A systematic review of causes of sudden and severe headache (Thunderclap Headache): should lists be evidence based?

Sudden and Severe Headache is a common reason for seeking urgent medical advice[1], primarily to exclude aneurysmal subarachnoid haemorrhage[2].

In the process of developing a guideline for managing acute headache we observed variation in the range of diagnoses published[3‐9], so we conducted a systematic review of literature to compile a comprehensive list of potential causes other than aneurysmal subarachnoid haemorrhage.

We estimate completeness of ascertainment of causes using capture-recapture methods, and discuss the implications of using systematic review methods for lists of causation, paying attention to the issue of publication bias.

We searched MEDLINE and EMBASE databases in September 2009 using pre-specified search criteria (Table 1), designed and implemented by a professional librarian (HN), as the Medical Subject Heading (MeSH term) for Thunderclap Headache excludes articles indexed prior to November 1999[10]. We screened titles of publications for potential cases, case series, cohort studies or academic reviews of people with a sudden AND severe headache. Cases were included if the presenting headache was both sudden in onset AND severe in intensity. Cases were excluded if a headache onset was not sudden or if onset was not reported (even the headache was severe or a significant aetiology was subsequently found). Similarly, if a sudden headache was described but there was no description of the severity of the pain, we excluded the case. We excluded publications concerning aneurysmal subarachnoid haemorrhage, as the major purpose of our systematic review was to identify other causes. Publications on Exploding Head Syndrome[11], Neuralgic disorders, such as Idiopathic Stabbing Headaches[12], or Trigeminal Neuralgia[13] were also excluded, as these are characteristic syndromes in their own right. However, these diagnoses could be included if they were reported as the final diagnosis in someone presenting with a sudden AND severe headache.

We included Academic Review articles, as we wanted to compare causes published in academic reviews with those obtained from the data sourced from our systematic review. Academic Review articles had to describe thunderclap headache or the differential diagnosis of thunderclap headache, and not just headache seen in the Emergency Department. We drew up lists of causes which were (a) identified in original articles only, (b) identified in academic review articles only and (c) identified in both original articles and academic reviews.

We were unable to use the International Headache Classification[14], as the majority of authors had not used criteria, and there was usually insufficient information to allow a retrospective classification. We therefore classified cases according to causation.

Our search strategy, executed in September 2009, identified 21,384 potential articles (Table 1). On review of titles we created a shortlist of 1224 publications. The abstracts of these 1224 full text articles were reviewed. 151 publications were duplicates (i.e. listed on both EMBASE and MEDLINE), leaving 1073 papers. Of these 1073, 70 required translation (which we did not have funding to do), and 27 were not traceable, even following inter-library loan requests.

Of the remaining 976 articles, 213 met inclusion criteria of describing a total of 2345 people with sudden and severe headache:

Only one study had prospective, unselected population-based information on the incidence of Sudden Headache - estimating an annual incidence of 43 cases per 100,000 adults[17].

A further 6 articles were identified which were English Language Academic Review articles on Thunderclap Headache that described causes of sudden AND severe i.e. ‘Thunderclap’ headache[3, 4, 6, 7, 18, 19].

This systematic review is therefore based upon a total of 219 English publications (213 original articles and 6 academic reviews). The 764 articles excluded articles were reviews related to acute headache, the investigation of headache, editorial comment or publications of new onset headache where onset AND severity were not reported.

Of the 70 non-English articles, we excluded 29 after using an online translation tool. Of the remaining 41 non-English Language articles, 22 were case reports which included 29 cases, none of which reported causes of sudden and severe headache that were unreported in our English Language papers. There were 8 case series and 4 cohort studies looking at unselected series of people with acute headache. A further 6 non-English academic review articles were identified that examined thunderclap headache[20‐25].

We present a comprehensive review of the literature on Sudden AND Severe Headache up to September 2009.

From our search, we estimate that we have identified 98% of all published causes of Sudden AND Severe Headache in the English Literature.

The literature on sudden and severe headache has some significant weaknesses, yet allows us to make some interesting observations on this potentially serious symptom and how information is reported in medical literature.

