Eight years ago, two years after she was diagnosed with multiple sclerosis, Cherry Willi ams-Howe ll started laughing.
"I was laughing at the ceiling, laughing at the couch, laughing at my husband," the 57-year-old Phoenix woman said.
"I was laughing at everything like it was the most hysterical thing I’d ever seen and couldn’t stop."
Williams-Howell’s behavior scared her husband and he took her to a doctor.
"I started laughing at the doctor," she said.
What caused Williams-Howell’s outburst was no laughing matter. She is one of more than a million people who suffer from pseudobulbar affect. The disorder causes episodes of uncontrollable laughing or crying that’s inappropriate or unrelated to the situation at hand, according to Scottsdale neurologist Dr. Timothy Vollmer, who is conducting a clinical trial to test a treatment.
"This becomes a problem from a social standpoint," Vollmer said. "If someone with pseudobulbar affect goes out to dinner with a group of friends, they may start laughing inappropriately or crying easily when they shouldn’t be. As a result, people around them become uncomfortable because it seems to be irrational. They become more and more socially isolated and it has a big impact on their quality of life, employment and family relationships."
The cause of pseudobulbar affect remains unknown. Doctors believe it’s related to lesions or injuries in certain pathways of the brain that normally allow people to control emotional expression.
"The reflexes involved in expressing emotions are pre-programmed at the brain stem level," Vollmer said. "When they are triggered by a provocative event like seeing a baby or something scary, the site is activated, but the reaction can be suppressed by the frontal lobes. When someone has MS, there is a disconnection between frontal lobes and the brain stem center. So when emotions are triggered, there is a hyperreactive reflex because it cannot be suppressed."
A significant number of people with neurological disorders suffer from pseudobulbar affect, including 10 percent of multiple sclerosis patients, 50 percent of people with Lou Gehrig’s disease, 40 percent of Alzheimer’s patients and 11 percent of stroke sufferers.
No specific treatment for pseudobulbar affect has been approved. But Vollmer and his team at Barrow Neurological Institute Clinical Research are one of 20 groups across the nation that are testing the ability of AVP-923, a promising new drug, to control the disorder.
The treatment is a combination of dextromethorphan and quinidine. Dextromethorphan has shown properties of reducing certain pathways of excessive neurotransmitter activity in the brain. But dextromethorphan is rapidly metabolized in most people. Quinidine inhibits the enzyme that metabolizes dextromethorphan and slows its elimination from the body.
"I can be very happy, but still break down crying and not understand why I’m crying," said Williams-Howell, who is participating in the study. "My husband was getting to the point where he didn’t want anything to do with me. You can’t function normally with this. So if there is any chance the medicine will work, I’m going to try it. People who have this desperately need help."
Seeking study participants
What: Researchers seek people 18 to 68 years old who have a clinical diagnosis of pseudobulbar affect and either stroke damage, Alzheimer’s disease, multiple sclerosis or Lou Gehrig’s disease. They should not have a sensitivity to quinidine or any opiate drugs. Participants will take part in clinical trials that test the safety and effectiveness of a pseudobulbar affect treatment known as AVP-923.
Where: Barrow Neurological Institute, 350 W. Thomas Road, Suite 300, Phoenix
Information: (602) 406-7711 or e-mail