The International Classification of Sleep Disorders (ICSD) is the most widely used classification system for sleep disorders. This article focuses on the most common sleep disorders physicians encounter in daily practice and an overview of their management.

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Insomnia

Insomnia is the most common sleep disorder. According to ICSD-3, it is defined as difficulty in initiation or maintenance of sleep, despite having adequate opportunities and circumstances to sleep, along with subsequent daytime consequences. It can be further sub-classified into;

1. Short-term insomnia (duration < 3 months)
2. Chronic insomnia (duration >3 months)

Daytime dysfunctions due to insomnia

In most cases, a threshold latency of 30 minutes is significant, i.e., a sleep onset latency of 30 minutes, prolonged awakening of more than 30 minutes at night or early morning awakening at least 30 minutes before the desired time.

As a result of insomnia, the patient experiences a variety of daytime dysfunctions:

• Poor attention span
• Fatigue
• Daytime sleepiness
• Mood disturbance
• Irritability
• Impulsive behaviour
• Hyperactivity, etc.

Insomnia needs to be differentiated from other common sleep disorders including:

1. Restless leg syndrome
2. Delayed and advanced sleep phase syndromes
3. OSA

Insomnia can be associated with other comorbid conditions like:

• Psychiatric conditions (depression, anxiety)
• Systemic ailments (rheumatological, cardiovascular, pulmonary, endocrinological)
• Neurodegenerative disorders (Parkinson’s disease, Alzheimer’s disease)
• Stroke
• Neuromuscular disorders
• Medication use

Self-report screening tools like the Insomnia Severity Index, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index can be used for characterising insomnia and follow-up.

Non-pharmacological therapy

Non-pharmacological therapy for insomnia includes:

• CBT (Cognitive Behavioural Therapy)
• Mindfulness-based interventions (meditation etc.)
• Brief behavioural therapy

Pharmacological therapies

These therapies work by modulating;

• GABA
• Orexin (hypocretin)
• Histamine
• Melatonin neurotransmitter systems

GABA- Benzodiazepines are GABA receptor agonists whose prolonged use must be avoided due to their long half-life and other side effects (sedation, habituation, dizziness, cognitive impairment, and delirium in the elderly).

The non-benzodiazepine GABA agonists (Zolpidem, Zaleplon, Eszopiclone) are the first-line therapies for insomnia. A lower dose is preferred in the elderly and one needs to be alert about complex sleep-related behaviours leading to injury.

Orexin (hypocretin)- The orexin antagonists (Suvorexant, Lemborexant, Daridorexant) are a new group of medications that induce sleep by blocking the orexin (hypocretin) system in the hypothalamus.

Adverse effects include somnolence, narcolepsy-like symptoms and rare cases of cataplexy.

Melatonin- Melatonin and Melatonin receptor agonists (Ramelteon) have a short half-life and are better suited for sleep induction than sleep maintenance.

Other less commonly used medications include Antihistaminic, sedating antidepressants (amitriptyline, mirtazapine), antiepileptics (gabapentin) and antipsychotics (quetiapine). 

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Restless legs syndrome

 1. According to ICSD-3 criteria, the diagnosis of Restless Legs Syndrome (RLS) requires the fulfilment of the following three:

1. An urge to move the legs is usually accompanied by or thought to be caused by uncomfortable and unpleasant sensations in the legs. The symptom must worsen with inactivity, be relieved by movement and must occur during the evening or night.
2. The symptoms listed above are not solely accounted for by a condition that mimics restless legs syndrome.
3. The symptoms cause concern, distress, sleep disturbance, or impairment in mental, physical, social, occupational, educational, behavioural, or other important areas of functioning.

2. RLS is twice as common in women and the prevalence increases with age; family history is present in 60% of the cases. The risk of RLS increases during pregnancy. RLS is associated with Iron deficiency states. Iron deficiency in CNS may lead to myelin deficit and activation of hypoxic pathways.

3. Further reduced nocturnal Dopamine levels may also have a role in potentiating the symptoms of RLS. The initial workup includes measuring serum ferritin levels and transferrin saturation. Other conditions that mimic RLS (night cramps, neuropathy, arthritis, myalgia, etc.) should be ruled out.

4. The dosage of Antidepressants and Antipsychotics might need reduction as they may worsen the symptoms of RLS. Iron replacement (either oral or I/V) is indicated if the serum ferritin level is less than 75 ng/mL or if transferrin saturation is less than 20% to 25%.

5. Dopaminergic medications (Pramipexole, Ropinirole, etc.) are commonly prescribed for RLS. They carry a risk of “Augmentation”, i.e. worsening of RLS symptoms requiring a reduction in the dose of medication.

6. The long-acting Rotigotine patch may reduce the risk of augmentation. α2δ ligands (Gabapentin, Pregabalin) are also effective medications for RLS with low risk of Augmentation. Dizziness, weight gain and sedation are common side effects. Opioids can be used when other treatment options have failed. 

