Abstract
Abstract
Objective
To look at cigarette smoking history (personal and secondary exposure as a child) in non-cluster headache trigeminal autonomic cephalalgias seen at a headache clinic and to determine smoking exposure prevalence utilizing previously published data.
Methods
Retrospective chart review and PubMed/Google Scholar search
Results
Forty-eight clinic patients met ICHD-3 criteria for non-cluster headache trigeminal autonomic cephalalgias. Four had paroxysmal hemicrania, 75% were smokers and secondary exposure was noted in all. 16 patients had short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), 12.5% were smokers and secondary exposure was noted in 91%. Twenty-eight patients had hemicrania continua, 21% were smokers and secondary exposure was found in 62.5%.
Since 1974 there have been 88 paroxysmal hemicrania, 50 SUNCT or SUNA and 89 hemicrania continua patients with a documented smoking exposure history. From current data and previous studies, a smoking history was noted in 60% paroxysmal hemicrania, 18% SUNCT and SUNA and 21% hemicrania continua patients.
Conclusion
A cigarette smoking history appears to be connected to paroxysmal hemicrania (personal and secondary exposure) and possibly to SUNCT/SUNA (secondary) and hemicrania continua (secondary).
Keywords
Introduction
The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders marked by trigeminal based head pain and cranial autonomic associated symptoms. Under the current International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria the TACs include cluster headache (CH), paroxysmal hemicrania (PH), short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), and hemicrania continua (HC) (1). Cluster headache is the most prevalent of all the TACs and has been the most extensively studied by headache researchers. What has been known for quite some time is that CH is associated with a personal history of tobacco use (2–5). The majority of CH sufferers have a past or current cigarette smoking history. In addition, they also appear to have a very high prevalence of significant secondary parental cigarette smoke exposure as a child (6). The United States Cluster Headache survey noted that only 12% of CH sufferers have had no prior tobacco exposure while the majority have a double exposure history with heavy contact as a child and then that same individual starts to smoke at some point in their lifetime typically prior to CH onset (7). Thus, exposure to cigarette smoke, and its toxins in some manner is potentially involved in CH pathogenesis (8). The exact cause-and-effect relationship is not yet fully elucidated. What has not been well reported however is the cigarette smoking history in non-cluster headache TACs. As all the TACs based on functional neuroimaging appear to have some form of hypothalamic modulatory abnormalities, and due to the fact that certain cigarette toxic metabolites alter the hypothalamic pituitary gonadal (HPG) axis, it would be important to ascertain if a personal and secondary cigarette smoke exposure history is also associated with the non-cluster headache TACS; thus also linking their pathogenesis to smoking (8–12). The goal of the present study was to look at the cigarette smoking history both personal and secondary in non-cluster headache TACs seen at an academic headache clinic and then to determine cigarette smoking exposure prevalence in PH, SUNCT, SUNA and HC utilizing both the present clinic data and any smoking history data previously published on these syndromes.
Methods
This was a retrospective chart review study. Patients with PH, SUNCT, SUNA, and HC were identified from the Mayo Clinic electronic medical record (EMR) utilizing International Classification of Diseases (ICD)-9 and/or ICD-10 codes from 2016 to 2021. All patients were seen by the same headache neurologist in the clinic where the diagnosis was made. All had to meet ICHD-3 criteria for each individual TAC (1). For both PH and HC indomethacin responsiveness was verified in subsequent patient visits. The EMR for this study was utilized to find patients that the author had previously seen in clinic with specific trigeminal autonomic cephalalgia diagnoses. Once the patient’s medical records were identified the author went through each chart individually verifying the diagnosis using ICHD-3 criteria as some of the patients had been first evaluated while ICHD-2 criteria were in use (13). In regard to the patient’s tobacco exposure history, the medical record requested a smoking history but in the majority of cases this information was absent. In addition, there was absolutely no information on secondary smoke exposure in the EMR. Thus, the EMR alone was not utilized to obtain the cigarette smoking exposure history. The data was obtained by looking over each chart individually. Every TAC patient consulted on by the author was asked about a personal smoking history at their original consultation visit. This was verified while re-investigating the charts for the current study. In every instance, personal tobacco exposure was via cigarettes. To be considered a smoker past or present the patient had to smoke cigarettes on a daily or near daily basis for at least one years’ time before onset of their headache syndrome. Many smoked daily for years to decades. Secondary cigarette smoking history as a child was defined as exposure within the first five years of lifetime in the house because one or both parents smoked and/or secondary exposure by grandparents if they were heavily exposed to that grandparent. In many instances the parent(s) who smoked were heavy smokers leading to secondary complications like lung cancer or emphysema. As the majority of parents continued to smoke at least into the patient’s teenage years the patient felt confident about their secondary smoke exposure history as a young child. A secondary smoke exposure history was not present in a certain number of charts on retrospective review (one patient with PH, eight patients with SUNCT or SUNA and 17 patients with HC). Thus, if this data was missing, then these individual patients were first contacted through the EMR portal system with the following statement:
“Previously (and or currently) you have been seen at the Headache Clinic at Mayo Clinic Florida and have been diagnosed with a trigeminal autonomic cephalalgia (paroxysmal hemicrania, hemicrania continua or SUNCT/SUNA)
We are doing a quick survey on secondary smoke exposure history for these headache conditions.
