Module 4 - Disorders of Excessive Sleepiness Flashcards
(250 cards)
1
Q
What is narcolepsy?
A
A disorder of sleep-wake instability. It involves fragmented sleep during the night and unwanted, excessive sleep during the day. It may also include REM sleep intruding into wakefulness.
2
Q
What causes narcolepsy?
A
The exact cause is unknown. There is likely a genetic component. Rare secondary causes include head injury, tumours, infections, or autoimmune attack.
3
Q
What is the role of orexin/hypocretin?
A
Orexin (aka hypocretin) is a neuropeptide that regulates arousal, wakefulness, and REM sleep suppression. In Narcolepsy Type 1, orexin is absent or very low.
4
Q
What is cataplexy?
A
Sudden, often emotionally triggered loss of muscle tone while awake, due to REM atonia intruding into wakefulness. Consciousness is preserved.
5
Q
What are the two main types of narcolepsy?
A
• Narcolepsy Type 1 (NT1): Excessive daytime sleepiness, Cataplexy, Low or absent orexin in CSF.
• Narcolepsy Type 2 (NT2): Excessive daytime sleepiness, No cataplexy, Normal orexin levels.
6
Q
What is the prevalence of narcolepsy with cataplexy (NT1)?
A
About 0.03–0.06% in the general population.
7
Q
What is the typical onset age of narcolepsy?
A
10–25 years (primary peak), with a second smaller peak at 35–45 years.
8
Q
How does narcolepsy differ in children?
A
Children often show: • Longer sleep periods • Less REM-related symptoms • Rapid weight gain • Complex cataplexy (e.g., facial slackening, unsteady gait)
9
Q
What is the classic tetrad of narcolepsy symptoms?
A
- Excessive Daytime Sleepiness (EDS) – 100% of cases 2. Cataplexy 3. Sleep paralysis 4. Hypnagogic/hypnopompic hallucinations.
10
Q
Describe the EDS seen in narcolepsy.
A
• Daily and severe • Irresistible sleep episodes, often brief and refreshing • Triggered by inactivity (e.g., driving, lectures) • Causes inattention, poor memory, reduced QoL • Episodes often include dreaming.
11
Q
How does EDS in narcolepsy differ from idiopathic hypersomnia?
A
Narcoleptic naps are brief and refreshing; idiopathic hypersomnia naps are long and unrefreshing.
12
Q
What triggers cataplexy?
A
Strong emotions like laughter, surprise, anger, elation, anticipation.
13
Q
Is awareness preserved during cataplexy?
A
Yes. Patients remain conscious and aware.
14
Q
What are the different forms of cataplexy?
A
• Partial cataplexy: Most common; jaw slackening, head drop, speech slurring • Full cataplexy: Sudden collapse affecting all voluntary muscles • Status cataplecticus: Rare prolonged form; can occur with medication withdrawal.
15
Q
How does cataplexy appear in children?
A
Often presents as: • Generalised hypotonia • Slack jaw, tongue protrusion, unsteady gait • Dyskinetic-like movements. These usually evolve into classic cataplexy over time.
16
Q
What is sleep paralysis?
A
A REM-related symptom where a person feels awake but unable to move or speak, typically occurring at sleep onset or awakening.
17
Q
Is sleep paralysis unique to narcolepsy?
A
No. It occurs in ~7.6% of the general population as an isolated symptom.
18
Q
What are hypnagogic and hypnopompic hallucinations?
A
Vivid, dream-like hallucinations at sleep onset (hypnagogic) or upon waking (hypnopompic), often visual or auditory.
19
Q
How can these hallucinations be misdiagnosed?
A
They may be mistaken for psychosis due to their vivid and disturbing nature.
20
Q
What dream-related phenomena are common in narcolepsy?
A
• Vivid and lucid dreams • Nightmares • Dream delusions (false memories from vivid dreams).
21
Q
How is nocturnal sleep affected in narcolepsy?
A
Fragmented sleep, increased light sleep, frequent awakenings, and higher rates of REM behaviour disorder and periodic limb movements (PLMs).
22
Q
What is the primary neurochemical abnormality in Narcolepsy Type 1?
A
Loss of orexin/hypocretin-producing neurons in the lateral hypothalamus.
23
Q
How do orexin neurons normally function?
A
They are active during wakefulness and suppressed during sleep. They stabilise transitions between sleep and wake states.
24
Q
What happens when orexin is absent or reduced?
A
Individuals cannot maintain stable sleep-wake states. REM sleep intrudes into wakefulness (e.g., cataplexy), and fragmented sleep occurs.
25
What HLA allele is strongly associated with NT1?
HLA DQB1*0602 — present in nearly all NT1 patients.
26
Is HLA typing diagnostic for narcolepsy?
No — it’s associated but not diagnostic. Up to 45% of NT2 patients also carry it.
27
What is the likely mechanism of hypocretin neuron destruction in NT1?
Autoimmune attack, possibly involving T-cell cross-reactivity with influenza antigens (molecular mimicry).
28
What evidence supports an autoimmune basis for NT1?
• Presence of CD4⁺ and CD8⁺ T-cells targeting hypocretin peptides • Association with HLA alleles • Pandemrix (H1N1 vaccine) spike in NT1 cases • Post-mortem findings show hypocretin neuron loss.
29
What neurotransmitters are implicated in narcolepsy beyond hypocretin?
• Cholinergic system: Regulates REM sleep; may be defective in narcolepsy • Monoamines (noradrenaline, serotonin): Modulate REM via cholinergic inhibition.
30
What are orexin’s broader roles in the CNS?
Beyond sleep-wake regulation, orexin influences: • Appetite • Body temperature • Blood pressure • Reward pathways.
31
What has post-mortem research shown in narcoleptic patients?
• Undetectable levels of pre-prohypocretin RNA • Loss of hypocretin-producing neurons in the hypothalamus.
32
What rare genetic finding has been identified in narcolepsy?
A mutation in the hypocretin gene was reported in one patient.
33
What is the link between narcolepsy and influenza vaccination?
In 2009–2010, children/adolescents in Europe developed NT1 soon after receiving the Pandemrix H1N1 vaccine, suggesting a vaccine-triggered autoimmune response.
34
Does narcolepsy present later in life?
Rarely, but there’s a smaller peak in onset around 35–45 years, and some cases even occur in older adults (e.g., cataplexy as first symptom post-60).
