Med thumb narcolepsy

Narcoleptics live in constant fear of sleep attacks — sudden bouts of exhaustion that can occur at any time, in any circumstance. Some sufferers of the neurological sleep disorder also experience cataplexy, episodes of muscle weakness often sparked by emotion. About one in 3,000 Americans have narcolepsy with cataplexy, and even more have the non-cataplexy variety, according to current estimates. While research has resulted in treatments to manage symptoms of the disease, and brought us closer to determining its cause, finding a cure for narcolepsy remains an uphill battle. Some aspects of our relationship with narcolepsy haven't changed much since its 17th-century debut in the medical literature, when caffeine became the treatment du jour. Still, we've made considerable progress in understanding the genesis and development of the disorder. Here's a look at how far we've come. 

The Research

Then

The 14th-century poet Dante may have been describing himself and his own narcolepsy in "The Divine Comedy": Throughout the work he lists the condition’s symptoms including excessive sleepiness, sudden falls and frequent napping. No wonder the guy often wrote about hell. 

But it is a report by Thomas Willis, a renowned 17th century English phyisician, that is acknowledged as the first documentation of classic narcolepsy. He described sufferers as having “… a sleepy disposition — they eat and drink well, go abroad, take care well enough of their domestick (sic) affairs, yet whilst talking or walking, or eating, yea their mouthes (sic) being full of meat, they shall nod, and unless roused by others, fall fast asleep.”

Now

In the '60s, the Stanford researcher and "father of sleep medicine" William Dement started a canine narcolepsy colony. Using narcoleptic dogs, Dement discovered the gene responsible for narcolepsy. Today, the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health, supports research on narcolepsy and other sleep maladies. 

The Classification

Then

In the late 1800s, French physician Jean Baptiste Edouard Gélineau and German physician Carl Friedrich Otto Westphal published cases of narcolepsy, noting that sufferers exhibited daytime sleepiness and cataplexy, defined as sudden episodes of muscle weakness triggered by emotions, typically laughing or joking. Though historically associated with epilepsy, the malady was described by Gélineau as a neurosis or functional condition and named it narcolepsie from the Greek for “seized by numbness.” As an example of cataplexy, Gélineau’s patient reported collapsing at the zoo while observing monkeys.

Now

NINDS categorizes narcolepsy as a chronic brain disorder. However, it is still unknown whether narcolepsy is the same disorder with and without cataplexy. 

Tired Worked_Narcolepsy

The Diagnosis

Then

In Gélineau and Westphal’s time, additional symptoms of narcolepsy included sleep paralysis, vivid dreaming, hypnagogic hallucinations, disturbed nocturnal sleep and weight gain. Daytime sleepiness, likely caused by sleep apnea or some other disorder, was often incorrectly lumped together with narcolepsy.

Now

The classic four symptoms of narcolepsy are excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. However, it is often misdiagnosed as epilepsy, depression, another sleep disorder or a side effect of medication. In fact, estimates suggest that only a quarter of people who have narcolepsy have received accurate diagnoses. In one study, 60 percent of patients were misdiagnosed.

The Treatment

Then

Willis prescribed caffeine. Gélineau administered various treatments including bromides, toxic ingredients now found in pesticides, phosphates, amyl nitrate vapors, hydrotherapy, electricity and cauterization of the neck — none of which worked to prevent sleep attacks. In the early 20th Century, attempted cures involved pumping air into the sufferer’s brain or spinal cord, removing cerebrospinal fluid and administering radiation to the brain's hypothalamic region. the 1950s first saw the use of amphetamine and Ritalin as treatments. 

Now

There is no cure for narcolepsy — only medications to manage major symptoms. The cerebral stimulants modafinil and pemoline, as well as newer antidepressants that block serotonin and nonadreanaline uptake, are used to treat excessive sleepiness and cataplexy. Recently, the FDA approved GHB — yes, the popular club drug GHB — for treatment as well.

The Cause

Then

Stories abound of head trauma as a trigger — famously in the case of Harriet Tubman, who is said to have developed narcolepsy after a two-pound weight struck her head. In their case descriptions, Gélineau and Westphal made note of hereditary causes as a potential basis for the disease. In the late 19th and early 20th centuries, doctors identified brain lesions as a main cause. 

Now

Scientists have confirmed that narcolepsy is caused by the loss of the brain chemical hypocretin (aka orexin), a neurotransmitter involved in regulating the sleep-wake cycle. While it's not clear what causes the loss of hypocretin, current research points to a combination of genetic and environmental factors that influence the immune system. The identification of hypocretin deficiency in human narcolepsy raised the possibility of new courses of treatment.