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Table of Contents    
ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1277-1281

Hypnic Headache: A Rare Primary Headache Syndrome in an Indian Population with a Mini Review of Literature


1 Department of Neurology, TD MCH, Alappuzha, Kerala, India
2 Department of Neurology, PVS Memorial Hospital, Kochi, Kerala, India
3 Department of Psychiatry, NIMHANS, Bengaluru, Karnataka, India

Date of Submission17-Nov-2016
Date of Decision10-Jan-2017
Date of Acceptance21-Mar-2017
Date of Web Publication30-Oct-2021

Correspondence Address:
K Rammohan
Department of Neurology, TD MCH, Alappuzha - 688 005, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.329541

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 » Abstract 


Context: Hypnic headache (HH) is a rare primary headache syndrome first described by Raskin in 1988.
Aim: To describe the occurrence of HH in Indian patients and compare its clinicoepidemiological features to those published in the literature and attempt to trace some of the evolving concepts regarding its etiology and clinical features since it was first described.
Materials and Methods: Patients attending the neurology outpatient department of a tertiary referral teaching hospital from 01-05-2011 to 30-04-2016 who were identified to have HH as per ICHD 3 beta criteria were included in the study. A meticulous history of the headache and comorbidities, clinical examination, Epworth Sleepiness Scale, blood counts, blood biochemistry, magnetic resonance imaging (MRI) scans of the brain and polysomnography (in selected patients) were done and the results were compared to selected international literature.
Results: A total of 11 patients with HH were identified during the study period, of which 8 (72.72%) were males and 3 (27.27%) were females. The age of the patients varied from a minimum of 53 years to a maximum of 78 years (Mean: 63.36, SD: 8.09). The frequency of attacks per month ranged from 5 to 46(Mean: 20.36, SD: 11.67). The duration of each headache episode ranged from a minimum of 30 minutes to a maximum of 4 hours (Mean: 1.93, SD: 1.23). The occurrence of the headaches was maximum during the time periods of 0.00–2.00am and 2.00–4.00am (38% and 36%, respectively). The pain was dull in a majority of patients, 7 (63.63%). Trigeminal autonomic features such as lacrimation, ptosis, or rhinorrhea were not recorded from our cohort. Motor activity was noted in 7 (63.63%) cases. Two (18.18%) patients had associated migraine headaches whereas 3 (27.27%) had associated tension-type headaches. None of the patients in our series had chronic obstructive pulmonary disease. Four (36.36%) patients had systemic hypertension and 1 patient (9.09%) had diabetes mellitus. Two (18.18%) patients had symptoms of obstructive sleep apnea syndrome. Three (27.27%) patients had symptoms of excessive daytime sleepiness according to the Epworth Sleepiness Scale. Blood examinations and MRI were normal in all patients, except for the findings of a few lacunar infarcts and nonspecific T2 weighted hyperintensities in 3 patients (27.27%).
Conclusion: Our study proves the existence of the newly described primary headache syndrome called HH in the Indian population. On comparing our results with the international literature, the similarities are much greater than the differences. MRI voxel-based morphometry to demonstrate the loss of gray matter in the posterior hypothalamus may prove to be a reliable test to diagnose primary HH in the future.


Keywords: Clinicoepidemiological aspects, hypnic headache, primary headache
Key Message: This observational study analyses the features of an extremely rare primary headache syndrome in a South Indian population and finds that for the most part they are comparable to that described in international literature with some interesting variations


How to cite this article:
Rammohan K, Shyma M M, Das S, Shaji C V. Hypnic Headache: A Rare Primary Headache Syndrome in an Indian Population with a Mini Review of Literature. Neurol India 2021;69:1277-81

How to cite this URL:
Rammohan K, Shyma M M, Das S, Shaji C V. Hypnic Headache: A Rare Primary Headache Syndrome in an Indian Population with a Mini Review of Literature. Neurol India [serial online] 2021 [cited 2021 Nov 28];69:1277-81. Available from: https://www.neurologyindia.com/text.asp?2021/69/5/1277/329541




Hypnic headache (HH) is a rare, sleep-related, benign headache disorder predominantly experienced by the elderly. It was first described by Raskin[1] in 1988 in 6 patients who were awakened regularly from sleep by a short-lasting headache. Hence, it has also been called “clockwise headache” or “alarm-clock headache”. The frequency of patients with HH is not known, however, the frequency of HH among patients attending tertiary headache centers is estimated to be between 0.07% and 0.35%.[2] Diagnostic criteria were first proposed in 1997,[3] and HH was included in the revised version of the headache classification of the International Headache Society (IHS) (Headache Classification Subcommittee 2004), 2nd edition[4] (ICHD-2). Because of the growing realization of the variations from the classical clinical picture, the criteria were modified in the ICHD-3 beta version. Because it is a rare primary headache syndrome, only limited numbers of cases have been described. For example, Liang et al.[5] in their authoritative review of HH could find only 250 reported cases of HH in adults till 2014. Knowledge regarding various aspects of HH including variations in clinical features in different geographic cohorts as well as treatment options are lacking and has come from case reports and small case series rather than randomized controlled trials.


