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Original Article
Development of persistent headache following stroke: A 3-year follow-up
Cephalalgia 0(0) 1–11 ! International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102414545894 cep.sagepub.com
Anne P Hansen1, Ninna S Marcussen1, Henriette Klit1, Helge Kasch2,3, Troels S Jensen1,3 and Nanna B Finnerup1 Abstract Background: Headache following stroke has been described in previous studies with an incidence of 23%–54%, but a clear description of headache developing after stroke onset is still lacking. The aim of this study was to determine the incidence and characteristics of persistent novel headache after stroke and to describe the use of medication, including dipyridamole. Methods: As a follow-up to a prospective study, a standardized questionnaire about characteristics of novel headache and medication use was sent out to surviving patients three years after their stroke. Results: The questionnaire was sent to 256 patients and returned by 222, of whom 12% (26/222) of patients reported persistent novel headache. Dipyridamole had no significant influence on the incidence. Stroke-attributed headache according to predefined criteria was reported in 7.2% (16/222) of patients, with tension-type-like headache in 50.0%, migraine-like in 31.3% and medication overuse in 6.25% of patients. More than half of patients experienced moderate to severe pain and had a score of 55 or above on the Headache Impact Test-6 scale. Conclusion: Novel headache after stroke affects one in 10 patients and seems to be unrelated to dipyridamole use. Persistent headache attributed to stroke is similar to tension-type headache for half of patients. Keywords Post-stroke headache, prospective study, medication overuse, dipyridamole, tension-type headache Date received: 4 June 2014; revised: 4 July 2014; accepted: 7 July 2014
Introduction Headache is a well-known symptom at stroke onset and has been reported in 9.3%–38% of patients (1–12). Persistent headache following stroke has, however, been described in only a few studies with an incidence of 10.8%–23.3% within two years after stroke (13–16). A few stroke studies have distinguished between preexisting and novel headache and between different types of headache, e.g. migraine or tension-type headache (2,16). Because both headache and stroke are prevalent conditions, it is necessary to distinguish between headache that existed before the stroke and persistent post-stroke headache and to know the time interval between the two phenomena if a causal relationship is to be postulated. Medication-overuse headache may arise when headache patients consume medication in order to achieve relief of headache or other pain (17–19). To our knowledge, the role of headache medication overuse after stroke has not previously been studied. Dipyridamole is
a frequently used antiplatelet with the well-known adverse event of headache in 9%–42% of patients (20,21), which is considered to be due to cyclic guanosine monophosphate activation and indirect adenosine-mediated activation of headache pathways, similar to findings in sildenafil and nitroglycerin provocations (22,23). The aim of this study was to determine the incidence of novel headache following stroke (International Headache Society (IHS) categories 6.1.1. and 6.2.1) and to describe the characteristics of this secondary 1 Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark 2 The Headache Clinic, Aarhus University Hospital, Aarhus, Denmark 3 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Corresponding author: Anne P Hansen, Danish Pain Research Center, Aarhus University Hospital, Norrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. Email:
[email protected]
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2 headache attributed to vascular disorder, including a sub-classification of migraine-like (IHS: 1) or tensiontype-like headache (IHS: 2). Finally, we wanted to examine the influence of headache medication overuse and dipyridamole use on the development of headache.
Methods Patients and initial examination The study is a three-year follow-up of patients with a stroke diagnosis (ICD-10 codes: I61, I63, I649, I676, I677) from a previously published prospective study on post-stroke pain (4). Patients with a diagnosis of transitory cerebral ischemic attack (G459) or subarachnoid hemorrhage (I609), communication problems (e.g. severe aphasia or dysarthria), dementia, somnolence, lack of consent to participate, or lack of Danish language skills were excluded. Two hundred and seventyfive stroke patients acutely admitted to the Stroke Unit at the Department of Neurology, Aarhus University Hospital, from February 2007 to July 2008, underwent a structured interview on persistent or recurring pain including headache within the three months preceding their stroke and questions on pain experienced in close temporal relation to stroke onset followed by a brief standardized sensory examination conducted by two of the authors (N.S.M and A.P.H) (4). Stroke etiology was determined in agreement with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification by two of the authors (N.S.M and A.P.H) (24,25). The Scandinavian Stroke Scale (SSS, 0–58) was used for measuring stroke severity, with a score of 45 or below representing a severe stroke (26,27).
