Uncommon (Group 4.0) Primary Headaches: Less Familiarity and More Missed Diagnosis
Keywords: Cough headache, exercise headache, hypnic headache, NDPH, nummular headache, other primary headaches, sexual headache
The entities included under group 4.0 of The International Classification of Headache Disorders third edition (ICHD-3) are easy to recognize if one is aware of their distinctive features. Although these are predominantly primary headache entities and generally short-lasting in duration without autonomic accompaniments, it is important to remember that all entities included in this group may occasionally be symptomatic of an underlying structural lesion. It is, therefore, imperative that they are investigated thoroughly with appropriate imaging and/or diagnostic testing. It is also necessary to take a proper history and pick up the right clues. The pathophysiology underlying these primary headaches is still not clear and their treatment is based on uncontrolled trials. Quite a few of them are, however, responsive to indomethacin.
In order that it does not become overwhelming to remember the conditions included in this group, the ICHD-3 has subgrouped these headache entities based on certain linkages. Some are activity related or can be precipitated by Valsalva maneuver, which leads to an increase in intra-abdominal and intra-thoracic pressure, a reduction of venous return, an increase in intracranial venous pressure, a rise in intracranial pressure, and stretch of the hypersensitive receptors on vessel walls, finally resulting in headaches. Primary cough headache is triggered by Valsalva maneuver, primary exercise headache follows sustained nonsexual physical exertion such as those related to sports, running, and workouts and primary headache associated with sexual activity occur before, during, or after orgasm. Since these three entities may rarely present in a thunderclap fashion, primary thunderclap headache has also been included here. Following next are the disorders linked to direct physical stimuli such as cold stimulus headache and external pressure headache, then the epicranial headaches such as primary stabbing headache and nummular headache where there is the involvement of the terminal branches of the sensory nerves of the scalp, and finally, there is the miscellaneous group, which includes hypnic headache syndrome (HHS) and new daily persistent headache (NDPH). These disorders have been listed in [Table 1].
There have been some additions and deletions to this group when compared with the second edition of the classification (ICHD-2). Primary stabbing headaches have been moved from rubric 4.1 to 4.7. Hemicrania continua have been moved out of this group to group 3.0. Cold stimulus headache and external pressure headache have been moved into this group from group 13 of ICHD-2. Nummular headache has been moved up from the Appendix. Hypnic headache syndrome is now included under rubric 4.9 from the earlier 4.5, and NDPH is now 4.10 from 4.8.
4.1. Primary cough headache
Primary cough headache is the commonest of activity-related headache. Cough headaches are mostly primary but may be symptomatic and secondary in up to 40%. The ICHD-3 criteria for primary cough headache are included in [Table 2].
The term “cough” headache tends to sometimes mislead because the same type of short-lasting, bilateral headache can be seen with not just cough alone but also with other Valsalva maneuvers such as sneezing, laughing, and straining. The main clinical feature is of a sudden onset pain, lasting from 1 s to 2 h, and brought on by Valsalva maneuvers. The pain reaches peak instantly and can occur anywhere in the head. Some patients may report associated nausea or vertigo.
Primary cough headache is usually seen in the elderly, beyond 50 years of age, the pain is nonoccipital in location and responds well to indomethacin. When it happens in young individuals or lasts <1 min, is occipital in location, and is not responsive to indomethacin, one should suspect a secondary cause and investigate. Symptomatic underlying causes may be seen in over 40% of all patients presenting with cough headaches. The most commonly seen structural lesion is a Chiari Type I malformation. Other less common causes of secondary cough headache are posterior fossa space occupation, spontaneous intracranial hypotension (SIH), and subdural hematoma. All patients with cough headache should, therefore, undergo magnetic resonance imaging (MRI) of the brain and cervical spine to exclude posterior fossa pathology. Headaches due to migraine, cluster headache, and idiopathic intracranial hypertension can sometimes be aggravated by coughing but they are not precipitated by coughing. Indomethacin 50–100 mg is useful for preventing cough headaches. Acetazolamide, topiramate, propranolol, and naproxen have also been found helpful for the prevention of cough headaches. For secondary cough headaches, treatment will depend on the underlying etiology. Cerebrospinal fluid (CSF) drainage of up to 40 mL provides relief in refractory situations.
