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.