 » Materials and Methods Top


Patients attending the neurology department of a major tertiary care referral hospital (Government TD Medical College, Alappuzha, Kerala) from 01-May-2011 till 30-Apr-2016 were identified to have HH as per the ICHD-3 beta criteria. The study was initiated with ICHD-2 criteria. However, during July 2013, the ICHD-3 beta criteria came into existence. Taking this into account, the inclusion criteria was modified to include the cases identified retrospectively. A detailed history regarding various aspects of the headache including duration, timing, frequency, site, severity, and character of pain was obtained. Epidemiological parameters, presence of other comorbidities such as chronic obstructive lung disease and systemic hypertension were noted. A detailed history was obtained from the spouse regarding the presence of snoring and obstructive sleep apnea symptoms, as well as any motor behavior during the headache episode. Epworth Sleepiness Scale was applied to all patients to assess the presence of excessive day time sleepiness. A detailed neurological and systemic examination including palpation of the skull was done. Routine blood biochemistry, blood counts, and erythrocyte sedimentation rate (ESR) were assessed for all patients. Magnetic resonance imaging (MRI) of the brain was done in all patients. Polysomnogram study was done in selected patients in whom Epworth Sleeepiness Scale was positive.


 » Results Top


A total of 11 patients with HH were identified during the study period. During this period, the total number of patients with primary headache attending the outpatient department was 14562. Among this, 8 (72.72%) were males and 3 (27.27%) females. The age of the patients varied from a minimum of 53 years to a maximum of 78 years (Mean: 63.36, SD: 8.09). The frequency of attacks per month ranged from 5 to 46(Mean: 20.36, SD: 11.67). The duration of each headache episode ranged from a minimum of 30 minutes to a maximum of 4 hours (Mean: 1.93, SD: 1.23), and the duration was consistent for each patient during all the episodes. The latencyperiod till diagnosis varied from 6 months to 5 years (Mean: 1.77 years, SD: 1.42). The occurrence of the headaches was maximum from 0.00–2.00amto2.00–4.00am (38% and 36%, respectively). The intensity of pain was reported to be mild in 2 patients (18.18%), moderate in 6 patients (54.54%), and severe in 3 patients (27.27%). The character of pain was dull in majority of patients 7 (63.63%). Headache was bilateral in 8 (72.72%) and holocranial in 6 patients (54.54%). Migrainous features such as mild nausea and phonophobia were described by 1 patient each (9.09%). Trigeminal autonomic features such as lacrimation, ptosis, or rhinorrhoea were not reported by our cohorts. In 2 (18.18%) patients, the headaches occurred consistently during daytime naps, and 1 (9.09%) patient reported occurrence of headache infrequently during daytime naps. Motor activity was noted in 7 (63.63%) cases. Two (18.18%) patients had associated migraine headaches whereas 3 (27.27%) had associated tension-type headaches. None of the patients in our series had chronic obstructive pulmonary disease. Four (36.36%) patients had systemic hypertension and 1 patient (9.09%) had diabetes mellitus. Two (18.18%) patients had symptoms of obstructive sleep apnea syndrome. Three (27.27%) patients had symptoms of excessive daytime sleepiness according to Epworth Sleepiness Scale. Blood examination and MRI were normal in all patients except for the findings of a few lacunar infarcts and nonspecific T2-weighted hyper-intensities in 3 patients (27.27%).


 » Discussion Top


HH is defined as per ICHD 3 beta version[6] as:

  1. Recurrent headache attacks fulfilling criteria B–E
  2. Developing only during sleep and causing wakening
  3. Occurring on 10 days per month for >3 months
  4. Lasting 15 minutes and for up to 4 hours after waking
  5. No cranial autonomic symptoms or restlessness
  6. Not better accounted for by another ICHD-3 diagnosis.