4.2 Primary exercise headache
Headache occurring after sustained nonsexual physical exertion in the absence of other structural disorders is labeled “primary exercise headache.” While primary cough headache is triggered by short-lasting effort or activity, primary exercise headache is precipitated by sustained physically strenuous exercise. The headache is sudden in onset, bilateral, throbbing, and long-lasting. Headache is usually experienced at the peak of exercise and gradually subsides when exercise stops. It is mandatory to exclude underlying secondary causes and also differentiate it from a migraine that is triggered by or worsened by exercise. A striking number of those with primary exercise headaches have a personal or family history of migraines. The ICHD-3 criteria for primary exercise headache are included in [Table 3].
As compared with primary cough headache, primary exercise headache is less commonly associated with an underlying secondary cause. All the same, it is necessary to exclude underlying causes such as mass lesions, intracranial hypotension, arterial dissection, and subarachnoid hemorrhage here too. MR imaging with angiography is, therefore, mandatory in all patients with exercise headaches. By way of treatment, exercise must be limited and prophylaxis with indomethacin or beta-blockers or flunarizine have been useful.,, In the elderly who present with a headache after exertion, one has to suspect and rule out cardiac cephalalgia secondary to myocardial ischemia. The headache in these patients improves with antianginal treatment.
4.3. Primary headache associated with sexual activity
This is a form of headache precipitated by sexual activity with other intracranial disorders being ruled out. The subforms in the earlier classification have now been merged as a single entity. The ICHD-3 criteria for these headaches are included in [Table 4]. The headache usually presents as a severe thunderclap headache that reaches the peak at orgasm and then gradually subsides within 1 to 4 h. One study that looked at clinical and imaging findings in sexual activity-related headaches found evidence of secondary causes in 67%. With sexually related headaches, it is imperative to always exclude underlying secondary causes such as subarachnoid hemorrhage, arterial dissection, and reversible cerebral vasoconstriction syndrome (RCVS). Detailed neurovascular imaging is, therefore, a must in such headaches, particularly to rule out RCVS. Postural headaches if they occur with sexual activity should raise the suspicion of spontaneous intracranial hypotension. By way of treatment, acute treatment is not possible for this type of headache. Short-term treatment with indomethacin 1–2 h before sexual activity is useful. Triptans may be an alternative option for those who cannot tolerate indomethacin. For long-lasting preventive treatment propranolol or topiramate has been tried successfully.
4.4. Primary thunderclap headache
All thunderclap headaches or sudden onset, severe headaches must be presumed secondary and will need urgent investigation. One should be familiar with causes of thunderclap headache such as subarachnoid hemorrhage, RCVS, intracranial hemorrhage, pituitary apoplexy, colloid cyst of the third ventricle, cerebral venous thrombosis, and intracranial hypotension. If after an exhaustive search with sophisticated imaging investigational methods, and CSF examination, one is unable to pinpoint or identify an underlying cause, one is justified in labeling it as a primary thunderclap headache. It is, therefore, a diagnosis of exclusion and it is essential to note that the earlier described entities of primary cough headache, primary exercise headache, and headache associated with sexual activity can all rarely present in thunderclap fashion. Tests have to be done in the right sequence, timing is important and tests may have to be repeated if necessary. Some experts, however, doubt the existence of such an entity called primary thunderclap headache.
4.5 Cold stimulus headache and 4.6 external pressure headache
The terms are self-explanatory. Cold stimulus headache is the pain of short duration, maybe of intense severity, triggered by the application of cold to head, or ingestion or inhalation of cold substance and resolves with the removal of the cold stimulus. External pressure headache is triggered by sustained compression or traction of the soft tissue of the cranium. Both these conditions are seen more often in those who also have a migraine. The clinical features of these headaches are included in [Table 5].
