Cephalalgia

The Clinical Trials Subcommittee of the International Headache Society published its first edition of the guidelines on controlled trials of drugs in tension-type headache in 1995. These aimed ‘to improve the quality of controlled clinical trials in tension-type headache’, because ‘good quality controlled trials are the only way to convincingly demonstrate the efficacy of a drug, and form the basis for international agreement on drug therapy’. The Committee published similar guidelines for clinical trials in migraine and cluster headache. Since 1995 several studies on the treatment of episodic and chronic tension-type headache have been published, providing new information on trial methodology for this disorder. Furthermore, the classification of the headaches, including tension-type headache, has been revised. These developments support the need for also revising the guidelines for drug treatments in tension-type headache. These Guidelines are intended to assist in the design of well-controlled clinical trials in tension-type headache.

The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.

Intravital microscopy on a closed cranial window allows one to measure change in the diameter of cranial blood vessels after intravenous (i.v.) administration of pharmacodynamic substances. Putative targets being pursued in migraine are large vasodilating peptide molecules such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase polypeptide (PACAP)-38. High i.v. doses are required to study their craniovascular pharmacology. Unfortunately, this leads to a drop in blood pressure (BP) that subsequently causes blood vessels to dilate by autoregulation. Hence it is difficult to decipher what effect is caused by direct receptor agonist interaction or contributed by autoregulation. In the present study we infused substances with an ingenious indwelling catheter in the common carotid artery in rats. Intracarotidly seven-, 12- and 17-fold lower doses of CGRP, PACAP-38 and capsaicin were required, respectively, compared with i.v. infusion to induce the same dilation in dural artery. Dilating intracarotid (i.c.) doses caused no or a minimal fall in BP, whereas equi-responsive i.v. doses caused a marked BP reduction. The CGRP blocking potential of olcegepant was amplified by > 20 times on i.c. infusion. Pial artery responses to CGRP did not change with i.c. infusion, demonstrating that dilations after i.v. CGRP are mediated by autoregulation rather than through specific receptors. We applied CGRP topically, which induced concentration-dependent dural vasodilation, but no effect on pial artery or on BP. In conclusion, this new approach offers an improvement of the existing model by allowing more accurate assessment of effects of pharmaca on the cranial vasculature without inducing significant systemic effects.

The aim of this study was to identify and diagnose headache in a temporomandibular joint and orofacial pain clinic population using the second edition of The International Classification of Headache Disorder criteria. In 502 temporomandibular disorder and orofacial pain patients, 246 patients (49%) were diagnosed with tension-type headache (TTH), followed by migraine without aura (14.5%), probable migraine (12.9%), migraine with aura (7%), probable TTH (4.8%) and cluster headache (0.2%). The prevalence of headaches was compared between male and female patients, and the prevalence of migraine was found to be higher in women than in men. In evaluating by age, the prevalence of migraine was highest in patients in their 20s and 30s and declined as age increased above 40. TTH showed the highest rate throughout all age groups, but it also decreased as age increased. In this study, the prevalence of migraine was lower than that reported in Dr Kim et al.'s study, and the prevalence of TTH much higher than that reported in the previous study. Of the headache patients, 81.1% presented with masseter muscle pain and 47.8% with temporal muscle pain. This finding suggests that pericranial muscle pain may be an inducing factor of primary headache.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden-onset recurrent ‘thunderclap’ headaches with reversible multifocal narrowing of the cerebral arteries, often associated with focal neurological deficits from ischaemic or haemorrhagic stroke. It has been associated with exposure to vasoconstrictive drugs, pregnancy, migraine, and a variety of other conditions. Whereas the pathophysiology of RCVS remains unclear, changes in the levels of female hormones are considered important because RCVS predominantly affects women and is frequently associated with pregnancy. We report a patient with angiographically confirmed RCVS whose MRI showed reversible brain oedema, suggesting an overlap between RCVS and the reversible posterior leucoencephalopathy syndrome. The only identified risk factor was oral contraceptive pills started 1 month prior to onset, supporting a role for female reproductive hormones in precipitating this overlap syndrome.