The ICHD 3 beta classification describes HH (Code 4.9) as frequently recurring headache attacks developing only during sleep, causing wakening, and lasting for up to 4 hours, without characteristic associated symptoms and not attributed to any other pathology. Descriptions of HH have been obtained from various geographic populations including France,[7] Germany,[8] Taiwan,[9] and Spain.[10]. However, till date it has not been described in an Indian population. In view of the rarity of this entity, we have attempted to describe the clinical features of HH in an Indian population, and compare it to that described in the international literature [Table 1]. For this, we compared our results with that of the exhaustive review by Holle et al.[11] Holle et al. reviewed all the cases of HH since its first description in 1998 till 2013, a total of 225 adult cases, and described their clinical and epidemiological features. In addition, to illustrate the changes in the previous concepts of HH, which have evolved over time, we compared our results with an older review by Evers et al.[12] who reviewed a total of 94 published cases of HH till 2005.
Table 1: Comparison of results

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It is interesting that the first ever case series description of HH by Raskin[1] had a strong male preponderance (5men and 1woman). However, all further case reports and case series showed a higher frequency in women with a male: female ratio ranging from 1.2:1 to1.6:1.[13] In most of the case reports and case series so far, HH is a disease of older age which starts occurring after the age of 50 years. In fact, in the second edition of the ICHD,[4] in which HH was included for the first time in 2004, in the subsection of other primary headaches (code 4.5), age over 50 years was fixed as one among several definite criteria to diagnose HH. However, with the recent descriptions of HH in younger patients[14] including pediatric cases,[15],[16] the age criterion of 50 years, which was incorporated in the ICHD-2 criteria for the diagnosis of HH was removed in the ICHD 3 beta version.[6] Our study conclusively proves that HH is a rare disease in our population, being found at a rate of one per 1324 patients of primary headache, which is comparable to the rate described in the headache clinic at mayo hospital, where one out of 1400 patients suffered from HH. With respect to other aspects also, the clinical features of HH, as described in our patients, were similar to those described in the international literature, the exceptions being the absence of trigeminal autonomic symptoms in our cohort, the lower frequency of motor activity in our patients, and the relatively equivalent occurrence of HH before and after 2:00 am.[17] The ICHD-3 beta[6] criteria expressly prohibit the presence of trigeminal autonomic symptoms in the diagnosis of HH. Despite this, such symptoms have been reported in various reviews and cohorts,[7],[8],[12],[18],[19] however, all authors are in agreement that these autonomic symptoms are mild and not enough to satisfy a criteria of trigeminal autonomic cephalalgia. Future editions of ICHD may take note of this and modify the criteria accordingly. Until then, it is important to note that the presence of mild trigeminal autonomic symptoms should not exclude the diagnosis of HH. Similarly, it may be noted that previously a dull character of pain was thought to be sine qua non for HH as per theICHD-2 criteria. With the description of different types of pain in HH, as seen in the appended table, the criteria of a dull character of pain was removed from ICHD-23 beta criteria.[4] Taking into account the wide variation of headache attacks ranging from a few per month to six per day,[19] the ICHD-3 beta criteria has reduced the frequency criteria to diagnose HH to a minimum of 10 per month from the previous 15 per month in the ICHD-2 criteria; no maximum limit has been specified. Motor activity (which was less in our cohort compared to previously published cases) during the headache attack is a peculiar characteristic of HH, being an aimless activity such as reading, eating, or drinking something or watching television; thus, being distinctly different and less in magnitude from the motor restlessness of cluster headache.[8],[11] The quality, nature, and character of pain in our study population more commonly resembled that of the tension-type headache in being dull, bilateral, and holocranial without trigeminal autonomic symptoms or significant associated migraine. This is accordance with the commonly held concept of HH. The ICHD-3 beta states in its comments on HH (code 4.9) that it generally resembles tension-type headache.[6]

