Cataplexy: what is it, symptoms, treatment, prognosis

What is cataplexy?

Cataplexy, physical feature narcolepsy, characterized by short-term episodes of voluntary muscle weakness provoked by strong emotions. Subjective descriptions of cataplexy can help identify narcolepsy, as this feature is almost unique to the disorder. Unfortunately, cataplexy is difficult to identify and often goes unnoticed. Although only 19% of patients diagnosed with narcolepsy are also diagnosed with cataplexy, it is estimated that approximately 70% of patients with narcolepsy have the disorder.

Symptoms and Signs

Cataplexy manifests as muscle weakness that can range from subtle relaxation of the facial muscles to complete muscle paralysis with postural collapse. The attacks are short, most lasting from a few seconds to several minutes, and usually involve drooping of the jaw, neck weakness, and / or knee curvature. Even with a full-blown collapse, people can usually avoid injury because they learn to notice the sensation of an impending cataplectic attack, and the fall is usually slow and gradual. Speech may be slurred and vision may be impaired (

double vision, inability to concentrate), but hearing and awareness remain normal.

Cataplexy attacks go away on their own and go away without medical intervention. If a person leans back comfortably, they may become drowsy, hypnagogic hallucinations, or enter REM sleep. Although cataplexy worsens with fatigue, it differs from narcoleptic sleep episodes and is usually, but not always, caused by severe emotional reactions such as laughter, anger, surprise, awe, and embarrassment, or sudden physical exertion, especially if the person taken by surprise. One well-known example of this was the reaction to the long jump at the 1968 Olympics. Medalist Bob Beamon, realizing that he had broken the previous world record by more than 0.5 meters (almost 2 feet), fell to his knees and shook his whole body. Cataplectic attacks can sometimes occur spontaneously, without any specific emotional trigger.

Causes and risk factors

Narcolepsy Type 1 (historically known as narcolepsy with cataplexy) is due to a deficiency in orexin-A, a peptide neurotransmitter that promotes wakefulness. There is an almost perfect association of type 1 narcolepsy with HLA-DQB1 * 06: 02, leading to the autoimmune hypothesis, which claims that the selective self-destruction of orexin-A-producing neurons is the driving force disorder. The onset of narcolepsy is seasonal and most often manifests itself in the spring, following an upper respiratory tract infection in the previous months.

Type 2 narcolepsy, on the other hand, is associated with the development of lateral lesions of the hypothalamus. In rare cases, lesions caused by arteriovenous malformations, cerebrovascular disorders, inflammatory processes and neoplasms, lead to the destruction of neurons that produce orexin-A. It is worth noting that other neurological disorders are common in people who develop secondary narcolepsy, as the lesions are usually not limited to the lateral hypothalamus.

Epidemiology

The exact number of patients with narcolepsy in Russia is unknown. In the United States, narcolepsy affects 1 in 2,000 people, with an equal gender distribution. Symptoms most often occur during adolescence; however, diagnosis is often delayed by an average of 15 years. There are two forms of narcolepsy: Form 1 is associated with cataplexy, while Form 2 is not. In the United States, type 1 narcolepsy affects 1–2 in 4,000 people.

Pathophysiology

In addition to the physical characteristics of cataplexy, type 1 narcolepsy differs from type 2 narcolepsy on a molecular level. In patients with type 1 narcolepsy, cerebrospinal fluid examination shows decreased levels of orexin-A, a peptide neurotransmitter that promotes wakefulness. Neurons located in the lateral hypothalamus produce orexin-A; it enhances the production of the following neurotransmitters: dopamine, histamine, norepinephrine and serotonin, which leads to the suppression of REM sleep (REM). Intense emotions transmitted from the medial prefrontal cortex to the amygdala, combined with the loss of orexin-A, reduce inhibitory REM sleep signals, ultimately suppressing motor neurons in the pons, leading to muscle paralysis and cataplexy.

Diagnostics

When diagnosing cataplexy narcolepsy, an accurate and detailed medical history must be obtained. The physician should examine behavioral (e.g., caffeine use, insufficient sleep, poor sleep hygiene, tobacco use, etc.) and alternative diagnoses (i.e. anemia, hypothyroidism, obstructive sleep apnea etc.) excessive daytime sleepiness. It is important to understand that patients with narcolepsy get good rest after a short sleep or an adequate night's sleep. sleep, however, symptoms of excessive daytime sleepiness appear for several hours after awakening. In addition to excessive daytime sleepiness, patients with type 1 narcolepsy experience symptoms of REM sleep dysregulation (eg, cataplexy, hypnagogic hallucinations, and sleep paralysis).

