Headache in transient ischemic attacks

Study populations

The period of recruitment of patients was from April 2014 till May 2016. The study population was admitted to the stroke unit of city hospital “New Hospital” in Yekaterinburg, Russia. Inclusion criteria were focal brain or retinal ischemia with resolution of symptoms within 24 h and without presence of new infarction on magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) or computed tomography(CT). Excluded were patients with previous cerebrovascular disease or other serious neurological disease and memory problems. All patients were evaluated within one day of admission, usually within a few hours by a neurologist. 62 patients had TIA < 6 h before admission to the hospital, 50 patients had TIA in interval from 6 to 12 h, 6 had TIA in interval from 13 to 24 h and two had TIA in interval from 24 to 36 h before admission.

A total of 131 patients were examined, 11 patients were excluded because most of them had difficulties to recall essential information and memory problems. 112 patients had MRI with DWI and 8 had CT. These examinations were done immediately after admission to the hospital. All TIA cases were subdivided into anterior and posterior circulation TIA.

As a control group we used patients who were admitted to the emergency room without acute neurological deficits or serious neurological or somatic disorders. We examined 225 controls.33 patients were excluded and 192 patients were included.

Evaluation

One neurologist (N.M.G.) collected patient data prospectively, using a standardized case-report form during face-to-face interviews during admission to the emergency room in controls. Information about patients, medical history and risk factors imaging and laboratory tests were recorded. We recorded history of headache during last year, during 1 week before TIA and at the time of TIA defined as within 24 h of TIA onset. We used extensive semi-structured interview forms that contained all necessary information to diagnose previous headaches.

Definitions and diagnostic criteria

TIA was defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction [12].

The diagnoses of previous and present headaches were made according to the explicit diagnostic criteria of the International Headache Society, the International Classification of Headache Disorders ICHD-3 [11]. We recorded headache within the last year and last week before TIA and within 24 h after onset of TIA. We distinguished between previous headache without change of characteristics, headache with change of characteristics and new type of headache. We defined a new type of headache in TIA as a headache which arose for the first time in the week before or within 24 h after onset of TIA. Migraine or tension type headache with changes of characteristics within the last week before TIA or within 24 h after onset of TIA as well as migraine or tension type headache as a new type of headache were defined as migraine-like headache and tension- type-like headache respectively. We did not apply the diagnostic criteria for “headache attributed to TIA” of the ICHD-3 because the purpose of the present study was to compare all kinds of headaches in patients with TIA to a matched control group.

Ethical considerations

The Medical Ethics Committee of the Urals State Medical University approved this study. All respondents were informed of the purpose of the survey. Written informed consent was obtained from all participants.

Statistical analysis

Statistical analyses were performed with SPSS 17.0 software. Continuous variables were summarized as means, and categorical variables as numbers and percentages. We used chi-squared to compare distributions of categorical variables between groups. We set statistical significance at P < 0.05. We first used binary logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI) for consulting and laboratory data. Prevalence estimates and 95% CI for the prevalence estimates of migraine and other headache were determined using previously described methods [13, 14].

Characteristics of patients with TIA and controls

The duration of TIA varied from 5 min to 24 h. 42 patients (35%) had resolution of all symptoms within 60 min. Among them 22 patients (18,3%) had duration of TIA from 2 till 15 min and 20 patients (16,7%) 16–60 min. 18 patients (15%) had duration of TIA from 1 h to 3 h and 60 patients (50%) had duration from 3 h to 24 h. 86 patients with TIA had sensory deficits, 68 patients had speech disturbances, 73 patients had unilateral motor weakness [14].

All patients with TIA underwent a stroke risk assessment according to the ABCD2 score. A low risk of stroke (0–3 points) was registered in 62 patients (51.6%), moderate risk (4–5 points) in 54 patients (45%), high risk (6–7 points) in 4 patients (3.3%).

Headache within last year (excepting last week) before TIA

Headache within the last week before TIA

Four patients (3.3%) had previous headache without changes of characteristics within a week of TIA and 10 controls (5.2%).Seven patients (5.8%) and no controls had migraine-like headaches within the last week before TIA. Patients with posterior circulation TIA had migraine-like headache more often (6 of 14, 42.8%) than patients with anterior circulation TIA (1 of 106, 0.9%). Four of 7 patients had a past history of migraine during the last year. Before TIA their migraine attacks became daily and stronger than usual. In three patients the migraine-like attacks appeared for the first time. All these seven patients could have sentinel or warning headache.

Fourteen patients (11.6%) had tension-type-like headache during the last week before TIA and 2 controls (1.0%). The percentage of patients with posterior circulation TIA with such headaches was much greater (57.1%) than the percentage with anterior circulation TIA (7.5%).12 of these patients had a past history of headache. They had increases in duration, frequency, and/or intensity of their previous headaches. The prevalence of TTH with changes of characteristics was significantly higher in TIA patients (10%) than in controls (1.0%). Two patients with TIA had a new tension-type- like headache and no controls. All these 14 patients with tension-type-like headache could have sentinel or warning headache.