4.7. Primary stabbing headache
This entity was earlier known by many different terms and refers to transient, sudden, severe short-lasting stabs of pain in the head. Attacks usually last less than 5 s and can occur multiple times in a day, and the pain most commonly occurs in the distribution of the first division of the trigeminal nerve, but may also involve extra trigeminal areas. More than half the cases have other primary headache conditions associated, most commonly migraine (40%). Primary stabbing headache is not associated with autonomic features and responds well to indomethacin and can, therefore, easily be differentiated from short-lasting neuralgiform headache and trigeminal neuralgia. Other medications that will help in this condition are cyclooxygenase-2 (COX-2) inhibitors, gabapentin, and melatonin.,,,
4.8 Nummular headache
Nummular headache is characterized by a very focal and circumscribed coin-shaped area of pain on the scalp. Most often the parietal region is involved and the pain is unilateral in 50% of cases. The area is round in shape and measures around 2–6 cm in diameter. There may be associated hypesthesia, dysesthesia, or paresthesia, and this pain is secondary to the involvement of terminal branches of sensory nerves. Underlying lesions involving the scalp, skull, or intracranial structures must be ruled out by careful palpation and neuroimaging. Patients with nummular headaches respond to analgesics, gabapentin, antidepressants, and peripheral nerve blocks. There are reports of improvement with botulinum toxin A, indomethacin, and carbamazepine in some patients.,,,,
4.9. Hypnic headache
Hypnic headache was first described by Raskin in 1988. It is an uncommon sleep-related primary headache entity. It is also known as alarm-clock headache and is characterized by recurrent attacks of head pain that wake the patient from sleep at nearly the same time. The attacks are seen more in the elderly, >50 years., usually occurring between 2 AM and 4 AM. The headache has more migrainous features and is not accompanied by autonomic symptoms or restlessness. The duration of the attacks is usually from 15 min to 3 h; there are case reports with a longer duration of attacks also. Other headaches that are nocturnal, waking the patient from sleep, need to be considered in the differential diagnosis. Cluster headache can also present in sleep but the headache is strictly unilateral and associated with autonomic features. Secondary causes need to be ruled out by imaging. Nocturnal blood pressure monitoring and polysomnography should also form part of the diagnostic work-up of hypnic headache. Lithium, indomethacin, and flunarizine are useful in the prevention of hypnic headache.,, Caffeine in the form of a cup of coffee at bedtime has also been found to be helpful.
4.10. New daily persistent headache
New daily persistent headache (NDPH) as the name suggests, is a new-onset headache, that occurs daily, is unremitting from the onset, in individuals who do not usually give a prior history of headache. The date of onset is clearly remembered, the headache can have phenotypic features of migraine or tension-type and may have one or two forms: a self-limiting form that resolves without therapy and a persistent refractory form that is resistant to aggressive treatment. Given the new-onset, secondary causes need to be excluded. Primary NDPH is a diagnosis of exclusion. MR imaging with contrast will help exclude infections, mass lesions, intracranial hypotension, or idiopathic intracranial hypertension.,,, Chronic migraine or chronic tension-type headache need to be excluded. NDPH is a de novo headache and not the escalation of a pre-existing headache. In many patients with NDPH, the headache begins with a flu-like infection or a stressful life event. The current diagnostic criteria for NDPH are provided in [Table 6]. The etiology is unknown. NDPH is difficult to manage. Treatment is based on the headache phenotype. Preventive treatment is as for migraine along with antidepressants where necessary. Care should be taken to avoid medication overuse headaches in patients with NDPH.
All the heterogeneous headache entities included under group 4 “other primary headaches” in ICHD-3 have distinctive clinical features, and the treatment is often specific. Diagnosis is not difficult once you rule out an underlying symptomatic cause. More research is needed to understand clearly the underlying pathophysiology of these entities.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]