Systematic literature review on the delays in the diagnosis and misdiagnosis of cluster headache.

INTRODUCTION: Patients with cluster headache (CH), the most common trigeminal autonomic cephalalgia, often face delayed diagnosis, misdiagnosis and mismanagement. OBJECTIVES: To identify, appraise and synthesise clinical studies on the delays in diagnosis and misdiagnosis of CH in order to determine its causes and help the management of this condition. METHODS: The systematic review was prepared, conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis. It was registered with International Prospective Register of Systematic Reviews. A systematic search of different electronic databases (Medline, EMBASE, PsycINFO, PubMed, CINAHL, BNI, HMIC, AMED, HBE and Cochrane Library) was carried out in May 2017. Reference lists of relevant articles were hand searched. RESULTS: The search identified 201 unique studies. Fifteen studies met the inclusion criteria of which 13 case series studies and two survey studies. Nine studies assessed the delays in diagnosis and misdiagnosis of CH, five studies the delays in diagnosis and one study the misdiagnosis of CH. The studies included 4661 patients. Delays in diagnosis, misdiagnosis and mismanagement have been reported in many European countries, Japan and in the USA with well-developed health services. The patients with CH often visited many different clinicians, surgeons and dentists and received multiple diagnosis prior to being correctly diagnosed. CONCLUSION: This systematic review shows that the delays in the diagnosis of CH are a widespread problem, the time to diagnosis still vary from country to country and both patients and physicians are responsible for the delays in diagnosis.

The comorbidity burden of patients with cluster headache: a population-based study.

BACKGROUND: Evidence is limited regarding the comorbidity burden of patients with cluster headache (CH). We aimed to characterize comorbid conditions in a cohort of CH patients diagnosed by headache experts, using electronic health record information from the Partners Research Patient Data Registry (RPDR). METHODS: We identified and reviewed the charts of unique patients diagnosed by headache specialists over an 11-year period, and a set of matched controls. Patients were categorized as having Definite, Unconfirmed or no CH. We calculated the prevalence of and tested for statistically significant differences of selected comorbid conditions in these populations. RESULTS: An RPDR query identified 170 patients with a free text or ICD diagnosis of cluster headache. 15 records belonging to Partners employees were excluded. 75 patients met diagnostic criteria for CH (Definite CH). 22 had headaches with some features of CH but the diagnosis was uncertain (Unconfirmed CH). In 58 the diagnosis was determined to be inaccurate due to data entry errors. Patients with Definite CH had an average age of 43.4 years; 80% were male. The average time from CH onset to diagnosis was 12.7 years (range 1-51). The average number of yearly emergency department and outpatient visits for the group of Definite CH patients was 4.5 and 25.4, respectively, compared with 1.1 and 6.9 in controls. Of the 55 examined conditions, four were statistically significantly less common in patients with definite CH compared with controls (diabetes, musculoskeletal/orthopaedic problems, "other gastrointestinal diagnoses" and skin conditions) and four were statistically significantly more common (smoking, depression, dental disorders and deviated septum). CONCLUSIONS: In this large population-based study, we identified a surprisingly small number of patients who met strict diagnostic criteria for CH. In these patients, however, we identified a distinct pattern of selected comorbidities. The pattern is somewhat but not entirely consistent with that of the "classic" CH patient depicted in the medical literature. CH patients are frequently diagnosed with sinus or dental problems. Many experience substantial delay in receiving a diagnosis. These things may in part explain the high frequency of medical visits in this population. It is difficult to distinguish conditions that are genuinely comorbid with CH from those that reflect misdiagnoses or medical scrutiny of patients in frequent contact with the healthcare system.

Diagnosis and clinical features of trigemino-autonomic headaches.

