Cephalalgia

Migraine is one of the most prevalent neurological disorders with some 30% of patients additionally suffering from focal neurological disturbances: the aura. The underlying mechanism behind the aura is generally considered to be a form of cortical spreading depression (CSD). We used mechanical stimulation to induce hyperaemia associated with CSD in cats and rats, and studied the effect of a glutamate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor, antagonist, and γ-aminobutyric acid (GABA)_A and GABA_B receptor agonists, to understand better the pharmacology of CSD. All three were able to inhibit CSD-associated cerebral blood flow changes in the rat and in a proportion of cats studied; non-responders showed altered speed of propagation and time to induction. The data suggest AMPA and GABA receptors may be targets of migraine therapy in inhibiting CSD and thus may alter the frequency of migraine aura.

We identified clinical, demographic and psychological predictive factors that may contribute to the development of chronic headache associated with mild to moderate whiplash injury [Quebec Task Force (QTF) ≤ II] and determined the incidence of this chronic pain state. Patients were recruited prospectively from six participating accident and emergency departments. While 4.6% of patients developed chronic headache attributed to whiplash injury according to the International Classification of Headache Disorders, 2nd edn criteria, 15.2% of patients complained about headache lasting > 42 days (QTF criteria). Predictive factors were pre-existing facial pain [odds ratio (OR) 9.7, 95% confidence interval (CI) 2.1, 10.4; P = 0.017], lack of confidence to recover completely (OR 5.5, 95% CI 2.0, 13.2; P = 0.005), sore throat (OR 5.0, 95% CI 1.5, 8.9; P = 0.013), medication overuse (OR 4.2, 95% CI 1.4, 12.3; P = 0.009), high Neck Disability Index (OR 4.0, 95% CI 1.3, 12.6; P = 0.019), hopelessness/anxiety (OR 3.8, 95% CI 1.3, 8.7; P = 0.024), and depression (OR 3.3, 95% CI 1.2, 9.4; P = 0.024). The lack of a control group limits the conclusions that can be drawn from this study. Identified predictors closely resemble those found in chronic primary headache disorders.

Our aim was to determine the prevalence of right-to-left shunt (RtLS) in patients with chronic migraine (CM), and to correlate the presence and grade of RtLS with aura and neurological symptoms, and duration and severity of disease. The prevalence of RtLS in migraine without aura is similar to that of the general population (between 20 and 35%). In migraine with aura, the prevalence is much higher (approximately 50%). The prevalence in CM, with or without aura, is unknown. Consecutive patients between the ages of 18 and 60 years with CM attending a tertiary care specialty headache clinic over an 8-week period were eligible. There were 131 patients in the study. A structured diagnostic interview was performed. Bubble transcranial Doppler with Valsalva manoeuvre determined RtLS presence and grade. Sixty-six percent (86/131) of patients had RtLS, a statistically significantly greater rate than those reported in the general population and in migraine with or without aura (P < 0.001). There was no difference in RtLS rate or grade between those with and those without aura. Specific headache features and the presence of neurological symptoms were similar between those with and those without RtLS. Compared with both the general population and the episodic migraine population (with and without aura), patients with CM, with or without aura, are more likely to have RtLS. The clinical implications of our findings need to be determined.

Data from the Prolonged Migraine Prevention (PROMPT) with Topiramate trial were evaluated post hoc to determine whether topiramate could prevent migraine auras, and whether its efficacy in preventing migraine headaches was similar in patients with (MA; n = 269) and without (MoA; n = 542) aura. Migraines and auras were recorded during prospective baseline, 6-month open-label (OL) topiramate and 6-month double-blind (DB), placebo-controlled phases. In the last 28 OL days, migraines without aura and migraine auras decreased by 43.1% and 54.1%, respectively, in MA patients. MoA patients experienced a 44.3% reduction in migraines. In the DB phase, increases in migraines with placebo vs. topiramate were similar to the full study, but were generally not statistically significant, probably due to lack of power in the subgroup analysis. Similarly, there were no statistically significant changes in number of auras between groups. Thus, topiramate appears to reduce migraine auras in parallel with headache reductions, which are similar in patients with and without aura.