35
What are the two core diagnostic pathways for Narcolepsy Type 1 (NT1)?
1. Clinical history of EDS and cataplexy + MSLT showing: • Mean sleep latency ≤ 8 minutes • ≥ 2 SOREMPs 2. Low CSF hypocretin-1 level (≤110 pg/mL).
36
What is required to diagnose Narcolepsy Type 2 (NT2)?
• EDS + MSLT showing: • Mean sleep latency ≤ 8 minutes • ≥ 2 SOREMPs • Normal orexin levels • No cataplexy.
37
What is the role of PSG in diagnosing narcolepsy?
• Rule out other causes of EDS (e.g., OSA, periodic limb movements) • Evaluate sleep efficiency and architecture • Detect nocturnal SOREMPs.
38
What PSG findings are typical in narcolepsy?
• Low sleep efficiency (≤85%) • Fragmented sleep • 40% have significant PLMs • No significant AHI (if OSA ruled out).
39
What does the MSLT assess?
Sleep propensity — how quickly someone falls asleep during 5 nap opportunities across the day.
40
How is the MSLT conducted?
• Five 20-minute nap trials, spaced every 2 hours • Performed the day after a PSG • Monitors time to sleep onset and occurrence of REM.
41
What are the diagnostic criteria on MSLT for narcolepsy?
• Mean sleep latency ≤ 8 minutes • ≥2 SOREMPs (REM within 15 mins of sleep onset).
42
When can MSLT give false positives?
• Sleep restriction • Untreated OSA • Medication effects (esp. withdrawal from REM-suppressing drugs) • Shift workers.
43
When is CSF hypocretin testing used?
• When MSLT is not possible or unreliable • In patients on multiple medications • In children or individuals with unusual symptoms.
44
What CSF hypocretin level supports NT1 diagnosis?
≤110 pg/mL (which is ≤1/3 of normal levels).
45
What is the function of hypocretin?
Maintains wakefulness and regulates REM sleep.
46
What HLA markers are associated with NT1?
HLA DR2 and more specifically DQB1*0602.
47
Is HLA typing diagnostic?
No — it supports the diagnosis but lacks specificity. 45% of NT2 patients may also carry the allele.
48
What should raise suspicion of narcolepsy in young patients?
Severe daytime sleepiness, especially if unresponsive to improved sleep hygiene and not explained by other conditions.
49
What might mislead diagnosis based on SOREMPs alone?
Night/shift work and certain medications can produce false positives.
50
How do Narcolepsy Type 1 and Type 2 differ in terms of orexin levels and clinical features?
• Type 1 (NT1): Characterised by low or absent orexin levels, presence of cataplexy, and ≥2 SOREMPs on MSLT. • Type 2 (NT2): Orexin levels are normal, cataplexy is absent, and ≥2 SOREMPs may be present, though some cases later evolve into NT1. • Both types have mean sleep latency ≤8 minutes, but only NT1 is consistently linked with the HLA DQB1*0602 allele.
51
What are the differences between MSLT, PSG, and CSF hypocretin testing in diagnosing narcolepsy?
• MSLT (Multiple Sleep Latency Test) measures how quickly a person falls asleep and whether they enter REM quickly during the day. It’s the gold-standard objective measure for diagnosing EDS and REM intrusion. • PSG (Polysomnography) is an overnight sleep study used to rule out other sleep disorders like OSA and assess sleep architecture; it’s always performed the night before an MSLT. • CSF Hypocretin Testing involves a lumbar puncture to measure orexin levels. It is diagnostic for NT1 if levels are ≤110 pg/mL and is used when MSLT results are inconclusive or can’t be obtained.
52
What are the main medication classes used to treat narcolepsy?
1. Wake-promoting agents (e.g., modafinil)
2. Stimulants (e.g., amphetamines, methylphenidate)
3. Sodium oxybate
4. Antidepressants (for cataplexy)
53
What is modafinil and how is it used in narcolepsy?
A wakefulness-promoting agent
First-line treatment for EDS in narcolepsy (PBS-listed in Australia)
Typical dose: 200–400 mg/day
54
What are the benefits of modafinil over amphetamines?
* Lower abuse potential
* No rebound hypersomnolence
* Longer half-life with R-modafinil (9–14 hrs)
* Fewer psychiatric side effects
55
What are the side effects and interactions of modafinil?
* Headache, nausea, nervousness
* Induces CYP450 → may reduce effectiveness of oral contraceptives
56
When are stimulants used in narcolepsy?
* Typically second-line, especially for severe EDS
* May be more effective than modafinil but with higher side effect risk
57
How do stimulants work?
Block reuptake of dopamine and other monoamines → increase arousal and alertness
58
Common side effects of stimulants?
Nervousness, irritability, headaches, palpitations, anorexia, insomnia, psychosis
59
What are concerns with stimulant use?
* Abuse potential (though rare)
* Tolerance and rebound effects
60
What is sodium oxybate and how is it used?
* The sodium salt of gamma-hydroxybutyrate (GHB)
* Used to treat cataplexy and improve nighttime sleep
* Can also reduce EDS at higher doses
* Dose: 4.5–9 g nightly in 2 doses (due to short half-life)
61
What are the benefits of sodium oxybate?
* Reduces cataplexy
* Improves nocturnal sleep (↑ SWS and REM)
* May improve daytime alertness at higher doses
62
What are the side effects and limitations of sodium oxybate?
* Dizziness, headaches, transient amnesia
* Abuse potential (is a known ‘date rape’ drug)
* Requires strict dosing and has high cost
* TGA-approved but not PBS-listed
63
Which antidepressants may be used to manage cataplexy?
SSRIs, SNRIs, and TCAs can suppress REM sleep and reduce cataplexy frequency
64
Why are antidepressants used in narcolepsy?
REM suppression helps reduce cataplexy, sleep paralysis, and hypnagogic hallucinations.
65
What behavioural strategies are recommended for narcolepsy management?
* Maintain consistent sleep-wake schedule
* Avoid shift work
* Practise good sleep hygiene
* Schedule short daytime naps (~15–30 min)
* Use caffeine strategically (avoid late in day)
* Avoid prolonged inactivity
* Incorporate daytime physical activity
* Manage stress
* Optimise weight (due to obesity risk)
66
What lifestyle modifications and supports are important in narcolepsy?
