Migraine and sleep have a complex relationship, as inadequate sleep can trigger migraine attacks while adequate sleep plays a therapeutic role. Their pathophysiology is linked, as both involve the hypothalamus and common signaling molecules like serotonin and dopamine. Disorders like insomnia, obstructive sleep apnea, bruxism, and restless legs syndrome frequently coincide with migraine due to shared risk factors and pathophysiology. Maintaining adequate sleep is important for migraine management as it allows the brain's glymphatic system to remove waste and prevents trigger buildup.

1. MIGRAINE & SLEEP

2. INTRODUCTION
 Migraine and sleep - a complex relationship
 Inadequate sleep – trigger for migraine attack
 Adequate sleep – can have a therapeutic role in migraine
 Common pathophysiology is suggested by
 Anatomic localization (hypothalamus)
 Common mediating signaling molecules (serotonin and dopamine)
 CNS waste removal (glymphatic system)
 Treatment with medication having sedative effect – may be necessary
Neurology 2016;87:309–313.
Headache. 2018 July ; 58(7): 1030–1039

3. WHY WE SLEEP? - SLEEP MECHANISM
 Sleep performs restorative role
 Helps in eliminating brain waste build up during day course
 Hypothalamus - the key player
 Sleep induction: Hypothalamus abruptly shut off the augmentation of
wakefulness pathways and simultaneously turn on sleep promoting pathways
by sending inhibitory output to arousal pathways
Chest 2015;147:1179–1192.
Nature 2005;437:1257–1263

4. PHYSIOLOGICAL CHANGES DURING SLEEP
 Cortical activity : Slow downs (over seconds to 1 minute) to NREM sleep
pattern
 Wave Progression: Slower reaching to Delta Wave (Lasting for 40 min to 1
hour) : initiation of restorative activity
 Abruption into REM sleep: Attributes both hypothalamic flip flop switch as
well as mesopontine tegmentum.
 Loss of muscle tone: REM (Dream/Nightmares)
 Age factor : Decrease in restorative sleep and increase in night time arousals
due to age progression
Sleep 1995;18:880–889
Semin Respir Crit Care Med 2010;31:618–633
J Sleep Res 1992;1:122–124

5. PATHOPHYSIOLOGY & MECHANISMS
 Bidirectional interactions - relationship between Sleep and Migraine.
 Nocturnal migraine
 may disrupt sleep
 decreases sleep frequency
 Common underlying pathophysiology
 Increased neuroscientific evidence
 new discoveries on anatomic localization
 roles of common mediating signaling molecules
 discovery of a new CNS waste removal system
Neurology 2016;87:309–313.
Headache. 2018 July ; 58(7): 1030–
1039

6. MIGRAINE & SLEEP DISORDER : INSOMNIA
 Insomnia: Difficulty with sleep initiation or maintenance with daytime
consequences despite adequate opportunity
 Most prevalent sleep complaint : contributing 1/3rd population with symptoms
while 6% general population with chronic insomnia.
 Symptoms coincide with migraine:
- Increased heart rate - Difficulty initiating sleep
- Increased cortisol levels - Inadequate sleep
- High frequency activity - lack of refreshment after sleep
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Sleep Med Rev 2002;6:97–111.
Headache 2005;45:904–910
Sleep Med 2003;4:385–391
J Headache Pain 2010;11:197–206.
Ann Indian Acad Neurol 2008;11:164–169

7. MIGRAINE & SLEEP DISORDER : INSOMNIA
 Frequent complaints of insomnia with migraine led to the possibilities of sleep
triggers in migraine endophenotype
 Sleep latency : Shown decrease in the sleep quality, efficiency and amount of
slow wave in the patient with migraine
 REM sleep and headache disorder : Lower arousal index during REM sleep and
lower cyclic alternating pattern at baseline is seen in the patient with migraine
Sleep Breath 2016;20:263–269
Pediatr Neurol 2008;39:6–11
J Headache Pain 2013;14:68.
Cephalalgia 2003;23:150–154

8. MIGRAINE & SLEEP DISORDER : INSOMNIA
 2/3rd of patients with migraine - occasional headaches disturbing sleep
cycle
 Insomnia during early morning migraine attacks
 Early morning migraine attacks increases with the age factor:
 16% patients twenties
 58% patients >60 years old.
 Insomnia if untreated in migraine – may affect quality of life
 CBT treatment
 Improvement in insomnia
 reduces headache in migraine
Headache 2007;47:1184–1188
Acta Neurol Belg 2012;112:183–187