Even though several primary headaches such as cluster headaches, chronic paroxysmal hemicranias, and even migraine are well-known to occur in sleep, HH is the only primary headache which occurs exclusively during sleep. Majority of the headaches occurred in the 2AM to 4AM period and usually recurred through the night at approximately2-hour intervals. This led credence to the supposition that HH used to occurs predominantly during REM sleep, as REM sleep tends to predominate towards the latter part of the sleep period and tends to recur every 90–120 minutes. This was also thought to be reasonable considering the profound changes during REM sleep namely increased cerebral blood flow, decreased systemic concentrations of serotonin, profound sympathetic activation, and marked reduction of the activity of dorsal raphe and locus ceruleus nuclei, which in conjunction with the periaqueductal gray matter constitutes the central antinociceptive network.[20],[21] However, recent reports have suggested that HH may arise from NREM sleep stages as well.[9],[22] In fact, HH onset during REM and NREM sleep have been recorded in a single patient in a polysomnogram in the same night, clearly contradicting the previous belief that HH occurs only in REM sleep.[13] The ICHD-3 beta[6] version takes note of these facts, as it notes in its comments that HH is not probably related to sleep stages. Because of financial and logistical reasons we could perform polysomnogram in selected cases, only, namely the 3 patients in whom Epworth Sleepiness Scale was positive. The polysomnogram studies in these patients were normal without any evidence of any obstructive or central sleep apneas. HH developed during the night of the recording in only one patient during the REM sleep stage. However, the supposition that HH is not related to sleep stages is supported by our findings that HH tended to occur almost equally in the first as well as second halves of sleep (actually with a slight preponderance in the first half), unlike the latter stage predominance which would be expected if occurrence of HH was predominantly in REM sleep. Moreover, 3 of our patients reported occurrence of HH during daytime naps. The depth of sleep associated with these brief daytime naps was not thought to be enough to reach the REM stage. One of our patients had symptoms of obstructive sleep apnea syndrome (OSAS). However, the headaches were strictly nocturnal and did not occur on awakening or during the daytime, which would be expected in OSAS. Three of our patients reported excessive daytime sleepiness. However, this was not very severe and was obtained after careful history taking and utilizing Epworth Sleepiness Scale. It could have been due to the repeated headache attacks disrupting the sleep architecture, thus suggesting an intrinsic relationship between HH and sleep rather than extrinsic causes such as OSAS. There has been a single case report of a patient with HH mimicking OSAS with oxygen de-saturation coinciding with the times of headaches in sleep.[20] However, the majority of studies in which polysomnograms were performed showed no temporal association between the headaches and decreased oxygen concentration in patients whom obstructive respiratory events occurred during the polysomnogram.[9] Hence, OSAS may be considered as a complicating factor in patients with HH possibly related to the increased age of these patients and not as an etiological factor of the disease.[13] In addition to OSAS, patients with nocturnal headaches should be investigated for conditions such aschronic obstructive lung disease, nocturnal hypertension, as well as conditions causing raised intracranial pressure such as brain tumors.[9] Of note is that none of our patients had chronic obstructive lung disease, another condition well known to be associated with nocturnal/early morning headaches. Similarly, all our patients with associated systemic hypertension were well controlled with medications, making the possibility of sustained nocturnal hypertension causing nocturnal headaches less likely. However, case reports have appeared in literature suggesting that nocturnal arterial hypertension may be a cause for secondary HH.[23] Hence, it is advisable to rule out nocturnal hypertension syndrome by 24-hour blood pressure monitoring.[24] Several secondary causes of HH have been described in the literature including posterior fossa meningioma,[25] pontine infarction,[26] pituitary tumors,[27] and cerebellar hemangioblastoma.[28] It is questionable whether such cases will come under the rubric of HH, as envisioned under the ICHD-3 beta criteria as it contains an exclusion criteria to rule out secondary causes. However, similar to the cases of other primary headaches, this emphasizes the necessity of a meticulous search for underlying causes before making a diagnosis of HH. None of our patients showed any significant abnormalitieson MRI except for lacunar infarcts in 2 patients and a few nonspecificT2-weightedhyperintensities in 1 patient, which were possibly age related and not in any way etiologically related to the headaches. Thus, in our series HH tended to be truly primary. In this context MRIvoxel-based morphometry study may prove to be helpful in the diagnosis of primary HH as it shows significant loss of gray matter in the posterior hypothalamus[29]indicating the importance of this area in the sleep wake regulating cycle, as well as the central antinociceptive network.

Here, other than generalized anxiety (GAD) in 3 patients, we did not find any major mental illness. This is an interesting finding and requires further validation with large number of patients to confirm if this is only an epidemiological phenomenon, for example, due to the higher prevalence of GAD in our population or an actual phenomenon due to neuronal networks subserving emotional well-being being involved in HH patients along with the central antinociceptive/sleep wake regulating networks described above. Unfortunately, treatment advice of HH till date is available only from anecdotal case reports and small uncontrolled case reports and includes lithium, indomethacin, caffeine, and melatonin.[6],[11]


 » Conclusions Top


Our study proves the existence of HH in the Indian population. HH, as described in our study, is a rare primary headache affecting individuals above 50 years of age. The clinical features of HH, as described in our patients, were similar to those described in the international literature, the exceptions being the absence of trigeminal autonomic symptoms in our cohorts, the lower frequency of motor activity in our patients, and the relatively equivalent occurrence of HH before and after 2:00 am. It has the characteristics of a tension-type headache and is probably not related to the REM stage, as thought previously. GAD was found in nearly one-third of our cases, which is a finding which needs further investigation. Significant medical comorbidities were not found in our patients. It is usually a benign headache but in some patients could be a potentially more serious problem with repeated disruption of the sleep cycles with excessive day time sleepiness. However, secondary causes are to be ruled out with neuroimaging, and in indicated cases, polysomnogram or 24-hour blood pressure monitoring to rule out nocturnal hypertension. MRI voxel-based morphometry to demonstrate the loss of gray matter in the posterior hypothalamus may prove to be a reliable test to diagnose primary HH in the future.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Holle D, Naegel S, Krebs S, Katsarava Z, Diener HC, Gaul C, et al. Clinical characteristics and therapeutic options in Hypnic headache. Cephalalgia 2010;30:1435-42.  Back to cited text no. 18
    
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