Understand and Conquer 

NARCOLEPSY

What is Narcolepsy?

Narcolepsy can be defined as a neurological dysfunction that is characterized by the significant modification of the sleep-wake cycle due to the brain’s inability to regulate the sleep architecture [1] Excessive Day Sleepiness (EDS) is the predominant symptom associated with this condition. Many persons with narcolepsy also encounter the disrupted and asymmetrical sleep patterns that can involve frequent nocturnal arousals. This can subsequently lead to chaos in the daytime activities. Cataplexy and sleep-hallucinations and sleep paralysis are some of the other symptoms of narcolepsy. 

A typical sleep cycle involves a sequence of stages, Rapid Eye Movement (REM) phase occurring about 60 to 90 minutes after sleep onset. Narcolepsy is marked by the premature occurrence of REM sleep, usually within 15 minutes after sleep onset. As a result, the muscle weakness or the phenomenon of acting out dreams can be experienced during the arousal periods or non-existent during sleep. Undetected or untreated narcolepsy conditions can have a significant impact on the intellectual, social and cognitive abilities and can hinder educational, professional and social functioning.

Types of Narcolepsy


Types of narcolepsy fall under two categories corresponding to International Classification of sleep Disorders, Third Edition (ICSD-3). [2] They are Narcolepsy Type 1 (NT1) and Narcolepsy Type 2 (NT2).

Narcolepsy Type 1 (NT1)

NT1 is correlated with the condition of Cataplexy. Cataplexy is the abrupt loss of muscle tone during wakefulness which leads to weakness and inability to control the involuntary muscles. NT1 was previously termed as ‘Narcolepsy with cataplexy’. The diagnosis of NT1 is based on findings of either the occurrence of relatively low levels of hypocretin or encountering cataplexy and experiencing EDS on a specialized sleep study. Hypocretin is a brain hormone that regulates wakefulness.

Narcolepsy Type 2 (NT2)

Individuals with NT2 may experience comparable symptoms as persons with NT1, although they do not undergo cataplexy or low hypocretin levels. This type was formerly known as “Narcolepsy without Cataplexy”. If Cataplexy is developed in an individual with NT2 in the late-phase, the diagnosis can be recategorized as NT1. Approximately 10% of the instances are estimated to have this alteration in the diagnosis.

What Causes Narcolepsy Symptoms?

Interpreting the symptoms of narcolepsy is the primary step towards meticulously prognosing and treating this persistent and potentially devitalizing dysfunction. Symptoms of this neurological disorder are generally correlated with the loss of brain cells that aids in the production of orexin. Orexins play a major role in the consolidation of wakefulness and restraint of REM sleep [5]. 


The lack of adequate orexin-producing neurons leads to the inappropriate patterns of sleep-wake cycles. The shortfall in the consolidation of sleep can make the individuals experience intense fatigue during the diurnal period with an urge to take frequent naps. It is quite typical for narcolepsy patients to feel the profound need for sleep at inappropriate times.


Narcolepsy makes the rapid transition of the body between the sleeping and arousal phases. Sleep onset and occurrence of REM sleep happens more quickly than those without this dysfunction. 


The probability of manifesting the partially awake and partially asleep states in the nighttime as cataplexy, sleep paralysis or hallucinations are to be taken into consideration. The association between the deficiency of orexins and narcolepsy symptoms is apparent, although not all narcolepsy patients have this deficiency. 


NT1 is connected with the lack of orexins. Individuals prognosed with NT1 have 85-95% lesser orexin-producing neurons [6] compared to the persons without this problem. patients have adequate levels of orexins and comparatively less critical symptoms. Causes of symptoms in patients with NT2 are not rightly apprehended.


Did you know?

The incidence rate of narcolepsy is relatively low. Considering 100,000 individuals, 20-67 persons are affected by Narcolepsy Type 1 in the United States.

In accordance with a demographic based analysis performed in Olmsted county Minnesota, NT1 is two-three fold more prevalent than NT2, which approximately troubles 20-67 people per 100,000.

Estimating the frequency of occurrence of narcolepsy is quite an arduous task due to underdiagnosis and diagnostic deferrals. A lot of patients are not detected with narcolepsy till years after the incidence of their initial signs and symptoms.

Consequently, some of the approximations mark the prevalence of this condition as inflated as 180 for every 100,000 individuals.

Gender cannot be considered as a primary discriminating factor in the case of narcolepsy as it occurs almost equally in both men and women 

This dysfunction can affect individuals in all age groups, although the onset is considered to be at the peak around the age of 15 and a second time around the age of 35.

