Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Secondary Headaches
3.2. Migraine
3.2.1. Clinical Features of Migraine with Nocturnal Attacks
- Circadian influences: The suprachiasmatic nucleus in the hypothalamus regulates circadian rhythms and interacts with brainstem nuclei involved in pain modulation. Dysregulation may predispose certain individuals to nocturnal attacks. Premonitory symptoms like mood states such as alert, tense, depressed, or tired, and changes in sleep quality have been described to occur up to 2 days before a migraine attack and were hypothesized to be related to a hypothalamic involvement in the prodromic phase of migraine [16,17].
- REM sleep instability: Migraine attacks have been observed to coincide with transitions into or out of REM sleep, a phase during which the brain is highly active and fluctuations in autonomic tone may occur [18].
- Melatonin dysregulation: Reduced nocturnal melatonin levels have been reported in both adults and children with migraine. Melatonin has both antioxidant and anti-nociceptive properties and may act as a migraine preventive agent [19].
3.2.2. Migraine Is Associated with Sleep Disorders
3.2.3. Management and Treatment
3.3. Cluster Headache
3.4. Hypnic Headache
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
M | Migraine |
MG | Migraine group |
NMG | Non-migraine group |
HFG | Headache-free group |
CH | Cluster headache |
HH | Hypnic headache |
SCN | Suprachiasmatic nucleus |
H | Hours |
Y | Years |
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Migraine | Cluster Headache | Hypnic Headache |
---|---|---|
A. At least five attacks fulfilling criteria B–D B. Headache attacks lasting 4–72 h (untreated or unsuccessfully treated) C. Headache has at least two of the following four characteristics:
| A. At least five attacks fulfilling criteria B–D B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15–180 min (when untreated) C. Either or both of the following:
–Nasal congestion and/or rhinorrhea –Eyelid oedema –Forehead and facial sweating –miosis and/or ptosis
E. Not better accounted for by another ICHD-3 diagnosis | A. Recurrent headache attacks fulfilling criteria B–E B. Developing only during sleep, and causing waking C. Occurring on ≥10 days/month for >3 months D. Lasting from 15 min up to 4 h after waking E. No cranial autonomic symptoms or restlessness F. Not better accounted for by another ICHD-3 diagnosis. |
Symptom or Clinical Feature | % of Serious Headaches | % of Non-Serious Headaches | p-Value |
---|---|---|---|
Nocturnal awakenings | 0 | 0.70% | 0.18 |
Visual disturbances | 29.10% | 1.60% | <0.001 |
Paraesthesia | 0 | 0.90% | 0.63 |
Cranial nerve palsies | 8.30% | 0.20% | <0.001 |
Pupillary abnormalities | 12.50% | 0.10% | <0.001 |
Nystagmus | 8.30% | 0.40% | <0.001 |
Dysmetria | 0 | 0.20% | 0.82 |
Ataxia | 16.70% | 0.90% | <0.001 |
Hyposthenia | 12.50% | 0.20% | <0.001 |
Strabismus | 8.30% | 0.20% | <0.001 |
Drowsiness | 33.30% | 0.20% | <0.001 |
Meningismus | 16.70% | 0 | <0.001 |
Authors, Publication Year | Study Design | Number of Patients Male:Female | Mean Age (Years) Age Range | Main Results |
---|---|---|---|---|
Bruni et al., 1997 [2] | Prospective, case-control | 283 (164 M; 119 T), 893 C 144:139 | 10.11 5–14.3 |
|
Masuko et al., 2014 [5] | Case-control | 20 M, 20 C 10:10 | 9.5 6–12 |
|
Armoni Domany et al., 2019 [21] | Retrospective | 256 M 104:152 | 12.65 4.8–18 |
|
Bruni et al., 2008 [4] | Retrospective, non-clinical population (students) | 1073 subjects 545:528 MG 70 NMG; 135 HFG 868 | 10.56 8−15 |
|
Voci et al., 2021 [22] | Prospective, questionnaire-based | 140 M 54:86 | 12.1 3–18 |
|
El-Heneedy et al., 2019 [23] | Prospective, case-control | 40 M20 C 17:23 | 11.1 5.4–16.8 |
|
Authors | N. | Male:Female | Chronic: Episodic | Onset (Years) | Family History | Location | Attack Duration | Frequency | Migrainous Accompanied Symptoms | Therapy | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Rescue | Preventive/ Transitional | Indometacin Response | ||||||||||
Isik et al., 2002 [29] | 3 | 2:1 | Episodic | 2–10 | Yes (1) | Often not clear | 15–60 min | Not specified | Photophobia | / | / | yes |
Evers et al., 2002 [42] | 1 | 1:0 | Chronic | / | Yes | Unilateral, periorbital | 45 min | Every other day | / | O2 | Refused | / |
Majumdar et al., 2009 [38] | 11 | 6:4 | Episodic (8)/ Chronic (3) | 2–14 | 6/11 | Unilateral, orbital, supraorbital, frontal | 72 min | Once a day | Neck stiffness, unilateral photophobia, phonophobia | O2, Dihidroergot., Zolmatriptan | Methysergide, verapamil | Yes (3) |