Three-year follow-up A standardized questionnaire designed to classify possible migraine or tension-type headache following stroke was developed based on the principles described by Olesen and Dodick (28) and tested in a post-stroke headache group recruited from another study (29). The final questionnaire was mailed to all surviving patients from the prospective study three years after stroke with an accompanying letter explaining the purpose of the study and requesting that the patient fill in the questionnaire or ask the investigator (A.P.H.) for assistance completing the questionnaire over the phone (4). Patients were asked if they had suffered from headache prior to their stroke and to indicate if the severity of their headache had changed after the stroke (more severe, unchanged, or better). The Headache Impact Test-6 (HIT-6) scale on impact of headache on daily life was applied (30,31).
Cephalalgia 0(0) If patients indicated development of novel headache after the stroke, they were asked: ‘‘Have you following your stroke experienced a new headache which you did not have before your stroke?’’ and ‘‘Have you had this novel headache within the last 4 weeks?’’ All patients who answered ‘‘yes’’ to both questions were included and asked specific questions about the onset, frequency, location, duration, intensity, and description of their headache, including characteristics such as nausea and vomiting, phono- and photophobia, possible treatment, and they were asked to score the impact of their headache on daily life on the HIT-6 scale. A reminder was sent out once, and non-responders were categorized as lost to follow-up. All drugs dispensed through pharmacies to all citizens in Denmark are registered in the Danish National Prescription Registry. Since headache is a well-known side effect of dipyridamole, a request was sent to the patients together with a written consent to access the database on dipyridamole prescriptions. No reminders were sent to non-responders. All patients gave written consent at stroke onset, and the study was conducted in accordance with the Declaration of Helsinki and approved by the Danish Data Protection Agency (2006-41-6900). The prospective study was approved by the local ethics committee (20060116).
Data analysis The patients were divided into two groups based on two criteria. First, their response about headache onset in the prospective study (4) and second, their positive response on headache development at the three-year follow-up to distinguish between stroke-attributed and non-stroke-attributed headache. The first group included patients who reported headache both at stroke onset and at the three-year follow-up. The second group included patients who had not reported headache at stroke onset, but reported novel headache at the three-year follow-up. The intensity of headache was classified as ‘‘mild’’ if the patients scored 3 or below on the numeric rating scale (NRS), ‘‘moderate’’ with a score between 4 and 7, and ‘‘severe’’ with a score of 8 or higher (32). The HIT-6 scale (range 36–78) was used as a measurement of impact of headache on daily life. A score below 50 indicated ‘‘no or little impact,’’ a score of 50– 55 ‘‘to have some impact,’’ a score of 56–59 ‘‘to have substantial impact,’’ and a score above 60 ‘‘to have severe impact’’ on the daily life of patients (31,33). While depression was not directly measured, possible depression was assessed by evaluation of self-reported use of antidepressant medicine both at stroke onset and at the three-year follow-up.
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3
Hansen et al. Headache was classified as probable migraine (G43.83) or probable tension-type headache (G.44.28), using the criteria from the second edition of The International Headache Classification (ICHD-2) (18). Patients presenting both with probable migraine and probable tension-type headache were classified as mixed headache. Patients who could not be classified as probable migraine, tension-type or mixed headache were categorized as having other headache. Headache medication overuse was diagnosed based on the self-reported use of headache relief medication as 15 days or triptans and/or opiates 10 days per month as well as on an underlying novel headache frequency of 14 days or more per month.
