Introduction:
Narcolepsy, a disorder involving swift onset REM sleep, is marked by excessive daytime sleepiness, frequent uncontrollable sleep attacks, and sleep disruptions. It may include cataplexy, sleep paralysis, and hypnagogic hallucinations. There are two types: narcolepsy type 1 (formerly with cataplexy) and narcolepsy type 2 (formerly without cataplexy). Cataplexy, a distinctive narcolepsy feature, is characterized by brief muscle weakness triggered by strong emotions, aiding in diagnosis. While a third of patients exhibit the classic narcolepsy tetrad, including cataplexy, two-thirds of narcolepsy patients are affected by cataplexy.
What Is Narcolepsy and Cataplexy?
Narcolepsy, a persistent neurological condition, disrupts the brain's ability to regulate sleep-wake cycles. Those affected may awaken feeling rested but battle excessive daytime sleepiness and irregular, interrupted sleep patterns. Daily activities are significantly impacted, with individuals involuntarily falling asleep during tasks like driving or eating. Additional symptoms include sudden muscle weakness (cataplexy), vivid dream-like hallucinations, and temporary paralysis around sleep transitions. Unlike a typical sleep cycle, narcolepsy results in a swift entry into rapid eye movement (REM) sleep, leading to dream-like states or muscle weakness during wakefulness. Untreated narcolepsy can impede psychological, social, and cognitive well-being, hindering academic, work, and social engagement.
Cataplexy, a physical manifestation of narcolepsy, involves brief episodes of voluntary muscle weakness triggered by intense emotions. Descriptions provided by individuals experiencing cataplexy can aid in identifying narcolepsy, as this symptom is nearly exclusive to the disorder. However, detecting cataplexy can be challenging, leading to underdiagnosis. While 19 percent of narcolepsy-diagnosed patients also have cataplexy, estimates suggest that around 70 percent of narcolepsy patients experience cataplexy.
What Are the Causes of Narcolepsy With Cataplexy?
Narcolepsy type 1 results from the near-complete loss of neurons containing orexin, possibly triggered by an autoimmune process linked to infections. HLA haplotype DQB1*0602 is found in 95% of narcolepsy type 1 patients, though it is also present in 20 percent of the general population without narcolepsy. The cause of narcolepsy type 2 is less clear, with hypotheses including limited orexin cell destruction, impaired orexin receptor signaling, or unknown mechanisms. Some narcolepsy type 2 patients may develop cataplexy over time, indicating disease progression. Trauma and tumors can also lead to narcolepsy, though less commonly.
In 2009, a rise in narcolepsy type 1 cases in Europe post AS03-adjuvanted A(H1N1) pandemic influenza vaccination raised concerns about adjuvant-related immune responses. However, similar adjuvant use in Canada did not result in a corresponding increase. Additionally, non-vaccinated individuals experienced an upsurge in narcolepsy cases after wild A(H1N1) influenza infection. Antibodies against streptococcal infections have been linked to narcolepsy type 1 onset, suggesting a potential autoimmune connection, even though a specific autoantibody correlating with the disease mechanism remains unidentified.
What Are the Signs and Symptoms of Narcolepsy With Cataplexy?
1. Daytime Sleepiness: Narcolepsy patients commonly experience significant daytime sleepiness.
2. Onset and Progression: Symptoms typically emerge in the mid-teens to mid-thirties, gradually intensifying. The diagnostic journey spans an average of approximately 15 years from symptom onset.
3. Key Diagnostic Symptom: The primary symptom of narcolepsy diagnosis is daily, uncontrollable lapses into rapid eye movement (REM) sleep, referred to as "sleep attacks," persisting for at least three months.
4. Cataplexy: Marked by sudden, bilateral muscle weakness during heightened emotions like laughter, cataplexy is pathognomonic for narcolepsy if present but not mandatory for narcolepsy type 2 diagnosis.
5. Sleep Paralysis: Occurs upon waking, characterized by being able to hear ambient noise but unable to open eyes or move, potentially causing a sensation of suffocation. Linked to narcolepsy but is also found in up to 50 percent of the general population.
6. Hypnagogic Hallucinations: Dream-like experiences during sleep transitions involving visual, auditory, or tactile sensations. Patients often perceive human faces or a presence in the room.