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Narcolepsy

1. Narcolepsy is a clinical syndrome that is characterised by the following tetrad:

• Excessive daytime sleepiness
• Cataplexy
• Hypnagogic hallucinations
• Sleep paralysis

2. It is subclassified into Narcolepsy:

• Low orexin, with cataplexy and Narcolepsy
• Normal orexin, no cataplexy

3. It typically begins in the teenage and early twenties and is caused by immune-mediated destruction of orexin (hypocretin)-producing neurons in the hypothalamus. Association with HLA-DQB1*06:02 has been found to be the strongest. Patients with Narcolepsy tend to rapidly fall asleep throughout the day regardless of the situation (Sleep Attacks).
4. They often feel refreshed after such brief naps. Cataplexy refers to transient muscle weakness triggered by emotions (laughter, excitement, anger, etc.).
5. The weakness may be partial (limited to the face or neck) or maybe generalised leading to the collapse of the patient with intact consciousness.
6. Hypnagogic Hallucinations are frightening, vivid hallucinations that happen as the patient is falling asleep. Sleep paralysis refers to the complete loss of body movements for a few minutes when awakening or falling asleep.

Diagnosis

Diagnosis is mostly clinical. Sleep studies are used for confirmation.

1. A Multiple Sleep Latency Test (MSLT) shows a mean sleep-onset latency of 8 minutes or less and two or more sleep-onset REM periods (i.e., the onset of REM sleep within 15 minutes of sleep onset). CSF orexin (hypocretin) levels are low in Narcolepsy-1.
2. Non-pharmacological therapy includes allowing scheduled daytime naps, avoiding drugs that worsen daytime drowsiness, and providing psychosocial support.
3. In patients with mild to moderate sleepiness, Modafinil and Armodafinil are the first-line wake-promoting agents. Besides these, other drugs like Pitolisant and Solriamfetol can be added to obtain better efficacy.
4. Methylphenidate and Dextroamphetamine are usually considered second-line agents because of their higher sympathetic activity and side effect profile.
5. In patients with severe and disabling sleepiness, Oxybates (sodium oxybate or mixed oxybate salts) are preferred. In those with severe cataplexy, venlafaxine, fluoxetine, duloxetine, and tricyclic antidepressants are known to have anti-cataplexy effects.

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Parasomnias

These refer to unusual and abnormal events that occur during sleep.

They are subdivided into:

1. Non–Rapid Eye Movement (non-REM) sleep parasomnia
2. REM sleep parasomnias

 

Non–Rapid Eye Movement (non-REM) sleep parasomnia

1. Sleepwalking is the most common NREM parasomnia.
2. Besides ambulation, other complex actions like violence, rearranging furniture, urinating, etc. can also be performed once the patient gets up from the bed. Another common NREM parasomnia is Sleep Terrors, which is characterised by episodes of intense fear with abrupt arousal, followed by diaphoresis, tachycardia, and tachypnoea.
3. Confusional Arousal refers to an altered state of consciousness and confusion with the individual still in bed and looking around till the episode has passed.
4. Another interesting NREM parasomnia refers to Exploding Head Syndrome which is characterised by a sudden sensation of loud noise in the head during wake-sleep transition or in the middle of the night.

REM sleep parasomnias

1. Amongst REM parasomnias, the most common is REM sleep behavioural disorder (RBD) in which muscle atonia during REM sleep is lost, leading to the enacting of dreams & vocalisations with subsequent injuries.
2. RBS is commonly seen in neurodegenerative diseases like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Another REM parasomnia is Recurrent Isolated Sleep Paralysis, in which the patient is unable to move the trunk or limbs for a few seconds after waking up, which may be associated with hallucinations and fear.
3. Nightmare Disorder refers to the occurrence of disturbing, frightening dreams that become recurrent leading to distress and functional impairment. It is commonly linked to underlying psychiatric disorders.

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Consequences of sleep deprivation

1. Sleep deprivation has a major role to play in the cognitive impairment of an individual. It impairs working memory and attention which is mediated by the prefrontal cortex. Vigilance, attention, executive function, and cognitive processing speed all tend to decline with decreasing sleep durations.
2. Chronic sleep deprivation is also associated with depression and is linked to anxiety and stress disorders. It also leads to labile mood, reduced emotional processing, irritability, hyperactivity and loneliness. Besides, sleep deprivation impairs the clearance of metabolites in the brain by the glymphatic system.
3. Long-term consequences include the accumulation of protein aggregates in the brain (β-amyloid and tau proteins) and the development of neurodegenerative diseases. Sleep deprivation increases pain sensitivity, increases the risk of stroke & epilepsy and provides a trigger for migraine headaches. 

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr. Annesh Bhattacharjee is a Consultant Neurologist from Guwahati.