9. MIGRAINE & SLEEP DISORDER: OBSTRUCTIVE SLEEP
APNEA
 OSA - Related to the symptoms of sleep apnoea
 Pattern of Symptoms varies like
-> Associated with Sleep Apnoea:
Sleepiness, Fatigue, Insomnia, Snoring, Subjective nocturnal and respiratory
disturbance.
-> Associated medical or psychiatric disorder includes:
Hypertension, Coronary artery disease, Atrial fibrillation, CHF, Stroke,
diabetes, Cognitive dysfunction, or mood disorder
 Absence of associated symptoms or disorders: ≥15 obstructive respiratory
events per hour satisfies the criteria
Chest 2014;146:1387–1394

10. MIGRAINE & SLEEP DISORDER: OBSTRUCTIVE SLEEP
APNEA
 Migraine attacks in the morning – Associated with breathing difficulties
snoring and sleep apnoea
 Polysomnographic studies
 patients with migraine have similar sleep apnea as the general
population.
 Shared risk factor for Migraine: Daily headaches, breathing difficulties,
snoring and obesity
Arch Intern Med 1999;159:1765–1768
Dent Clin North Am 2001;45:685–700.
Sleep and migraine: An actigraphic study. Cephalalgia 2004;24:134–139.
Pain 1993;53:65–72

11. MIGRAINE & SLEEP DISORDER: OBSTRUCTIVE SLEEP
APNOEA
 Low threshold for hypoxemia inducing headaches of OSA - can occur in the
patient with migraine
 Both migraine and OSA are commonly encountered
 The underdiagnosed OSA in migraine – may lead to future vascular events
 Clinical evaluation of migraine - should also include OSA screening
Headache 2008;48:16–25.

12. MIGRAINE & SLEEP DISORDER:
PARASOMNIAS & SLEEP-RELATED MOVEMENT
 Dopamine – an important neurotransmitter in migraine pathophysiology
 Dopaminergic dysfunction implicates parasomnias and sleep-related movement disorders in
several neurologic diseases
 Dopamine dysfunction may trigger migraine prodrome
 Common disorders in migraine
 Non-REM parasomnia
 Bruxism
 Restless legs syndrome
Cephalalgia 2007;27:1308–1314.

13. MIGRAINE & SLEEP DISORDER: SOMNAMBULISM
 Studies of both children and adult with migraine
 Higher rate of childhood Somnambulism
 predominate in the patient of migraine with aura
 Increased Somnambulism in children – may be seen in migraine or tension type headache
 Symptoms like Motion sickness, recurrent limb pain, recurrent abdominal pain, sleep talking,
and bruxism - prevalent in children with migraine
 Adult migraine patient
 May have childhood somnambulism (33%)
 relationship even persists when they are controlled for depression, daytime sleepiness and
insomnia
Cephalalgia 1997;17:492–498
Neurology 2005;65:1334–1335
Pediatr Neurol 2010;43:420–424

14. MIGRAINE & SLEEP DISORDER: BRUXISM
 Bruxism with temporomandibular joint dysfunction (TMD)
 highly prevalent with the migraine patient
 Bruxism
 trigger migraine attack in association with TMD
 increased peripheral activities of trigeminal nerve
 Same central etiologies proposes sleep bruxism-migraine association
 sleep microarousals
 sleep transitions
Clin J Pain 2017;33:835–843.
Clin Pediatr (Phila) 2015;54:469–478
J Orofac Pain 2013;27:14–20.

15. MIGRAINE & SLEEP DISORDER: RESTLESS LEGS
SYNDROME
 RLS and migraine: decrease in sleep efficiency or difficulty initiating sleep
 Dopamine plays important role
 Dopamine dysfunction leads to RLS - decreased A11 neuron from Hypothalamus to the
spinal cord
 Migraine
 higher frequency of dream-enacting behavior (DEB)
 worse headache-related disability
 increased frequency of nightmares
Cephalalgia 2014;34:777–794
Eur J Neurol 2014;21:1205–1210
Mov Disord 2007;22:1451–1456
Cephalalgia 2007;27:1308–1314.