We used multimodal magnetic resonance (MR) techniques [brain diffusion-weighted magnetic resonance imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), ¹H-MRS; and skeletal muscle phosphorous MRS, ³¹P-MRS] to investigate interictal brain microstructural changes and tissue energy metabolism in four women with genetically determined familial hemiplegic migraine type 2 (FHM2), belonging to two unrelated families, compared with 10 healthy women. Brain DWI revealed a significant increase of the apparent diffusion coefficient median values in the vermis and cerebellar hemispheres of FHM2 patients, preceding in two subjects the onset of interictal cerebellar deficits. ³¹P-MRS revealed defective energy metabolism in skeletal muscle of FHM2 patients, while brain ¹H-MRS showed a mild pathological increase in lactate in the lateral ventricles of one patient and a mild reduction of cortical N-acetyl-aspartate to creatine ratio in another one. Our MRS results showed that a multisystem energy metabolism defect in FHM2 is associated with microstructural cerebellar changes detected by DWI, even before the onset of cerebellar symptoms.

Seventy-nine patients with intracranial aneurysms were evaluated in the presurgical period, and followed up to 6 months after surgery. We compare patients who fulfilled with those that did not post-craniotomy headache (PCH) diagnostic criteria, according to the International Classification of Headache Disorders. Semistructured interviews, headache diaries, Short Form-36 and McGill Pain Questionnaire were used. Seventy-two patients (91%) had headaches during the follow-up period. The incidence of PCH according to the International Headache Society diagnostic criteria was 40%. Age, sex, type of surgery, temporomandibular disorder, vasospasm, presence and type of previous headaches, and subarachnoid haemorrhage were not related to headache classification. There were no differences in the quality of life, headache frequency and characteristics or pain intensity between patients with headache that fulfilled or not PCH criteria. We proposed a revision of the diagnostic criteria for PCH, extending the headache outset after surgery from 7 to 30 days, and including the presence of headaches after surgery in patients with no past history of headaches, or an increase in headache frequency during the first 30 days of the postsurgical period followed by a decrease over time. Using these criteria we would classify 65% of our patients as having PCH.

Logistic regression was used to evaluate the relationship between self-reported medical diagnosis of migraine, self-reported depressive symptomology (RDS) and self-reported anxious symptomology (RAS) in the National Health Interview Survey (n = 30 852). Semipartial squared correlations evaluated the population-level variability between RDS, RAS and migraine impairment. Migraine prevalence was 15.2% (overall), 20.5% (women) and 9.4% (men). Migraine risk was higher in participants with RAS [odds ratio (OR) 2.30, 95% confidence interval (CI) 2.09, 2.52), with RDS (OR 2.23, 95% CI 1.93, 2.58), who smoked (OR 1.19, 95% CI 1.09, 1.30), or who consulted a mental health provider (OR 1.45, 95% CI 1.27, 1.65). Although migraine risk was increased in both women (OR 1.93) and men (OR 2.42) with RAS (P < 0.001), men with RAS had a higher migraine risk than did women with RAS (P < 0.001). Only 7% of the variability in migraine impairment (population level) was predicted by variability in RDS and/or RAS.

Studies performed in selected populations have shown a poor utilization of triptans for migraine. Our study was aimed at establishing patterns of triptans utilization in a large community using the pharmaceutical prescriptions database of two consecutive years in a regional Health Authority in Italy. About 0.5% of the population observed received triptans prescriptions in a year, but > 50% of the cases received only one prescription. On the other hand, 46% of triptan users did not receive a triptan prescription in the following year (past users): in 80% of cases, patients received only 1–2 triptan packages. The evaluation of the discontinued triptan type has shown percentages varying between 30 and 70%. The percentage of triptan users who received a triptan prescription for the first time in the successive year of study (new users) was 52%. These findings together highlight a high turnover in triptans utilization. Less than 15% of subjects received more than one triptan product in the 2 years. In conclusion, we observed a low percentage of triptan users and a low rate of utilization, associated with a high percentage of discontinuation and new utilization (high turnover), without any substantial increase in triptans utilization during the years. All these data probably do not support optimal satisfaction with triptan therapy.