* Driving restrictions and fitness-to-drive assessment
* Workplace and school accommodations (e.g., nap breaks, flexible schedules)
* Regular follow-up to monitor symptoms and adjust treatment
* Patient education about the chronic nature of the condition
67
Which treatments target EDS vs. cataplexy?
* **EDS**: Modafinil, amphetamines, sodium oxybate (high dose)
* **Cataplexy**: Sodium oxybate (low dose), antidepressants
68
What is idiopathic hypersomnia (IH)?
A central disorder of hypersomnolence characterised by excessive daytime sleepiness despite adequate or prolonged nighttime sleep, without another identifiable cause (e.g., narcolepsy, OSA).
69
What are the hallmark symptoms of IH?
* Severe, constant daytime sleepiness
* Prolonged, unrefreshing naps
* Difficulty waking (sleep inertia or “sleep drunkenness”)
* Sleep duration often >10 hours in 24 hours
* Long and deep nocturnal sleep
* Autonomic dysfunction in some (headaches, temperature dysregulation, orthostatic issues)
70
How do naps in IH differ from those in narcolepsy?
IH naps are long and unrefreshing, while narcoleptic naps are short and restorative.
71
What is the prevalence of IH?
Seen in 1–10% of patients presenting to sleep clinics for EDS.
72
How is IH diagnosed?
* Clinical history of EDS
* PSG showing high sleep efficiency and long TST (>660 mins)
* MSLT with mean sleep latency ≤8 mins and 0–1 SOREMPs
* Rule out other causes: OSA, narcolepsy, psychiatric disorders, medications
73
What are the PSG findings in IH?
* Normal architecture
* Decreased latency to sleep
* TST >660 mins
* High sleep efficiency (>90%)
74
What are the MSLT findings in IH?
* Mean sleep latency ≤8 mins
* *Fewer than 2* SOREMPs
(*SOREMPs are a key differentiator from narcolepsy*)
75
What are the key differences between IH and Narcolepsy Type 1/2?
**Cataplexy**: Present only in NT1
* **Orexin**: Low in NT1; normal in IH
* **SOREMPs**: ≥2 in narcolepsy; 0–1 in IH
* **Sleep duration**: Often prolonged in IH (>10 hrs)
* **Naps**: Refreshing in narcolepsy; unrefreshing in IH
* **REM Intrusions**: Common in narcolepsy (hallucinations, sleep paralysis); rare in IH
* **Hypocretin testing**: Abnormal only in NT1
* **Dream delusions**: More common in narcolepsy
76
What comorbid conditions are common in IH?
* Autonomic symptoms (Raynaud’s, temperature dysregulation)
* Headaches
* Potential viral onset in some cases
* Psychiatric symptoms like depression and anxiety (as in narcolepsy)
77
Can IH resolve spontaneously?
Yes — spontaneous remission is reported in up to 14% of cases.
78
Is histamine implicated in IH?
Possibly — low CSF histamine levels have been reported, but findings remain controversial.
79
What psychiatric comorbidities are common in narcolepsy?
* Depression
* Anxiety
* Obsessive-compulsive disorder
* Rarely: psychosis
* ADHD-like symptoms (especially in children and adolescents)
80
Are ADHD symptoms in narcolepsy purely due to sleepiness?
No — even after treating EDS, many patients show persistent executive dysfunction, suggesting intrinsic neurocognitive deficits.
81
What sleep-related comorbidities are common in narcolepsy?
* REM Sleep Behaviour Disorder (20–60%)
* Periodic Limb Movements of Sleep (PLMS) – ≥15/hour in 10%
* Disrupted nocturnal sleep with frequent awakenings
82
What autonomic dysfunctions are reported in NT1?
* Blunted heart rate response to arousals
* Lack of normal nocturnal BP dip (nondipping pattern)
* Possible contribution to metabolic issues
83
How does narcolepsy affect day-to-day functioning?
* Impaired academic and occupational performance
* Memory lapses and inattention
* Frequent, unwanted sleep episodes
* Emotional distress due to cataplexy and hallucinations
* Social withdrawal due to unpredictability of symptoms
84
How can narcolepsy affect driving and employment?
* Increased risk of motor vehicle accidents (MVA)
* Driving restrictions may be required
* Job dismissal, early retirement, and work disability are more common
* Sleepiness during work hours affects productivity and safety
85
What was the result of the large US study on narcolepsy burden (n=55,871)?
* Higher healthcare utilisation and medical costs
* Increased rates of disability leave
* Greater personal and economic impact than matched controls
86
What school or workplace accommodations might patients with narcolepsy need?
* Scheduled nap breaks
* Flexibility with start/end times
* Movement breaks
* Avoiding prolonged sedentary tasks
* Time allowances for memory/attention lapses
87
Why is narcolepsy often underdiagnosed or misdiagnosed?
* EDS is a nonspecific symptom often attributed to lifestyle
* Symptoms like hallucinations and paralysis may be mistaken for psychiatric illness
* Cataplexy may be overlooked if partial or mistaken for clumsiness
* Lack of awareness among general practitioners
88
What symptom is unique to narcolepsy and helps distinguish it from other conditions?
Cataplexy
89
How is sleepiness defined physiologically?
Sleepiness is a multicausal physiological need state, not simply a symptom. It represents a drive to sleep and is influenced by homeostatic, circadian, and neurobiological factors.
90
How did the scientific view of sleepiness evolve?
In the 1960s, EDS began to be recognised as a legitimate, measurable, and medically important symptom — not just laziness or narcolepsy.
91
What are the main determinants of sleepiness?
1. Quantity and quality of prior sleep
2. Circadian phase
3. Central nervous system disorders or dysfunction
4. Sleep fragmentation or interruption
5. Neurochemical signalling (e.g., adenosine, GABA, dopamine, orexin)
92
What brain regions are involved in sleep-wake regulation and alertness?
* **Ascending reticular activating system (ARAS)**
* **Hypothalamus** (lateral and ventrolateral preoptic areas)
* **Basal forebrain**
* **Thalamus**
* **Brainstem nuclei**
* **Cerebral cortex** (for subjective perception and responsiveness)
93
What role does the hypothalamus play in sleepiness?
It integrates circadian and homeostatic signals and regulates transitions between sleep and wake via orexin and VLPO-mediated GABA release.
94
Which neurotransmitters promote wakefulness?
