Cataplexy

Not to be confused with Catalepsy.

Cataplexy
Specialty	Neurology

Cataplexy is a sudden and transient episode of loss of muscle tone accompanied by full conscious awareness, often triggered by emotions such as laughing, crying, terror, etc. It is a rare disease (prevalence of fewer than 5 per 10,000 in the community), but affects roughly 70% of people who have narcolepsy. However, in rare cases, cataplexy occurs without the co-occurrence of narcolepsy. The exact cause of cataplexy is unknown, but the condition is strongly linked to experiencing intense emotions and reduced levels of the neurochemical hypocretin. Cataplexy can also be present as a side effect of SSRI Discontinuation Syndrome.

The term cataplexy originates from the Greek κατά (kata, meaning "down"), and πληξις (plēxis, meaning "stroke").

Presentation

Cataplexy manifests itself as muscular weakness which may range from a barely perceptible slackening of the facial muscles to the dropping of the jaw or head, weakness at the knees, trembling of mesenteric muscles, rictus, dysarthria, may drop objects held in hands or a total collapse. Usually the speech is slurred, vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. The person will lie there, fully conscious, for a few seconds to several minutes. As the attack continues the patient may experience sleepiness, hallucinations, or sleep-onset REM period. A full-blown attack may occur and results in complete muscle paralysis with postural collapse and possible injury. However, most often patients with postural collapse have the capability to avoid injury because the fall is slow and progressive. Cataplexy is different from narcoleptic sleep attack because it is usually precipitated by strong emotional reactions or by sudden physical effort, especially if the person is caught off guard.

These attacks are triggered by strong emotions such as exhilaration, anger, fear, surprise, orgasm, awe, embarrassment, and laughter. An effort to catch a suddenly thrown object can trigger a cataplectic attack. Guilleminault, Wilson, and Dement (1974) noted that even people who did not have cataplexy sometimes will lose muscle strength after a bout of intense laughter; explaining why people go "weak" from laughing too hard.

Cataplexy can cause serious social and parenting challenges because cataplexy can occur when one is attempting to discipline their child or when making love.

Occurrence

In a 24-hour period, cataplectic attacks usually occur between the hours of 10 am and 9 pm and very few attacks occur between the hours of 10 pm and 9 am. Attacks can last from a few seconds up to ten minutes, and may occur up to several times per week [4-6 times]. Cataplexy is considered “typical” when it is always of short duration (< 5 minutes).

Physiology

In this simplified brain circuit, damage to orexin-secreting neurons in the hypothalamus can lead to inhibition of motor neurons, thus lowering muscle tone.

Cataplexy is considered secondary when it is due to specific lesions in the brain that cause a depletion of the hypocretin neurotransmitter. Secondary cataplexy is associated with specific lesions located primarily in the lateral and posterior hypothalamus. Cataplexy due to brainstem lesions is uncommon particularly when seen in isolation. The lesions include tumors of the brain or brainstem and arterio-venous malformations. Some of the tumors include astrocytoma, glioblastoma, glioma, and subependynoma. These lesions can be visualized with brain imaging, however in their early stages they can be missed. Other conditions in which cataplexy can be seen include ischemic events, multiple sclerosis, head injury, paraneoplastic syndromes, and infections such as encephalitis. Cataplexy may also occur transiently or permanently due to lesions of the hypothalamus that were caused by surgery, especially in difficult tumor resections. These lesions or generalized processes disrupt the hypocretin neurons and their pathways. The neurological process behind the lesion impairs pathways controlling the normal inhibition of muscle tone drop, consequently resulting in muscle atonia.

Theories for episodes

A phenomenon of REM sleep, muscular paralysis, occurs at an inappropriate time. This loss of tonus is caused by massive inhibition of motor neurons in the spinal cord. When this happens during waking, the victim of a cataplectic attack loses control of his or her muscles. Where as in REM sleep, the person continues to breathe and is able to control eye movements.

Studies

A study of 40 cataplectic patients (age range 13–23 years) reported that sagging of the jaw, inclined head, drooping of the shoulders, and transient buckling of the knees were the most common presentations. Slurred speech may be present. However, diaphragmatic paralysis resulting in central apneas has not been reported. There is an isolated form that involves facial muscles exclusively. Cataplexy may rapidly reoccur repeatedly, giving birth to "status cataplecticus", and to the "limp man syndrome" as described by Stalh et al. "Status cataplecticus" is rare and can be extremely disabling to the individual. Cataplexy also occurs more frequently in times of emotional stress and when patients are deprived of napping while sleepy.