Symptoms of Narcolepsy


The term used to denote narcolepsy symptoms is tetrad which elucidates the presence of four potential symptoms: Excessive Daytime Sleepiness, Sleep Paralysis, sleep-related hallucinations and cataplexy. Though every single person with narcolepsy experiences EDS, the other symptoms are less prevalent. 


An estimate of 10-15% individuals with narcolepsy encounter the whole tetrad of symptoms. 

  • Excessive Daytime Sleepiness (EDS)

  • Sleep Paralysis

  • Hallucinations

  • Cataplexy

  • Nighttime Sleep Disruption

1. Excessive Daytime Sleepiness (EDS)

EDS is considered to be the primary symptom of narcolepsy. 


Persistence of sleepiness occurs irrespective of the nocturnal sleep hours and it often amplifies when the person is occupied with dull and tedious activities, including watching television or attending the classes. People may feel alertness when doing interesting or exciting tasks. Sleep attacks are typically considered as a part of narcolepsy. 


Rapid incidence of intense sleepiness and the uncontrollable urge to sleep usually develop during the time of a sleep attack. The onset of brief naps with duration of few seconds to minutes happens at any time. Arousal from these short naps can make the person more vigilant and wide awake. 


During pauses in consciousness or the momentary snoozes, narcolepsy patients engage in activities with literally no awareness. When performing usual tasks, they may doze and mechanically carry on with the tasks. Thus the effectiveness in the implementation of the activities reduces to agreate extent. 


For instance, the writing is converted into a scribbled script during the momentary sleep attacks.

2. Sleep Paralysis

This condition is characterized by a short-term loss of voluntary muscle control during arousal or sleep onset. 


Sleep paralysis is associated with a sleeper's inability to move or speak despite complete consciousness. Durations of sleep paralysis span for several minutes and after arousal, the ability to move or speak is restored. 


An estimate of 25% persons with narcolepsy encounter the condition of sleep paralysis [8]. Incidence of REM sleep typically occurs 60 to 90 minutes after sleep onset. REM phase involves elevated brain activity, lucid dreaming and atonia-a short-term muscle paralysis. Acting out the dreams is prevented by atonia and it usually ends after waking up from the sleep. 


In the case of persons with narcolepsy, entry to the REM phase is quite quicker (15 minutes after sleep onset). Consequently, the experiences usually developed in the REM phase may turn into wakefulness. Sleep paralysis occurs due to the persistent prevalence of atonia during the awakening. 

3. Hallucinations

Hallucinations affect one-third of narcolepsy patients and it frequently develops during the periods of sleep onset or arousals. Hallucinations are visually perceptive in general, but in some instances multiple senses may also be involved. 

4. Cataplexy

Cataplexy can be defined as the rapid loss of muscle tone during awakenings. Individuals encountering cataplexy continue to stay fully alert unlike the conditions like fainting and seizure disorders. 


Cataplexy is precipitated by intense emotions [9] such as annoyance, laughter, surprise and exhilaration. Cataplexy is associated with Narcolepsy Type 1 only. Mild cataplexy episodes span for a few seconds and consist of a lesser count of muscle groups like eyelids. 


Severe cataplexy episodes may persist for several minutes and encompass a complete loss of voluntary control of muscles, leading to a short-term, total paralysis.

5. Nighttime Sleep Disruption

This can be considered as a common symptom of narcolepsy although it does not include in standard tetrad of narcolepsy symptoms. About 30-95% of patients [10] are affected with disrupted nighttime sleep. 


This symptom might be a stand-alone one or could be developed due to an underlying sleep dysfunction. Narcolepsy patients generally sleep for the same duration as individuals without this disorder but the former category lacks the consolidation of sleep.

Better Sleep = Better Health




What Causes Narcolepsy?


The precise sources and risk factors associated with narcolepsy are not completely realized even with the advancing perceptions and related research.

Causes of NT1

The fundamental aspect of NT1 is the loss of hypocretin-generating hormones, known as orexins. A significant loss of about 90% of hypocretin-producing hormones characterizes NT1 condition leading to the poor regulation of sleep and wakefulness [2]. 


A genetically vulnerable person may encounter loss of these neurons in an autoimmune manner following an environmental activator. Some research studies explore the correlation of NT1 with influenza virus. Though exceptionally rare, possibilities of NT1 onset could be noticeable after the H1N1 epidemic and with a specific vaccine brand administered for H1N1. 


Probabilistic links with other infection categories have been observed as well. On the grounds of these analytical data, it can be perceived that an external triggering factor stimulates the immune system and makes it to damage hypocretin-making neurons. This sort of autoimmune response is not the sole cause as its nature is quite inconsistent. 


