[Headache in adults; article for education and training purposes]. / Hoofdpijn bij volwassenen.

Headache is one of the most common complaints for which patients request help from the general practitioner (GP). Anxiety and fear of serious illness are the most common reasons for consulting the GP, but a request for medication and worries about daily functioning can also prompt the consultation. In this educational article we describe a practical approach to the symptom 'headache' in adults on the basis of a number of questions. Our aim is to enable the general practitioner to: recognise alarm signals; identify the type of primary headache correctly; discuss, implement and evaluate the appropriate treatment; and reassure the patient.

Anticonvulsants in migraine prophylaxis: a Cochrane review.

Several trials have asserted that some anticonvulsant drugs seem to be useful for the prophylaxis of migraine, but systematic reviews are sparse. We independently searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials until 2005, as well as Headache and Cephalalgia through April 2006, for prospective, controlled trials of anticonvulsant drugs. Data were calculated and pooled across studies and expressed as standardized mean differences, odds ratios and numbers-needed-to-treat. Anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo, and more than double the number of patients for whom migraine frequency is reduced by > or = 50% relative to placebo. Sodium valproate/divalproex sodium and topiramate were better than placebo, whereas acetazolamide, clonazepam, lamotrigine and vigabatrin were not; gabapentin, in particular, needs further evaluation. Trials designed with sufficient power to compare different drugs are also necessary.

Objective assessment of cortical excitability in migraine with and without aura.

Recent progress in the genetics of migraine has refocused attention on cortical dysfunction as an important component of the pathophysiology of this disorder. In previous work, we have demonstrated functional changes in the visual cortex of migraine patients, using an objective transcranial magnetic stimulation technique, termed magnetic suppression of perceptual accuracy (MSPA). This study aimed to replicate previous findings in migraine with aura (MA) and to use the technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA patients and 13 migraine-free controls participated. MSPA assessments were undertaken using a standardized protocol in which computer-presented letter targets were followed at a variable delay interval by a single magnetic pulse delivered over the occiput. MSPA performance is expressed as a profile of response accuracy across target-pulse delay intervals. The profiles of migraine-free controls exhibited a normal U-shape. MA patients had significantly shallower profiles, showing little or no suppression at intermediate delay intervals. MoA patients had profiles that were similar to controls. Recent animal evidence strongly indicates that the U-shape of the normal MSPA function is caused by preferential activation of inhibitory neurons. Shallower MPSA profiles in MA patients are therefore likely to indicate a functional hyperexcitability caused by impaired inhibition. The finding of normal MPSA profiles in MoA patients is novel and will require further investigation.

Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS.

We examined the effect of standard migraine prophylaxis with sodium valproate on repeated measures of occipital excitability using transcranial magnetic stimulation (TMS). We predicted that, comparing pre- and post-treatment assessments, a reduction in clinical migraine parameters would be paralleled by a decrease in excitability measurements.A total of 31 migraine patients enrolled in the study, for assessment prior to and 1 month after commencement of sodium valproate prophylaxis. At each assessment, we used a standardized protocol to stimulate the occipital cortex with a 90-mm circular (coil A) and 70 mm figure-of-eight (coil B) coil. We recorded the threshold stimulation intensity at which subjects just perceived phosphenes. Subjects kept detailed records of headache parameters 1 month before and also during the study period. Valproate therapy significantly improved headache indexes, as expected. In MA subjects assessed with coil B, phosphene thresholds were significantly higher post-treatment than pre-treatment, but those for MO did not change. Modest correlations were observed in MA patients between increase in phosphene threshold and decrease in headache index. Although preliminary, the findings with coil B lend some support to the notion that effective migraine prophylaxis may be achieved through lowering cortical excitability by gamma-aminobutyric acid (GABA)-ergic intervention. Further investigation of the effect of sodium valproate or other similarly acting substances on cortical excitability in migraine is warranted.

Visual cortex excitability in migraine with and without aura.

OBJECTIVES: Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls. METHODS: Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output. RESULTS: There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack. CONCLUSION: Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura.

Suppression of perception in migraine: evidence for reduced inhibition in the visual cortex.

BACKGROUND: Results from transcranial magnetic stimulation (TMS) studies of visual cortex have confirmed visual cortical hyperexcitability in patients with migraine. It has been speculated that this may be due to deficient intracortical inhibitory tone. However, the TMS induction of phosphenes relies on the reporting of a subjective experience, and may thus be subject to bias. METHODS: Seven migraineurs with visual aura and seven sex- and age-matched controls were studied. Fifty-four different three-letter combinations were briefly displayed and followed by a magnetic pulse at 40, 70, 100, 130, 160, and 190 msec. Subjects were required to report as many letters as they thought they had recognized. RESULTS: In the migraine group, the mean proportion of correctly identified letters was significantly higher at 100 msec, as was the proportion of trials with two or three letters correctly reported. The time window in which perceptual suppression could be introduced was narrower in migraineurs compared to controls. CONCLUSION: These findings suggest that inhibitory systems are activated to a lesser extent by TMS pulses in patients. This observation is in agreement with the hypothesized deficiency of intracortical inhibition of the visual cortex, at least in migraineurs with aura.