7. Fragmented Nighttime Sleep: Despite excessive daytime sleepiness, narcolepsy patients find naps refreshing. Nighttime sleep is significantly fragmented.
8. Diagnostic Process: A thorough physical exam is crucial to exclude other potential causes of hypersomnia.
9. Association with Obesity: Obesity is a common feature of narcolepsy, increasing the risk of sleep apnea.
10. Clinical Features in Children: In children, clinical features may include motor overactivity, restlessness, inattentiveness (misinterpreted as seizures), drop attacks, aggression, irritability, and falls.
How to Diagnose Narcolepsy With Cataplexy?
To begin with, ensure the patient consistently gets at least six hours of sleep nightly for two weeks, preferably confirmed by actigraphy and a sleep log due to potential overestimation. If the patient meets this criterion, proceed to a polysomnogram (PSG) to rule out other sleep disorders like sleep apnea. If PSG is normal, conduct a multiple sleep latency test (MSLT) the following day, offering four to five nap opportunities at two-hour intervals. A positive result indicates rapid REM sleep onset (less than 15 minutes) at least twice and a shortened mean sleep latency (less than eight minutes). If MSLT is negative but suspicion persists, consider repeating the test.
During MSLT, let the patient sleep naturally after the PSG to avoid false positives. Lack of sleep or early testing may cause initial SOREMPs, especially in those with chronic insufficient sleep or shift workers. Narcolepsy type 1 diagnosis may involve checking cerebrospinal fluid for low hypocretin-1 (<110 pg/mL). While HLA DQB1*0602 is common in narcolepsy type 1, it isn't diagnostically useful.
What Is the Treatment for Narcolepsy With Cataplexy?
Behavior modification proves effective with strategically scheduled 15 to 20-minute naps and maintaining a proper nighttime sleep routine. Primary pharmacologic treatment for excessive daytime sleepiness involves Modafinil (twice daily) or Armodafinil (once daily). Amphetamines are a second-line option. Sodium oxybate is the first line for cataplexy, administered in bed due to rapid onset (5 to 15 minutes), with a second dose after 2.5 to 4 hours. Sodium Oxybate is a controlled substance from a central pharmacy, and concerns about abuse lack post-market validation. Tricyclic antidepressants (Protriptyline, Clomipramine) and SNRI/SSRIs (Venlafaxine, Fluoxetine) have shown success in cataplexy treatment.
Nonpharmacological measures include promoting good sleep hygiene, offering emotional support, providing mental health counseling, assisting with disability forms and obtaining medications, and educating about the risks of alcohol and illicit drug use.
While CNS stimulants are used, none guarantee 100 percent effectiveness. Methylphenidate improves sleep but has side effects like anxiety. Modafinil induces wakefulness, but safety in children is uncertain. Armodafinil, effective for narcolepsy, shares side effects with Methylphenidate. Sodium oxybate, the FDA-approved cataplex treatment, should not be combined with other depressants or alcohol. Pitolisant (a histamine H3 receptor antagonist), recently FDA-approved for narcolepsy, shows promise in improving sleep based on early studies. For children, currently, no drug has been approved by the FDA (Food and Drug Adminstration).
Conclusion:
Narcolepsy with cataplexy, affecting 0.02 percent of adults globally, is a debilitating sleep disorder marked by severe daytime sleepiness, sudden muscle tone loss (cataplexy), sleep-onset or sleep-offset paralysis, hallucinations, sleep disturbances, and weight gain. Sleep monitoring reveals rapid sleep onset and abnormal, shortened rapid-eye-movement sleep latency day and night. Typically emerging in adolescence or young adulthood, narcolepsy with cataplexy persists throughout life. Pathophysiological studies indicate early loss of hypocretin-producing neurons in the hypothalamus, a wakefulness-associated neurotransmitter in cerebrospinal fluid. Autoimmune mechanisms, potentially linked to the HLA DQB1*0602 allele, are implicated. Treatment includes stimulant drugs for daytime sleepiness, antidepressants for cataplexy, and gamma-hydroxybutyrate for symptom relief. Due to under-recognition, early identification of abnormal daytime sleepiness by general practitioners and primary health-care workers is crucial.
