, then perhaps I can start immunotherapy—if there is still room for me in the trial. But if new tumors keep popping up, it will be an endless cycle: I’ll get a scan that finds a new tumor, get radiation, get a new scan that finds another new tumor, and on and on and on. I can’t keep radiating every single one—I’ll have no brain left. Meanwhile, I’ll be locked out of the clinical trial. They have very stringent timelines for being included, and no doubt there are many other desperate people eager to take my place.

  This is my only shot.

  I’m supposed to start the trial tomorrow.

  What do I do?

  The sky is so blue. What a glorious day.

  No. No question. I’m doing this. It’s my only hope.

  I’m not going to say anything about the new tumors to anyone. I’m not telling Dr. Atkins what Dr. Aizer said, and I’m not telling Mirek or Kasia or Witek or my sister. I’m making this decision for myself, by myself. Nothing is going to stop me from entering this clinical trial. I would rather take my chances than die without trying it.

  That night at home, I mention nothing to Mirek. When Kasia calls, I calmly tell her I’m looking forward to the next day. I share nothing about my dilemma or the choice I’ve made.

  I maintain my strategic silence the next morning when I march into the hospital and head with Mirek into the infusion unit, a large room with individual patient cubicles partitioned by curtains. After I sign in and sit in my cubicle, Dr. Atkins enters with his entourage of smiling nurses and greets me.

  “Are you ready?” he asks.

  It’s my last chance to call this off.

  “So, everything is okay, yes?” I ask.

  “Yes,” he says.

  “Will you be doing brain scans during this therapy? To check for any new tumors?”

  “No, we won’t need them for another three months,” he says. “This is going to work.”

  I watch him walk away. I feel like a paratrooper jumping off a plane into the dark night, hoping that my parachute will open.

  I jump.

  As I sit in a reclining chair, the nurse punctures my arm for an IV that begins to drip the drugs into my bloodstream.

  I rest my head on the back of the chair and close my eyes.

  Maybe this will kill me. But I’ll definitely die without it. Dr. Atkins believes it will work. And I trust this immunotherapy even more than I trust him.

  I will live, I tell myself. I will live.

  On the drive home, I tell Mirek my secret. “Dr. Aizer found three new tumors in my brain yesterday but I didn’t tell Dr. Atkins,” I say. “Nothing is keeping me from this trial.”

  Mirek’s smile is hesitant but he nods his approval. “I understand,” he says. I call Kasia and tell her too. To my surprise, she—like Mirek—approves of my decision.

  “Brave mum,” she says to me in Polish.

  A few days later, Kasia and I have a phone conference with Dr. Aizer. He reiterates that it could be dangerous for me to continue with immunotherapy with three new tumors growing in my brain. When I tell him I will not be getting any brain scans for three months, he becomes even more worried. But Kasia and I remain united around my decision. We listen but we really don’t want to hear his concerns. I don’t know it at the time, but after we hang up, Dr. Aizer goes into my sister’s office at the Brigham and tells her he is very worried about me. She hears him out but she knows I have made up my mind. She keeps the conversation to herself until long after I have completed my treatment.

  On May 5, three weeks after my first infusion, I go in for my second. Mirek and I awaken early and drive to the Georgetown hospital to try to find a precious parking spot in the underground garage of the old, cramped complex. We proceed through a maze of corridors to the Lombardi cancer center, passing by a portrait of the pope that the hospital staff use as a landmark for giving directions. (“Go straight by the pope to get to the infusion center,” they say, or “Turn right by the pope if you’re here for an MRI.”)

  As usual, the waiting room at Lombardi is filled with patients, some bald from chemotherapy, some in wheelchairs, some limping on their canes. But most look healthy and normal. The techs draw my blood and we wait for the lab results. After a couple of hours, we see the doctor, who evaluates the blood tests to decide whet
her I am well enough to receive an infusion that day. It feels like waiting to learn if I’ve won the lottery. As before, I obsess that I will be rejected because of an abnormal blood result or some other lurking danger.

  But it doesn’t happen. Physically strong and optimistic against all odds, I go through the second cycle of immunotherapy without major problems. I am now halfway through the twelve weeks of the clinical trial and feeling good. With each IV drip, I imagine my newly emboldened T cells leading the army of my immune system to attack and defeat every melanoma cell in my body. I will it to happen, I will all of the cancer cells to die. They must die.

  I’m full of hope and energy. Nearly every day, I run or walk a few miles. Nearly every day, I go to work and complete my tasks with no problem. With every bone in my body, every neuron in my brain, I believe that I am on the mend.

  And then—everything breaks down.

  I never see it coming.

  4

  Derailed

  Sometime after the second infusion, my body turns on me.

  Modified by the drugs to sense danger everywhere, my immune system has been on high alert since the first infusion. Now, after the second one, it begins to attack not just the tumors in my brain but healthy tissue throughout my body. This autoimmune reaction causes inflammation in my skin, thyroid glands, and pituitary gland, a tiny structure in the innermost part of the brain that controls the flow of hormones to the body’s other glands, including the adrenals. Soon, my thyroid stops functioning, forcing me to take replacement thyroid hormones; I also begin taking prednisone to stop the rashes and fill in for the natural steroids that my adrenal glands have stopped producing and without which I would experience serious fatigue, muscle weakness, and weight loss.