Strangely, however, I cannot fully resurrect the emotions of that time. It’s much harder to recall how I reacted and what I was feeling. On the infrequent occasions when my family tells me about something odd that happened, I listen carefully but cannot connect the factual description to the turmoil they went through. I don’t remember any of that. It’s as if my emotional memory resides somewhere else, someplace to which I still have no access. Maybe the feelings were never encoded in my brain at all.
Mirek asks, “Remember that awful dinner after we picked you up from the hospital? You were breaking my heart with your empty eyes, frozen facial expression, harsh words. You were so mean, so cold.”
I try hard to recall. I ask about the details—what I made for dinner that night, where we were sitting, who said what.
“Kasia and I got up from the table and went into the kitchen to cry. It was unbearable to see that you were not your normal self. We thought you were gone forever,” Mirek says, and he chokes with emotion. “You reminded us of Kai, the little boy from Hans Christian Andersen’s fairy tale ‘The Snow Queen.’” My husband’s eyes fill with tears.
I strain my brain again, and the images emerge as if from a movie I’d watched years before.
Yes, the dinner, I remember. I was cooking and it was not coming out as I expected. There was something weird about that dinner. But what? Was I distant and cold? Did they cry; were they sad? I don’t remember. Maybe it happened to another me, another person entirely?
I do, however, remember the story of the little boy named Kai. The tale terrified me when I read it as a child. The story goes that two children, Kai and Gerda, live in fairy-tale happiness until a mean goblin with the power to turn beauty into ugliness breaks his magic mirror. Hundreds of millions of pieces scatter around the world. One splinter pierces Kai’s heart; another one gets into his eye. His heart turns into a lump of ice; his eyes see only evil. Kai becomes cruel and aggressive. He abandons Gerda and his loving family and chooses to live in the eternal winter of the glacial palace of the Snow Queen.
A nasty goblin must have embedded a shard in my brain and made me insensitive to the ones I love. He turned me into a callous and unloving caricature of myself.
Now my icy heart is thawing and I am crawling back to life, one dreamlike recollection at a time.
How is it that these memories are returning?
The brain has a remarkable ability to heal itself after various kinds of injuries and assaults, a capacity that amazes scientists and doctors. Even patients with severe brain damage can sometimes recover nearly fully. While it’s clear that excellent medical care and therapy can assist in recovery from a brain injury, how the healing process works remains unknown. The BRAIN initiative that President Obama launched in 2013 is aimed at revolutionizing our understanding of the brain, including how it recovers from injury and disease. But at this point, frankly, the brain’s ability to repair itself seems nothing short of miraculous.
Unlike cells in other parts of the body, which constantly replace themselves, neurons in the brain do not as a rule regenerate. Experiments in mice have shown that a limited number of new neurons may grow in the hippocampus, the part of the brain that stores memories and one of the first regions affected by Alzheimer’s disease. But it’s probably an insignificant number of neurons, and it’s unclear whether they ever become fully functional. It’s also unknown if the same phenomenon occurs in the human hippocampus. We do know that in the brain regions critical for thinking, such as the prefrontal cortex, the neurons that emerged in infancy and probably even before remain the same throughout a person’s life.
The fact that we retain the same neurons from the beginning to the end of our lives may be one reason we can consider ourselves “ourselves.” What may change, however, are the connections between cells and among brain regions. Some connections grow stronger; some wither; some are damaged. If a region of the brain becomes impaired, new connections between cells may grow and help us recover some or most of the disabled function. But does that modify who we are?
I’m always surprised how little we change throughout our lives, even after traumatic experiences and serious illnesses. I was kind of myself—some version of myself—even when one-third of my brain was dramatically swollen. I am still myself now, as I continue to recover. But the tumors, the radiation, the brain swelling—all of these may leave their marks on my brain and my personality. They may lead to scarring, which can result in lingering damage to the brain. People who’ve received radiation to the brain or chemotherapy or immunotherapy may have ongoing cognitive problems, including memory issues.
