Diagnostic dilemma: A brain lesion gave a woman a lifetime of joyless laughing fits

The patient: A 31-year-old woman

The symptoms: The woman visited a clinic because she had long experienced bursts of uncontrollable laughter, which doctors described as “mirthless” in a report of her case. According to the patient, she had been having these intermittent bursts of involuntary laughter since infancy, but her condition had never been formally investigated or diagnosed.

She said that before each episode started, she would experience a “feeling of dread” in her neck and chest. During the involuntary laughing incidents, she could not speak or swallow, and she had difficulty breathing. Each outburst lasted a few seconds and typically occurred about once per day, usually shortly after the woman awoke in the morning.

The woman noted that, when she was a child, each episode would last several minutes and occurred more frequently — about six or seven times a day, and sometimes while she was asleep. Her parents did not recognize the laughter as being beyond her control. Rather, they thought her laughing was deliberate and would ask her to stop, the patient reported. As she grew older, the bouts of laughter became shorter and happened less frequently.

What happened next: Prior to the patient’s visit to the clinic, MRI and electroencephalography (EEG) of her brain showed no abnormalities. However, when the clinicians examined videos of her laughing episodes, they noted that they closely resembled gelastic seizures. This type of seizure commonly triggers uncontrolled laughing, giggling or smirking, but it can also cause grunting, mumbling or lip smacking. It is named after the Greek word for laughter (“gelastikos“).

Gelastic seizures are typically focal, meaning they’re caused by abnormal electrical activity in one specific part of the brain. On a second MRI, doctors discovered an area of abnormality in the hypothalamus, a key structure for maintaining homeostasis. The abnormality measured about 0.2 inches (5 millimeters) wide.

The diagnosis: They identified the lesion as a hypothalamic hamartoma, a noncancerous lesion that occurs during fetal development. Gelastic seizures that provoke bursts of involuntary laughter, during which the individual is aware of their actions but can’t control them, are a hallmark of this lesion. The exact reason these lesions trigger giggling fits isn’t fully understood.

The treatment: The patient had previously taken trial doses of the anti-seizure drugs levetiracetam and lamotrigine, which are used to treat epilepsy, with no effect. Because her episodes were not severe, the woman decided that she did not want medication.

She was not experiencing any other behavioral or cognitive issues and the attacks had declined in severity and frequency over time, so the doctors at the clinic determined that no additional treatment was required.

What makes the case unique: Hypothalamic hamartomas are rare, but when they do occur, they are typically accompanied by cognitive and behavioral impairment. In children, the growths can cause developmental delays or trigger the early onset of puberty, because the hypothalamus helps regulate hormones. Patients that have gelastic seizures triggered by these lesions often develop more severe forms of epilepsy and experience other types of seizures down the line.

The woman’s case is highly unusual because her symptoms naturally declined to a manageable level. This benign outcome of epilepsy associated with hypothalamic hamartomas, “to our knowledge, has not been previously reported,” the doctors wrote.

For more intriguing medical cases, check out our Diagnostic Dilemma archives.