It began with a word. It was not the meaning of the word but its pronunciation. A few months passed and there were even more words that couldn’t come out right. First, he noticed that they were longer words, and in time, he was having problems with shorter words too. The words would eventually land chaotically in the air. One syllable after another choppy syllable. Any hints of grace or fluency were gone. In time, he started leaving out adjectives and conjunctions.
He flew to the Mayo Clinic for help. The diagnosis: apraxia of speech. He got quieter at work, which wasn’t easy making real estate deals and managing his company. Emailing filled the spoken void. Getting words out of his mouth so that they are understood, that was his only problem.
It is now four years later, and he and his wife have traveled to the Memory and Aging Center at UCSF to figure out what is wrong with his brain. He’s heard many opinions over the years, and he wants to understand the root of his language problems. He joined the study a few years ago. This is his third annual visit. He’s spent the morning conducting all manner of tests – neurological exams, cognitive and language tests, blood draws, a spinal tap. His wife met with a nurse and a psychologist to get a sense of how things have progressed.
By early afternoon, his team – a neurologist, a neuropsychologist, a geneticist, a nurse and a research coordinator – come together to share their own assessments. They also want to know what is wrong with their patient. It is still a puzzle. His memory is fine. His comprehension solid. He is a great multi-tasker and goes out three days a week to play hockey with his buddies.
The experts present his history, and one by one pieces of the puzzle are laid down. Here is what they know: he recognizes faces and the emotions attached to them. His balance is impeccable. He has no trouble swallowing, although the team learns that he has had an injection of Botox into his larynx that a physician told him might help with his apraxia. He takes a baby aspirin a day and co-enzyme Q10, sleeps a solid five to 7 hours a night.
Bruce Miller, the neurologist who directs the MAC, listens to his colleagues discuss their findings. Before the brain scan goes up on a screen, he wants to know what everyone thinks the diagnosis is. More to the point, he wants to know what they think the pathology in his brain will show and what gene mutation could explain his singular and worsening problem.
Primary progressive aphasia is an umbrella term for language problems. But there are so many possible things that can go bump in the brain and cause deficits in how we process language. People can have word finding trouble, word usage problems, issues with putting words in a sentence in the correct order, spelling, or word comprehension problems. Each one of these symptoms suggests a different underlying problem, and scientists now have a better sense of what language problems are tied to the genetics that is now coming to light.
Dr. Miller has his suspicions but asks his team: So, what do you think?
Over 120 years ago, German psychiatrist and neuropathologist Arnold Pick would point out abnormalities in the frontal and temporal lobe regions of the brain that he linked back to three patients he treated with progressive language problems. He also described patients with behavior and personality changes and a kind of social dementia – many exhibited antisocial and impulsive behaviors – that today is known as frontotemporal dementia. Later, he studied the brains of Alzheimer’s patients under his microscope and identified in some of those cases a build-up of proteins in neurons that became known as Pick’s bodies. Today, scientists know that these aggregates are made up of toxic tau proteins.
Many in the room suspect that their patient suffers from some type of primary progressive aphasia. But there are subtypes: agrammatic, semantic or logopenic. Any one of these PPAs can trigger language problems. Maybe it’s corticobasal syndrome, which can also present with language problems. There is no evidence that the patient has behavioral variant frontotemporal dementia. There are no behavior or personality changes.
Dr. Miller was hoping that the brain scan would reveal the actual problem. The computer presented slice after thin slice with nothing remarkable. There was a collective shaking of the heads. This wasn’t going to be easy.
The patient and his wife were welcomed into the room. Everyone stood until the couple were settled in seats next to Dr. Miller. The neurologist is warm and friendly and interested in hearing what the patient and his wife think about the problem. At one point, the 59-year old looks at the neurologist and says haltingly: “I feel normal when I’m not speaking.”
Dr. Miller went through the man’s history, which included dyslexia diagnosed in elementary school. The neurologist went through the usual stuff on a neurological exam: touch your nose to my finger, make a fist, push, pull. He was asked to repeat words, then sentences.
Do you think you ever lost consciousness during a hockey game? The patient had spent a year as a professional hockey player but said that he never blanked out when smashing into goals or walls or other players. They talked about dyslexia. It did not stop him from loving books throughout his life. They talked about work. He has designed workarounds to his speech problems.
Talking took great effort. The words sounded like they were spoken under water. The order of words was a bit off but he did not appear to have an obvious problem with pronouns.
“I just want to know what’s wrong,” he said. “Do I have PPA, Alzheimer’s, ALS or something else?”
Dr. Miller wishes he could tell him something definitive, but they still don’t know. His best guess is that the diagnosis is non-fluent variant-primary progressive aphasia, but it is not a typical case. The neurologist and others made recommendations, including speech therapy that could help with some of the apraxia. Keep exercising. Eat well. Do whatever you are doing because you are looking strong and healthy. What they don’t know is how the disease will spread. The geneticists are now working on identifying his mutation, if any. There are several suspect genes involved with PPA. Some people with a progranulin mutation do go on to develop abnormal gait and hand movements. The disease could morph into corticobasal syndrome or progressive supranuclear palsy.
By the end of the meeting, even without a definitive diagnosis, the patient was content with the honesty in the room. He was now part of the team. He would continue coming back to participate in research. He would continue to work and play hockey and hope that treatments for whatever he has will be available, soon.
Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaboration between University of California, San Francisco and Trinity College in Dublin. She will be spending several months at UCSF’s Memory and Aging Center writing about the inner workings of the brain and giving voice to patients and the doctors, nurses, psychologists, geneticists and researchers involved in building the foundation for a whole body of non-Alzheimer dementias that are often missed, lost or ignored.