Prospective, longitudinal studies of unselected cases are crucial for determining accurate frequencies of incidence or cause. The only estimate of population-based incidence is from Sweden, at 43 cases per 100,000 adults per annum, which was estimated from a sub-set of the population in their study[17]. This figure is important as it is the only one that can inform service planning for the assessment of sudden and severe headache across a large population.

Our understanding of causes of sudden and severe headache is evolving, yet we do not have a precise knowledge of trends or causes of this symptom in a population over time. An emerging theme are the cerebral vasoconstriction syndromes which are attracting a lot more attention in the medical literature and since our literature review have been the subject of several major reviews[275, 276], yet this cause was not described in any of the large cohort studies we found in our systematic review.

In cohort studies, where neurologists assigned diagnosis, headaches of unspecified cause, uncertain cause or a primary headache accounted for the majority of cases in unselected populations. This is contrary to hospital based clinical practice where a diagnosis of migraine, tension-type headache or cluster headache would hardly ever be used in the context of an abrupt onset of severe headache. Sudden and severe headache which remains unexplained following appropriate investigation would normally be called Primary or Idiopathic Thunderclap Headache. Reasons for this large number of unexplained or uncertain headaches remain obscure.

Another seemingly important cause of headache in a population is cervicogenic headache, which was identified in about 4% of adults in the Vaga Study[277]. The cohort studies identified a small number of ‘musculoskeletal’ related headaches[31] and there was one case series of occipital neuralgia presenting acutely to hospital[34], but otherwise this common headache is unreported as causing sudden and severe headache, yet seems a plausible candidate for many of the ‘uncertain’ or ‘unclassified’ cases.

Intracranial Hypotension is an important cause which featured in both cohort and case-based studies - so is both common enough to see in practice, and its treatable nature makes it reportable.

An up to date population-based study could make an important contribution to our current knowledge of sudden and severe headache, specifically the true incidence and prognosis of vasoconstriction syndromes, and better assessment of the clinical features and prognosis of those with ‘uncertain’ or ‘unclassifiable’ headaches.

Cases identified from series are important, as they aggregate information on relatively low frequency conditions as a reference for other clinicians. However, they distort the overall frequency of causes of headaches in our review eg pituitary apoplexy was not reported in the major cohorts. Nonetheless, accumulating cases of specific sub-types can greatly inform clinical practice and generate research hypotheses. An example of this is Headache Associated with Sexual Activity where a recent case series from Taiwan has identified the Reversible Cerebral Vasoconstriction Syndrome in almost 2/3rds of cases[278].

By their nature, case reports will focus on the esoteric or unusual, but our review has highlighted some important associations including systemic conditions like Aortic Dissection[233, 234, 279, 280], Cardiac Cephalalgia[26, 227‐229, 231, 232, 281‐283], Phaeochromocytoma[236, 237], serious infections like Dengue Haemorrhagic Fever[74] and Q-Fever[72], as well as Erve Virus[68, 71]. Rare vasculopathies such as Vogt-Kayanagi-Harada Disease[121, 122], or cerebral vasculitis[119] do appear on the differential diagnosis. Another important presentation, identified in case reports only, was basilar artery dissection manifesting as a coital headache[92].

Cerebral vasculitis is commonly mentioned in discussions about sudden and severe headache, but in numeric terms, we only identified 6 cases of an ‘inflammatory arteriopathy’ compared to 234 cases of a likely vasoconstriction.

This paper presents what we regard as a definitive list of associations of Sudden and Severe Headache. This list is important as it demonstrates that the differential diagnosis of sudden and severe headache is substantial. Our review confirms that a wide range of diseases and provoking circumstances are associated with sudden and severe headache, specifically, haemorrhage, thrombosis, dissection, arterial expansion, extremes of intracranial pressure, infection, inflammation and even intracranial air. In large unselected cohorts the majority of cases are assigned a primary headache diagnosis or have a cause of headache that does not meet any specific diagnostic criteria.

New cases of sudden and severe headache associated with conditions which are not represented in our list should be considered for publication in the medical literature as novel causes.