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Dr. Schiffer’s patient was thirty-seven when he laughed his way through his best friend’s funeral. At that time he had been confined to a wheelchair for five years by multiple sclerosis. He had been laughing his way through virtually everything for nearly two. Not because he was amused, but because he could not control his laughter. He suffered as many as eighty outbursts of raucous laughter a day, yet his mental state was profoundly depressed.
This patient suffered from a condition known variously as emotional lability, pseudobulbar affect, emotional incontinence, and pathological laughing and weeping. While little known outside the neurological community, it’s surprisingly common, affecting as many as 10% of patients with multiple sclerosis, 15% of patients with Alzheimer’s, and up to 49% of patients with ALS (Lou Gehrig’s disease). It can also affect patients with stroke, head trauma, epilepsy, or almost any other condition that seriously affects the neurological system. It is characterized by uncontrollable laughing or crying without underlying feelings of amusement or sadness.
The condition can be socially crippling for the people who suffer from it. Many retreat from contact with a society that will not understand their apparent emotional outbursts. Even families and caregivers can have a difficult time dealing when their loved one cries and/or laughs continuously or inappropriately.
At the time this particular patient came to the Center for Brain Research in 1985, there was no treatment for pathological laughing and weeping. Dr. Schiffer diagnosed his patient as profoundly depressed and prescribed an antidepressant – amitriptyline. To everyone’s surprise the uncontrollable laughter stopped within a day of the first dose, leaving the patient able to reliably control his emotional expression for the first time in years. Surprised and excited, Dr. Schiffer and his colleagues, Drs. Herndon and Rudick made a small trial of twelve similarly afflicted patients. Eight responded positively to treatment with amitriptyline. Other trials showed another antidepressant – levadopa – had similar positive effects. Oddly, in both cases, the drugs acted within 48 hours of the initial dosing – far faster than their antidepressant effects, which can take up to two weeks to show – and with smaller dosages than the therapeutic levels for depression. Also oddly, the worst afflicted patients were the most likely to improve with treatment, while those with less frequent or spectacular outbursts were more likely to not be helped at all.
In the twenty-five twenty years since, there have been a few studies of pathological laughing and weeping, but its mode of action is still largely a mystery. One of its alternate names – pseudobulbar affect, arises from the apparent involvement of the brainstem, while the possible involvement of an entirely different area of the brain led to the testing of dextromethorphan, a common cold medication, as a possible treatment. A new formulation, called Neurodex by its manufacturer, Avanir, is currently being tested for approval by the FDA. If approved, it would be the first drug specifically for pathological laughing and weeping.
In an unusual twist, there have been some protests over the new drug, despite the promising results of the first round of tests. A group called the Alliance for Human Research Protection (AHRP) claims that Avenir is inventing or exaggerating the syndrome in order to sell patients the new drug. The intended patient base for Neurodex, AHRP says, is already dealing with major neurological disease. Do they really need to be trying to treat a physically benign syndrome that is only a minor symptom of the real problem?
Yet for many patients, pathological laughing and weeping is far from benign. It may not cause a physical fallout, but it can alienate them from the world – keeping them away from all the myriad social interactions that keep people connected. To some, being in a wheelchair may be far less devastating than laughing at a friend’s funeral. To others, their uncontrolled, unwanted laughing and weeping may be one of the few aspects of their disease that can be treated. For all the advances in recent years, neurology largely remains “the differential diagnosis of incurable disease”. Advances in treating the symptoms may not look like much, but when the symptoms are all you can treat, at least it’s something.
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