Could you please reply to these questions and forward back:
When you were a child (specifically 5 years of age or younger) did either of your parents smoke in the house and if so who smoked: father, mother or both If either of your parents were smokers would you state they were heavy, moderate or mild smokers? Did either of your parents develop smoking related complications including emphysema or lung cancer?”
If after two weeks, there was no response to this communication then two subsequent phone calls were made to the patient to try to obtain this data. If after two calls, there was either no response and/or no return call after a voicemail message was left then no further attempts of communication were made.
In total we were able to get email/telephone confirmation of secondary smoke exposure data for 1/1 of the PH patients, 3/8 of the SUNCT and SUNA patients and 5/17 of the HC patients leaving five and 12 subjects without this information respectively.
The author then searched PubMed/Google Scholar with the following search criteria from 1974–2022: paroxysmal hemicrania, chronic paroxysmal hemicrania, episodic paroxysmal hemicrania, SUNCT, SUNA, hemicrania continua, remitting hemicrania continua, and unremitting hemicrania continua. The starting date of 1974 was chosen as this was the first published report of paroxysmal hemicrania. Only published manuscripts which utilized ICHD criteria were included in the study. The exception was several manuscripts published prior to the ICHD criteria and these only included the original descriptions of the unique TAC syndromes authored by well-known headache specialists. Exclusion criteria were cases with overt secondary underlying etiologies (e.g: post stroke or bleed, pituitary tumor, artery dissection). The author then looked at every available study from case reports to case series to larger epidemiologic surveys for any documentation of personal and secondary smoke exposure. Most published manuscripts including the largest case series on these conditions lacked any smoking history documentation and no secondary smoke exposure history was noted. For PH the largest number of reported cases in a single study with a documented tobacco exposure history was 74 patients (lacked sex distribution), SUNCT and SUNA 20 patients and for HC a study of 34 patients (no sex distribution was noted) (14–16). All pediatric and adolescent investigations had no personal or secondary cigarette smoke exposure data (17–19). None of the original case descriptions for each of these unique conditions mentioned a smoking history (20–22).
Ethics
This study was approved by the Mayo Clinic Institutional Review Board-IRB number: 19-002635 and receipt of a waiver of the need to consent subjects was obtained.
Statistical analysis
This was primarily a descriptive study and thus no statistical analysis was utilized.
Results
From the retrospective chart review a total of 48 patients met ICHD-3 criteria for non-cluster headache TACs. Patient demographics, clinical symptomatology, and cigarette smoking history data (personal and secondary) are included in Table 1.
Patient demographics.
EPH, Episodic Paroxysmal Hemicrania; CPH, Chronic Paroxysmal Hemicrania; SUNCT, Short Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing; SUNA, Short Lasting Unilateral Neuralgiform Headache Attacks with Autonomic Symptoms; rHC, Remitting Hemicrania Continua; HC, Unremitting Hemicrania Continua; P, Ptosis; CI, Conjunctival Injection; L, Lacrimation; R, Rhinorrhea; A, Agitation.