The sudden onset of muscle weakness characterizes cataplexy. These episodes are temporary, lasting from seconds to minutes, and are triggered by strong emotions. Cataplectic attacks are more often provoked by positive emotions (for example, laughter, excitement, etc.), than negative ones (i.e. anger, fear, frustration, etc.), with laughter being the most frequent reason. It is the complete or partial paralysis of the voluntary muscles that is the cause of the weakness associated with cataplexy; however, it should be noted that the muscles of the eyes and respiration are not affected during these attacks. Suppression of serotonergic and noradrenergic neural circuits allows complete or partial paralysis of voluntary muscles. Consciousness, however, is not compromised during cataplectic attacks, as the histaminergic signals that promote awakening are retained. Cataplectic attacks usually develop in a crescendo pattern, first affecting the muscles of the face and neck, and then moving on to the muscles of the trunk and limbs. Physical signs depend on the severity of each episode, ranging from drooping face and slurred speech (partial seizures) to collapse (full seizures). Episodes of cataplexy are often resolved within two minutes, and those who suffer do not have long-term consequences.

The Multiple Sleep Latency Test (MSLT) is often done to quantify daytime sleepiness.

Treatment

While behavioral modifications (eg, planned sleep, adequate night sleep) play a role in managing excessive daytime sleepiness associated with type 1 narcolepsy, the treatment for cataplexy is purely pharmacological. The duration of therapy is uncertain, as type 1 narcolepsy is incurable. It should be mentioned that treatment options include various combinations of drugs, often constituting an individualized treatment. Clinicians can use the Epworth Sleepiness Scale to track response to treatment. For the sake of completeness, the pharmacological treatment of type 1 narcolepsy in general is presented below:

Successful treatment of excessive daytime sleepiness often requires the use of wakefulness aids, as behavior modification does not provide complete relief. Modafinil (100 to 400 mg orally once a day every morning) and its isolated R-enantiomer, armodafinil (150 to 250 mg orally once a day every morning), are considered first-line pharmacological agents for the treatment of excessive daytime sleepiness. Although the mechanism of action of these agents is not fully understood, it is believed that their effects are associated with an increase in dopaminergic signaling through inhibition of dopamine reuptake. In 2019, two more drugs were approved in the United States: Pitolysant and Solriamphetol. Pitolysant (8.9 to 35.6 mg orally once a day every morning) is an inverse agonist of histamine-3 receptors, and solriamphetol (75 to 300 mg orally once a day every morning) is a selective reuptake inhibitor dopamine / norepinephrine.

Successful treatment of cataplexy requires the use of drugs that suppress REM sleep. These drugs increase the concentration of norepinephrine and serotonin. The following pharmacological agents are considered first-line drugs for the treatment of cataplexy: selective serotonin reuptake inhibitors (fluoxetine 10 to 80 mg orally daily every morning), norepinephrine reuptake inhibitors (atomoxetine 40-80 mg orally daily every morning), serotonin / reuptake inhibitors norepinephrine (extended-release venlafaxine 37.5-150 mg orally once a day every morning) and tricyclic antidepressants (clomipramine 10-150 mg orally daily every morning). Prescribers, as previously mentioned, should consider the following:

• Tricyclic antidepressants (TCAs) have ceased to be used to treat cataplexy due to their anticholinergic side effects (e.g. delirium, dryness of mucous membranes, hyperthermia, intestinal obstruction, mydriasis, tachycardia and urinary retention). Moreover, an overdose of TCAs can lead to toxicity: anticholinergic symptoms, cardiotoxicity, and neurotoxicity. Cardiotoxicity includes delayed interventricular conduction (QRS lengthening), right axis deviation, and tachycardia (anticholinergic effect).
• Serotonin Syndrome diagnosed clinically using Hunter's criteria: administration of a serotonergic agent under conditions of inducible clonus with agitation or sweating. This can happen when one serotonergic agent is taken as directed / in excess, or when several serotonergic agents are taken at the same time. Its manifestations are associated with an increase in the level of serotonin in the central nervous system. Typical manifestations include an altered mental state, increased autonomic activity, and neuromuscular changes. Great care is needed to avoid administering multiple serotonergic agents to the same patient.

Currently, only one drug is approved for the treatment of both cataplexy and excessive daytime sleepiness associated with narcolepsy: sodium oxybate, the sodium salt of gamma-hydroxybutyrate. The mechanism of action of this medication is unknown; however, it is a known metabolite of gamma-aminobutyric acid (GABA). Therefore, it is believed to act through the GABA-B receptor. This medication is initially given at bedtime, followed 2.5-4 hours later and has significant salt content from 1100 mg to 1640 mg at a dosage in the effective range (from 6 to 9 g at night in two reception).

Forecast

Patients should be able to defend their interests by accurately describing their symptoms to the doctor in order to facilitate the diagnosis of cataplexic narcolepsy. Although narcolepsy is an incurable neurological disease, there are treatment options available to address the symptoms. For patients with narcolepsy with cataplexy, there are many individual pharmacological drugs intended only for symptomatic treatment of cataplexy and excessive daytime sleepiness, with the exception of sodium oxybate, which targets all signs of narcolepsy 1st type.

Complications

Severe episodes of cataplexy leading to complete collapse can lead to musculoskeletal injury and intracranial hemorrhage. Factors that determine the severity of the consequences after a cataplectic fall include age, composition surface of the earth, growth, pre-existing metabolic bone disease and surrounding items.