Our aim was to assess the 1-year prevalence of migraine headache in a rural population within the catchment area of the Haydom Lutheran Hospital in northern Tanzania. From December 2003 until June 2004 a community-based door-to-door survey was carried out, using a questionnaire based on the criteria of the International Headache Society, including 1192 households with 7412 individuals selected by multistage cluster-random sampling. The overall 1-year prevalence of migraine headache was found to be 4.3% [316/7412, 95% confidence interval (CI) 3.8, 4.7] with an age-adjusted rate of 6.0% and a male : female ratio of 1:2.94 (P < 0.001). Of these individuals, 132 did not fulfil all criteria for migraine headache, hence, these patients had to be classified as migrainous disorders with a crude prevalence rate of 1.8% (132/7412. 95% CI 1.5, 2.1). The remaining 184 patients met all criteria for migraine resulting in a 1-year prevalence of 2.5% (184/7412, 95% CI 2.1, 2.9) and a male : female ratio of 1:2.51 (P < 0.001). The present survey shows that migraine headache is not uncommon in northern Tanzania. The recorded prevalence of migraine headache is located within the median of previous African prevalence surveys, which confirms the trend of lower migraine frequencies in rural Africa compared with western countries.

There is growing evidence that alterations in the insulin and glucose metabolism may be involved in the pathogenesis of migraine. Nitric oxide (NO) stress has been associated with migraine. However, the role of NO on the insulin and glucose metabolism in migraineurs has remained elusive to date. The aim of the present study was to investigate the insulin and glucose metabolism in migraineurs and to determine possible interactions with the NO pathway. One hundred and twenty non-obese probands participated in this study, including 48 migraineurs and 72 healthy volunteers. Various parameters of the NO pathway, glucose metabolism as well as body measurement parameters were determined. We found a highly significantly increased insulin and Homeostasis Model Assessment (HOMA)-index in migraine patients, whereas fasting glucose was decreased. Logistic regression revealed an odds ratio of 5.67 for migraine, when comparing the lowest with the highest quartile of HOMA. Multivariate analysis showed that HOMA, waist-to-length ratio and nitrite as parameters of NO stress were highly significantly correlated. We show here that hyperinsulinaemia is associated with migraine and, furthermore, is correlated with increased NO stress. These findings represent a new pathophysiological mechanism that may be of clinical relevance.

The aim of this review was to summarize population-based studies reporting prevalence and/or incidence of chronic migraine (CM) and to explore variation across studies. A systematic literature search was conducted. Relevant data were abstracted and estimates were subdivided based on the criteria used in each study. Sixteen publications representing 12 studies were accepted. None presented data on CM incidence. The prevalence of CM was 0–5.1%, with estimates typically in the range of 1.4–2.2%. Seven studies used Silberstein–Lipton criteria (or equivalent), with prevalence ranging from 0.9% to 5.1%. Three estimates used migraine that occurred ≥ 15 days per month, with prevalence ranging from 0 to 0.7%. Prevalence varied by World Health Organization region and gender. This review identified population-based studies of CM prevalence, although heterogeneity across studies and lack of data from certain regions leaves an incomplete picture. Future studies on CM would benefit from an International Classification of Headache Disorders consensus diagnosis that is clinically appropriate and operational in epidemiological studies.