We showed reduced motor intracortical inhibition (ICI) and paradoxical increase of intracortical facilitation (ICF) to 1 Hz repetitive transcranial magnetic stimulation (rTMS) in patients affected by migraine with aura (MA). In conditions of enhanced excitability due to a reduced inhibition, high-frequency rTMS was found to potentiate intracortical inhibition. Here we explored the conditioning effects of high-frequency priming stimulation of motor cortex with the aim of normalizing excitability reverting paradoxical facilitation by 1 Hz rTMS in MA. Nine patients with MA and nine healthy controls underwent a paired-pulse TMS paradigm to evaluate motor intracortical excitability (ICI and ICF) before and after the following rTMS conditions: 1 Hz alone or preceded by a real or sham conditioning high-frequency (10 Hz) rTMS. Sham was used to control for rTMS specificity. In baseline, ICI was significantly lower in migraineurs with respect to controls. One hertz stimulation reduced motor evoked potential amplitude and ICF in healthy controls, while it caused a significant paradoxical ICF increase in migraineurs. High-frequency rTMS conditioning normalized excitability in migraine, increasing short ICI and so reversing the paradoxical effects of 1 Hz rTMS. These findings raise the possibility that the interictal reduced intracortical inhibition in migraine could be normalized by high-frequency rTMS. This would open perspectives for new treatment strategies in migraine prevention.

Whereas there are many H₂ ¹⁵O-positron emission tomography (PET) studies demonstrating neuronal activation during acute migraine attacks, little information is available on the interictal (headache-free period) glucose metabolic changes in migraine. We therefore conducted voxel-based statistical parametric mapping analysis of ¹⁸F-fluorodeoxyglucose-PET to evaluate interictal metabolic differences between 20 episodic migraine patients (four with aura; three men; mean age 34.0 ± 6.4 years) and 20 control subjects. Separate correlation analyses were performed to delineate a possible relationship between regional glucose metabolism and disease duration or lifetime headache frequency in migraine patients. Group comparison showed that migraine patients had significant hypometabolism in several regions known to be involved in central pain processing, such as bilateral insula, bilateral anterior and posterior cingulate cortex, left premotor and prefrontal cortex, and left primary somatosensory cortex (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Correlation analyses showed that regional metabolism of the insula and anterior cingulate cortex had significant negative correlations with disease duration and lifetime headache frequency (uncorrected P < 0.001, corrected P < 0.05 with small volume corrections). Our findings of progressive glucose hypometabolism in relation to increasing disease duration and increasing headache frequency suggest that repeated migraine attacks over time lead to metabolic abnormalities of selective brain regions belonging to the central pain matrix.

Migraine is a very common neurological disorder worldwide. Its prevalence is lower in developing countries. There were no data concerning the general population in Benin. We aimed to determine the prevalence of migraine in a rural community of Benin. A cross-sectional study was conducted in a rural area of Abomey from February to April 2003 and included 1113 persons selected by a two-stage survey. A case was defined according to International Headache Society criteria (1988). Of the 1113 persons, 37 had migraine. The lifetime prevalence of migraine was 3.3% (male 2.2%, female 4.0%). The peak prevalence was found in persons in the second decade of life. Higher levels of education were associated with migraine. Migraine without aura was the more frequent form (67.5%). The most frequent triggers of migraine were annoyance (73.0%), exposure to the sun (73.0%), heat (65.0%) and anxiety (51.4%). The low prevalence rate of migraine in Benin confirmed the results of the few available African studies. The disease is severe and occurs in a young population and could lead to a high socio-economical burden.

