Betrayed by the brain

Charlotte Wendel practices piano. She endured more than two years of minimal consciousness.
Charlotte Wendel practices piano. She endured more than two years of minimal consciousness. (MICHAEL S. WIRTZ / Staff Photographer)

A tricky encephalitis that mimics mental illness can now be diagnosed and treated. But some don't respond, and it's not known why.

Posted: April 02, 2013

In hindsight, Susan Wendel thinks her daughter was sick months before she wound up in a coma.

Charlotte's second-grade teacher that fall complained that she was disruptive. That was a big change from first grade, but her mother wrote it off as growing pains.

Other behavior was a little odd, too. "She did things like wear her sweater backwards and pull her pockets inside out," Wendel said. Still, Charlotte was 7. Eccentricity isn't unusual at that age.

But, as 2009 ended, Charlotte crashed. Unable to walk or talk, she landed in an intensive care unit at Children's Hospital of Philadelphia.

In a way, she was lucky. Doctors there quickly figured out that she had a form of encephalitis, or brain inflammation, that was caused by her own immune system. It often starts with psychiatric symptoms that can lead doctors astray for months.

Cases like Charlotte's once would have remained mysterious, but researchers at neighboring Hospital of the University of Pennsylvania had discovered anti-NMDA receptor encephalitis in 2005 and created a test for it in 2007. They also had identified a series of treatments that helped most patients.

This is where Charlotte was not so lucky. Even with very quick treatment, she spent more than two years in a minimally conscious state. She's on the mend now, but has only recently begun to walk again and returned to school.

"She has made miraculous progress," said Susan Wendel, a Schwenksville chemist who works in research and development at Johnson & Johnson.

No one knows why Charlotte still struggles while many others respond better to treatments and recover completely.

The disease has had its few minutes of fame lately as Susannah Cahalan, a young New York Post reporter, toured to market her book, Brain on Fire: My Month of Madness, about her harrowing experience with anti-NMDAR encephalitis.

Cahalan went through manic and psychotic phases before a doctor in New York realized that a neurologic symptom - an inability to draw a clock properly - proved that the right side of her brain was inflamed. He had read about an autoimmune disorder affecting young women that a neuro-oncologist at the University of Pennsylvania, Josep Dalmau, was studying. Tests confirmed she had the newly named encephalitis.

Dalmau, who now works primarily in Barcelona, Spain, and his team at Penn went on to diagnose hundreds with the disorder, which causes the immune system to attack the NMDA receptor, a key juncture in the brain's chemical communication system. Eric Lancaster, a Penn neurologist who has worked with Dalmau, said it is what goes haywire when people take PCP, or angel dust.

The team found the condition in people of all ages, but it was more common in younger women and girls. Many patients had ovarian teratomas, ugly but usually benign tumors. Typically, the encephalitis starts with what seems like a viral illness, Lancaster said. Then patients have memory problems, psychosis, and personality changes. They often progress to strange writhing and need breathing machines. In a Penn study published this year, 6 percent of 501 patients died.

Doctors at Penn and elsewhere have now identified other autoimmune forms of encephalitis with equally inscrutable names. There are GABA-B and AMPA, which both cause seizures and memory problems. LGI1 attacks a synaptic protein, leading to seizures and profound memory and thinking problems. Caspr2 can affect the brain or peripheral nerves. Some patients get seizures and cognitive problems. Others have muscle twitching and stiffness.

Penn and Children's Hospital together see one or two patients a month, Lancaster said.

Viral encephalitis is treated with antiviral medicines. Autoimmune forms are treated with steroids, intravenous immunoglobulin, and retuximab, a chemotherapy.

In the past, Lancaster said, doctors likely would have figured out that patients with these newly named diseases had encephalitis, but they wouldn't have known what to do about it. "You're just operating in this fog of confusion," he said.

While patients with anti-NMDAR encephalitis may appear mentally ill at first, he said, studies have not found evidence of the disease in groups of people with psychiatric diagnoses.

Emily Gavigan was a normal college sophomore in 2009 when she became hyper and paranoid. She was admitted to a psychiatric hospital and emerged, as she put it, "zombied out" on psych drugs.

Doctors thought she had schizophrenia. One told her parents she would never be able to go back to school or work, her father, Bill, said. When physical symptoms started, doctors near the family's Wilkes-Barre home said she had multiple sclerosis.

In 2010, after an aunt saw author Cahalan on television and Emily had a seizure, Bill Gavigan had her taken to Penn. She couldn't walk or speak.

Now 23, she has finished college and works in her father's printing business in Scranton. She worries that others will be misdiagnosed. "I'm so glad that we're spreading awareness about this," she said.

Charlotte Wendel's illness came to a head on Dec. 29, 2009. While waiting for a movie, she seemed sleepy and started having trouble talking. "My teeth," she said. "My teeth are in the way."

Her mother skipped the show; they headed for Children's Hospital. Within 10 hours, Charlotte couldn't walk or talk. She had a seizure, and doctors found a congenital ovarian teratoma the size of a baseball.

Charlotte received all the usual treatments for anti-NMDAR, but they didn't seem to work. She was minimally conscious for 30 months. After she had spent 265 days in the hospital, the family's church remodeled the Wendels' house so she could come home.

In March 2012, Charlotte's care team told Susan Wendel they had done all they could. Her daughter wouldn't get better.

But she did. Last June, she began talking and moving.

Susan Wendel estimates that Charlotte, now 10, functions at first-grade level. Her latest MRI showed some brain atrophy. Her mother doesn't know how much she can improve.

Now a giggly, energetic child, Charlotte has goals that are "very concrete," her mother said. "She wants to be able to walk like her friends. She wants to go swimming."

While Susan Wendel concedes that her daughter's illness was traumatic, there was also beauty in it. The church started a prayer chain, and strangers sent lovely gifts. The rehab project spawned a nonprofit - Happy 2 Be Home - that helps other children come home. Neighbors brought food and cared for Charlotte's older sister, Emily, while her mother stayed near the hospital. Emily, now 16, plans to be a doctor.

Susan Wendel says she doesn't waste time thinking about what she has lost. "I feel so happy to be able to communicate with her," she said.

Contact Stacey Burling at 215-854-4944 or

comments powered by Disqus