cataplexy

What is Cataplexy?

Cataplexy is a sudden and transient loss of muscle tone, caused by a strong emotion or a rice crisis. The affected person suddenly collapses to the ground without losing consciousness.

Cataplexy is a rare neurological disorder, but common in people with narcolepsy (occurs in about 70% of cases). It can manifest itself with a series of physical changes, partial or generalized: from the difficulty in articulating the words (dysarthria), to the weakness of the knees, up to the complete atony. During a cataplectic attack, the subject loses voluntary muscle control and can fall to the ground, but always remains conscious and alert. The episodes can last a few minutes and are often triggered by an emotional stimulus such as laughter, fear, anger, surprise or excitement. The treatment involves the use of anticataplectic drugs (sodium oxybate or antidepressants).

Causes

The exact cause of cataplexy is unknown, but the condition is strongly associated with emotional stimuli. Emotions that can trigger a catapletic event include laughter, fear, anger, frustration, irritation, nervousness, embarrassment and sadness. As soon as the stimulation is reduced, the person regains normal muscle control. Emotions can also be modest, while at other times an attack takes place spontaneously, in the absence of an apparent cause.

The loss of muscle tone, which occurs in cataplexy, resembles the interruption of muscular activity that occurs naturally during REM sleep: the sudden weakness of the muscles of the body could be caused by a massive inhibition of the motor neurons in the spinal cord, caused by a dysfunction of the sleep-wake cycle. Using an animal model, scientists learned that this same group of neurons is inactive during cataplexy attacks.

Role of hypocretin

Cataplexy is associated with significantly reduced levels of hypocretin, a neuropeptide produced in the hypothalamus, of primary importance in the regulation of sleep, as well as states of excitation. According to some researchers, an autoimmune mechanism would be the basis of this depletion

Other considerations

Cataplexy can also manifest itself as a side effect of the SSRI withdrawal syndrome (the "selective serotonin reuptake inhibitors" belong to the pharmaceutical class of non-tricyclic antidepressants).

Narcolepsy and Cataplexy

Cataplexy is often found in association with narcolepsy, a chronic neurological disorder characterized by excessive daytime sleepiness (hypersomnia) and sudden sleep crises. When patients experience both conditions, we speak of Gélineau syndrome .

Cataplexy attacks make the diagnosis of narcolepsy more certain, especially when signs such as excessive daytime sleepiness (EDS), hallucinations and other unwanted manifestations accompanying REM sleep occur. However, it is important to remember that not all narcoleptic patients show episodes of cataplexy.

Associated conditions

Cataplexy may be associated with other pathological conditions. In particular, it is considered secondary when it is caused by specific brain lesions, mainly located in the lateral hypothalamus (responsible for hypocretin depletion). On the other hand, lesions of the brain stem can determine isolated cases of cataplexy; these include: encephalic tumors (for example: astrocytoma, glioblastoma, glioma and subependimoma) and arteriovenous malformations. Other conditions in which cataplexy can be found include: ischemic events, multiple sclerosis, head trauma, paraneoplastic syndromes and infections, such as encephalitis. Cataplexy can also occur transiently or permanently due to lesions of the hypothalamus caused by surgery, especially in the case of particularly complex tumor resections.

Symptoms

Cataplexy is extremely unpredictable, both in terms of gravity and frequency. The loss of muscle tone varies from a barely perceptible weakening of the facial muscles, to the failure of the upper or lower limbs, up to the complete muscular atony. These sudden manifestations can cause postural collapse and the patient's fall. During cataplexy attacks, both mild and severe, the person remains fully conscious, therefore he is aware of everything that happens around (hence the hypothesis of sleep-wake dysfunction: the atony of the muscles is verified as during the phase REM, but the subject is vigilant). Cataplexy occurs more frequently in times of emotional stress and in case of lack of sleep.

Cataplexy is an easily overlooked and often undiagnosed disorder that can affect the most basic activities of everyday life.

Cataplexy should not be confused with an epileptic seizure :

• Cataplectic attack : occurs quickly, during periods of emotional stimulation; the subject maintains his state of consciousness unchanged and recovers almost immediately;
• Epileptic crisis : occurs during periods of quiet and stimulation; the person recovers more slowly and may not remember what happened.

Duration of cataplectic attacks

In most cases, attacks are transient and abruptly cease after a few seconds or minutes. A cataplectic episode is considered "typical" when it is short-lived (<5 minutes). However, in some cases, repeated attacks can persist up to 30 minutes. Rarely, the subject may fall into a sleep of extended duration: the condition is known as a cataplectic state.

Cataplexy may occur occasionally, with one or two episodes in a year, or several times a day.

Treatment

Cataplexy is rarely found during an outpatient visit and the diagnosis can be made by a specialist who is familiar with the condition. Measurement of hypocretin levels in cerebrospinal fluid can confirm the diagnosis.

Cataplexy is treated pharmacologically. The first product approved by the FDA for the treatment of cataplexy in relation to narcolepsy is Xyrem ® (sodium oxybate). Symptoms can be suppressed with the help of tricyclic antidepressants and serotonin reuptake inhibitors. Despite its relationship with narcolepsy, in most cases, cataplexy has to be treated separately.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)

SSRIs and SNRIs can be used to help alleviate the symptoms of cataplexy and other manifestations associated with REM sleep, such as hypnagogic hallucinations (consisting of hallucinations, especially visual, present at the beginning or end of sleep) and sleep paralysis ( disorder characterized by the temporary inability to move or speak, before falling asleep or upon awakening). They include fluoxetine and venlafaxine. Serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) have fewer side effects than tricyclics.

Sodium oxybate (Xyrem ®)

This drug is highly effective for cataplexy associated with narcolepsy. Sodium oxybate improves night rest and, in high doses, can also help control daytime sleepiness. Xyrem ® can have serious side effects, such as nausea, enuresis and worsening of sleepwalking. Taking sodium oxybate together with other sleeping medications, narcotic analgesics or alcohol can lead to difficulty breathing, coma and death.

Tricyclic antidepressants

For many years, cataplexy has been treated with drugs such as imipramine, clomipramine or protriptyline. The main characteristic of tricyclic antidepressants is their ability to inhibit the re-uptake of noradrenaline and serotonin at the level of nerve endings. However, these can have unpleasant side effects (eg dry mouth and lightheadedness) and because of this they have been replaced by new drugs, such as venlafaxine.

Emerging therapies

Promising treatments for cataplexy include gene therapy to promote hypocretin expression and immunotherapy, but more research is needed to confirm their effectiveness.