When someone asks me how I’m doing—meaning, is my brain operating as it used to—I say, “I’m functioning just like before.” But is it true? My attention span often seems shorter, and I get tired more easily. It’s harder for me to concentrate. I cannot run or swim or cycle as fast, and my balance is not as good as it used to be. When I ask my family if I’ve changed and how, they say they’re unsure. But it’s clear this ordeal has affected all of us. There’s no question that it has aged me. It has aged them too.
Despite the relief I get from steroids easing my brain’s swelling, and the fact that radiation is killing the visible tumors, my family and I are acutely aware that there are melanoma cells lurking in my body. New tumors will most likely grow, and probably soon. They will spread wildly, out of control, and take over my brain like weeds invading a neat flower bed. Although I’ve received a kitchen sink full of therapy—radiation and a combination of two immunotherapy drugs—I need more treatment, perhaps a whole bathtub of it.
So Dr. Atkins is adding targeted therapy, a final option that was floated at the very beginning of my treatment. Although there are some novel drugs in the research pipeline that I’m hearing about, at present, targeted therapy is the only option left for me to try. He says that I should be treated right away with a combination of trametinib and dabrafenib, two drugs newly designed specifically for a mutated gene involved in melanoma, BRAF. Trametinib inhibits the MEK1 and MEK2 proteins, and dabrafenib inhibits the BRAF protein. All three act in the same cell-signaling pathway, which becomes overly stimulated in melanoma cells and leads to their uncontrollable growth and proliferation. Two mutations, called BRAF V600E and BRAF V600K, account for over 95 percent of mutations in the BRAF gene found in melanoma patients. If a patient has no mutation in the BRAF gene, he’s carrying what’s called BRAF wild type and will not benefit from these drugs because the pathway in which they act is not abnormally overactivated by the faulty BRAF.
My tumor was tested genetically in March 2015, shortly after it was removed from my occipital cortex, and found to have a rare mutation, BRAF A598T, which occurs in less than 5 percent of melanoma tumors. In the genome, it is situated very close to the more common mutations, so it’s possible that this gene makes a faulty BRAF protein just like they do. But nobody knows for sure. If my mutation does behave like the common mutations, then the BRAF/MEK1/MEK2–inhibitor drugs may be able to block the haywire activation of my melanoma cells and halt their proliferation. In any case, that’s the plan. We’re hoping the combination of both drugs will finish off my cancer.
These new drugs seem to be my last chance for survival. They are small molecules that can easily cross the hard-to-penetrate blood-brain barrier and get into the brain. By contrast, the antibodies employed in immunotherapies are large proteins, which, if taken orally, are quickly digested like all other protein products that we eat. That’s why they have to be given as infusions delivered directly into the bloodstream. Immunotherapy drugs don’t actually get into the brain; instead, they modify immune cells (T cells), which can reach the brain. Trametinib and dabrafenib come in the form of very innocent-looking pills, which is much more convenient than an infusion; I won’t have to go to the hospital to receive my doses.
But these drugs are not FDA-approved for my rare mutation so we need to convince my insurance company to pay for them. This may be a serious challenge b
ecause the scientific evidence that they will work for me is scant, at best. And the treatment is going to cost a fortune: hundreds of thousands of dollars. Dr. Atkins predicts that the insurance company will deny his first request, and within a few days, it does just that. Jake’s mother and her husband offer to cover the full cost of the drugs, and Mirek’s mother, in Poland, wants to send us her life savings. But Dr. Atkins suggests we wait. He’s hopeful that he’ll find scientific support to get me the drugs for free or at a minimal cost.
Dr. Atkins writes a detailed letter explaining that my rare BRAF mutation warrants treatment with these drugs. We wait a day, then two. Then another day. On the fourth or fifth day, Dr. Atkins calls me: The drug company has agreed to give me the drugs for “compassionate use.” This term refers to using a new, unapproved drug to treat a patient when there are no other options. In other words, She’s going to die anyway, and there’s a slight chance this might help, so why don’t we try it as a last resort? The treatment will be free.