16. MIGRAINE & SLEEP DISORDER: NARCOLEPSY
 Increased level of tension type of headache and migraine in the patient with
Narcolepsy.
 Clinical statistics reports :
-> 23.5% increased rate of migraine
-> 41.2% with primary hypersomnia
 Further research is ongoing to evaluate the clinical relationship between Narcolepsy
and migraine
Cephalalgia 2003;23:786– 789.
Cephalalgia 2003;23:14–19

17. MIGRAINE & SLEEP DISORDER: NARCOLEPSY IN CHILDREN
 13 incident cases with narcolepsy – children – 0-17 yrs
 Patients with Migraine
 a greater risk of developing narcolepsy than patients without migraine
 adjusted hazard ratio = 5.30, 95% CI: 1.61, 17.4; p = 0.006
 Persisted after controlling for potential confounders - baseline
comorbidities and concurrent medication uptake, migraine subtypes.
PLoS One. 2017; 12(12): e0189231.
Migraine is an independent risk factor for narcolepsy development in children.

18. SLEEP FACTOR: MIGRAINE INFLUENCER
 Insomnia - part of the migraine prodrome or incites the migraine attack
 Frequent nighttime awakenings - sleep-related migraine attacks
 Serotonin (5-HT) vital role - regulates sleep, mood (depression and anxiety), appetite, sexual function,
and pain
 Serotonin: responsible for wakefulness and inhibit REM sleep
 In migraine
 Low serotonin state interictally
 Increased 5HT movement from intracellular store early migraine attack
Sleep 2007;30:494–505
Cephalalgia 2006;26:1225–1233
J Neurol 2007;254:789–796

19. SLEEP FACTOR: MIGRAINE INFLUENCER
 How serotonin levels - participate in the trigeminovascular nociceptive
pathway is unclear
 The transition from NREM to REM sleep is based on dorsal raphe nucleus
 cessation of serotonin neuron firing is vital in initiating REM
 Decreased in the REM cycle in case of migraine possibly due to dysfunction of
serotonin.
Sleep Breath 2016;20:263–26
Headache 2006;46:34–39
Am J Physiol 1997;273:R451–455

20. SLEEP FACTOR: MIGRAINE INFLUENCER
 Hypothalamus: Targeted as a central & early player in migraine pathophysiology
 PET imaging
 alteration in the hypothalamus activity and coupling of spinal trigeminal nuclei
with in 24 hours of pain onset
 Hypothalamus: Implicated in migraine by producing gonadotropin-releasing
hormone.
 With serotonin, Dopamine also plays important role in monitoring pre phase of
migraine.
 Dopamine modulating neuronal firing: suggested by Symptoms like
 yawning, drowsiness, mood changes, irritability, and hyperactivity
Nature 2005;437:1257–1263
Ann N Y Acad Sci 2008;1129:275–
286.
Neurol Sci 2008;29(Suppl 1):S166–

21. ADEQUATE SLEEP: AS MIGRAINE THERAPEUTIC
Sleep disruption
↓
Disturbances in glymphatic flow
↓
Accumulation of waste products
↓
Trigger migraine
J Neurosci 2017;37:2904–2915

22. ADEQUATE SLEEP: AS MIGRAINE THERAPEUTIC
Chronic sleep disruption
↓
Accumulation of more toxic substances
(e.g. beta-amyloid and metalloproteinases)
↓
Chronic Migraine

23. ADEQUATE SLEEP: AS MIGRAINE THERAPEUTIC
 Sleep can often terminate a migraine attack
 Restorative impact of sleep helps in tackling migraine attack - may not be effective in
chronic migraine
 Sleep - facilitates and restores brains day time activity.
 Glymphatic System is active during sleep
 Removes the interstitial waste via perivascular space created by astrocytic end feet
 Restorative role of glymphatic system has shown the possible mechanism in the
migraine management
Science 2013;342:373–377.

24. CONCLUSION
 Sleep and migraine relationship - common pathophysiology.
 Received more attention in the last 2 decades
 Clinical approach should be to view the cause of migraine pathophysiology linked to sleep
problems
 Further research to drive possible migraine management mechanism
 Treatment of sleep problems in patients with migraine will also help in reducing headache
days and disability.