Chronic migraine accompanied by medication overuse is particularly difficult to treat. The number of treatment investigations is limited, few have included follow-up beyond 6 months and almost none has examined whether treatment leads to concurrent improvements in disability and functional impairment. This open-label study addresses these limitations. We have been prospectively following an initial cohort of 84 chronic migraine patients with medication overuse, who at the time of this evaluation had been reduced to 58, for an extended period to assess longer-term maintenance of effects, using measurement procedures identical to those in the original investigation. Thus, the specific aim was to determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated and followed prospectively for 5 years. All patients completed a brief inpatient treatment programme, in which they were withdrawn from their offending medications and subsequently placed on more appropriate preventive antimigraine medications. Both end-point, wherein missing data points were estimated, and continuer analyses, wherein data analysis was limited to the 58 individuals with complete datasets, revealed significant improvement on all measures studied—headache days per month, analgesic consumption and Migraine Disability Assessment (MIDAS) total score. The percentage reduction from baseline to 5 years for the MIDAS total score was 76.0%, while the percentage of individuals revealing improvements of clinically significant magnitude (≥ 50%) on the MIDAS was 91.9%. MIDAS total scores were lower at 5 years than at some of the intervening follow-up intervals. Comparisons of those who completed the 5-year follow-up (n = 58) with those who did not revealed no differences at baseline. This finding, coupled with the nearly identical results for the end-point and continuers analyses, suggests that attrition did not have a bearing on outcome. None of the patients completing the 5-year follow-up had relapsed since the prior 3-year follow-up assessment. High levels of maintenance were revealed at 5 years, with disability scores showing some continued improvement over time. The implications of these findings and the limitations of the study are discussed.

A 27-year-old woman was admitted to the Emergency Department with right upper-extremity numbness and mild weakness followed by a bifrontal throbbing headache for 30 min, which was similar to a headache lasting for 12 h that had occurred 3 days ago. Laboratory tests were unremarkable except for cerebrospinal fluid (CSF) lymphocytic pleocytosis. On the following day, a headache episode with left hemiparesis and hemihypoaesthesia, left hemifield visio-spatial inattention, anosagnosia and confusion recurred. The headache was diagnosed as headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) syndrome according to the criteria of the second edition of the International Classification of Headache Disorders. Simultaneously performed magnetic resonance imaging (MRI) revealed swelling of the grey matter, CSF enhancement in the sulci of the right temporal and occipital regions and hypoperfusion of the same brain regions. During the following 10 days two more similar episodes recurred and during the ensuing 12 months the patient remained headache free. Neuroimaging findings of the HaNDL syndrome are always thought as virtually normal. MRI abnormalities in our patient have not been reported in HaNDL syndrome previously, although they have been reported in hemiplegic migraine patients before. The findings in our case suggest that hemiplegic migraine and HaNDL syndrome may share a common pathophysiological pathway resulting in similar imaging findings and neurological symptoms.

A survey of 148 family doctors attending a continuing medical education migraine update lecture was performed to assess whether family doctors like to treat migraine and other common disorders and the prevalence of migraine. Doctors were asked to respond to the following statement using a five-point Likert scale (from 1, strongly disagree to 5, strongly agree): ‘I like to treat patients with this disease or symptom’. The response rate was 53% with a mean age of 51.5 years. Doctors reported liking to treat general medical conditions more (mean = 4.40) than migraine (mean = 3.38) and other neurological diseases (mean = 3.20). Doctors reported a personal history of migraine in the prior 1 year of 22.8% and 45.6% lifetime, with 17% becoming aware for the first time that they personally had migraine after attending the lecture. Respondents with a personal history of migraine liked to treat migraine more than those without a history.

The standard clinical advice for individuals who suffer from recurrent headaches is that the best way to prevent headaches is to avoid the triggers. This editorial challenges that advice from a number of perspectives. First, there is little empirical support for such advice. Second, cognate literatures in the fields of chronic pain, stress and anxiety raise concerns about avoidance as a strategy. Third, studies have demonstrated that short exposure to a headache trigger results in increased sensitivity and prolonged exposure results in decreased sensitivity. Conclusions include that one aetiological pathway to developing a primary headache disorder may be via attempts to avoid triggers resulting in increased sensitivity to triggers. Also, clinicians need to become more flexible in the advice they give pertaining to triggers, namely they should think ‘coping with triggers’ rather than avoiding all triggers, as avoidance will sometimes be the preferred strategy, but often it will not be.