Secondary hypnic headache or symptomatic nocturnal hypertension? Two case reports

Introduction

According to current criteria, hypnic headache (HH) syndrome is a rare condition diagnosed in subjects complaining of exclusively sleep-related dull headache attacks. At least two of the following features must be present: recurrence > 15 times per month; persistence of pain ≥ 15 min after waking; age at onset > 50 years; absence of autonomic symptoms and no more than one of the following features: nausea, photophobia or phonophobia. The pain should not be attributable to any other condition (1). Its pathophysiology is still poorly understood, but it has been considered a chronobiological disorder (2).

Although HH is regarded as an idiopathic headache syndrome, secondary cases have been described (3–8). These disorders may be an incidental finding or may be related to HH to some extent, as their suppression has significantly changed the clinical course.

To the best of our knowledge, there have been six case reports of secondary HH because of: obstructive sleep apnoea (3); posterior fossa meningioma (4); ischaemic stroke in the pontine reticular formation (5); nocturnal arterial hypertension (6); pituitary macroadenoma (7); and transient HH syndrome after withdrawal of long-term lithium treatment (8).

Here we describe two patients with a HH syndrome according to International Headache Society (IHS) criteria in whom nocturnal arterial hypertension was detected and its correction resulted in headache resolution.

Clinical cases

Case 1

A 58-year-old white female patient had been awakened almost every night around 05.00 h by a moderate, non-pulsating bilateral fronto-parietal headache for the past 6 months. No autonomic symptoms were reported. Paracetamol or aspirin provided pain relief in 30–40 min, resuming sleep.

The patient's medical history was notable for episodic migraine that improved after menopause, seizures since the age of 19 controlled with sodium valproate, and chronic lumbar pain that required diclophenac sodium 50 mg b.i.d. on a daily basis for the last 18 months. She did not suffer from mood disturbances, snoring or airflow arrest during sleep.

Neurological and physical examination were unremarkable. Blood pressure (BP) was 135/80 mmHg and heart rate 72 bpm. Standard blood chemistries, complete blood count, erythrocyte sedimentation rate (ESR), electroencephalography and brain magnetic resonance imaging (MRI) were normal.

Indomethacin retard 75 mg was started at bedtime and diclophenac sodium was stopped. The nocturnal headaches completely disappeared after the first dose of indomethacin. After 1 month she required only 25 mg at bedtime. If she forgot to take indomethacin the headache reappeared.

On the third visit, the BP was 135/90 mmHg. Ambulatory blood pressure monitoring (ABPM) was performed and indomethacin was stopped. She awoke that night with her usual headache at 04.30 h; BP was 162/90 mmHg, lasting around 90 min. The BP measurements 60 and 30 min previously had been 135/80 mmHg and 140/82 mmHg, respectively. The headache resolved in 2 h. The 24-h BP measurements are presented in Table 1.

Table 1.

Case 1 blood pressure measurements

		Hypertensive peak
	Mean BP (mmHg)	Systolic	Diastolic	N	Duration	bpm
Daytime	145/98 ± 13/10	165–171	110–134	10	< 30 min	72
Night-time	137/80 ± 15.7/8	160–165	95–100	2	90–120 min	69
24 h	144/95 ± 13.7/11.9	—	—	—	—	—

The diagnosis of essential hypertension was reached according to an extensive clinical work-up. Nifedipine retard was started and indomethacin and diclophenac were discontinued. A control ABPM was performed 6 months later, revealing normal BP measurements. At the 24-month follow-up, the patient reported no new nocturnal headache.

Case 2

This 64-year-old man reported a 4-month history of recurrent episodes of moderate holocranial non-pulsating headache attacks exclusively at night-time. No nausea, photophobia, phonophobia, or autonomic symptoms were observed. The attacks occurred between 02.00 and 03.00 h for 2–3 h on > 15 nights per month, awakening him. During the headache, he remained seated or paced. Ibuprofen provided some benefit.

The patient's medical history was remarkable only for diabetes and hypercholesterolaemia.

Neurological and physical examinations were unremarkable. His BP was 120/80 mmHg.

A brain MRI, blood tests and ESR were normal. Lithium 400 mg at night was started, lessening the headache. Because of disturbing side-effects the medication was discontinued. Indomethacin 50 mg was administered at bedtime with complete resolution of the headache.

An ABPM was performed. Indomethacin was stopped that night. During the ABPM he awoke with his nocturnal headache at 02.00 h; BP was 167/95 mmHg, lasting for 2 h. Thirty minutes before it had been 130/70 mmHg. The headache did not improve and after 3 h he took ibuprofen, 1 h later he was pain free. Table 2 summarizes the BP measurements.

Table 2.

Case 2 blood pressure measurements

		Hypertensive peak
	Mean BP (mmHg)	Systolic	Diastolic	N	Duration	bpm
Daytime	131/79 ± 12/7.7	160–150	90	2	15 min	71
Night-time	130/71 ± 17/13	167	95	1	120 min	62
24 h	131/77 ± 13/9.7	—	—	—	—	—

He was diagnosed with essential hypertension after an extensive clinical work-up. Nifedipine retard was prescribed and for the following 4 months he did not report any new nocturnal headache. A control ABPM 4 months later revealed normal BP values.

Discussion

We present two cases of HH which might be considered secondary to nocturnal hypertension.

Although it is assumed that most patients affected by essential hypertension complain of episodes of headache, a convincing relationship between headache and the BP fluctuations over a 24-h period has never been demonstrated, especially in mild to moderate hypertension (9, 10). Some of these hypertensive patients suffer from nocturnal headaches; the circadian rhythm of their BP shows a peak significantly shifted toward the nocturnal hours, probably indicating that the nocturnal timing of BP circadian rhythm may play a role in the recurrence of headaches (11). The mechanism by which nocturnal hypertensive peaks can cause headache is not clear.

Hypothetically, there may be patients with no known arterial hypertension or even with normal diurnal BP in isolated measurements, whose nocturnal headaches might also be related to nocturnal hypertensive peaks. In the two patients described, the fact that the headache improved after appropriate control of nocturnal hypertension offers evidence that the nocturnal hypertension is involved in the pathophysiology of their HH. In spite of this, the influence of antihypertensive treatment on headache may be manifold. Several drugs known to be effective in arterial hypertension are also successfully used in treatment of headache independent of the effect on BP (12). Regarding the use of nifedipine, we can not conclude whether the benefit observed was due to the normalization of BP or other mechanisms.

Arterial hypertension frequently coexists in patients with HH, but only a few published cases have included 24-h BP monitoring (6,13,14). So it is not known how many patients with HH suffer from nocturnal hypertension. The present cases illustrate the value of ABPM to differentiate HH from other nocturnal forms of headache, leading to effective treatment. If there is nocturnal hypertension in some patients fulfilling diagnostic criteria for HH, the challenge is to know whether these two phenomena are merely occurring in parallel or whether they are causally related to some extent. This coexistence also raises the question of what should be the principal diagnosis. If HH can be attributed to a secondary cause it automatically excludes such a diagnosis, following which IHS classification and headache attributed to hypertensive crisis without hypertensive encephalopathy (IHC 10.3.2) should be considered. A second consequence of these two cases is to provide important clinical features of the associated headache that may help to reformulate the diagnostic criteria, thus making the classification a useful working instrument.