Within a few days, I receive two boxes, one the size of a countertop refrigerator filled with ice and my very pricey dream drug trametinib, and a smaller one containing the dabrafenib. Excited, I take pictures of the boxes. What a joy! Christmas in July!
They have to work—they’re far too expensive to fail me.
I immediately swallow the first dose of the pills. And wait.
A few days go by without much of an effect. Then the rash appears.
Skin inflammation is one of the most common adverse side effects of the trametinib/dabrafenib treatment. This reaction to the drugs is experienced by more than half of patients who take them. The two-drug combination, in contrast to each drug by itself, increases the toxicity. There’s only one pleasant side effect, which comes out of the blue: my eyelashes grow very long, lush, and coal black, the bottom lashes brushing the tops of my cheeks.
Since I have insomnia from the steroids, I get maybe two to three hours of sleep at night. I’m very tired and catnap frequently; I add sedatives and sleeping pills to my growing medical arsenal. Yet I continue power-walking every day, as far as eight miles, in the early morning or at sunset to avoid sun and heat. I cannot swim because of the rash and my very dry skin, but I bike from time to time in the early morning, sometimes for an hour and a half. Like a soldier always ready for battle in this protracted war with cancer, I am determined to stay in shape.
By mid-July the rash explodes with a force we had not expected. Scary reddish welts cover large areas of my body, and my skin feels as if it’s on fire. Dr. Atkins decreases the dose of dabrafenib by half (since it is likely to be dabrafenib, rather than trametinib, that is causing the rash). A few days later, less than two weeks after I started taking one of the drugs upon which all my hopes are pinned, he directs me to stop taking it entirely because my whole body is covered in horrific splotches. This type of out-of-control rash can actually endanger my life, he tells me.
Still, my mind seems to be working well. I am able to read, keep notes, and hold teleconferences with my colleagues at work.
I am coming back to life. But my family and I don’t talk much about what we experienced during my mental decline and crash. We’re terrified that it will return without warning.
I’m scheduled for another brain scan on July 21. It will be the first one I’ve had since the catastrophic MRI on June 19 that revealed the new tumors and swelling in my brain. Strangely, I’m not worried about this upcoming scan. I’m resigned to hearing bad news again, so I continue planning for death. I clean out my closets and drawers, the accumulated stuff of my life. But deep inside, against all odds, I am hoping for a miracle.
On July 21, a few hours after the MRI, Mirek, Kasia, and I gather in a room at the Lombardi Comprehensive Cancer Center and wait for Dr. Atkins to deliver my sentence. The wait is long. It’s late afternoon, and we’re all very tired. Our anxiety is so intense that we don’t talk to one another but stare into the distance, biting our nails, breathing deeply, and sighing.
Finally, Dr. Atkins walks in. He is beaming.
“Great news!” he announces. “It worked!”
Before we can absorb his words, he continues. “All of your tumors shrank considerably or disappeared altogether, and there are no new lesions in your brain,” he says. “The trametinib/dabrafenib combo therapy was a success!”
Instead of focusing on this remarkable news, I start to argue.
“Dr. Atkins, how do we know?” I say. “How can we attribute my improvement to dabrafenib and trametinib? I was taking them for such a short time. Is it possible they could work so fast? Maybe what worked was the combination of immunotherapy and radiation—or those two plus the targeted therapy. Oh no, we’ve lost the chance to really know for sure! We’ll never know what the magic bullet was!”
Dr. Atkins gives me a dismissive half-smile. “I don’t care what worked and neither should you,” he says. “The tumors are disappearing. We should be grateful for that.”
I am grateful. But the scientist in me is annoyed. Perhaps only another scientist can really understand, but I’m dissatisfied by not getting a precise answer to what succeeded in this unique experiment—the experiment of me.
My brain scans from June 19 (left) and July 21 (right). The swelling (the areas in white) has decreased dramatically, and the tumors, including the one in my frontal cortex, have all but disappeared.
Dr. Atkins offers to show us the brain scan on his computer, and Kasia peers at it, amazed at the change.