* Dopamine
* Noradrenaline
* Histamine
* Acetylcholine
* Orexin (hypocretin)
95
Which neurotransmitters promote sleep or suppress wakefulness?
* GABA
* Adenosine
* Serotonin (in some contexts)
* Melatonin (circadian signal)
96
What is the role of adenosine in sleepiness?
Adenosine accumulates during wakefulness and promotes sleep drive by inhibiting wake-active neurons. Caffeine promotes alertness by blocking adenosine receptors.
97
What is the function of orexin in regulating alertness?
Orexin stabilises wakefulness by activating wake-promoting systems. Its absence leads to narcolepsy with REM intrusion (NT1).
98
How do homeostatic and circadian processes interact to regulate sleepiness?
* **Homeostatic sleep drive** increases the longer you’re awake.
* **Circadian rhythms** modulate alertness independent of sleep need, with dips (e.g., early afternoon) and peaks (late morning, early evening).
99
When is sleepiness most likely to occur based on circadian phase?
* Early morning (e.g., ~3–6 a.m.)
* Early afternoon (post-lunch dip)
100
Can monotony cause sleepiness?
No — it can unmask latent sleepiness but is not a cause. True physiological sleepiness results from underlying biological processes.
101
What is the most widely used subjective scale for measuring sleepiness?
The Epworth Sleepiness Scale (ESS)
102
What does the Epworth Sleepiness Scale assess?
A person’s likelihood of dozing in eight routine daytime situations (e.g., watching TV, sitting in traffic), rated 0–3 for each; total score 0–24.
103
What ESS score indicates clinically significant sleepiness?
* **>10** is considered abnormally sleepy
* **>15** suggests severe EDS
104
What does the MSLT measure?
* **Mean sleep latency** (how quickly one falls asleep)
* **Number of SOREMPs** (sleep-onset REM periods)
105
How is the MSLT conducted?
* 5 nap opportunities, 2 hours apart
* Each nap lasts 20 minutes unless sleep occurs
* Performed after a full overnight PSG to rule out other causes
106
What MSLT results indicate abnormal sleepiness?
* **Mean sleep latency ≤8 minutes**
* **≥2 SOREMPs** suggests narcolepsy
* **0–1 SOREMPs** with short latency suggests IH
107
Limitations of MSLT?
* Doesn’t reflect real-world functioning
* Can produce false positives (e.g., sleep restriction, medication withdrawal)
* Doesn’t assess ability to resist sleep
108
What does the MWT measure?
Ability to stay awake in a quiet, non-stimulating environment — i.e., behavioural alertness.
109
How is the MWT different from MSLT?
* MWT assesses **resistance to sleep**, not sleep propensity
* Better suited to assessing **real-world safety** (e.g., fitness to drive)
110
When is the MWT used clinically?
* Assessing treatment response (e.g., to modafinil)
* Legal/occupational evaluations (e.g., pilots, drivers)
* Determining fitness to drive
111
What MWT result indicates normal wakefulness?
Ability to stay awake for ≥40 minutes on 4 trials is generally considered normal.
112
What are some emerging or alternative ways of assessing sleepiness?
* **Psychomotor vigilance testing (PVT)**: reaction time to visual stimuli
* **EEG and pupillometry**: physiological correlates of alertness
* **Actigraphy + subjective scales**: used in field settings
113
Why is sleepiness assessment important beyond diagnosis?
To monitor treatment response, assess functional capacity, and ensure safety (e.g., driving).
114
Why is excessive daytime sleepiness (EDS) considered a public health issue?
* It impairs performance, alertness, and reaction time
* Increases risk of accidents (esp. driving & workplace injuries)
* Reduces quality of life and functional capacity
* Carries significant economic costs (e.g., absenteeism, healthcare usage)
115
What real-world domains are most affected by sleepiness?
* **Occupational performance**
* **Driving and transport safety**
* **Academic performance**
* **Cognitive function (attention, memory, decision-making)**
* **Social and emotional functioning**
116
How does EDS impact psychosocial wellbeing?
* Contributes to low mood, irritability, and frustration
* Can lead to social withdrawal and relationship strain
* Associated with psychiatric conditions like depression and anxiety
117
What are the occupational consequences of untreated sleepiness?
* Reduced productivity and efficiency
* Increased errors and risk of injury
* Absenteeism and presenteeism
* Higher rates of disability claims and job loss
118
How does sleepiness compare to alcohol in terms of impairment?
Being awake for 18–24 hours can impair driving performance to a degree equivalent to a BAC of 0.05–0.10%.
119
What professions are at higher risk due to sleepiness?
* Shift workers
* Healthcare professionals
* Transport operators (pilots, truck drivers)
* Machine operators
* Students (due to sleep restriction and irregular schedules)
120
What cognitive functions are impaired by sleepiness?
* Attention and vigilance
* Working memory
* Executive function and decision-making
* Reaction time
121
Q: Does sleepiness impair performance uniformly across tasks?
No — monotonous, low-stimulation tasks (e.g., driving, surveillance) are affected the most.
122
What are the chronic effects of long-term EDS if untreated?
* Increased risk of depression and anxiety
* Diminished QoL and wellbeing
* Strained interpersonal relationships
* Occupational instability
* Higher healthcare use and medical costs
123
What population-wide strategies can reduce the burden of sleepiness?
* Public education about sleep hygiene and circadian health
* Screening and treatment of sleep disorders
* Workplace fatigue management programs
* Regulation of shift work and transport industry safety
124
What is the difference between sleepiness and fatigue?
* **Sleepiness**: A physiological drive to sleep; involves the tendency to fall asleep
* **Fatigue**: A subjective lack of energy or mental/physical exhaustion without necessarily feeling sleepy
125
How do patients describe fatigue vs. sleepiness?
* **Fatigue**: “Drained”, “exhausted”, “burned out”
* **Sleepiness**: “Can’t keep my eyes open”, “nodding off”, “dozing during the day”
126
Why is it clinically important to differentiate sleepiness from fatigue?
* They have different causes and treatment pathways
* Fatigue may stem from anaemia, depression, chronic illness, or deconditioning
* Sleepiness points more toward sleep disorders or circadian misalignment
127
What can help clarify the distinction during clinical history taking?
* Ask about *dozing off* vs. *feeling tired*
* Inquire about **refreshment after naps** (usually not seen in fatigue)
* Use validated scales like ESS (sleepiness) or fatigue-specific questionnaires
128
What should a clinical assessment of EDS include?
