Rolf Salvesen

Management of Medication Overuse Headache: 1-Year Randomized Multicentre Open-Label Trial

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month x headache intensity x headache hours) at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had ≥ 50% reduction in monthly headache days compared with 25% in the withdrawal group (P = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).

Prednisolone does not reduce withdrawal headache: A randomized, double-blind study

Introduction: Medication overuse headache is a condition where abrupt drug withdrawal is considered the treatment of choice. Objective: To study whether prednisolone given orally the first 6 days after medication withdrawal reduces headache intensity during the same period. Methods: From August 2003 through November 2005, we included patients aged 18 to 70 years with probable medication overuse headache. The study was randomized, double-blind, and placebo controlled. The patients were hospitalized for 3 days to start medication withdrawal. They were randomly assigned to receive prednisolone 60 mg on days 1 and 2, 40 mg on days 3 and 4, and 20 mg on days 5 and 6 (Group A) or placebo tablets for 6 days (Group B). Headache intensity was recorded in a diary for a month before withdrawal (baseline) and throughout the study period of 28 days. The primary endpoint was a calculated mean headache (MH), based on number of days with headache and mean intensity the first 6 days after withdrawal. Results: We included 26 men and 74 women. Sixty-five had migraine, 13 had tension-type headache, and 22 had both migraine and tension-type headache. Baseline headache days were 25.4 (CI 24.3 to 26.4). Baseline MH was 1.6 (CI 1.41 to 1.69). Fifty-one received Regimen A, and 49 received Regimen B. Baseline features were similar. During the first 6 days after withdrawal, headache was similar in Groups A and B (MH 1.48 [CI 1.28 to 1.68] vs 1.61 [CI 1.41 to 1.82], p = 0.34). Conclusion: Prednisolone has no effect on withdrawal headache in unselected patients with chronic daily headache and medication overuse.

Headache research strategy

It has been stated that it is not the lack of financial means that hinders progress in medical research, but rather the lack of ideas. This may be so also in the headache field. If viewed from the outside, much of the research activity in this field over the past decades may be considered repetitions or only slight variations on old themes, without any breakthroughs. The abnormalities that have been discovered are mostly consequences and not causes of the actual headache. The research strategy with regard to the various headache forms is an important but also a most sensitive topic. Individual backgrounds, previous experience, present setting and facilities, and even, to some extent, bias mingle to form the entire scientific approach of a given group.

Chronic daily headache with medication overuse: predictors of outcome 1 year after withdrawal therapy

Background and purpose:  We examined prospectively the results of withdrawal therapy in 80 patients with probable medication overuse headache. The aim was to identify baseline patient characteristics that might predict outcome after 1 year (end of study).

Seasonal variation in migraine

Our group has previously shown that migraineurs, as opposed to individuals with other headaches, are more likely to have headache during the bright arctic summer than during the polar night season. We set out to investigate the impact of seasonal light exposure in migraine with and without aura. We performed a questionnaire-based study of 169 female volunteer migraineurs in an arctic area where light conditions during summer and winter seasons are extreme. We included 98 patients with migraine with aura (MA) and 71 with migraine without aura (MoA). One hundred and seven patients (63%) reported seasonal variation in migraine attack frequency. Close to half (47%) of patients with aura, but only 17% of patients without aura, reported more frequent attacks during the light season (P < 0.001). Patients with MA reported interictal light hypersensitivity and light exposure as an attack precipitating factor significantly more often than individuals with MoA. They also reported significantly more frequent use of sunglasses to prevent attacks. We found no significant differences between MA and MoA as regards sleep disturbances, use of oral contraceptives, impact of headache or circadian variations. Seasonal periodicity of migraine in an arctic population with more frequent attacks during the light season is a convincing phenomenon in MA but not in MoA. The amount of light exposure seems to be pivotal to this variation.

