What Is the Diagnosis?

Ms. X was a successful high school math teacher and was well liked by her students and co-workers. When she was 45 years old, her husband and children began noticing that she exhibited uncharacteristic lewd and rude behaviors. She began to tell sexually explicit stories to family, friends, and colleagues and to make inappropriate comments about strangers at restaurants. When people talked to her, she would echo back their last sentence. Sometimes, she became irritable and would pace around a room. She started to put non-food items in her mouth. She laughed and giggled a lot and didn't seem to care if others were embarrassed and annoyed.

Until these behaviors surfaced, Ms. X had been a well mannered woman and had behaved appropriately in all regards. She had no prior history of psychiatric or neurological illnesses.

The only noteworthy family history of psychiatric illness was major depression in one of her two sisters.

KNOWING THIS MUCH OF THE HISTORY, WHAT DO YOU THINK IS THE MOST LIKELY PSYCHIATRIC DIAGNOSIS?

As time went on, Ms. X exhibited these behaviors more frequently and her friends and family became increasingly distressed. She was required to take a leave of absence from her job. Despite this, Ms. X didn't seem concerned. Over time, her sleeping patterns became disrupted. Sometimes, she would get up and start her day in the middle of the night.

HAVE YOU CHANGED YOUR OPINION ABOUT THE DIAGNOSIS?

Ms. X became increasingly quiet and withdrawn. She understood conversations but did not appear to be willing or able to vocalize her thoughts.

Gradually, she started to lose certain cognitive abilities. She would forget where she parked her car at the grocery store, and she started driving erratically. She was unable to figure out a tip at a restaurant and made errors when writing checks to pay household bills.

NOW WHAT YOU ARE THINKING IN TERMS OF DIAGNOSIS?

Eventually, Ms. X became mute and needed help with everyday tasks, including dressing and bathing. If she ventured outside the house, she might wander off and get lost.

Ms. X was evaluated by a psychiatrist, who ordered an MRI brain scan. The results of this scan demonstrated an unusual brain shape - the front part was markedly shrunken compared to the middle and back parts of her brain.

Unfortunately, Ms. X ultimately wandered away from home, fell into a pond, and died.

The family agreed to an autopsy. The brain was examined by a neuropathologist, who used various staining techniques to test for the presence of unusual proteins that might have accumulated in the brain. These stains showed the accumulation of a large number of clumps of a protein called TDP-43 in the shrunken parts of the brain.

The clinical course of Ms. X's symptoms, the results of the MRI scan, and the demonstration of TDP-43 accumulation in the brain are all consistent with a diagnosis of behavioral variant frontotemporal dementia (bvFTD), a form of progressive dementia.

If you thought that the illness initially sounded like bipolar disorder, you were thinking correctly. Early symptoms of bvFTD can be mistaken for mania. Over time, however, this woman's illness did not follow the usual course of bipolar disorder and increasingly took on the characteristics of a neurodegenerative illness.

In people between the ages of 45 and 65, frontotemporal dementias are responsible for as many cases of dementia as Alzheimer's disease. Because dementias are relatively uncommon in people of this age, however, many doctors are unaware of frontotemporal dementias.

There are currently no treatments that slow down the progression of bvFTD or that are very helpful with the dramatic symptoms of this disorder. Death usually occurs within about 6 to 11 years after the onset of symptoms.

On a positive note, substantial research progress is being made and we are learning a lot about different clinical subtypes of the frontotemporal dementias. It is important that research continues to be funded to study this and other devastating neuropsychiatric disorders.

This column was co-written by Eugene Rubin MD, PhD and Charles Zorumski MD.