What causes narcolepsy?
There is some hereditary component to the occurrence of narcolepsy. Researchers identified the gene that causes narcolepsy. The gene allows cells in the hypothalamus (the part of the brain that regulates sleep behavior) to receive messages from other cells. When this gene is abnormal, cells cannot communicate properly, and abnormal sleeping patterns develop. The disorder sometimes runs in families, but most people with narcolepsy have no relatives with the
disorder. Researchers believe that the inheritance of narcolepsy is similar to that of heart disease. In heart disease, several genes play a role in being susceptible to the disorder, but it usually does not develop without an environmental trigger of some sort
Narcolepsy may be associated with damage to the amygdala. A cerebral protein has recently been discovered that is decreased in a large number or all narcolepsy patients. The protein involved is called hypocretin or orexin. Hypocretin levels in human subjects with narcolepsy have been found to be undetectable or low in several recent studies of patients with narcolepsy. Hypocretin appears to modulate activity in the hypothalamus (the part of the brain associated with sleep). The deficiency of hypocretin might produce sleep attacks. Modafinil (a drug) useful in the treatment of narcolepsy is believed to activate hypocretin-containing nerve cells.
The neural control of normal sleep states and the relationship to narcolepsy are only partially understood. In humans, narcoleptic sleep is characterized by a tendency to go abruptly from a waking state to REM sleep with little or no intervening non-REM sleep. The changes in the motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, spinal and brainstem alpha motor neuron hypopolarization produces almost complete atonia of skeletal muscles via an inhibitory descending reticulospinal pathway. Acetylcholine may be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy is believed identical to that seen in normal REM sleep.
It has been theorized that narcolepsy may be an autoimmune disease, in which the immune system may be tricked into perceiving its own proteins to be antigens. (Antigens are foreign substances targeted for attack by immune factors in the body.) In the case of narcolepsy, such an attack occurs against cells containing hypocretin, possibly because of their resemblance to some actual antigen, such as a virus. However, evidence to date does not support the autoimmune theory.