1. Detailed sleep history (duration, timing, quality)
2. Work schedule and shift patterns
3. Medication, substance use (incl. caffeine, alcohol, sedatives)
4. Mood and psychiatric history
5. Use of standardised tools (e.g., ESS, sleep diaries)
6. Possible need for objective tests (MSLT, PSG)
129
When should you refer a patient for objective testing (MSLT/PSG)?
* When symptoms persist despite adequate sleep
* If narcolepsy, idiopathic hypersomnia, or other central hypersomnolence is suspected
* If EDS interferes with safety, work, or quality of life
130
What are red flags that suggest true pathological sleepiness?
* Sleep attacks during active situations
* Involuntary dozing while driving, eating, or in conversation
* History of vivid hallucinations or cataplexy-like symptoms
* ESS score >15
131
What are the three major contributors to excessive sleepiness?
1. **Sleep restriction or fragmentation**
2. **Circadian misalignment**
3. **Pathologic CNS conditions (e.g., narcolepsy)**
132
What makes sleepiness a distinct and measurable physiological state?
* It involves identifiable neurochemical changes (e.g., adenosine, GABA, orexin)
* It can be objectively measured (e.g., MSLT, MWT)
* It has clear behavioural and performance correlates
133
Why must sleepiness be taken seriously in clinical care?
* It’s a symptom with significant safety, psychiatric, and functional consequences
* Underlying causes are often treatable
* Misdiagnosis (e.g., confusing with fatigue) delays intervention and support
134
What sleep disorder is most commonly confused with IH?
Narcolepsy, particularly NT2 (without cataplexy) — due to overlapping symptoms like EDS and long naps .
135
How can IH be differentiated from Narcolepsy Type 1 (NT1)?
* NT1 usually has **cataplexy**, **≥2 SOREMPs**, and **low/absent CSF hypocretin-1**
* IH often shows **long sleep times**, **sleep inertia**, **high sleep efficiency**, and **0–1 SOREMPs**
136
What role does CSF hypocretin-1 play in distinguishing IH from narcolepsy?
* **Normal in 100%** of IH patients
* **Low in NT1**; may be low in NT2 if symptoms evolve
* Low CSF hypocretin reclassifies patients to NT1 under ICSD-3
137
What other conditions must be ruled out before diagnosing IH?
* **Sleep-disordered breathing** (e.g., UARS)
* **Insufficient sleep syndrome**
* **Medication effects**
* **Depression/psychiatric disorders**
* **Delayed sleep-wake phase disorder**
* **Other neurologic/metabolic disorders**
138
What is Kleine-Levin Syndrome (KLS)?
A rare, relapsing-remitting disorder characterised by recurrent episodes of severe hypersomnia, cognitive dysfunction, derealisation, and behavioural changes
139
What is the typical clinical presentation of KLS?
* Mostly **adolescent males**
* Sudden episodes of **18–20 hours sleep/day**, lasting 1–3 weeks
* **Mutism**, derealisation, disinhibited or childlike behaviour
* **Hyperphagia/hypersexuality** in some
* Complete recovery between episodes
140
What are the diagnostic criteria for KLS?
* ≥2 recurrent hypersomnia episodes (2 days–5 weeks)
* Return to normal between episodes
* At least one of: cognitive dysfunction, altered perception, eating disorder, disinhibited behaviour
* Not better explained by other sleep/medical/psychiatric conditions
141
How is KLS monitored?
* **Emergency sleep studies** during episodes
* **24–48hr EEG/PSG + behavioural observations**
* Report total sleep time, inappropriate behaviours, demeanour
142
What is known about the cause of KLS?
Unclear — but autoimmune, genetic, and metabolic theories exist. Brain imaging often shows hypoperfusion in the parietotemporal and hypothalamic areas
143
How common are sleep-wake disturbances after TBI?
* **73%** in subacute TBI
* **52%** in chronic TBI (2+ years post-injury)
* Most common issues: **EDS**, **hypersomnia**, **insomnia**, **fatigue**
144
What distinguishes sleep problems in subacute vs. chronic TBI?
* Subacute: **insomnia** most common
* Chronic: **EDS and hypersomnia** dominate
145
What is posttraumatic hypersomnia?
The need for 2+ extra hours of sleep per day compared to baseline, not explained by another disorder
146
Why are sleep-wake disturbances often missed in TBI patients?
TBI survivors often underestimate their sleep symptoms. Objective assessments (e.g., MSLT, actigraphy) are more reliable
147
What causes posttraumatic sleep-wake disturbances?
* Multifactorial: direct brain injury, secondary complications, circadian disruption, psychiatric comorbidities
* Up to **43%** have **no identifiable cause**, suggesting a **primary neurologic** basis
148
What are long-term outcomes associated with sleep issues post-TBI?
* Reduced **rehabilitation outcomes**
* Increased **psychiatric comorbidity**
* Persisting symptoms (e.g., fatigue, EDS) **3+ years** post-injury
149
Are circadian rhythm disturbances seen post-TBI?
Yes — includes delayed sleep phase and irregular sleep-wake rhythm; reduced melatonin output has been documented
150
Is there a standard treatment protocol for KLS?
No. There is no established treatment, but some interventions show class IV evidence for benefit.
151
What pharmacological treatments have shown some efficacy in KLS?
* **Lithium**: May reduce episode frequency in patients with frequent episodes (>4/year)
* **IV corticosteroids**: May reduce duration of prolonged episodes (>30 days)
* **Estrogen-progesterone**: May help in menstrual-related KLS (limited data)
* **Antiepileptics & antidepressants**: Not shown to be effective
152
What is the general management approach during KLS episodes?
* Allow the patient to sleep in a **familiar home environment**
* **Avoid hospitalisation** unless necessary, to reduce anxiety
* Educate families not to forcibly awaken or stimulate the patient
* **Prohibit driving** during episodes due to altered perception and risk of accidents
* Support and reassure families, document episodes via diaries or video
153
What risks are associated with lithium therapy?
* **Thyroid and renal toxicity**
* Requires monitoring of serum lithium, TSH, and creatinine
* May be tapered after several years of sustained benefit or after age 30
154
What is the presumed cause of KLS?
Unknown, but evidence supports:
* **Autoimmune origin**
* **Genetic predisposition**
* Possibly a **localized recurrent encephalitis**
155
What brain areas are affected in KLS according to imaging studies?