Although severe short-lasting headaches are rare, they can be considered disabling conditions with a major impact on the quality of life of patients. These headaches can divided broadly in to those associated with autonomic symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few or no autonomic symptoms. The TACs include cluster headache, paroxysmal hemicranias, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms as well as short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. In all of these syndromes, half-sided head pain and ipsilateral cranial autonomic symptoms such as lacrimation or rhinorrhea are prominent. The paroxysmal hemicranias have, unlike cluster headaches, a very robust response to indomethacin, leading to a notion of indomethacin-sensitive headaches. The diagnosis of TACs is exclusively a clinical task. Because of the fact that cluster headache is strictly half-sided, typically involves the region around the eye and temple and often starts in the upper jaw, most patients first consult a dentist or ophthalmologist. No single instrumental examination has yet been able to define, or ensure, the correct diagnosis, or differentiate idiopathic headache syndromes. It is crucial that a trained neurologist sees these patients early so that management can be optimized and unnecessary procedures can be avoided. Although TACS are, in comparison to migraine, quite rare, they are nevertheless clinically very important for the neurologist to consider as they are easy to diagnose and the treatment is very effective in most patients.

Cluster-like headache. A comprehensive reappraisal.

Among the primary headaches, cluster headache (CH) presents very particular features allowing a relatively easy diagnosis based on criteria listed in Chapter 3 of the International Classification of Headache Disorders (ICHD-II). However, as in all primary headaches, possible underlying causal conditions must be excluded to rule out a secondary cluster-like headache (CLH). The observation of some cases with clinical features mimicking primary CH, but of secondary origin, led us to perform an extended review of CLH reports in the literature. We identified 156 CLH cases published from 1975 to 2008. The more frequent pathologies in association with CLH were the vascular ones (38.5%, n = 57), followed by tumours (25.7%, n = 38) and inflammatory infectious diseases (13.5%, n = 20). Eighty were excluded from further analysis, because of inadequate information. The remaining 76 were divided into two groups: those that satisfied the ICHD-II diagnostic criteria for CH, 'fulfilling' group (F), n = 38; and those with a symptomatology in disagreement with one or more ICHD-II criteria, 'not fulfilling' group (NF), n = 38. Among the aims of this study was the possible identification of clinical features leading to the suspicion of a symptomatic origin. In the differential diagnosis with CH, red flags resulted both for F and NF, older age at onset; for NF, abnormal neurological/general examination (73.6%), duration (34.2%), frequency (15.8%) and localization (10.5%) of the attacks. We stress the fact that, on first observation, 50% of CLH presented as F cases, perfectly mimicking CH. Therefore, the importance of accurate, clinical evaluation and of neuroimaging cannot be overestimated.

Female cluster headache in the United States of America: what are the gender differences? Results from the United States Cluster Headache Survey.