A genetic mutation, known as DQB1*0602 which plays a prominent role in immune function is linked with the genetic vulnerability in 98% of the NT1 cases [11]. 


This justification is not conclusively validated yet broadly recognized. Individuals with family history of NT1 have a 1-2% probability of experiencing this neurological sleep disorder. In rare cases, underlying medical conditions that damage the brain parts that constitute orexins. This can happen from brain trauma or infection in Central Nervous System.

Causes of NT2

The biology of NT2 and its risk factors are poorly understood. According to some experts, NT2 is a less evident loss of hypocretin-making hormones even though the persons with NT2 are typically not deficient in hypocretin [2]. 


Others believe that NT2 is an antecedent to NT1 but Cataplexy condition tends to develop in 10% of instances with initial prognosis of NT2. NT2 can even develop due to some medical issues affecting the brain including head trauma and multiple sclerosis.

Diagnosing Narcolepsy


Diagnostic procedure of narcolepsy is a prolonged process which incorporates several medical analysis and sleep studies. The symptoms, review of health history and a physical examination are taken into account for analysing EDS. 


Subjective responses to the sleep-related questions aid the primary care physician to evaluate the drowsiness. Specialized sleep studies including Polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT) may be performed to rule out other causes and substantiate narcolepsy prognosis.

Polysomnography (PSG)

In PSG, the breathing pattern, eye movements, muscle action and brain function are taken into account through an overnight sleep analysis. PSG tracks the sleep phases and arousals and it can unveil the presence of other sleep dysfunctions.

Multiple Sleep Latency Test (MSLT)

MSLT is conducted in the daytime soon after doing PSG. MSLT involves measuring the sleep onset time and time required to enter REM sleep at five distinct intervals by making use of the same sensors employed in PSG.

The outcomes of these sleep studies are significant in narcolepsy diagnosis. The test results become valid only if preparations such as stabilization of sleep cycle for a week, cessation of sleep-interfering drugs or substances and usage of sleep log for documenting sleep are done properly.


In addition to these sleep studies, testing the level of hypocretin-producing hormones by the lumbar puncture procedure. In this, a small quantity of Cerebrospinal Fluid is removed from the lower spinal area. Low levels of hypocretin indicate the presence of NT1. Human Leukocyte Antigen (HLA) is another test to find out whether the mutation is noticeable in a gene DQB1*06:02. 


This variation in gene cannot provide a prognostic result for narcolepsy because the mutation can occur in people without narcolepsy.


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Diagnosting Criteria for NT1 and NT2


Determining whether the condition satisfies the diagnostic criteria is based on the entire information including symptoms, physical analysis and outcomes from specialized sleep studies. Criteria for NT1 and NT2 are discrete. Cataplexy is the major factor in distinguishing the two dysfunctions as it only develops in NT1. 


Following are the diagnostic criteria for NT1 and NT2 [12].

NT1

The patients must satisfy both of these criteria

  • EDS that lasts for a period of 3 or more months

  • Any one of:


    1. Cataplexy related symptoms and results from sleep studies (PSG/MSLT) that manifests rapid sleep onset and early arrival of REM sleep
    2. Low levels of hypocretin

NT2

All these 5 criteria must be met

  • EDS that lasts for a period of 3 or more months

  • Outcomes from sleep studies (PSG/MSLT) that manifests rapid sleep onset and early arrival of REM sleep

  • Absence of cataplexy symptoms

  • Normal hypocretin-levels

  • No underlying conditions

There is a possibility of changing the diagnosis over time. Reclassification of narcolepsy occurs in approximately 10% of individuals. At the outset, they may be diagnosed with NT2, but with the incidence of cataplexy, the diagnostic decision can be changed to NT1.

Treatment for Narcolepsy


As narcolepsy leads to significant effects on daily life, treatment usually focuses on the improvement of overall health. Narcolepsy is an incurable long-term condition. Majority of people remain consistent over time. Progressive improvement of symptoms becomes notable as the age advances. The treatment methodologies are tailored based on the age, overall wellness, symptoms and personal choices, Treatment for narcolepsy falls under two categories. 

1. Behavioral Approaches

This type of technique involves the modifications in lifestyle and daily routine for effective management of symptoms and to reduce the probability of physical or cognitive troubles. 


Behavioral approaches include:

  • Planned Naps: Scheduling the naps can aid the individuals to combat diurnal fatigue. These sorts of naps make the people feel more alert during the important parts of daytime and prevent them from involuntary sleep onsets.