Self-reported photophobic symptoms in migraineurs and controls are reliable and predict diagnostic category accurately.

OBJECTIVES: To assess the reliability of self-reported photophobia across different patient populations and to examine how visual stress thresholds and photophobic symptoms may be predictive of diagnosis. BACKGROUND: Relatively little is known about interictal photophobia in migraine. In particular, the variability of photophobia across different patient groups has not previously been studied, and a pathophysiological hypothesis to account for the symptoms is not agreed upon. METHODS AND RESULTS: Study 1 compared 99 self-selected Dutch patients and 101 headache-free controls using survey methods. Patients both with and without aura were significantly more likely to report symptoms, such as the wearing of sunglasses in normal daylight, consistent with interictal photophobia. Study 2 replicated these findings in a series of consecutive referrals to a headache clinic in the United States. Study 3 used a specially designed laboratory test to examine the threshold for visual stress in those patients who had participated in study 2. Visual stress thresholds were significantly lower in patients than in controls. A discriminant function analysis of data from both studies 2 and 3 showed that diagnostic category (migraine; control) could be predicted from photophobic symptoms and visual stress thresholds at a level significantly better than chance. CONCLUSIONS: We suggest that interictal photophobia is common in migraine and similar across different patient populations. One pathophysiological hypothesis is that interictal photophobia is associated with cortical hypersensitivity to stimulation. The predictive validity of interictal photophobic symptoms suggests that clinical diagnosis may be aided by questioning the patient about light sensitivity in the period between attacks.

Cortical hyperexcitability is cortical under-inhibition: evidence from a novel functional test of migraine patients.

Recent studies of the visual cortex in patients with migraine have generally concluded that migraine (particularly migraine with aura) is associated with a state of functional cortical hyperexcitability. The mechanisms giving rise to this hyperexcitability have hitherto been unclear. This paper reports two studies that used a novel investigative technique, derived from basic research in vision science, to examine specific deficits of inhibitory processing in primary visual cortex. The technique is termed the metacontrast test, and it examines visual masking under highly specified conditions. In Study 1, 12 migraine with aura patients (MA), 12 age-matched migraine without aura patients (MO) and 12 age- and sex-matched headache-free control subjects (C) were compared using the metacontrast test. MA patients were significantly less susceptible to visual masking in the metacontrast test than both MO and C groups: this result is highly consistent with a deficit in cortical inhibitory processing in MA patients. Study 2 examined MA patients taking a variety of migraine prophylactics, again using the metacontrast test. Test results normalized in those MA patients taking sodium valproate, but not in those taking other prophylactics. Sodium valproate is a GABA-A agonist that is known to cross the blood-brain barrier: GABA-ergic networks act as the primary inhibitory mechanism in visual cortex. Taken together, the results of these studies argue that cortical hyperexcitability, at least in MA patients, is likely to be a result of deficient intracortical inhibitory processes.

Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better.

Medicines work better if taken, which must be true of migraine prophylaxis. There is evidence that compliance with regular medication can be badly deficient. To assess how serious the problem might be in routine migraine management, we undertook a covert observational 2-month survey in a specialist headache clinic using objective measures of compliance. Subjects were 38 patients needing prophylaxis with medication prescribed once (od), twice (bd), or three times daily (tds). Medication was dispensed, unknown to them, in Medication Event Monitoring Systems (MEMS) to record openings in real time. Number, timing, and pattern of actual openings were compared with what was expected. Compliance rates averaged 66%, although returned pill counts indicated 91%. A substantial and significant difference was shown between od and bd or tds regimens. Measures of dosing interval--used-on-schedule rate and therapeutic coverage--averaged between 44% and 71%. Once-daily treatment was associated with a used-on-schedule rate more than double those of multiple daily dosing, but still only 66%. We conclude that routine use of drug prophylaxis in migraine may be so seriously undermined by poor compliance that it has little chance of efficacy. Returned-pill counting is inadequate for compliance assessment.

Visual system dysfunction in migraine: a review of clinical and psychophysical findings.

This paper reviews both clinical and experimental literature relating to visual dysfunction in migraine, starting with the eye and progressing via the retina and visual pathways to the visual cortex. Migraine is associated with (i) a pupillary sympathetic hypofunction, and (ii) a cortical hypersensitivity to visual stimuli (perhaps only in migraine with aura), the pathogenesis of which remains to be determined. Various hypotheses are discussed, and it is proposed that the methods of visual psychophysics may represent a useful approach in the future study of cortical hyperexcitability in migraine. Paradoxically, little research has been directed towards understanding (i) the photophobia of migraine attacks, and (ii) how migraine may be triggered by visual stimuli. Research aimed at elucidating the mechanisms of these phenomena may enhance understanding of the pathogenesis of migraine.