* Hypoperfusion in **parietotemporal** and **mesiotemporal associative cortices**
* During episodes: ↓ activity in **right dorsomedial prefrontal cortex** and **right parietotemporal junction**
* Some correlation with **derealisation severity**
156
What histopathologic findings support a neuroinflammatory process in KLS?
* **Perivascular lymphocytes** in hypothalamus, amygdala, thalamus, temporal lobes, midbrain
* In some cases: reduced pigmentation in substantia nigra, smaller locus coeruleus
* Supports theory of **mild, localized encephalitis**
157
Is there evidence for autoimmune involvement in KLS?
* Onset often follows **infection**, **head trauma**, or **alcohol use**
* Partial benefit from **IV steroids**
* No confirmed **HLA associations** or specific autoantibodies
* Some cases may involve **reversible CSF hypocretin-1** or histamine changes
158
Are there known genetic risk factors for KLS?
* Rare familial cases (~8%)
* Variants in **LMOD3** and **TRANK1** genes have been found
* No clear monogenic cause; likely **polygenic susceptibility**
159
What must be ruled out before diagnosing KLS?
* **Acute confusional states** in teenagers
* **Substance intoxication** or withdrawal
* **Tumours** (e.g., colloid cysts, craniopharyngiomas)
* **Encephalitis**, **seizures**, **autoimmune disease**
* **Basilar migraine**, **porphyria**, **inborn errors of metabolism**
* **Bipolar disorder**, **seasonal affective disorder**, and other psychiatric illness
160
What tests help exclude other causes in suspected KLS?
* **EEG** (to exclude seizure activity; may show nonspecific slowing in KLS)
* **MRI** or **CT** (to rule out mass lesions or stroke)
* Blood tests: serum ammonia, B12, pyruvate, lactate
* Consider **spinal tap** if febrile, to exclude CNS infection
* Psychiatric assessment to rule out mood disorders
161
How can KLS be differentiated from psychiatric disorders?
* Episodes are **stereotyped**, **abrupt**, and **followed by full recovery**
* Sleep duration and **derealisation** are **much more pronounced** in KLS
* Brain imaging may show characteristic **hypoperfusion patterns**
* Family and patient history (e.g., amnesia, altered speech, out-of-character behaviour) is key
162
What are the proposed mechanisms of posttraumatic sleep-wake disturbance?
* Direct injury to **sleep-wake regulation centres** (hypothalamus, brainstem)
* **Secondary effects** (swelling, hypoxia, neuroinflammation, pain)
* Disruption of **neurotransmitter systems** (e.g., orexin, dopamine, histamine)
* **Hypocretin neuron damage** → possible transient narcolepsy phenotype
163
What brain structures are commonly affected in TBI-related hypersomnia?
Hypothalamus, midbrain, and thalamus – especially areas involved in arousal and circadian regulation
164
What is the general treatment approach to posttraumatic sleep-wake disorders?
* **Multidisciplinary**: sleep specialists, neurologists, rehab
* **Treat comorbidities** (pain, depression, insomnia)
* **Behavioural strategies**: sleep hygiene, routine
* **Pharmacologic support** (e.g., modafinil for EDS/hypersomnia, melatonin for circadian disruption)
165
Is modafinil effective for posttraumatic hypersomnia or EDS?
May improve alertness, but evidence is limited and variable. Should be tailored to individual cases.
166
What role does melatonin play post-TBI?
May help with circadian rhythm realignment, especially if melatonin secretion is impaired
167
What conditions must be ruled out before diagnosing posttraumatic hypersomnia or EDS?
* **Obstructive sleep apnoea**
* **Insufficient sleep syndrome**
* **Depression or anxiety**
* **Medication effects** (sedatives, opioids)
* **Secondary narcolepsy** (if cataplexy, hallucinations, SOREMPs present)
168
What term has been proposed to describe prolonged sleep post-TBI without EDS?
Pleiosomnia – ≥2 hrs more sleep than pre-TBI baseline without subjective sleepiness
169
Can TBI cause secondary narcolepsy?
Rarely. Typically lacks classic cataplexy, but may show SOREMPs and low hypocretin due to hypothalamic damage
170
What circadian disorders are reported after TBI?
* **Delayed sleep-wake phase disorder**
* **Irregular sleep-wake rhythm**
* Occurs in **up to 36%** of TBI patients with insomnia complaints
* Often associated with **blunted or delayed melatonin secretion**
171
How can circadian disorders be diagnosed post-TBI?
* **Actigraphy**
* **Salivary melatonin rhythms**
* **Core body temperature** tracking
172
What is the relationship between TBI and sleep misperception?
Patients frequently underestimate sleep duration and fail to report hypersomnia/EDS. Objective tools (e.g., actigraphy, MSLT) are essential
173
What’s the impact of sleep-wake disorders on TBI recovery?
* Poorer **rehabilitation outcomes**
* Longer hospital stays
* Worse **cognitive performance, mood, and fatigue**
* Decreased **quality of life** and **functional independence**
174
What comorbid symptoms exacerbate sleep issues post-TBI?
Pain, anxiety, PTSD, and depression — all worsen sleep and increase disability risk
175
What are emerging biomarkers for sleepiness being researched?
These include:
* Molecular markers (e.g., blood, urine, saliva proteins)
* Genetic targets (e.g., gene expression post-wake)
* Proteomic responses to homeostatic sleep pressure
* Wearables capturing **accelerometry** and **light exposure**
* PVT-based reaction time as a behavioural biomarker
However, none are clinically validated yet
176
What are dream delusions in narcolepsy?
Dream delusions are false memories formed from vivid or lucid dreams that are misinterpreted as real experiences. They’re more common in narcolepsy due to REM intrusion and dream realism, and may lead to confusion or mistaken beliefs about events.
177
What role does the histaminergic system play in sleep-wake regulation?
Histamine is a CNS arousal-promoting neurotransmitter. Its activity helps maintain wakefulness, and low histaminergic tone may contribute to excessive sleepiness.
178
What is the relevance of H3 antagonists in narcolepsy treatment?
H3 receptor antagonists/inverse agonists (e.g., pitolisant) increase histamine release by blocking presynaptic inhibition. They represent an emerging class of wake-promoting agents for narcolepsy and other hypersomnias, especially where stimulants are contraindicated.
179
What is sleep inertia and how is it associated with idiopathic hypersomnia (IH)?