  • Better Sleep Hygiene: Good Sleep Habits consider the consolidation of daily practices as well as the sleep environment to have a better sleep. Suggestions to enhance sleep quality include:


    1. Following a stable sleep schedule
    2. Avoid the consumption of alcohol and substances that create sleep disruption
    3. Avoid caffeine intake prior to bedtime
    4. Reduce the use of electronic gadgets during nighttime.
    5. Create a sleep-favourable environment


  • Prevention of accidents: Probability of accidents is higher for a person with narcolepsy. Excessive Daytime Sleepiness can cause a potential life-threat during driving, running heavy machines or other critical activities. Monotonous and uninteresting activities worsen EDS. Repetitive long-distance driving schedules need to be avoided for effectively preventing accidents. Planning brief naps prior to driving ensures safety. 

  • Searching out for support: Symptoms associated with narcolepsy tend to create a social stigma which may lead to withdrawal and isolation of the patient. Finding support from the family, friends and acquaintances can enhance the patient’s emotional well-being. 


  • Healthy Diet Plan: As narcolepsy can be linked with elevated risk of obesity, following a healthy diet plan is significant. Timing of the meals are quite important to avoid sleep disruptions. Avoid consuming heavy meals before performing the activities that require vigilance.  

  • Daily exercise: Doing routine exercises can help the individuals in maintaining a healthy body mass. Physical activity is also linked with emotional wellness and sound sleep.

  • Ceasing the habit of smoking: Cigarette smoking can deteriorate sleep quality and cause other medical issues. 

  • Choosing the right nutritional supplements: Consuming appropriate dietary supplements impede and alleviate some of the potential symptoms of narcolepsy. The nutritional regimen includes over-the-counter supplements such as L-Tyrosine, Acetyl-L-Carnitine, 5 HTP and Vitamin B12. 

2. Pharmacological Approaches

Use of prescription medications to control narcolepsy symptoms is an approach that has potential benefits, side effects as well as drug interactions. 

Treatment for Excessive Daytime Sleepiness

Medicines that promote alertness play a major role in reducing EDS. Most of these drugs can be used for the treatment of both NT1 and NT2.

  • Modafinil: Modafinil is considered as the typical first-line drug [13] for narcolepsy. According to research studies, Modafinil is a well-tolerated drug that can enhance alertness. Headache, nausea, loss of appetite and anxiety are some of the common side effects of this drug. 

  • Armodafinil: A similar medicine that has similar benefits and risks as that of Modafinil.

  • Methylphenidate: This is the most commonly prescribed medication. It aids in improving alertness but it has more noticeable side effects compared to Modafinil. Some of the adverse issues are appetite loss, irritability and nighttime sleep disruption.

  • Pitolisant: It is FDA-approved drug that augments wakefulness due to its action on histamines. It reduces EDS in both NT1 and NT2 [14]. Common side effects are insomnia, nausea and headache.

  • Solriamfetol: This drug improves EDS by its actions on brain chemicals such as dopamine and norepinephrine. Probable adverse effects are appetite loss, nausea and insomnia.

Cataplexy Treatment

Medications such as Sodium Oxybate and Pitolisan that can reduce the probability of recurrence of cataplexy episodes are prescribed.

Treatment for Disrupted Sleep

Common sleep-enhancing drugs have a strong sedative action that can prevail in the daytime, aggravating EDS. Hence, these sorts of drugs are prescribed with narcolepsy patients along with a warning. Sodium oxybate is an effective drug to combat nighttime sleep disruptions. Being a central nervous system depressant, it can have adverse effects such as seizures and breathing impairments

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Narcolepsy in Children


Treatment for Narcolepsy in Children

Symptoms of Narcolepsy in Children

Excessive Daytime Sleepiness is the major symptom experienced during the initial phases of narcolepsy, usually in the childhood or adolescence. Hypersomnia is a condition characterized by longer sleep durations due to the amplified drowsiness. 


Progressing further, the nighttime sleep develops into a more disrupted sleep pattern which can result in vivid dreams and nocturnal arousals. Despite the fact that narcolepsy is a chronic disorder, progressive worsening of symptoms does not usually occur as the age advances.

Treatment for Narcolepsy in Children

Treatment approaches for children remain similar as that of adults, but supplementary precautions need to be taken in selecting the drugs and dosages. American Academy of Pediatrics recommends a cardiovascular examination prior to the onset of consuming stimulant drugs. 

Narcolepsy Treatment During Pregnancy


Treatment for Narcolepsy During Pregnancy

Little is known about the safety of narcolepsy medications in pregnant and lactating women. According to some surveys, the majority of the specialists recommend discontinuing the narcolepsy drugs during the periods of gestation and lactation and even when trying for conception, To combat symptoms after discontinuing the drugs, effective implementation of behavioral approaches becomes essential.

Better Sleep = Better Health