Statistical analysis Data were analyzed with STATA 11 software (StataCorp LP, College Station, TX, USA). Pearson’s 2 test or Fisher’s exact test was conducted for comparison of categorical variables depending on group sizes. T-test and Wilcoxon rank-sum were applied for continuous variables. Odds ratio (OR) was used to estimate risk factors. Two-tailed probability (p) values 14 and 21 (women and men) units per week, % (n/N) Smoker, % (n/N) Current Prior Never Diabetes, % (n/N) Hypertension, % (n/N) Atrial fibrillation, % (n/N) History of acute myocardial infarction, % (n/N) Intermittent claudication, % (n/N) Prior stroke, % (n/N) Prior TIA (transient cerebral attack), % (n/N)
Patients with headache (26/222)
Patients without headache (196/222)
42.3 63.5
(11/26) (36–90)
55.1 68.7
(108/196) (27–95)
84.6 15.4
(22/26) (4/26)
90.8 9.2
(178/196) (18/196)
73.1
(19/26)a
50.0
(93/186)
9.1 13.6 40.9 0.0 36.4 0.0 49.5 26.9 7.7
(2/22) (3/22) (9/22) (0/22) (8/22) (0/22) (20–58) (7/26) (2/26)
13.5 13.5 39.9 3.4 20.8 1.1 52.0 18.7 11.8
(24/178) (24/178) (71/178) (6/178) (37/178) (2/178) (2–58) (36/193) (23/195)
42.3 34.6 23.1 4.8 59.1 11.8 8.3 19.1 19.2 3.9
(11/26) (9/26) (6/26) (1/21) (13/22) (2/17)b (2/24) (4/21) (5/26) (1/26)
37.4 31.8 30.8 15.2 66.1 13.4 6.9 5.0 16.9 8.3
(73/195) (62/195) (60/195) (25/164) (109/165) (19/142) (13/189) (9/179) (32/189) (15/181)
a
p ¼ 0.027. p ¼ 0.035. SSS: Scandinavian Stroke Scale.
b
62.5% of patients reported a moderate to severe intensity (NRS 4). The headache was described as pressing by 75%, pulsating by 18.8%, and as various other characteristics by 6.2% of patients (Table 2). Only 18.8% of patients reported the headache to be aggravated or induced by movement. Nausea or vomiting was reported by 18.8% of patients, phonophobia affected 31.2%, and photophobia 18.8%. Probable tension-type headache was found in 50.0% of patients (Tables 2 and 3). Probable migraine was found in 31.3% of patients, and one of these patients was additionally diagnosed with medication-overuse headache (Table 4). Two patients (12.5%) had mixed headache and one patient (6.2%) had other headache. The average HIT-6 scale score was 58 (range 36–78), with 37.5% of patients reporting severe impact on daily
life, 31.2% substantial impact, 12.5% some impact, and 18.8% no or little impact. The risk of developing stroke-attributed headache in patients with pre-existing headache was 17.3% (nine of 52; 95% CI ¼ 8.2%–30.3%) compared with 4.1% (seven of 170; 95% CI ¼ 1.7%–8.3%) in patients without pre-existing headache.
Non-stroke-attributed headache Ten patients reported non-stroke-attributed headache. One patient reported daily headache, one patient headache more than 14 days per month, and eight patients headache between two and 14 days per month (Table 2). The headache lasted less than one hour for two of the patients, less than a day for one patient, one
1
1
4
1
4
2
2
2
4
4
1
7
8
9
10
11
12
13
14
15
16
Bilateral Unilateral Unilateral Bilateral
> 1 day
< 1 day
1 day
2–14
Daily
2–14
2–14
Unilateral
Varies
Mild
Moderate
Moderate
Severe
Mild
Average
Intensityb
(CEP)
2–14
2–14
2–14
2–14
2–14
2–14
2–14
Unilateral Unilateral
6
2–14
2–14