Sleep inertia refers to prolonged grogginess, disorientation, and cognitive sluggishness upon waking. It is a hallmark of IH and may last minutes to hours. Unlike narcolepsy, patients with IH often find waking extremely difficult and naps unrefreshing.
180
How common is insomnia after TBI?
Prevalence varies widely (5–70%) due to differences in definitions and methods. It’s often over-reported subjectively and under-detected by PSG
181
What contributes to insomnia after TBI?
Pain, anxiety, depression, dizziness, PTSD, and poor sleep hygiene.
182
What are the functional consequences of post-TBI insomnia?
Worsened attention, headaches, fatigue, impaired rehab, increased disability risk.
183
What parasomnias are seen after TBI?
* Hypnagogic hallucinations (53%)
* Sleep paralysis (15%)
* REM sleep behaviour disorder (up to 9%)
* Nightmares (up to 41%)
* Nocturnal eating, sleepwalking, and enuresis in some patients
All suggest trauma to sleep-regulating brain circuits.
184
How is dreaming affected post-TBI?
* Decreased or absent dream recall early post-injury
* Reduced vividness and frequency even during recovery
* Increased nightmares later, which may worsen sleep fragmentation
185
Which movement disorders may emerge post-TBI?
* **Bruxism** (jaw clenching) – may contribute to post-traumatic headache
* **Restless Legs Syndrome (RLS)** – appears pre-existing in most cases
* **PLMS** – unclear if incidence increases; more common in spinal cord injury patients
186
What are the key findings in paediatric TBI sleep research?
* Few studies exist, but show **persistent sleep disruption up to 2 years**
* Includes prolonged sleep onset, poor sleep maintenance, and reduced efficiency
* Parental report often reveals issues even when children don’t self-report
* Sleep problems worsen functional outcomes and learning
187
What is the primary purpose of the Multiple Sleep Latency Test (MSLT)?
To objectively measure daytime sleepiness and support diagnoses such as narcolepsy or idiopathic hypersomnia.
188
What two main outcomes does the MSLT report?
1. Mean Sleep Latency (MSL)
2. Number of Sleep Onset REM Periods (SOREMPs)
189
What are the protocol requirements before conducting an MSLT?
• Nocturnal PSG with ≥6 hours sleep
• Sleep diary and/or actigraphy for 2 weeks
• Withdrawal of REM-affecting medications for 2+ weeks
• No caffeine or stimulants on test day
• Urine drug screen if needed
190
How many naps are conducted during an MSLT and at what intervals?
Five nap opportunities are offered, spaced every 2 hours, beginning 1.5 to 3 hours after PSG wake-up.
191
When is an MSLT nap trial terminated?
1. After 20 minutes if no sleep occurs.
2. If sleep occurs, continue monitoring for 15 minutes to detect REM sleep.
192
Define a Sleep Onset REM Period (SOREMP).
REM sleep occurring within 15 minutes (clock time) after sleep onset.
193
What is the diagnostic criteria for narcolepsy type 1 using MSLT/PSG?
MSL ≤ 8 minutes and ≥2 SOREMPs (can include PSG SOREMP) + cataplexy or low CSF hypocretin-1.
194
What is the diagnostic criteria for narcolepsy type 2?
MSL ≤ 8 minutes and ≥2 SOREMPs without cataplexy. Other causes of sleepiness must be excluded.
195
What are common causes of false-positive MSLT results?
• Shift work
• Circadian delay
• Recent REM-suppressant withdrawal
• Inadequate sleep
• Untreated OSA
196
List the standard subjective measures of daytime sleepiness.
• Stanford Sleepiness Scale
• Epworth Sleepiness Scale (ESS)
• Karolinska Sleepiness Scale
197
What is the difference between the MSLT and the MWT?
MSLT assesses ability to fall asleep; MWT assesses ability to stay awake in boring conditions.
198
What is the standard procedure for a Maintenance of Wakefulness Test (MWT)?
Four 40-minute trials every 2 hours. Patient remains awake in a semi-upright position in a dimly lit room.
199
What sleep onset criteria ends an MWT trial early?
Three epochs of stage 1 sleep or one epoch of any other stage ends the trial before 40 minutes.
200
What factors influence mean sleep latency (MSL) on MSLT?
• Age
• Sleep deprivation
• Circadian rhythm
• Stimulants/sedatives
• Nap number (shortest latency in nap 3 or 4)
201
What MSL values indicate severity of sleepiness?
<5 min = Severe
5–10 min = Moderate
10–15 min = Mild
>15 min = Normal
202
What are common causes of SOREMPs besides narcolepsy?
• Depression
• Untreated OSA
• Shift work
• Delayed Sleep-Wake Phase Disorder
• REM-rebound after drug withdrawal
203
What is the significance of documenting a SOREMP on the PSG prior to MSLT?
A SOREMP on PSG can substitute for one of the two required SOREMPs in diagnosing narcolepsy (especially NT1).
204
What is the role of actigraphy before an MSLT?
Actigraphy documents sleep duration and regularity for 1–2 weeks prior and helps confirm adequate sleep before testing.
205
Why should the MSLT not follow a split night or CPAP titration study?
Because sleep deprivation or altered sleep architecture may affect results, making the MSLT unreliable.
206
What are key clinical documentation elements accompanying an MSLT?
• Patient perception of sleep
• Technologist observations
• 2-week sleep diary
• PSG results
• Urine drug screen
• Medication changes
207
What substances can confound MSLT results if not discontinued?
• Stimulants
• Sedatives
• THC/marijuana
• SSRIs, SNRIs, TCAs (REM suppressants)
208
What does the ICSD-3-TR say about diagnosing NT1 without PSG/MSLT?
If cataplexy is present and CSF hypocretin-1 is low, PSG/MSLT is not required to confirm NT1.
209
What pattern of SOREMP onset is typical in NT1 vs idiopathic hypersomnia?
NT1 SOREMPs tend to arise from stage N1; in hypersomnia or insufficient sleep, SOREMPs often arise from stage N2.
210
What is the typical distribution of SOREMPs across MSLT naps?
SOREMPs are most common in naps 1–3, particularly nap 2; least likely in nap 4.
211
When is repeating an MSLT recommended?
When initial study has ambiguous results, inadequate conditions, or strong clinical suspicion persists despite negative results.
212
What is the recommendation for number of naps in an MSLT?
