Abstract
Background
Headache is common in patients with Moyanoya angiopathy (MMA), but usually underestimated in its management and not well characterized.
Methods
A validated self-administered headache screening questionnaire and a telephone interview were used in order to investigate headache characteristics, frequency and pain intensity in a large cohort of 55 German patients with MMA.
Results
Thirty-seven patients (67.3%) had suffered from headache in the past year. Headache intensity was rated 3.2 ± 1.3 on a verbal rating scale from 0 to 10. Seventeen patients (47.9%) reported migraine-like headache, 10 patients (27.0%) reported tension type-like headache and 10 patients (27.0%) had a combination of both. The majority of patients with migraine-like headache (n = 10, 58.8%) described migrainous aura. Headache frequency and intensity improved significantly after revascularization surgery; however, nine patients developed new-onset headache postoperatively.
Conclusion
Headache is very common in MMA, often with a migraine-like phenotype. Tension type-like headache was also found in 27% of patients, which is a new finding that has not been reported before.
Introduction
Moyamoya angiopathy (MMA) is a rare vasculopathy that is characterized by bilateral progressive narrowing and occlusion of the intracranial portion of the internal carotid artery, the middle cerebral artery and the anterior cerebral artery. MMA usually presents early in childhood and adolescence with cerebrovascular events due to haemodynamic insufficiency and cerebral haemorrhage, often being caused by the rupture of fragile collateral vessels. Headache occurring independently of these potentially life-threatening conditions is a common symptom in MMA, being frequently underestimated in its clinical management. Several available studies confirmed the high prevalence of headache in MMA; however, their precise clinical characteristics and possible association with underlying pathology remain unclear (1,2). Moreover, data concerning the surgical revascularization effect are conflicting (1,3–7).
We aimed to evaluate systematically headache symptoms as well as the effect of bypass intervention in a large cohort of Caucasian adults with MMA.
Methods
The study was approved by the local ethics committee and informed written consent was obtained from all patients. Patients with idiopathic MMA were recruited during the first German-speaking Moyamoya patients’ meeting in September 2012 at the Alfried-Krupp Hospital in Essen, Germany. Exclusion criteria included known concomitant diseases defining Moyamoya syndrome, such as cerebral vasculitis, etc. All study participants received a screening headache questionnaire based on the diagnostic criteria of the International Headache Society and as validated previously (8). Additionally, several questions were included in order to evaluate the prevalence of other MMA-associated symptoms/events (e.g. stroke, bleeding and epileptic seizure). Those patients who underwent surgical treatment were also asked to remember the frequency and intensity of headaches in the year before and after bypass surgery. Participants with headaches were called again for a second detailed semi-structured telephone interview, performed by a neurologist (S-IL).
Statistics
Data are presented in a descriptive manner. Group comparisons were performed using the Wilcoxon test or χ2-test where appropriate. Kruskal–Wallis tests were used for exploring differences between headaches in those patients in whom headaches improved after surgery. Statistical analysis was completed with SPSS version 13.0 (SPSS, Inc., Chicago, IL, USA). The level of significance was set to p < 0.05.
Results
Study sample
The study sample consisted of 55 Caucasian patients (12 men and 43 women). A unilateral variant of Moyamoya angiopathy (with assumed idiopathic aetiology) was diagnosed in 15 patients (27.3%), while bilateral idiopathic disease was found in 40 patients (72.7%). The mean age was 37.6 years (median: 34; SD: ±13.2 years; range: 16–69 years) at the time of questionnaire completion. At the time of first diagnosis, the patients were 31.6 years old (median: 31 ± 14.31; range: 3–61 years).
Moyamoya symptoms
The patients were asked dichotomously for earlier symptoms of MMA and given the possibility of answering ‘yes’ or ‘no’. A total of 65.5% answered that they suffered from stroke, 63.5% from transient ischemic attacks, 76.4% from headaches, 23.6% from seizures and 5.5% from cerebral bleedings.
Headache
In terms of the prevalence, frequency and intensity of headache, 37 out of 55 patients (67.3%) suffered from headache in the past year. Headache intensity was rated 3.2 ± 1.3 (median: 3; range: 1–6) on a numeric rating scale (NRS) ranging from 0 to 10 (0 = no pain, 10 = worst imaginable pain). Headache frequency was 6.2 ± 7.8 days (median: 3; range: 1–30) per month. No correlation between unilateral or bilateral MMA, location and presence of headache was found (χ2 = 0.217; p < 0.7). Moreover, no correlation was found between the presence of headache and gender (χ2 = 0.088; p < 0.8).