OBJECTIVE: To present results from the United States Cluster Headache Survey regarding gender differences in cluster headache demographics, clinical characteristics, diagnostic delay, triggers, treatment response and personal burden. BACKGROUND: Very few studies have looked at the gender differences in cluster headache presentation. The United States Cluster Headache Survey is the largest study of cluster headache sufferers ever completed in the United States and it is also the largest study of female cluster headache patients ever presented. METHODS: The total survey consisted of 187 multiple choice questions which dealt with various issues related to cluster headache including: demographics, clinical characteristics, concomitant medical conditions, family history, triggers, smoking history, diagnosis, treatment response and personal burden. A group of questions were specifically targeted to female cluster headache patients. The survey was placed on a website from October to December 2008. For all survey responders the diagnosis of cluster headache needed to be made by a neurologist but there was no validation of the headache diagnosis by the authors. RESULTS: 1134 individuals completed the survey (816 male, 318 female). Key Points that define the differences between female and male cluster headache include: a. Age of onset: women develop cluster headache at an earlier age than men and are more likely to develop a second peak of cluster headache onset after 50 years of age. b. Family history: woman cluster headache sufferers are more likely to have a family history of both cluster headache and migraine and have an increased familial risk of Parkinson's disease. c. Comorbid conditions: female cluster headaches sufferers are significantly more likely to experience depression and have asthma than males. d. Aura issues: aura with cluster headache is equally common in both sexes, but aura duration is shorter in women. Women are much more likely to experience sensory, language and brainstem auras. e. Pain location: cluster headache pain is typically retro-orbital in location in both sexes but women are significantly more likely to experience cluster headache pain in the jaw, cheek and ear than men. f. Associated symptoms: women with cluster headache develop more "migrainous" associated symptoms than men, especially nausea and they are also more likely to have self-injurious behavior than men. g. Triggers: women with cluster headache are much less likely to have alcohol trigger a headache, but are significantly more likely to have "migrainous" triggers for their cluster headaches than men. h. Smoking issues: women are much less likely to have a smoking history than male cluster headache sufferers, more likely to have never smoked prior to cluster headache onset. i. Cycle issues: spring and fall are the most common time to start a cluster headache cycle in both sexes. Women are statistically significantly less likely to start a cluster headache cycle in the months of October­December than men. Women have more attacks per day and higher pain intensity nighttime attacks than men. j. TREATMENT: in regard to acute treatment women statistically were less response to sumatriptan injectable and nasal spray than men, but statistically more likely to respond to inhaled lidocaine. There was equal efficacy in the sexes to inhaled oxygen but slower response in women. For preventive treatment no significant gender differences were noted, but overall women were less responsive to almost all preventives than men. k. Diagnostic delay: there remains a significant diagnostic delay for cluster headache patients in both sexes but women were more likely to be diagnosed after 10 years of symptom onset than males and significantly fewer women were diagnosed correctly at an initial physician visit than men. l. Female specific issues: cluster headache does not appear to be influenced by menses or menopause but 50% of the survey responders stated their headaches improved with pregnancy. Cluster headache does not appear to alter fertility rates in female cluster headache sufferers. m. Personal burden: cluster headache causes significantly more personal burden in women than men with more loss of employment and/or need of disability, as well as more homebound days. CONCLUSION: Overall women and men with cluster headache have a similar presentation but there are some distinct differences that have been suggested in smaller studies of female cluster headache that we have now verified, while some of our study conclusions have not been shown previously. One major limitation to the study is a lack of validation of diagnosis. A substantial false positive cluster headache diagnosis rate, especially in females, cannot be excluded by the study methods utilized.

Features involved in the diagnostic delay of cluster headache.

BACKGROUND: Cluster headache (CH) is a comparatively rare, very severe primary headache. Although circumscript and recognisable criteria are available, the diagnosis is often missed or delayed. Besides, while adequate and evidence based treatment is available in diagnosed cases, CH seems to be poorly managed. The authors performed a nationwide survey among CH patients, and looked for factors involved in the diagnostic delay. METHODS: The authors performed a nationwide mailing to all Dutch general practitioners (about 5800), and neurologists (about 560) and invited them to refer patients in whom the diagnosis CH was made or considered. Patients could also apply via the Dutch Headache Patients Society. A variety of clinical characteristics were assessed by means of questionnaires. Specifically, patients were asked about the time between their first episode and the diagnosis. RESULTS: The IHS criteria for CH were met by 1429 of 2001 responders, and 1163 of these filled in an extended questionnaire. The male to female ratio was 3.7:1. Mean age at onset was 32 (SD 14) years. Seventy three per cent had episodic CH, 21% had chronic CH, and in 6% the periodicity was undetermined. The time between the first episode and the diagnosis ranged from 1 week to 48 years (median 3 years): 34% had consulted a dentist and 33% an ENT specialist before the diagnosis was established. Among factors that increased the diagnostic delay were the presence of photophobia or phonophobia, nausea, an episodic attack pattern and a low age at onset (p<0.01). Sex or presence of restlessness during episodes did not influence the diagnostic delay. CONCLUSION: CH remains unrecognised or misdiagnosed in many cases for many years. Photophobia or phonophobia and nausea were in part responsible for this delay, and should be recognised as part of the clinical spectrum of CH. Many patients were first seen by a dentist or ENT specialist for their CH episodes, so more attention should be paid to educate first line physicians to recognise CH, to improve the diagnostic process and so to expose patients to earlier and better treatment of CH.