Paroxysmal Hemicrania
Four patients had PH (two chronic PH and two episodic PH). Three of our four PH patients (75%) had a personal smoking history (2/2 with EPH and 1/2 with CPH). All PH patients were women thus all smokers were female. Average age of onset of PH in smokers was 46 years and in non-smokers was 59 years. Parental secondary smoke exposure was noted in all patients. Double exposure was noted in all smokers and for those patients both parents smoked.
SUNCT and SUNA
Sixteen patients had SUNCT (13) or SUNA (3). There were nine females and seven males. Of these patients only two of 16 (12.5%) had a personal smoking history. Both had SUNCT, both were males, and both were past smokers. Average age of onset of SUNCT and SUNA in smokers was 52 years and in non-smokers was 54 years. Parental secondary smoke exposure was noted in 10/11 patients (91%) in whom we have data, while double exposure was noted in only two patients; thus 80% of SUNCT and SUNA patients who had secondary smoke exposure never smoked themselves.
Hemicrania Continua
Twenty-eight patients had HC (two remitting, 26 unremitting; 24 female and 4 male ) of which six were smokers (21%) and all had the unremitting form. Regarding sex distribution five of six smokers were women. Average age of onset of HC in smokers was 44 years and in non-smokers was 41 years. Parental secondary smoke exposure was noted in 10 of 16 patients (62.5%) that we have data on. Double exposure was noted in only two of 10 patients (20%).
Previously Published Cases
Table 2 lists the smoking exposure history of non-cluster headache TACs that have been previously published in the literature (14–16,23–48). Overall, this is very scant data. When looking at case reports, case series and large survey studies, rarely was a smoking history documented and outside of our present study, no secondary smoke exposure history as a child has ever been reported in either the adult or pediatric literature for these syndromes. The present clinic study has the second largest account of patients with a cigarette smoking exposure history for PH, SUNCT, SUNA and HC ever documented.
Cigarette smoking history in non-cluster headache trigeminal autonomic cephalalgias: Current and past studies.
EPH, Episodic Paroxysmal Hemicrania; CPH, Chronic Paroxysmal Hemicrania; SUNCT, Short Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing; SUNA, Short Lasting Unilateral Neuralgiform Headache Attacks with Autonomic Symptoms; rHC, Remitting Hemicrania Continua; HC, Unremitting Hemicrania Continua.
Including the present clinic data, 88 PH patients have been reported with a personal smoking exposure history (positive or negative). The largest study was by Boes and Dodick in 2002 documenting 74 patients (in 73 patients they had a documented smoking history) of which 57% smoked cigarettes and in 1% a cigar/pipe user (14). This study however did not include the sex distribution of the smokers and non-smokers although the majority of the patients were women. From all investigations 53 of 88 PH patients (60%) were smokers (32 current, 21 past) (14,23–31). The majority of published cases were CPH in which 51/85 subjects (60%) smoked. Regarding sex distribution seven patients were males while three were female, but again the largest study did not include sex distribution (Table 2).
For SUNCT and SUNA there have been 50 cases with smoking exposure documented histories that have been published (15,32–40). Only 9/50 or 18% had a personal smoking history (one cigar smoker). From the two largest studies which compile 72% of all cases only 5/36 or 14% were cigarette smokers (15) (Table 2). There was only one SUNA positive case while the remainder were diagnosed with SUNCT. For the reported cases with documented sex distribution (six cases) all but one was male. The largest study however did not note the sex of their patients who smoked (15).
Finally, for HC a total of 89 cases have been reported of which 19 cases had a personal smoking history or 21% (16,41–48). From the two largest studies (70% of all cases) only 11/62 or 18% smoked (16) (Table 2). Regarding the sex distribution of smoking exposed versus non exposed that have been documented 10 of 14 cases were women.
Discussion
From this investigation, both a personal and secondary cigarette smoking history appears to be linked to PH. The prevalence of a personal cigarette smoking history in PH is lower but approaching that noted in CH and is much higher than the United States and worldwide cigarette smoking prevalence (2–7,49,50) (Figure 1). Double exposure history (noted in all of our patients) may surpass that noted in CH although the number of PH patients reported is much smaller (7).