“It’s dramatic,” she exclaims. “The tumors have almost all disappeared.”
I don’t look at the images. I cringe at the thought of seeing photos of my wounded brain. Mirek and I sit in silence, too traumatized to express our happiness. This date marks an amazing breakthrough that we are not ready to trust.
The next morning, July 22, Mirek writes a short note in his diary: We enjoyed the news as much as we could.
His diary entry sounds like an unimportant footnote. In truth, we are all in a state of shock. Our emotions have been battered for months. Everyone expected me to die, then I got a pardon, then more bad news, and now another reprieve: the tumors have disappeared.
None of us remembers anything else from that day.
Dr. Atkins believes it was the dabrafenib/trametinib combination that worked so spectacularly, so he directs me to resume taking a half dose of dabrafenib. The next days and weeks are troubling, as new side effects appear: bleeding sores on my hands, lips, and face. When I awaken at night and go to the bathroom, the image in the mirror is terrifying: blood seeping from my lips has dried around my mouth and onto my neck. I look like a vampire after a busy night. My pillow is stained with blood, and so are the sheets. The skin on my feet is dry and so cracked that every step is painful, and my heels are bleeding too.
On some nights, I have a fever as high as 103 degrees, with chills so profound that in the middle of the hot summer I sleep under two thick quilts and a pile of blankets with a gray wool cap on my head. The shivers nearly knock me off the bed.
There is worse to come. Very early one morning, as Mirek is exercising in the basement, he hears an unusual bang and races upstairs. He finds me unconscious on the bathroom floor, my body slick with sweat, my pajamas drenched. The top of my head is bleeding, and a chair lies toppled next to me. I have fainted and hit my head on the tile wall or stone floor—he can’t tell which. I soon come to with no idea what happened. Mirek insists that from that point on, we leave every door inside the house open so he can hear if I’m in distress.
Dr. Atkins decides I need to take a break from dabrafenib again, and then also from trametinib, and he takes me off them. My skin improves and I start feeling well. And, despite my not having any treatment for two weeks, the next MRI, on September 1, shows no new tumors. And the old ones have shrunk even more or disappeared. Every six weeks, I get new brain scans. Over the next few months, several small tumors appear and are treated with CyberKnife radiation. They grow slightly and then shrink. Dr.
Atkins keeps me off the dabrafenib but puts me back on the trametinib.
Over the fall of 2015, I continue to have rashes and experience bleeding on my hands, arms, and the top of my skull. But I seem to have returned to the person I was before all of this began. I don’t get lost walking around the neighborhood. I remember how to make my favorite recipes. I’m not snapping nonstop at my family. I talk by phone each day with Kasia and Maria in my normal, loving fashion. Mirek and I have friends over for lighthearted dinners. My grandsons come to visit and I play with them happily.
Over time, Mirek shares, bit by bit, how I behaved in June and July. He reveals how I was someone different than the person he knew, a shadow self, and how they all worried the real me was gone forever.
I promise him that I will never again be so mean to him and our family. But inside, I know it’s a promise I may not be able to keep if my brain fails me once more.
From time to time, I make stupid jokes, pretending to lose my mind, faking that I don’t know where I am. He doesn’t laugh. It’s cruel, I realize, and I stop doing it. After all, I’m the only one who didn’t witness what happened. I’m the one—in a way—who suffered least.
In January 2016, after a year of aggressive cancer treatments, the torment of new scans, and anxiety over whether they would reveal new tumors in my brain, I sit on the couch in my living room. My arm is swollen and tender. It’s the lymphedema from my breast cancer, exacerbated by immunotherapy for melanoma.
Why haven’t I done something about this sooner? I can’t believe I’ve never taken care of it.
I do a computer search for nearby clinics with physical therapists who specialize in lymphedema. Oh, here’s one close by, at Inova Fairfax Hospital. I pick up the phone and call the office. The receptionist schedules me for an appointment in just a few days, on January 15. I wait patiently for the date to come.
The Neuroscientist Who Lost Her Mind Page 16