Seventeen patients (47.9%) fulfilled the diagnostic criteria for migraine-like headache. Ten of them (27%) reported migraine with aura. Aura symptoms were visual in eight patients (47.1%), sensory in eight patients (47.1%) and involved motor weakness in four patients (23.5%) and speech disturbances in four patients (23.5%) Tension type-like headache was found in 10 patients (27%), and a combination of migraine-like and tension type-like headache was found in 10 patients (27%; Figures 1 and 2 and Table 1).
Presentation of migraine-like headache in Moyamoya angiopathy. Presentation of tension type-like headache in Moyamoya angiopathy. Frequency (days) and intensity (numeric rating scale) of different subtypes of headaches in a large cohort of Caucasian Moyamoya angiopathy patients.
Effect of revascularization surgery
Intensity and frequency of headaches divided by headache subtypes with changes in the frequency (Δ days) and intensity of headaches (Δ NRS) after revascularization surgery.
Discussion
According to the current criteria of the Research Committee of the Japanese Ministry of Health and Welfare, headache is considered one of the most frequent symptoms of MMA (6). In our survey, we confirmed a high prevalence of headache in a large cohort of adult Caucasian MMA patients. Interestingly, the majority of these patients (72.9%) reported migraine-like headache either alone or combined with tension type-like headache. The relevant clinical question remains as to whether these headaches represent a specific and causally related symptom of MMA.
Few hypotheses concerning the headache pathophysiology by MMA have been discussed so far (2,9). Dilated leptomeningeal collaterals stimulating dural nociceptors was suggested as a possible origin of headache (2). On the other hand, microvascular ischaemia can trigger cortical spreading depression, which might account for the surprisingly high number of migraine-like headaches with aura in our study. In addition, chronic cerebral hypoxia, being recognized as one potential pathophysiological mechanisms for other headache disorders, must be taken into account in MMA (10). A subgroup of patients may also suffer from coincidental primary headaches. Even in these cases, the chronic psychological stress, anxiety and depression associated with this potentially life-threatening disease may result in a higher headache frequency (11). Most importantly, headaches are frequent in MMA, and their origin is complex and probably includes both primary and secondary mechanisms.
One of the most relevant clinical questions is the effect of surgical treatment on the course of headaches in MMA. In our cohort, revascularization surgery significantly improved both headache frequency as well as intensity. This is in line with results from paediatric MMA (3,4). This finding, as well as the predominantly migraine-like phenotype in patients, suggests a paramount role of secondary, probably vascular mechanisms in MMA-associated headaches. Surprisingly, there was no difference in headache frequency changes after surgery between respondents with different headaches subtypes. This raises the question as to whether headache improvement after surgery could be a placebo effect.
Furthermore, how should those nine patients in whom headache newly occurred after surgery be interpreted? This remains inconclusive and patients must be informed preoperatively regarding this possible side effect. In Seol et al.’s study, some children also developed new-onset headache, which was discussed as a marker of successful collateralization (1).
More profound is that prospective studies are warranted in order to better characterize these patients in terms of their individual courses of disease, with a special emphasis on the localization, duration and clinical phenotype of these new-onset headaches, in order to identify potential risk factors.
Unfortunately, our study has several limitations that have to be addressed. The study was retrospective and so recall bias must be considered when the results are interpreted. As a consequence, the indication of bypass surgery with headache as an isolated symptom in MMA without other clinical symptoms and the para-clinical data pointing to relevant haemodynamic insufficiency should be considered with great caution. The strengths of our study are the size of the cohort and the systematic characterization of headaches with a validated questionnaire according to the International Classification of Headache Disorders (8) and reconfirmed by a telephone interview with a neurologist.
In conclusion, headaches are very common in MMA, but their precise pathophysiological mechanisms remain unclear. The majority of patients present with migraine-like headache with a high prevalence of aura symptoms. Despite the overall postoperative improvement, some patients may also develop new-onset headache after surgery. Symptomatic treatment remains unclear. Common side effects of typical headache medication have to be considered (e.g. vasoconstriction caused by triptans (which is also shown in the superficial temporal artery) or drops in blood pressure when using β-blockers or calcium channel blockers).
The pathophysiology and therapeutic implications of these different headache subtypes require further investigation, but should be recognized by the treating physicians and carefully assessed in the course of disease management.
Clinical implications
Headache is an important symptom of Moyamoya angiopathy. The characterization of headache symptoms revealed that the majority of patients had migraine-like symptoms, often with aura.
Footnotes
Acknowledgments
We thank Professor Hans Christoph Diener, University Clinic of Essen, for important help in evaluating the study results.
Declaration of conflicting interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.