We conducted a double-blinded, placebo-controlled, crossover study to investigate the occurrence of adverse effects such as headache as well as pain and mechanical sensitivity in pericranial muscles after oral administration of monosodium glutamate (MSG). In three sessions, 14 healthy men drank sugar-free soda that contained either MSG (75 or 150 mg/kg) or NaCl (24 mg/kg, placebo). Plasma glutamate level, pain, pressure pain thresholds and tolerance levels, blood pressure (BP), heart rate and reported adverse effects were assessed for 2 h. No muscle pain or robust changes in mechanical sensitivity were detected, but there was a significant increase in reports of headache and subjectively reported pericranial muscle tenderness after MSG. Systolic BP was elevated in the high MSG session compared with low MSG and placebo. These findings add new information to the concept of MSG headache and craniofacial pain sensitivity.

Spatial changes in pressure pain hypersensitivity are present throughout the cephalic region (temporalis muscle) in both chronic tension-type headache (CTTH) and unilateral migraine. The aim of this study was to assess pressure pain sensitivity topographical maps on the trapezius muscle in 20 patients with CTTH and 20 with unilateral migraine in comparison with 20 healthy controls in a blind design. For this purpose, a pressure algometer was used to assess pressure pain thresholds (PPT) over 11 points of the trapezius muscle: four points in the upper part of the muscle, two over the levator scapulae muscle, two in the middle part, and the remaining three points in the lower part of the muscle. Pressure pain sensitivity maps of both sides (dominant/non-dominant; symptomatic/non-symptomatic) were depicted for patients and controls. CTTH patients showed generalized lower PPT levels compared with both migraine patients (P = 0.03) and controls (P < 0.001). The migraine group had also lower PPT than healthy controls (P < 0.001). The most sensitive location for the assessment of PPT was the neck portion of the upper trapezius muscle in both patient groups and healthy controls (P < 0.001). PPT was negatively related to some clinical pain features in both CTTH and unilateral migraine patients (all P < 0.05). Side-to-side differences were found in strictly unilateral migraine, but not in those subjects with bilateral pain, i.e. CTTH. These data support the influence of muscle hyperalgesia in both CTTH and unilateral migraine patients and point towards a general pressure pain hyperalgesia of neck-shoulder muscles in headache patients, particularly in CTTH.

The aim was to examine pharmacological treatment of migraine patients admitted to a tertiary care pain clinic. A retrospective review of 100 consecutive migraine patients admitted to The Wasser Pain Management Centre was conducted. Patients included met the 2nd Edition of the International Classification of Headache Disorders criteria for diagnosis of migraine. Data were collected with regard to nicotine and alcohol consumption, family history of migraine headaches, other pain diagnoses and pharmacological treatment. Twenty-two per cent of these patients were male as opposed to 78% female. The mean age of patients admitted for migraine was 43.4 years. Of the patients admitted, 48% had tried at least one triptan in the past and only 31% were actively using triptan(s). The most commonly used triptan in the past had been sumatriptan, whereas the most common triptan used on admission was rizatriptan. Opiate use was much more prevalent; 72% of admitted patients were using an opiate and 27% used multiple opiates. A significant number of patients had not yet been tried on a triptan despite meeting the diagnostic criteria for migraine and having significant disability. More education of the general medical community may be beneficial in implementing a stratified care approach to migraine management.

Unilateral head pain focused on frontal, orbital or parietal regions is a leading symptom of migraine attacks. Rarely, head pain in migraine can extend involving the maxillary or mandibular region of the face, sometimes isolated facial pain is the only and atypical presentation of migraine. The prevalence of these unusual symptoms in migraine is unknown. We aimed to estimate the true prevalence of facial pain in migraine in a population-based sample of 517 migraine patients in Germany. In 46 (8.9%) cases migraine pain involved the head and the lower half of the face. Patients with facial pain suffer more trigemino-autonomic symptoms than migraine patients (47.8% vs. 7.9%; α² = 66.23, P < 0.001). In one case isolated facial pain without headache was the leading symptom of migraine. Our results demonstrate that facial pain is not unusual in migraine, whereas isolated facial migraine is extremely rare.