Totally 22 patients (14 with tension-type-like headache, 7 with migraine-like headache and one with thunderclap headache) had sentinel or warning headache within the last week before TIA.

Headache at the time of TIA

A previous headache with changed characteristics was found in 9 of 120 patients (7.5%) and no in controls. Four of these patients had migraine-like headache and 5 tension-type-like headache. Six patients had TIA in the posterior circulation (42.8%) and 3 in the anterior circulation (2.8%). Four patients had a past history of migraine without aura and 5 a history of TTH. They had increased intensity, frequency or altered localization or they became refractory to usual treatment Seven patients had headache at the same time as TIA and two after TIA. Six patients had duration of TIA more than 3 h and three patients had duration 10–15 min.

Eight of 120 patients (6.6%) and 9 controls (4.6%) had a usual headache without any changes. Four patients had TIA in the posterior circulation and the remaining four in the anterior circulation. Six patients had headache at the same time as TIA and two after TIA. Six patients had duration of TIA more than 3 h and two patients had duration 15–30 min.

We performed follow-up of 118 out of 120 patients with TIA, the average follow-up period was 30 months. Four patients reported repeated TIA. Ischemic strokes happened in 7 patients. We found only one case of migraine with aura which was missed during the first interview.

Previous studies of headache in TIA

Only few studies have attempted to characterize headache in patients with TIA and no studies were performed in the past 10 years [1–10]. In most studies headaches were analyzed in TIA patients together with stroke patients [1, 2, 4, 9] but two studies analyzed TIA patients separately [5, 10]. Patients were asked in one study about the presence and localization of headache at symptom onset and to describe the quality of headache according to predefined categories: dull, pressing, stabbing, burning, pulsate, or circular [2]. In the other study patients were asked about the presence and nature (throbbing versus constant) of headache [4]. In three other studies patients were asked about onset, duration, location and quality of headache [1, 5, 9, 10]. Patients were asked about headache prior to TIA only in two studies [1, 5]. All previous studies used CT but not MRI with DWI for detection of infarct and many studies therefore may have included small infarcts. Besides no study could make a specific diagnosis of headache because of absence of classification that time or lack of information about necessary characteristics of the headache. The few studies with a big number of TIA patients did not use a detailed interview about previous and current headache [2, 3]. Therefore, it is difficult to compare our results with previous studies. The character of headaches at TIA onset was different in different studies: throbbing [1, 9] or diffuse [5] or generalized non-localized [10]. The overall prevalence of headache at the time of TIA varied from 16% to 36% and is thus in accordance with our results [1–10].

Methodological considerations

Several principles should be taken into account in studies of headache in TIA patients. First of all, it is impossible to know the exact diagnosis of headache without using the diagnostic criteria of the International classification of headache [11]. This requires a professional semi-structured interview about previous and current headache, preferably face to face, because some important characteristics of headache can otherwise be missed in acutely ill patients. It is also necessary to record the exact timing of headache and TIA and to use a generally accepted definition of transient ischemic attacks including MRI with DWI to exclude acute infarcts.

Headache can only manifest in a limited number of ways. Thus, most secondary headaches including headache in TIA patients have the characteristics of tension-type headache or migraine without aura. If there is a close temporal relation, it must, however, be classified as a secondary headache attributed to the causative disorder according to ICHD-3 [11]. Since most of the headaches encountered in the present study were new or had altered characteristics and occurred significantly more often than in the control group, we have chosen to call those occurring in the week before or at the time of TIA migraine–like headaches and tension-type-like headaches.

Significance of our findings

Our results have important clinical implications and also bespeak to some extent the possible mechanisms of headache and migraine.

Strengths and weaknesses of the present study

To the best of our knowledge this is the first study that has examined headache in TIA patients using a professional, face to face, semistructured interview describing all relevant characteristics of headaches associated with TIA.

One limitation of this study is the quick disappearance of clinical symptoms in TIA patients before admission to the hospital. Some of them could not remember details which are important in the differential diagnosis of TIA and MA. For example, some patients could have missed gradual spread of symptoms or presence of succession of symptoms. Some patients could not describe the characteristics of headache during TIA very well. Therefore some cases of MA could have been missed. However, we performed follow-up of 118 out of 120 patients with TIA. The period of follow-up varied from 6 months till 4 years. We found only one case of migraine with aura which was missed during the first interview. This patient experienced three more similar attacks of migraine with aura during two following years.

The weakness of the present study was using only CT in 8 patients which is not an accurate method for detection of small infarcts, especially in the posterior territory. However we performed a follow-up of these 8 patients during 3 years and nobody from them had recurrent episodes and other neurological problems. Also, the inaccuracy of patient’s recall of headache during the last year may have been a limiting factor.