Narcolepsy causes frequent daytime sleepiness and falling asleep spontaneously even if the afflicted person gets a normal amount of sleep at night. These “sleep attacks” can last from several seconds to more than 30 minutes and can include cataplexy (loss of muscle control during emotional situations), hallucinations and temporary paralysis upon awakening. The disorder is usually hereditary though it can be brought on by brain damage or neurological disease. Increasingly, it is considered an autoimmune diseases. Symptoms usually appear during adolescence. In the United States, an estimated 250,000 people have this disorder.
In the popular imagination, narcolepsy is often confused with cataplexy – the sudden loss of muscle tone and falling asleep. Most narcoleptics do not have cataplexy, and both narcolepsy and cataplexy come in varying degrees of severity. People who collapse all of the sudden are pretty rare. Interestingly, cataplectic episodes are triggered by emotion, often positive emotion such as laughter.
Narcoleptics have frequent nighttime awakenings that may be imperceptible to the patient (microarousals) but which can show up on EEGs. The level of sleep fragmentation corresponds to the level of daytime sleepiness.
Narcolepsy also makes it tough to maintain concentration and memory, and often results in blurry vision. Narcoleptics are also much more prone to confusing dreams with reality.
Some narcoleptics seem to have a gene that disposes them to the condition. It is estimated that 5% of narcolepsy can be classified as familial and 95% as sporadic. Mutations in a gene (hypocretin receptor 2 gene (Hcrtr 2)) cause familial narcolepsy in dogs; the precise gene has not been located in humans. The environmental causes of sporadic narcolepsy are not understood and there may be more than one. Head trauma and viral infections are believed to be causes. Most narcoleptics come down with it as teens but it can occur later in life after strokes or car accidents.
All narcoleptics have very low (or even undetectable) levels of orexins in their cerebrospinal fluid. Orexins are neurotransmitters that play a part in keeping us awake. Indeed, the death of orexin-releasing neurons in the brain appears to either cause or be a symptom of narcolepsy.
The death of orexin neurons causes most or all cases of narcolepsy. The brain cells that contain secrete orexins make connections with many brain regions involved in regulating the sleep-wake cycle. There are fewer than 200,000 of these cells in a brain. The brains of narcoleptics may have damage to these cells. That, at least, is the dominant hypothesis today. Autopsies of people who had narcolepsy find the number of orexin neurons is only 10% of normal. What causes or opens up the orexins to this attack is not clear, but scientists have ideas.
An auto-immune disease
Scientists have long suspected the body’s own immune system is responsible for narcolepsy. Only recently has hard evidence come that the disorder can properly be classified as an autoimmune disorder. Narcoleptics have a type of T-cells (a component of the immune system) that tract to orexin proteins critical in keeping us awake.
There is a genetic predisposition to narcolepsy. The gene for narcolepsy in dogs has been identified, and about 10% of humans with the condition have a close family member who also has it. (This is in sharp contrast to the less than 0.2% of the population with narcolepsy.) This is not to say narcolepsy is an inherited condition, but that more probably the vulnerability to the environmental causes is inherited.
If you have narcolepsy, don’t worry about passing it to your children too much. The risk of this happening is small, estimated at under 2% even for parents with the form of narcolepsy that results in cataplexy.
Diagnosis of Narcolepsy
When patients are evaluated with the Multiple Sleep Latency Test and the sleep latency is fewer than eight minutes, this is diagnostic support for narcolepsy. The difference between hypersomnia and narcolepsy is that the MSLT shows narcoleptics go into a period of rapid eye movement within 15 minutes of sleep onset. The patient’s own experience and testimony of family members who have observed the patient’s excessive daytime sleepiness also contribute to a diagnosis
Doctors have to be careful when diagnosing narcolepsy as it can be confused with other disorders or the EDS may be caused by another ailment. There is also the suspicion of malingering people looking for a diagnosis to get a prescription for stimulants or as an excuse to go on disability.
Alternative diagnostic routes
Although it may be possible to take samples of cerebrospinal fluid and measure orexin levels, this is not done in clinical practice to diagnose narcolepsy. (It involves a lumbar puncture -spinal tap.) Standards for establishing what constitutes normal and what constitutes narcolepsy have not been established.
Elements of the immune system called human leukocyte antigens are useful for investigating autoimmune disorders. Most narcoleptics have detectable levels of HLA-DQB1*0602 in their blood, and this antigen can be a biomarker.but it is not feasible for diagnosis because so many people without narcolepsy also have this antigen.
Narcolepsy is a chronic, life-long disease. It cannot be cured. It can be managed and the symptoms lessened.
Stimulants, antidepressants and other drugs can help control the symptoms. Behavioral measures to control symptoms include strategically timed naps, regular timing of nighttime sleep and avoidance of alcohol and heavy meals. Although it can be a difficult condition to live with (and some narcoleptics have to quit their jobs), most manage their illnesses with medical help.
Narcolepsy is usually treated with stimulants, including amphetamine or amphetamine-like compounds, and modafinil. The most common amphetamine-like drugs are dextroamphetamine, pemoline methamphetamine, and methylphenidate (Ritalin). These are classified as Central Nervous System (CNS) stimulants. Modafinil is marketed as Provigil and Nuvigil. Dextroamphetamine has a varying duration of action while methamphetamine and modafinil have a longer duration of action. Modafinil is well tolerated by the body and has fewer side effects although it is generally lower potency than the amphetamine-like drugs.
Another treatment strategy takes a different route: sodium oxybate is prescribed for narcoleptics to make them sleep deeper during the night in hopes they will not experience excessive daytime sleepiness during the day.
Scientists have recently found that the drug baclofen, which has been around for years and which is widely used by multiple sclerosis patients, can be useful in treating narcolepsy. Baclofen is a GABA agonist and works in a manner similar to sodium oxybate. Researchers will probably continue to pursue this avenue of treatment for narcoleptics.