Study Notes on Sleep Disorders

Presenter Information:
- Eli Matta, Neurologist and Sleep Physician
- Affiliation: Royal Prince Albert Hospital
- Position: Clinician Scientist at the University of Sydney
Objective of the Talk:
- Introduce the realm of sleep disorders with emphasis on neurological and non-respiratory types, which constitute the majority seen in general and specialty practice.
- Classification of major categories of non-respiratory sleep disorders.
- Identify hallmark clinical features of:
- Narcolepsy (Part 1)
- Restless Legs Syndrome, REM Sleep Behavior Disorder, and other parasomnias (Part 2)
Expected Outcomes:
- Understand broad management principles of these conditions.
- Recognize the link between sleep disorders and neurological diseases.

Sleep Duration:
- Humans spend a third of their lives sleeping.
- Evolutionary perspective: If sleep had no significant function, it would have been eliminated.
Functions of Sleep:
- Critical for various bodily systems including:
- Brain health and cognitive function
- Emotional reactivity and mood regulation
- Learning and memory
- Attention, creativity, and decision making
Recent Research Highlights:
- Glymphatic System:
- Helps in clearing metabolic waste from the brain during sleep, especially during sleep deprivation.
- Link between sleep and:
- Cardiovascular System:
  - Epidemiological evidence indicating spikes in cardiovascular mortality during daylight savings time.
- Metabolic System:
  - Associated with type 2 diabetes, obesity, and fertility issues.
- Immune System:
  - Sleep plays a role in regulating immune health and core body temperature.

Health Risks:
- Sleep deprivation linked to:
- Cardiovascular diseases
- Cancer (classified as a carcinogen by the WHO, especially related to night shift work).
- Dysfunction in hormones and metabolism.
Neurodegeneration Link:
- Sleep disorders contribute to neurodegenerative diseases.
- Even one night of sleep deprivation can lead to accumulation of beta amyloid, associated with Alzheimer's disease.

Brain Areas Involved:
- Circuits for sleep and wakefulness are found in:
- Brainstem (medulla, pons, midbrain)
- Basal forebrain (cholinergic system)
- Lateral hypothalamus (promotes sleep)
Disrupted Circuits:
- Conditions such as narcolepsy involve loss of cells in the lateral hypothalamus.
- REM sleep behavior disorder stems from neuropathology in pontine circuits regulating REM sleep.

International Classification of Sleep Disorders (ICSD):
- Published by the American Academy of Sleep Medicine, now in its third edition.
Major Categories Identified in ICSD:
- Insomnia Disorders:
- Most common disorder.
- Sleep-Related Breathing Disorders:
- To be covered in other lectures.
- Central Disorders of Hypersomnolence:
- Includes narcolepsy.
- Circadian Rhythm and Sleep-Wake Disorders:
- Disruptions in normal day/night rhythm.
- Parasomnias:
- Abnormal behaviors during sleep.
- Sleep-Related Movement Disorders:
- Includes restless leg syndrome and periodic limb movements.
- Other Disorders:
- Examples include exploding head syndrome, catathrenia, etc.
- Medical and Neurological Disorders Affecting Sleep:
- E.g., autoimmune encephalitis.

Three Primary Problems in Sleep Disorders:
1. Difficulty Falling Asleep:
- Linked to insomnia, circadian rhythm disorders, sleep apneas, nocturia.
1. Excessive Sleepiness During the Day:
- Associated with central hypersomnolence disorders and medication issues.
1. Abnormal Sleep-Related Behaviors:
- Includes restless legs syndrome and various parasomnias.
Contributing Factors to Consider:
- Comorbid medical conditions
- Medications
- Mood and pain levels
- Exercise and light exposure
- Food timing, caffeine, nicotine, and alcohol intake.

Tools Used for Investigation:
- Questionnaires:
- Specific for types of sleep disorders.
- Sleep Diaries:
- Help to identify circadian rhythm issues.
- Actigraphy:
- Monitors activity levels to distinguish wakefulness and sleep.
- Overnight Polysomnography:
- Combined sensor signals to examine sleep stages, respiration, etc.
- Additional Tests:
- Blood tests, genetic testing, MRI, CSF sampling as needed.

Case Presentation:
- Patient: Tara, 19-year-old university student
- Symptoms:
- Difficulty staying awake in lectures, needing daytime naps.
- History of sleepiness since age 15.
- Episodes triggered by strong emotions leading to muscle weakness (cataplexy).
- Fragmented sleep with multiple awakenings at night, no apnea.
Diagnosis:
- Narcolepsy Type 1, characterized by:
- Daily periods of irrepressible sleep need.
- Cataplexy episodes triggered by emotions, no loss of consciousness.
Mechanism of Narcolepsy:
- Loss of orexin (hypocretin) cells in the lateral hypothalamus (approx. 10,000 B cells lost).
- Thought to be immune-mediated; common genetic variant present (HLA DQB10602).

Essential Features:
- Strong, uncontrollable need to sleep for at least 3 months.
- Episodes of cataplexy with retention of consciousness.
Associated Features:
- Hallucinations during sleep transitions.
- Sleep paralysis post-REM sleep.
- Termed fragmented sleep, although naps can be refreshing.
Diagnostic Tests:
- Profile of symptoms, history, and genetic testing (HLA DQB0602 allele).
- Polysomnography to exclude sleep apnea and identify early REM periods.
- Daytime sleep tests to observe sleep onset and REM onset during naps.
- Orexin levels in CSF as definitive biomarker.

Management Strategies:
- Schedule naps and optimize sleep conditions.
- Address comorbid conditions (sleep apnea, depression).
- Use of wake-promoting and anti-cataplexy medications:
- Examples include venlafaxine (anti-cataplexy).
Emerging Treatments:
- Orexin-2 receptor agonists are being researched and show promise.

Summary:
- The first part focused on narcolepsy and its features.
- The second part will address restless legs syndrome, REM sleep behavior disorders, and other parasomnias.