Antonaci et al., 2010 [39] | 1 | 1:0 | Episodic | 10.5 | No | Unilateral, orbital | 60–180 min | 1–3/day | Phono-photophobia | O2 | Steroids + cyproheptadine, verapamil | / |
Kaciński et al., 2009 [35] | 1 | / | 1 | Yes | Sovraorbital | 12–240 min | Every 4–5 days- 4/day | Vomiting, nausea, abdominal pain, phono-photophobia | ibuprofen | Verapamil, propanolol, pizotifen | / | |
Garg et al., 2010 [41] | 1 | / | Episodic | 8 | Yes | Forehead and vortex | 1–2 h | 3–4/day | Vomiting | O2 | / | yes |
Arruda et al., 2011 [30] | 3 | 2:1 | Episodic | / | Yes (1) | Periorbital unilateral | 40–60 min | Every other day-1–2/day | / | O2 | Verapamil, prednisone, topiramate, melatonin | yes |
Mariani et al., 2014 [43] | 11 | 6:5 | Episodic | 10 | Yes | Orbital (8), fronto-orbital (2), frontal (1) | 86 min | 1–4/day | Phono-photophobia | / | Prednisone | Yes (1) |
Taga et al., 2018 [33] | 38 | 1:1.1 | Episodic (31)/ chronic (6) | <13 | Yes | Right-sided (17) | 15–30 min | 3–7/day | Nausea, vomiting, phono-photophobia, osmophobia | / | / | / |
Eberhard et al., 2024 [37] | 22 | 1:1.7 | Episodic (7)/ Chronic (2) | / | / | / | 15–180 min | 1/sett- several/day | Nausea, vomiting, phono-photophobia, osmophobia | O2, intranasal zolmitriptan, subcutaneous dihydroergotamine, eletriptan, and ubrogepant, subcutaneous sumatriptan | Steroid, propanolol, gabapentin, verapamil, topiramate, biofeedback, occipital nerve block | / |
Reference | Gender, Age (y) of Attacks Onset | Time of Attacks | Character of Pain | Localization | Intensity of Pain | Features of Migraine | Duration of Attacks (Min) | Frequency of Attacks (Days/Month) | Family History of Headache | Acute Treatment | Prophylactic Therapy Treatment |
---|---|---|---|---|---|---|---|---|---|---|---|
Grosberg et al., 2005 [51] | F, 9 | 5–6 h after falling asleep | Throbbing | Right frontal and temporal | Moderate to severe | None | 30 | 8–12 | Negative | No | No |
Scagni et al., 2008 [50] | F, 3 | 2–4 a.m. | Pulsating | Frontal | Severe | None | 30–60 | 1 | Positive | Acetaminophen with benefit | No |
Cerminara et al., 2011 [49] | M, 7 | 1–3 h after falling asleep | Na | Fronto-temporal | Moderate | None | 20–30 | 2 | Positive (mother: migraine) | No | No |
M, 11 | 1–2 a.m. and 4–5 a.m. | Dull | Fronto- temporal | Moderate to severe | Occasional nausea | 10–20 | 20–25 (2–3/night) | Negative | No | Melatonin with benefit | |
F, 10 | 1–2 h after falling asleep | Pulsating | Fronto or fronto- temporal | Moderate to severe | Occasional nausea | 10–30 | 10–15 (2–3/night) | Negative | No | Melatonin with benefit | |
Prakash et al., 2008 [53] | M, 15 | 1–2 a.m., 3–4 h after falling asleep | Non-throbbing | Left frontal and temporal areas | Moderate to severe | None | 30 min, 5 h | not evaluable: relapsing– remitting type disturbance | N/A | Oral sumatriptan, oral rizatriptan, and oxygen inhalation without benefit | Sodium valproate, amitriptyline, duloxetine, naproxen, ibuprofen, and propranolol without benefit. Indomethacin with benefit |
Bender, 2012 [52] | F, 15 | 2.5–3 h after falling asleep | Stabbing | Frontal, temporal, and periocular | N/A | Occasional photophobia | N/A | 12–16 (seems to have a seasonal feature) | N/A | na | Treated for OSAS with mandibular advancement oral appliance with benefit |
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Baldo, B.; Bonemazzi, I.; Morea, A.; Rossi, R.; Ferretti, A.; Sciruicchio, V.; Raffagnato, A.; Raieli, V.; Versace, A.; Toldo, I. Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review. Life 2025, 15, 1198. https://doi.org/10.3390/life15081198
Baldo B, Bonemazzi I, Morea A, Rossi R, Ferretti A, Sciruicchio V, Raffagnato A, Raieli V, Versace A, Toldo I. Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review. Life. 2025; 15(8):1198. https://doi.org/10.3390/life15081198
Chicago/Turabian StyleBaldo, Beatrice, Ilaria Bonemazzi, Antonella Morea, Roberta Rossi, Alessandro Ferretti, Vittorio Sciruicchio, Alessia Raffagnato, Vincenzo Raieli, Antonia Versace, and Irene Toldo. 2025. "Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review" Life 15, no. 8: 1198. https://doi.org/10.3390/life15081198
APA StyleBaldo, B., Bonemazzi, I., Morea, A., Rossi, R., Ferretti, A., Sciruicchio, V., Raffagnato, A., Raieli, V., Versace, A., & Toldo, I. (2025). Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review. Life, 15(8), 1198. https://doi.org/10.3390/life15081198