The aim was to describe the use of and adherence to migraine preventives among insured patients meeting the International Classification of Headache Disorders, 2nd edn (ICHD-II) criteria for migraine headaches. A retrospective, case–control study was conducted using data from a telephone interview linked with health insurance claims data. Subjects were health plan enrollees aged 18–55 years who had incurred at least one encounter between June 2000 and November 2001. Interview responses were used to identify cases meeting the ICHD-II criteria for strict and probable migraine and a random sample of controls. Pharmacy claims data were used to construct measures of use and adherence. Differences in outcomes by adherence status were evaluated using generalized linear models. We identified 2517 cases and 941 controls. Among cases, the prevalence of antidepressant use was 4%, anticonvulsant use was 1.9%, antihypertensive use was 8.9%. Combined use was 13.4% among cases and did not differ significantly from that observed among controls (12.4%). Mean adherence rate between the first and last dispensing during the year was high (88%) and did not differ by migraine status. When the entire 12-month period is considered, adherence was substantially lower (56%). Patients who were adherent between dispensings reported significantly less migraine-related disability and incurred higher prescription drug costs, but did not differ in their total medical care costs. Patients with migraine are unlikely to be users of preventive medications. Among users, few are taking preventive medications continuously. Patients with migraine—especially those without a medical diagnosis for migraine or headaches—are not receiving the benefits available from existing pharmacotherapy options.

This study investigates the influence of obesity on the severity of migraine in children. One hundred and twenty-four patients (77 female, 36 with aura; mean age 12.9 ± 2.8 years; age range 4.0–17.0 years) were included. Headache features such as number and duration of attacks, pain severity and associated symptoms were compared between obese, overweight and normal weight patients. The percentage of obesity was 17.7. Although pain severity and duration were not different among groups, obese patients had more frequent attacks than the overweight and normal weight patients (5.3 ± 2.4, 4.4 ± 2.4 and 3.8 ± 2.4 attacks/month, respectively, P = 0.018). There was also a positive correlation between relative body mass index and number of attacks (P = 0.026, r = 0.20). Obesity did not have an influence on migraine-associated symptoms including aura, phono/photophobia, nausea and vomiting. In this study, obesity appeared to be related to the frequency of headache attacks in children and adolescents with migraine.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome represents a serious therapeutic and diagnostic challenge, since it is usually refractory to most drugs and lacks biological markers. Response to intravenous lidocaine administration has been reported in some patients while it has failed in others. We report a patient with SUNCT syndrome who showed a clear-cut and consistent response to intravenous lidocaine therapy, which proved superior to placebo in a single-blinded fashion. Intravenous lidocaine should be considered in all patients with SUNCT syndrome. Response to this therapy could represent a diagnostic tool.

Little is known about the pathophysiology of cluster headache (CH), one of the most debilitating primary headaches. Interestingly, associations of lung affecting diseases or lifestyle habits such as smoking and sleep apnoea syndrome and CH have been described. Certain genotypes for alpha 1-antitrypsin (α₁-AT) are considered risk factors for emphysema. Our aim was to investigate possible associations between common genotypes of the SERPINA1 gene and CH. Our study included 55 CH patients and 55 controls. α₁-AT levels in serum and the genotype were analysed. Patients CH characteristics were documented. We could not detect any association between CH and a genotype that does not match the homozygous wild type for α₁-AT. Interestingly, there is a significant difference of CH attack frequency in patients who are heterozygous or homozygous M allele carriers. We conclude that the presence of an S or Z allele is associated with higher attack frequency in CH.

A male, 34 years of age, suffers from headaches, red and watery eyes. The headaches began in childhood; the frequency of headaches has increased over the years and in the last decade headaches have occurred on a daily basis. If he wakes up before sunrise he feels much better and free of a headache; however, once he continues to sleep during and after sunrise, he suffers from tiredness, headache and nervousness. On magnetic resonance imaging (MRI), benign neuroepithelial cysts or a chronic infarct area was reported at the junction of the left medio-lateral zone of hypothalamus. After repeated MRI examinations, it was decided that the lesion on the left medio-lateral zone of hypothalamus may have disrupted the pineal gland and changed melatonin secretion. It was decided to treat him with 3 mg melatonin daily before going to bed. After a week of treatment, the patient reported that he felt very fresh and was virtually free of headaches.