Five naps are recommended, especially if MSL is 5–10 min or if there is only one SOREMP including PSG.
213
What are the components of a standard MSLT report?
• Summary of history
• Medications and changes
• PSG findings
• Sleep diary and drug screen
• Results of each nap
• MSL and SOREMP count
• Diagnostic impression
214
What are FDA-approved treatments for residual sleepiness in OSA?
Alerting agents such as modafinil, solriamfetol, and pitolisant (note: stimulants also used off-label).
215
Why must patients be out of bed between MSLT naps?
To prevent inadvertent napping, which would invalidate the test results.
216
What is the minimal total sleep time (TST) required on the PSG for MSLT to be valid?
360 minutes (6 hours).
217
What finding during PSG suggests prior sleep restriction?
High sleep efficiency and high percentage of REM sleep.
218
How is sustained sleep latency defined, and how does it help in diagnosis?
Time to three epochs of stage 1 or one epoch of any other stage; shorter sustained latency is more specific to narcolepsy.
219
What is the significance of a high REM percentage and short REM latency on PSG before MSLT?
It may suggest prior sleep restriction or sleep deprivation, which can lead to false-positive MSLT results.
220
Why is the MSLT not suitable for shift workers?
Because circadian misalignment may mimic narcolepsy, resulting in false-positive findings (short MSL, SOREMPs).
221
In the diagnosis of NT2, what must be ruled out in addition to cataplexy?
Insufficient sleep, untreated OSA, medication effects, psychiatric conditions, and circadian rhythm disorders.
222
How is cataplexy defined in NT1 diagnosis?
Brief, emotionally triggered loss of muscle tone with bilateral involvement, typically lasting under 2–3 minutes.
223
What is the role of HLA-DQB1*06:02 in narcolepsy diagnosis?
It supports a diagnosis of NT1 when combined with cataplexy; nearly all NT1 patients are HLA-positive.
224
What MSLT finding strongly supports NT1 when cataplexy is also present?
A SOREMP on PSG alone is sufficient to diagnose NT1 when cataplexy is present.
225
What PSG/MSLT pattern is common in patients misdiagnosed with narcolepsy due to sleep deprivation?
High sleep efficiency, high REM %, short sleep latency, and multiple SOREMPs due to prior sleep debt.
226
How does the MSLT help differentiate idiopathic hypersomnia from narcolepsy?
Idiopathic hypersomnia often lacks SOREMPs and shows longer, variable sleep latencies with fragmented sleep.
227
What is the implication of REM sleep onset via stage N2 instead of N1 on MSLT?
It suggests the SOREMP is more likely due to insufficient sleep or hypersomnia than narcolepsy.
228
What is the typical sleep stage progression into REM for narcolepsy patients?
REM sleep often occurs directly from wakefulness or stage N1 in narcolepsy, especially NT1.
229
What adolescent-specific factors complicate MSLT interpretation?
Delayed sleep phase and higher likelihood of SOREMPs in early naps can mimic narcolepsy.
230
What is the specificity of ≥3 SOREMPs on MSLT for narcolepsy?
Very high—indicates strong likelihood of narcolepsy, especially NT1.
231
Why should actigraphy include weekends before MSLT?
To capture variability in sleep patterns and confirm consistency of adequate sleep duration.
232
What is the role of audiovisual recording during MSLT?
Required during nap trials to confirm behavior and support scoring; recordings between naps are optional.
233
In what situation is the MSLT result insufficient to diagnose NT2?
When SOREMPs and low MSL are present but insufficient sleep, medication, or psychiatric factors are not excluded.
234
What is the purpose of biocalibration before each MSLT nap?
To ensure accurate signal quality for EEG, EOG, and EMG channels before lights out.
235
What are the sensitivity and specificity ranges of the MSLT for diagnosing narcolepsy?
Sensitivity ranges from 78–92%; specificity from 71–95%, with better accuracy for NT1 than NT2.
236
What are common causes of false-positive MSLT findings?
Sleep deprivation, shift work, recent withdrawal of REM-suppressing medications, or delayed sleep phase disorder.
237
What are common causes of false-negative MSLT results?
Use of REM-suppressing medications, stimulants, anxiety, noise, or suboptimal test timing.
238
In a clinical case, what features led to misdiagnosis of narcolepsy in a new parent?
High REM %, high sleep efficiency, short MSL, and 2 SOREMPs due to chronic sleep deprivation during postpartum care.
239
What MSLT/PSG findings supported a diagnosis of narcolepsy despite treated OSA?
3 SOREMPs on MSLT with MSL of 2.5 minutes despite 60/60 days of CPAP use with good adherence and normal AHI.
240
How should patients with persistent sleepiness despite treated OSA be evaluated?
Repeat PSG on CPAP followed by MSLT on CPAP to rule out comorbid narcolepsy.
241
What finding during PSG suggests a risk for MSLT misinterpretation due to sleep restriction?
REM % >25% and sleep efficiency >95% may indicate prior sleep deprivation.
242
What MSLT patterns are commonly misinterpreted in adolescents?
SOREMPs in naps 1–2 due to delayed sleep phase, not narcolepsy; interpretation should consider sleep schedule.
243
How does age affect MSL and SOREMP prevalence?
MSL tends to increase with age; adolescents may show more SOREMPs early in the day due to circadian factors.
244
What is the clinical significance of ≥3 SOREMPs on MSLT?
Very high specificity for narcolepsy, especially NT1.
245
What minimum total sleep time is required on PSG for valid MSLT interpretation?
360 minutes (6 hours) of recorded sleep on PSG.
246
When is a fifth MSLT nap recommended?
If average MSL after 4 naps is 5–10 minutes or if only one SOREMP (including PSG) has occurred.
247
What is the recommended procedure for handling alerting medications before an MSLT?
Withdraw for ≥2 weeks; taper gradually to avoid rebound effects; consider half-life (e.g., fluoxetine may need 6 weeks).
248
What is the threshold for increased accident risk based on MWT latency?
A mean sleep latency <19 minutes on MWT correlates with a fivefold increased accident risk.
249
What factors must be ruled out before diagnosing NT2 with MSLT?
Insufficient sleep, psychiatric disorders, medications, circadian misalignment, and untreated OSA.
250
How is a nocturnal SOREMP used in narcolepsy diagnosis?
Can replace one MSLT SOREMP in diagnosing NT1; highly specific when present.