Personal cigarette smoking prevalence in non-cluster headache trigeminal autonomic cephalalgias compared with United States and worldwide population prevalence.
SUNCT and SUNA syndrome from the current study data and prior reports is not linked to a personal history of cigarette smoking as the smoking prevalence is less than that seen in the United States and general worldwide population (49,50) (Figure 1). However, SUNCT and SUNA appear to be linked to secondary smoke exposure as a child as 91% of our patients were born into a household with parents who smoked. This has never been previously documented. Unlike CH and PH, double exposure does not appear to be prevalent in this TAC population.
Finally, HC does not appear to be linked to a personal cigarette smoking history with a prevalence which is less than or almost equal to that noted in the United States and worldwide population (Figure 1). HC however, like PH and SUNCT may have an association with secondary cigarette smoking exposure history as a child with more than 60% being exposed. This however is not as frequent as noted in CH, PH and the SUNCT/SUNA populations.
Paroxysmal hemicrania is the most phenotypically similar to CH and now it appears that both conditions are in some manner influenced by cigarette smoking exposure specifically double exposure. SUNCT syndrome may also be secondary to heavy secondary smoke exposure as a child. Our data also suggests some possible influence of secondary cigarette smoke exposure on the pathogenesis of HC. SUNCT, SUNA and HC patients smoked the least of the TAC populations and it is feasible the lack of a personal smoking history is part of the reason why they present differently than CH and PH. Hypothetically this could relate to how much cigarette smoke toxin that individual’s HPG axis is exposed to prior to the headache syndrome initiating. There has been some thought that HC should not be part of the TAC spectrum (51). Based on our current study results and if indeed cigarette smoke is involved in the pathogenesis of the TACs then HC should belong to the spectrum. A definitive statement on the sex distribution in smoking exposed and non-exposed non-cluster headache TAC populations cannot be made as the largest studies for all these syndromes did not document the sex distribution of their smokers and non-smokers.
Limitations
The main limitation of this clinic-based study is that we do not have secondary smoke exposure data for all of our reported patients thus definitive statements on how this issue effects non-cluster headache TACs cannot be made. Even in the secondary smoke exposure positive cases there may be recall bias issues as the patient cannot definitively state they were exposed at age five years and younger unless validated by the parents. However, the fact that the parents still chronically smoked at least into the patients’ teenage years suggests the secondary exposure history is accurate. The greatest limitation is the lack of smoking data altogether in the published literature for PH, SUNCT, SUNA and HC. Thus, some possible connections can be suggested but certainly not defined without more data. Our data also did not allow an analysis of the possible dosage-dependent effects of smoking exposure on the non-cluster headache TACs. Finally, it is feasible that some single case reports with a smoking exposure history were missed as this was an extensive literature search and each individual report had to be combed through for smoking data as it was almost never mentioned outright.
Conclusion
Tobacco exposure appears to be connected not only to CH, but to PH, SUNCT, SUNA and feasibly to HC. It seems clear that if we want to get a better understanding of the underlying pathogenesis of the TACs we must delve further into their connection with tobacco exposure. The author has already suggested a possible pathogenic connection in CH, but further study is necessary for all these conditions (8). Future investigative studies of the TACs should take into account cigarette smoking exposure history as imaging and laboratory studies may differ in smokers versus non-smokers or double exposed versus single exposed and thus influence results and subsequently the understanding of these unique syndromes.
Article highlights
Cluster headache is the most well studied of the trigeminal autonomic cephalalgias and most sufferers have a personal smoking history and a high prevalence of secondary parental smoke exposure as a child. What has not been well reported is the tobacco exposure history in non-cluster headache TACs. From this investigation paroxysmal hemicrania is associated with a tobacco exposure history both personal and secondary. In all cases both parents were smokers. SUNCT/SUNA is not associated with a personal smoking history but appears to be associated with secondary exposure. Hemicrania continua is not linked to a personal history of smoking but may be associated with secondary smoke exposure as a child.
Footnotes
Declaration of conflicting interests
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author received no financial support for the research, authorship, and/or publication of this article.