A survey of 100 cataplectic patients from the Stanford Sleep Disorders Clinic (age range 14–24 years) reported that 93 percent of the attacks lasted less than two minutes, 6 percent reported events lasting up to five minutes, and 0.94 percent reported events lasting longer than five minutes. There is a bimodal pattern of the age of onset of symptoms; either at 15 or 35 years. It has also been reported past the age of forty. Guilleminault et al. investigated 51 prepubertal children with narcolepsy; in 10 subjects (5 years and younger) cataplexy was the symptom first recognized. Cataplectic symptoms in general tend to decrease with age. A review of 100 patients with cataplexy at the Stanford Sleep Disorders Clinic (age range 12–20 years) reported that 62 of these patients stopped taking anti-cataplectic medications after 10 years. However, the general decrease in cataplectic symptoms with aging may be reversed after the experience of a significant emotional upset, such as a loss of spouse in older subjects.

Orexin

The hypothalamus region of the brain regulates basic functions of hormone release, emotional expression and sleep. A study in 2006 in "Tohoku Journal of Experimental Medicine" concluded that the neurochemical hypocretin, which is regulated by the hypothalamus, was significantly reduced in study participants with symptoms of cataplexy. Orexin, also known as Hypocretin, is a primary chemical important in regulating sleep as well as states of arousal. Hypocretin deficiency is further associated with decreased levels of histamine and epinephrine, which are chemicals important in promoting wakefulness, arousal and alertness.

Treatment

Cataplexy is treated pharmacologically. There are no behavioral treatments for cataplexy. The cholinergic and noradrenergic neurotransmitter systems are targeted in the treatment of cataplexy. Despite its relation to narcolepsy, in most cases, cataplexy must be treated differently and separate medication must be taken. For many years, cataplexy has been treated with tricyclic antidepressants such as imipramine, clomipramine or protriptyline. The main feature of tricyclics is their ability to inhibit the reuptake of norepinephrine and serotonin at the nerve endings. However these can have unpleasant side-effects and so have been generally replaced by newer drugs such as venlafaxine.

For cataplexy associated with narcolepsy, Xyrem (sodium oxybate) is often recommended.

Monoamine oxidase inhibitors may be used to manage both cataplexy and the REM sleep-onset symptoms of sleep paralysis and hypnagogic hallucinations.

Wise (2004) noted that people with narcolepsy will often try to avoid thoughts and situations that they know are likely to evoke strong emotions because they know that these emotions are likely to trigger cataplectic attacks.

A newer class of antidepressants with selective serotonergic reuptake blocking properties known as the selective serotonin reuptake inhibitors fluoxetine, paroxetine, sertraline, citalopram has become popular for the treatment of cataplexy. This class of drugs has an active metabolite with norepinephrine reuptake blocking properties (such as nor-fluoxetine). Serotonin reuptake inhibitors (SSRIs) have fewer side effects compared to the tricyclics and can be used in adults and children. A side effect worth mentioning regarding tricyclic antidepressants and SSRIs is the risk of development of REM behavior disorder (RBD) due to elimination of the normal REM sleep atonia. These drugs are known to decrease stage REM sleep. They can also decrease muscle atonia associated with REM sleep and consequently dissociate REM sleep. As a consequence, the subject may act out his or her dreams and cause harm to himself/herself or others.

Emerging therapies

Emerging therapies include Hypocretin Gene Therapy and Hypocretin Cell Transplantation for narcolepsy-cataplexy.

The newest agent for the treatment of cataplexy is sodium oxybate (gamma-hydroxybutyrate [GHB]), known commercially as Xyrem. Although its mechanism is unknown, it reduces cataplectic attacks and other manifestations of REM sleep. GHB increases slow wave sleep, decreases nighttime awakenings, and consolidates REM sleep. Sodium oxybate is the only medication that will improve both cataplexy and daytime sleepiness. Cataplectic symptoms are improved much faster. Because it can cause daytime sleepiness, during this time, sodium oxybate should be taken concomitantly with a stimulant.

See also

• Neurodegenerative disease
• Niemann Pick disease

External links

• Narcolepsy Association UK
• BBC's article on the condition
• National Niemann Pick Disease Foundation: Children with Niemann Pick Type C often suffer from cataplexy