Living in the Moment

The guy is good with people, that’s for sure. Handsome, athletic, good-witted. His gaze has its own smile. He’s charming. It took him three years to get here and since his first arrival last August he’s been back two more times. He is wearing a pair of gray REI shorts, a pullover and black sneakers that will be untied and removed from his feet in 90 minutes. He needs help backing into his chair. In better days, I bet you he would sweep his wife off her feet. His arms still look strong.

Jokes come easy and this lightens the room. I don’t even know what is wrong – yet – but I do know this much: his gait is about as unsteady as a toddler taking his first steps. He balances with a walker but at any moment he tilts to the left or right or back and looks as if he might go all the way to the ground. Falls come as easily as his jokes these days.

Mid-way through this exam with a neurology fellow I learn that his father had been diagnosed with a rare genetic mutation called Gerstmann-Sträussler-Scheinker syndrome – GSS for short. His father died around a decade ago and now the son, in his 50s, is following in his unsteady footsteps. His father’s doctor, Michael Geschwind, figured out it was a rare, familial prion disease. Now, his son is here at the Memory and Aging Center.

GSS is progressive and fatal, and there are only a handful of unlucky families in the world with the neurodegenerative disease. The infectious prion protein is wiping away pieces of his brain. The guy who spent his life playing sports and cycling struggles to make his leg muscles work. (It doesn’t stop him from doing the things he loves. He and his wife bought a tandem recumbent trike, and they took it apart and packed it on a plane for a two-week holiday last year, despite his problems walking.)

This loss of muscle control is also affecting his speech. It is hard to understand him. In short order, this disease can also take over the muscles in his throat and make swallowing difficult too. And like sporadic forms of prion disease, it will also damage the parts of his brain that allow him to think clearly and remember.

The neurology fellow is a young woman with such sensitivity that I realize she has been gently cupping his hand for ten minutes. Later, I learn that she was trying to calm his hand, which seems as busy as someone working against a clock on an assembly line. His hand has a mind of its own. It picks at the hem of his shorts. The fingers tap against one another.

He falls two or three times a week. Last Thanksgiving, he broke a few ribs. His wife remembers four years ago when he tripped as they were walking to dinner. He and his wife looked at one another. No words were spoken but they were thinking the same thing: maybe it’s GSS. Last summer, he made an appointment with Geschwind, who had diagnosed his father.

Michael Geschwind almost didn’t make it to medical school. He was drawn into politics in high school in Berkeley Heights, New Jersey, and was a youth governor of his state. He was chosen as one of 200 of the most politically active young people in America in 1981. The award culminated in a weeklong debate camp. His topic: nuclear energy. He was opposed to it – until he did his research and changed his argument. Understanding both sides of the argument led to his position paper becoming the first to be submitted to the President of the United States as the voice of American youth.

He went off to Cornell and by the time he was set to fling his cap in the air – it was 1985 – this neurobiology major was still thinking politics. He took the Foreign Service exam and passed everything but English. That night, he went home and reread the classic Elements of Style. The next day, he had an interview on the Hill and the young aide handed him a letter to edit. Ten minutes later, the red pen had done its job, rather brilliantly. He got a volunteer job on the Hill and spent the next several months writing speeches and position papers for the Congressman as well as letters to constituents.

He hated politics and transitioned into the private sector doing economic environmental consulting for the Environmental Protection Agency. He was also volunteering at a medical clinic at night, and he loved that. With a career in politics off the table, he followed his brother Daniel into an MD/PhD program. Medicine was a natural choice for the Geschwind brothers. Their father was a physicist and his cousin, Norman Geschwind, was one of the first and most famous behavioral neurologists of his day. (It was said that he coined the term and ignited the field.) He was chair of Neurology at the Boston VA Hospital and made his name in unraveling aphasia, dyslexia and epilepsy.

The cousins shared a love of the brain. Michael headed into a neurology residency. One of his first patients walked into the hospital complaining that he couldn’t control his legs. He was somewhat unsteady on his feet, and his speech was slightly slurred. They could not finish all their testing over the weekend, so on Friday they gave the patient a weekend pass. He walked out of the hospital, but returned on Monday in a wheelchair, unable to walk. He died less than a month later.

It was prion disease. After that, he saw several cases of prion disease over the next few months. The other residents began joking that Geschwind was a magnet for the mutant prion protein. Maybe he is.

UCSF was just building its first behavioral neurology program when Geschwind arrived in 2000. He was 37. Many unusual cases were being sent to this new behavioral neurology team. By this time, everyone knew about the rogue prion protein that was killing young people infected with the protein that had made its way into the food chain. Mad cow disease had swept through herds across the United Kingdom (and then to other European countries), and tainted beef was at the heart of the rise in this variant Creutzfeldt-Jakob disease in humans.

Some people showed up at the California clinic saying they were sure they had CJD. Others had been sent by their doctors. Geschwind was busy collecting blood and spinal cord fluid, working with others to develop improved diagnostic tests. Thankfully, he determined that many of the patients did not have prion disease. Geschwind realized that many doctors were not trained to work up patients with rapidly progressive dementia. In fact, he was becoming the go-to guy for these types of conditions.

And that is when a man in his 60s showed up barely able to walk. Doctors were not sure what he had. Bruce Miller, the founder and director of UCSF’s Memory and Aging Center, saw the man in clinic and thought his condition was most like multiple system atrophy, but Miller said there was something rather unusual in the man’s history, including that his father had a movement disorder. Miller referred him to Geschwind, who then acquired copies of this new patient’s medical records. He realized the father’s diagnosis was wrong, and that he had an ataxic disorder similar to his son. The father had little control of his limbs when moving but he also had rigidity and dementia. Miller and Geschwind puzzled over the cause of this man’s worsening symptoms and agreed it could be GSS.

A genetic test came back positive.

Geschwind’s patient lived for five years, maybe even longer, after the first symptoms. Now, it is his son who has signed on to the research program. This is his third visit in less than a year.

Several years ago, Geschwind began following people at risk for GSS and other genetic prion diseases, before they develop any symptoms. He wants to identify the earliest markers of disease onset. All research patients undergo about two days of testing every visit. He sees presymptomatic patients every year or so and symptomatic patients every month or every few months to measure how fast the disease might be progressing.

Although his current patient has some cognitive impairment, these have not reached the level of dementia, yet. Tests to measure attention show a slight worsening since August but his mood is upbeat. The next day, his research team meets to analyze the results from the two days of testing. The brain scans are always the last piece of the puzzle to go up on the screen. They want to understand the patient’s signs and symptoms and progression before they look inside the brain. Most everyone on the team seems to be able to eye even the slightest variation on the scans.

The brain tells the whole sad story. The shrinking tissue is right in an area that modulates movement.

In the end, the father could not speak. At the time, Geschwind offered to assess and test the man’s two sons. They declined. Back then, the son who today is participating in Geschwind’s study, told his wife: “I don’t want to know. I just want to live my life.”

And now he knows, and he is still doing just that.


Jamie Talan is an Atlantic Fellow at the Global Brain Health Institute, a collaborative program between University of California, San Francisco and Trinity College 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.