Prophylaxis of migraine with melatonin A randomized controlled trial

Background: A previous open-label study of melatonin, a key substance in the circadian system, has shown effects on migraine that warrant a placebo-controlled study. Method: A randomized, double-blind, placebo-controlled crossover study was carried out in 2 centers. Men and women, aged 18–65 years, with migraine but otherwise healthy, experiencing 2–7 attacks per month, were recruited from the general population. After a 4-week run-in phase, 48 subjects were randomized to receive either placebo or extended-release melatonin (Circadin®, Neurim Pharmaceuticals Ltd., Tel Aviv, Israel) at a dose of 2 mg 1 hour before bedtime for 8 weeks. After a 6-week washout treatment was switched. The primary outcome was migraine attack frequency (AF). A secondary endpoint was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). Results: Forty-six subjects completed the study (96%). During the run-in phase, the average AF was 4.2 (±1.2) per month and during melatonin treatment the AF was 2.8 (±1.6). However, the reduction in AF during placebo was almost equal (p = 0.497). Absolute risk reduction was 3% (95% confidence interval −15 to 21, number needed to treat = 33). A highly significant time effect was found. The mean global PSQI score did not improve during treatment (p = 0.09). Conclusion: This study provides Class I evidence that prolonged-release melatonin (2 mg 1 hour before bedtime) does not provide any significant effect over placebo as migraine prophylaxis. Classification of evidence: This study provides Class I evidence that 2 mg of prolonged release melatonin given 1 hour before bedtime for a duration of 8 weeks did not result in a reduction in migraine frequency compared with placebo (p = 0.497).

Cluster headache sine headache: Case report

We examined a 22-year-old man who was experiencing frequent attacks of left-sided miosis and ptosis, accompanied by left-sided nasal stuffiness. He reported one to three attacks every day for a period of a few weeks, each attack lasting between 1 and 2 hours. There was no accompanying pain for the overwhelming majority of attacks. During two attacks we observed left-sided miosis and ptosis as well as an injection of the left conjunctiva. Asymmetry of sweating from the forehead was apparent with dryness on the left side. A neurologic examination performed outside attack disclosed no abnormality. Results of MRI of the head and neck were normal, as were results of a chest radiograph. After 6 weeks, the attacks ceased. Six years later, the patient presented with left-sided miosis and ptosis, which was continuously present, although accentuated during attacks of severe pain in and around the left orbit. …

Insomnia and Circadian Variation of Attacks in Episodic Migraine

Objectives.—To assess the influence of insomnia on the 24‐hour temporal pattern of migraine.

Migraine, as compared to other headaches, is worse during midnight-sun summer than during polar night. A questionnaire study in an Arctic population.

Objective.—To investigate potential seasonal variation of migraine and other headaches in an Arctic population where light conditions are extreme during both winter and summer.

Brain Magnetic Resonance Imaging White-Matter Lesions and Cerebrospinal Fluid Findings in Patients with Acute Intermittent Porphyria

Background: Case reports display similaritiesbetween multiple sclerosis and acute intermittent porphyria (AIP). This study examines whether patients with AIP in general demonstrate white-matter lesions on brain magnetic resonance imaging (MRI) and/or abnormalities in plasma and/or cerebrospinal fluid (CSF) when examined outside attacks. We looked particularly for the presence of oligoclonal bands (OB) of immunoglobulin (Ig) in liquor. Methods:Eight AIP gene carriers without previous episodes of porphyria, mean age 42.8 years (range 30–60), and 8 AIP gene carriers with previous episodes of porphyria, mean age 42.8 years (range 33–62), were examined with brain MRI, venous blood samples and lumbar punctures. Results: Two male AIP gene carriers with previous episodes of porphyria, 58 and 35 years of age, had multiple white-matter, high-signal lesions on T2- weighted MRI sequences. Two AIP gene carriers without previous episodes of porphyria, 1 male and 1 female, had less than 5 such lesions. No OB were seen in the CSF in any patient, but 1 carrier had an increased level of protein in the CSF. Seven of 16 subjects (44%) had increased levels of HbA1c (>6.0), suggesting protracted hyperglycemia, and 3 further subjects had borderline levels (5.9). Conclusion: T2-weighted MRI sequences demonstrated multiple white-matter, high-signal lesions in 4 out of 16 AIP gene carriers (25%). No carrier demonstrated OB of Ig in CSF, making it unlikely that demyelinating lesions play a pivotal role in the pathogenesis of CNS symptoms in AIP. Only 1 AIP gene carrier had an increased level of protein in CSF; this contrasts with studies during acute attacks of porphyria. Seven subjects (44%) had abnormally high levels of HbA1c, in spite of the fact that no patient had a previous diagnosis of diabetes mellitus.